This document contains all of the lectures of the course molecular principles of brain disorders. It also includes images with matching explanation when the lecturer explained the image.
Lecture 15 Bright side of mental illness ........................................................................................................ 104
Part 1 Creativity & Psychiatric conditions....................................................................................................... 104
Part 2 Neurobiology of Resilience ................................................................................................................... 109
1
,Lecture 0 Introduction course
Week Lecture Datum
Week 1 L1: Etiology of mental traits and 02-11-22
conditions
L2: Depression part 1,2 Whenever you want
L3: Etiology of brain disorders (paper 04-11-22
discussion)
L4: Depression part 3 04-11-22
(L4: brain basics (necessary knowledge
for course, not actively part of exam))
Week 2 L5: General mechanisms in 09-11-22
neurodegeneration
L6: Dementia 10-11-22
L7: Synucleopathies/ prion and prion-like 11-11-22
Week 3 L8: Stem cell technology in 16-11-22
neurodegenerative disease
L9: Therapy 1 16-11-22
L10: Therapy 2+3 17-11-22
L11: 100+ study (guest lecture) 17-11-22
L12: ADHD (same as in brein & 18-11-22
maatschappij) PRERECORDED
L13: ADHD & ASD neurodiversity (same as 18-11-22
in brein & maatschappij) PRERECORDED
Week 4 Intro literature assignment 22-11-22
Literature review assignment part 1 22-11-22 > DEADLINE
literature key references
L14: Schizophrenia 23-11-22
Literature review assignment 23-11-22
L15: Bright side of mental illness
Deadline literature review – backbone 24-11-22
Week 5 MC-exam 02-12-22
Week 6-8 Literature review > no obligatory
meetings anymore
Deadline literature review 23-12-22
2
,Lecture 1 Etiology of mental traits and conditions
Trait (eigenschap) or disorder?
- Impulsivity, mood, (anti) social behavior, stress-sensitivity, resilience and vulnerability are
behavioral traits
- Each trait exists along a spectrum
- Impulsivity (extremely thoughtful, difficulties decision taking – extremely impulsive)
- Border between normal and abnormal behavior?
- A variation or a disorder?
- Other traits: IQ, extraversion, blood pressure…
- Disorders: diabetes, obesitas, autism (?), depression, schizophrenia
- HOW do traits and disorders arise in general?
Which factors can contribute to traits / (mental) characteristics and brain
disorders?
➢ Genes
➢ Environmental factors
Nature – nurture discussion
• Past: tendency to explain disease via ‘nurture’ concept (je ontwikkelt jezelf door sociaal
economische factoren)
• Autism = ‘refrigerator mother’ (autism occurs because of the behavior of the mother)
>> not true
• Homosexual orientation = overly present mother (not true)
• These ideas are no longer valid
• Later: the role of biological factors more clear (‘nature’) (DNA and genes influence the
development)
Etiology
- Classic nature – nurture discussion:
- Hard reductionism: ‘all psychiatric illness is best explained solely in terms of molecular
neuroscience’ > not correct
- Etiological models for psychiatric disease need to be pluralistic or multilevel (= complicated
phenomena you can explain not only by biological factors but also social and cultural factors
etc)
o Best understood from biological, psychological, and sociocultural, economic
perspectives
Break down dichotomy between nature-nurture, but view brain as in constant interaction with
environment, society and culture via plasticity
• Most brain disorders complex,
Etiology
multifactorial disorders
- Complex puzzle
• Both genetic and environmental
- Genes
factors involved in etiology
- Environmental factors
• Often: complex interactions and
- HOW can environmental factors exert their influence?
causal loops
- Altered gene expression via
– Stress system
– Epigenetics
- Interactions gene-environment
3
,Genes
➢ To study the effect of genes on psychiatric disorders:
➢ From twin + adoption studies: several behavioral traits and psychiatric diseases moderate /
high heritability
o Heritability = proportion of variance in symptoms that is explained by the variance in
genetic factors ( in dutch: de variatie die we zien in het voorkomen van bepaalde
eigenschappen dat we kunnen verklaren door genen)
• Major depression 40-50%, low heritability
• ADHD: 75%, genes play an interesting rol
• Autism, bipolar disorder, schizophrenia around 80%
o Genes play a large role in shaping on the likelihood (kans) of someone getting it and
the degree of severity
In post – ‘human genome project’ era
➢ Expectation: easy to find risk genes
o Contrary: very difficult
o ‘missing heritability’(moeilijk om risicogenen te vinden)
➢ Outcome: model of single / few risk genes =
overly simplistic paradigm (tijdelijke waarheid)
Genes and psychiatry
Classic theory
• Single abnormal gene > abnormal gene product > neuronal malfunction >
mental illness = theory that is overly simplistic
• Single abnormal gene is not sufficient to cause mental disorders
• What is pathway from gene to mental illness?
New explanations, new hypotheses, new models for pathway ‘genotype to phenotype’
1. ‘Complex Genetics’ or ‘Diathesis-Risk Model’ (explained in lecture Etiology)
2. ‘Differential Susceptibly to Environment Hypothesis’ (explained in lecture ‘Neurobiology of
Resilience’)
3. ‘Balancing Selection Hypothesis’ (explained in lecture ‘Bright side of mental illness)
- New hypotheses and new models are more complex
- New ways of doing research and ‘unravel’ these pathways from ‘genotype to phenotype’:
‘endophenotype approach’ (tussen phenotype en genotype)
• Stress – diathesis (risico) model (diathesis = ‘risk’)
= Predisposition (genetic) + environmental stress > gives a larger probability at disease
New paradigm:
➢ Hypothesis: mental illness is caused by multiple small contributions from several genes, all
interacting with environmental stressors
‘Complex genetics’= complex set of risk factors (& environmental factors) that bias (meer kans
geven op) a person toward illness but do not cause it (inherits risk not disease)
• Reaching tipping point: high probability developing disorder
>> Concept also applies to hypertension, obesitas, diabetes…
4
, Endophenotype approach
• Path from gene > mental illness
• New ways of doing research and ‘unravel’ these pathways
from ‘genotype to phenotype’: ‘endophenotype approach’
• Pathway ‘genotype to phenotype’
MUCH MORE COMPLEX!
SOLUTION:
Important intermediaries between gene (genotype) and
disease/behavior (phenotype)
‘endophenotypes’:
• Measurable, inheritable and closely linked to disease
• More precisely measurable than illness
• Two types:
– Biological endophenotypes
– Symptom/system endophenotypes
Genes and psychiatry
1. Biological endophenotypes (more close to genotype)
- Measurable biological phenomena
– Electrophysiological response to startle
– Neuroimaging response to information processing
– Activation of certain brain circuit
2. Symptom/system endophenotypes (more close to phenotype)
- Single symptoms associated with mental illness:
– Insomnia
– Executive dysfunction > prefrontale hersenkwab werkt niet goed
– Hallucinations
– Poor fear conditioning
– Anhedonia > inability to experience pleasure (measure with a questionaire)
→ Gene > molecules > circuits > information processing (biological phenotype) > single
symptom (system endophenotype) > full syndrome of mental disorder
→ Closer to gene on pathway > more readily linked to gene: Link gene to endophenotype
easier than to disease
→ Genes only loosely linked to psychiatric disorders, therefore hard to identify
Psychopathology and brain circuits
- Etiology of psychiatric disorders is moving beyond single molecule explanations/ receptors,
enzymes and other molecules as causes for mental illness
- New paradigm: psychiatric symptoms are increasingly linked to malfunctioning specific brain
circuits
- Genes + environmental risk factors conspire to produce inefficient information processing in
neuronal circuitry
- Brain imaging > focus on brain circuits
5
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