Psyco

INTRODUCTION TO

PSYCHOLOGY

CLASS #6

Dr. Charles-Etienne Benoit

Today’s Lecture

 Genes and behavior

 Brain disorders

 Huntington’s disease

 Alzheimer’s disease

 Parkinson’s disease

 Schizophrenia

 Depression

 Attention deficit hyperactivity disorder

 Traumatic brain injury

 External / Internal traumas

 Stroke

Genetic material

 Genes are made of DNA which is passed on from one generation to the next.

 DNA is made of two strands, each of which has a deoxyribose-phosphate

backbone attached to a series of four subunits called nucleotides.

Desoxyribonucleic Acid (DNA)

Chromosomes

Map of normal human chromosomes illustrate their distinctive morphologies.

Epigenetics

 Epigenetics represents the science

for the studying heritable changes

of DNA, not involving changes in

DNA sequence, that regulate gene

expression.

 Research on the changes in a

chromosome without alterations in

the DNA sequence

 Histone modifications

 DNA methylation

Epigenetic code

Gene silencing

Epigenetic marks:

Small chemical tags on top of

chromatin and help instruct it

whether to open or to compact.

Epigenetic effects

Twins differences in gene expression

Epigenetic differences arise during the lifetime of monozygotic twins

Fraga, et al. PNAS, 2005; https://doi.org/10.1073/pnas.0500398102

The 50-year-old twin pair shows

abundant changes in the pattern of

DNA methylation observed by the

presence of green and red signals

that indicate hypermethylation and

hypomethylation events, whereas the

3-year-old twins have a very similar

distribution of DNA methylation

indicated by the presence of the

yellow color obtained by equal

amounts of the green and red dyes

Twins: identical vs fraternal

Familial risk of psychiatric disorders

 Correlations between monozygotic twins for psychiatric disorders are

considerably greater than those between dizygotic wins.

 The risk of developing schizophrenia is greater in close relatives of a

schizophrenic patient.

Familial risk of other disorders

 Comparing Identical and

Fraternal Twins: A higher

percentage of disease

incidence in both identical

twins is the first indication

of a genetic component.

 Percentages lower than

100% in identical twins

indicates that DNA alone

does not determine

susceptibility to disease.

Epigenetic differences arise during the lifetime of monozygotic twins

Wong, et al. Human Molecular Genetics, 2005, https://doi.org/10.1093/hmg/ddi116

Genetic disease

 An autosomal dominant disease is aquire if you get the abnormal gene from

only one parent. Often, one of the parents may also have the disease.

 An autosomal recessive disorder means two copies of an abnormal gene must

be present in order for the disease or trait to develop.

Huntington’s disease

 He contributed a classic clinical description of the disease

that bears his name in 1872.

 Huntington disease is a hereditary autosomal dominant

disorder that affects men and women equally at a

frequency of 5 to 10 per 100,000 individuals.

 The onset of the disease occurs most often after the third

decade of life and is characterized by the gradual

development of motor symptoms abnormalities.

 Nonmotor disturbances such as depression, behavioral

disturbances, and cognitive impairment are also very

common. Death occurs as the result of medical

complications of the underlying neurological disease, in

most cases 15 to 20 years after onset.

George Huntington

1850–1916

Long-Island, USA

Huntingtin gene and protein

Huntingtin gene and protein

 A CAG tri-nucleotide sequence is called the polyglutamine repeat

(codes for 23 of the amino acid).

 Expansion of this repeat region is what causes Huntington’s disease.

 It translates to an unstable polyglutamine repeat in the huntingin

protein (repeats in excess of 40 are considered to be pathological.)

C h ro

m o so

m e

4 in

h u m

a n

CAG repeat

This figure shows

that the longer the

length of the chain

of CAG repeats in

the gene, the earlier

the age of disease

onset.

Effects on the neuron

This mutant protein may

lead to abnormal

endocytosis and

secretion in neurons. In

addition, it causes

striatal neurons to die

by the process of

apoptosis.

Effects on the brain

 The first target is always the striatum, a part of the basal ganglia.

 As the disease progresses, other areas of the brain are also ravaged and in the

end no brain structure is completely spared.

Basal ganglia

 The basal ganglia are a

group of structures found

deep within the cerebral

hemispheres.

 The separate nuclei all have

extensive roles of their own,

but when referring to them as

one network the function most

frequently associated with the

basal ganglia involves

movement.

Parkinson’s disease

 He contributed a classic clinical description of the

disease that bears his name in 1817 in his An Essay on

the Shaking Palsy.

 This disease is neurodegenerative and leads to motor,

cognitive and affective impairments.

 People of every ethnicity and sex are affected and the

prevalence of PD is estimated at 0.3% while reaching

1% in elderly people over the age of 60 years old.

 Every year, 8 to 18 per 100 000 people risk to newly

develop the pathology.

James Parkinson

1755–1824

London, United-Kingdom

Parkinson’s disease

 Motor features

 Resting tremor

 Bradykinesia

 Rigidity

 Postural instability

 Non motor features

 Autonomic

 Cognitive

 Increase chances of falls.

Left: Healthy individual; Right: Parkinson’s patient

Neural correlate

 Symptoms appear when 80% of striatal dopamine and 50% of the nigra compacta cells of the basal ganglia undergo degeneration.

 They are asymmetric to the affected brain areas and worsen over time bilaterally.

Alpha-synuclcein inclusion

 The surviving dopaminergic neurons are characterized by the presence of

alpha-synuclein inclusions.

 Misfolded alpha-synuclein proteins are converted into pathological

oligomers and aggregates that form fibrils and deposit into Lewy bodies

and Lewy neurites in affected neurons of the PD brain.

Pathway to cell death

Known genes in Parkinson’s disease

Effects of dopamine depletion

Dopamine replacement

Stage of the disease

 First the disease reach the locus coeruleus (norepinephrine)

 Sleep

 Mood

 The reach the substentia negra (dopamine)

 Motor manifestations

 Finally in the later stage affect the cortex

 Dementia

 Behavioral symptoms

Dementia

 Symptoms include loss of memory, judgment and

reasoning, and changes in mood and behavior.

 Can be caused by conditions that may be treatable,

such as depression, thyroid disease, infections or drug

interactions but can also be due to damage to the

nerve cells in the brain.

 A lot of individual variability.

Alzheimer’s disease

 It is the most common form of dementia.

 Clinical description of the disease that bears his

name in 1906.

 It is a slowly progressive disease of the brain

that is characterized by impairment of memory

and eventually by disturbances in reasoning,

planning, language, and perception.

 The pooled incidence rate of AD among people

65+ years of age in Europe was 19.4 per 1000

person-years.

 The pooled data of population-based studies in

Europe suggests that the age-standardized

prevalence in people 65+ years old is 6.4 % for

dementia and 4.4 % for AD.

Aloysius Alzheimer

1864 -1915

Breslau, Germany

Effects on the brain

Hippocampus

 Research has found that one of

the first areas in the brain

affected by Alzheimer’s

disease is the hippocampus.

 Atrophy was correlated to the

hippocampal areas with the

presence of Alzheimer's disease.

 It explain why one of the early

symptoms involve memory

impairments.

Amyloid and tau deposit

 Both amyloid plaques and neurofibrillary tangles are visible by microscopy in brains

of those afflicted.

 Plaques are dense, mostly insoluble deposits of amyloid-beta peptides.

 Tangles (neurofibrillary tangles) are aggregates of the microtubule-associated

protein tau accumulate inside the cells themselves.

Alzheimer’s disease

Known genes in Alzheimer’s disease

Alzheimer’s medication

Familial vs Idiopathic

 Another feature observed in most common neurodegenerative

diseases (as well as in other common disorders) is a dichotomy

between familial (rare) and seemingly nonfamilial (common)

forms.

 The latter are also frequently described as “sporadic” or

“idiopathic,” although there is a growing body of evidence

suggesting that a large proportion of these cases are also

significantly influenced by genetic factors.

 Mental condition involving

distorted perceptions of

reality and inability to

function in most aspects of life

Schizophrenia

 Most common mental illness – 1-2% of the population.

 Common in all cultures, genders, and races but men tend to develop symptoms earlier.

Etiologie

 There is not one essential symptom that must be present for a

diagnosis.

 Instead, patients experience different combinations of the main

symptoms of schizophrenia.

 There are positive and negative symptoms

Symptoms

 Exaggerations or distortions of normal processes or

behaviors

 Delusions (somebody is after them, possession of their soul,

they are famous or powerful, etc.)

 Hallucinations (unreal perception, happen is all 5 senses)

 Disorganized speech (speak very little, change thought

mid-sentence)

 Thought disturbances (psychosis, lack of touch with reality)

 Motor disturbances (frozen limbs, catatonia)

 Innapropriate behavior (childlike behavior, violence)

 Positive symptoms are generally more responsive to

treatment than negative symptoms

Positive symptoms (increase of)

 Behavioral deficits that endure beyond an acute

episode of schizophrenia

 Anhedonia (inability to feel pleasure, interest or enjoyment)

 Avolition (lack of energy to engage in routine or activities)

 Alogia (lack of meaningful speech, quantity or quality)

 Asociality (impairments in social relationships)

 Flat affect (absence of normal behavior or emotion)

 Some negative symptoms might be secondary to

medications and/or institutionalization

Negative symptoms (lack of)

 Familial genetics predispositions

 Prenatal damage (malnutrition, viruses)

 Environment (stress, trauma, drug intake)

 Neurotransmitters disregulation

 High dopamine

 Low serotonine and glutamate

 Brain abnormalities

 Reduced number of neurons

 Enlarged ventricles

 Thalamus abnormalities

Causes unknown

Twin mystery

Lost of grey matter

In early onset schizophrenia there is a wave of gray matter

loss that begins in the parietal cortex and spreads forward.

Treatments

 Use of anti-psychotic drugs (block and alter dopamine and serotonin receptors), but many patients are non-responsive.

 To responsive patients it reduce symptoms but have side- effects (tremor, dystonia, weight-gain)

 Cognitive psychological therapy

and goal directed occupations.

Autistic spectrum disorder

 Autism spectrum disorder is a neurological and developmental disorder that begins

early in childhood and lasts throughout a person's life.

 It affects how a person acts and interacts with others, communicates, and learns.

Autistic savant

 Savant syndrome is a condition in which someone with significant

mental disabilities demonstrates certain abilities far in excess of

average (look for Daniel Tammet).

 The skills at which savants excel are generally related to

memory. This may include rapid calculation, artistic ability, map

making, or musical ability. Usually just one special skill is present.

 Those with the condition generally have

a neurodevelopmental disorder such as autism

spectrum disorder or have a brain injury.

Kim Peek, who was the inspiration for the main character in the movie Rain Man

Depression

 Depression is a heterogeneous disorder with complex and

mutifactorial factors - ranging from genes (e.g., serotonine) to

environment (epigenetic).

 Family, twin, and adoption studies provide ample evidence of the

importance of genetic and familial factors in the development of

mood disorders.

Two categories of core symptoms:

 Hyperactive and impulsive behaviors occur together

 Inability to sit still or inhibit behavior

 Observed by age 4, peaks age 7-8, then hyperactive

symptoms decline but impulsive symptoms persist

 Inattention

 Reduced ability to focus attention, reduced speed of

cognitive processing and responding

 Apparent at 8-9 years old, usually lifelong

Attention deficit/hyperactivity disorder

Attention deficit/hyperactivity disorder

 School age children 8-10%

 Most common neurobehavioral disorder of childhood

 More common in boys than girls

 Male to female ratios:

 4:1 for predominantly hyperactive type

 2:1 for predominantly inattentive type

 Overall prevalence 2-18%

Etiologies

Genetic factors account for ~80% of etiology

 Twin studies demonstrate concordance as high as 92% in monozygotic twins and 33% in dizygotic twins

 5-6x higher risk of first degree relatives affected

 Genes that may play a role:

 Dopamine and serotonin receptors and transporters

 Dopamine beta-hyroxylase

 Glutamate receptors

Neurobiology

 Frontal-striatal dysfunction  mediated by GABA

 modulated by catecholamines

 Catecholaminergic dysregulation

 Delay in cortical maturation

Comorbid disorders

Prevalence of comorbid disorders for

children with ADHD vs those without

Larson et al, 2007

Treatment

 Preschool children (4-5 years-old)

 Behavior therapy administered by parent or teacher

 Addition of medication (stimulant) if fails behavioral

therapy

 School age children (6-11 years-old) and

adolescents (12-18 years-old).

 Medication and behavioral therapy

 Treat coexisting conditions concurrently with ADHD

Brain scalp anatomy

 Scalp

 Skull

 Epidural Space

 Dura

 Subdural Space

 Arachnoid

 Subarachnoid Space

 CSF

 Brain

Traumatic brain injury

Falls, 28%

Motor Vehicle-

Traffic, 20% Struck

By/Against, 19%

Assault, 11%

Unknown,

9%

Other, 7%

Pedal Cycle

(non MV), 3%

Suicide, 1%

Other Transport,

2%

A nondegenerative, noncongenital insult to the brain from an external mechanical force,

possibly leading to permanent or temporary impairments of cognitive, physical and

psychosocial functions with an associated diminished or altered state of consciousness

Close or open head injury

Coup contre coup

 When the head is struck,

the impact causes the

brain to bump the

opposite side of the skull.

 Damage occurs at the

area of impact and on the

opposite side of the brain.

Stroke

 Also called apoplexy or cerebrovascular accident.

 A blockage or hemorrhage of a blood vessel leading to the brain.

Cerebrovascular system

Localize brain damage

Frontal

lobe Parietal

lobe

Occipital

lobe Temporal

Lobe

Limbic

Lobe

Frontal lobe

 The frontal lobe is the area of the brain

responsible for our “executive skills” - higher

cognitive functions.

 These include:

 Problem solving

 Spontaneity

 Memory

 Language

 Judgment

 Impulse control

 Social and sexual

Temporal lobe

 The temporal lobe plays a role in

emotions, and is also responsible

for smelling, tasting, perception,

memory, understanding music,

aggressiveness, and sexual

behavior.

 The temporal lobe also contains

the language area of the brain.

Parietal lobe

 The parietal lobe plays a role

in our sensations of touch,

smell, and taste. It also

processes sensory and spatial

awareness, and is a key

component in eye-hand co-

ordination and arm movement.

 It also contains a specialized

area called Wernicke’s area

that is responsible for matching

written words with the sound of

spoken speech.

Occiptal lobe

 The occipital lobe is at

the rear of the brain

and controls vision and

recognition.

Limbic system

 The limbic system is the area

of the brain that regulates

emotion and memory. It

directly connects the lower

and higher brain functions.

That’s it for today!

Life goes on even with mental disorders.