Original Article A population-based morphometric MRI study in patients with first-episode psychotic bipolar disorder: comparison with geographically matched healthy controls and major depressive disorder subjects Pe´rico CA-M, Duran FLS, Zanetti MV, Santos LC, Murray RM, Scazufca M, Menezes PR, Busatto GF, Schaufelberger MS. A population-based morphometric MRI study in patients with first-episode psychotic bipolar disorder: comparison with geographically matched healthy controls and major depressive disorder subjects. Bipolar Disord 2011: 13: 28–40. ª 2011 The Authors. Journal compilation ª 2011 John Wiley & Sons A ⁄ S. Objectives: Many morphometric magnetic resonance imaging (MRI) studies that have investigated the presence of gray matter (GM) volume abnormalities associated with the diagnosis of bipolar disorder (BD) have reported conflicting findings. None of these studies has compared patients with recent-onset psychotic BD with asymptomatic controls selected from exactly the same environment using epidemiological methods, or has directly contrasted BD patients against subjects with first-onset psychotic major depressive disorder (MDD). We examined structural brain differences between (i) BD (type I) subjects and MDD subjects with psychotic features in their first contact with the healthcare system in Brazil, and (ii) these two mood disorder groups relative to a sample of geographically matched asymptomatic controls. Methods: A total of 26 BD subjects, 20 subjects with MDD, and 94 healthy controls were examined using either of two identical MRI scanners and acquisition protocols. Diagnoses were based on DSM-IV criteria and confirmed one year after brain scanning. Image processing was conducted using voxel-based morphometry. Results: The BD group showed increased volume of the right dorsal anterior cingulate cortex relative to controls, while the MDD subjects exhibited bilateral foci GM deficits in the dorsolateral prefrontal cortex (p < 0.05, corrected for multiple comparisons). Direct comparison between BD and MDD patients showed a focus of GM reduction in the right-sided dorsolateral prefrontal cortex (p < 0.05, corrected for multiple comparisons) and a trend (p < 0.10, corrected) toward left- sided GM deficits in the dorsolateral prefrontal cortex of MDD patients. When analyses were repeated with scanner site as a confounding covariate the finding of increased right anterior cingulate volumes in BD patients relative to controls remained statistically significant (p = 0.01, corrected for multiple comparisons). Conclusions: These findings reinforce the view that there are important pathophysiological distinctions between BD and MDD, and indicate that subtle dorsal anterior cingulate abnormalities may be relevant to the pathophysiology of BD. Cintia de Azevedo-Marques Pe ´ rico a , Fabio L S Duran a , Marcus V Zanetti a , Luciana C Santos a , Robin M Murray b , Marcia Scazufca a , Paulo R Menezes c , Geraldo F Busatto a and Maristela S Schaufelberger a a Laboratory of Psychiatric Neuroimaging (LIM-21), Department and Institute of Psychiatry, Faculty of Medicine, University of Sa ˜o Paulo, Sa ˜ o Paulo, Brazil, b Department of Psychiatry, Institute of Psychiatry, KingÕs College, London, UK, c Department of Preventive Medicine, Faculty of Medicine, University of Sa ˜ o Paulo, Sa ˜ o Paulo, Brazil doi: 10.1111/j.1399-5618.2011.00896.x Key words: anterior cingulate gyrus – depression – first-episode psychosis – mania – prefrontal cortex – voxel based-morphometry Received 23 October 2009, revised and accepted for publication 16 December 2010 Corresponding author: Cintia de Azevedo-Marques Pe ´ rico, M.D. Departamento de Psiquiatria (LIM 21) Faculdade de Medicina Universidade de Sa ˜o Paulo Rua Ovı ´dio Pires Campos s ⁄ n – CEP 05403-903 Sa ˜ o Paulo, SP, Brazil Fax: 55-11-30698132 E-mail: cazevedomarques@hotmail.com The authors of this paper do not have any commercial associations that might pose a conflict of interest in connection with this manuscript. Bipolar Disorders 2011: 13: 28–40 ª 2011 John Wiley and Sons A/S BIPOLAR DISORDERS 28