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Scott A. Schobel, MD; Nicole M. Lewandowski, PhD; Cheryl M. Corcoran, MD; Holly Moore, PhD; Truman Brown, PhD; Dolores Malaspina, MD, MSPH; Scott A. Small, MD

Arch Gen Psychiatry. 2009;66(9):938-946.

Context  Because schizophrenia and related disorders have a chronic time course and subtle histopathology, it is difficult to identify which brain regions are differentially targeted.

Objective  To identify brain sites differentially targeted by schizophrenia, we applied a high-resolution variant of functional magnetic resonance imaging to clinically characterized patients and matched healthy controls and to a cohort of prodromal subjects who were prospectively followed up. Additionally, to explore the potential confound of medication use, the fMRI variant was applied to rodents receiving an antipsychotic agent.

Design  Cross-sectional and prospective cohort designs.

Setting  Hospital clinic and magnetic resonance imaging laboratory.

Participants  Eighteen patients with schizophrenia, 18 controls comparable in age and sex, and 18 prodromal patients followed up prospectively for 2 years. Ten C57-B mice received an antipsychotic agent or vehicle control.

Main Outcome Measures  Regional cerebral blood volume (CBV), as measured with magnetic resonance imaging, and symptom severity, as measured with clinical rating scales.

Results  In a first between-group analysis that compared patients with schizophrenia with controls, results revealed abnormal CBV increases in the CA1 subfield and the orbitofrontal cortex and abnormal CBV decreases in the dorsolateral prefrontal cortex. In a second longitudinal analysis, baseline CBV abnormalities in the CA1 subfield differentially predicted clinical progression to psychosis from a prodromal state. In a third correlational analysis, CBV levels in the CA1 subfield differentially correlated with clinical symptoms of psychosis. Finally, additional analyses of the human data set and imaging studies in mice suggested that antipsychotic agents were not confounding the primary findings.

Conclusions  Taken as a whole, the results suggest that the CA1 subfield of the hippocampal subregion is differentially targeted by schizophrenia and related psychotic disorders. Interpreted in the context of previous studies, these findings inform underlying mechanisms of illness progression.

Author Affiliations: Departments of Neurology (Drs Lewandowski and Small), Psychiatry (Drs Schobel, Corcoran, and Moore), and Radiology (Dr Brown), Columbia University, College of Physicians and Surgeons, and Department of Psychiatry, New York University Medical Center (Dr Malaspina), New York, New York.

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