4.3.5 - Biological explanations for schizophrenia

The biological frame

Why does schizophrenia run in some families, and why might a neutral event suddenly feel personally significant? Biological explanations investigate inherited vulnerability and brain mechanisms. They distinguish evidence about risk across people from evidence about a particular symptom. Neither a family history nor a brain scan can, by itself, explain everything about one person's experience.

For schizophrenia, the biological route has three linked ideas:

Strong exam answers avoid one-cause thinking. A biological explanation can be powerful without being complete. The best wording is that genes, dopamine and brain activity increase vulnerability or are associated with symptoms, often interacting with environmental triggers such as stress, trauma, cannabis use or family conditions. That keeps the answer accurate and prepares the ground for AO3.

Genetic vulnerability

The genetic explanation argues that some people inherit biological vulnerability to schizophrenia. This does not mean they inherit schizophrenia itself. It means their genetic profile may make the disorder more likely if other risk factors are also present.

Classic family and twin evidence supports a genetic contribution. Gottesman (1991) reviewed family studies and found that risk generally increased with genetic similarity to a person with schizophrenia. The commonly cited AQA figures are about 48% concordance for monozygotic twins and 17% for dizygotic twins, with lower risk for siblings and parents. Since monozygotic twins share virtually all their genes while dizygotic twins share about half, the difference supports a genetic explanation.

However, the same figures also limit the explanation. Concordance well below 100% challenges a simple fully penetrant genetic account. Measurement, age at follow-up, developmental processes and environmental differences also matter when interpreting this evidence. More recent register-based evidence reaches the same balanced conclusion. Hilker et al. (2018) used Danish twin-register data and estimated schizophrenia heritability at about 79%, but the probandwise concordance rate was 33% for monozygotic twins and 7% for dizygotic twins. That supports substantial genetic influence, while still showing that genes are not destiny. Heritability describes variation in liability in a population under studied environmental conditions; it is not a 79% probability that an individual will develop schizophrenia.

Early explanations sometimes sounded as if researchers were looking for "the schizophrenia gene". Current evidence is much more complex. Ripke et al. (2014) conducted a very large genome-wide association study and reported 108 schizophrenia-associated genetic loci. Later work by the Psychiatric Genomics Consortium expanded the picture further, reporting many more loci. The exam point is not that students must memorise gene names. The point is that schizophrenia is polygenic and biologically complex.

Schizophrenia is also aetiologically heterogeneous. One person may have one pattern of genetic risk, another person a different pattern, and both may receive the same diagnosis. This helps explain why symptoms and treatment responses vary between individuals.

Biological vulnerability need not involve an obvious family history. A de novo mutation is a new DNA change rather than a variant inherited unchanged from a parent. Brown et al. (2002) found an association between advanced paternal age and offspring schizophrenia-spectrum risk. New mutations in sperm are one proposed explanation, but age is not a direct measurement of mutation and other influences may contribute. This association alone does not establish the mechanism.

Adoption evidence makes the AO3 even stronger. Tienari et al. (2004) found that adoptees at high genetic risk were more sensitive to adverse rearing environments than adoptees at low genetic risk. Adoption does not remove prenatal influences or guarantee random placement, so it cannot perfectly isolate genes. Twin comparisons also assume that relevant environments are sufficiently comparable: greater similarity of MZ environments could contribute to greater concordance. The adoption finding supports a gene-environment interaction: genetic vulnerability matters most when it combines with environmental stressors.

AO2 example: Maya has an uncle and a mother diagnosed with schizophrenia. She asks whether this means she will definitely develop it. A biological explanation would say her genetic risk is likely higher than average, but the outcome is not fixed. Her actual risk depends on many genes and on environmental factors across development.

Worked reasoning: concordance is not individual destiny

Hilker's MZ rate of 33% exceeds the DZ rate of 7% by 26 percentage points. Because MZ twins are more genetically similar, the direction of this comparison supports inherited vulnerability. However, MZ twins may also share more similar relevant environments, so the difference is not a clean experiment on genes.

The MZ rate is also well below 100%. That challenges a simple account in which the same inherited genotype inevitably produces the same diagnosis. It does not identify which environmental or developmental process explains discordance. Nor does 79% heritability mean that 79% of one person's illness is genetic: it is an estimate of population variation in liability under the conditions studied. These are three different claims, and only the first is a direct comparison of concordance rates.

The dopamine hypothesis

The dopamine hypothesis is the best-known neurochemical explanation of schizophrenia. It argues that symptoms are linked to abnormal dopamine activity in particular brain pathways.

The original dopamine hypothesis was relatively simple: schizophrenia was caused by too much dopamine activity. This fitted some drug evidence. Antipsychotic drugs often reduce positive symptoms and many work by blocking dopamine D2 receptors. Drugs that increase dopamine activity, such as amphetamines, can worsen psychotic symptoms or produce schizophrenia-like experiences in some people.

The original version was useful, but too broad. It could explain positive symptoms such as hallucinations and delusions better than negative symptoms such as avolition or speech poverty. It also risked implying that dopamine was simply excessive everywhere in the brain.

The revised dopamine hypothesis is more precise. Davis et al. (1991) argued that schizophrenia may involve both: