5.1.3, 5.1.6 - Biological accounts of schizophrenia

Dopamine and signalling

A neurotransmitter account explains symptoms through the functioning of chemical communication between neurons, rather than through the chemical's mere presence.

At a synapse, the sending neuron releases neurotransmitter into the gap between cells. Binding to suitable receptors influences the receiving cell; removal or breakdown helps end the signal. Dopamine normally contributes to processes including motivation and the assignment of importance to events. It is not a substance that is harmful simply because it exists.

The early dopamine hypothesis proposed excessive dopamine activity as an explanation of schizophrenia. A more differentiated account distinguishes increased subcortical dopamine activity from reduced prefrontal activity. The former has been linked to positive symptoms; the latter has been proposed in relation to negative and cognitive difficulties. These are explanatory proposals, not a rule that every person has the same imbalance throughout the brain.

Howes and Kapur's 2009 revised account emphasises increased presynaptic striatal dopamine function: changes in dopamine production and release before it reaches the receiving receptor. They propose that diverse risk factors can converge on this pathway. Aberrant salience means that events acquire inappropriate significance. If an ordinary coincidence feels unusually important, a person may try to explain it through a delusional belief. This offers a link from altered signalling to experience, but explaining psychosis does not automatically explain the whole syndrome of schizophrenia. Howes and Kapur's original review.

Neurotransmitter evidence and limits

Different sources of evidence can support a neurotransmitter account, but they answer different causal questions.

Many antipsychotic drugs act at dopamine D2 receptors and can reduce positive symptoms. This makes dopamine signalling a plausible treatment target. However, symptom improvement after modifying a system does not prove that a defect in that system was the original cause. A treatment can act on a later step in a longer pathway, and variable response shows that one account does not explain every case equally well.

Neurochemical imaging offers evidence beyond treatment response. Howes and Kapur reviewed imaging alongside genetic, environmental and other research to support their revised dopamine model. Measuring a proposed biological mechanism strengthens the explanation compared with inferring it solely from successful medication. Nevertheless, a measured association still requires caution: symptoms, medication, substance use and other differences may affect measurements. Studies of untreated people and measurements before onset can help address some of these alternatives, without establishing every step of a causal chain.

Dopamine is also part of a wider network. Glutamate is an important excitatory neurotransmitter; GABA is an important inhibitory neurotransmitter. A network account considers how these systems can alter each other's activity, rather than treating dopamine as an isolated switch. Carlsson and colleagues' prescribed 2000 review develops this approach in its own study lesson. Here the implication is that a single-chemical explanation may be too narrow. Carlsson et al.'s original abstract.

The strongest conclusion is that neurotransmitter functioning contributes to some symptoms and provides testable mechanisms. It is weaker to claim that one chemical explains every feature, all developmental influences and every person's outcome.

Genes and vulnerability

A genetic explanation proposes inherited differences in vulnerability, not an inherited certainty that schizophrenia will develop.

Genes contain information used in making biological products. Genetic variants can influence developing neurons, synaptic organisation and signalling. Schizophrenia is polygenic: many variants contribute to risk, rather than one universal schizophrenia gene. Trubetskoy and colleagues' 2022 genome-wide association study identified associations at many genomic locations and implicated neuronal and synaptic processes. Such associations provide clues for mechanisms; they do not make a variant a personal diagnostic test. Original study record.

Family and twin research asks whether risk increases with genetic relatedness. Concordance is the occurrence of the same condition in both members of a pair. If identical twins, who share almost all their inherited DNA, are more often concordant than non-identical twins, a genetic contribution is plausible. However, related people also share environments, and identical twins may experience more similar treatment than non-identical twins. Genetic similarity is not experimentally assigned. Concordance below complete agreement also shows that shared inherited DNA does not determine the outcome by itself.