It appears that a heterogeneous population of interneurons is implicated in schizophrenia. Further studies are needed to determine whether specific interneuron subpopulations are altered or whether common or distinct upstream pathways are responsible for interneuron deficits in schizophrenia.

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Abnormalities within the corpus callosum (CC) have been identified in schizophrenia brains and are thought to affect inter-hemispheric communication, which in-turn is postulated to underlie some schizophrenia symptoms. Furthermore, hemisphere asymmetry of fractional anisotropy, detected by diffusion tensor imaging, left-higher-than-right- has been observed in normal individuals in the CC genu. This asymmetry is significantly reduced in the left CC genu of first-episode and chronic schizophrenia subjects. We examined the protein expression profile of the CC genu, including the profiles from the left and right hemisphere, in schizophrenia brains compared to controls using two-dimensional gel electrophoresis and mass spectrometry techniques. Proteins involved in cytoskeletal structure and function, neuroprotective function and energy metabolism were identified as differentially expressed, suggesting these proteins may underlie abnormal CC genu structure and function. Proteins in these functional categories also displayed different expression levels in the left CC genu compared to the right in both control and schizophrenia brains and therefore may be involved in normal CC asymmetry and reduced asymmetry in schizophrenia individuals. This initial pool of protein candidates and abnormal functional pathways opens up avenues for further investigation of molecular mechanisms involving the CC in schizophrenia pathogenesis and symptoms.

Background Reduced synaptic connectivity in frontal cortex may contribute to schizophrenia symptoms. While altered mRNA and protein expression of various synaptic genes has been found, discrepancies between studies mean a generalisable synaptic pathology in schizophrenia has not been identified. Methods We determined if mRNAs encoding presynaptic proteins enriched in inhibitory [vesicular GABA transporter (VGAT) and complexin 1] and/or excitatory [vesicular glutamate transporter (VGluT1) and complexin 2] terminals are altered in the dorsolateral prefrontal cortex of subjects with schizophrenia (n=37 patients, n=37 controls). We also measured mRNA expression of markers associated with synaptic plasticity/neurite outgrowth [growth associated protein 43 (GAP43) and neuronal navigators 1 and 2 (NAV1 and NAV2)]; and mRNAs of other synaptic-associated proteins previously implicated in schizophrenia: dysbindin and vesicle-associated membrane protein (VAMP1) mRNAs using quantitative RT-PCR. Results No significant changes in complexin 1, VGAT, complexin 2, VGluT1, dysbindin, NAV2, or VAMP1 mRNA expression were found, however we observed reduced expression of mRNAs associated with plasticity/cytoskeletal modification (GAP43 and NAV1) in schizophrenia. Although dysbindin mRNA did not differ in schizophrenia compared to controls, dysbindin mRNA positively correlated with GAP-43 and NAV1 in schizophrenia, but not in controls, suggesting low levels of dysbindin may be linked to reduced plasticity in the disease state. No relationships between three dysbindin genetic polymorphisms previously associated with dysbindin mRNA levels were found. Conclusions A reduction in the plasticity of synaptic terminals supports the hypothesis that reduced modifiability of synaptic terminals may contribute to neuropathology and working memory deficits in schizophrenia.