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Results of a Voxel-Based Morphometry Study

Daniel P. Dickstein, MD; Michael P. Milham, MD, PhD; Allison C. Nugent, PhD; Wayne C. Drevets, MD; Dennis S. Charney, MD; Daniel S. Pine, MD; Ellen Leibenluft, MD

Arch Gen Psychiatry. 2005;62:734-741.

Context  While numerous magnetic resonance imaging (MRI) studies have evaluated adults with bipolar disorder (BPD), few have examined MRI changes in children with BPD.

Objective  To determine volume alterations in children with BPD using voxel-based morphometry, an automated MRI analysis method with reduced susceptibility to various biases. A priori regions of interest included amygdala, accumbens, hippocampus, dorsolateral prefrontal cortex (DLPFC), and orbitofrontal cortex.

Design  Ongoing study of the pathophysiology of pediatric BPD.

Setting  Intramural National Institute of Mental Health; approved by the institutional review board.

Patients  Pediatric subjects with BPD (n = 20) with at least 1 manic or hypomanic episode meeting strict DSM-IV criteria for duration and elevated, expansive mood. Controls (n = 20) and their first-degree relatives lacked psychiatric disorders. Groups were matched for age and sex and did not differ in IQ.

Main Outcome Measures  With a 1.5-T MRI machine, we collected 1.2-mm axial sections (124 per subject) with an axial 3-dimensional spoiled gradient recalled echo in the steady state sequence. Image analysis was by optimized voxel-based morphometry.

Results  Subjects with BPD had reduced gray matter volume in the left DLPFC. With a less conservative statistical threshold, additional gray matter reductions were found in the left accumbens and left amygdala. No difference was found in the hippocampus or orbitofrontal cortex.

Conclusions  Our results are consistent with data implicating the prefrontal cortex in emotion regulation, a process that is perturbed in BPD. Reductions in amygdala and accumbens volumes are consistent with neuropsychological data on pediatric BPD. Further study is required to determine the relationship between these findings in children and adults with BPD.

Author Affiliations: Mood and Anxiety Disorders Program, National Institute of Mental Health, Bethesda, Md (Drs Dickstein, Nugent, Drevets, Pine, and Leibenluft); Department of Psychiatry, New York University School of Medicine (Dr Milham), and Department of Psychiatry, Mount Sinai School of Medicine (Dr Charney), New York.

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