PREFERENTIAL INVOLVEMENT OF EXCITATORY NEURONS IN MEDIAL TEMPORAL-LOBE IN SCHIZOPHRENIA

Background The anatomical basis of schizophrenia involves the cytoarch itecture of the cerebral cortex, but the phenotype;of the affected neu rons and synapses remains unclear. In mice, the presynaptic protein co mplexin I is a marker of axosomatic (inhibitory) synapses, whereas com plexin II is a marker of axodendritic (mainly excitatory) synapses. Th ese findings suggest that the complexins might be useful in the invest igation of the synaptic pathology of schizophrenia. Methods We charact erised the expression of the complexins in tissue taken at necropsy fr om human medial temporal lobe (hippocampus, parahippocampal gyrus) and cerebellum using in-situ hybridisation and immunoautoradiography. We then measured the concentrations of the complexins and their messenger RNAs (mRNAs) in the medial temporal lobe of 11 patients with schizoph renia and 11 non-schizophrenic controls. Findings The distribution of complexin I and II was consistent with the data on mice, with predomin ant expression of complexin I by inhibitory neurons, and complexin II by excitatory neurons. The amounts of both complexin mRNAs were lower in schizophrenic than in control patients (p<0.001), but the differenc e of complexin II mRNA was greater. The amount of complexin I protein was unchanged in schizophrenia, but complexin II protein was decreased (p<0.001). For both mRNA and protein, the complexin II/complexin I ra tio was lower in schizophrenia, confirming the relatively greater loss of the excitatory marker. The findings did not seem attributable to m edication. Interpretation The synaptic pathology of schizophrenia, at least in medial temporal robe, primarily affects excitatory (glutamate rgic) neurons. The inferred imbalance between excitatory and inhibitor y circuitry may contribute to the involvement of this region in the pa thophysiology of the disorder.