Subcortical brain structure and suicidal behaviour in major depressive disorder: a meta-analysis from the ENIGMA-MDD working group.
Rentería ME., Schmaal L., Hibar DP., Couvy-Duchesne B., Strike LT., Mills NT., de Zubicaray GI., McMahon KL., Medland SE., Gillespie NA., Hatton SN., Lagopoulos J., Veltman DJ., van der Wee N., van Erp TGM., Wittfeld K., Grabe HJ., Block A., Hegenscheid K., Völzke H., Veer IM., Walter H., Schnell K., Schramm E., Normann C., Schoepf D., Konrad C., Zurowski B., Godlewska BR., Cowen PJ., Penninx BWJH., Jahanshad N., Thompson PM., Wright MJ., Martin NG., Christensen H., Hickie IB.
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.