Neuropathological studies of synaptic connectivity in the hippocampal formation in schizophrenia.

Cytoarchitectural changes in the hippocampal formation have been prominent among the various neuropathological abnormalities reported in schizophrenia. Replicated positive findings include decreased neuronal size and alterations in presynaptic and dendritic markers. These findings, in the absence of neurodegenerative changes, suggest that there are alterations in the neural circuitry in schizophrenia. These may represent the anatomical correlate of the aberrant functional connectivity described in neuroimaging studies, which in turn contributes to the psychotic and cognitive symptomatology of the disorder. The identity of the affected hippocampal circuits remains unclear; there is evidence for both glutamatergic and GABAergic involvement, and perhaps for a gradient of pathology in which changes are most apparent in CA4 and the subiculum, and least in CA1. The data, their interpretation, and their limitations are discussed, with particular emphasis upon molecular and immunological studies of synaptic protein gene expression.