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  • 1. Research in Clinical Psychology
    • Research in etiology of major mental disorders (costly/common problems):
      • Schizophrenia, other chronic psychoses
      • Major affective disorders
      • Alcoholism, drug abuse
      • Criminality, antisocial behavior
      • Other disorders
  • 2. Research in Clinical Psychology, cont’d
    • Research in etiology
      • Biological factors
      • Psychosocial factors
      • Not not research on complementary influences of these two factors
    • Research on assessment
    • Research on treatment
  • 3. Research on Biological Etiological Factors
    • Three questions about factor X:
      • (1) Does X make a difference?
        • Risk for disorder
        • Development of disorder (e.g., age of onset)
        • Phenomenology (symptoms) of disorder
        • Course of disorder over time
      • (2) How much difference does X make?
      • (3) What is mechanism for X to influence disorder?
  • 4. Classes of Biological Factors
    • Genetics
    • Neurochemistry, including neuroendocrine
    • Structural brain abnormalities
      • Gross anatomy
      • Microstructural changes/deficits
    • Neuropsychological (functional brain) abnormalites
  • 5. Designs for Studying Factors
    • Case-control
      • Depressives vs. normals, compared on serum cortisol
      • Schizophrenics vs. depressives, compared on dopamine receptor counts
      • The “taraxein”/coffee problem (confounding variables)
  • 6. Designs, cont’d
    • Experimental psychopathology: provoke/ heighten/dissect abnormality in disordered group vs. controls
      • tryptophan depletion in depressives
      • frontal lobe-demanding tasks in schizophrenics)
    • Family-genetic studies
      • nuclear family (no control)
      • twin & twin-family (DZ twin = control), adoption
      • pedigree linkage (control provided by null hypothesis)
  • 7. Designs, cont’d
    • Animal models, where possible
      • Feeding & satiety---eating disorders
      • Drug-seeking---psychoactive substance use disorders
      • Stereotyped behavior in monkey/rat---OCD?
  • 8. Types of Genetic Studies I
    • Family studies---yield ambiguous results
    • Liability = hypothetical (unobserved) trait, with genetic AND environmental causes, that controls risk for developing disorder
    • Heritability = degree to which liability is controlled by additive genetic factors in population
    • Twin studies (see next slide)
    • Adoption studies (see slide after that)
  • 9. Twin Studies
    • Twin studies: MZ vs. DZ twins
      • h 2 = 2(r MZ – r DZ )
      • General population twin registries
      • Twins enrolled at psychiatric institutions
    • Twins reared apart (MZA) studies
      • h 2 = r MZA
      • Too hard to do for less common conditions
  • 10. Adoption Studies
    • Adopted-away offspring
    • Relatives of disordered adoptees, vs. those of normal adoptees
    • Cross-fostering
    • Twins-reared-apart design is really an adoption design
    • Need adoptees reared by non-relatives, from early age
  • 11. Types of Genetic Studies II
    • Segregation studies (e.g., familial hyper-cholesterolemia): fit math models to family data
    • Linkage studies (e.g., Alzheimer disease in N = 2,000 Venezuelan pedigree): fit math models to family data with markers
    • Candidate gene studies (e.g., D5 receptor in schizophrenia), gene cloning & identification
    • Animal studies
      • e.g. “Knockout” studies in the mouse
  • 12. Heston Adoption Study
    • Design: adopted-away offspring
      • Schizophrenic mothers
      • Psychiatrically normal controls
    • Dependent variable: rate of schizophrenia
      • Also look at “schizoid” personality
    • Result: big rate in at-risk adoptees, zero in controls
    • Criticism: diagnoses not blind
  • 13. Subsequent Copenhagen Adoption Studies
    • Adopted-away design (Rosenthal)
    • Biological vs. adoptive relatives of schizophrenic & control adoptees design (Kety)
    • Cross-fostering design (Wender)
      • Didn’t really get off the ground---too hard to find schizophrenic adoptive parents
  • 14. How Much Effect? Twin Studies
    • Twin studies from 1920’s to today
    • Every study shows r MZ > r DZ
    • Average heritability about .42 (bipolar is higher, about .7)
    • Older studies (inpatients) give higher heritability than newer studies (more outpatients), e.g., h 2 = .7
    • Severity predicts risk to co-twin
  • 15. Segregation Studies
    • In schizophrenia, segregation analyses (i.e., analyses of fit of family distribution of illness data, to genetic models) hasn’t convinced most that there’s a common single major gene for schizophrenia
    • In some panic disorder families, and maybe some Tourette families, there may be a major gene
  • 16. Linkage Studies
    • This would provide best evidence (short of actually identifying gene) for operation of a genetic factor in mental disorder ABC
    • Many reports of linkage for schizophrenia (C5, C6); essentially zero confirmations from independent labs
    • Mixed confirmation for gene (short arm of X) in a fraction of cases of bipolar illness
  • 17. Types of Neurological Studies
    • Neuroimaging
      • Obsolete technologies---pneumoencephalogram
      • Modern technologies---CT, MRI (structural) SPECT, PET, fMRI (functional)
    • Neuroanatomy (gross, microscopic)
    • Neurotransmitter (receptor) studies
    • Neuropsychological (functional) studies
  • 18. Principal Findings
    • Skull, brain (esp. frontal) of schizophrenics (& bipolars?) smaller on average (CT, MRI)
      • As skull forms around brain in utero , this is developmental process
    • Enlarged cerebral ventricles (& sulci?) in schizophrenia---many replications (CT, MRI)
      • Esp. 4 th ventricle
      • Not artifact of institutionalization or meds---present in teen-aged schizophrenics
      • Effect size sensitive to selection of controls
  • 19. Findings, cont’d
    • Brains of schizophrenics relativel y more hypoactive frontally, when engaged in tasks calling on frontal lobe function
    • Midbrain---hippocampal cell derangement in schizophrenia
    • Excess D2 receptors (esp. in hippocampus?), excess D2 receptor sensitivity in schizophrenics
      • Hotly disputed (Johns Hopkins vs. Karolinska)