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

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Abstract
Objective: The limbic structures in early-onset schizophre- nia-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 with- outpsychosis,19 with BPD withpsychosis, 20with SZ, and 29 healthy controls (HC), similar in age (6-17 years) and sex,underwent structuredand clinicalinterviews,neurolog- icalexamination,andcognitivetesting.Structuralmagnetic 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. How- ever, there were diagnosis-by-sex interactions in the amyg- dala and hippocampus, structures that are rich in sex hormone receptors. In addition, smaller thalamus was asso- ciated with SZ while larger right NA volumes were most re- lated 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 neuro- pathology associated with disease expression.