Alterations in the cortical serotonergic system in schizophrenia: a postmortem study.
Previous studies have suggested a disturbance in the cortical serotonergic (5-HT) system in schizophrenia; however, these studies have been confounded by suicide in the patients groups, which in itself is associated with alterations in the 5-HT system. In this study we characterized various components of the 5-HT system in 14 areas of the frontal and parietal cortex in tissue obtained at postmortem from aged chronically hospitalized nonsuicidal schizophrenics compared to age-matched controls. We found no differences between control and schizophrenic subjects in the density of 5-HT uptake sites or other markers of 5-HT innervation. In Brodmann areas 24 and 6 the concentration of 5-HT2A,C receptors was decreased in all schizophrenics regardless of their antipsychotic treatment history. In all other areas examined 5-HT2A,C receptor concentrations were dramatically decreased in schizophrenics patients on drugs at time of death, whereas those off drugs at death showed the same values as control subjects. The density of 5-HT1A receptors was increased in areas 24, 9a (caudal part of area 9), 44, and 6 in subjects with schizophrenia. Antipsychotic treatment did not appear to have a significant effect. Thus, the specific pattern of alterations in the 5-HT system in schizophrenia may depend on the patient population and on antemortem antipsychotic treatment. These data also provide evidence that regulation of the 5-HT2 receptor may be involved in antipsychotic action.
Gurevich
E V
EV
Christopher Center for Parkinson's Disease Research, Sun Health Research Institute, Sun City, Arizona 85372, USA.
Joyce
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JN
D000368:Aged; D000369:Aged, 80 and over; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use; D001344:Autopsy; D001345:Autoradiography; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D011869:Radioligand Assay; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D050637:Receptors, Dopamine D3; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D012701:Serotonin / Q000378:metabolism*
D014150:Antipsychotic Agents; C493593:DRD3 protein, human; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D011985:Receptors, Serotonin; D012701:Serotonin