Automated MRI parcellation study of regional volume and thickness of prefrontal cortex (PFC) in antipsychotic-naı¨ve schizophrenia Venkatasubramanian G, Jayakumar PN, Gangadhar BN, Keshavan MS. Automated MRI parcellation study of regional volume and thickness of prefrontal cortex (PFC) in antipsychotic-naı¨ve schizophrenia. Objective: Prefrontal cortical dysfunction is considered to be critical in the pathogenesis of schizophrenia. However, structural magnetic resonance imaging (MRI) studies on the PFC have yielded inconsistent results because of various confounding factors. Method: In this study we examined the volume and thickness abnormalities of the PFC in antipsychotic-naı¨ve schizophrenia patients (n = 51) in comparison with age-, sex-, and handedness-matched (as a group) healthy comparison subjects (n = 47) using a newly described automated MRI parcellation analysis. Results: Schizophrenia patients showed i) significant volume deficits in bilateral lateral orbitofrontal and left medial orbitofrontal cortices as well as bilateral pars triangularis; and ii) significant thickness deficit in bilateral medial orbitofrontal cortices. Negative syndrome score had a significant negative correlation with the thickness of the left medial orbitofrontal cortex. Conclusion: The study findings emphasize that prefrontal deficit in schizophrenia is differential and involves primarily the regions essential for Ôsocial cognitionÕ. G. Venkatasubramanian 1 , P. N. Jayakumar 2 , B. N. Gangadhar 1 , M. S. Keshavan 3 Departments of 1 Psychiatry and 2 Neuroimaging and Interventional Radiology, National Institute of Mental Health and Neurosciences, Bangalore, India and 3 Department of Psychiatry & Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI, USA Key words: schizophrenia; prefrontal cortex; magnetic resonance imaging Ganesan Venkatasubramanian, Department of Psychia- try, National Institute of Mental Health and Neuro- sciences, Bangalore 560029, Karnataka, India. E-mail: gvs@nimhans.kar.nic.in; venkat.nimhans@yahoo.com Accepted for publication March 31, 2008 Significant outcomes • Prefrontal cortex deficit is differential in antipsychotic-naı¨ve schizophrenia patients and it involves the orbitofrontal region and pars triangularis. • Medial orbitofrontal cortex deficits are associated with negative syndrome in schizophrenia. • Findings of this study support the Ôsocial brain theoryÕ of schizophrenia. Limitations • The study population was devoid of substance abuse or dependence. While this avoided the confounding influence of substance on brain image analysis, it might restrict the generalizability of study findings. • No structured interview was used to assess healthy controls. However, to partially compensate for this, they were evaluated in detail to rule out any psychiatric disorder by i) General Health Questionnaire screening, ii) comprehensive history collection, and iii) a thorough mental status examination. • IQ assessment was not carried out; however, none of the subjects had any delayed developmental mile stones. Also, careful history elicitation was done to rule out any subtle mental retardation. Acta Psychiatr Scand 2008: 117: 420–431 All rights reserved DOI: 10.1111/j.1600-0447.2008.01198.x Copyright Ó 2008 The Authors Journal Compilation Ó 2008 Blackwell Munksgaard ACTA PSYCHIATRICA SCANDINAVICA 420