DECREASED BRAINSTEM AND PUTAMEN SERT BINDING POTENTIAL IN DEPRESSED SUICIDE ATTEMPTERS USING [11C]-ZIENT PET IMAGING

Abstract

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. 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 depression) was used for group comparison. SERT binding potential (BPND ) in eight MRI-based brain regions of interest (ROI) were compared in high-resolution PET images. 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. 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 suicide.