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A Postmortem Morphometric Study of Schizophrenia and Huntington Disease

Grazyna Rajkowska, PhD; Lynn D. Selemon, PhD; Patricia S. Goldman-Rakic, PhD

Arch Gen Psychiatry. 1998;55:215-224.

Background  The cortex of patients with schizophrenia exhibits a deficit in neuropil, but the nature and extent of cellular abnormalities remain unclear. To gain further insight into this abnormality, neuronal and glial somal size were analyzed in postmortem brains from 9 patients with schizophrenia, 10 normal (control) patients, and 7 patients with Huntington disease, the latter representing a known neurodegenerative disorder.

Methods  A 3-dimensional image analyzer was used to measure the perimeters of 10722 neuronal and 19913 glial profiles in Brodmann areas 9 and 17. Neurons and glia were classified by size and layer to assess specific vulnerabilities with respect to cortical architecture and circuitry.

Results  The schizophrenic prefrontal cortex was characterized by a downward shift in neuronal sizes accompanied by 70% to 140% per layer increases in the density of small neurons. In layer III only, a significant reduction in mean neuronal size was associated with a significant decrease in the density of very large neurons in sublayer IIIc. Neither neuronal size in occipital area 17 nor glial size in prefrontal or occipital cortexes were reduced. In cortex with Huntington disease, neuronal degeneration was evidenced by concurrence of reduced neuronal size, decreased density of large neurons, and dramatic elevation in density of large glia.

Conclusions  Distinct cytometric abnormalities support the hypothesis that neuronal degeneration in the prefrontal cortex is not a prominent feature of the neuropathological changes in schizophrenia, although an ongoing process in Huntington disease. Rather, schizophrenia appears to involve more subtle abnormalities, with the largest corticocortical projection neurons of layer IIIc expressing the greatest somal reduction.

From the Departments of Psychiatry and Human Behavior (Dr Rajkowska) and Anatomy (Drs Selemon and Goldman-Rakic), University of Mississippi Medical Center, Jackson; and the Section of Neurobiology (Drs Selemon and Goldman-Rakic), Yale University School of Medicine, New Haven, Conn.

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