Altered immunoreactivity of complexin protein in prefrontal cortex in severe mental illness.
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.
Sawada
K
K
Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada V5Z 1L8.
Young
C E
CE
Barr
A M
AM
Longworth
K
K
Takahashi
S
S
Arango
V
V
Mann
J J
JJ
Dwork
A J
AJ
Falkai
P
P
Phillips
A G
AG
Honer
W G
WG
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
D033942:Adaptor Proteins, Vesicular Transport; D009419:Nerve Tissue Proteins; C095992:complexin I; C095993:complexin II