title: Altered immunoreactivity of complexin protein in prefrontal cortex in severe mental illness.
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.
authors.affiliation: Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada V5Z 1L8.
authors.forename: K
authors.initials: K
authors.lastname: Sawada
authors.forename: C E
authors.initials: CE
authors.lastname: Young
authors.forename: A M
authors.initials: AM
authors.lastname: Barr
authors.forename: K
authors.initials: K
authors.lastname: Longworth
authors.forename: S
authors.initials: S
authors.lastname: Takahashi
authors.forename: V
authors.initials: V
authors.lastname: Arango
authors.forename: J J
authors.initials: JJ
authors.lastname: Mann
authors.forename: A J
authors.initials: AJ
authors.lastname: Dwork
authors.forename: P
authors.initials: P
authors.lastname: Falkai
authors.forename: A G
authors.initials: AG
authors.lastname: Phillips
authors.forename: W G
authors.initials: WG
authors.lastname: Honer
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport; D000328:Adult; D000368:Aged; D000818:Animals; D002423:Cause of Death; D003866:Depressive Disorder / Q000378:metabolism* / Q000401:mortality; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012044:Regression Analysis; D012559:Schizophrenia / Q000378:metabolism* / Q000401:mortality; D013405:Suicide
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D009419:Nerve Tissue Proteins; C095992:complexin I; C095993:complexin II