College aantekeningen
molecular principles of brain disorders module 1: psychiatric disorders. 10 lectures
molecular principles of brain disorders module 1. it includes all the lectures of that part, the workgroup and learning outcomes.
[Meer zien]Voorbeeld 4 van de 35 pagina's
Voorbeeld 4 van de 35 pagina's
In winkelwagengesponsord bericht van onze partner
Verkoper
Volgen
Voorbeeld van de inhoud
MODULE 1: PSYCHIATRIC DISORDERSLecture 1 + 2: Etiology of mental traits and conditions
Behavior traits: impulsivity, mood, social behavior, stress-sensitivity, resilience and vulnerability.
- Each trait exists along a spectrum
o Example: Impulsivity (extremely thoughtful, difficulties decision taking – extremely
impulsive)
- What creates a trait? Is there a border between normal and abnormal behavior?
- Other traits: iq, extraversion, blood pressure
- Disorders: diabetes, obesities, autism (?), depression, schizophrenia
What factors can contribute to traits / (mental) characteristics and brain disorders
- Genetics
- Environmental factors
o Stress, infection, food, pregnancy, alcohol, trauma, family situation, etc.
Nature – nurture discussion:
- Past: tendency to explain disease via nurture concept.
o Autism = refrigerator mother
o Homosexual orientation= overly present mother
- Later: role biological factors more clear (nature)
- Hard reductionism: all psychiatric illness is best explained solely in terms of molecular
neuroscience
- Etiological models for psychiatric disease need to be pluralistic (= trueth is more than reality,
with a multiplicity of principles) or multilevel
- 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 are complex, multifactorial disoders
- Both genetic and environmental factors involved in etiology.
- Often complex interactions and causal loops, Complex puzzle
- Genes and environmental factors
- How can environmental factors exert their influence?
o Altered expression via
▪ Stress system
▪ Epigenetics
- Interactions gene-environment
Genes
- From twin + adoption studies: several behavioral traits and psychiatric diseases moderate /
high heritability
- Heritability: proportion of variance in symptoms (of a certain condition) that is explained by
the variance in genetic factors
o Major depression 40-50%
o ADHD: 75%
2
, o Autism, bipolar disorder, schizophrenia around 80%
o NOT: when your parents have ADHD, you have 75% change getting it. trueth: you can
explain a trait (impulsivity) 75% by the genetics.
- In post – humane genome project era
o Expectation: easy to find risk genes
o Contrary: it was very difficult to identify the risk genes; ‘Missing heritability’
o Model of single / few risk genes = overly simplistic paradigm. (genetic risk is not
really a thing. It increases the risk only by a tiny amount. It is difficult to spot this).
Genes and psychiatry
- Classic theory: Single abnormal gene → abnormal gene product → neuronal malfunction →
mental illness
o Single abnormal gene is not sufficient to cause mental conditions
o What is pathway from gene to mental conditions?
- New explanations, new hypotheses, new models for pathway ‘genotype to phenotype’.
o 1. ‘Complex genetics’ or ‘diathesis-stress model’ (explained in lecture etiology)
o 2. ‘Differential susceptibly to environment hypothesis’ (explained in lecture
neurobiology of resilience)
o 3. ‘balancing selection hypothesis’ (explained in lecture mental illness & creativity)
- new hypotheses and new models are complex
- new ways of doing research and unravel these pathways from genotype to phenotype:
‘endophenotype approach’
1. stress – diathesis (=risk) model : predisposition (genetic) + environmental stress → disease
new paradigm:
- hypothesis: mental conditions are caused by multiple small contributions from several genes,
all interacting with environmental stressors.
- ‘Complex genetics’
o Complex set of risk factors that bias person toward condition/illness but do not cause
it (inherits risk not disease). it is about probability. Every risk factor is tiny.
o Reachting tipping point: high probability developing condition/disorder. (critical
point in an evolving situation that leads to a new and irreversible development)
o Concept also applies to hypertension, obesity, diabetes, etc.
Endophenotype approach: from genotype to phenotype
- path from gene → mental illness
- new ways of doing research and unravel’ these pathways from ‘genotype to phenotype’:
endophenotype approach
- pathway genotype to phenotype is much more complex!
- solution: important intermediaries between gene (genotype) and
disease/behavior(phenotype)
- endophenotypes:
o measurable, inheritable and closely linked to disease condition
o more precisely measurable than disease/condition
o two types:
▪ biological endophenotypes (more close to genotype site)
▪ symptom/system endophenotypes (more close to the phenotype site)
3
,biological endophenotype: measurable biological phenomena
o electrophysiological response to startle
o neuroimaging response to information processing
o activation of certain brain circuit
symptom/system endophenotypes: single symptoms associated with mental disease/condition:
o insomnia
o executive dysfunction
o hallucinations
o poor fear conditioning
o anhedonia (easily with a questionnaire)
genes and psychiatry
- gene → molecules → circuits → information processing (biological phenotype) → single
symptom (system endophenotype) → full syndrome or mental condition/disorder
o closer to the gene on pathway → more readily linked to gene (so the link gene to
endophenotype is easier than to the condition / disease)
o genes only loosely linked to psychiatric conditions/disorders, therefore hard to
identify
psychopathology and brain circuits
- etiology of psychiatric conditions is moving beyond receptors, enzymes and other molecules
as causes. (depression is often explained by to low numbers of serotonin, this is not etiology
good explained).
- 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
Why are subtle molecular abnormalities not more ‘penetrant ‘at behavioral level?
- Multiple genes complementary / redundant effects ‘healthy compensatory backup system’.
- Risk genes are not necessary sufficient to cause mental conditions / disorders
- Combination with environmental risk factors (stress, life events, biological stressors such as
viruses, toxins…)!!!
Socio-ecological framework: no single factor can explain
- There is a dynamic interplay of multiple risk and protective factors.
o Risk and protective factors are along a social ecology continuum: (small to big)
▪ Individual (also genes belong to this) – Relationship - Cultural /
environmental
o Environmental:
▪ Pre/peri natal risk factors: maternal stress during pregnancy, maternal
nutritional deficiency, maternal use of tobacco / alcohol / drugs /
medication.
▪ Birth complications
▪ Perinatal nutrition deficiency, maternal separation
4
, ▪ Abuse,(sexual / emotional / physical) , neglect, poor parental care
▪ Infections, toxins, brain trauma, drugs use
▪ Stressful life events
▪ Low SES, poverty, community violence
▪ Mental health care & health care policy (assessment, stigmatization of
mental health problems)
▪ Minority group position, cultural factors, religious factors
HOW can environmental factors exert their influence?
- Altered gene expression via (two pathways)
o stress system
o epigenetics
stress system:
every cell in the body has cortisol receptors.
Cortisol is often in a negative context, but it
is an adaptive response, it is not a bad thing.
It increases hart rate, blood pressure, and
helps to concentrate. It can have negative
effects, for example it is toxic for the brain. It
has a negative feedback loop.
the brain has specific cortisol receptors. The
receptor is a protein. The amount of brain
cortisol receptors. A healthy stress system, a
healthy apa axis, is a system with a plenty Figure 1
of cortisol receptors in the brain. This is the
only way a negative feedback can happen. Negative feedback: it inhibits its
own expression. When there is to little cortisol brain receptors, it is not able
to shut down the system.
HPA-axis (hypothalamic-pituitary-adrenal)
- stress → hormone cortisol
- cortisol important in defense response: protective + promote
adaptation
- cortisol binds to glucocorticoid receptor (GR) in body
- GR acts as transcription factor and can alter gene expression
- GR also in several brain areas
- GR in hypothalamus, hypophysis and hippocampus: negative
feedback loop → shut down CRF release Figure 2, normal situation of the negative
Figure 2 loop In brain. Cortisol binding →
feedback
Sustained high levels of cortisol → harmful → hypertension, release less crh, acth, enz. And in the and
cortisol. Also look at the places were the
immunosuppression, cardiovascular disease, structural effects hippocampus receptors are.
+ amygdala, increased chance psychopathology
- Early life stress ( year 1 and 2) → life long overacting HPA-axis (eg. Less GR=less negative
feedback to shut system down
- Hope: evidence that prenatal stress can be moderated by quality of post natal care!
5
Dit zijn jouw voordelen als je samenvattingen koopt bij Stuvia:
Bewezen kwaliteit door reviews
Studenten hebben al meer dan 850.000 samenvattingen beoordeeld. Zo weet jij zeker dat je de beste keuze maakt!
In een paar klikken geregeld
Geen gedoe — betaal gewoon eenmalig met iDeal, creditcard of je Stuvia-tegoed en je bent klaar. Geen abonnement nodig.
Direct to-the-point
Studenten maken samenvattingen voor studenten. Dat betekent: actuele inhoud waar jij écht wat aan hebt. Geen overbodige details!
Veelgestelde vragen
Wat krijg ik als ik dit document koop?
Je krijgt een PDF, die direct beschikbaar is na je aankoop. Het gekochte document is altijd, overal en oneindig toegankelijk via je profiel.
Tevredenheidsgarantie: hoe werkt dat?
Onze tevredenheidsgarantie zorgt ervoor dat je altijd een studiedocument vindt dat goed bij je past. Je vult een formulier in en onze klantenservice regelt de rest.
Van wie koop ik deze samenvatting?
Stuvia is een marktplaats, je koop dit document dus niet van ons, maar van verkoper vustudent3rdyear. Stuvia faciliteert de betaling aan de verkoper.
Zit ik meteen vast aan een abonnement?
Nee, je koopt alleen deze samenvatting voor €3,49. Je zit daarna nergens aan vast.
Is Stuvia te vertrouwen?
4,6 sterren op Google & Trustpilot (+1000 reviews)
Afgelopen 30 dagen zijn er 66184 samenvattingen verkocht
Opgericht in 2010, al 15 jaar dé plek om samenvattingen te kopen