Disorders of Development or Aging
Eveteg
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Chapter 15
Neurological Disorders
Chapter Outline
15.1 Tumors and Seizures (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch15lev1sec1#ch15lev1sec1) 483 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch15#page_483)
Tumors (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch15lev1sec1#ch15lev2sec1) 483 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch15#page_483)
Seizures (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch15lev1sec1#ch15lev2sec2) 486 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch15lev1sec1#page_486)
15.2 Cerebrovascular Accidents (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch15lev1sec2#ch15lev1sec2) 489 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch15lev1sec1#page_489)
Causes (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch15lev1sec2#ch15lev2sec3) 489 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch15lev1sec1#page_489)
Treatments (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch15lev1sec2#ch15lev2sec4) 490 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch15lev1sec2#page_490)
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15.3 Traumatic Brain Injury (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch15lev1sec3#ch15lev1sec3) 494 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch15lev1sec2#page_494)
Causes (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch15lev1sec3#ch15lev2sec5) 494 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch15lev1sec2#page_494)
Treatments (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch15lev1sec3#ch15lev2sec6) 495 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch15lev1sec3#page_495)
15.4 Disorders of Development (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch15lev1sec4#ch15lev1sec4) 496 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch15lev1sec3#page_496)
Toxic Chemicals (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch15lev1sec4#ch15lev2sec7) 496 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch15lev1sec3#page_496)
Inherited Metabolic Disorders (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch15lev1sec4#ch15lev2sec8) 496 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch15lev1sec3#page_496)
Down Syndrome (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch15lev1sec4#ch15lev2sec9) 498 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch15lev1sec4#page_498)
15.5 Degenerative Disorders (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch15lev1sec5#ch15lev1sec5) 500 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch15lev1sec5#page_500)
Transmissible Spongiform Encephalopathies (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch15lev1sec5#ch15lev2sec10) 500 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch15lev1sec5#page_500)
Parkinson’s Disease (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch15lev1sec5#ch15lev2sec11) 501 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch15lev1sec5#page_501)
Huntington’s Disease (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch15lev1sec5#ch15lev2sec12) 506 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch15lev1sec5#page_506)
Amyotrophic Lateral Sclerosis (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch15lev1sec5#ch15lev2sec13) 508 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch15lev1sec5#page_508)
Multiple Sclerosis (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch15lev1sec5#ch15lev2sec14) 508 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch15lev1sec5#page_508)
Dementia (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch15lev1sec5#ch15lev2sec15) 510 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch15lev1sec5#page_510)
Korsakoff ’s Syndrome (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch15lev1sec5#ch15lev2sec16) 514 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch15lev1sec5#page_514)
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15.6 Disorders Caused by Infectious Diseases (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch15lev1sec6#ch15lev1sec6) 516 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch15lev1sec6#page_516)
Encephalitis (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch15lev1sec6#ch15lev2sec17) 516 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch15lev1sec6#page_516)
Meningitis (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch15lev1sec6#ch15lev2sec18) 517 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch15lev1sec6#page_517)
Learning Objectives LO 15.1 Describe the primary symptoms, causes, and treatments for brain tumors.
LO 15.2 Describe the primary symptoms, causes, and treatments for seizures.
LO 15.3 Explain how cerebrovascular accidents can occur.
LO 15.4 Explain how treatments can be used to address the immediate and long-term symptoms of cerebrovascular accidents.
LO 15.5 Identify some causes of traumatic brain injury.
LO 15.6 Describe treatments for traumatic brain injuries.
LO 15.7 Describe the effects of alcohol on development of the nervous system.
LO 15.8 Contrast the symptoms, causes, and treatments of inherited metabolic disorders.
LO 15.9 Identify symptoms, cause, and interventions for Down syndrome.
LO 15.10 Describe how transmissible spongiform encephalopathies cause brain damage.
LO 15.11 Describe the symptoms, causes, and treatments for Parkinson’s disease.
LO 15.12 Describe the symptoms, causes, and treatments for Huntington’s disease.
LO 15.13 Describe the symptoms, causes, and treatments for amyotrophic lateral sclerosis.
LO 15.14 Describe the symptoms, causes, and treatments for multiple sclerosis.
LO 15.15 Describe the symptoms, causes, and treatments for Alzheimer’s disease.
LO 15.16 Describe the symptoms and causes of Korsakoff ’s syndrome.
LO 15.17 Identify the symptoms, causes, and treatments for encephalitis.
LO 15.18 Identify the symptoms, causes, and treatments for meningitis.
Mrs. R., a divorced, 50-year-old elementary school teacher, was sitting in her car, waiting for a traffic light to change. Suddenly, her right foot began to shake. Afraid that she would inadvertently press the accelerator and move forward into the intersection, she quickly turned the car off. First her lower leg was shaking, then her upper leg as well. She felt her body, then her arm, begin to shake in rhythm with her leg. The shaking
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slowed and finally stopped. By this time the light had changed to green, and the cars behind her began honking. She missed that green light, but by the time the light changed again, she had recovered enough to drive home.
The next evening, some close friends visited her apartment for dinner. After dinner, her right foot began shaking again. This time she was standing up, and the shaking—much more violent than before—caused her to fall. Her friends heard the noise and came running to see what had happened. They saw Mrs. R. lying on the floor, her legs and arms held out stiffly before her, shaking uncontrollably. She was unconscious and did not respond to her friends as they tried to help her. The shaking stopped less than a minute later. Mrs. R. regained consciousness but seemed confused.
Mrs. R. was brought by ambulance to a hospital. After hearing a description of Mrs. R.’s symptoms, the emergency room physician immediately called a neurologist, who ordered a CT scan. The scan showed a small, circular white spot between the frontal lobes, above the corpus callosum. Two days later, a neurosurgeon removed a small benign tumor, and Mrs. R. fully recovered. She was relieved to learn that her type of brain tumor rarely produces brain damage if it is removed in time.
*****
The case of Mrs. R. highlights several important themes in this chapter. Mrs. R. experienced seizures as a result of a benign tumor. As you will read, there are different types of tumors and several different conditions that can produce seizures. Seizures can involve physical symptoms in restricted parts of the body or they can involve the entire body and include changes in consciousness. Amnesia and confusion following a seizure (as Mrs. R. experienced) are common, and most seizures end within a short period of time.
Although the brain is the most protected organ, many pathological processes can damage it or disrupt its functioning. Because much of what we have learned about the functions of the human brain has been gained by studying people with brain damage, you have already encountered many neurological disorders in this book: movement disorders, such as Parkinson’s disease; perceptual disorders, such as visual agnosia and blindness caused by damage to the visual system; language disorders, such as aphasia, alexia, and agraphia; and memory disorders, such as Korsakoff ’s syndrome.
This chapter describes the major categories of the neuropathological conditions that the brain can sustain —tumors and seizures, cerebrovascular accidents, traumatic brain injury, disorders of development, degenerative disorders, and finally disorders caused by infectious diseases. Each section discusses the behavioral effects of these conditions and their treatments. The figure below shows the basal ganglia and substantia nigra, which we will be paying particular attention to in our examination of these conditions.
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Basal ganglia and substantia nigra.
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Chapter 17
Stress, Anxiety, and Neurodevelopmental Disorders
Chapter Outline
17.1 Stress (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec1#ch17lev1sec1) 554 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17#page_554)
Physiology of the Stress Response (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec1#ch17lev2sec1) 555 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec1#page_555)
Health Effects of Long-Term Stress (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec1#ch17lev2sec2) 556 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec1#page_556)
Effects of Stress on the Brain (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec1#ch17lev2sec3) 557 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec1#page_557)
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Psychoneuroimmunology (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec1#ch17lev2sec4) 560 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec1#page_560)
17.2 Posttraumatic Stress Disorder (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec2#ch17lev1sec2) 564 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec1#page_564)
Symptoms (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec2#ch17lev2sec5) 564 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec1#page_564)
Heritability (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec2#ch17lev2sec6) 564 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec1#page_564)
Brain Changes (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec2#ch17lev2sec7) 565 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec2#page_565)
Treatment (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec2#ch17lev2sec8) 567 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec2#page_567)
17.3 Anxiety Disorders (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec3#ch17lev1sec3) 568 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec2#page_568)
Symptoms (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec3#ch17lev2sec9) 568 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec2#page_568)
Heritability (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec3#ch17lev2sec10) 570 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec3#page_570)
Brain Changes (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec3#ch17lev2sec11) 570 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec3#page_570)
Treatment (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec3#ch17lev2sec12) 570 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec3#page_570)
17.4 Obsessive-Compulsive Disorder (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec4#ch17lev1sec4) 573 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec3#page_573)
Symptoms (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec4#ch17lev2sec13) 573 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec3#page_573)
Heritability (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec4#ch17lev2sec14) 574 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec4#page_574)
Brain Changes (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec4#ch17lev2sec15) 575 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec4#page_575)
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Treatment (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec4#ch17lev2sec16) 575 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec4#page_575)
17.5 Autism Spectrum Disorder (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec5#ch17lev1sec5) 578 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec4#page_578)
Symptoms (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec5#ch17lev2sec17) 579 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec5#page_579)
Heritability (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec5#ch17lev2sec18) 579 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec5#page_579)
Brain Changes (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec5#ch17lev2sec19) 580 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec5#page_580)
17.6 Attention-Deficit/Hyperactivity Disorder (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec6#ch17lev1sec6) 583 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec5#page_583)
Symptoms (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec6#ch17lev2sec20) 583 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec5#page_583)
Heritability (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec6#ch17lev2sec21) 584 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec6#page_584)
Brain Changes (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec6#ch17lev2sec22) 585 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec6#page_585)
Learning Objectives LO 17.1 Compare the SAM system and HPA axis in coordinating a stress response.
LO 17.2 Describe the negative health outcomes associated with chronic stress.
LO 17.3 Compare the effects of long-term glucocorticoid exposure and early nurturing experiences on the brain in response to stress.
LO 17.4 Summarize the relationship between the immune and nervous systems in response to stress.
LO 17.5 List the symptoms of PTSD.
LO 17.6 Describe the roles of genetic and environmental factors in the development of PTSD.
LO 17.7 Describe changes in the brain associated with PTSD.
LO 17.8 Summarize treatments for PTSD.
LO 17.9 List the symptoms of anxiety disorders.
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LO 17.10 Describe the roles of genetic and environmental factors in the development of anxiety disorders.
LO 17.11 Describe changes in the brain associated with anxiety disorders.
LO 17.12 Summarize treatments for anxiety disorders.
LO 17.13 List the symptoms of OCD.
LO 17.14 Describe the roles of genetic and environmental factors in the development of OCD.
LO 17.15 Describe changes in the brain associated with OCD.
LO 17.16 Summarize treatments for OCD.
LO 17.17 List the symptoms of ASD.
LO 17.18 Describe the roles of genetic and environmental factors in the development of ASD.
LO 17.19 Describe changes in the brain associated with ASD.
LO 17.20 List the symptoms of ADHD.
LO 17.21 Describe the roles of genetic and environmental factors in the development of ADHD.
LO 17.22 Describe changes in the brain associated with ADHD.
Graciela is a busy college student, six weeks away from graduation. She is involved in intramural sports and works as an undergraduate researcher in a neuroscience lab on campus. Her hockey team is playing in the championship next week, and she is completing a study of serotonin cells that her advisor believes could be published in a prestigious journal. Graciela’s week is filled with classes, time in the lab, hockey practices, and homework. She has also applied to six graduate programs and four full-time laboratory technician positions in hopes of beginning a career after graduation. She has three exams next week and has been staying up very late to study, but is having trouble remembering facts that used to come easily to her. On top of everything else, she has had a sinus infection for nearly a week, which is further draining her energy.
Hurrying across campus so she wouldn’t be late to class one day, she suddenly felt herself filled with an intense fear. Her mind began racing. Did she complete all of her assignment? Had she shut down the equipment in the lab? Did she send in her final job application? She began having difficulty breathing. She was able to take only short, shallow breaths, and her hands and arms were tingling. She could feel her heart pounding and her body shaking. Terrified, Graciela suddenly fell to the ground. She wondered if she were having a heart attack. A friend saw Graciela fall, rushed to her side, and called an ambulance.
At the hospital doctors ran an EKG test to record the activity of Graciela’s heart. They also ran a number of other stress tests. Fortunately, the tests indicated that Graciela’s heart was healthy and she had not had a heart attack. The consensus was that Graciela suffered a panic attack, a period of symptoms that can include shortness of breath, irregularities in heartbeat, and other autonomic symptoms accompanied by intense fear. Recurrent panic attacks are one of the criteria for a diagnosis of panic disorder.
*****
Graciela’s experience illustrates that both physiological symptoms, such as shortness of breath and increased heart rate, and emotional symptoms, such as the experience of fear, can accompany anxiety disorders such as panic disorder. As you read this chapter, consider how elements of Graciela’s experience reveal the role of the nervous system in stress and immune responses, and the experience of anxiety. In
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addition to information about panic disorder and other anxiety disorders, this chapter includes sections on stress, obsessive-compulsive disorder, and two neurodevelopmental disorders: autism spectrum disorder and attention-deficit/ hyperactivity disorder.
The chapter begins with a description of stress, a physiological reaction that many people experience as part of their daily lives. Next, we will explore some of the disorders that can include elements of a chronic or pathological stress response: posttraumatic stress disorder, anxiety disorders, and obsessive- compulsive disorder. The final sections include information about two neurodevelopmental disorders: autism spectrum disorder and attention-deficit/hyperactivity disorder. The figure below displays parts of the limbic system, which will be of particular relevance to us as we study many of these disorders.
Structures of the limbic system.
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17.1 Stress Aversive stimuli can harm people’s health. Many harmful effects are produced not by the stimuli themselves but by our reactions to them. Walter Cannon, the physiologist who criticized the James-Lange theory described in Chapter 11 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch11#ch11) , introduced the term stress (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/glos01#ch17gloss1) to refer to the physiological reaction caused by the perception of aversive or threatening situations.
The word stress was borrowed from engineering, in which it refers to the action of physical forces on mechanical structures. The word can be a noun or a verb, and the noun can refer to situations or the individual’s response to them. When we say that someone was subjected to stress, we really mean that someone was exposed to a situation that elicited a particular reaction in that person: a stress response. (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/glos01#ch17gloss2)
The physiological responses that accompany the negative emotions prepare us to threaten rivals or fight them, or to run away from dangerous situations. Walter Cannon introduced the phrase fight-or-flight response (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/glos01#ch17gloss3) to refer to the physiological reactions that prepare us for the strenuous efforts required by fighting or running away. Usually, once we have fought with an adversary or run away from a dangerous situation, the threat is over, and our physiological condition can return to normal. The fact that the physiological responses may have adverse long-term effects on our health is unimportant as long as the responses are brief. But sometimes, the threatening situations are continuous rather than episodic, producing a more or less continuous stress response. And as we will see in the section on posttraumatic stress disorder, sometimes threatening situations are so severe that they trigger responses that can last for months or years.
Physiology of the Stress Response LO 17.1 Compare the SAM system and HPA axis in coordinating a stress response.
As we saw in Chapter 11 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch11#ch11) , emotions consist of behavioral, autonomic, and endocrine responses. The latter two components, the autonomic and endocrine responses, are the ones that can have adverse effects on health. (The behavioral components can, too, if, say, a person rashly gets into a fight with someone who is much bigger and stronger.) Because threatening situations generally call for vigorous activity, the autonomic and endocrine responses that accompany them are catabolic; that is, they help to mobilize the body’s energy resources. The sympathetic branch of the autonomic nervous system is active, and the adrenal glands secrete epinephrine, norepinephrine, and steroid stress hormones. Because the effects of sympathetic activity are similar to those of the adrenal hormones, we will limit our discussion to the hormonal responses. The release of catecholamine stress hormones (epinephrine and norepinephrine) is controlled by the sympathetic adrenal-medullary system, while release of the glucocorticoid hormones is controlled by the hypothalamic pituitary adrenal axis.
SYMPATHETIC ADRENAL-MEDULLARY SYSTEM
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The release of catecholamine stress hormones is under the control of the sympathetic adrenal- medullary system (SAM system). (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/glos01#ch17gloss4) In response to a stressful stimulus or environment, the hypothalamus and the sympathetic nervous system stimulate the adrenal medulla to release epinephrine and norepinephrine. Together, these catecholamine hormones initiate a rapid activation of the sympathetic nervous system (see Chapter 3 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch03#ch03) for review of sympathetic nervous system functions). (See Figure 17.1 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec1#ch17fig1) .)
Figure 17.1 Control of Secretion of Stress Hormones The diagram illustrates control of the secretion of glucocorticoids by the adrenal cortex and of catecholamines by the adrenal medulla.
Epinephrine affects glucose metabolism, causing the nutrients stored in muscles to become available to provide energy for strenuous exercise. Along with norepinephrine, the hormone also increases blood flow to the muscles by increasing the output of the heart. In doing so, it also increases blood pressure, which, over the long term, contributes to cardiovascular disease.
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Besides serving as a stress hormone, norepinephrine is (as you know) secreted in the brain as a neurotransmitter. Some of the behavioral and physiological responses produced by aversive stimuli appear to be mediated by noradrenergic neurons. For example, microdialysis studies have found that stressful situations increase the release of norepinephrine in the hypothalamus, frontal cortex, and lateral basal forebrain (Cenci et al., 1992 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio1) ; Yokoo et al., 1990 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio2) ). Montero et al. (1990) found that destruction of the noradrenergic axons that ascend from the brain stem to the forebrain prevented the rise in blood pressure that is normally produced by social isolation stress. The stress- induced release of norepinephrine in the brain is controlled by a pathway from the central nucleus of the amygdala to the locus coeruleus, the nucleus of the brain stem that contains norepinephrine-secreting neurons (Van Bockstaele et al., 2001 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio4) ).
HYPOTHALAMIC PITUITARY ADRENAL AXIS
The other stress-related hormone is cortisol, a steroid secreted by the adrenal cortex. Cortisol is called a glucocorticoid (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/glos01#ch17gloss5) because it has profound effects on glucose metabolism. In addition, glucocorticoids help to break down protein and convert it to glucose, help to make fats available for energy, increase blood flow, and stimulate behavioral responsiveness, presumably by affecting the brain. They decrease the sensitivity of the gonads to luteinizing hormone (LH), which suppresses the secretion of the sex steroid hormones. In fact, Singer and Zumoff (1992 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio27a) ) found that the blood level of testosterone in male hospital residents (doctors, not patients) was severely depressed, presumably because of the stressful work schedule they were obliged to follow. Glucocorticoids have other physiological effects, too, some of which are only poorly understood. Almost every cell in the body contains glucocorticoid receptors, which means that few of them are unaffected by these hormones.
The release of glucocorticoid is controlled by the activity of the hypothalamic pituitary adrenal axis (HPA axis). (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/glos01#ch17gloss6) The secretion of glucocorticoids is controlled by neurons in the paraventricular nucleus of the hypothalamus (PVN), whose axons terminate in the median eminence, where the hypothalamic capillaries of the portal blood supply to the anterior pituitary gland are located. (The pituitary portal blood supply was described in Chapter 3 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch03#ch03) .) The neurons of the PVN secrete a peptide called corticotropin-releasing hormone (CRH), (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/glos01#ch17gloss7) which stimulates the anterior pituitary gland to secrete adrenocorticotropic hormone (ACTH). (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/glos01#ch17gloss8) ACTH enters the general circulation and stimulates the adrenal cortex to secrete glucocorticoids. (See Figure 17.1 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec1#ch17fig1) .)
CRH (also called CRF, or corticotropin-releasing factor) is also secreted within the brain, where it serves as a neuromodulator/neurotransmitter, especially in regions of the limbic system that are involved in emotional responses, such as the periaqueductal gray matter, the locus coeruleus, and the central nucleus of the amygdala. The behavioral effects produced by an injection of CRH into the brain are similar to those produced by aversive situations; thus, some elements of the stress response appear to be produced by the release of CRH by neurons in the brain. For example, intracerebroventricular injection of CRH decreases the amount of time a rat spends in the center of a large open chamber (which is considered an anxiety-like
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behavior, Britton et al., 1982 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio6) ), enhances the acquisition of a classically conditioned fear response (Cole and Koob, 1988 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio7) ), and increases the startle response elicited by a sudden loud noise (Swerdlow et al., 1986 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio8) ). On the other hand, intracerebroventricular injection of a CRH antagonist reduces the anxiety caused by a variety of stressful situations (Heinrichs et al., 1994 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio9) ; Kalin et al., 1988 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio10) ; Skutella et al., 1994 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio11) ).
Critical Concepts
The secretion of glucocorticoids does more than help an animal react to a stressful situation: It helps the animal to survive. If a rat’s adrenal glands are removed, the rat becomes much more susceptible to the effects of stress. In fact, a stressful situation that a normal rat would take in its stride might be fatal to one whose adrenal glands have been removed. And physicians know that if an adrenalectomized person is subjected to stressors, he or she must be given additional amounts of glucocorticoid (Tyrell and Baxter, 1981 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio12) ).
Health Effects of Long-Term Stress LO 17.2 Describe the negative health outcomes associated with chronic stress.
Many studies of people who have been subjected to chronic or repeated stressful situations have found evidence of ill health. For example, survivors of concentration camps, who were subjected to long-term stress, have had generally poorer health later in life than other people of the same age (Cohen, 1953 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio13) ). Drivers of subway trains that injure or kill people are more likely to suffer from illnesses several months later (Theorell et al., 1992 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio14) ). Air traffic controllers, especially those who work at busy airports where the danger of collisions is greatest, show a greater incidence of high blood pressure, which gets worse as they grow older (Cobb and Rose, 1973 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio15) ). (See Figure 17.2 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec1#ch17fig2) .) They also are more likely to suffer from ulcers or diabetes.
Figure 17.2 Stress and Hypertension The graph shows the incidence of hypertension in various age groups of air traffic controllers at high-stress and low-stress airports.
(Based on data from Cobb and Rose, 1973.)
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A pioneer in the study of stress, Hans Selye suggested that most of the harmful effects of stress were produced by the prolonged secretion of glucocorticoids (Selye, 1976 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio16) ). Although the short-term effects of glucocorticoids are essential and often beneficial, the long-term effects of sustained glucocorticoid exposure are damaging. These effects include increased blood pressure, damage to muscle tissue, steroid diabetes, infertility, inhibition of growth, inhibition of the inflammatory responses, and suppression of the immune system. High blood pressure can lead to heart attacks and stroke. Inhibition of growth in children who are subjected to prolonged stress prevents them from attaining their full height. Inhibition of the inflammatory response makes it more difficult for the body to heal itself after an injury, and suppression of the immune system makes an individual vulnerable to infections. Long-term administration of steroids to treat inflammatory diseases often produces cognitive deficits and can even lead to steroid psychosis, whose symptoms include profound distractibility, anxiety, insomnia, depression, hallucinations, and delusions (de Kloet et al., 2005 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio17) ; Lewis and Smith, 1983 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio18) ).
A growing collection of research suggests that impaired regulation of the HPA axis is involved in many of the harmful effects of long-term stress (McEwen, 2006 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio18a) ). Allostasis (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/glos01#ch17gloss9) is a term to describe the process of responding to stimuli and regaining and maintaining homeostasis. Allostasis may include a change in the set point of a system to respond to stimuli that are outside the range of typical homeostatic functioning (McEwen and Wingfield, 2010 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio20a) ; Sterling & Eyer, 1988 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio29a) ). Related, allostatic load (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/glos01#ch17gloss10) refers to the cumulative and collective wear and tear on body systems when there is too much stress response or when the stress response is not turned off. Allostatic load has been implicated in the negative health effects of prolonged or exaggerated stress response in stress and anxiety disorders. Fortunately, interventions such as physical activity and social integration can help restore healthy HPA axis regulation (McEwen & Gianaros, 2010).
The adverse effects of stress on healing were demonstrated in a study by Kiecolt-Glaser et al. (1995 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio22) ), who performed
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punch biopsy wounds in the participants’ forearms, a harmless procedure that is used often in medical research. The participants were people who were providing long-term care for relatives with Alzheimer’s disease—a situation that is known to cause stress—and control participants of the same approximate age and family income. The investigators found that wound healing took significantly longer in the caregivers (48.7 days versus 39.3 days). (See Figure 17.3 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec1#ch17fig3) .) A subsequent study (Kiecolt-Glaser et al., 2005 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio15a) ) found that the wounds of couples who displayed high levels of hostile behavior healed more slowly than those of couples with more friendly interactions. A similar study found impaired wound healing among students during an exam period, compared to summer vacation (Marucha et al., 1998 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio17a) ).
Figure 17.3 Stress and Healing of Wounds The graph shows the percentage of caregivers and control participants whose wounds had healed as a function of time after the biopsy was performed.
(Based on data from Kiecolt-Glaser et al., 1995.)
Effects of Stress on the Brain LO 17.3 Compare the effects of long-term glucocorticoid exposure and early nurturing experiences
on the brain in response to stress.
Stress can have long-lasting effects on the brain. This section will explore some of the research documenting brain changes following exposure to stress, as well as the unique contributions of early life stressors and new research on stress resilience.
Sapolsky and his colleagues have investigated one rather serious long-term effect of stress: brain damage. As you learned in Chapter 14 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch14#ch14) , the hippocampal formation plays a crucial role in learning and memory, and evidence suggests that one of the causes of memory loss that occurs with aging is degeneration of this brain structure. Research with animals has shown that long- term exposure to glucocorticoids destroys neurons located in the CA1 field of the hippocampal formation. The hormones appear to destroy the neurons by decreasing the entry of glucose and decreasing the
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reuptake of glutamate (McEwen and Sapolsky, 1995; Sapolsky, 1992 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio26) , 1995 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio27) ). Both of these effects make neurons more susceptible to potentially harmful events, such as decreased blood flow, which often occurs as a result of the aging process. The increased amounts of extracellular glutamate permit calcium to enter through NMDA receptors. (You will recall that the entry of excessive amounts of calcium can kill neurons.) Perhaps, then, the stressors to which people are subjected throughout their lives increase the likelihood of memory problems as they grow older. In fact, Lupien et al. (1996 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio28) ) found that elderly people with elevated blood levels of glucocorticoids learned a maze more slowly than did those with normal levels.
Even brief exposure to stress can have adverse effects on normal brain functioning. Diamond and his colleagues (Diamond et al., 1999 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio29) ; Mesches et al., 1999 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio30) ) placed rats individually in a Plexiglas box and then placed the box in a cage with a cat for 75 minutes. Although the cat could not harm the rats, the cat’s presence (and odor) elicited a stress response; the stressed rats’ blood glucocorticoid concentration increased to approximately five times its normal level. The investigators found that this short-term stress affected the functioning of the animals’ hippocampi. The stressed rats’ ability to learn a spatial task was impaired, and primed-burst potentiation (a form of long-term potentiation) was impaired in hippocampal slices taken from stressed rats. (See Figure 17.4 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec1#ch17fig4) .) A study by Thomas et al. (2007 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio31) ) found that acute stress diminished the long-term survival of hippocampal neurons produced by the process of neurogenesis. As we saw in Chapter 16 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch16#ch16) , impaired hippocampal neurogenesis appears to play a role in the development of depression.
Figure 17.4 Acute Stress, Glucocorticoid Level, Synaptic Plasticity, and Learning The graphs show the effects of acute stress caused by exposing a rat to the sight and smell of a cat. The stress raised the glucocorticoid level (corticosterone, in the case of a rat), impaired the development of primed-burst potentiation (PBP, a form of long-term potentiation) in slices taken from these animals, and interfered with learning of a spatial task that requires the hippocampus.
(Based on data from Diamond et al., 1999.)
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Uno et al. (1989 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio32) ) found that if long-term stress is intense enough, it can even cause severe brain damage in young primates. The investigators studied a colony of vervet monkeys housed in a primate center in Kenya. They found that some monkeys died, apparently from stress. Vervet monkeys have a hierarchical society, and monkeys near the bottom of the hierarchy are picked on by the others; thus, they are almost continuously subjected to stress. (Ours is not the only species with social structures that cause a stress reaction in some of its members.) The deceased monkeys had gastric ulcers and enlarged adrenal glands, which are signs of chronic stress. Upon examination of their brains, researchers discovered that neurons in the CA1 field of the hippocampal formation were completely destroyed. Severe stress appears to cause brain damage in humans as well; Jensen et al. (1982 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio33) ) found evidence of brain degeneration in CT scans of people who had been subjected to torture. Stress early in life also appears to affect brain development. van Harmelen et al., (2010 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio34) ) found that episodes of emotional maltreatment during childhood were associated with an average 7.2 percent reduction in the volume of the dorsomedial prefrontal cortex. (See Figure 17.5 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec1#ch17fig5) .) You will read more about the effects of early life stress on brain development in the next section on prenatal stress.
Figure 17.5 Exposure to Early Life Stress Reduces the Volume of the Dorsomedial Prefrontal Cortex
The volume of the dorsomedial prefrontal cortex was reduced 7.2 percent in people who experienced emotional maltreatment during childhood.
(Based on van Harmelen et al., 2010)
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Several studies have confirmed that the stress of chronic pain has adverse effects on the brain and on cognitive behavior. Apkarian et al. (2004b (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio35) ) found that each
year of severe chronic back pain resulted in the loss of 1.3 cm3 of gray matter in the cerebral cortex, with the greatest reductions seen in the dorsolateral prefrontal cortex. In addition, Apkarian et al. (2004a) found that chronic back pain led to poor performance on a task that has been shown to be affected by prefrontal lesions.
PRENATAL STRESS
Prenatal stress can cause long-lasting malfunctions in learning and memory by interfering with normal development of the hippocampus. Son et al. (2006 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio37) ) subjected pregnant mice to stress caused by periodic restraint in a small chamber. They found that this treatment interfered with the establishment of hippocampal long-term potentiation in the offspring of the stressed females, along with impairments in a spatial learning task that requires the participation of the hippocampus. In humans, some studies have reported that prenatal and early life stress can reduce hippocampal volume in adulthood (Woon & Hedges, 2008 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio32a) ).
Brunson et al. (2005 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio39) ) confirmed that stress early in life can cause the deterioration of normal hippocampal functions later in life. During the first week after birth the investigators placed female rats and their newborn pups in cages with hard floors and only a small amount of nesting material. When the animals were tested at 4–5 months of age, their behavior was normal. However, when they were tested at 12 months of age, the investigators observed impaired performance in the Morris water maze and deficient development of long-term potentiation in the hippocampus. They also found dendritic atrophy in the hippocampus, which might have accounted for the impaired spatial learning and synaptic plasticity.
Salm et al. (2004 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio40) ) found that mild prenatal stress can affect brain development and produce changes that last the animal’s lifetime. Once a day during the last week of gestation, they removed pregnant rats from their cage and gave them an injection of a small amount of sterile saline—a procedure that lasted less than five minutes. This mild stress altered the development of the rat pups’ amygdalae. The investigators found that the volume of the lateral nucleus of the amygdala, measured in adulthood, was increased by approximately 30 percent in the animals that sustained mild prenatal stress. (See Figure 17.6 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec1#ch17fig6) .) As previous
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experiments have shown, prenatal stress increases fearfulness in a novel environment (Ward et al., 2000 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio41) ). Presumably, the increased size of the lateral nucleus contributes to this fearfulness.
Figure 17.6 Prenatal Stress and the Amygdala The graph shows volumes of nuclei of the amygdala in control rats and rats that had been subjected to prenatal stress.
(Based on data from Salm et al., 2004.)
At least some of the effects of prenatal stress on the fetus appear to be mediated by the secretion of glucocorticoids. Barbazanges et al. (1996 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio42) ) subjected pregnant female rats to stress and later observed the effects of this treatment on their offspring once they grew up. They found that the prenatally stressed rats showed a prolonged secretion of glucocorticoids when they were subjected to restraint stress as adults. However, if the mothers’ adrenal glands had been removed so that glucocorticoid levels could not increase during the stressful situation, their offspring reacted normally in adulthood. (The experimenters gave the adrenalectomized mothers controlled amounts of glucocorticoids to maintain them in good health.) (See Figure 17.7 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec1#ch17fig7) .)
Figure 17.7 Prenatal Stress and Glucocorticoids in Adulthood The graph shows the effects of prenatal stress and glucocorticoid level on the stress response of adult rats. Adrenalectomy of the mother before she was subjected to stress prevented the development of an elevated stress response in the offspring during adulthood.
(Based on data from Barbazanges et al., 1996.)
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RESILIENCE
The news about stress and the brain is not all bad, however. Researchers are increasingly interested in studying resilience and plasticity in the brain. The vast majority of individuals exposed to early life or long-term stress maintain healthy brain and psychological functioning. Factors such as the presence of various protective hormones (such as testosterone, neuropeptide Y, and a hormone called DHEA that mediates negative effects of excess cortisol) and controlled exposure to stress-related stimuli can promote resilience in the event of stress. Researchers are actively investigating brain changes, gene expression, and endocrine function to evaluate the brain basis for resilience (Russo et al., 2012 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio23a) ). (See Figure 17.8 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec1#ch17fig8) .)
Figure 17.8 Factors Related to Stress Resilience
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In research with laboratory animals, a study by Fenoglio et al. (2006 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio44) ) found that some experiences that occur during early life can reduce reactivity to stressful situations in adulthood. Fenoglio et al. removed rat pups from their cage, handled them for 15 minutes, and then returned them to their cage. Their mother immediately began licking and grooming the pups. This nurturing behavior activated several regions of the pups’ brains, including the central nucleus of the amygdala and the paraventricular nucleus of the hypothalamus, the location of neurons that secrete CRH. The result of this treatment was to reduce the production of CRH in response to stressful stimuli, which conferred a lifelong attenuation of the hormonal stress response.
Psychoneuroimmunology LO 17.4 Summarize the relationship between the immune and nervous systems in response to
stress.
As we have seen, long-term stress can be harmful to one’s health and can even result in brain damage. The most important cause of these effects is an elevated level of glucocorticoids, but high blood pressure caused by epinephrine and norepinephrine also plays a contributing role. In addition, the stress response can impair the functions of the immune system, which protects us from assault by viruses, microbes, fungi, and other types of parasites. Study of the interactions between the immune system and behavior (mediated by the nervous system) is called psychoneuroimmunology. (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/glos01#ch17gloss11) Some research in this field is described in the following section.
THE IMMUNE SYSTEM
The immune system is one of the most complex systems of the body. Its function is to protect us from infection, and because infectious organisms have developed devious tricks through the process of evolution, our immune system has evolved devious tricks of its own. The description we provide here is abbreviated and simplified, but it presents some of the important elements of the system.
The immune system derives from white blood cells that develop in the bone marrow and in the thymus gland. Some of the cells roam through the blood or lymphatic system; others reside permanently in one place. Two types of specific immune reaction occur when the body is invaded by foreign organisms, including bacteria, fungi, and viruses: chemically mediated and cell-mediated reactions. Chemically mediated immune reactions involve antibodies. Infectious microorganisms have unique proteins on their surfaces, called antigens. (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/glos01#ch17gloss12) These proteins serve as the invaders’ calling cards, identifying them to the immune system. Through exposure to the microorganisms, the immune system learns to recognize these proteins. The result of this learning is the development of special lines of cells that produce specific antibodies— (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/glos01#ch17gloss13) proteins that recognize antigens and help to kill the invading microorganisms.
One type of antibody is released into the circulation by B-lymphocytes (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/glos01#ch17gloss14) (or B cells), which receive their name from the fact that they develop in bone marrow. These antibodies, called immunoglobulins, (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/glos01#ch17gloss15) are chains of protein. Each type of immunoglobulin (there are five of them) is identical except for one end,
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which contains a unique receptor. A particular receptor binds with a particular antigen, just as a molecule of a hormone or neurotransmitter binds with its receptor. When the appropriate line of B-lymphocytes detects the presence of an invading bacterium, the cells release their antibodies, which bind with the antigens present on the surface of the invading microorganisms. The antigens either kill the invaders directly or attract other white blood cells, which then destroy them. (See Figure 17.9 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec1#ch17fig9) a.)
Figure 17.9 Immune Reactions (a) Chemically mediated reaction. The B-lymphocyte detects an antigen on a bacterium and releases a specific immunoglobulin. (b) Cell-mediated reaction. The T-lymphocyte detects an antigen on a bacterium and kills it directly or releases a chemical that attracts other white blood cells.
The other type of defense by the immune system, cell-mediated immune reactions, is produced by T- lymphocytes (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/glos01#ch17gloss16) (or T cells), which originally develop in the thymus gland. These cells also produce antibodies, but the antibodies remain attached to the outside of their membrane. T-lymphocytes primarily defend the body against fungi, viruses, and multicellular parasites. When antigens bind with their surface antibodies, the cells either directly kill the invaders or signal other white blood cells to come and kill them. (See Figure 17.9 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec1#ch17fig9) b.)
The reactions illustrated in Figure 17.9 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec1#ch17fig9) are much simplified; actually, both chemically mediated and cell-mediated immune reactions involve several different types of cells. The communication between these cells is accomplished by cytokines, (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/glos01#ch17gloss17) chemicals that stimulate cell division. The cytokines that are released by certain white blood cells when an invading microorganism is detected (principally interleukin-1 and interleukin-2) cause other white blood cells to proliferate and direct an attack against the invader. The primary way in which glucocorticoids suppress specific immune responses is by interfering with the messages conveyed by the cytokines (Sapolsky, 1992 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio26) ).
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NEURAL CONTROL OF THE IMMUNE SYSTEM
As we will see in the next section, the stress response can increase the likelihood of contracting infectious diseases. What is the physiological explanation for these effects? One answer, probably the most important one, is that stress increases the secretion of glucocorticoids, and as we saw, these hormones directly suppress the activity of the immune system.
Earlier in this chapter, you read about the results of studies of chronic stress on wound healing in caregivers of patients with Alzheimer’s disease. Additional research in this population has revealed the relationship between stress and immune function. A direct relationship between stress and the immune system was demonstrated by Kiecolt-Glaser et al. (1987 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio46) ). Using several different laboratory tests, these investigators found that caregivers of family members with Alzheimer’s disease, who certainly underwent considerable stress, showed weaker immune systems. One measure of the quality of a person’s immune response is the amount of antibodies produced in response to a vaccination. Glaser et al. (2000 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio47) ) found that people taking care of spouses with Alzheimer’s disease maintained lower levels of IgG antibodies after receiving a pneumococcal bacterial vaccine. (See Figure 17.10 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec1#ch17fig10) .) Bereavement, another source of stress, also suppresses the immune system. Schleifer et al. (1983 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio48) ) tested the husbands of women with breast cancer and found that their immune response was lower after their wives died. Knapp et al. (1992 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio49) ) even found that when healthy participants imagined themselves reliving unpleasant emotional experiences, the immune response measured in samples of their blood was decreased. Finally, people facing the psychological stress of undergoing surgery (Ahlers et al., 2008 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio1a) ), taking an academic exam (Paik et al., 2000 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio21a) ), or perhaps even experiencing Facebook-induced social stress (Campisi et al., 2012 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio5a) ) display various degrees of immune suppression.
Figure 17.10 Effect of Stress on Immune Function The graph shows levels of antibodies produced in response to a pneumococcal bacterial vaccine in the blood of controls and former and current caregivers of spouses with Alzheimer’s disease.
(Based on data from Glaser, R., Sheridan, J., Malarkey, W. B., MacCallum, R. C., and Kiecolt- Glaser, J. K., Chronic stress modulates the immune response to a pneumococcal pneumonia vaccine, Psychosomatic Medicine, 2000, 62, 804–807.)
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Several studies indicate that the suppression of the immune response by stress is largely (but not entirely) mediated by glucocorticoids (Keller et al., 1983 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio53) ). Because the secretion of glucocorticoids is controlled by the brain (through its secretion of CRH), the brain is responsible for the suppressing effect of these hormones on the immune system. Neurons in the central nucleus of the amygdala send axons to CRH-secreting neurons in the paraventricular nucleus of the hypothalamus; thus, we can reasonably expect that the mechanism that is responsible for negative emotional responses is also responsible for the stress response and the immunosuppression that accompanies it.
STRESS AND INFECTIOUS DISEASES
Often when a married person dies, his or her spouse dies soon afterward, frequently of an infection. In fact, a wide variety of stress-producing events in a person’s life can increase the susceptibility to illness. For example, Glaser et al. (1987 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio54) ) found that medical students were more likely to contract acute infections and to show evidence of suppression of the immune system during the time that final examinations were given.
Stone et al. (1987 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio55) ) attempted to determine whether stressful events in people’s daily lives might predispose them to upper respiratory infection. If a person is exposed to a microorganism that might cause such a disease, the symptoms do not occur for several days; that is, there is an incubation period between exposure and signs of the actual illness. Thus, the authors reasoned that if stressful events suppressed the immune system, one might expect to see a higher likelihood of respiratory infections several days after such stress. To test their hypothesis, they asked volunteers to keep a daily record of desirable and undesirable events in their lives over a 12-week period. The volunteers also kept a daily record of any discomfort or symptoms of illness.
The results were as predicted: During the three- to five-day period just before showing symptoms of an upper respiratory infection, people experienced an increased number of undesirable events and a
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decreased number of desirable events in their lives. (See Figure 17.11 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec1#ch17fig11) .)
Figure 17.11 Role of Desirable and Undesirable Events on Susceptibility to Upper Respiratory Infections The graph shows mean percentage change in frequency of undesirable and desirable events during the 10-day period preceding the onset of symptoms of upper respiratory infections.
(Based on data from Stone et al., 1987.)
Stone et al. (1987 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio55) ) suggest that the effect is caused by decreased production of a particular immunoglobulin that is present in the secretions of mucous membranes, including those in the nose, mouth, throat, and lungs. This immunoglobulin, IgA, serves as the first defense against infectious microorganisms that enter the nose or mouth. They found that IgA is associated with mood; when a person is unhappy or depressed, IgA levels are lower than normal. Other studies have reported reductions in IgA associated with stress induced by academic exams, with reductions lasting as long as two weeks beyond the end of the stressor (Deinzer at al., 2000 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio8a) , Deinzer & Schüller, 1998 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio7a) ). The results suggest that the stress caused by undesirable events may, by suppressing the production of IgA, lead to an increase in the likelihood of upper respiratory infections.
The results of the study by Stone et al. were confirmed by an experiment by Cohen et al. (1991 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio59) ). The investigators found that participants who were given nasal drops containing cold viruses were much more likely to develop colds if they reported stressful experiences during the past year and if they said they felt threatened, out of control, or overwhelmed by events. (See Figure 17.12 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec1#ch17fig12) .)
Figure 17.12 Colds and Psychological Stress
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The graph shows the percentage of volunteers with colds as a function of an index of psychological stress.
(Based on data from Cohen et al., 1991.)
Section Review
Stress
LO 17.1 Compare the SAM system and HPA axis in coordinating a stress response.
The SAM system consists of hypothalamic and sympathetic nervous system activation of the adrenal medulla to release epinephrine and norepinephrine. These hormones contribute to glucose metabolism and increased blood pressure. The HPA axis consists of activation of the hypothalamus, resulting in release of corticotropin-releasing hormone (CRH). CRH activates the anterior pituitary to release adrenocorticotropic hormone (ACTH). ACTH causes the adrenal glands to release glucocorticoids which contribute to glucose metabolism, stimulate behavioral responsiveness, increase blood flow, and result in suppressed secretion of sex steroid hormones. Altogether activation of the SAM system and HPA axis contribute to generating a stress response to enable an individual to respond to the stressor (often by fighting or fleeing).
LO 17.2 Describe the negative health outcomes associated with chronic stress.
Although increased levels of epinephrine and norepinephrine can raise blood pressure, most of the harm to health comes from glucocorticoids. Prolonged exposure to high levels of these hormones can lead to hypertension, damage muscle tissue, lead to infertility, inhibit growth, inhibit the inflammatory response, and suppress the immune system. These effects can contribute to increased incidence of ulcers, diabetes, heart attack, stroke, increased wound-healing time, and growth inhibition in children.
LO 17.3 Compare the effects of long-term glucocorticoid exposure and early nurturing experiences on the brain in response to stress.
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Prolonged glucocorticoid exposure can damage the hippocampus and acute stress can impair hippocampal functioning. Exposure to stress during prenatal or early postnatal life can affect brain development including impaired hippocampus function and increased size of the amygdala. Stress also decreases the survival rate of hippocampal neurons produced by adult neurogenesis. These changes appear to predispose animals to react more to stressful situations. In humans the stress of chronic pain can cause loss of cerebral gray matter, especially in the prefrontal cortex, with accompanying deficits in behaviors that involve the prefrontal cortex. Early life exposure to nurturing behavior activated several regions of rat pups’ brains, including the central nucleus of the amygdala and the paraventricular nucleus of the hypothalamus, the location of neurons that secrete CRH. The result of this treatment was to reduce the production of CRH in response to stressful stimuli, which conferred a lifelong attenuation of the hormonal stress response.
LO 17.4 Summarize the relationship between the immune and nervous systems in response to stress.
Psychoneuroimmunology is a field of study that investigates interactions between behavior and the immune system, mediated by the nervous system. A variety of stressful situations have been shown to increase people’s susceptibility to infectious diseases. The most important mechanism by which stress impairs immune function is through increased blood levels of glucocorticoids produced by the HPA axis. The neural input to the bone marrow, lymph nodes, and thymus gland may also play a role.
Thought Question
As part of a college mentoring program, you have agreed to mentor a first-year student during their first semester at your school. As an experienced student, you may have noticed that you and your friends are more likely to get sick during stressful points in the semester—when exams or projects are competing for your time and attention. You know that the release of glucocorticoids is likely responsible for increased risk of infections during these times. Being a good mentor, you want to share this information with your mentee and help them avoid getting sick. Write an e-mail to your mentee explaining how glucocorticoids can put them at risk of getting sick. Make suggestions to your mentee to help them avoid or minimize the risk of immune suppression during their first year in college.
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17.2 Posttraumatic Stress Disorder The aftermath of tragic and traumatic events such as those that accompany wars, violence, and natural disasters often includes psychological symptoms that persist long after the stressful events are over. According to the DSM-5, posttraumatic stress disorder (PTSD) (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/glos01#ch17gloss18) consists of the “development of characteristic symptoms following exposure to one or more traumatic events” (American Psychiatric Association, 2013 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio60) , p. 274 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch09lev1sec3#page_274) ). The likelihood of developing PTSD is increased if the traumatic event involved danger or violence from other people, such as assault, rape, or wartime experiences (Yehuda and LeDoux, 2007 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio61) ). Although men are exposed to traumatic events more often than women are, women are more likely to develop PTSD after being exposed to such events (Fullerton et al., 2001 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio62) ). The lifetime prevalence of PTSD is 8.7 percent in the United States (American Psychiatric Association, 2013 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio60) ; Kessler et al., 2005 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio14a) ); however rates of approximately 0.5–1 percent are reported in Europe and most Asian, African, and Latin American countries (Hinton and Lewis-Fernandez, 2011 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio12a) ). The onset and severity of PTSD varies across cultures, and culture may influence the expression of PTSD symptoms (Hinton and Lewis-Fernandez, 2011 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio12a) ).
Symptoms LO 17.5 List the symptoms of PTSD.
The symptoms of PTSD include recurrent dreams or recollections of the traumatic event, feelings that the traumatic event is recurring (“flashback” episodes), and intense psychological distress. These dreams, recollections, or flashback episodes can lead the person to avoid thinking about the traumatic event, which often results in diminished interest in social activities, feelings of detachment from others, suppressed emotional feelings, and a sense that the future is bleak and empty. Other psychological symptoms include difficulty falling or staying asleep, irritability, outbursts of anger, difficulty in concentrating, and heightened reactions to sudden noises or movements. As this description indicates, people with PTSD have impaired mental health functioning. They also tend to have generally poor physical health (Zayfert et al., 2002 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio67) ). (See Table 17.1 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec2#ch17tbl1) .)
Table 17.1 Symptoms of PTSD
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Recurring memories, dreams, or flashbacks related to the traumatic event that cause distress
Avoiding stimuli related to the traumatic event
Changes in mood or thoughts related to the traumatic event, such as memory loss related to the event, increased negative emotions (e.g., fear, anger, guilt), decreased positive emotions, and decreased participation in significant activities or social interactions
Physiological reactions (e.g., increased heart rate or breathing) to stimuli related to the traumatic event
Increased irritability, hypervigilance and increased startle response, anger, aggression, self-destructive behavior, problems concentrating, and insomnia
Source: Based on American Psychiatric Association, 2013.
Heritability LO 17.6 Describe the roles of genetic and environmental factors in the development of PTSD.
The risk for PTSD depends on both genetic and environmental factors. Kolassa et al. (2010 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio68) ) studied 424 survivors of the genocide in the Rwanda. They found that the likelihood of developing PTSD increased with the number of traumatic events the person had experienced. (See Figure 17.13 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec2#ch17fig13) .) They also found that people with a particular allele of the gene responsible for the production of COMT, the enzyme that destroys catecholamines present in the interstitial fluid, were more likely to develop PTSD. This allele (the Val158Met polymorphism) is associated with slower destruction of catecholamines, which supports the conclusion from other research that these neurotransmitters are associated with the deleterious effects of stress.
Figure 17.13 Prevalence of PTSD and Traumatic Events This graph shows the prevalence of PTSD in survivors of the Rwanda genocide as a function of the number of traumatic events they had suffered.
(Based on data from Kolassa et al., 2010.)
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Twin studies have shown that the overlap between PTSD and panic disorder, generalized anxiety disorder, and depressive disorder is at least partly a result of shared genetic factors (Nugent et al., 2008 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio69) ). Presumably, these genetic factors make some people more sensitive to the effects of stress. Evidence from twin studies suggests that genetic factors also play a role in a person’s susceptibility to develop PTSD. In fact, genetic factors influence not only the likelihood of developing PTSD after being exposed to traumatic events but also the likelihood that the person will be involved in such an event (Stein et al., 2002 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio70) ). For example, people with a genetic predisposition toward irritability and anger are more likely to be assaulted, and those with a predisposition toward risky behavior are more likely to be involved in accidents. A few studies have identified specific genes as possible risk factors for developing PTSD. These genes include those responsible for the production of dopamine D2 receptors, dopamine transporters, and 5-HT
transporters (Nugent et al., 2008 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio69) ).
Brain Changes LO 17.7 Describe changes in the brain associated with PTSD.
As we saw in the previous subsection, studies with laboratory animals have shown that prolonged exposure to stress can cause brain abnormalities, particularly in the hippocampus and amygdala. At least two MRI studies have found evidence of hippocampal damage in veterans with combat-related posttraumatic stress disorder (Bremner et al., 1995 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio72) ; Gurvits et al., 1996 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio73) ). In the study by Gurvits et al., the volume of the hippocampal formation was reduced by over 20 percent, and the loss was proportional to the amount of combat exposure the veteran had experienced. Lindauer et al., (2005 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio74) ) found that police officers with PTSD had a smaller hippocampus than those who had also been exposed to trauma but had not developed the disorder.
An intriguing study by Gilbertson et al. (2002 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio75) ) suggests that at least part of the reduction in hippocampal volume seen in people with PTSD may predate the exposure to stress. In other words, a smaller hippocampus may be a predisposing factor in the acquisition of PTSD. Gilbertson et al., studied 40 pairs of monozygotic twins in which only one member went to Vietnam and experienced combat during the Vietnam War. Almost half of the men who experienced combat developed PTSD. As expected, the hippocampal volumes of these men were smaller than those of the men who did not develop PTSD after their combat experience. In addition, a smaller hippocampus was associated with more severe PTSD. The interesting fact is that the twin brothers of the PTSD patients who stayed home also showed smaller-than-average hippocampal volumes. Given that monozygotic twins are genetically identical and usually have very similar brains, this finding suggests that a person with a small hippocampus is more likely to develop PTSD after exposure to psychological trauma. (See Figure 17.14 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec2#ch17fig14) .)
Figure 17.14 Hippocampal Volumes of Pairs of Monozygotic Twins
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The graph shows that the size of the hippocampus of twins not exposed to combat was similar to the size of their combat-exposed co-twins whether or not the co-twins had PTSD. These results suggest that hippocampal size is a genetically determined trait that predates the exposure to combat.
(Based on data from Gilbertson et al., 2002.)
What role might the hippocampus play in a person’s susceptibility to developing PTSD? One possibility is that the hippocampus, which is involved in contextual learning, participates in recognition of the context in which a traumatic event occurs. The hippocampus then aids in distinguishing safe from dangerous contexts (Yehuda and LeDoux, 2007 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio61) ). Consider a person who has been attacked by another person. The sight of other people who even slightly resemble the attacker or situations that even slightly resemble the one in which the attack occurred might then activate the amygdala and trigger an emotional response. However, a normally functioning hippocampus would detect the difference between the present context and the one associated with the attack and inhibit the activity of the amygdala.
You read a few paragraphs ago that most people who are exposed to a potentially traumatic event manage to suppress their emotional reaction. What brain mechanisms suppress the emotional reaction and enable a person to recover? As we saw in Chapters 11 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch11#ch11) and 16 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch16#ch16) , the prefrontal cortex can exert an inhibitory effect on the amygdala and suppress emotional reactions. For example, the medial prefrontal cortex plays an essential role in the extinction of conditioned emotional responses. In fact,
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Milad et al. (2004 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio77) ) found that the medial prefrontal cortex was thicker in people who showed rapid extinction of a conditioned emotional response. And as we also saw earlier, van Harmelen et al. (2010 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio78) ) found a reduction in the volume of the ventromedial prefrontal cortex in adults who had sustained emotional maltreatment during childhood.
Several studies have found evidence that the amygdala is responsible for emotional reactions in people with PTSD and that the prefrontal cortex plays a role in these reactions in people without PTSD by inhibiting the activity of the amygdala (Rauch et al., 2006 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio79) ). For example, a functional-imaging study by Shin et al. (2005 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio80) ) found that, when shown pictures of faces with fearful expressions, people with PTSD show greater activation of the amygdala and smaller activation of the prefrontal cortex than did people without PTSD. In fact, the symptoms of the people with PTSD were positively correlated with the activation of the amygdala and negatively correlated with the activation of the medial prefrontal cortex. (See Figure 17.15 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec2#ch17fig15) .)
Figure 17.15 Amygdala and Medial Prefrontal Cortex Activation in PTSD The graph shows the activation of the amygdala and medial prefrontal cortex in response to the sight of happy or fearful faces in control participants and participants with PTSD.
(Based on data from Shin et al., 2005.)
A growing body of research is investigating the relationship between traumatic brain injury (TBI) and PTSD. As described in Chapter 15 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch15#ch15) , TBI is defined as “a blow or jolt to the head that disrupts brain function resulting in a brief loss or alternation of consciousness” (also known as a concussion; Simmons and Matthews, 2012, (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio26a) p. 599 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch18lev1sec1#page_599) ). Individuals
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involved in combat, motor vehicle accidents, or sports injuries may sustain TBI that can cause injury to axons and contribute to neuropsychiatric symptoms. PTSD and TBI are found to co-occur in many individuals, particularly those involved in military combat. PTSD and TBI share several common features such as anxiety and increased vigilance (Kaplan et al., 2010 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio13a) ). Overlapping brain regions in the frontal cortex and changes in BDNF (brain-derived neurotrophic factor) may be involved in both TBI and PTSD (Kaplan et al., 2010 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio13a) ; Simmons and Matthews, 2012 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio26a) ).
Treatment LO 17.8 Summarize treatments for PTSD.
Many individuals display resilience in the face of trauma. Although many people are exposed to potentially traumatic events during their lives, most people recover rapidly and do not develop PTSD (Kessler et al., 1995 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio85) ). For example, Rothbaum and Davis (2003 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio86) ) reported that two weeks after having been raped, 92 percent of the individuals they studied showed symptoms that met the criteria for PTSD. However, within 30 days, the symptoms in most of the victims had subsided. The most common treatments for PTSD are cognitive behavior therapy, group therapy, and antidepressants. Boggio et al. (2010 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio87) ) reported on the results of a clinical trial of transcranial magnetic stimulation (TMS) of the dorsolateral prefrontal cortex in 30 patients with PTSD. They found that 10 sessions of stimulation of the left or right dlPFC significantly reduced the symptoms of PTSD and that the beneficial effects were still seen three months later. (See Figure 17.16 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec2#ch17fig16) .) Treatment with SSRIs resulted in reduced symptoms, improved cognitive function, and increased hippocampal volume in patients with PTSD (Bossini et al., 2007 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio2a) ; Vermetten et al., 2003 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio31a) ). In addition, psychotherapy for PTSD is associated with decreased amygdala activity and increased activity in the prefrontal cortex, dorsal anterior cingulate cortex, and hippocampus (Thomaes et al., 2014 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio30a) ).
Figure 17.16 Transcranial Magnetic Stimulation and PTSD The graph shows the effects of TMS of the dorsolateral prefrontal cortex on symptoms of PTSD.
(Based on data from Boggio et al., 2010.)
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Some treatment strategies focus on preventing PTSD following a traumatic event. In a recent review of preventative pharmacological therapies, Searcy et al. (2012 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio24a) ) described studies that included administration of cortisol to patients immediately after experiencing trauma, with the goal of providing additional negative feedback to the HPA axis to reduce its activity. This counterintuitive strategy appeared to be effective, and patients receiving cortisol were subsequently less likely to meet criteria for PTSD than patients receiving a placebo. In the same review, Searcy et al., (2012 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio24a) ) also reported on the effectiveness of blocking catecholamine stress hormones (epinephrine or norepinephrine) and enhancing GABAergic activity using drug administration immediately following exposure to a traumatic event. Although the results are currently limited to a few studies, it appears that administrating drugs to manipulate stress response immediately after a traumatic event may be a promising treatment development for PTSD (Searcy et al., 2012 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio24a) ).
Section Review
Posttraumatic Stress Disorder
LO 17.5 List the symptoms of PTSD.
Symptoms of PTSD include recurrent dreams or recollections of the event; feelings that the traumatic event is recurring (“flashback” episodes); and intense psychological distress, such as difficulty falling or staying asleep, irritability, outbursts of anger, difficulty in concentrating, and heightened reactions to sudden noises or movements.
LO 17.6 Describe the roles of genetic and environmental factors in the development of PTSD.
The risk for developing PTSD depends on both genetic and environmental factors. Environmental factors can include number of traumatic events experienced, and danger or violence from other
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people, such as assault, rape, or wartime experiences. Predisposing genetic factors appear to involve differences in the genes for D2 receptors, dopamine transporters, and 5-HT transporters. Decreased
hippocampal volume is a predisposing factor for the development of PTSD.
LO 17.7 Describe changes in the brain associated with PTSD.
Reduced volume and damage to the hippocampus is associated with PTSD. The prefrontal cortex of people who are resistant to the development of PTSD following severe stress appears to inhibit the amygdala. The prefrontal cortex appears to be hypoactive in people with PTSD. TBI and PSTD are found to co-occur and may involve overlapping brain changes.
LO 17.8 Summarize treatments for PTSD.
Treatments for PTSD include psychotherapy and antidepressants. Transcranial magnetic stimulation of the dorsolateral prefrontal cortex appears to reduce the symptoms of PTSD. Interventions to prevent developing PTSD following a traumatic event are currently being studied.
Thought Question
As an intern in a community mental health organization, your supervisor has asked you to help design educational materials for PTSD. Your supervisor tells you that some community members do not believe that PTSD has a biological basis. Because of this belief, many people do not seek treatment. Write an e-mail to your supervisor describing promotional materials you would design explaining the brain changes associated with PTSD. In your e-mail, include information about how therapeutic treatment can produce changes in the brain.
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17.3 Anxiety Disorders Anxiety disorders (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/glos01#ch17gloss19) are characterized by unrealistic, unfounded fear and anxiety. With a lifetime prevalence of approximately 28 percent, anxiety disorders are the most common psychiatric disorders. In addition, anxiety disorders contribute to the occurrence of depressive and substance abuse disorders (Tye et al., 2011 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio94) ). This section describes four anxiety disorders with evidence for contributing biological factors: panic disorder, agoraphobia, generalized anxiety disorder, and social anxiety disorder. Although obsessive-compulsive disorder has traditionally been classified as an anxiety disorder, it has different symptoms from the other anxiety disorders and involves different brain regions, so it is discussed separately in the next section.
Symptoms LO 17.9 List the symptoms of anxiety disorders.
People with panic disorder (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/glos01#ch17gloss20) suffer from episodic attacks of acute anxiety—periods of acute and unremitting terror that grip them for variable lengths of time, from a few seconds to a few hours. The prevalence of this disorder is approximately 3–5 percent among adults in the United States (Schumacher et al., 2011 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio95) ); however, rates are lower in Asian, African, and Latin American countries (approximately 0.1–0.8 percent; Lewis-Fernández et al., 2010 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio16a) ). Cultural differences and expectations are involved in the experiences of panic disorder (American Psychiatric Association, 2013 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio60) ). Women are approximately twice as likely as men to suffer from panic disorder, and this difference emerges in early adolescence (American Psychiatric Association, 2013 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio60) ). Some research has associated differences in the COMT gene with panic disorder in females; however, many factors are likely involved (Domschke et al., 2007 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio9a) ).
Panic attacks include many physical symptoms, such as shortness of breath, clammy sweat, irregularities in heartbeat, dizziness, faintness, and feelings of unreality. The victim of a panic attack often feels that he or she is going to die and often seeks help in a hospital emergency room. Between panic attacks many people with panic disorder suffer from anticipatory anxiety (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/glos01#ch17gloss21) —the fear that another panic attack will strike them.
This anticipatory anxiety is a symptom of another anxiety disorder: agoraphobia (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/glos01#ch17gloss22) (agora means “open space”). The symptoms of agoraphobia include intense fear or anxiety about leaving home, being in open spaces, or being in enclosed spaces or in lines or crowds. People with agoraphobia may avoid these situations and experience fear or anxiety about these situations that is out of proportion to the actual
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threat or danger they pose. Agoraphobia can be severely disabling; some people with this disorder have stayed inside their homes for years, afraid to venture outside where they might have a panic attack in public.
The primary characteristics of generalized anxiety disorder (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/glos01#ch17gloss23) are excessive anxiety and worry, difficulty in controlling these symptoms, clinically significant signs of distress and disruption of people’s lives. The prevalence of generalized anxiety disorder is approximately 3 percent, and the incidence is approximately two times greater in women than in men. People of European descent and individuals from developed countries experience generalized anxiety disorder more frequently than those of non-European descent or from developing countries (Lewis-Fernández et al., 2010 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio16a) ).
Social anxiety disorder (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/glos01#ch17gloss24) (also called social phobia) is a persistent, excessive fear of being exposed to the scrutiny of other people that leads to avoidance of social situations in which the person is called on to perform (such as speaking or performing in public). If such situations are unavoidable, the person experiences intense anxiety and distress. The prevalence of social anxiety disorder, which is almost equally likely in men and women, is approximately 5 percent. In the United States, non-Hispanic Caucasian individuals experience higher rates of social anxiety disorder than persons of Asian, Latino, African American, and Afro-Caribbean descent (Lewis-Fernández et al., 2010 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio16a) ). The experience of social anxiety disorder differs by culture. In Japan and Korea, individuals may experience taijin kyofusho or anxiety that the person is making others uncomfortable. Research suggests that both taijin kyofusho and social anxiety disorders symptoms can be effectively treated with drugs that increase activity in the serotonin system, suggesting shared neural networks (Stein, 2009 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio28a) ). (See Table 17.2 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec3#ch17tbl2) .)
Table 17.2 Symptoms of Anxiety Disorders
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Panic Disorder Agoraphobia Generalized Anxiety Disorder
Social Anxiety Disorder
Panic attacks, consisting of physiological symptoms, intense discomfort, and intense fear with a rapid onset within a few minutes
Fear or anxiety related to situations, such as being in a crowd or a place from which escape is difficult, or being outside of a safe place and alone
Excessive anxiety and worry across many different situations and contexts
Fear or anxiety in situations that can include evaluation by others
Persistent worry about the occurrence of panic attacks
Fear of the situation is disproportionate to the actual context
Worry that is difficult to control
Social situations are avoided
Changes in behavior, such as avoiding places in which panic attacks have occurred
Avoidance of the situations that cause fear or anxiety
Restlessness, fatigue, problems with memory or concentration, tension, and insomnia
Intense fear in social situations that cannot be avoided
Source: Based on American Psychiatric Association, 2013.
Heritability LO 17.10 Describe the roles of genetic and environmental factors in the development of anxiety
disorders.
Family studies and twin studies indicate that panic disorder, generalized anxiety disorder, and social anxiety disorder all have a hereditary component (Hettema et al., 2001 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio103) ; Merikangas and Low, 2005 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio104) ). Genetic investigations indicate that variations in the gene that encodes production of the BDNF protein may play a role in anxiety disorders. BDNF regulates neuronal survival and differentiation during development, plays a role in long-term potentiation and memory, and is associated with anxiety and depression (Yu et al., 2009 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio105) ). A particular allele of the BDNF gene (Val66Met) impairs extinction of conditioned fear memory in both humans and mice, and results in atypical activity of frontal cortex–amygdala circuitry. This allele does not normally occur in mice, but it can be inserted into their genome. Soliman et al., (2010 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio106) ) found that the presence of the Val66Met allele altered the circuitry of the vmPFC and impaired the extinction of a conditioned fear response in both mice and humans. In addition, the presence of this allele decreased the activity of the vmPFC during extinction.
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Panic attacks can be triggered in people with a history of panic disorder by a variety of treatments that activate the autonomic nervous system, such as through injections of lactic acid (a by-product of muscular activity), yohimbine (an α2 adrenoreceptor antagonist), or doxapram (a drug used by anesthesiologists to increase breathing rate) or by breathing air containing an elevated amount of carbon dioxide (Stein and Uhde, 1995 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio107) ). Lactic acid and carbon dioxide both increase heart rate and rate of respiration, just as exercise does; yohimbine has direct pharmacological effects on the nervous system.
Brain Changes LO 17.11 Describe changes in the brain associated with anxiety disorders.
Functional-imaging studies suggest that the amygdala and the cingulate, prefrontal, and insular cortexes are involved in anxiety disorders. Fischer et al. (1998 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio108) ) witnessed an unexpected panic attack in a participant while her regional cerebral blood flow was being measured by a PET scanner. They observed decreased activity in the right orbitofrontal cortex and anterior cingulate cortex. Pfleiderer et al. (2007 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio109) ) also observed a panic attack in a participant undergoing fMRI scanning and saw increased activity in the amygdala. Phan et al. (2005 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio110) ) found that people with social anxiety disorder showed increases in the activation of the amygdala when they looked at pictures of faces with angry, disgusted, or fearful expressions. In addition, the activation of the amygdala was positively correlated with the severity of the people’s symptoms. Monk et al. (2008 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio111) ) found that adolescents with generalized anxiety disorder showed increased activation of the amygdala and decreased activation of the ventrolateral prefrontal cortex while looking at angry faces. They also found evidence that activation of the ventromedial prefrontal cortex (vmPFC) suppressed amygdala activation in healthy control participants but not in those with anxiety disorder. (As you will recall from Chapter 11 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch11#ch11) , the vmPFC plays a critical role in extinction and inhibition of fear and anxiety.) Stein et al. (2007 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio112) ) found that college students with a high level of anxiety (but without a diagnosis of one of the anxiety disorders) showed increased activation of the amygdala and the insular cortex, both of which correlated positively with students’ anxiety measures.
Tye et al. (2011 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio94) ) found that optogenetic stimulation of the terminals of neurons of the basolateral nucleus of the amygdala that formed synapses with neurons in the central nucleus caused an immediate termination of anxious behavior of mice. Conversely, optogenetic inhibition of these same terminals induced anxious behaviors. Optogenetic methods, described in Chapter 5 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch05#ch05) , hold the promise of discovery of the neural circuits involved in the development and control of anxiety.
Treatment LO 17.12 Summarize treatments for anxiety disorders.
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Anxiety disorders are sometimes treated with benzodiazepines. As we just saw, increased activity of the amygdala is a common feature of the anxiety disorders. The amygdala contains a high concentration of GABAA receptors, which are the target of the benzodiazepines. (See Figure 17.17.) Paulus et al. (2005
(http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio114) ) found that administration of a benzodiazepine (lorazepam) decreased the activation of both the amygdala and the insula of participants looking at emotional faces. Administration of flumazenil, a benzodiazepine antagonist (having an action opposite that of benzodiazepines), produces panic in patients with panic disorder but not in control participants (Nutt et al., 1990 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio115) ).
Critical Concepts
Benzodiazepines are often used for emergency medical treatment of anxiety disorders because the therapeutic effects of these drugs have a rapid onset. However, they are less appropriate for long-term treatment. They cause sedation, they induce tolerance and withdrawal symptoms, and they have a potential for abuse. For these reasons, researchers have been seeking other drugs to treat anxiety disorders. Benzodiazepines exert their effects by interacting with GABAA receptors at a specific binding
site (Sigel and Buhr, 1997 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio25a) ). Chemicals that activate one of the known binding sites on this receptor, the neurosteroid binding site, enhance the activity of the GABAA receptor. During anxiety attacks, the synthesis of neurosteroids—and hence the activity of
the GABAA receptor—is suppressed. A recently developed drug, XBD173, enhances the synthesis of
neurosteroids and hence increases the activity of the GABAA receptor. Tests with human patients have
shown that the drug reduces panic and does not produce sedation or withdrawal symptoms after seven days of treatment (Nothdurfter et al., 2011 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio117) ). Thus, this drug appears to be a promising candidate for treatment of anxiety disorders.
Figure 17.17 Benzodiazepines Bind to GABAA Receptors
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As we saw in Chapter 16 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch16#ch16) , serotonin appears to play a role in depression. Much evidence suggests that serotonin plays a role in anxiety disorders, too. Even though the symptoms of the anxiety disorders discussed in this subsection are very different from those of obsessive-compulsive disorder (described in the next section), specific serotonin reuptake inhibitors (SSRIs; such as fluoxetine), which serve as potent serotonin agonists, have become the first-line medications for treating all of these disorders—preferably in combination with cognitive behavior therapy (Asnis et al., 2001 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio118) ; Ressler and Mayberg, 2007 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio119) ). Figure 17.18 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec3#ch17fig18) shows the effect of fluvoxamine, an SSRI, on the number of panic attacks in patients with panic disorder. (See Figure 17.18 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec3#ch17fig18) .)
Figure 17.18 Fluvoxamine and Panic Disorder The graph shows the effects of fluvoxamine (an SSRI) on the severity of panic disorder.
(Based on data from Asnis et al., 2001.)
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As we also saw in Chapter 16 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch16#ch16) , administration of indirect agonists of the NMDA receptor that attach to the glycine binding site have been used experimentally to successfully treat the symptoms of schizophrenia. Preliminary research suggests that the same may be true for anxiety disorders. Several studies have successfully used D-cycloserine (DCS) in conjunction with cognitive behavior therapy to treat patients with anxiety disorders. For example, studies have shown that DCS facilitates treatment of social anxiety disorder and panic disorder. (See Figure 17.19 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec3#ch17fig19) .)
Figure 17.19 D-Cycloserine and Anxiety Disorders The graphs show the effects of D-cycloserine (DCS) and placebo in conjunction with cognitive behavior therapy on the symptoms of acrophobia (fear of heights), social phobia, and panic disorder.
(Based on data from Ressler et al., 2004 [acrophobia], Guastella et al., 2010b [social phobia], and Otto et al., 2010 [panic disorder]).
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In the treatment of anxiety disorders, cognitive behavior therapy often uses procedures that desensitize patients to the objects or situations they fear. For example, Ressler et al. (2004
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(http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio120) ) used a computer program to expose their patients to a virtual glass elevator, gradually bringing them higher and higher from the ground. This procedure appears to work by extinguishing a conditioned emotional response. In fact, a study by Walker et al. (2002 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio121) ) found that injections of D-cycloserine facilitated the extinction of a conditioned emotional response in rats. The drug had no effect on performance of a conditioned emotional response unless it was administered along with extinction training. Injections of the drug by itself had no effect. Presumably, D-cycloserine exerts its therapeutic effect by augmenting the ability of cognitive behavior therapy to extinguish fear responses.
Section Review
Anxiety Disorders
LO 17.9 List the symptoms of anxiety disorders.
The anxiety disorders are characterized by unrealistic, unfounded fear and anxiety. Panic disorder is characterized by panic attacks that include physical symptoms of excessive autonomic activation and anticipatory anxiety. Agoraphobia includes intense fear or anxiety in unfamiliar situations or situations from which escape would be difficult. Generalized anxiety disorder includes excessive fear and worry across many different situations. Social anxiety disorder includes fear and worry in social situations.
LO 17.10 Describe the roles of genetic and environmental factors in the development of anxiety disorders.
Family and twin studies support a genetic component to anxiety disorders. Genes for BDNF likely play a role in anxiety disorders. Environmental factors contributing to the experience of anxiety disorders are supported by laboratory studies of lactic acid and carbon dioxide used to induce panic attacks.
LO 17.11 Describe changes in the brain associated with anxiety disorders.
Functional-imaging and optogenetic studies suggest that increased activity in the amygdala and decreased activity in the prefrontal cortex are involved in anxiety disorders. Other research suggests that the cingulate and insular cortexes are also involved.
LO 17.12 Summarize treatments for anxiety disorders.
Anxiety disorders can be treated with benzodiazepines, SSRIs, cognitive behavioral therapy, densensitization procedures, and D-cycloserine
Thought Question
Most reasonable people would agree that a person with a mental disorder cannot be blamed for his or her thoughts and behaviors. For example, most of us would sympathize with someone whose life is disrupted by panic attacks, and we would not see their plight as a failure of will power. After all, whether these disorders are caused by traumatic experiences or brain abnormalities (or both), the afflicted person has not chosen to experience these symptoms. But what about less dramatic examples: Should we blame people for their shyness or hostility or other maladaptive personality traits? If, as many psychologists believe, people’s personality characteristics are largely determined by their
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heredity (and thus by the structure and chemistry of their brains), what are the implications for our concepts of “blame” and “personal responsibility”?
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17.4 Obsessive-Compulsive Disorder As the name implies, people with an obsessive-compulsive disorder (OCD) (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/glos01#ch17gloss25) suffer from obsessions— (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/glos01#ch17gloss26) persistent and involuntary thoughts, images, or urges that will not leave them—and compulsions— (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/glos01#ch17gloss27) behaviors that they cannot keep from performing. The incidence of obsessive-compulsive disorder is 1–2 percent both in the United States and internationally. Females are slightly more likely than males to have this diagnosis. The symptoms of OCD most commonly begin in young adulthood (Robbins et al., 1984 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio122) ).
Symptoms LO 17.13 List the symptoms of OCD.
Obsessions include concern or disgust with bodily secretions, dirt, germs, and the like; fear that something terrible might happen; or a need for symmetry, order, or exactness. Most compulsions fall into one of four categories: counting, checking, cleaning, and avoidance. For example, people might repeatedly check burners on the stove to see that they are off and windows and doors to be sure that they are locked. Some people will wash their hands hundreds of times a day, even if their hands become covered with painful sores. Other people meticulously clean their house or endlessly wash, dry, and fold their clothes. Some become afraid to leave home because they fear contamination, and refuse to touch other members of their family. If they do accidentally become “contaminated,” they usually have lengthy purification rituals.
Obsessions are seen in a variety of mental disorders, including schizophrenia. However, unlike people with schizophrenia, people with obsessive-compulsive disorder recognize that their thoughts and behaviors are irrational. Compulsions often become more and more demanding until they interfere with people’s careers and daily lives. Although OCD is often associated with the other anxiety disorders, it is now believed to more closely align with other disorders that feature dysfunctional thoughts and repetitive behaviors such as hoarding or trichotillomania (hair-pulling disorder) (American Psychiatric Association, 2013 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio60) ). (See Table 17.3 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec4#ch17tbl3) .)
Some investigators believe that the compulsive behaviors seen in OCD are forms of species-typical behaviors—for example, grooming, cleaning, and attention to sources of potential danger—that are released from normal control mechanisms by a brain dysfunction (Rapoport and Wise, 1988 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio124) ). Fiske and Haslam (1997 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio125) ) suggest that the behaviors seen in OCD are simply pathological examples of typical human behaviors to develop and practice social rituals. For example, people perform cultural rituals to mark transitions or changes in social status, to diagnose or treat illnesses, to restore relationships with deities, or to ensure the success of hunting or planting. Consider the following scenario (from Fiske and Haslam, 1997 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio125) ):
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Imagine that you are traveling in an unfamiliar country. Going out for a walk, you observe a man dressed in red, standing on a red mat in a red-painted gateway. . . . He utters the same prayer six times. He brings out six basins of water and meticulously arranges them in a symmetrical configuration in front of the gateway. Then he washes his hands six times in each of the six basins, using precisely the same motions each time. As he does this, he repeats the same phrase, occasionally tapping his right finger on his earlobe. Through your interpreter, you ask him what he is doing. He replies that there are dangerous polluting substances in the ground, . . . [and that] he must purify himself or something terrible will happen. He seems eager to tell you about his concerns. (p. 211 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch07lev1sec3#page_211) )
Why is the man acting this way? Is he a priest following a sacred ritual, or does he have obsessive- compulsive disorder? Without knowing more about the rituals followed by the man’s culture, we cannot say. Fiske and Haslam compared the features of OCD and other psychological disorders in descriptions of rituals, work, or other activities in 52 cultures. They reported that the features of OCD were found in rituals in these cultures. The features of other psychological disorders were much less common. On the whole, the evidence suggests that the symptoms of OCD represent an exaggeration of typical human behavior.
Zhong and Liljenquist (2006 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio127) ) found that students at Northwestern University in the United States, apparently unknowingly consider cleansing rituals to “wash away their sins.” The investigators had the participants recall in detail either an ethical or an unethical deed they had committed in the past. Later, they were asked to complete some word fragments by filling in letters where blanks occurred. Some word fragments could be made into words that did or did not pertain to cleansing. For example, W—H, SH–ER, and S–P could be wash, shower, and soap, or they could be wish, shaker, and step. The participants who had described a misdeed were much more likely to think of cleansing-related words. And when offered a free gift—either a pencil or an antiseptic wipe—participants who described a misdeed were more likely to choose the antiseptic wipe.
Table 17.3 Symptoms of Obsessive-Compulsive Disorder
Obsessive-Compulsive Disorder
Obsessions: Recurring and unwanted concerns, thoughts, or urges that can cause anxiety or distress; attempts may be made to ignore or suppress the obsessions, often by performing a compulsive behavior
Compulsions: Repetitive behaviors performed in response to an obsession; compulsions prevent or decrease anxiety or distress related to the obsessions
Obsessions and compulsions take time away from other activities and reduce quality of life for the individual
Source: Based on American Psychiatric Association, 2013.
Heritability
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LO 17.14 Describe the roles of genetic and environmental factors in the development of OCD.
Evidence indicates that hereditary factors play at least some part in the development of obsessive- compulsive disorder. Several studies have found a greater concordance for obsessions and compulsions in monozygotic twins than in dizygotic twins (Hettema et al., 2001 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio103) ). Family studies have found that OCD is associated with a neurological disorder that appears during childhood (Pauls and Leckman, 1986 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio129) ; Pauls et al., 1986 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio130) ). This disorder, Tourette’s syndrome, (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/glos01#ch17gloss28) is characterized by muscular and vocal tics: facial grimaces, squatting, pacing, twirling, barking, sniffing, coughing, grunting, or repeating specific words (especially vulgarities). Leonard et al. (1992a (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio131) , 1992b (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio132) ) found that many patients with obsessive-compulsive disorder had tics and that many patients with Tourette’s syndrome showed obsessions and compulsions. Grados et al. (2001 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio133) ) found a family association between OCD and tic disorders (a broad category that includes Tourette’s syndrome). Both groups of investigators believe that the two disorders are produced by the same underlying genotype. It is not clear why some people with this genotype develop Tourette’s syndrome and others develop obsessive- compulsive disorder.
As with schizophrenia, not all cases of OCD have a genetic origin; the disorder sometimes occurs after brain damage caused by various means, such as birth trauma, encephalitis, and head trauma (Berthier et al., 1996 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio134) ; Hollander et al., 1990 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio135) ). In particular, the symptoms appear to be associated with damage to or dysfunction of the basal ganglia, cingulate gyrus, and prefrontal cortex (Giedd et al., 1995 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio136) ; Robinson et al., 1995 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio137) ).
Tic disorders (including OCD) can be caused by a group A β-hemolytic streptococcal infection (Kawikova et al., 2010 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio138) ; Perlmutter et al., 1998 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio139) ). This infection can trigger several autoimmune diseases, in which the patient’s immune system attacks and damages certain tissues of the body, including the valves of the heart, the kidneys, and—in this case—parts of the brain. Figure 17.20 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec4#ch17fig20) shows the parallel course of a child’s symptoms and the level of antistreptococcal DNA-B in her blood, which indicates the presence of an active infection.
Figure 17.20 OCD and Streptococcal Hemolytic Infection The graph shows the parallel course of a child’s symptoms and the level of antistreptococcal DNA-B in her blood, which indicates the presence of an active infection. This relationship provides evidence that a group A β-hemolytic
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streptococcal infection can produce tics and the symptoms of OCD, presumably by affecting the basal ganglia.
(Based on data from Perlmutter et al., 1998.)
The symptoms of OCD appear to be produced by damage to the basal ganglia. Bodner et al., (2001 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio140) ) report the case of a 25-year-old man whose untreated sore throat developed into an autoimmune disease that produced obsessions and compulsions. The investigators found antibodies to type A β-hemolytic streptococcus, and MRI scans indicated abnormalities in the basal ganglia. An MRI study of 34 children with streptococcus- associated tics or OCD by Giedd et al., (2000 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio141) ) found an increase in the size of the basal ganglia that they attributed to an autoimmune inflammation of this region.
Brain Changes LO 17.15 Describe changes in the brain associated with OCD.
Several functional-imaging studies have found evidence of increased activity in the frontal lobes and caudate nucleus in patients with OCD. A review by Whiteside et al. (2004 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio142) ) found that functional-imaging studies consistently found increased activity of the caudate nucleus and the orbitofrontal cortex. Guehl et al., (2008 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio143) ) inserted microelectrodes into the caudate nuclei of three patients with OCD who were being evaluated for neurosurgery. They found that two of the patients, who reported the presence of obsessive thoughts during the surgery, showed increased activity in neurons in the caudate nucleus. The third patient, who did not report obsessive thoughts, showed a lower rate of neural activity.
A review by Saxena et al. (1998 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio144) ) described several studies that measured regional brain activity in patients with OCD before and after successful treatment
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with drugs or cognitive behavior therapy. In general, the improvement in a patient’s symptoms was correlated with a reduction in the activity of the caudate nucleus and orbitofrontal cortex. The fact that cognitive behavioral therapy and drug therapy produced similar results is especially remarkable: It indicates that very different procedures may bring about physiological changes that alleviate a serious mental disorder.
Treatment LO 17.16 Summarize treatments for OCD.
Three drugs are regularly used to treat the symptoms of OCD: clomipramine, fluoxetine, and fluvoxamine. These effective antiobsessional drugs are specific blockers of 5-HT reuptake; thus, they are serotonergic agonists. In general, serotonin has an inhibitory effect on species-typical behaviors, which has tempted several investigators to speculate that these drugs alleviate the symptoms of obsessive-compulsive disorder by reducing the strength of innate tendencies for counting, checking, cleaning, and avoidance behaviors that may underlie this disorder. Brain regions that have been implicated in OCD, including the orbitofrontal cortex and the basal ganglia, receive input from serotonergic terminals (El Mansari and Blier, 1997 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio145) ; Lavoie and Parent, 1990 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio146) ).
The importance of serotonergic activity in inhibiting compulsive behaviors is underscored by three interesting compulsions: trichotillomania, onychophagia, and acral lick dermatitis. Trichotillomania is compulsive hair pulling. People with this disorder (almost always females) often spend hours each night pulling hairs out one by one, sometimes eating them (Rapoport, 1991 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio147) ). Onychophagia is compulsive nail biting, which in its extreme can cause severe damage to the ends of the fingers. (For those who are sufficiently agile, toenail biting is not uncommon.) Double-blind studies have shown that both of these disorders can be treated successfully by clomipramine, the drug of choice for OCD (Leonard et al., 1992a (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio131) ).
Acral lick dermatitis is a disease of dogs, not humans. Some dogs will continuously lick at a part of their body, especially their wrist or ankle (called the carpus and the hock). The licking removes the hair and often erodes away the skin as well. The disorder seems to be genetic; it is seen almost exclusively in large breeds such as Great Danes, Labrador retrievers, and German shepherds, and it runs in families. A double- blind study found that clomipramine reduces this compulsive behavior (Rapoport et al., 1992 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio149) ).
We saw in the previous subsection that an NMDA receptor agonist, D-cycloserine, appears to be useful in treating the symptoms of a variety of anxiety disorders. This drug appears to help in the treatment of the symptoms of OCD as well. A double-blind study by Wilhelm et al. (2008 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio150) ) found that compared with patients who received a placebo, patients who received D-cycloserine along with sessions of cognitive behavior therapy showed a greater decrease in their obsessive symptoms and retained this improvement after the sessions ended. Presumably, the drug facilitated the extinction of the maladaptive thoughts and behaviors, just as it facilitates the extinction of conditioned emotional responses in patients with anxiety disorders. (See Figure 17.21 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec4#ch17fig21) .)
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Figure 17.21 D-Cycloserine and OCD The graph shows the effects of D-cycloserine and placebo in conjunction with cognitive behavior therapy on the symptoms of obsessive-compulsive behavior.
(Based on data from Wilhelm et al., 2008.)
Some patients with severe OCD have been successfully treated with cingulotomy—surgical destruction of specific fiber bundles in the subcortical frontal lobe, including the cingulum bundle (which connects the prefrontal and cingulate cortexes with the limbic cortex of the temporal lobe) and a region that contains fibers that connect the basal ganglia with the prefrontal cortex (Ballantine et al., 1987 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio151) ; Mindus et al., 1994 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio152) ). These operations have a reasonably good success rate (Dougherty et al., 2002 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio153) ). Another reasonably successful surgical procedure, capsulotomy, destroys a region of a fiber bundle (the internal capsule) that connects the caudate nucleus with the medial prefrontal cortex (Rück et al., 2008 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio154) ). Brain lesions cannot be undone, so such procedures must be considered only as a last resort. As Rück et al. report, some patients suffer from adverse side effects after surgery, such as problems of planning, apathy, or difficulty inhibiting socially inappropriate behavior.
As we saw in Chapter 15 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch15#ch15) , deep brain stimulation (DBS) has been found to be useful in treating the symptoms of Parkinson’s disease. Because OCD, like Parkinson’s disease, appears to involve abnormalities in the basal ganglia, several clinics
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have tried to use DBS of the basal ganglia or fiber tracts connected with them to treat this disorder. This form of therapy appears to reduce the symptoms of OCD in some patients (Abelson et al., 2005 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio155) ; Larson, 2008 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio156) ). Le Jeune et al. (2010 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio157) ) found that DBS of the subthalamic nucleus, which plays an integral role in the cortical–basal ganglia circuitry, reduces the symptoms of OCD. One of the more modern forms of psychosurgery is destruction of the internal capsule. Goodman et al. (2010 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio158) ) found that DBS of the internal capsule reduced the symptoms of OCD in four of six patients with severe, treatment-resistant OCD. A significant benefit of DBS is that, unlike psychosurgical procedures that destroy brain tissue, it is reversible: If no benefit is obtained from the stimulation, the electrodes can be removed.
As we saw in Chapters 8 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch08#ch08) and 14 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch14#ch14) , the principal parts of the basal ganglia, the caudate nucleus and the putamen, receive information from the cerebral cortex. As this information is processed by the basal ganglia, it flows through two pathways before it passes to the thalamus and is sent back to the cortex. The direct pathway is excitatory, and the indirect pathway is inhibitory. (See Figure 17.22 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec4#ch17fig22) .) Saxena et al. (1998 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio144) ) suggest that the symptoms of OCD may be a result of overactivity of the direct pathway. They propose that one of the functions of this pathway is control of previously learned behavior sequences that have become automatic so that they can be executed rapidly. The orbitofrontal cortex, which is involved in recognizing situations that have personal significance, can activate this pathway and the behaviors that it controls. The inhibitory indirect pathway is involved in suppressing these automatic behaviors, permitting the person to switch to other, more adaptive behaviors. Thus, obsessive-compulsive behavior could be a result of an imbalance between the direct and indirect pathways.
Figure 17.22 Direct and Indirect Pathways in the Basal Ganglia (a) The locations of the components of the basal ganglia and associated structures. (b) The major connections of the basal ganglia and associated structures. Excitatory connections are shown as black lines; inhibitory connections are shown as red lines.
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Section Review
Obsessive-Compulsive Disorder
LO 17.13 List the symptoms of OCD.
Obsessive-compulsive disorder (OCD) is characterized by obsessions—unwanted thoughts—and compulsions—uncontrollable behaviors, especially those involving cleanliness and attention to danger.
LO 17.14 Describe the roles of genetic and environmental factors in the development of OCD.
OCD has a heritable basis and is related to Tourette’s syndrome, a neurological disorder characterized by tics and vocalizations. It can also be caused by brain damage at birth, encephalitis, and head injuries, especially when the basal ganglia are involved. A type A β-hemolytic streptococcus infection can stimulate an autoimmune attack—presumably on the basal ganglia—that produces symptoms of OCD.
LO 17.15 Describe changes in the brain associated with OCD.
Functional imaging indicates that people with obsessive-compulsive disorder tend to show increased activity in the orbitofrontal cortex, cingulate cortex, and caudate nucleus. Drug treatment or cognitive behavior therapy that successfully reduces the symptoms of OCD generally reduces the activity of the orbitofrontal cortex and caudate nucleus.
LO 17.16 Summarize treatments for OCD.
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The most effective drugs for treating OCD are SSRIs such as clomipramine, fluoxetine, and fluvoxamine. Three other compulsions—hair pulling, nail biting, and (in dogs) acral lick syndrome—are also suppressed by clomipramine. In conjunction with cognitive behavior therapy, D-cycloserine, which acts as an indirect agonist at NMDA receptors, also appears to reduce the symptoms of OCD. Some investigators believe that clomipramine and related drugs alleviate the symptoms of OCD by increasing the activity of serotonergic pathways that play an inhibitory role in species-typical behaviors. In severe cases of OCD that do not respond to other treatments, surgical procedures such as cingulotomy and capsulotomy may provide relief. Deep brain stimulation with implanted electrodes has been shown to be effective in some patients and, unlike cingulotomy and capsulotomy, has the benefit of being reversible.
Thought Question
Imagine that you have a relative who was recently diagnosed with obsessive-compulsive disorder. You learn that your loved one is struggling to decide which treatment strategy is best for them. Your relative calls you to ask about which treatment strategies have brain-based evidence to support them. To help your relative be informed in making this difficult decision, briefly outline the treatments and explain their effects in the nervous system.
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17.5 Autism Spectrum Disorder The following sections of this chapter discuss two neurodevelopmental disorders: autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). Characteristics of ASD and ADHD are present very early in life. Both ASD and ADHD have a higher prevalence among males. Our focus first will be on ASD.
Parents typically expect to love and cherish their child and to be loved and cherished in return. Unfortunately, some infants are born with a disorder that impairs their ability to return their parents’ affection. The symptoms of autism spectrum disorder (ASD) (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/glos01#ch17gloss29) (often simply referred to as autism) include a failure to develop typical social relations with other people, impaired development of communicative ability, and the presence of repetitive, stereotyped behaviors, fixated interests, or inflexible adherence to routines Most people with ASD display cognitive impairments. The syndrome was named and characterized by Kanner (1943 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio160) ), who chose the term (auto, “self,” -ism, “condition”) to refer to the child’s apparent self-absorption.
The prevalence of ASD is approximately 1 percent in both the United States and other countries (Brugha et al., 2011 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio3a) ). The disorder is four times more common in males than in females. However, if only cases of autism with intellectual disability are considered, the ratio falls to 2:1, and if only cases of high-functioning autism are considered (those with average or above-average intelligence and reasonably good communicative ability), the ratio rises to approximately 7:1 (Fombonne, 2005 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio162) ). These data suggest that the social impairments are much more common in males, but the cognitive and communicative impairments are more evenly shared by males and females. A related diagnosis, Rett syndrome is a genetic neurological syndrome seen in girls that accompanies an arrest of normal brain development that occurs during infancy.
At one time, clinicians believed that ASD was more prevalent in families with higher socioeconomic status, but more recent studies have found that the frequency of diagnosis is the same in all socioeconomic classes. The reported incidence of ASD has increased in the past two decades, but evidence indicates that the apparent increase is a result of heightened awareness of the disorder and broadening of the diagnostic criteria.
Studies have failed to find evidence that autism is linked to childhood immunization with vaccines. In fact, the investigator who originally claimed to have obtained evidence for a linkage between immunization and autism was found guilty of dishonesty by the U.K. General Medical Council, and the article that first made this claim was retracted by the journal that published it, The Lancet (Dwyer, 2010 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio163) ).
Symptoms LO 17.17 List the symptoms of ASD.
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According to the DSM-5, a diagnosis of autism spectrum disorder requires the presence of two broad categories of symptoms: “persistent impairment in reciprocal social communication and social interaction”, as well as “restricted, repetitive patterns of behavior, interests, or activities. These symptoms are present from early childhood and limit or impair everyday functioning” (American Psychiatric Association, 2013, (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio60) p. 53 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch02lev1sec3#page_53) ). Social impairments are the first symptoms to emerge. Infants with ASD may appear ambivalent to being held, or they may arch their backs when picked up, as if they do not want to be held. They do not look or smile at their caregivers. If they are ill, hurt, or tired, they will not look to someone else for comfort. As they get older, they do not enter into social relationships with other children and will avoid eye contact with people. In severe cases, individuals with ASD may not seem to recognize the existence of other people.
The language development of people with autism spectrum disorder may be abnormal, delayed, or nonexistent. People with ASD often echo what is said to them, and they may refer to themselves as others do—in the second or third person. For example, they may say, “You want some milk?” to mean “I want some milk.” They may learn words and phrases by rote, but they fail to use them productively and creatively. Those who do acquire reasonably good language skills may talk about their own preoccupations without understanding other people’s interests. People with ASD may interpret other people’s speech literally. For example, when a person with ASD is asked, “Can you pass the salt?,” the response might simply be “Yes”—and not because they are trying to be funny or sarcastic.
People with autism spectrum disorder may show unusual interests and behaviors. For example, they may show stereotyped movements, such as flapping their hand back and forth or rocking back and forth. They may become obsessed with investigating objects, sniffing them, feeling their texture, or moving them back and forth. They may become attached to a particular object and insist on carrying it around with them. They may become preoccupied in lining up objects or in forming patterns with them, oblivious to everything else that is going on around them. Individuals with ASD often insist on following precise routines and may become upset when they are hindered from doing so. They show no make-believe play and are not interested in stories that involve fantasy. Although many people with ASD have impaired cognitive abilities, not everyone with this diagnosis does. Some individuals with ASD may be physically adept and graceful. Some have exceptional but isolated skills, such as the ability to multiply two four-digit numbers very quickly, without apparent effort. (See Table 17.4 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec5#ch17tbl4) .)
Table 17.4 Symptoms of Autism Spectrum Disorder
Autism Spectrum Disorder
Deficits in communication and social interaction across many situations
Limited or repetitive behaviors, interests, or activities
Symptoms are present in childhood
Source: Based on American Psychiatric Association, 2013.
Heritability LO 17.18 Describe the roles of genetic and environmental factors in the development of ASD.
Evidence indicates that autism spectrum disorder is strongly heritable. The best evidence for genetic factors comes from twin studies. These studies indicate that the concordance rate for ASD in monozygotic
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twins is approximately 70–90 percent, while the rate in dizygotic twins studied so far is approximately 5– 10 percent (Sebat et al., 2007 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio165) ). A study by Ozonoff et al. (2011 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio166) ) found that an infant with an older sibling with ASD has an 18.7 percent likelihood of developing the disorder. Having multiple older siblings with ASD increased the risk to 32.2 percent. Genetic studies indicate that ASD can be caused by a wide variety of rare mutations, especially those that interfere with neural development and communication (Betancur et al., 2009 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio167) ).
The fact that autism spectrum disorder is highly heritable is presumptive evidence that the disorder is a result of structural or biochemical abnormalities in the brain. In addition, a variety of medical disorders— especially those that occur during prenatal development—can produce the symptoms of autism. Evidence suggests that approximately 10 percent of all cases of ASD have definable biological causes, such as rubella (German measles) during pregnancy, prenatal thalidomide, encephalitis caused by the herpes virus, and tuberous sclerosis, a genetic disorder that causes the formation of benign tumors in many organs, including the brain (DeLong, 1999 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio168) ; Fombonne, 2005 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio162) ; Rapin, 1999 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio170) ). Ploeger et al. (2010 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio171) ) suggest that interference with a particular stage of prenatal development can cause ASD. Early organogenesis is a stage of embryonic development that occurs during days 20–40 after fertilization. During this stage, major organs are beginning to develop, and factors that interfere with typical development can cause many abnormalities, including limb deformities, malformations of the skull and face, and brain pathologies. In the 1960s, many pregnant women took thalidomide, a drug that suppressed the symptoms of morning sickness. Unfortunately, it was discovered later that this drug caused severe birth defects—including autism spectrum disorder. Because most women knew when they had taken thalidomide, the time of drug exposure could be correlated with the development of autism in the women’s children. It turned out that the sensitive period, during which exposure to thalidomide was most likely to cause the development of autism, was 20 to 36 days postfertilization, which coincides with the stage of early organogenesis. Presumably, drug-induced interference with typical brain development at this time set the stage for later development of ASD.
Brain Changes LO 17.19 Describe changes in the brain associated with ASD.
Evidence indicates significant changes in the development of the brains of children with autism spectrum disorder. Courchesne et al. (2005 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio172) , 2007 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio173) ) note that in ASD, although the brain is, on average, slightly smaller at birth, it begins to grow unusually quickly, and by two to three years of age it is about 10 percent larger than the brain of an age-matched, typically-developing child. Following this early spurt, grown in the brain of a person with ASD slows down, so by adolescence it is only about 1–2 percent larger than normal.
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Not all parts of the brain show the same pattern of growth in autism spectrum disorder. The regions that appear to be most involved in the functions that are impaired in autism show the greatest growth early in life and the slowest growth between early childhood and adolescence. For example, the frontal cortex and temporal cortex grow quickly during the first two years of life but then show little or no increase in size during the next four years in ASD, whereas these two regions grow by 20 percent and 17 percent, respectively, in typically-developing brains. However, the growth pattern of some regions of the cerebral cortex, such as the striate cortex and extrastriate cortex, are relatively typical in the brains of individuals with ASD. The amygdala also shows an unusual pattern of growth during development. By four years of age it is larger in children with ASD. By the time of early adulthood it is the same size as the amygdala of typically-developing people but contains fewer neurons (Schumann and Amaral, 2006 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio174) ).
The brains of people with autism also show changes in white matter. In a study of the brains of people with autism, Herbert et al. (2004 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio175) ) found that the volume of white matter containing short-range axons was increased but that the volume of white matter containing long-range axons that connect distant regions of the brain was not. Courchesne et al. (2005 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio172) , 2007 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio173) ) suggest that the production of excessive numbers of neurons early in development may cause the development of such a large number of short-range axons that the development of long-range axons is inhibited. The apparent hyperconnectivity of local regions of the cerebral cortex might possibly account for the exceptional isolated talents and skills shown by some people with ASD.
Frith et al., (1991 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio178) ) suggest that some of the social impairments of autism spectrum disorder stem from changes in the brain that prevent people from forming a “theory of mind.” That is, they are unable “to predict and explain the behavior of other humans in terms of their mental states” (p. 434 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch13lev1sec6#page_434) ). They cannot infer the thoughts, feelings, and intentions of other people from their emotional expressions, tone of voice, and behavior.
Researchers have employed structural- and functional-imaging methods to investigate the neural basis of the three categories of symptoms in autism spectrum disorder. For example, Castelli et al. (2002 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio179) ) showed typically- developing volunteers and high-functioning people with ASD animations that depicted two triangles interacting in various goal-directed ways (for example, chasing or fighting) or in a way that suggested that one triangle was trying to trick or coax the other. For example, one typically-developing volunteer described an animation in this way: “Triangles cuddling inside the house. Big wanted to persuade little to get out. He didn’t want to . . . cuddling again” (p. 1843). People with ASD were able to accurately describe the goal-directed interactions of the triangles, but they had difficulty accurately describing the “intentions” of a triangle trying to trick or coax the other. In other words, they had difficulty forming a theory of mind. Functional imaging during presentation of the animations showed normal activation of early levels of the visual association cortex (the extrastriate cortex), but activation of the superior temporal sulcus (STS) and the medial prefrontal cortex was much lower among people with autism. (See Figure 17.23 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec5#ch17fig23) .) Previous research has shown that the STS plays an important role in detection of stimuli that indicate the actions of another individual (Allison et al., 2000 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio180) ).
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Figure 17.23 Theory of Mind The graph shows relative activation of specific brain regions of adults with autism and control participants viewing a “theory of mind” animation of two triangles moving interactively with implied intentions. STS = superior temporal sulcus.
(Based on data from Castelli et al., 2002.)
The lack of interest in or understanding of other people by people with autism spectrum disorder is reflected in the response to the sight of the human face. As we saw in Chapter 6 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch06#ch06) , the fusiform face area (FFA), in the extrastriate cortex, is involved in the recognition of individual faces. A functional-imaging study by Schultz (2005 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio181) ) found little or no activity in the FFA of adults with autism spectrum disorder looking at pictures of human faces. (See Figure 17.24 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec5#ch17fig24) .) People with ASD have difficulty recognizing facial expressions of emotion or the direction of another person’s gaze and have low rates of eye contact with other people. In autism, it seems likely that the FFA fails to respond to the sight of the human face because very little time may be spent studying other people’s faces and hence expertise in interpersonal interactions does not develop. Grelotti et al. (2005 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio182) ) reported the case of a boy with ASD who had an extreme interest in Digimon cartoon characters. Functional imaging showed no activation of the FFA when the boy viewed photos of faces, but photos of Digimon characters evoked strong activation of this region. This case supports the conclusion that the failure of the sight of faces to activate the FFA in people with autism is caused by of lack of interest in or experience with faces, not by abnormalities in the FFA.
Figure 17.24 Fusiform Face Area and Autism Scans show activation of the fusiform face area in typically-developing peers, but not in people with autism while looking at pictures of human faces.
(Based on Schultz, R. T. International Journal of Developmental Neuroscience, 2005, 23, 125–141.)
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A study by Pelphrey et al. (2002 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio183) ) found that people with autism spectrum disorder who were asked to identify the emotions shown in photographs of faces failed to look at other people’s eyes, which are informative in making judgments of emotion. This tendency likely contributes to impairment in analyzing social information. The abnormal development of the amygdala in people with autism may be at least partly responsible for the low rates of eye contact with other people and difficulty in assessing other people’s emotional state.
Many investigators have noted that the presence of repetitive, stereotyped behavior and obsessive preoccupations with particular subjects in autism spectrum disorder resemble the symptoms of obsessive-compulsive disorder. As we saw earlier in this chapter, the symptoms of OCD appear to be related to increased activity of the caudate nucleus. Research suggests that the same may be true for the behavioral symptoms of autism. Several studies have observed increased volume of the caudate nucleus in autism (Langen et al., 2007 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio184) ; Sears et al., 1999 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio185) ). In fact, Hollander et al., (2005 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio186) ) found that the volume of the right caudate nucleus was positively correlated with ratings of repetitive behavior in patients with ASD. (See Figure 17.25 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec5#ch17fig25) .)
Figure 17.25 Caudate Nucleus and Stereotyped Behavior in Autism The graph shows repetitive behavior scores of people with autism spectrum disorder as a function of the volume of the right caudate nucleus. Larger volumes are associated with higher scores.
(Adapted from Hollander et al., 2005.)
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Chapters 8 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch08#ch08) and 11 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch11#ch11) described the role of a circuit of mirror neurons plays a rolein the perception of emotions and behavioral intentions. This circuit is activated when we see another person produce an expression of emotion or perform a goal-directed action, and feedback from this activity helps us to understand what the person feels or is trying to accomplish. In other words, the mirror neuron system may be involved in our ability to understand what people are trying to do and to empathize with their emotions.
Iacoboni and Dapretto (2006 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio187) ) suggest that the social deficits seen in autism may be a result of abnormal development of the mirror neuron system. In fact, a functional-imaging study by Dapretto et al. (2006 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio188) ) observed deficient activation in the mirror motor neuron system of children with ASD, and a structural MRI study by Hadjikhani et al. (2006 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio189) ) found that the cerebral cortex in the mirror neuron system was thinner in people with ASD. A study by Senju et al. (2007 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio190) ) even found that children with autism failed to yawn when they saw a video of other people yawning. Typically-developing volunteers showed an increased rate of yawning during or immediately after seeing videos that depicted yawning but not those that depicted other kinds of mouth movements. Presumably, the mirror neuron system is involved in this type of imitation.
Baron-Cohen (2002 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio191) ) noted that the behavioral characteristics of people with autism spectrum disorder appear to be exaggerations of the traits that tend to be associated with males. As we saw, the incidence of ASD is four times more prevalent in males. Baron-Cohen hypothesized that these disorders may be a reflection of an “extreme male brain.” For example, he noted that on average, females are better than males at inferring the thoughts or intentions of others, are more sensitive to facial expressions, are more likely to respond empathetically to the distress of others, and are more likely to share with others and take turns with them. On average,
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males are less likely to display these characteristics, and they are more likely to compete with their peers, to engage in rough-and-tumble play, and to establish dominance hierarchies. Males also tend to show more interest in toy vehicles, weapons, and building blocks and in pursuits such as engineering, metal- working, and computer programming and are generally better at map reading. In other words, males generally exhibit more interest in working with physical objects and logical systems than with social relations. According to Baron-Cohen, people with ASD show an exaggerated pattern of masculine interests and behaviors. For example, the lack of interest in other people and an obsession with counting and lining- up objects in a row that is seen in many people with autism are seen as extreme examples of masculine traits.
We saw in Chapter 10 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch10#ch10) that sexual differentiation of the brain is largely controlled by exposure to prenatal androgens. Auyeung et al. (2009 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio192) ) used two tests that measure symptoms of autism spectrum disorder to assess the behavior of typically-developing children whose mothers had undergone amniocentesis (removal of a small amount of amniotic fluid during pregnancy). Auyeung et al. found a significant positive correlation in both males and females between fetal testosterone levels and scores on these tests. In addition, Knickmeyer et al. (2006 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio193) ) found that females with congenital adrenal hyperplasia, who were exposed to abnormally high levels of androgens during fetal development, had a greater number of traits associated with autism. Even if Baron-Cohen’s hypothesis is correct, we cannot conclude that autism is caused by prenatal exposure to excessive amounts of testosterone. An “extreme masculine brain” could be caused by genetic abnormalities that increase the sensitivity of a developing brain to androgens, and there could be (and probably are) other causes of autism that have nothing to do with masculinization of the brain.
In addition to changes in steroid hormones, changes in neuropeptide signaling may also be involved in the symptoms of autism. As we saw in Chapter 10 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch10#ch10) , oxytocin, a peptide that serves as a hormone and neuromodulator, facilitates pair bonding and increases trust and closeness to others. Modahl et al. (1998 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio194) ) reported that children with ASD had lower levels of this peptide. Studies suggest that oxytocin can improve sociability of people with ASD. Guastella et al. (2010a (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio195) ) found that administration of oxytocin increased the performance of adolescent males with ASD on a test of emotional recognition. Andari et al. (2010 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio196) ) found that oxytocin improved the performance of adults with ASD on a computerized ball-toss game that required social interactions with fictitious partners. Other researchers have suggested that changes in the genetic code for the oxytocin receptor may underlie social deficits in ASD (Campbell et al., 2011 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio4a) ).
New treatment approaches to autism have begun to focus on brain-based changes. Several research groups are pursuing development of oxytocin-based interventions (Gordon et al., 2013 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio11a) ; Preti et al., 2014 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio22a) ) or deep brain stimulation of the prefrontal cortex (Enticott et al., 2014 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio10a) ) as new avenues of treatment for autism.
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Section Review
Autism Spectrum Disorder
LO 17.17 List the symptoms of ASD.
Autism spectrum disorder (ASD) symptoms include impaired social interaction and communication as well as restricted, repetitive interests, activities or patterns of behavior. Symptoms are present early in life.
LO 17.18 Describe the roles of genetic and environmental factors in the development of ASD.
Genetic studies have shown that autism is highly heritable but that many different genes are responsible for its development. ASD can also be caused by events that interfere with prenatal development, such as prenatal thalidomide exposure or maternal infection with rubella.
LO 17.19 Describe changes in the brain associated with ASD.
MRI studies indicate that the brains of babies who are later diagnosed with ASD show abnormally rapid growth until two to three years of age and then grow more slowly than the brains of unaffected children. The amygdala follows a similar pattern of development. Regions of the brain involved in higher-order processes such as communicative functions and interpretation of social stimuli develop more quickly in people with ASD but then fail to continue to develop normally. People with ASD tend not to pay attention to other people’s faces, as reflected in the lack of activation of the fusiform face area when they do so, and their ability to perceive emotional expressions on other people’s faces is impaired. The volume and connectivity of white matter in the brain is changed in ASD. Activation of the STS and prefrontal cortex in tasks requiring theory of mind is different in ASD. Reduced activation of the mirror neuron system may be involved in ASD. Increased activity in the caudate nucleus may be involved in some of the behavioral symptoms of ASD. Reduced levels of the neuropeptide oxytocin or changes in the oxytocin receptor may also be involved in social symptoms of ASD.
Thought Question
Have you heard about research suggesting that childhood immunizations are associated with the development of autism? Have you heard (before reading this chapter) that the publication that reported this research and its principal author were discredited? Why do you think that many parents are still fearful about having their children immunized?
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17.6 Attention-Deficit/Hyperactivity Disorder Some children have difficulty concentrating, remaining still, and working on a task. At one time or another, most children exhibit these characteristics. But children with attention-deficit/hyperactivity disorder (ADHD) (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/glos01#ch17gloss30) display these symptoms so often that they interfere with the children’s ability to learn. Symptoms of ADHD can affect individuals in both childhood and adulthood.
Symptoms LO 17.20 List the symptoms of ADHD.
ADHD is the most common behavior disorder that shows itself in childhood. It is usually first discovered in the classroom, where children are expected to sit quietly and pay attention to the teacher or work steadily on a project. Some children’s inability to meet these expectations then becomes evident. They have difficulty withholding a response, act without reflecting, often show reckless and impetuous behavior, and let interfering activities intrude into ongoing tasks.
According to the DSM-5, the diagnosis of ADHD requires the presence of six or more of nine symptoms of inattention and/or six or more of nine symptoms of hyperactivity and impulsivity that have persisted for at least six months. Symptoms of inattention include such things as “often had difficulty sustaining attention in tasks or play activities” or “is often easily distracted by extraneous stimuli,” and symptoms of hyperactivity and impulsivity include such things as “often runs about or climbs excessively in situations in which it is inappropriate” or “often interrupts or intrudes on others (e.g., butts into conversations or games)” (American Psychiatric Association, 2013 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio60) , pp. 59 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch03lev1sec1#page_59) –60).
ADHD can be very disruptive of a child’s education and that of other children in the same classroom. The prevalence of ADHD is approximately 5 percent of children in most cultures (American Psychiatric Association, 2013 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio60) ). Boys are about 10 times more likely than girls to receive a diagnosis of ADHD, but in adulthood the ratio is approximately 2 to 1, which suggests that many girls with this disorder fail to be diagnosed. Because the symptoms can vary—some children’s symptoms are primarily those of inattention, some are those of hyperactivity, and some show mixed symptoms—most investigators believe that this disorder has more than one cause. Diagnosis is often difficult because the symptoms are not well defined. ADHD is often associated with aggression, conduct disorder, learning disabilities, depression, anxiety, and low self- esteem. Approximately 60 percent of children with ADHD continue to display symptoms of this disorder into adulthood, at which time a disproportionate number develop antisocial personality disorder and may be diagnosed with a substance abuse disorder (Ernst et al., 1998 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio203) ). Adults with ADHD are also more likely to show cognitive impairments and lower occupational attainment than would be predicted by their education (Seidman et al., 1998 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio204) ).
Table 17.5 Symptoms of Attention-Deficit/Hyperactivity Disorder
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A persistent pattern of inattention and/or hyperactivity-impulsivity that interferes with functioning or development
Inattention: Decreased attention to details; makes careless mistakes or fails to follow directions or complete activities; has difficulty in organization; avoids activities that require sustained attention; easily distracted, forgetful; often loses things
Hyperactivity and impulsivity: Fidgets or squirms, leaves seat when sitting is expected, runs or climbs when inappropriate, talks excessively, interrupts or responds before question is finished, has difficulty waiting
Symptoms are present in childhood
Source: Based on American Psychiatric Association, 2013.
According to Sagvolden and his colleagues (Sagvolden and Sergeant, 1998 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio205) ; Sagvolden et al., 2005 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio206) ), the impulsive and hyperactive behaviors that are seen in children with ADHD are the result of a delay of reinforcement gradient that is steeper than normal. As we saw in Chapter 13 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch13#ch13) , the occurrence of an appetitive stimulus can reinforce the behavior that just preceded it. For example, a piece of food can reinforce the lever press that a rat just made, and a smile can reinforce a person’s attempts at conversation. Reinforcing stimuli are most effective if they immediately follow a behavior: The longer the delay, the less effective the reinforcement. Sagvolden and Sergeant suggest that deficiencies in dopaminergic transmission in the brains of people with ADHD increase the steepness of their delay of reinforcement gradient, which means that immediate reinforcement is even more effective in these children, but even slightly delayed reinforcement loses its potency. (See Figure 17.26 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec6#ch17fig26) .)
Figure 17.26 Hypothetical Delay of Reinforcement Gradient in ADHD The graph illustrates different delay of reinforcement gradients as a function of time. Sagvolden and Sergeant (1998 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio207)
) hypothesize that a steeper gradient is responsible for the impulsive behavior of children with ADHD.
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Why would a steeper delay of reinforcement gradient produce the symptoms of ADHD? According to Sagvolden and his colleagues, for people with a steep gradient, reinforcement with a short delay will be even more effective, thus producing overactivity. On the other hand, these people will be less likely to engage in behaviors that are followed by delayed reinforcement, as many of our behaviors (especially classroom activities) are. In support of this hypothesis, Sagvolden et al. (1998 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio207) ) trained typically- developing boys and boys with ADHD on an operant conditioning task. When a signal was present, responses would be reinforced every 30 seconds with coins or small prizes. When the signal was not present, responses were never reinforced. The typically-developing boys learned to respond only when the signal was present. When the signal was off, they waited patiently until it came on again. In contrast, the boys with ADHD showed impulsive behavior—intermittent bursts of rapid responses whether the signal was present or not. According to the investigators, this pattern of responding was what would be expected by a steep delay of reinforcement gradient.
Heritability LO 17.21 Describe the roles of genetic and environmental factors in the development of ADHD.
There is strong evidence from both family studies and twin studies that hereditary factors play an important role in determining a person’s likelihood of developing ADHD. The estimated heritability of ADHD is high, ranging from 75 percent to 91 percent (Thapar et al., 2005 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio209) ).
Good evidence that the levels of dopamine in the human prefrontal cortex have effects on behavior comes from studies of people with two different variants of the gene for an enzyme that affects dopamine levels in the brain. COMT (catechol-O-methyltransferase) is an enzyme that breaks down catecholamines (including dopamine and norepinephrine) in the extracellular fluid. Although reuptake is the primary means of removing catecholamines from the synapse, COMT also plays a role in deactivating these neurotransmitters after they are released. Mattay et al. (2003 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio210) ) noted that the clinical effects of amphetamine (which are similar to those of methylphenidate) are variable. In some people, amphetamine increases positive mood and facilitates performance on cognitive tasks, but in other people it has the opposite effect. Mattay et al. tested the effect of amphetamine on tasks that made demands on working memory in people with two different variants of the COMT gene. They found that people with the val-val variant, who have lower brain levels of catecholamines, performed better when they were given low doses of amphetamine. In contrast, administration of amphetamine to people with the met-met variant, who have higher brain levels of catecholamines, actually impaired their performance. Presumably, the first group was pushed up the U-shaped curve, and the second group, already around the top of the curve, was pushed down the other side. (See Figures 17.27 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec6#ch17fig27) and 17.28.)
Figure 17.27 Interactions Between Amphetamine and COMT Alleles in Working Memory The graph shows the differential effects of amphetamine on the performance on a working-memory task of people with two different variants of the gene for the COMT enzyme. The performance of people with the val-val variant was enhanced by amphetamine, and the performance of people with the met-met variant was reduced.
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(Based on data from Mattay et al., 2003.)
Brain Changes LO 17.22 Describe changes in the brain associated with ADHD.
We saw in the previous section that the brains of children with autism develop differently from those of typically-developing children. Castellanos et al. (2002 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio6a) ) have reported decreased total brain volume among children with ADHD compared to typically-developing peers. A study by Shaw et al., (2007 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio212) ) found differences in the development of the brains of children with ADHD as well. The investigators found that cortical growth was delayed in children with ADHD. In fact, the cortical thickness of the brains of children with ADHD at age 10.5 years was about the same as that of the brains of unaffected children at 7.5 years. Ultimately, the growth of the brains of the children with ADHD caught up with those of unaffected children.
The symptoms of ADHD resemble those produced by damage to the prefrontal cortex: distractibility, forgetfulness, impulsivity, poor planning, and hyperactivity (Aron et al., 2004 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio213) ). As we saw in Chapter 13 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch13#ch13) , the prefrontal cortex plays a critical role in short-term memory. We use short-term memory to remember what we have just perceived, to remember information that we have just recalled from long-term memory, and to process (“work on”) all of this information. For this reason, short-term memory is often referred to as working memory. The prefrontal cortex uses working memory to guide thoughts and behavior, regulate attention, monitor the effects of our actions, and organize plans for future actions (Arnsten, 2009 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio214) ). Damage or abnormalities in the neural circuits that perform these functions give rise to the symptoms of ADHD.
The most common treatment for ADHD is administration of methylphenidate (Ritalin), a drug that inhibits the reuptake of dopamine. Amphetamine, another dopamine agonist, also reduces the symptoms of ADHD, but this drug is used much less often. As we saw in Chapter 16 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch16#ch16) , the fact that dopamine antagonists were discovered to reduce the positive symptoms of schizophrenia suggested the hypothesis
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that schizophrenia is caused by overactivity of dopaminergic transmission. Similarly, the fact that methylphenidate, a dopamine agonist, alleviates the symptoms of ADHD has suggested the hypothesis that this disorder is caused by underactivity of dopaminergic transmission. As we saw in Chapter 13 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch13#ch13) , normal functioning of the prefrontal cortex is impaired by low levels of dopamine receptor stimulation in this region, so the suggestion that abnormalities in dopaminergic transmission play a role in ADHD seems reasonable.
Berridge et al. (2006 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio215) ) administered methylphenidate to rats and established a moderate dose that improved their performance on tasks that required attention and working memory—tasks that involve the participation of the prefrontal cortex. They used microdialysis to measure the release of dopamine and norepinephrine and found that the drug increased the levels of both of these neurotransmitters in the prefrontal cortex but not in other brain regions. A follow-up study by Devilbiss and Berridge (2008 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio216) ) found that a moderate dose of methylphenidate increased the responsiveness of neurons in the prefrontal cortex. A high dose of methylphenidate profoundly suppressed neural activity.
Many studies have shown that the effect of dopamine levels in the prefrontal cortex on the functions of this region follow an inverted U-shaped curve. (See Figure 17.28 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/ch17lev1sec6#ch17fig28) .) Graphs of many behavioral functions have an inverted U shape. For example, moderate levels of motivation increase performance on most tasks, but very low levels fail to induce a person to perform, and very high levels tend to make people nervous and interfere with their performance. The dose-response curve for the effects of methylphenidate also follow an inverted U-shaped function, which is why Berridge et al. tested different doses of the drug to find a dose that optimized the animals’ performance. Clinicians have found the same to be true for the treatment of ADHD: Doses that are too low are ineffective, and doses that are too high produce increases in activity level that disrupt children’s attention and cognition.
Figure 17.28 An Inverted U Curve The graph illustrates an inverted U-curve function, in which low and high values of the variable on the horizontal axis are associated with low values of the variable on the vertical axis and moderate values are associated with high values. Presumably, the relationship between brain dopamine levels and the symptoms of ADHD follow a function like this one.
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We mentioned that Berridge et al. (2006 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio215) ) found that methylphenidate increased the level of both dopamine and norepinephrine in the prefrontal cortex. It appears that both of these effects improve the symptoms of ADHD. Drugs that block α2 receptors (one of the families of receptors that respond to norepinephrine) impair performance of monkeys on working- memory tasks and produce the symptoms of ADHD. Conversely, drugs that stimulate these receptors improve performance (Arnsten and Li, 2005 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio218) ). Evidence suggests that optimal levels of both dopamine and norepinephrine in the prefrontal cortex facilitate the functions of this region, and the effects of methylphenidate on both of these neurotransmitters is responsible for the drug’s therapeutic effects.
Most investigators believe that ADHD is caused by abnormalities in a network of brain regions that involves the striatum (caudate nucleus and putamen) as well as the prefrontal cortex, which has reciprocal connections with the striatum. Functional-imaging studies lend support to this hypothesis. Studies have reported decreased activation of the caudate nucleus (Durston et al., 2003 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio219) ; Rubia et al., 1999 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio220) ; Vaidya et al., 2005 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio221) ) or medial prefrontal cortex (Rubia et al., 1999 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio220) ; Tamm et al., 2004 (http://content.thuzelearning.com/books/Carlson.0505.17.1/sections/bib01#ch17biblio223) ) while participants with ADHD were performing tasks that required careful attention and the ability to inhibit a response. Given the importance of dopaminergic innervation of both regions, this provides additional support to the idea that abnormalities in dopaminergic transmission may be responsible for the alterations in brain functions observed in ADHD.
Section Review
Attention-Deficit/Hyperactivity Disorder
LO 17.20 List the symptoms of ADHD.
Children with ADHD show symptoms of inattention, hyperactivity, and impulsivity.
LO 17.21 Describe the roles of genetic and environmental factors in the development of ADHD.
Family and twin studies indicate a heritable component in this disorder. Molecular genetic studies have found an association between ADHD and different alleles for COMT, an enzyme that deactivates monoamines. Evidence suggests that a steeper delay of reinforcement gradient may account for impulsiveness and hyperactivity.
LO 17.22 Describe changes in the brain associated with ADHD.
Growth of the brains of children with ADHD follows that of the brains of unaffected children, but the rate of growth is slower. Most investigators believe that ADHD is caused by abnormalities in a network of brain regions that involves the striatum and the prefrontal cortex. Functional-imaging studies have shown hypoactivation of these structures in the brains of people with ADHD while they are performing tasks that require careful attention and the ability to inhibit a response. The most common medical
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treatment is methylphenidate, a dopamine agonist, which suggests this disorder is caused by underactivity of dopaminergic transmission.
Thought Question
The Parents and Teachers Organization of a local elementary school has invited you to speak about brain changes associated with ADHD at their next meeting. To get ready, prepare several highlights as speaking points and anticipate answers to three possible questions that the audience members may have.
Chapter Review Questions 1. Describe the physiological responses to stress and their effects on health.
2. Discuss psychoneuroimmunology and the interactions between the immune system and stress.
3. Discuss posttraumatic stress disorder.
4. Describe the symptoms and possible causes of panic disorder.
5. Describe the symptoms and possible causes of obsessive-compulsive disorder.
6. Describe the symptoms and possible causes of autism spectrum disorder.
7. Describe the symptoms and possible causes of attention-deficit/hyperactivity disorder.
