Biological Explanations of Schizophrenia

Biological explanations of schizophrenia focus on genetic inheritance, neurochemical imbalances, and structural abnormalities in the brain. These explanations have been supported by a substantial body of research, though they have also attracted criticism for being reductionist and deterministic. In this lesson we examine the genetic basis, the dopamine hypothesis, and neural correlates of schizophrenia.

Key Definition: Biological explanations propose that schizophrenia is caused primarily by physiological factors — genes, neurotransmitter activity, and brain structure — rather than psychological or social factors.

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The Genetic Basis of Schizophrenia

The observation that schizophrenia tends to run in families led researchers to investigate its genetic component using family studies, twin studies, and adoption studies.

Family Studies

Family studies compare the rates of schizophrenia among biological relatives of a diagnosed individual. The closer the genetic relationship, the higher the concordance rate:

Relationship	Shared Genes (approx.)	Risk of Schizophrenia
General population	—	~1%
Sibling	50%	~9%
Child of one affected parent	50%	~13%
Dizygotic (DZ) twin	50%	~17%
Monozygotic (MZ) twin	100%	~48%
Child of two affected parents	50% from each	~46%

These data clearly show that risk increases with genetic relatedness. However, family members also share environments, so family studies alone cannot distinguish genetic from environmental influences.

Twin Studies

Gottesman and Shields (1966) reviewed hospital records of 57 twin pairs where at least one twin had been diagnosed with schizophrenia. They found concordance rates of:

• 42% for MZ twins (identical)
• 9% for DZ twins (fraternal)

The significantly higher concordance in MZ twins strongly suggests a genetic component, since MZ twins share 100% of their DNA while DZ twins share approximately 50%.

However, the fact that concordance for MZ twins is not 100% demonstrates that genes alone do not determine whether a person develops schizophrenia. Environmental factors must also play a role — supporting a diathesis-stress interpretation.

Exam Tip: When discussing twin studies, always note the limitation that MZ twins may share more similar environments than DZ twins (e.g., they are more likely to be treated identically by parents). This makes it difficult to completely separate genetic from environmental influences — a point that strengthens the case for adoption studies.

Adoption Studies

Adoption studies are considered the gold standard for separating nature from nurture. Tienari et al. (2004) followed 155 adopted-away offspring of Finnish mothers with schizophrenia and compared them with 186 adopted-away offspring of non-schizophrenic mothers. They found that 6.7% of the high-risk adoptees developed schizophrenia, compared with 2% of controls. This effect was amplified in dysfunctional adoptive family environments — supporting both genetic vulnerability and the diathesis-stress model.

Molecular Genetics

Advances in genomic technology have enabled researchers to search for specific genes associated with schizophrenia:

• Ripke et al. (2014) conducted a genome-wide association study (GWAS) involving over 36,000 patients and 113,000 controls. They identified 108 genetic loci associated with schizophrenia, including genes involved in dopamine signalling (DRD2), glutamate signalling, and immune function.
• No single gene has been found to "cause" schizophrenia; rather, it appears to be polygenic — involving the combined effects of many genes, each contributing a small amount of risk.

Key Definition: Polygenic means that a trait or disorder is influenced by the combined action of many genes, each having a small effect. Schizophrenia is estimated to involve hundreds of genetic variants.

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The Dopamine Hypothesis

The dopamine hypothesis is the most influential neurochemical explanation of schizophrenia. It exists in two main versions:

The Original Hypothesis

The original dopamine hypothesis proposed that schizophrenia is caused by excessive activity of dopamine in the brain, particularly at D2 receptors in the mesolimbic pathway. Evidence supporting this came from several sources:

1. Amphetamines — drugs that increase dopamine activity can induce schizophrenia-like symptoms (psychosis) in healthy individuals and worsen symptoms in patients
2. Antipsychotic drugs — chlorpromazine and other typical antipsychotics work by blocking D2 receptors, and their clinical effectiveness correlates with their ability to bind to these receptors
3. L-DOPA — used to treat Parkinson's disease (which involves dopamine deficiency), L-DOPA can produce psychotic symptoms as a side effect

The Revised Hypothesis

Davis and Kahn (1991) proposed a revised version of the dopamine hypothesis. They argued that schizophrenia involves:

• Hyperdopaminergia (excess dopamine) in the mesolimbic pathway — accounting for positive symptoms (hallucinations, delusions)
• Hypodopaminergia (dopamine deficiency) in the mesocortical pathway (projecting to the prefrontal cortex) — accounting for negative symptoms (avolition, cognitive deficits)

This revised model is more sophisticated because it explains why typical antipsychotics (which primarily block D2 receptors) are effective against positive symptoms but often fail to improve — and may even worsen — negative symptoms.