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Preliminary Findings

Gorazd Rosoklija, MD, PhD; Glen Toomayan, BS; Steven P. Ellis, PhD; John Keilp, PhD; J. John Mann, MD; Norman Latov, MD, PhD; Arthur P. Hays, MD; Andrew J. Dwork, MD

Arch Gen Psychiatry. 2000;57:349-356.

Background  Postmortem studies of the subiculum from subjects with schizophrenia have detected smaller pyramidal cell bodies and diminished immunoreactivity for the dendritic protein, microtubule-associated protein 2. While these findings suggest that subicular pyramidal cell dendrites may be structurally altered in subjects with schizophrenia, this possibility had not been tested directly.

Methods  Rapid Golgi impregnation of archival brain specimens was used to compare the morphologic characteristics of subicular dendrites in subjects with schizophrenia (n=13) and mood disorders (n=6) with subjects without psychiatric disease (n=8). The specimens were processed and analyzed by physicians blind to diagnosis. The extent of dendritic trees in the subiculum and fusiform gyrus was examined by Sholl analysis. Spine density on apical dendrites of subicular pyramidal cells was determined at a fixed distance from the cell body.

Results  Spine density and arborization of subicular apical dendrites were significantly related to diagnostic group. Spine density was significantly lower in the schizophrenia and mood disorder groups than in the nonpsychiatric group. Among the mood disorder cases, diminished spine density was apparently related to a strong family history of major psychiatric diseases. There were no significant effects of diagnostic group on Sholl analysis of nonapical subicular dendrites nor on Sholl analysis of dendrites of neocortical pyramidal cells in the fusiform gyrus.

Conclusions  We have observed an association between schizophrenia and major mood disorders and structural abnormalities of subicular apical dendrites. Further studies are needed to test this association in a larger sample and to evaluate the potential role of family history and of confounding factors, such as medications and chronic institutionalization.

From the Departments of Psychiatry, Division of Neuroscience (Drs Rosoklija, Mann, and Dwork), Neurology (Dr Latov), and Pathology, Division of Neuropathology (Drs Hays and Dwork), College of Physicians & Surgeons of Columbia University, New York, NY; Duke University School of Medicine (Mr Toomayan), Durham, NC; and the Department of Neuroscience, Division of Neuropathology (Drs Ellis, Keilp, and Dwork), and the Schizophrenia Research Unit (Dr Dwork), New York State Psychiatric Institute, New York.

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