Original Article A magnetic resonance imaging study of mood stabilizer- and neuroleptic-naı¨ve first-episode mania Bipolar disorder (BD) is a serious psychiatric condition that commonly manifests in adolescence and early adulthood. Although several hypotheses have been postulated, the precise neurobiological underpinnings of this disorder remain unknown. A number of neuroimaging studies have previously reported alterations in various brain structures in bipolar patients who have had multiple mood episodes (1, 2). These studies cannot tell us whether the changes observed were present at disease onset and thus predisposed the subject to develop the disorder or whether these changes developed dur- ing the course of the disorder, either due to effects of multiple episodes or as a consequence of treatment with psychotropic agents. Assessment of brain structures using neuroim- aging methods in first-episode (FE) manic patients may have the potential to provide answers to some of these questions. However, to date, only one group (3–7) has actively pursued this area and the findings have not been consistent. For instance, the first study reported an increased third ventricular to cerebral volume ratio and gray matter to white matter ratio in FE manic patients compared with controls (4), but neither of these findings was Yatham LN, Lyoo IK, Liddle P, Renshaw PF, Wan D, Lam RW, Hwang J. A magnetic resonance imaging study of mood stabilizer- and neuroleptic-naı¨ve first-episode mania. Bipolar Disord 2007: 9: 693–697. ª Blackwell Munksgaard, 2007 Objectives: Patients with bipolar disorder have changes in brain structures but it is unclear if these are present at disease onset and thus predispose subjects to develop the disorder, or whether they develop during the course of the disorder, either due to the effects of multiple episodes or as a consequence of treatment with psychotropic agents. Studies in first-episode (FE) manic patients have the potential to provide answers to these questions. Methods: Voxel-based morphometry (VBM) was used to assess magnetic resonance imaging scans of 15 FE manic patients and 15 matched healthy controls. Results: Using a priori defined statistical criteria, no significant differences in brain structures were noted between the two groups. However, there was approximately a 6% reduction in left anterior cingulate, left precuneus and right posterior cingulate volume in FE patients and these reductions were significant (p £ 0.002) at uncorrected levels. Conclusions: First-episode manic patients have reductions in left anterior, right posterior cingulate as well as left precuneus volumes, but these reductions are smaller and likely worsen with further mood episodes in bipolar patients. Lakshmi N Yatham a , In Kyoon Lyoo b , Peter Liddle c , Perry F Renshaw d , Dante Wan a , Raymond W Lam a and Jaeuk Hwang b a Division of Mood Disorders, University of British Columbia, Vancouver, BC, Canada, b Department of Psychiatry, Seoul National University, Seoul, South Korea, c Department of Psychiatry, University of Nottingham, Nottingham, UK, d Department of Psychiatry, McLean Hospital, Boston, MA, USA Key words: anterior cingulate – first-episode mania – magnetic resonance imaging – mania – mood stabilizer – naı ¨ve – precuneus Received 5 December 2005, revised and accepted for publication 7 July 2006 Corresponding author: Lakshmi N Yatham, MBBS, FRCPC, Division of Mood Disorders, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC V6T 2A1, Canada. Fax: +1 604 822 7922; e-mail: yatham@interchange.ubc.ca The authors of this paper do not have any commercial associations that might pose a conflict of interest in connection with this manu- script. Bipolar Disorders 2007: 9: 693–697 Copyright ª Blackwell Munksgaard 2007 BIPOLAR DISORDERS 693