Childhood trauma, stress and suicide: Towards a better understanding of the precise causal mechanisms.

自杀是世界范围内的主要死亡原因，占所有死亡人数的1.5%(世卫组织，2014年)。自杀行为的原因尚未完全了解；确定风险和保护因素将有助于预测自杀风险并确定改善自杀预防的干预目标(Mann等人，1999年)(O‘Connor，2011年)。最近的证据表明，以皮质醇水平衡量的下丘脑-垂体-肾上腺(HPA)轴活动失调已被确定为自杀的一个潜在危险因素(McGirr等人，2010年)。为了支持这一观点，O‘Connor等人(2017)发现，与对照组相比，以前有过自杀企图的参与者在实验室应激源的反应中皮质醇水平显著降低。越来越多的证据表明，静息皮质醇水平也与自杀行为有关(O‘Connor等人，2016)。梅尔赫姆等人(2017)报告说，与对照组相比，有自杀未遂史的人头发皮质醇浓度较低。这表明，头发皮质醇可能是自杀行为的生物标志物，它可能与皮质醇对压力的反应有关。皮质醇是暴露在慢性压力下的一种衡量标准。然而，这是一个需要进一步调查的领域。最近，奥康纳等人。(2018)发现，在试图结束自己生命的人中，童年创伤水平越高，成年后静息皮质醇水平越低，皮质醇对压力的反应越迟钝。这些发现的重要性在于，童年创伤的经历可能使个人更容易自杀，因为这会导致HPA轴活动迟钝，以应对压力和以后生活中的休息。Lovallo等人(2013)开发的一个理论模型表明，暴露在早期逆境中与对压力的皮质醇反应迟钝有关，并以更冲动的行为形式改变认知功能，发现了将暴露于逆境与发展更冲动的行为风格和更不稳定的情绪调节联系起来的证据。O‘Connor等人的研究成果。(2018)提出，发展更冲动的行为方式和先兆，如童年创伤和执行功能受损，可能会增加自杀行为的风险。因此，儿童创伤程度高的个体在应对压力和休息时HPA轴活动迟钝的发现为Lovallo等人(2013)提出的途径之一提供了证据，并将他的模型扩展到自杀行为。然而，关于童年创伤对自杀背景下的压力和皮质醇过程的影响，人们知之甚少。因此，重要的是阐明儿童创伤、低水平皮质醇和自杀风险以及脆弱个体的执行功能、冲动和自尊之间的确切因果机制。Franklin等人的元分析工作。(2017)指出，预测自杀想法和行为的能力有限，因为风险因素很弱且不准确，而且研究通常调查单一的风险因素，这进一步限制了预测的实用性。大多数纳入Meta分析的研究都有较长的随访间隔(5-10年)，但较长的跟踪间隔并不能提高预测能力。因此，作者建议使用微观纵向方法来提高预测能力，这将在这里使用。这一博士项目旨在了解童年创伤与慢性压力和自杀之间的联系机制。该项目有三个方面：首先，进行一项大规模的在线调查，以调查童年创伤与自杀意念或自杀未遂史之间的联系，以及与自我报告的压力、执行控制和冲动的关系。大规模调查从未包括与童年创伤、自杀和冲动有关的执行功能测量，因此将证明

Suicide is a major cause of death worldwide, responsible for 1.5% of all mortality (WHO, 2014). The causes of suicidal behaviour are not fully understood; identification of risk and protective factors would help predict the risk of suicide and identify targets for intervention to improve suicide prevention (Mann et al., 1999)(O'Connor, 2011). Recent evidence has suggested that dysregulated hypothalamic-pituitary-adrenal (HPA) axis activity, as measured by cortisol levels, has been identified as one potential risk factor for suicide (McGirr et al., 2010). In support of this notion, O'Connor et al., (2017) found that participants who had made a previous suicide attempt exhibited significantly lower cortisol levels in response to a laboratory stressor compared with controls. Evidence is also converging to suggest that resting cortisol levels are also associated with suicide behaviour (O'Connor et al., 2016). Melhem et al., (2017) reported that those with a suicide attempt history had lower hair cortisol concentration compared to controls. Suggesting that hair cortisol, a measure of exposure to chronic stress, could be a biomarker for suicidal behaviour and it could be related to cortisol reactivity to stress. However, this is an area that requires further investigation. More recently, O'Connor et al. (2018) have found that higher levels of childhood trauma are associated with lower resting cortisol and blunted cortisol reactivity to stress in adulthood in individuals who have attempted to take their own life. The importance of these findings is that experience of childhood trauma may predispose individuals to vulnerability to suicide by leading to blunted HPA axis activity in response to stress and during rest later in life. A theoretical model developed by Lovallo et al., (2013), suggested that exposure to early adversity wasassociated with blunted cortisol reactivity to stress and altered cognitive function in the form of greater impulsive behaviours, finding evidence linking exposure to adversity to the development of a more impulsive behavioural styles and less stable mood regulation. O'Connor et al. (2018) proposes that the development of a more impulsive behaviour style and precursors such as childhood trauma and impaired executive functioning are likely to increase the risk of suicidal behaviour. As such, the findings of blunted HPA axis activity in response to stress and during rest in individual's with high levels of childhood trauma provide evidence for one of the pathways suggested by Lovallo et al., (2013) and extend his model to suicidal behaviour. However, relatively little is known about the effects of childhood trauma on stress and cortisol processes in the context of suicide. Therefore, it is important to elucidate the precise causal mechanisms linking childhood trauma, low levels of cortisol and suicide risk, alongside executive functioning, impulsivity and self-esteem in vulnerable individuals. The meta-analytic work of Franklin et al. (2017) suggested there is a limited ability to predict suicidal thoughts and behaviours as the risk-factors are weak and inaccurate and the studies commonly investigate single risk-factors which further limits predictive utility. Most studies included in the meta-analysis had long follow-up intervals (5-10 years), yet longer intervals did not improve predictive ability. The authors thus suggest using micro-longitudinal methods to improve predictive ability, which will be employed here. This PhD project aims to understand the mechanisms linking childhood trauma to chronic stress to suicide. The project is threefold; first, to conduct a large scale online survey to investigate the association between childhood trauma and history of suicidal ideation or attempt, and the relation with self-reported stress, executive control and impulsivity. A large-scale survey has never included executive function measures, in relation to childhood trauma, suicide and impulsivity, thus will provi