Childhood Trauma, Genetics Associated With Suicidal Behavior in Bipolar Disorder

Boy covering his head with his arms
A history of such childhood trauma as emotional neglect and abuse, in addition to genetic variants, are linked to suicidal behavior in individuals with bipolar disorder.

Childhood trauma and certain genetic variants may increase risk for suicidal behavior among patients with bipolar disorder, according to cross-sectional data published in the Journal of Affective Disorders.

Investigators recruited 135 outpatients from the Bipolar Disorder Program in Spain, extracting both retrospective data on illness course and current data on sociodemographic and clinical features. Patients underwent assessment for childhood trauma and suicidal behavior per the Childhood Trauma Questionnaire and the Columbia Suicide Severity Rating Scale, respectively. In addition, genotyping was performed with participant blood samples. A set of 8 hypothalamic pituitary adrenal axis genes and 28 single nucleotide polymorphisms (SNPs) were selected for analysis per prior literature on the genetics of bipolar disorder.

Among 135 participants, 57 (42.2%) were men, and the mean (standard deviation) age was 47.90 (±11.69) years. A total of 62.0% of participants presented with suicidal behavior. The most commonly endorsed trauma subtype was emotional neglect (40.5%), followed by emotional abuse (27.6%), physical neglect (23.7%), sexual abuse (20.7%), and physical abuse (10.2%). Individuals with suicidal behavior had higher total Childhood Trauma Questionnaire score (P =.003) and higher subscale scores for emotional abuse (P =.001), sexual abuse (P =.005), and emotional neglect (P =.005).

Single-marker analyses indicated that suicidality may be associated with certain SNPs of the corticotropin releasing hormone-binding protein (CRH-BP) and the FK506 binding protein 5 (FKBP5). Specifically, CRH-BP rs7728378-C carriers (odds ratio [OR], 3.05; 95% CI, 1.41-6.57; P =.004) and FKBP5 rs2766533-GG genotypes (OR, 2.93; 95% CI, 1.02-8.42; P =.001) were associated with increased risk for suicidal behavior. In addition, FKBP5 rs3777747-AA genotypes were associated with decreased risk for suicidality (OR, 0.34; 95% CI, 0.19-0.98; P =.039). Only the rs2766533 SNP of FKBP5 remained significant after multiple test corrections. No significant interaction effects were observed between childhood maltreatment and genetic variants on the risk for suicidal behavior.

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These data indicate that childhood maltreatment, particularly emotional and sexual abuse, may increase risk for suicidality among adult patients with bipolar disorder. In addition, genetic variability analyses identified 1 CRH-BP and 2 FKBP5 SNPs as associated with suicidal behavior, although only the FKBP5 rs2766533 polymorphism remained significant after permutation correction. Researchers noted that no interaction between genes and the environment was found. Further research in a larger cohort is necessary to explore these findings.

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Segura AG, Mitjans M, Jiménez E, et al. Association of childhood trauma and genetic variability of CRH-BP and FKBP5 genes with suicidal behavior in bipolar patients [published online May 8, 2019]. J Affect Disord. doi:10.1016/j.jad.2019.05.014