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Robert B. Zipursky, MD; Evelyn K. Lambe, MSc; Shitij Kapur, MD, PhD; David J. Mikulis, MD

Arch Gen Psychiatry. 1998;55:540-546.

Background  Structural brain differences including decreased gray matter and increased cerebrospinal fluid volumes have been observed in the brains of chronically ill patients with schizophrenia. We hypothesized that deficits in gray matter volume would be present in patients presenting with a first episode of nonaffective psychosis.

Methods  We used magnetic resonance imaging to compare the brains of 77 patients assessed as having a first episode of psychosis (meeting DSM-III-R criteria for schizophrenia, schizophreniform disorder, schizoaffective disorder, delusional disorder, or psychotic disorder not otherwise specified) with those of 61 healthy controls matched for age, sex, race, and parental socioeconomic status. Axial, dual-echo scans of the whole brain were segmented into gray matter, white matter, and cerebrospinal fluid compartments using a computerized volumetric approach. These measures were corrected for the significant effects of intracranial volume and age prior to performing between-group comparisons.

Results  The first episode psychosis group had significantly smaller gray matter volume (t[136]=-2.2; P =.03) and greater cerebrospinal fluid volume (t[136]=2.5; P=.02) than normal controls. In the patient group, gray matter volumes were positively correlated with estimates of IQ but not with age of onset, duration of illness, or measures of premorbid functioning.

Conclusions  Deficits in gray matter volume are present in patients experiencing first episode nonaffective psychosis. The magnitude of these differences is smaller than has been described in more chronically ill patients.

From the Clarke Institute of Psychiatry (Drs Zipursky and Kapur), The Toronto Hospital—Western Division (Dr Mikulis), and the Departments of Psychiatry (Drs Zipursky and Kapur) and Medical Imaging (Dr Mikulis), and the Institute of Medical Science (Ms Lambe), University of Toronto School of Medicine, Toronto, Ontario. Ms Lambe is now with the Interdepartmental Neuroscience Program, Yale University, New Haven, Conn.

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