ETIOLOGY OF SCHIZOPHRENIA

BY - Dr. Sridhar.L

MSRMC, B’lore

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FAMILY STUDIES – Better research techniques

yielded estimates of an average lifetime risk of around 5-10% among 1st degree relatives of people with schizophrenia vs 0.2-0.6% among 1st degree relatives of controls.

GENETIC FACTORS

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TWIN STUDIES – Concordance rate for MZ twins is

40-50% vs 10% for DZ twins. Among Discordant MZ twins, the risk of schizophrenia is increased equally in children of both the affected and unaffected twin.

ADOPTION STUDIES- children of affected mothers separated within 3 days of birth vs control.

MODE OF INHERITANCE- Follows non-Mendelian mode with genes acting as risk factors and not determinants.

GENETIC FACTORS (Contd..)

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OBSTETRIC COMPLICATIONS - APH, DM, LBW, Birth

Asphyxia, Rh incompatibility. MATERNAL INFLUENZA – Suggested that Influenza

infection esp in 2nd trimester . Other infections like toxoplasmosis, HSV-2, Rubella.

MATERNAL MALNUTRITION – Children born to mothers who experience famine early in pregnancy have higher risk.

WINTER BIRTH PATERNAL AGE – Increased risk of 50% for every 10

yr increase in paternal age. SUBSTANCE USE – Prior use of cannabis

(controversial)

ENVIRONMENTAL FACTORS

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NEUROBIOLOGY

The following CT changes were observed by Johnstone et al (1976) :-

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NEUROPATHOLOGY

CEREBRAL BLOOD FLOW- Decreased in Frontal lobe “HYPOFRONTALITY”.

FMRI – Decreased frontal activity esp Prefrontal cortex during working memory tasks.

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DOPAMINE – Use of PET and SPET scan to image dopamine

receptors and dopamine synthesis in brain provided evidence of “HYPERDOPAMINERGIA” in acute schizophrenia.

Changes – a) Slight increase in D2 receptors. b) Mainly- Increased occupancy of D2 receptors by dopamine.

GLUTAMATE – It was found that antagonists of NMDA type of glutamate receptors(Ketamine) can induce schizophrenia like psychosis.

NMDA Receptor Hypo functionality Model – Genetic component involved and autoimmune anti NMDA receptor Abs present.

NEUROCHEMICAL

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NEUROCHEMICAL(Contd..)

GABA – Major inhibitory NT in brain. a) Decrease in GAD activity in cortex. b)Decrease in GABAergic neurons and synaptic terminals.

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EEG – Increased theta activity, fast and

paroxysmal activity.

Abnormal sensory evoked potentials and eye tracking.

NEUROPHYSIOLOGY

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OCCUPATION AND SOCIAL CLASS – Lower SE status. PLACE OF RESIDENCE- Disadvantaged inner city

areas. MIGRATION AND ETHNICITY – Afro-Caribbean origin. SOCIAL ISOLATION– Living alone, not married ,no

friends LIFE EVENTS – Moving house, losing job, new job. Paykel calculated that experiencing major life events doubles the risk of developing schizophrenia in the subsquent 6 months. CHILDHOOD TRAUMA AND ABUSE

SOCIAL AND PSYCHOSOCIAL

FACTORS

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NEUROPSYCHOLOGICAL FACTORS – Model by Gray et al

suggested that positive symptoms arise from failure to integrate stored memory with current stimuli.

FAMILY THEORY- 2 forms of abnormal family patterns a) Marital skew- 1 parent yields to other’s eccentricities. b) Marital schism- parents maintained contrary views and child had divided loyalties.

PERSONALITY FACTORS- Suggested that schizophrenia was more common in asthenic body type.

PSYCHOLOGICAL FACTORS

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NEURODEVELOPMENTAL HYPOTHESIS-

Schizophrenia is a disorder of brain development at any time of life – prenatal, adolescent or the interaction between the two.

CURRENT ETIOLOGICAL HYPOTHESIS

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ABERRANT CONNECTIVITY HYPOTHESIS – Activities of

different brain regions / circuits is aberrant in schizophrenia.

STRESS VULNERABILITY MODEL( Syn- STRESS DIATHESIS MODEL )

It incorporates development ,but emphasizes the interaction of early events (genetic/biological/social) with later stressors (substance use/ Life events). Early factors confer vulnerability to develop Schizophrenia , while the latter stressors explains onset and course.

CURRENT ETIOLOGICAL HYPOTHESIS(Contd..)

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SUMMARY

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THANK YOU