ORIGINAL ARTICLE Fronto-limbic brain structures in suicidal and non-suicidal female patients with major depressive disorder ES Monkul 1,2,3 , JP Hatch 1,4 , MA Nicoletti 1 , S Spence 1 , P Brambilla 5,6 , ALT Lacerda 7 , RB Sassi 8 , AG Mallinger 9 , MS Keshavan 10 and JC Soares 1,2,11 1 MOOD-CNS Program (Mood Disorders Clinical Neurosciences Program), Department of Psychiatry, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA; 2 South Texas Veterans Health Care System, Audie L Murphy Division, San Antonio, TX, USA; 3 Department of Psychiatry, Dokuz Eylu ¨ l University School of Medicine, Izmir, Turkey; 4 Deparment of Orthodontics, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA; 5 Department of Pathology and Experimental and Clinical Medicine, Section of Psychiatry, University of Udine, Udine, Italy; 6 Scientific Institute IRCCS E Medea, Pasian di prato, Udine, Italy; 7 Interdisciplinary Lab of Neuroimaging and Cognition (LiNC), Department of Psychiatry, Federal University of Sao Paulo, Sao Paulo, Brazil; 8 Institute of Psychiatry, University of Sao Paulo School of Medicine, Sao Paulo, Brazil; 9 Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, Pittsburgh, PA, USA; 10 Department of Psychiatry and Behavioral Sciences, Wayne State School of Medicine, Detroit, MI, USA and 11 Department of Radiology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA Our knowledge about the neurobiology of suicide is limited. It has been proposed that suicidal behavior generally requires biological abnormalities concomitant with the personality trait of impulsivity/aggression, besides an acute psychiatric illness or psychosocial stressor. We investigated fronto-limbic anatomical brain abnormalities in suicidal and non-suicidal adult female patients with unipolar depression. Our sample consisted of seven suicidal unipolar patients, 10 non-suicidal unipolar patients and 17 healthy female comparison subjects. The criterion for suicidality was one or more documented lifetime suicide attempts. A 1.5T GE Signa Imaging System running version Signa 5.4.3 software was used to acquire the magnetic resonance imaging images. All anatomical structures were measured blindly, with the subjects’ identities and group assignments masked. We used analysis of covariance with age and intracranial volume as covariates and the Tukey–Kramer procedure to compare suicidal patients, non-suicidal patients and healthy comparison subjects. Suicidal patients had smaller right and left orbitofrontal cortex gray matter volumes compared with healthy comparison subjects. Suicidal patients had larger right amygdala volumes than non-suicidal patients. Abnormalities in the orbitofrontal cortex and amygdala in suicidal patients may impair decision-making and predispose these patients to act more impulsively and to attempt suicide. Molecular Psychiatry (2007) 12, 360–366. doi:10.1038/sj.mp.4001919; published online 5 December 2006 Keywords: suicide; depression; mood disorders; affective disorders; magnetic resonance imaging; limbic system Introduction The risk for suicide is 10–20 times higher in people with mood disorders than in the general population 1 and our knowledge about the neurobiology of suicide is still limited. Although suicide is a potentially preventable cause of death, efforts to reduce suicide rates have had minimal success. The clinical markers of patients at high risk for suicide may detect most patients who will commit suicide, but may also be found in a large number of patients who will never commit suicide. 2 Understanding the neural correlates of suicidal behavior may be helpful in reducing suicide rates in major depression and other psychia- tric disorders. Serotonergic and noradrenergic abnormalities in regions of the prefrontal cortex, as well as the dorsal raphe nucleus and locus ceruleous are implicated in suicide. Neurochemical studies show that there is serotonin hypofunction in suicide victims, there are fewer presynaptic serotonin transporter binding sites and more post-synaptic serotonin receptors in their Received 3 February 2006; revised 8 August 2006; accepted 13 September 2006; published online 5 December 2006 Previous presentations: Society of Biological Psychiatry Annual Meeting, April 29th–May 1st, 2004, NY, USA and 18th ECNP Congress, October 22–26, 2005, Amsterdam, The Netherlands. Correspondence: Dr JC Soares, Division of Mood and Anxiety Disorders, Department of Psychiatry, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA. E-mail: soares@uthscsa.edu Molecular Psychiatry (2007) 12, 360–366 & 2007 Nature Publishing Group All rights reserved 1359-4184/07 $30.00 www.nature.com/mp