Structural brain alterations associated with suicidal thoughts and behaviors in young people: results from 21 international studies from the ENIGMA Suicidal Thoughts and Behaviours consortium

Abstract

Identifying brain alterations associated with suicidal thoughts and behaviors (STBs) in young people is critical to understanding their development and improving early intervention and prevention. The ENIGMA Suicidal Thoughts and Behaviours (ENIGMA-STB) consortium analyzed neuroimaging data harmonized across sites to examine brain morphology associated with STBs in youth. We performed analyses in three separate stages, in samples ranging from most to least homogeneous in terms of suicide assessment instrument and mental disorder. First, in a sample of 577 young people with mood disorders, in which STBs were assessed with the Columbia Suicide Severity Rating Scale (C-SSRS). Second, in a sample of young people with mood disorders, in which STB were assessed using different instruments, MRI metrics were compared among healthy controls without STBs (HC; N = 519), clinical controls with a mood disorder but without STBs (CC; N = 246) and young people with current suicidal ideation (N = 223). In separate analyses, MRI metrics were compared among HCs (N = 253), CCs (N = 217), and suicide attempters (N = 64). Third, in a larger transdiagnostic sample with various assessment instruments (HC = 606; CC = 419; Ideation = 289; HC = 253; CC = 432; Attempt=91). In the homogeneous C-SSRS sample, surface area of the frontal pole was lower in young people with mood disorders and a history of actual suicide attempts (N = 163) than those without a lifetime suicide attempt (N = 323; FDR-p = 0.035, Cohen’s d = 0.34). No associations with suicidal ideation were found. When examining more heterogeneous samples, we did not observe significant associations. Lower frontal pole surface area may represent a vulnerability for a (non-interrupted and non-aborted) suicide attempt; however, more research is needed to understand the nature of its relationship to suicide risk.

Neuroimaging alterations of the suicidal brain and its relevance to practice: an updated review of MRI studies

“…However, Richard-Devantoy et al used a Go-No-Go task and found that deficits in cognitive inhibition (in relation to the IFG, thalamus, OFC, and parietal cortex) were related to the depressive, but not specifically, STB vulnerability risk ( 27 ). In contrast, the meta-analysis involving neuroimaging studies using the monetary incentive delay task and the stop signal task with over 5,000 participants aged 9–11 could not delineate between those with suicidal ideation from those with suicidal behaviors ( 28 ). Although our belief is that there is a difference in this domain between those with suicidal ideation and those who attempt, evidence is scant and will depend on future work of our own and others.…”

Concurrent validity and reliability of suicide risk assessment instruments: A meta-analysis of 20 instruments across 27 international cohorts.

“…Our study is a comprehensive assessment of how well different suicide risk assessment instruments relate to each other and the extent to which they can be used interchangeably. Harmonization reduces heterogeneity and increases power for discovery analyses, but also enables the assessment of the generalizability of studies and opens up the opportunity to investigate other aspects such as interactions and individual variation analysis (van Harmelen et al, 2021). Identification of correlates of suicide risk may be improved by increasing sample sizes, and by pooling data across studies to detect small effect sizes, which may result from large variance in underlying mechanisms.…”

“…Examples of these consortia include the International Suicide Genetics Consortium (Mullins et al, 2022) and the Enhancing NeuroImaging Genetics through Meta-Analysis Suicidal Thoughts and Behaviour (ENIGMA-STB) consortium (van Velzen et al, 2022). The aim of ENIGMA-STB is to study the neural correlates of STB, by bringing together research groups around the world that have collected both neuroimaging data and assessed STB in individuals with and without mental disorders.…”

A Systematic Review of MRI Studies and the “Emotional paiN and social Disconnect (END)” Brain Model of Suicidal Behavior in Youth

“…The two studies that met this definition showed a general agreement with the END model, highlighting frontotemporal structural and right OFC functional aberrations in youth with bipolar disorder and self-harm [ 60 , 61 ]. The largest study among the 8 additional studies was the ENIGMA Suicidal Thoughts and Behaviours (ENIGMA-STB) consortium study (comprised of multiple samples, including a sample of 577 young people with mood disorders and a transdiagnostic sample with 253 healthy controls, 432 clinical controls, and 91 young people with a history of a suicide attempt), which did not show any morphological findings in the heterogeneous cohort of young people with a history of suicide attempts but showed a correlation of suicide attempt history with a smaller surface area of the frontal pole in the mood disorder cohort [ 65 ]. Even though the absence of findings in the heterogeneous cohort makes this study not directly comparable with the END model, it is worth mentioning that the frontal pole is adjacent to the lateral OFC, which may point to compatibility with the model.…”