Evidence for progression of brain structural abnormalities in schizophrenia: beyond the neurodevelopmental model.
OBJECTIVE
Clinical, neuroimaging, neuropathological and neuropsychological evidence suggests that, in schizophrenia, there is structural and functional disturbance of the hippocampus. The purpose of this paper is to present published findings concerning the nature, timing and course of these putative disturbances of hippocampal function and the pathophysiological mechanisms involved, and to explore whether schizophrenia is a disorder of neurodevelopment, neurodegeneration or a combination of both processes.


METHODS
The available cross-sectional and longitudinal evidence for hippocampal involvement in schizophrenia is reviewed and a model of hippocampal involvement in this disorder, which derives from our own cross-sectional and longitudinal hippocampal imaging data, is described.


RESULTS
We propose a three-hit model in which an early neurodevelopmental lesion renders the hippocampus vulnerable to further insult later in life during the transition phase to active illness. The available evidence suggests that the left hippocampus is particularly vulnerable during these early stages, while further insult involving the hippocampus bilaterally occurs in those who develop a chronic form of the illness.


CONCLUSIONS
Intervention strategies should target the most vulnerable stages of the illness, in particular the transition phase to psychosis, when novel treatments may prevent the illness or ameliorate its effects.
Velakoulis
D
D
Cognitive Neuropsychiatry Research and Academic Unit, University of Melbourne and Sunshine Hospital, St Albans, Victoria, Australia. dev@cortex.mhri.edu.au
Wood
S J
SJ
McGorry
P D
PD
Pantelis
C
C
D001921:Brain / Q000002:abnormalities* / Q000473:pathology; D003952:Diagnostic Imaging; D018450:Disease Progression; D004292:Dominance, Cerebral / Q000502:physiology; D006624:Hippocampus / Q000002:abnormalities / Q000503:physiopathology; D006801:Humans; D009483:Neuropsychological Tests; D012307:Risk Factors; D012559:Schizophrenia / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control