Etiology of brain diseases Flashcards
What is the concept of Heritability
Heritability: proportion of variance in symptoms that is explained by the variance in genetic factors.
High heritability: variety of symptoms is more explained by the variety in genes
Low heritability: variety of symptoms is more explained by environmental factors.
What is the heritability of depression, ADHD, ASPD, Bipolar Disorder, autism and schizophrenia?
Depression - 40-50% ADHD - 75% ASPD - 40-50% BD - 80% Autism - 80% Schizophrenia - 80%
describe the contribution of genes and environmental factors to the etiology of complex multifactorial psychiatric disorders.
Gene expression is a short term adaptation to environmental circumstances. This is done through 2 pathways:
1) the stress system
2) Epigenetic modifications
Explain the stress-diathesis model, and elaborate on the concept of
“complex genetics”
” Complex Genetics” = a set of risk factors that bias a person toward lines, but do not cause it.
–> a person inherits the risk for a disorder, not the disorder itself.
Stress-diathesis Model = A combination of environmental risk factors (stress, life events, biological stressors such as viruses) with the risk genes can cause mental illness.
Explain the paradigm “Brain circuits”
Psychiatric symptoms are increasingly linked to malfunctioning brain circuits
Genes + environmental risk factors comprise to produce inefficient information processing in neuronal circuity.
What are Biological Endophenotypes
Endophenotypes: to fragmentise a disorder and find risk genes that are linked to one of those fragments.
” The phenomena of a disorder believed to be in the causal chain between genetic contributions to a disorder and diagnosable symptoms of disease”
examples:
- Electrophysiological response to startle
– Neuroimaging response to information processing
– Activation of certain brain circuit
What are system endophenotypes?
system endophenotypes can be (single) symptoms.
- -> e.g.: increased amygdala in depression
- -> usually used as biomarkers.
Look for genes that cause the increased amygdala, so that symptom van be a fragment of the biological endophenotype.
what are environmental risk factors for psychiatric disorders in general
- stress
- life events
- biological stressors (viruses and toxins)
- sleep deprivation
- pollution
how do environmental risk factors exert their influence on the body and brain via the stress system?
- fast-acting pathway –> (nor)adrenaline (fast acting- not long lasting)
- slow-acting pathway –> endocrine system –> hormones –> cortisol
(slow-acting and long-lasting)
what glands are important in the stress system
Hypothalamus and the Pituitary gland
these two glands are important in the HPA axis
explain the HPA axis pathway in the slow-acting stress system
- Body senses stress
- Hypothalamus secretes corticotropin (CRH)
- Pituitary gland secretes adrenocorticotropic (ACTH)
- ACTH binds with adrenal cortex
- release of cortisol
What occurs after cortisol secretion by adrenal cortex?
- Cortisol binds with cortisol receptors (GR’s)
- GR’s translocate to the nucleus of cell
- Act as transcription factor
- stimulates gluconeogenesis (increased glucose levels) and activates anti-inflammatory and anti-stress pathways
Long-term harmful cortisol leads to:
hypertension, immunosuppression, cardiovascular disease, structural effects
hippocampus
how do environmental risk factors exert their influence on the body and brain via epigenetic modifications?
Epigenetics: the study of certain kinds of chemical switches that turn genes on or off, thereby altering gene expression.
- Methylation : prevents binding of transcription factors
- Acetylation ; create distance between histones, TF can bind.
which brain area’s incorporate the negative feedback loop for cortisol?
hippocampus, hypothalamus, and hypophysis (HHH)
does a healthy person have a lot of GR’s/ few GR’s?
Healthy people have a lot of GR’s, since
Less GR = less negative feedback to shut system down
