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Schizophrenia Bulletin Advance Access originally published online on November 13, 2007
Schizophrenia Bulletin 2008 34(1):37-46; doi:10.1093/schbul/sbm120
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© The Author 2007. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org.

Diagnostic and Sex Effects on Limbic Volumes in Early-Onset Bipolar Disorder and Schizophrenia

Jean A. Frazier1,2,3,4, Steven M. Hodge5, Janis L. Breeze2,3, Anthony J. Giuliano2,3,6, Janine E. Terry3, Constance M. Moore2,3,7, David N. Kennedy3,5,8, Melissa P. Lopez-Larson2,3,4, Verne S. Caviness5,8,9, Larry J. Seidman2,6,10, Benjamin Zablotsky3 and Nikos Makris5,11
2 Department of Psychiatry, Harvard Medical School
3 Child and Adolescent Neuropsychiatric Research Program, Cambridge Health Alliance
4 Department of Psychiatry, McLean Hospital
5 Center for Morphometric Analysis, Massachusetts General Hospital
6 Department of Psychiatry, Massachusetts Mental Health Center at the Beth Israel Medical Center
7 Brain Imaging Center, McLean Hospital
8 Department of Neurology, Harvard Medical School
9 Department of Pediatric Neurology, Massachusetts General Hospital
10 Department of Psychiatry, Massachusetts General Hospital
11 Department of Neurology, Massachusetts General Hospital

1 To whom correspondence should be addressed; tel: 781-306-8631, fax: 781-306-8644, e-mail: JFrazier{at}challiance.org.

Objective: The limbic structures in early-onset schizophrenia-spectrum illness (SZ) and bipolar disorder (BPD) were studied to discern patterns associated with diagnosis and sex. Methods: Thirty-five youths with DSM-IV BPD without psychosis, 19 with BPD with psychosis, 20 with SZ, and 29 healthy controls (HC), similar in age (6-17 years) and sex, underwent structured and clinical interviews, neurological examination, and cognitive testing. Structural magnetic resonance images (MRIs) were acquired on a 1.5 Tesla, General Electric Signa Scanner. Differences in subcortical brain volumes, including the amygdala and hippocampus, were evaluated using two-way (diagnosis, sex) univariate analyses covarying for total cerebral volume and age. Results: Youth with SZ and BPD showed no differences in amygdala and hippocampal volumes. However, boys with SZ had smallest left amygdala and girls with BPD had the smallest left hippocampal volumes. In exploratory analyses, SZ showed reduced thalamic volumes bilaterally and both BPD groups had larger right nucleus accumbens (NA) volumes relative to HC. Conclusion: There were no limbic volumetric differences between BPD and SZ. However, there were diagnosis-by-sex interactions in the amygdala and hippocampus, structures that are rich in sex hormone receptors. In addition, smaller thalamus was associated with SZ while larger right NA volumes were most related to BPD. This study underscores the importance of assessing diagnostic effects and sex effects on the brain in future studies and provides evidence that boys and girls with SZ and BPD may have differential patterns of neuropathology associated with disease expression.

Keywords: mood disorders / psychosis / brain imaging technique / child psychiatry


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