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.