Genetic Factors

Biological Explanations of Schizophrenia: Genetics and Neural Correlates

Biological explanations propose that schizophrenia arises from genetic predispositions and underlying neurobiological abnormalities — in brain structure, connectivity, and neurotransmitter systems. The evidence base is substantial but points to a complex, polygenic, and probabilistic biological contribution rather than a simple deterministic cause.

Genetic Evidence

Family studies establish that schizophrenia runs in families — but cannot separate genetic from environmental transmission. The risk of developing schizophrenia rises with genetic relatedness to an affected individual: ~1% in the general population; ~10% for first-degree relatives; ~17% for dizygotic twins; ~48% for monozygotic twins; ~46% for offspring of two affected parents.

Twin studies: Gottesman and Shields (1966, 1982) conducted a major twin study using hospital records in the UK. Concordance for schizophrenia was approximately 48% in MZ pairs and 17% in DZ pairs. The substantially higher MZ than DZ concordance strongly implicates genetic factors. However, MZ concordance well below 100% indicates that environmental factors also play an essential role — identical genes do not produce identical outcomes.

Adoption studies: Heston (1966) studied the offspring of mothers with schizophrenia who were adopted away shortly after birth. Approximately 10% of these adoptees developed schizophrenia — significantly higher than controls adopted from non-schizophrenic mothers — confirming a genetic contribution independent of shared family environment.

Candidate genes: genome-wide association studies (GWAS) have identified several risk genes. The C4 gene (complement component 4) — involved in synaptic pruning — shows variants associated with schizophrenia risk (Sekar et al., 2016). DISC1 (Disrupted in Schizophrenia 1) — involved in neurodevelopment and synapse formation. COMT (catechol-O-methyltransferase) — regulates dopamine breakdown in the prefrontal cortex. No single gene has large effect; schizophrenia is highly polygenic (estimated 100+ contributing loci, each with small effect).

Neural Correlates

Enlarged ventricles: post-mortem and neuroimaging studies consistently find that schizophrenic patients have enlarged lateral and third ventricles — spaces in the brain filled with cerebrospinal fluid. Enlarged ventricles imply reduced surrounding brain tissue (grey matter loss). Johnstone et al. (1976) first reported this using CT scanning. Crow (1980) linked enlarged ventricles specifically to the negative symptom (Type II) subtype. The finding is highly replicated but non-specific — ventricular enlargement occurs in other conditions.

Reduced prefrontal grey matter: multiple meta-analyses confirm reductions in grey matter volume in the prefrontal cortex, temporal lobes, and hippocampus. Prefrontal hypofrontality — reduced metabolic activity in the dorsolateral prefrontal cortex (DLPFC) during cognitive tasks — has been linked to negative symptoms and cognitive deficits.

Neurodevelopmental hypothesis: Weinberger (1987) proposed that schizophrenia arises from early neurodevelopmental disruptions — during prenatal brain development or early postnatal life — that do not manifest as psychosis until the brain matures in late adolescence or early adulthood. Evidence includes: maternal infection during pregnancy (particularly influenza in the second trimester), obstetric complications, and winter/spring excess of schizophrenia births (consistent with prenatal viral exposure).