PS371: Biological perspectives

Genotype

genetic makeup from biological parents

Allele

one or two or more alternate forms of a gene that arise by mutation, found at same place on chromosome

each inherits two alleles from each of our biological parents

Phenotype

observable physical/behavioral characteristics

Heritability

proportion of variation between individuals in a given population (believed) due to genetic variation

Historical perspective

• Disease model: each disorder has underlying cause, interpersonal and intrapersonal

  • Maladaptive behavioral trends internal conflicts

  • Reflects errors in personal development, each mental problem has underlying physiological cause (hormones, genetic defects)

  • Each one is unique

Emil Kraepelin

first formal system for classifying mental health disorders, published in textbook, physical diseases based

Assumption that each disorder had a different

• Cluster of symptoms

• Course

• Age of onset

• Cause

Genome-wide associated studies

identify specific genetic markers (single-nucleotide polymorphisms)
attempts to identify specific genetic variants, analyze risks for psychiatric disease, increase/decrease probability of disorders

Two primary models of GWAS

• Common Disease / Common Variant (CDCV)

• Multiple Rare Variant (MRV)

• Example: Wray et al. (2013) on CDCV strategy

  • Evidence of genetic overlap between schizophrenia (Scz), bipolar disorder, major depression, attention deficit hyperactivity disorder, and autism?

  • Findings include that people w/ these disorders more likely to have suspect genetic variation at same 4 chromosomal sites, although overlap still relatively modest

  • Overlap in genetic variations highest between Scz & bipolar (15% heritability), intermediate for bipolar & depression (10%), lowest between Scz & autism (3%)

Genetic linkage analyses

• examine unique traits with known genetic coding, traits viewed as potential markers for disorder (know about location)

• ex. saccadic eye movement (schizophrenia)

  • rapid/simultaneous movement, outside of conscious awareness

  • relatives have difficulty in pursuit of fast moving objects

Twin/adoption/family studies

• members demonstrate similarity in a variety of traits

• twin: identical vs. fraternal similarities and differences analyzed

• adoption: twins reared apart from biological parents, each other

• family study method: expression of traits among relatives as a function of degree of relatedness

Gottesman (1991) … on Schizophrenia

• Identical twins: 48% concordance

• Fraternal twins: 17% concordance

Torrey et al. (1994)

• Identical twins: 28% concordance

• Fraternal twins: 6% concordance

• How do they define identical/fraternal twinness?

General public prevalence of schizophrenia

~1%

Genetics summary

• No individual genes lead to the expression of psychiatric disorder (contribute substantially)

• Likely multi-genetic, more consistent with CDCV hypothesis

• Risk influenced by psychological factors (not just genetic influence)

Evolutionary perspective

How long in human history has particular condition existed? (significance to the development and survival of a species)

How did people from far-flung cultures across time come up with similar explanations for abnormal behavior?

Might also ask:

What function does psychopathology serve? Any adaptive value?

Evidence of pathology across human history, or is it more recent?

Evidence that psychopathology qualitatively different from “normal”?

Factors associated with pathology protective?

World Health Organization on Schizophrenia

Remarkably similar across cultures

Comparable risk level

Not disappearing despite lower childbirth among people with Scz

Hindbrain

• Brainstem

• pons, medulla, cerebellum

• Physiological arousal,

• Control of posture, balance, movement

Midbrain

• Brainstem

• Reticular activating system

• Arousal, experience of tension

Diencephalon

• Brainstem

• thalamus, hypothalamus

• Behavioral and emotional regulation

• Circuits that run from brain stem to cortical to subcortical structures

Basal ganglia

• Sub-cortical

• Caudate nucelus

• Putamen

• Globus pallidus

Limbic system

• Sub-cortical

• Amygdala

• Hippocampus

Sub-cortical

relevant to complex motor behavior, memory, emotional expression, cognition, impulse control, sex, aggression, hunger, thirst

Cerebral cortex

• >80% of all neurons in CNS

• Left hemisphere: linguistic, analytic

• Right hemisphere: spatial, holistic

Occipital

Processing/integration of visual input

Parietal

Touch recognition and body sensation

Temporal

Recognition of sights/sounds, aspects of language processing/expression, long-term memory storage

Frontal

Reasoning, planning, thinking / problem solving, moral / social judgment, aspects of memory, inhibition of inappropriate behavior, mental flexibility

Serotonin

• at least 15 sites

• Midbrain → higher cortical

• Influence behavior, mood & thought

• Low rates associated with reduced inhibition, impulsivity, tendency to overreact to various situations, aggression

Gamma aminobutyric acid

• reduces post-synaptic activity

• Inhibit wide range behavior, emotions

• e.g., anger, hostility, aggression, even some positive emotional states such as eager anticipation and pleasure

• best known effect = reduce anxiety

Norepinephrine

• best known effects on arousal

• Release increased by stress

• Likely general behavioral regulator

• Appears to influence mood and behavior

Dopamine

• at least 5 sites

• Associated with exploratory, outgoing, pleasure-seeking

• Influences attention, mood, motivation

• Key role in muscle movement

• people with too little natural of this availability tend to engage in seeking activities, such as substance use or risky / exciting behavior (e.g., sky diving)

• many major circuits merge with / cross major serotonin circuits

Psychotherapies

• Cognitive-behavioral, psychodynamic models dominant perspectives

• Real world interventions: many options

• Individual … Couples … Family … Group … Self-Help

• Most major conceptual frameworks well represented

• Empirical support / validation is key

Early biological therapies

• Except for primarily opium-based sedatives, little prior to 1930’s

• 1950’s … introduction of Neuroleptics (reserpine)

• Drugs modify presence / effect of brain chemistry by increasing / decreasing the presence or effect of neurotransmitters

Contemporary drug therapy

• primary mechanisms of action

• Agonists: mimics action of NT at receptor sites, increasing NT’s effect

• Antagonists: decreases / blocks action of NT at receptor sites, decreasing NT’s effect

• Atypical: complex mechanisms of action / effect

Comparing treatment strategies

Diathesis-Stress model

• Diathesis = physiological vulnerability

• Inherit vulnerability for disorder

• Risk for expression influenced by stress

• Stress not constant … risk for expression of disorder relatively fluid

• Contemporary models also allow for psychosocial diatheses

Reciprocal Gene-Environment model

• more dynamic

• Assumes that genetically-coded traits increase or decrease probability that we’ll encounter stressful experiences