Clinical, demographic, and genetic risk factors of treatment-attributed suicidality in >10,000 Australian adults taking antidepressants

TY - JOUR

T1 - Clinical, demographic, and genetic risk factors of treatment-attributed suicidality in >10,000 Australian adults taking antidepressants

AU - Campos, Adrian I.

AU - Byrne, Enda M.

AU - Iorfino, Frank

AU - Fabbri, Chiara

AU - Hickie, Ian B.

AU - Lewis, Cathryn M.

AU - Wray, Naomi R.

AU - Medland, Sarah E.

AU - Rentería, Miguel E.

AU - Martin, Nicholas G.

N1 - Funding Information: Data collection for this project was possible thanks to funding from the Australian National Health & Medical Research Council (NHMRC) to Nicholas G. Martin (GNT1086683). Adrian I. Campos is supported by a UQ Research Training Scholarship from The University of Queensland (UQ). Miguel E. Rentería thanks the support of the NHMRC (GNT1102821). CML and Chiara Fabbri are part‐funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. Sarah E. Medland and the Australian Genetics of Bipolar Study are funded by the NHMRC (GNT1103623 and GNT1138514). The views expressed are those of the authors and not necessarily those of the affiliated or funding institutions. Open access publishing facilitated by The University of Queensland, as part of the Wiley ‐ The University of Queensland agreement via the Council of Australian University Librarians. Funding Information: Data collection for this project was possible thanks to funding from the Australian National Health & Medical Research Council (NHMRC) to Nicholas G. Martin (GNT1086683). Adrian I. Campos is supported by a UQ Research Training Scholarship from The University of Queensland (UQ). Miguel E. Rentería thanks the support of the NHMRC (GNT1102821). CML and Chiara Fabbri are part-funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. Sarah E. Medland and the Australian Genetics of Bipolar Study are funded by the NHMRC (GNT1103623 and GNT1138514). The views expressed are those of the authors and not necessarily those of the affiliated or funding institutions. Open access publishing facilitated by The University of Queensland, as part of the Wiley - The University of Queensland agreement via the Council of Australian University Librarians. Publisher Copyright: © 2022 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics published by Wiley Periodicals LLC.

PY - 2022/9

Y1 - 2022/9

N2 - Emergence of suicidal symptoms has been reported as a potential antidepressant adverse drug reaction. Identifying risk factors associated could increase our understanding of this phenomenon and stratify individuals at higher risk. Logistic regressions were used to identify risk factors of self-reported treatment-attributed suicidal ideation (TASI). We then employed classifiers to test the predictive ability of the variables identified. A TASI GWAS, as well as SNP-based heritability estimation, were performed. GWAS replication was sought from an independent study. Significant associations were found for age and comorbid conditions, including bipolar and personality disorders. Participants reporting TASI from one antidepressant were more likely to report TASI from other antidepressants. No genetic loci associated with TAS I (p < 5e-8) were identified. Of 32 independent variants with suggestive association (p < 1e-5), 27 lead SNPs were available in a replication dataset from the GENDEP study. Only one variant showed a consistent effect and nominal association in the independent replication sample. Classifiers were able to stratify non-TASI from TASI participants (AUC = 0.77) and those reporting treatment-attributed suicide attempts (AUC = 0.85). The pattern of TASI co-occurrence across participants suggest nonspecific factors underlying its etiology. These findings provide insights into the underpinnings of TASI and serve as a proof-of-concept of the use of classifiers for risk stratification.

AB - Emergence of suicidal symptoms has been reported as a potential antidepressant adverse drug reaction. Identifying risk factors associated could increase our understanding of this phenomenon and stratify individuals at higher risk. Logistic regressions were used to identify risk factors of self-reported treatment-attributed suicidal ideation (TASI). We then employed classifiers to test the predictive ability of the variables identified. A TASI GWAS, as well as SNP-based heritability estimation, were performed. GWAS replication was sought from an independent study. Significant associations were found for age and comorbid conditions, including bipolar and personality disorders. Participants reporting TASI from one antidepressant were more likely to report TASI from other antidepressants. No genetic loci associated with TAS I (p < 5e-8) were identified. Of 32 independent variants with suggestive association (p < 1e-5), 27 lead SNPs were available in a replication dataset from the GENDEP study. Only one variant showed a consistent effect and nominal association in the independent replication sample. Classifiers were able to stratify non-TASI from TASI participants (AUC = 0.77) and those reporting treatment-attributed suicide attempts (AUC = 0.85). The pattern of TASI co-occurrence across participants suggest nonspecific factors underlying its etiology. These findings provide insights into the underpinnings of TASI and serve as a proof-of-concept of the use of classifiers for risk stratification.

KW - antidepressants

KW - genetics

KW - suicide

UR - http://www.scopus.com/inward/record.url?scp=85134220163&partnerID=8YFLogxK

U2 - 10.1002/ajmg.b.32913

DO - 10.1002/ajmg.b.32913

M3 - Article

C2 - 35833543

AN - SCOPUS:85134220163

SN - 1552-4841

VL - 189

SP - 196

EP - 206

JO - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics

JF - American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics

IS - 6

ER -