Structural brain changes in bipolar disorder using deformation ¢eld morphometry Jair C. Soares, 1,2,3,CA Peter Kochunov, 4 E. Serap Monkul, 1,3,5 Mark A. Nicoletti, 1 Paolo Brambilla, 6 Roberto B. Sassi, 7 Alan G. Mallinger, 8,9 Ellen Frank, 8,10 David J. Kupfer, 8 Jack Lancaster 4 and Peter Fox 4 1 Division of Mood and Anxiety Disorders, Department of Psychiatry; 2 Department of Radiology; 3 SouthTexas Veterans Health Care System, Audie L. Murphy Division, San Antonio, Texas, USA; 4 Research Imaging Center, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA; 5 Department of Psychiatry, Dokuz Eylˇl University School of Medicine, Izmir, Turkey; 6 Department of Pathology and Experimental and Clinical Medicine, Section of Psychiatry, University of Udine, Udine, Italy; 7 Department of Psychiatry, University of Sao Paulo School of Medicine, Sao Paulo, Brazil; 8 Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine; 9 Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA; 10 Department of Psychology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA CA,1 Corresponding Author and Address: soares@uthscsa.edu Received13 January 2005; accepted 9 February 2005 The objective of this study was to investigate anatomical brain ab- normalities in adult bipolar patients using a deformation ¢eld mor- phometry technique. Our sample consisted of 32 right-handed bipolar I patients (men/women¼ 16/16) and 32 right-handed, age and gender matched healthy controls. Deformation ¢eld morphometry analysis was performed on three-dimensional spoiled gradient recalled acquisition images. We found gender- speci¢c structural di¡erences between bipolar patients and healthy individuals. Bipolar men had signi¢cantly larger lateral ventricles (especially pronounced in the left hemisphere) and smaller left dorsolateral prefrontal cortex than healthy male controls. Our results are complementary to the ¢ndings of functional imaging and post-mortem studies that demonstrate abnormalities in the dorsolateral prefrontal cortex in bipolar patients. NeuroReport 16:541^544  c 2005 Lippincott Williams & Wilkins. Key words: Bipolar disorder; Mood disorders; Magnetic resonance imaging; Morphometry; Neuroimaging; Structural INTRODUCTION Advances in automated brain imaging methods have brought new possibilities for in-vivo studies of the human brain. Voxel-based morphometry [1] and deformation-based morphometry [2] are two examples of these automated methods, using three-dimensional (3-D) magnetic resonance images of the brain to detect anatomical differences. Deformation-based morphometry, introduced by Ashburner and colleagues [1], is used to characterize differences in deformation fields attributed to gross anatomical differences in brain shape in small groups (Nr20). Groups to be evaluated are aligned using nonlinear deformations [3] to a common brain template, and differences in deformation fields are analyzed using multivariate analysis of covariance and canonical variates analysis. Unfortunately, this method was not sensitive to small, regional differences due to the use of extensive spatial smoothing (8–16 mm full-width at half-maximum Gaussian kernel). An alternative approach called deformation field mor- phometry (DFM) was developed for the assessment of regional anatomical differences within small groups (NB20) [4]. It is based on a fast 3-D warping algorithm, called octree spatial normalization [5,6], and the concept of group- representative brains [7]. This method was used to test for differences in the interhemispheric cerebral asymmetry in right-handed Caucasian men, where it reliably detected all common interhemispheric asymmetries such as frontal and occipital petalias [4]. Neuroanatomic studies of bipolar disorder have identi- fied structural changes in anterior limbic networks, includ- ing decreased volumes of prefrontal subregions, amygdala and striatal enlargement, cerebellar atrophy and ventricu- lomegaly [8]. Lateral ventriculomegaly is a frequently reported finding in bipolar disorder; several studies have reported abnormally enlarged brain ventricles in bipolar disorder, although to a lesser degree than in schizophrenia [9]. Lateral ventriculomegaly is thought to be related to repeated affective episodes and greater illness severity [10], and to be a result of decreased volumes in periventricular structures. Strakowski and colleagues [10] reported that multiple-episode bipolar patients had significantly greater ventricular volumes than first-episode patients. Addition- ally, they showed that the multiple-episode patients did not have decreased volumes of periventricular structures like the hippocampus or striatum to explain the ventriculome- galy, and suggested it might be white matter loss resulting in ventricular expansion. A recent report on morphometric differences observed in a large population of people diagnosed with schizophrenia [11] indicated that gender played an important role in the magnitude of observed differences, in accordance with the suggestions that me- chanisms underlying psychotic disorders involve sexually BRAIN IMAGING NEUROREPORT 0959-4965  c Lippincott Williams & Wilkins Vol 16 No 6 25 April 2005 541 Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.