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 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. 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 suicide.
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 depressedpatients 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 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. RESULTS:SERT binding potential was significantly decreased in the midbrain/pons (P = .029) and putamen (P = .04) of depressedpatients 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 suicide.
Authors: Manesh Gopaldas; Francesca Zanderigo; Serena Zhan; R Todd Ogden; Jeffrey M Miller; Harry Rubin-Falcone; Thomas B Cooper; Maria A Oquendo; Gregory Sullivan; J John Mann; M Elizabeth Sublette Journal: J Affect Disord Date: 2019-07-05 Impact factor: 4.839
Authors: Maria A Oquendo; Hanga Galfalvy; Gregory M Sullivan; Jeffrey M Miller; Matthew M Milak; M Elizabeth Sublette; Sebastian Cisneros-Trujillo; Ainsley K Burke; Ramin V Parsey; J John Mann Journal: JAMA Psychiatry Date: 2016-10-01 Impact factor: 21.596