Project overview
This meta-analysis synthesizes findings from 62 studies involving 4,857 individuals with schizophrenia and 3,211 controls to evaluate the roles of dopamine, glutamate, GABA, and serotonin in the disorder’s pathophysiology. Dopaminergic dysregulation, particularly elevated D2/3 receptor activity, showed the strongest effect size (0.91), reinforcing dopamine’s central role in positive symptoms like hallucinations. However, significant glutamatergic disruptions—especially reduced NMDA receptor function (effect size ~0.67)—support a broader model implicating excitatory neurotransmission in cognitive and negative symptoms. GABAergic abnormalities, including decreased GAD67 expression, revealed a moderate effect (0.59), suggesting impaired inhibition contributes to executive dysfunction. Serotonergic changes, particularly elevated 5-HT2A receptor binding, showed smaller but meaningful effects (~0.48), potentially influencing hallucinations and mood symptoms. The findings highlight schizophrenia as a multi-transmitter disorder rather than purely dopaminergic.
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