Epigenetic Effects of Childhood Adversity in the Brain and Suicide Risk

Abstract

With prevalence estimates ranging between 6.4% and 10.1% [–5], major depression ranks first among the most significant causes of disability and premature death, thus imposing a continual economic burden on society. For instance, in the United States, the direct and indirect costs are estimated at U.S.$44 billion/year [6]. The greatest loss to our society, however, is the associated mortality by suicide related to major depression. Indeed, it has been estimated that between 50% and 70% of suicide completers will die during an episode of major depression [7,8] and prospective follow-up studies of major depression suggest that between 7% and 15% of these patients will die by suicide [–12].Suicide is a complex problem, which is believed to result from the interaction of several different factors [13,14]. Indeed, psychological factors and personality traits such as impulsivity and negative affect [14,15], social factors [16,17], environmental factors such as early-life adversity [–20], genetic factors [21], and neurobiological factors [22] have been proposed to induce behavioral alterations, which in turn may predispose certain individuals to develop depressive and suicidal behaviors. However, since these factors alone are unlikely to explain suicide and suicide risk, it may be more readily explained when considering the interaction between these different sources of variation [23,24].Among these risk factors, early-life adversity, particularly childhood sexual abuse (CSA) and childhood physical abuse (CPA), is one of the strongest predictors of mental disorders [25,26] and suicide [18,19]. For example, studies have shown that CSA is associated with early onset of depression, chronic course, and more severe depressive outcome [–29] but, more importantly, with 12 times higher odds of suicidal behaviors [26,30]. Although less consistently, CPA and neglect have also been associated with suicidal behaviors [19,31]. CSA and CPA have been associated with higher odds of self-harm [,,–34], suicidal ideation [35,36], and suicide attempts [,–39]. Moreover, the prevalence of suicidal ideation and suicide attempts has been shown to increase with the severity and intensity of the abuse [35,36,38].