Childhood maltreatment and polygenic risk in bipolar disorders

Abstract

Background Childhood maltreatment is a well‐known risk factor for developing a more severe and complex form of bipolar disorders (BD). However, knowledge is scarce about the interactions between childhood maltreatment and underlying genetic vulnerability on the clinical expression of BD. Method We assigned a BD‐polygenic risk score (BD‐PRS), calculated from the Psychiatric Genomics Consortium, to each individual in a sample of 402 cases with BD. The lifetime clinical expression of BD was characterized using structured interviews and patients completed the Childhood Trauma Questionnaire (CTQ) to assess the severity of childhood maltreatment. Results Cases who reported more severe childhood maltreatment had a lower BD‐PRS (rho = −0.12, P = .01), especially when considering emotional abuse (rho = −0.16, P = .001). An interaction between BD‐PRS and childhood maltreatment was observed for the risk of rapid cycling (P = .01). No further interactions between BD‐PRS and childhood maltreatment were observed for other clinical characteristics (age at onset, suicide attempts, number of mood episodes, mixed features, substance use disorders and psychotic symptoms). Conclusion Our study is the first to show that less genetic risk may be needed to develop a more unstable form of BD when exposed to childhood maltreatment. Our study supports childhood trauma as an independent risk factor for BD.

Interaction between adverse childhood experiences and polygenic risk in patients with bipolar disorder

“…Recent studies have suggested that a high BD-PRS may be associated with the presence of psychotic features during mood episodes 17,18 , while BD-PRS has been suggested to not be associated with an earlier AAO 19 . An additional recent study reported the interaction between childhood maltreatment and PRS in patients with BD and found that BD-PRS and childhood maltreatment interacted to increase the risk of rapid cycling 11 .…”

“…From this cohort, we obtained 1 615 subjects with BD I, who were of European ancestry to heighten homogeneity. Participants provided written informed consent according to institutional review board protocols and were evaluated using the Diagnostic Interview for Genetic Studies (DIGS) 11,13 . DIGS is a specific clinical interview for evaluating mood and psychotic disorders through a semistructured design corresponding to a wide spectrum of DSM-IV criteria.…”

“…A detailed description of the sample and genotyping procedures has been previously described 11 . Genotyping of the BiGS sample was conducted using the Affymetrix Genome-Wide Human SNP Array 6.0 (Santa Clara, CA, USA).…”

“…Thus, high PRS could mean high BD genetic predisposition. Some investigators have found that individuals with high PRS instead of single SNP, and exposure to childhood abuse are particularly at risk for developing major depressive disorder compared to normal controls and rapid cycling within BD patients 10,11 ; however, no previous studies have investigated the relationship between PRS and various ACEs as well as abuse. We hypothesized that ACEs interact with the genetic predisposition to BD, and that both of these factors would induce earlier AAO and worse clinical outcomes of BD.…”

Prevalence of Prediabetes and Diabetes Mellitus Type II in Bipolar Disorder

“…Regarding environmental risk contributing to T2D in BD, several studies report an unhealthy life style in patients including physical inactivity especially in depressive phases (26,27), higher alcohol and illegal substance consumption, nicotine dependence and greater intake of unhealthy food (28)(29)(30)(31), and increased rates of psychological trauma/maltreatment in childhood (32,33). Additionally, several endocrine and metabolic pathways could be playing a role in conveying a greater risk of T2D in BD, such as dysregulation of different neuropeptides (for example leptin, ghrelin, and adiponectin) and disturbances in the hypothalamus-pituitary-adrenal gland axis (34,35).…”