1. ¹Department of Psychiatry & Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA
2. ²Laboratory of NeuroImaging, Department of Neurology, University of California, Los Angeles, CA, USA
3. ³Department of Psychiatry, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
4. ⁴Department of Biochemistry and Bipolar Disorders Program, Federal University of Rio Grande do Sul, Porto Alegre, Brazil
5. ⁵Department of Psychiatry, University of Sao Paulo School of Medicine, Sao Paulo, Brazil
6. ⁶Department of Psychiatry, UNC Chapel Hill School of Medicine, Chapel Hill, NC, USA
7. ⁷Scientific Institute IRCCS, E. Medea, Udine, Italy
8. ⁸Section of Psychiatry, Department of Pathology and Experimental & Clinical Medicine, University of Udine, Udine, Italy
9. ⁹Department of Psychiatry, Massachusetts General Hospital, Harvard University, Boston, MA, USA
10. ¹⁰Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

Correspondence: Dr CE Bearden, Department of Psychiatry & Biobehavioral Sciences, University of California, Los Angeles, 300 Building Medical Plaza, Suite 2265, Los Angeles, CA 90095, USA. Tel: +1 310 206 2983; Fax: +1 310 794 9517; E-mail: cbearden@mednet.ucla.edu

Received 20 December 2006; Revised 31 May 2007; Accepted 8 June 2007; Published online 8 August 2007.

Abstract

Declarative memory impairments are common in patients with bipolar illness, suggesting underlying hippocampal pathology. However, hippocampal volume deficits are rarely observed in bipolar disorder. Here we used surface-based anatomic mapping to examine hippocampal anatomy in bipolar patients treated with lithium relative to matched control subjects and unmedicated patients with bipolar disorder. High-resolution brain magnetic resonance images were acquired from 33 patients with bipolar disorder (21 treated with lithium and 12 unmedicated), and 62 demographically matched healthy control subjects. Three-dimensional parametric mesh models were created from manual tracings of the hippocampal formation. Total hippocampal volume was significantly larger in lithium-treated bipolar patients compared with healthy controls (by 10.3%; p=0.001) and unmedicated bipolar patients (by 13.9%; p=0.003). Statistical mapping results, confirmed by permutation testing, revealed localized deficits in the right hippocampus, in regions corresponding primarily to cornu ammonis 1 subfields, in unmedicated bipolar patients, as compared to both normal controls (p=0.01), and in lithium-treated bipolar patients (p=0.03). These findings demonstrate the sensitivity of these anatomic mapping methods for detecting subtle alterations in hippocampal structure in bipolar disorder. The observed reduction in subregions of the hippocampus in unmedicated bipolar patients suggests a possible neural correlate for memory deficits frequently reported in this illness. Moreover, increased hippocampal volume in lithium-treated bipolar patients may reflect postulated neurotrophic effects of this agent, a possibility warranting further study in longitudinal investigations.