Dataset Information

Brain Correlates of Suicide Attempt in 18,925 Participants Across 18 International Cohorts.

ABSTRACT:

Background

Neuroimaging studies of suicidal behavior 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 pooled data from 18 international cohorts with neuroimaging and clinical measurements in 18,925 participants (12,477 healthy control subjects and 6448 people with depression, of whom 694 had attempted suicide). We compared regional cortical thickness and surface area and measures of subcortical, lateral ventricular, and intracranial volumes between suicide attempters, clinical control subjects (nonattempters with depression), and healthy control subjects.

Results

We identified 25 regions of interest with statistically significant (false discovery rate < .05) differences between groups. Post hoc examinations identified neuroimaging markers associated with suicide attempt including smaller volumes of the left and right thalamus and the right pallidum and lower surface area of the left inferior parietal lobe.

Conclusions

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. 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 suicidal behaviors may focus on understanding how these regions relate to the neurobiological mechanisms of suicide attempt risk.

SUBMITTER: Campos AI

PROVIDER: S-EPMC8324512 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Publications

Brain Correlates of Suicide Attempt in 18,925 Participants Across 18 International Cohorts.

Campos Adrian I AI Thompson Paul M PM Veltman Dick J DJ Pozzi Elena E van Veltzen Laura S LS Jahanshad Neda N Adams Mark J MJ Baune Bernhard T BT Berger Klaus K Brosch Katharina K Bülow Robin R Connolly Colm G CG Dannlowski Udo U Davey Christopher G CG de Zubicaray Greig I GI Dima Danai D Erwin-Grabner Tracy T Evans Jennifer W JW Fu Cynthia H Y CHY Gotlib Ian H IH Goya-Maldonado Roberto R Grabe Hans J HJ Grotegerd Dominik D Harris Matthew A MA Harrison Ben J BJ Hatton Sean N SN Hermesdorf Marco M Hickie Ian B IB Ho Tiffany C TC Kircher Tilo T Krug Axel A Lagopoulos Jim J Lemke Hannah H McMahon Katie K MacMaster Frank P FP Martin Nicholas G NG McIntosh Andrew M AM Medland Sarah E SE Meinert Susanne S Meller Tina T Nenadic Igor I Opel Nils N Redlich Ronny R Reneman Liesbeth L Repple Jonathan J Sacchet Matthew D MD Schmitt Simon S Schrantee Anouk A Sim Kang K Singh Aditya A Stein Frederike F Strike Lachlan T LT van der Wee Nic J A NJA van der Werff Steven J A SJA Völzke Henry H Waltemate Lena L Whalley Heather C HC Wittfeld Katharina K Wright Margaret J MJ Yang Tony T TT Zarate Carlos A CA Schmaal Lianne L Rentería Miguel E ME

Biological psychiatry 20210321 4

<h4>Background</h4>Neuroimaging studies of suicidal behavior 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.<h4>Methods</h4>Here, we pooled data from 18 international cohorts with n ...[more]

PMID: 34172278

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Project description:ObjectiveA rapid-cycling course in bipolar disorder has previously been identified as a risk factor for attempted suicide. This study investigated factors associated with suicide attempts in patients with rapid-cycling bipolar I or II disorder.MethodCross-sectional data at the initial assessment of patients who were enrolled into 4 clinical trials were used to study the factors associated with suicide attempt. An extensive clinical interview and the Mini-International Neuropsychiatric Interview were used to ascertain DSM-IV diagnoses of rapid-cycling bipolar disorder, substance use disorders, anxiety disorders, psychosis, and other clinical variables. Chi-square, t test, and logistic regression or Poisson regression were used to analyze the data where appropriate, with odds ratios (ORs) for relative risk estimate. The data were collected from September 1995 to June 2005.ResultsIn a univariate analysis, 41% of 561 patients had at least 1 lifetime suicide attempt. Earlier age of depression onset, bipolar I subtype, female sex, unmarried status, and a history of drug use disorder, panic disorder, sexual abuse, and psychosis were associated with significantly higher rates of attempted suicide (all p < .05). After considering 31 potential confounding factors in the stepwise logistic regression model (n = 387), any Axis I comorbidity (OR = 2.68, p = .0219), female sex (OR = 2.11, p = .0005), psychosis during depression (OR = 1.84, p = .0167), bipolar I subtype (OR = 1.83, p = .0074), and history of drug abuse (OR = 1.62, p = .0317) were independent predictors for increased risk of attempted suicide. However, white race was associated with a lower risk for suicide attempt (OR = 0.47, p = .0160). Psychosis during depression (p = .0003), bipolar I subtype (p = .0302), and physical abuse (p = .0195) were associated with increased numbers of suicide attempts by 248%, 166%, and 162%, respectively; white race was associated with a 60% decrease in the number of suicide attempts (p = .0320).ConclusionIn this highly comorbid group of patients with rapid-cycling bipolar disorder, 41% had at least 1 suicide attempt. Among the demographics, female sex was positively associated, but white race was negatively associated, with the risk for suicide attempt. Independent clinical variables for increased risk and/or number of attempted suicides were any Axis I comorbidity, psychosis during depression, bipolar I subtype, a history of drug abuse, and physical abuse.

Project description:Suicide accounts for nearly 800,000 deaths per year worldwide with rates of both deaths and attempts rising. Family studies have estimated substantial heritability of suicidal behavior; however, collecting the sample sizes necessary for successful genetic studies has remained a challenge. We utilized two different approaches in independent datasets to characterize the contribution of common genetic variation to suicide attempt. The first is a patient reported suicide attempt phenotype asked as part of an online mental health survey taken by a subset of participants (n = 157,366) in the UK Biobank. After quality control, we leveraged a genotyped set of unrelated, white British ancestry participants including 2433 cases and 334,766 controls that included those that did not participate in the survey or were not explicitly asked about attempting suicide. The second leveraged electronic health record (EHR) data from the Vanderbilt University Medical Center (VUMC, 2.8 million patients, 3250 cases) and machine learning to derive probabilities of attempting suicide in 24,546 genotyped patients. We identified significant and comparable heritability estimates of suicide attempt from both the patient reported phenotype in the UK Biobank (h2SNP = 0.035, p = 7.12 × 10-4) and the clinically predicted phenotype from VUMC (h2SNP = 0.046, p = 1.51 × 10-2). A significant genetic overlap was demonstrated between the two measures of suicide attempt in these independent samples through polygenic risk score analysis (t = 4.02, p = 5.75 × 10-5) and genetic correlation (rg = 1.073, SE = 0.36, p = 0.003). Finally, we show significant but incomplete genetic correlation of suicide attempt with insomnia (rg = 0.34-0.81) as well as several psychiatric disorders (rg = 0.26-0.79). This work demonstrates the contribution of common genetic variation to suicide attempt. It points to a genetic underpinning to clinically predicted risk of attempting suicide that is similar to the genetic profile from a patient reported outcome. Lastly, it presents an approach for using EHR data and clinical prediction to generate quantitative measures from binary phenotypes that can improve power for genetic studies.

Dataset Information

Brain Correlates of Suicide Attempt in 18,925 Participants Across 18 International Cohorts.

Background

Methods

Results

Conclusions

Publications

Brain Correlates of Suicide Attempt in 18,925 Participants Across 18 International Cohorts.

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