Brain correlates of suicide attempt in 18,925 participants across 18 international cohorts
Authors: Campos Adrian I. , Thompson Paul M. , Veltman Dick J. , Pozzi Elena , van Veltzen Laura S. , Jahanshad Neda , Adams Mark J. , Baune Bernhard T. , Berger Klaus , Brosch Katharina , Bülow Robin , Connolly Colm G. , Dannlowski Udo , Davey Christopher G. , de Zubicaray Greig I. , Dima Danai , Erwin-Grabner Tracy , Evans Jennifer W. , Fu Cynthia H.Y. , Gotlib Ian H. , Goya-Maldonado Roberto , Grabe Hans J. , Grotegerd Dominik , Harris Matthew A. , Harrison Ben J. , Hatton Sean N. , Hermesdorf Marco , Hickie Ian B. , Ho Tiffany C. , Kircher Tilo , Krug Axel , Lagopoulos Jim , Lemke Hannah , McMahon Katie , MacMaster Frank P. , Martin Nicholas G. , McIntosh Andrew M. , Medland Sarah E. , Meinert Susanne , Meller Tina , Nenadic Igor , Opel Nils , Redlich Ronny , Reneman Liesbeth , Repple Jonathan , Sacchet Matthew D. , Schmitt Simon , Schrantee Anouk , Sim Kang , Singh Aditya , Stein Frederike , Strike Lachlan T. , van der Wee Nic J.A. , van der Werff Steven J.A. , Völzke Henry , Waltemate Lena , Whalley Heather C. , Wittfeld Katharina , Wright Margaret J. , Yang Tony T. , Zarate Carlos A. , Schmaal Lianne , Rentería Miguel E. ,   for the ENIGMA-MDD working group
Published: May 2020

Background

Suicidal behavior is highly heterogeneous and complex. A better understanding of its biological substrates and mechanisms could inform the design of more effective suicide prevention and intervention strategies. Neuroimaging studies of suicidality 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 pool data from eighteen international cohorts with neuroimaging and clinical measurements in 18,925 participants (12,477 healthy controls and 6,448 people with depression, of whom 694 had attempted suicide). We compare regional cortical thickness and surface area, and measures of subcortical, lateral ventricular and intracranial volumes between suicide attempters, clinical controls (non-attempters with depression) and healthy controls.

Findings

We identified 25 regions of interest with statistically significant (FDR<0.05) differences between groups. Post-hoc examinations identified neuroimaging markers associated with suicide attempt over and above the effects of depression, including smaller volumes of the left and right thalamus and the right pallidum, and lower surface area of the left inferior parietal lobe.

Interpretation

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 to avoid reaching biased or misleading conclusions. 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 suicidality may focus on understanding how these regions relate to the neurobiological mechanisms of suicide attempt risk.