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Impact of Normal Sexual Dimorphisms on Sex Differences in Structural Brain Abnormalities in Schizophrenia Assessed by Magnetic Resonance Imaging
Jill M. Goldstein, PhD;
Larry J. Seidman, PhD;
Liam M. O'Brien, MS;
Nicholas J. Horton, ScD;
David N. Kennedy, PhD;
Nikos Makris, MD, PhD;
Verne S. Caviness, Jr, MD, DPhil;
Stephen V. Faraone, PhD;
Ming T. Tsuang, MD, PhD
Arch Gen Psychiatry. 2002;59:154-164.
Background Previous studies suggest that the impact of early insults predisposing
to schizophrenia may have differential consequences by sex. We hypothesized
that brain regions found to be structurally different in normal men and women
(sexual dimorphisms) and abnormal in schizophrenia would show significant
sex differences in brain abnormalities, particularly in the cortex, in schizophrenia.
Methods Forty outpatients diagnosed as having schizophrenia by DSM-III-R were systematically sampled to be comparable within sex with
48 normal comparison subjects on the basis of age, ethnicity, parental socioeconomic
status, and handedness. A comprehensive assessment of the entire brain was
based on T1-weighted 3-dimensional images acquired from a 1.5-T magnet. Multivariate
general linear models for correlated data were used to test for sex-specific
effects regarding 22 hypothesized cortical, subcortical, and cerebrospinal
fluid brain volumes, adjusted for age and total cerebrum size. Sex x
group interactions were also tested on asymmetries of the planum temporale,
Heschl's gyrus, and superior temporal gyrus, additionally controlled for handedness.
Results Normal patterns of sexual dimorphisms were disrupted in schizophrenia.
Sex-specific effects were primarily evident in the cortex, particularly in
the frontomedial cortex, basal forebrain, cingulate and paracingulate gyri,
posterior supramarginal gyrus, and planum temporale. Normal asymmetry of the
planum was also disrupted differentially in men and women with schizophrenia.
There were no significant differential sex effects in subcortical gray matter
regions or cerebrospinal fluid.
Conclusion Factors that produce normal sexual dimorphisms may be associated with
modulating insults producing schizophrenia, particularly in the cortex.
From the Harvard Medical School Department of Psychiatry at Massachusetts
Mental Health Center, Boston (Drs Goldstein, Seidman, Faraone, and Tsuang);
Veterans Affairs Boston Healthcare System, Brockton, Mass (Drs Goldstein,
Seidman, Faraone, and Tsuang); Harvard Institute of Psychiatric Epidemiology
and Genetics (Drs Goldstein, Seidman, Faraone, and Tsuang); Departments of
Biostatistics (Mr O'Brien) and Epidemiology (Dr Tsuang), Harvard School of
Public Health; Department of Epidemiology and Biostatistics, School of Public
Health, and School of Medicine, Boston University (Dr Horton); and Departments
of Neurology and Radiology Services, Center for Morphometric Analysis, Harvard
Medical School, Massachusetts General Hospital (Drs Kennedy, Makris, and Caviness),
Boston.
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