A multivariate approach to aggression and the orbital frontal cortex in psychiatric patients David A. Gansler a,b, ⁎ , Nicole C.R. McLaughlin c , Lisa Iguchi a , Matthew Jerram a , Dana W. Moore d , Rafeeque Bhadelia e , Carl Fulwiler f,g a Department of Psychology, Suffolk University, Boston, MA, USA b Department of Psychiatry, Tufts University School of Medicine, Boston, MA, USA c Department of Psychiatry and Human Behavior, Warren Alpert Medical School of Brown University, Providence, RI, USA d Mount Sinai Medical Center, New York City, NY, USA e Department of Radiology, Beth Israel Deaconess Medical Center, Boston, MA, USA f Lemuel Shattuck Hospital, Jamaica Plain, MA, USA g University of Massachusetts Medical School, Worcester, MA, USA Received 1 January 2008; received in revised form 19 March 2008; accepted 20 March 2008 Abstract The association between orbital frontal cortex (OFC) volume and aggression was investigated in an at-risk psychiatric population. Forty-one psychiatric patients were referred for magnetic resonance imaging and a standardized psychometric assessment of aggression (Lifetime History of Aggression-Revised). Nineteen matched controls had lower levels of aggression and greater OFC volume, establishing the appropriateness of the psychiatric group for studying aggression pathophysiology. Consistent with study hypotheses, left OFC gray matter volume predicted 34% of the variance in self-reported aggression ratings. When impulsivity was not controlled for, left OFC gray matter only accounted for 26% of aggression variance, suggesting a complex relationship between impulsivity and OFC–aggression pathophysiology. Contrary to study hypotheses, right OFC gray matter volume did not predict degree of aggressive behavior. Current models do not account for lateralization, yet this may be quite important. Greater consideration should be given to laterality in OFC regulation of social/emotional behavior. Regulatory focus theory, positing two motivational systems, promotion and prevention, lateralized to the left and right hemispheres, respectively, may provide an explanatory framework for these results. Dysregulation of the left hemisphere ‘promotion’ motivational system may help to explain the aggressive behavior present in psychiatric populations. © 2008 Elsevier Ireland Ltd. All rights reserved. Keywords: Community violence; Neuropsychiatry; Impulsivity 1. Introduction While knowledge of the association of orbital frontal dysfunction and aggression has historically stemmed from neurologic lesion populations (e.g., Grafman et al., 1996), there is increasing scholarship concerning this Available online at www.sciencedirect.com Psychiatry Research: Neuroimaging 171 (2009) 145 – 154 www.elsevier.com/locate/psychresns ⁎ Corresponding author. Suffolk University, Department of Psychol- ogy, 41 Temple Street, Boston, MA 02114, USA. Tel.: +1 617 305 6397; fax: +1 617 367 2924. E-mail address: dgansler@suffolk.edu (D.A. Gansler). 0925-4927/$ - see front matter © 2008 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.pscychresns.2008.03.007