title: Alterations in the serotonin system in schizophrenia: a systematic review and meta-analysis of postmortem and molecular imaging studies.
abstract: 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.
authors: Medical Research Council, Clinical Sciences Centre, Institute of Clinical Sciences, Hammersmith Hospital Campus, Imperial College London, London W12 0NN, UK; Department of Psychiatry and Behavioural Sciences, The University of Texas Health Science Centre at Houston, Houston, TX, USA. Electronic address: sudhakar.selvaraj@uth.tmc.edu.
authors: Sudhakar
authors: S
authors: Selvaraj
authors: Centre for Affective Disorders, Institute of Psychiatry, King's College London, London SE5 8AF, UK.
authors: Danilo
authors: D
authors: Arnone
authors: Medical Research Council, Clinical Sciences Centre, Institute of Clinical Sciences, Hammersmith Hospital Campus, Imperial College London, London W12 0NN, UK; Forensic Outreach Service & Inreach Team HMP Wandsworth, South West London & St George's NHS Mental Health Trust, Springfield Hospital, Glenburnie Road, London SW17 7DJ, UK.
authors: Alessandra
authors: A
authors: Cappai
authors: Medical Research Council, Clinical Sciences Centre, Institute of Clinical Sciences, Hammersmith Hospital Campus, Imperial College London, London W12 0NN, UK; Department of Psychosis Studies, Institute of Psychiatry, King's College London, London SE5 8AF, UK.
authors: Oliver
authors: O
authors: Howes
mesh_terms: D001921:Brain / Q000378:metabolism*; D006801:Humans; D057054:Molecular Imaging; D011985:Receptors, Serotonin / Q000378:metabolism*; D012559:Schizophrenia / Q000378:metabolism*
chemical_list: D011985:Receptors, Serotonin
keywords: 5-HT1A receptor; 5-HT2A receptor; Neuroimaging; Positron Emission Tomography (PET); Postmortem; Prefrontal cortex; Psychosis; Schizophrenia; Serotonin or 5-HT