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

ENIGMA Suicidal Thoughts and Behaviours Consortium

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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.

Original languageEnglish (US)
Pages (from-to)4550-4560
Number of pages11
JournalMolecular psychiatry
Volume27
Issue number11
DOIs
StatePublished - Nov 2022

Bibliographical note

Funding Information:
This work was supported by the MQ Brighter Futures Award MQBFC/2 (LS, LC, LV, MRD, LvV, ALvH, HB) and the U.S. National Institute of Mental Health under Award Number R01MH117601 (LS, LvV, NJ). LvV received funding through the National Suicide Prevention Research Fund, managed by Suicide Prevention Australia. LS is supported by an NHMRC Career Development Fellowship (1140764). ALvH is funded through the Social Safety and Resilience program of Leiden University. SA, NB, FP, and GS acknowledge that data collected in IRCCS Santa Lucia Foundation, Rome, Italy was funded by a study funded by the Italian Ministry of Health grant RC17-18-19-20-21/A. ZB, KC, B K-D acknowledge data collected at the University of Minnesota was funded by the National Institute of Mental Health (K23MH090421), the National Alliance for Research on Schizophrenia and Depression, the University of Minnesota Graduate School, the Minnesota Medical Foundation, and the Biotechnology Research Center (P41 RR008079 to the Center for Magnetic Resonance Research), University of Minnesota, and the Deborah E. Powell Center for Women’s Health Seed Grant, University of Minnesota. HB acknowledges data collected at the Yale School of Medicine, New Haven, CT, USA, was funded by: MQ Brighter Futures, R61MH111929RC1MH088366, R01MH070902, R01MH069747, American Foundation for Suicide Prevention, International Bipolar Foundation, Brain and Behavior Research Foundation, For the Love of Travis Foundation and Women’s Health Research at Yale. LC is supported by Interdisziplinäres Zentrum für Klinische Forschung, UKJ. BCD was funded by a CJ Martin Fellowship (NHMRC app 1161356). BCD research leading to these results has received funding from the program “Investissements d’avenir” ANR-10-IAIHU-06. CGD and BJH acknowledge that data collected in Melbourne, Australia, was supported by Australian National Health and Medical Research Council of Australia (NHMRC) Project Grants 1064643 (principal investigator, BJH) and 1024570 (principal investigator, CGD). BJH and CGD were supported by NHMRC Career Development Fellowships (1124472 and 1061757, respectively). UD and TH acknowledge data collected at the FOR2107-Münster was funded by the German Research Foundation (DFG, grant FOR2107-DA1151/5-1 and DA1151/5-2 to UD, and DFG grants HA7070/2-2, HA7070/3, HA7070/4 to TH). AJ and TK acknowledges data collected at the FOR2107-Marburg was funded by the German Research Foundation (DFG, grant FOR2107-JA 1890/7-1 and JA 1890/7-2 to AJ, and DFG, grant FOR2107-KI588/14-1 and FOR2107-KI588/14-2 to TK). KD acknowledges data collected for the Münster Neuroimaging Cohort was funded by the Medical Faculty Münster, Innovative Medizinische Forschung (Grant IMF KO 1218 06 to KD). JMF, PBM, BJO, and GR acknowledge that the “Kids and Sibs” Study was supported by the Australian National Medical and Health Research Council (Program Grant 1037196 and Investigator Grant 1177991 to PBM, Project Grant 1066177 to JMF), the Lansdowne Foundation, Good Talk and the Keith Pettigrew Family Bequest (PM). JMF gratefully acknowledges the Janette Mary O’Neil Research Fellowship. IHG is supported in part by R37MH101495. Support for TAD comes from the National Institute of Mental Health (K01MH106805). TH acknowledges support for TIGER includes the Klingenstein Third Generation Foundation, the National Institute of Mental Health (K01MH117442), the Stanford Maternal Child Health Research Institute, and the Stanford Center for Cognitive and Neurobiological Imaging. TCH receives partial support from the Ray and Dagmar Dolby Family Fund. KAM, ABM, MAS acknowledge data collected at Harvard University was funded by the National Institute of Mental Health (R01-MH103291). IN is supported by grants of the Deutsche Forschungsgemeinschaft (DFG grants NE2254/1-2, NE2254/3-1, NE2254/4-1).This study was supported by the National Center for Complementary and Integrative Health (NCCIH) R21AT009173 and R61AT009864 to TTY; by the National Center for Advancing Translational Sciences (CTSI), National Institutes of Health, through UCSF-CTSI UL1TR001872 to TTY; by the American Foundation for Suicide Prevention (AFSP) SRG-1-141-18 to TTY; by UCSF Research Evaluation and Allocation Committee (REAC) and J. Jacobson Fund to TTY; by the National Institute of Mental Health (NIMH) R01MH085734 and the Brain and Behavior Research Foundation (formerly NARSAD) to TTY. YC acknowledges the Medical Leader Foundation of Yunnan Province (L2019011) and Famous Doctors Project of Yunnan Province Plan (YNWR-MY-2018-041). DTG, BCF and RAA wish to thank all PAFIP patients and family members who participated in the study as well as PAFIP´s research team and Instituto de Investigación Marqués de Valdecilla. Work by the PAFIP group has been funded by Instituto de Salud Carlos III through the projects PI14/00639, PI14/00918 and PI17/01056 (Co-funded by European Regional Development Fund/European Social Fund “Investing in your future”) and Fundación Instituto de Investigación Marqués de Valdecilla (NCT0235832 and NCT02534363). MER received support from the Australian National Health and Medical Research Council (NHMRC) Centre for Research Excellence on Suicide Prevention (CRESP) [GNT1042580]. ETCL is supported by grants from NIAAA (K01AA027573, R21AA027884) and the American Foundation for Suicide Prevention. All authors thank the participants for volunteering their time and supporting our research.

Funding Information:
IBH was an inaugural Commissioner on Australia’s National Mental Health Commission Sydney. The BMC operates an early-intervention youth service at Camperdown under contract to headspace. He is the Chief Scientific Advisor to, and a 5% equity shareholder in, InnoWell Pty Ltd. deliver the $30M Australian Government-funded Project Synergy (2017–20; a 3-year program forInnoWell was formed by the University of Sydney (45% equity) and PwC (Australia; 45% equity) to the transformation of mental health services) and to lead the transformation of mental health services internationally through the use of innovative technologies. ETCL has previously received salary support for the effort in kind from a Janssen-sponsored study at the University of Texas at Austin. JCS has received research grants from Compass, Alkermes, and Allergan; and has served as a consultant for Pfizer, Sunovion, Sanofi, Johnson & Johnson, Livanova, and Boehringer Ingelheim. NJ and PMT received partial grant support from Biogen, Inc. for research unrelated to this manuscript. All other authors have no financial relationships with commercial interests to report.

Publisher Copyright:
© 2022, Crown.

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