Elsevier

Biological Psychiatry

Volume 90, Issue 4, 15 August 2021, Pages 243-252
Biological Psychiatry

Archival Report
Brain Correlates of Suicide Attempt in 18,925 Participants Across 18 International Cohorts

https://doi.org/10.1016/j.biopsych.2021.03.015Get rights and content

Abstract

Background

Neuroimaging studies of suicidal behavior have so far been conducted in small samples, prone to biases and false-positive associations, yielding inconsistent results. The ENIGMA-MDD Working Group aims to address the issues of poor replicability and comparability by coordinating harmonized analyses across neuroimaging studies of major depressive disorder and related phenotypes, including suicidal behavior.

Methods

Here, we pooled data from 18 international cohorts with neuroimaging and clinical measurements in 18,925 participants (12,477 healthy control subjects and 6448 people with depression, of whom 694 had attempted suicide). We compared regional cortical thickness and surface area and measures of subcortical, lateral ventricular, and intracranial volumes between suicide attempters, clinical control subjects (nonattempters with depression), and healthy control subjects.

Results

We identified 25 regions of interest with statistically significant (false discovery rate < .05) differences between groups. Post hoc examinations identified neuroimaging markers associated with suicide attempt including smaller volumes of the left and right thalamus and the right pallidum and lower surface area of the left inferior parietal lobe.

Conclusions

This study addresses the lack of replicability and consistency in several previously published neuroimaging studies of suicide attempt and further demonstrates the need for well-powered samples and collaborative efforts. Our results highlight the potential involvement of the thalamus, a structure viewed historically as a passive gateway in the brain, and the pallidum, a region linked to reward response and positive affect. Future functional and connectivity studies of suicidal behaviors may focus on understanding how these regions relate to the neurobiological mechanisms of suicide attempt risk.

Section snippets

Samples

We analyzed pooled data (mega-analysis) across 17 ENIGMA-MDD Working Group cohorts with clinical and neuroimaging data available for participants fulfilling MDD criteria (33) (n = 2533) and healthy control subjects (n = 4066) and participants from the UK Biobank (n = 12,366). We defined three groups: suicide attempters; clinical control subjects, that is, participants with depression and no history of suicide attempt; and healthy control subjects. Descriptive statistics for each sample are

Suicide Attempt Prevalence and Sample Demographics

Details on the sample of each cohort included in this analysis are summarized in Table 1 and Table S1. Notably, not all cohorts had cases of suicide attempt, but still contributed data to the healthy or clinical control groups. The pooled mean age (SD) was 56.22 (15.17) years. Differences in age and sex composition across cohorts were detected (Table S1) and used as covariates for all the analyses. The total sample size comprised 18,925 subjects, of which 3.67% (n = 694) had at least one past

Discussion

This study addressed the lack of statistical power, which may have resulted in low replicability and consistency, in previous neuroimaging studies of suicide attempt. Our analyses revealed four regions associated explicitly with suicide attempt, above and beyond the effect of MDD, supporting the hypothesis of suicidality-associated neural differences (30). The relatively few regions identified and the overall small effect sizes should be taken as a warning for future studies attempting to

Acknowledgments and Disclosures

The work reported here was supported in part by many public and private agencies across the world. Core funding for ENIGMA was provided by the National Institutes of Health (NIH) Big Data to Knowledge (BD2K) program (Consortium Grant No. U54 EB020403 [to PMT]), the University Medical Center Göttingen and the German Federal Ministry of Education and Research (Bundesministerium fuer Bildung und Forschung, BMBF: 01 ZX 1507, ‘‘PreNeSt - e:Med’’ [to AFFDIS]), as well by support to the BiDirect study

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