The hippocampus in schizophrenia: a review of the neuropathological evidence and its pathophysiological implications

Abstract

This paper puts the case for the hippocampus as being central to the neuropathology and pathophysiology of schizophrenia. The evidence comes from a range of approaches, both in vivo (neuropsychology, structural and functional imaging) and post mortem (histology, morphometry, gene expression, and neurochemistry). Neuropathologically, the main positive findings concern neuronal morphology, organisation, and presynaptic and dendritic parameters. The results are together suggestive of an altered synaptic circuitry or "wiring" within the hippocampus and its extrinsic connections, especially with the prefrontal cortex. These changes plausibly represent the anatomical component of the aberrant functional connectivity that underlies schizophrenia. Glutamatergic pathways are prominently but not exclusively affected. Changes appear somewhat greater in the left hippocampus than the right, and CA1 is relatively uninvolved compared to other subfields. Hippocampal pathology in schizophrenia may be due to genetic factors, aberrant neurodevelopment, and/or abnormal neural plasticity; it is not due to any recognised neurodegenerative process. Hippocampal involvement is likely to be associated with the neuropsychological impairments of schizophrenia rather than with its psychotic symptoms.