Diagnostic and sex effects on limbic volumes in early-onset bipolar disorder and schizophrenia

UMMS Affiliation

Department of Psychiatry

Publication Date


Document Type



Adolescent; Age of Onset; Amygdala; Bipolar Disorder; Child; Female; Hippocampus; Humans; Limbic System; *Magnetic Resonance Imaging; Male; Schizophrenia, Childhood; Severity of Illness Index; Sex Factors


Mental Disorders | Nervous System | Neuroscience and Neurobiology | Psychiatry


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.


mood disorders, psychosis, brain imaging technique, child psychiatry

DOI of Published Version



Frazier JA, Hodge SM, Breeze JL, Giuliano AJ, Terry JE, Moore CM, Kennedy DN, Lopez-Larson MP, Caviness VS, Seidman LJ, Zablotsky B, Makris N. Diagnostic and sex effects on limbic volumes in early-onset bipolar disorder and schizophrenia. Schizophr Bull. 2008 Jan;34(1):37-46. Epub 2007 Nov 13. Erratum in: Schizophr Bull. 2009 Nov;35(6):1197. PubMed PMID: 18003631; PubMed Central PMCID: PMC2632388. Link to article on publisher's site

Journal/Book/Conference Title

Schizophrenia bulletin

Related Resources

Link to Article in PubMed

PubMed ID