Decreased brainstem and putamen SERT binding potential in depressed suicide attempters using [11C]-zient PET imaging

Depress Anxiety. 2013 Oct;30(10):902-7. doi: 10.1002/da.22049. Epub 2013 Mar 22.

Abstract

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.

Keywords: biological markers; brain imaging/neuroimaging; depression; measurement/psychometrics; suicide/self-harm.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Biomarkers / metabolism
  • Brain Mapping / methods
  • Brain Stem / diagnostic imaging
  • Brain Stem / metabolism*
  • Case-Control Studies
  • Depressive Disorder, Major / diagnostic imaging
  • Depressive Disorder, Major / metabolism*
  • Female
  • Humans
  • Image Processing, Computer-Assisted / methods
  • Magnetic Resonance Imaging
  • Male
  • Nortropanes
  • Positron-Emission Tomography / methods*
  • Putamen / diagnostic imaging
  • Putamen / metabolism*
  • Serotonin Plasma Membrane Transport Proteins / metabolism*
  • Suicide, Attempted*
  • Young Adult

Substances

  • 2-carbomethoxy-3-(4'-(2-iodoethenyl)phenyl)nortropane
  • Biomarkers
  • Nortropanes
  • Serotonin Plasma Membrane Transport Proteins