Subcortical brain structure and suicidal behaviour in major depressive disorder: a meta-analysis from the ENIGMA-MDD working group

Abstract

The aetiology of suicidal behaviour is complex, and knowledge about its neurobiological mechanisms is limited. Neuroimaging methods provide a noninvasive approach to explore the neural correlates of suicide vulnerability in vivo. The ENIGMA-MDD Working Group is an international collaboration evaluating neuroimaging and clinical data from thousands of individuals collected by research groups from around the world. Here we present analyses in a subset sample (n=3097) for whom suicidality data were available. Prevalence of suicidal symptoms among major depressive disorder (MDD) cases ranged between 29 and 69% across cohorts. We compared mean subcortical grey matter volumes, lateral ventricle volumes and total intracranial volume (ICV) in MDD patients with suicidal symptoms (N=451) vs healthy controls (N=1996) or MDD patients with no suicidal symptoms (N=650). MDD patients reporting suicidal plans or attempts showed a smaller ICV (P=4.12 × 10−3) or a 2.87% smaller volume compared with controls (Cohen’s d=−0.284). In addition, we observed a nonsignificant trend in which MDD cases with suicidal symptoms had smaller subcortical volumes and larger ventricular volumes compared with controls. Finally, no significant differences (P=0.28–0.97) were found between MDD patients with and those without suicidal symptoms for any of the brain volume measures. This is by far the largest neuroimaging meta-analysis of suicidal behaviour in MDD to date. Our results did not replicate previous reports of association between subcortical brain structure and suicidality and highlight the need for collecting better-powered imaging samples and using improved suicidality assessment instruments.

Imaging suicidal thoughts and behaviors: a comprehensive review of 2 decades of neuroimaging studies

“…These mixed findings could perhaps be explained if additional involvement of the amygdala and hippocampus in STBs beyond their role in mental disorders is subtle with small effects only apparent in studies with very large sample sizes. This is consistent with a post hoc power analysis based on observed effect sizes in the largest study on subcortical volumes in STBs to date [110]. Alternatively, mesial temporal structural alterations may only be present in specific subgroups of people with STBs.…”

“…With regard to the thalamus, higher volumes were reported in veterans with traumatic brain injury and SAs [133] and higher 5-HT synthesis was reported in adult SAs with a mix of psychiatric diagnoses [39]. However, other studies, including the largest study to date of individuals with STBs (N = 451), have not detected associations of striatum and thalamus volume with STBs [32,37,110].…”

“…However, findings reported have been inconsistent. Larger amygdala volumes were reported in adult SAs with MDD [108] and SZ [109], but more studies have not detected significant amygdala findings [32,37,99,100,[110][111][112]. Smaller hippocampal volumes were reported in adult SAs with MDD [113] and adolescent and young adult SAs with BD [35], and one study reported a smaller parahippocampal gyrus [114].…”

Machine learning in major depression: From classification to treatment outcome prediction

“…The ENIGMA MDD working group includes brain scans of around >5000 MDD patients and >9000 controls from 35 research samples of 14 different countries worldwide. Its primary aim is to identify imaging markers that robustly discriminate MDD patients from healthy controls cross‐site with standardized image processing and statistical analysis protocols . More recently, a predictive analytics competition (PAC), a major depression classification challenge with the goal of automatic classification of patients suffering from major depression, and healthy individuals based on sMRI data have been carried out (https://www.photon-ai.com/pac).…”

Subcortical Shape Alterations in Major Depressive Disorder: Findings from the ENIGMA Major Depressive Disorder Working Group

“…All participating sites collected anatomical T1-weighted MRI brain scans locally at each site, where they were analyzed using the fully-automated and validated segmentation software FreeSurfer version 5.3 (Fischl 2002), with the exception of 3 sites which used version 5.0 or 5.1 (see Table S1). A subset of these subcortical measures have been previously published Renteria et al 2017;Schmaal et al 2016); however, none of these prior meta-analyses from the MDD Working Group of ENIGMA conducted shape analyses. Image acquisition parameters and software descriptions for each sample are presented in supplemental Table S1.…”