Pharmacological And Biological Approaches To Clinical And Health Psyschology
Institution
Universiteit Leiden (UL)
Book
Psychopharmacology
This document has all you need for the exam! It is a large summary of all lectures, articles from the reader and the textbook.
Dit document heeft alles dat je nodig hebt voor het tentamen! Het is een grote samenvatting van al de colleges, artikelen van de reader en het boek.
Week 1
DNA = deoxyribonucleic acid: long molecule that contains our unique genetic code
Strands → sides of the ladder, formed by alternating sugar (deoxyribose) and phosphate molecules
Bases → rungs of the ladder, 4 nitrogen-containing compounds: adenine, thymine, guanine, cytosine
Base Pair → adenine always binds to thymine, and guanine always binds to cytosine
Nucleotide → a single base + its associated sugar and phosphate group
The information on the DNA guides the production of proteins through a 2-step process:
1. Transcription = the process of making an RNA copy of a gene sequence. This copy, called
a messenger RNA (mRNA) molecule, leaves the cell nucleus and enters the cytoplasm (and
reaches the ribosomes), where it directs the synthesis of the protein, which it encodes
2. Translation = the process in which ribosomes in the cytoplasm or endoplasmic reticulum
synthesises proteins after the process of transcription of DNA to RNA in the cell's nucleus.
The polypeptide later folds into an active protein and performs its functions in the cell
These processes convert the genetic information at one gene (genotype) into the protein that, in
concert with other genes their proteins and environmental exposures, determines the phenotype
Phenotype = observable outward appearance of a cell or organism (e.g. eye colour, behaviour, etc.)
Genotype = the genetic make-up of a cell or organism: > 99% of DNA is similar across humans
Mutations = a change in a DNA sequence: happens in less than 1% in populations
Polymorphisms = (poly = many, common genes) one of two or more variants of a particular DNA
sequence: happens more frequently, more than/equal to 1%. These may take a few different forms:
1. The presence or absence of an entire stretch of DNA (insertion/deletion polymorphisms), a
variation of which involve DNA replication called copy number variation (CPV)
2. Repeating patterns of DNA that vary in the number of repeats: each repeating “unit” may
vary from 2 - hundreds of base pairs long and may repeat a few - hundreds of times
3. A single-base pair change, called a single-nucleotide polymorphism (SNP) → most common
polymorphism: non-synonymous SNPs lead to a change in amino acid sequence of the
resultant protein, whereas synonymous SNPs do not result in amino acid change
,Locus = the location along the DNA strand at which a particular allele is present
Wild Type = what geneticists decided to call the form of the gene that is most common in the pop
Isoforms = the different proteins where the different alleles in the case of SNPs (only
non-synonymous) result in production of these forms of protein for which the gene is responsible
Homozygous = individuals with two copies of the same allele
Heterozygous = individuals with two copies of different alleles
Dominant → one that is expressed in different copies of the gene are present (heterozygous)
Recessive → one that is expressed only when two copies of the gene are present (homozygous)
Additive/Per-Allele Model = if two differing protein isoforms resulting from different alleles
share function → this is a model of inheritance: our genetic model (same as dominant & recessive)
Hardy-Weinberg Equilibrium (HWE) = states that if there are two alleles at a particular locus,
named A and a, with frequency p and q, respectively, then after one generation of random mating
the genotype frequencies of the AA, Aa and aa groups in the population will be p2, 2pq and q2
Deviations from the HWE in the population may be due to the following:
1. Inbreeding → marrying close relatives: because HWE depends on random mating
2. Genetic Drift → process in which a population is isolated, limited number of matings
3. Migration → the movement of people from one place to another: less mating options
4. New Mutations → equilibrium is usually reached within 1 generation in a large population
5. Selection → a selective disadvantage of a particular allele that leads to fatal death
Linkage Analysis = the presence of certain stretches of DNA or genes in family members with
disease and their absence in those without disease
Linkage Disequilibrium = non-random association of alleles at different loci in a population
Some of the most commonly examined genes in relation to psychiatric disorders: serotonin
transporter, monoamine-oxidase A, dopamine receptor D4 & D2, catechol-O-methyltransferase
(COMT) and brain-derived neurotrophic factors (BDNF)
There are two stress-related messengers in the brain: cortisol & noradrenaline
The two brain structures which release these messengers are: adrenal cortex & locus coeruleus
,Serotonin-Transporter-Linked Polymorphic Region (5-HTTLPR) = genetic polymorphism:
plays a role in transporting serotonin from synapses to presynaptic neurons → consists of a short (s)
allele (lower levels) and a long (l) allele (higher levels) implicated in serotonin transport
Caspi et. al. → showed that the s-allele genotypes were at higher risk of depression and suicidality
compared to the l-allele genotype, but only if they had experienced childhood maltreatment
MAOA-Gene = located on the X-chromosome and encodes enzymes that are involved in degrading
other neurotransmitters such as dopamine, serotonin, and norepinephrine
Carriers of the genotype conferring low levels of MAOA gene expression showed higher levels of
adulthood antisocial behaviour, but only if they also experience maltreatment in childhood
● Implication → moderated by gender, with effects being stronger in boys compared to girls
Catechol-O-Methyltransferase (COMT) = a protein coding gene located on chromosome 22, the
enzyme product of which is involved in degradation of catecholamine neurotransmitters such as
dopamine, epinephrine and norepinephrine → GxE research on schizophrenia typically sought to
investigate the role of COMT in relation to environmental factors that have consistently been
linked to schizophrenia (e.g. obstetric complications at birth, cannabis use and stress)
● Implication → some study designs and measurements
Differential Susceptibility Theory = proposes that in addition to greater sensitivity to
maladaptive environments and subsequent emerging behaviour problems, susceptibility traits may
show greater sensitivity to supportive environments and greater susceptibility to adaptive outcomes
Diathesis-Stress Model → challenged by ^: mental and physical disorders develop from a genetic or
biological predisposition for that illness (diathesis) combined with stressful conditions
Vantage Sensitivity Model → challenged by ^: some people benefit more from the positive effects of
supportive experiences than others as a function of inherent characteristics, e.g. genetic differences
Genome-Wide Association Studies (GWAS) = an approach used in genetics research to associate
specific genetic variations with particular diseases → involves scanning the genomes from many
different people and looking for genetic markers that can be used to predict the presence of a disease
Genome-Wide Environment Interaction Studies (GWEIS) = an approach to see if different
effect of an environmental exposure on disease risk in subjects with different genotypes
, Polygenic Score-X-Environment Interaction Studies (PGS) = the number of trait-associated
alleles possessed by each individual in target sample, weighted by their effect sizes from a discovery
sample: it can be limited to genome-wide significant variants, or series of more liberal thresholds
Nature/Hereditary = transmission of characteristics of a person is based on genetic material
Nurture/Environment = the surroundings of a person affect the development & characteristics
Genotype → individual’s genetic constitution, overall/at specific gene: <1% differs across individuals:
1. Mutations = cause a permanent change in DNA, for example: base-change, depletion of
base-segments and duplication of base segments
2. Polymorphisms = (inherited) multiple frequent variants of gene in population
(transmitted to subsequent generations without causing defects in biological functions)
Mendelian Inheritance = patterns of inheritance that are characteristic of organisms that
reproduce sexually → dominant vs recessive alleles & homozygous vs heterozygous
Not for every cell all proteins encoded in the DNA are needed → protein production is dynamic &
continuously influenced by various factors, for instance:
1. Epistasis = interactions of genes: allele at one locus interferes/masks an allele at another
2. Epigenetics = regulation of gene expression: a series of biochemical processes through
which changes in gene expression are achieved throughout the lifecycle of an organism
without a change in DNA sequence, i.e. genes are switched on/off by environmental factors
Epigenome = is changeable: multitude of chemical compounds that can tell the genome what to do
Epigenetic signals from inside cell and neighbouring cells (development of tissue) & from exterior
Examples of environmental epigenetic factors: diet, season (daylight), exercise, diseases exposed to,
drugs used, negative life events (e.g. maltreatment) & social support: risk factors vs protective
G x E Studies = the modification of genetic risk factors by environmental risk and protective
factors and to the role of specific genetic risk factors in determining individual differences in
vulnerability to environmental risk factors. Comparing cases and controls in:
1. Pedigree (Family) Studies → particularly good for a rare disease caused by rare mutation
2. Twin Studies → similar genes (monozygotic twins), different epigenome due environments
3. Population Studies → studies including various populations
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