Summary MPBD: Etiology of mental traits and disorders
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Course
Molecular Principles Of Brain Disorders
Institution
Vrije Universiteit Amsterdam (VU)
This document contains a brief summary of the Etiology of mental traits and disorders lectures and powerpoints. It also includes the paper study about “Epigenetic programming by maternal behavior”.
MPBD: Etiology of mental traits and disorders
Impulsivity, mood, (anti)social behaviour, The classic theory stated that a single abnormal
stress-sensitivity, resilience and vulnerability gene, leads to an abnormal gene product and that
are behavioural traits. Each of these traits leads to neuronal malfunction and mental illness.
exists along a spectrum. But a single abnormal gene is not sufficient to
cause mental conditions, but what is the pathway
Which factors can contribute to traits/ from gene to mental conditions? What is the
(mental) characteristics and brain disorders? relationship between the genotype and the
• Genetics phenotype? How can genes lead to certain
• Environmental factors such as pregnancy, behaviour? There are new models and
stress, family situation, food intake, war, hypotheses to investigate this pathway:
alcohol or concussions. 1) Complex genetics/diathesis-stress model
2) Differential susceptibly to environment
In the past, it was common to explain these hypothesis
diseases via a nurturing concept, for example, 3) Balancing selection hypothesis
that autism is caused by having a cold, distant
“refrigerator mother” or that homosexuality Stress-diathesis model
is caused by an overly present mother. Later Diathesis means risk. This model is based on the
they discovered that the role of biological fact that predisposition (genes) + environmental
factors is more “nature” than “nurture”. It is stress can lead to disease. The hypothesis is:
therefore important to break down the mental conditions are caused by multiple small
dichotomy between nature-nurture, and view contributions from several genes, all interacting
the brain as in constant interaction with the with environmental stressors. This is also called
environment, society and culture via complex genetics causes a complex set of risk
plasticity. Plasticity is the brain's capacity to factors that can bias a person toward conditions/
adapt or change over time by creating new illnesses but do not cause them, you can inherit
neurons and building new networks. the risk but not the disease itself.
There are new ways of research to unravel the
Most brain disorders are complex, pathways from genotype to phenotype, because
multifactorial disorders where both genetic the pathway is complex the solution is to use
and environmental factors are involved in the intermediaries between the genes and disease/
etiology. There are often interactions and behaviour.
causal loops involved.
Endophenotypes
Twin + adoption studies showed that several These are variables that
behavioural traits and psychiatric diseases could measure the link
are moderate/highly heritable. In between the genotype and
monozygotic twins the genes are 100% the the phenotype/inheritance
same, in dizygotic twins, this is 50%. and disease.
Heritability is the proportion of variance in There are two types of
symptoms that are explained by the variance endophenotypes:
in genetic factors. 1) Biological endophenotypes
On the population level, there is a 75% chance 2) Symptom/system endophenotypes
to develop ADHD of which 25% is caused by
the environment and 75% is explained in the Biological endophenotypes
genes. For autism, bipolar disorder, and These are closer to the genotype side and
schizophrenia this is 80%. measure biological phenomena such as
electrophysiological responses to startling,
By the time human genome sequencing was neuroimaging responses to information
possible they found out that there are certain processing, and activation of certain brain
“risk genes”. Though, this is an overly circuits. For example, depression is linked to an
simplistic paradigm since risk genes only overactive amygdala.
increase the risk of developing a certain
disease by a tiny amount.
, Symptom/system endophenotypes There is a social-ecological framework that cannot
These are closer to the phenotype and are be explained by one single factor. There is a
associated with single symptoms in certain dynamic interplay of multiple risks and protective
mental diseases such as insomnia, executive factors that occur along a social ecology continuum
dysfunction, hallucinations, poor fear (WHO, 2014). These factors are individual,
conditioning and anhedonia. relationship and cultural/environmental factors.
Genetic factors in this case fall under individual
Though it is easier to link the endophenotypes factors.
to genes than to the condition/disease, cause
genes are only loosely linked to psychiatric Pre/perinatal risk factors
conditions/disorders and therefore hard to • Maternal stress during pregnancy
identify. • Maternal nutritional deficiency
• Maternal use of tobacco/alcohol/drugs/
The etiology of psychiatric conditions is medications
moving beyond receptors, enzymes and other • Birth complications
molecules as causes. A new paradigm is that • Perinatal nutritional deficiency
psychiatric symptoms are increasingly linked • Maternal separation
to malfunctioning brain circuits. Genes and • Abuse
environmental risk factors conspire to produce • Neglect
inefficient information processing in neuronal • Poor parental care
circuitry. Brain imaging can be used to study
these brain circuits. An example of this is that Other risk factors
in depression the whole neuronal network • Infections
malfunctions instead of only one molecule such • Toxins
as serotonin. All the proteins play a role in the • Brain trauma
network and all of the subparts in the brain • Drug use
need to function properly for communication. • Stressful life events
• Low social economical status
• Poverty
• Community violence
• Lack of mental health care and stigmatization of
mental health problems
• Minority group position
• Cultural factors
• Religious factors
The stress system
How can these environmental factors exert their
But why are subtle molecular abnormalities influence? These factors can alter gene expression
not more penetrant at the behavioural level? via the stress system and epigenetics.
This comes to the fact that there is a healthy
compensatory backup system and risk genes
are not necessarily sufficient to cause mental
conditions/disorders since it is an combination
with environmental risk factors. We need 100+
different risk factors both in genes and
environment to develop a disorder.
The fast-acting pathway works via the sympathetic
nervous system and the slow-acting pathway uses
hormonal systems and involve the hypothalamus-
pituitary-adrenal (HPA) axis. During the fast-
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