Project overview
This meta-analysis examined the role of key neurotransmitters—dopamine, glutamate, GABA, and serotonin—in the pathophysiology of schizophrenia, synthesizing data from 62 studies involving 4,857 patients and 3,211 controls. Findings confirmed dopamine’s central role, with significantly increased D2 receptor availability and dopamine release (effect size ~0.91). Glutamatergic dysfunction, especially reduced NMDA receptor activity, also showed strong associations (effect size ~0.67), suggesting a contribution to cognitive and negative symptoms. GABAergic deficits, marked by reduced GAD67 expression and GABA levels, had a moderate effect (~0.59), correlating with impaired inhibitory control. Serotonergic alterations, particularly elevated 5-HT2A receptor binding, demonstrated a modest but significant effect (~0.48), influencing psychotic and affective symptoms. While dopamine remains pivotal, the involvement of other neurotransmitter systems supports a multidimensional model of schizophrenia.
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