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Citation |
Sawada K, Young CE, Barr AM, Longworth K, Takahashi S, Arango V, Mann JJ, Dwork AJ, Falkai P, Phillips AG, Honer WG. Mol. Psychiatry 2002; 7(5): 484-492. |
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Copyright |
(Copyright © 2002, Nature Publishing Group) |
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DOI |
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PMID |
12082566 |
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Abstract |
Recent imaging and postmortem studies suggest that impaired connectivity is involved in the pathophysiology of schizophrenia and major affective disorders. We investigated the presynaptic proteins complexin (Cx) I and Cx II in postmortem prefrontal cortex in schizophrenia (n = 13; six suicide, seven nonsuicide), major depression (n= 11, all suicide) and controls (n = 11) with an enzyme-linked immunoadsorbent assay (ELISA). Overall analysis indicated a significant difference between groups (F = 3.93, P = 0.007). Cx I (enriched in inhibitory terminals) was decreased 33% in schizophrenia (26% in schizophrenia/nonsuicide, 42% in schizophrenia/suicide) and 27% in major depression. Cx II (enriched in excitatory terminals) was not significantly different. Analysis of the ratio of Cx II/Cx I was carried out as an indication of the balance of excitatory to inhibitory terminals. A significant difference between groups (ANOVA, F = 6.42, P = 0.005) was observed. The mean value of Cx II/Cx I was significantly increased by 34% in schizophrenia (26% in schizophrenia/nonsuicide and 43% in schizophrenia/suicide) and by 32% in depression compared with control (Student-Newman-Keuls test, P = 0.05). Immunoreactivities of the two complexins were highly correlated in all groups. However, compared with controls and depression, samples from cases with schizophrenia appeared to have relatively less Cx I for similar amounts of Cx II. Immunocytochemical studies of rat frontal cortex after 3 weeks treatment with chlorpromazine, trifluoperazine or haloperidol revealed no differences in complexins, synaptophysin, SNAP-25, syntaxin or VAMP in comparison with animals treated with vehicle. Alterations of complexins may contribute to the molecular substrate for abnormalities of neural connectivity in severe mental disorders. Language: en |
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Keywords |
Adaptor Proteins, Vesicular Transport; Adult; Aged; Animals; Cause of Death; Depressive Disorder; Humans; Immunohistochemistry; Male; Middle Aged; Nerve Tissue Proteins; Prefrontal Cortex; Rats; Rats, Sprague-Dawley; Reference Values; Regression Analysis; Schizophrenia; Suicide |