DEPRESSION AND ANXIETY 30:902–907 (2013) Neurobiology DECREASED BRAINSTEM AND PUTAMEN SERT BINDING POTENTIAL IN DEPRESSED SUICIDE ATTEMPTERS USING [ 11 C]-ZIENT PET IMAGING Jonathon A. Nye, 1 David Purselle, 2 Christophe Plisson, 1 Ronald J. Voll, 1 Jeffrey S. Stehouwer, 1 John R. Votaw, 1 Clinton D. Kilts, 2 Mark M. Goodman, 1,2 and Charles B. Nemeroff 2∗ Background: Deficits in serotonergic neurotransmission have been implicated in the pathogenesis of depression and suicidality. The present study utilized a novel positron-emission tomography (PET) ligand to quantitate and compare brain regional serotonin transporter (SERT) binding potential in depressed patients with a past history of suicide attempts to that of healthy comparison subjects. Method: We used [ 11 C]-ZIENT PET to label SERT in the serotonergic cell body rich brainstem, and forebrain projection fields. Quantitative PET emission data from 21 adults (10 healthy controls and 11 drug-free patients with major depres- sion) was used for group comparison. SERT binding potential (BP ND ) in eight MRI-based brain regions of interest (ROI) were compared in high-resolution PET images. Results: SERT binding potential was significantly decreased in the midbrain/pons (P = .029) and putamen (P = .04) of depressed patients with a past suicide attempt relative to comparison subjects. Forebrain SERT binding was also reduced in the patient sample, though these region effects did not survive a multiple comparison correction. Conclusion: These results suggest that decreased availability of the brainstem and basal ganglia SERT represents a biomarker of depression and thus confirm and extend the role of dysregulation of brain serotonergic neurotransmission in the pathophysiology of depression and sui- cide. Depression and Anxiety 30:902–907, 2013. C  2013 Wiley Periodicals, Inc. Key words: brain imaging/neuroimaging; depression; measurement/ psychometrics; biological markers; suicide/self-harm 1 Departments of Radiology, Emory University School of Medicine, Atlanta, Georgia 2 Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, Georgia Contract grant sponsor: NARSAD Distinguished Investigator Award; Contract grant sponsor: AFSP Established Investigator Award; Contract grant sponsor: NARSAD Young Investigator. ∗ Correspondece to: Charles B. Nemeroff, Department of Psychia- try and Behavioral Sciences, Leonard M. Miller School of Medicine, University of Miami, 1120 NW 14th Street, Suite 1455 (D-21), Miami, FL 33136. E-mail: CNemeroff@med.miami.edu Received for publication 9 August 2012; Revised 28 November 2012; Accepted 2 December 2012 DOI 10.1002/da.22049 Published online 22 March 2013 in Wiley Online Library (wileyonlinelibrary.com). INTRODUCTION Major depression and suicidality are highly comorbid. Abnormalities of serotonergic neurotransmission have been consistently implicated in the pathophysiology of depression. In addition, postmortem brain tissue and in vivo brain imaging studies support brain seroton- ergic dysregulation in the neurobiology of suicide. [1,2] Recently, Gos and co-workers [3] reported decreased proliferative activity of dorsal raphe nucleus neurons in depressed suicide victims, a finding consistent with ev- idence for increased markers of serotonergic neuronal morphometrics in the brainstem of suicide victims. [4] Research related to the neuropathophysiology of depres- sion and suicide has focused on the serotonin transporter (SERT), a critical regulator of the dynamics of seroton- ergic neurotransmission. [5,6] Reduced SERT binding and decreased SERT mRNA expression in postmortem brain tissue of suicide victims with major depression has C  2013 Wiley Periodicals, Inc.