Childhood maltreatment and HPA axis gene expression in bipolar disorders: A gene network analysis.

International audienceIntroduction: Bipolar disorder (BD) is highly associated with childhood maltreatment (CM), the exposure to such early adversity being suggested to disrupt the expression of several biological pathways. This study aims at exploring associations between the mRNA levels of 9 HPA axis genes in lymphoblastoid cell lines from patients with BD according to their self-reported exposure to CM.Methods: The sample consisted of 33 Caucasian patients with a diagnosis of BD type 1, assessed for the exposure to CM with the Childhood Trauma Questionnaire (CTQ). Quantitative RT-PCR was performed on 9 transcripts of the HPA axis genes: DGKH, FKBP5, NR3C1, SGK1, SGK2, SGK3, SKA2, STAT5A and UCN. RT-qPCR data were analyzed using the method of disjoint gene networks with SARP.compo package for R.Results: We found no associations between CTQ total score and the amount of HPA axis transcripts neither in univariate analyses, nor with network analyses. Emotional abuse (EA) was associated with a significant decreased expression of two transcripts, DGKH (p = 0.009) and NR3C1 (p = 0.04). This was confirmed by the disjoint network analysis, which showed that NR3C1 and DGKH were expressed differently from the rest of the HPA axis network in presence of emotional abuse.Discussion: This study described the expression levels of a comprehensive set of HPA axis genes according to childhood maltreatment in a sample of patients with BD type 1 and suggested that emotional abuse decreased the expression of NR3C1 and DGKH. Our results require further replication in independent larger samples

Influence of childhood maltreatment on prevalence, onset, and persistence of psychiatric comorbidities and suicide attempts in bipolar disorders

International audienceAbstract Background Psychiatric comorbidities and suicide attempts are highly prevalent in Bipolar Disorders (BD). We examined the associations between childhood maltreatment, psychiatric comorbidities, and suicide attempts, in terms of lifetime prevalence, sequence of onset, and current symptoms. Methods We assessed 3,047 individuals with BD for suicide attempts, anxiety disorders, substance use disorders, and eating disorders. Participants completed a self-report for the assessment of childhood maltreatment. Associations between childhood maltreatment and characteristics of comorbidities (lifetime prevalence, current symptoms, and age at onset) were examined using logistic regressions and network analyses. Results Psychiatric comorbidities were frequent with a mean number per individual of 1.23 (SD = 1.4). Most comorbidities occurred prior to the onset of BD. Participants who reported higher levels of childhood maltreatment had more frequent and multiple comorbidities, which were also more currently active at inclusion. Childhood maltreatment did not decrease the age of onset of comorbidities, but was associated with a faster accumulation of comorbidities prior to the onset of BD. Logistic regression and network analyses showed that emotional abuse and sexual abuse might play a prominent role in the lifetime prevalence of psychiatric comorbidities and suicide attempts. Conclusions Childhood maltreatment was associated with suicide attempts, and with frequent, multiple, and persistent psychiatric comorbidities that accumulated more rapidly prior to the onset of BD. Hence, childhood maltreatment should be systematically assessed in individuals with BD, in particular when the course of the disorder is characterized by a high comorbid profile or by a high suicidality

Association between childhood maltreatment and the clinical course of bipolar disorders: a survival analysis of mood recurrences

International audienceObjectives: Childhood maltreatment, also referred as childhood trauma, increases the severity of Bipolar Disorders (BD). Childhood maltreatment has been associated with more frequent mood recurrences, however mostly in retrospective studies. Since scarce, further prospective studies are required to identify whether childhood maltreatment may be associated with the time to recurrence in BD.Methods: Individuals with BD (N=2008) were assessed clinically and for childhood maltreatment at baseline, and followed-up for two years. The cumulative probability of mood recurrence over time was estimated with the Turnbull's extension of the Kaplan-Meier analysis for interval-censored data, including childhood maltreatment as a whole, and then maltreatment subtypes as predictors. Analyses were adjusted for potential confounding factors.Results: The median duration of follow-up was 22.3 month (IQR:12.0-24.8). Univariable analyses showed associations between childhood maltreatment, in particular all types of abuses (emotional, physical and sexual) or emotional neglect, and a shorter time to recurrence (all p values <0.001). When including potential confounders into the multivariable models, the time to mood recurrence was associated with multiple/severe childhood maltreatment (i.e. total score above the 75th percentile) (HR=1.32 95%CI(1.11-1.57), p=0.002), and more specifically with moderate/severe physical abuse (HR=1.44 95%CI(1.21-1.73), p<0.0001). Living alone, lifetime anxiety disorders, lifetime number of mood episodes, baseline depressive and (hypo)manic symptoms and baseline use of atypical antipsychotics were also associated with the time to recurrence.Conclusions: In addition to typical predictors of mood recurrences, an exposure to multiple/severe forms of childhood maltreatment, and more specifically to moderate to severe physical abuse, may increase the risk for a mood recurrence in BD. This leads to the recommendations of more scrutiny and denser follow-up of the individuals having been exposed to such early life stressors