733. Effects of early life adversity on stress markers and emotion circuitry in adults with a history of suicide attempts

Abstract

Abstract Background Early life adversity (ELA) has been highlighted as strong distal factor for emergence of suicide behaviors (SB), however not all persons that experience ELA will engage in SB. Dispositional factors, such as stress system responsivity, emotion dysregulation, and brain structure and connectivity are hypothesized as critical precipitates for SB in individuals with a history of ELA. Aims & Objectives The primary aim of this research was to elucidate the mechanisms through which ELA contributes to SB by investigating specific dispositional and biological mediators. Specifically, four studies were conducted to evaluate stress system, dispositional factors and brain structure and connectivity in SB group or at-risk groups. Method Study 1 investigated long-term stress system via hair stress hormones using LC-MS/MS protocol in recent SB (n=22), clinical control (CC; n=31) and control (n=22) groups. Hormones were investigated with linear-mixed-models and related to ELA. Study 2 investigated association between ELA and self-aggression in SB (n=139) and CC (n=24) with regression and parallel-mediation models. Study 3 investigated moderating effects of ELA on the association between emotion processing facets and hopelessness, a risk-factor for SB across depressive disorders (n=50) and control group (n=70) using regression models. Study 4 investigated association among prospective SB (n=40) and brain structure and connectivity in female youth via one-way analyses of covariances compared to prospective suicide ideation (n=33) and CC groups (n=19). All studies used corrected thresholds (pcorr<.05). Results Study 1 showed an effect of group on the hair dehydroepiandrosterone (DHEA; p=.02) but not cortisol or cortisone levels. ELA was not related to any stress hormone (pcorr>.5). Study 2 reported that the levels of ELA and dispositional factors did not differ between SB and CC groups (pcorr>.1). Within SB ELA and dispositional factors associated and parallel mediation showed that ELA had indirect effect on self-aggression through impulsivity and inward anger (pcorr<.07). In study 3, the association between emotion processing facets and hopelessness were predominantly not moderated by ELA (pcorr>.4) and their association was significant only for emotion self-regulation (puncorr=.09). Study 4 showed lower cortical thickness in inferior frontal gyrus, and lower fractional anisotropy in fronto-temporal tracts in prospective SB compared to CC (puncorr<0.05). There were no differences between prospective suicide ideation and SB. Discussion & Conclusions Findings partially support the stress system hormones as a biopsychosocial feature of recent SB. The association among ELA and emotion dysregulation and aggressiveness is strong in SB. However, results from study 2 and 3 show that the risk-behavioral factors may relate to general psychopathology severity and are unspecific to self-oriented factors. Moreover, behavioural factors are themselves strongly associated to SB and are not necessarily reflecting effects of ELA. Importantly comparisons with well-defined CC groups or suicide ideation do not differ in behavioural or brain factors. These studies confirm heterogeneity within the SB population and indicate multiple risk-factors associated with SB. Results also highlight need for better behavioural constructs or questionnaires specified for SB populations. Overall, the studies highlight dispositional factors as potential psychobehavioral treatment targets for broader vulnerable populations.