Physiology of mental illness

1
Physiology of mental illness

• Schizophrenia
• Depression and mania
• Anxiety disorders

2
Schizophrenia

• Broad set of symptoms
• Positive and negative symptoms
• Genetic factors in etiology
• 1 of general population
• 10 in first-degree relatives of probands
• 45 in identical twins of probands
• Same rate in children of probands (16.8) as in
  children of their non-schizophrenic identical
  twins (17.4) (Gottesman and Bertelsen, 1989)

3
Etiological factors

• Inherited susceptibility or several genes are
  involved
• Retrospective strangeness in childhood behavior
• Stress trigger
• Dopamine hyperactivity is found in schizophrenia,
  but the genes for the five types of DA receptors
  found so far are not linked to schizophrenia
  (Coon et al., 1993)

4
Environmental factors in etiology

• We will see that dopamine hyperactivity relates
  to the positive symptoms of schizophrenia.
• The negative symptoms may be due to brain damage
  Some people with no family history of
  schizophrenia or any related disorder develop
  schizophrenia

5
Prenatal damage factors Epidemiology

• Incidence of schizophrenia increases with
• season of birth late winter/early spring
• viral epidemics in second trimester
• population density and latitude
• malnutrition or refeeding after thiamine
  deficiency
• prenatal stress

6
More on brain damage

• NADPH-d and cellular migration
• Monochorionic monozygotic twins
• More likely to be mirror-image twins
• Monochorionic concordance 60
• Dichorionic MZ concordance 10.7
• DZ dichorionic concordance 10
• Concordant MZ twins have nearly identical
  fingerprints and palm prints non-concordant MZ
  twins do not.

7
Evidence of brain damage in schizophrenia

• Neurological symptoms
• Catatonia and facial dyskinesias
• Unusual rates of blinking, staring
• Avoidance of eye contact
• No blink reflex to a tap on the forehead
• Stopped speech w/ looking away, esp. to right
• Jerky eye movements and poor visual tracking
• Interdependence of eye and head movements
• Impaired reaction of pupils to light changes

8
More evidence of brain damage

• Structural symptoms
• Doubling of size of lateral ventricles
• Abnormalities in temporal and frontal lobes and
  in medial diencephalon
• Smaller anterior hippocampus smaller neurons
• Decreased gray matter in left temporal lobe
• Damage to left temporal lobe in adults may
  produce schizophrenia de novo
• Low activity in prefrontal cortex (hypofrontality)

9
Dopamine hypothesis

• Hypofrontality lowers tonic release of DA in
  nucleus accumbens
• Nucleus accumbens DA receptors become
  hypersensitive
• Normal DA activity from VTA triggers positive
  symptoms of schizophrenia