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Amygdala and Hippocampal Volumes in Adolescents and Adults With Bipolar Disorder
Hilary P. Blumberg, MD;
Joan Kaufman, PhD;
Andrés Martin, MD, MPH;
Ronald Whiteman, BA;
Jane Hongyuan Zhang, PhD;
John C. Gore, PhD;
Dennis S. Charney, MD;
John H. Krystal, MD;
Bradley S. Peterson, MD
Arch Gen Psychiatry. 2003;60:1201-1208.
Background The purported functions of medial temporal lobe structures suggest their involvement in the pathophysiology of bipolar disorder (BD). Previous reports of abnormalities in the volume of the amygdala and hippocampus in patients with BD have been inconsistent in their findings and limited to adult samples. Appreciation of whether volumetric abnormalities are early features of BD or whether the abnormalities represent neurodegenerative changes associated with illness duration is limited by the paucity of data in juvenile samples.
Objective To investigate amygdala and hippocampal volume in adults and adolescents with BD.
Setting and Participants Subjects included 36 individuals (14 adolescents and 22 adults) in outpatient treatment for BD type I at a university hospital or Veterans Affairs medical center or in the surrounding community, and 56 healthy comparison subjects (23 adolescents and 33 adults).
Design and Main Outcome Measures Amygdala and hippocampal volumes were defined and measured on high-resolution anatomic magnetic resonance imaging scans. We used a mixed-model, repeated-measures statistical analysis to compare amygdala and hippocampal volumes across groups while covarying for total brain volume, age, and sex. Potential effects of illness features were explored, including rapid cycling, medication, alcohol or other substance dependence, duration, and mood state.
Results For both the amygdala and hippocampal regions, we found an overall significant volume reduction in the BD compared with the control group (P<.0001). Amygdala volume reductions (15.6%) were highly significant (P<.0001). We observed a nonsignificant trend (P = .054) toward reductions in hippocampal volumes of lesser magnitude (5.3%). Effects of illness features were not detected.
Conclusions These results suggest that BD is associated with decreased volumes of medial temporal lobe structures, with greater effect sizes in the amygdala than in the hippocampus. These abnormalities are likely manifested early in the course of illness, as they affected adolescent and adult subjects similarly in this sample.
From the Departments of Psychiatry (Drs Blumberg, Kaufman, and Krystal) and Diagnostic Radiology (Dr Gore), and the Yale Child Study Center (Dr Martin), Yale University School of Medicine, New Haven, Conn; the Department of Psychiatry, Veterans Affairs Connecticut Healthcare System (Drs Blumberg and Krystal), and the Department of Veterans Affairs Cooperative Studies Program Coordinating Center (Dr Zhang), West Haven, Conn; the Department of Psychiatry, Columbia College of Physicians and Surgeons (Mr Whiteman and Dr Peterson), and the New York State Psychiatric Institute (Dr Peterson), New York; the Mood and Anxiety Disorders Research Program, National Institute of Mental Health, Bethesda, Md (Dr Charney); and the Department of Radiology, Vanderbilt University Medical Center, Nashville, Tenn (Dr Gore).
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