Citation

Bartlett EA, Zanderigo F, Stanley B, Choo TH, Galfalvy HC, Pantazatos SP, Sublette ME, Miller JM, Oquendo MA, Mann JJ. Eur. Neuropsychopharmacol. 2023; 70: 1-13.

Copyright

(Copyright © 2023, Elsevier Publishing)

DOI

10.1016/j.euroneuro.2023.01.006

PMID

36780841

Abstract

We examined relationships between the serotonin system and stress in major depression and suicidal behavior. Twenty-five medication-free depressed participants (13 suicide attempters) underwent same-day [(11)C]DASB and [(11)C]CUMI-101 positron emission tomography (PET) imaging. Binding potential (BP(ND)) to the serotonin transporter (5-HTT) and serotonin 1A (5-HT(1A)) receptor, respectively, was quantified using the NRU 5-HT atlas, reflecting distinct spatial distributions of multiple serotonin targets. Ecological momentary assessment (EMA) measured current stress over one week proximal to imaging. EMA stress did not differ between attempters and non-attempters. In all depressed participants, 5-HTT and 5-HT(1A) BP(ND) were unrelated to EMA stress. There were region-specific effects of 5-HTT (p=0.002) and 5-HT(1A) BP(ND) (p=0.03) in attempters vs. nonattempters. In attempters, region-specific associations between 5-HTT (p=0.03) and 5-HT(1A) (p=0.005) BP(ND) and EMA stress emerged. While no post-hoc 5-HTT BP(ND) correlations were significant, 5-HT(1A) BP(ND) correlated positively with EMA stress in attempters in 9/10 regions (p-values<0.007), including the entire cortex except the largely occipital region 5. Brodmann-based regional analyses found diminished effects for 5-HTT and subcortically localized positive corrrelations between 5-HT(1A) and EMA stress, in attempters only. Given comparable depression severity and childhood and current stress between attempters and nonattempters, lower 5-HTT binding in attempters vs. nonattempters may suggest a biological risk marker. Localized lower 5-HTT and widespread higher 5-HT(1A) binding with stress among attempters specifically may suggest that a serotonergic phenotype might be a key determinant of risk or resiliency for suicidal behavior.

Language: en

Keywords

suicidal behavior; current stress; ecological momentary assessment; major depression; serotonin 1A receptor; Serotonin transporter