Alterations in the Serotonin System in Schizophrenia: a Systematic Review and Meta-analysis of Postmortem and Molecular Imaging Studies

Serotonergic dysfunction is thought to contribute to the pathophysiology of schizophrenia but the evidence has not been systematically synthesised before. We therefore systematically reviewed postmortem and in vivo molecular imaging studies of serotonin function in schizophrenia. We identified fifty relevant studies investigating eight different serotonin receptor systems in a total of 684 patients and 675 controls. Meta-analysis of postmortem studies found an elevation in prefrontal 5-HT1A receptors with a moderate to large effect size (N=8, 85 patients and 94 controls, SMD=0.60; CI: 0.17-1.03; p=0.007) and a reduction with a large effect size in prefrontal 5-HT2A receptors (N=8, 168 patients and 163 controls, SMD=-0.73; CI: -1.33, -0.12; p=0.019) in schizophrenia vs healthy controls. The evidence for alterations in serotonin transporter availability or other serotonin receptors (5-HT1B; 5-HT1D; 5-HT3; 5-HT4; 5-HT7) is limited. There are fewer studies investigating 5-HT receptors in schizophrenia with neuroimaging. Findings indicated possible 5-HT alterations at psychosis onset, although due to the limited number it was not possible to combine studies in a meta-analysis. Further in vivo studies, particularly in drug naive patients using radiotracers that can index high affinity states, will help determine if the postmortem findings are primary or secondary to other factors.