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

自杀是全世界死亡的一个主要原因，占所有死亡人数的1.5%（世卫组织，2014年）。自杀行为的原因尚不完全清楚；识别风险和保护因素将有助于预测自杀风险，并确定干预目标，以改善自杀预防（Mann et al., 1999）（O'Connor, 2011）。最近的证据表明，通过皮质醇水平测量的下丘脑-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 et al., 2010）。为了支持这一观点，O’connor等人（2017）发现，与对照组相比，之前有过自杀企图的参与者在实验室压力源下表现出明显较低的皮质醇水平。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 et al., 2016）。Melhem等人（2017）报告称，与对照组相比，有自杀企图史的人头发皮质醇浓度较低。这表明毛发皮质醇，一种暴露于慢性压力下的测量，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。然而，这是一个需要进一步调查的领域。最近，O’connor等人（2018）发现，在试图自杀的个体中，童年创伤程度越高，其成年后的静息皮质醇水平越低，皮质醇对压力的反应也越弱。这些发现的重要性在于，童年创伤的经历可能会导致HPA轴在应激反应和以后的休息中活动减弱，从而使个体易受自杀的影响。Lovallo等人（2013）开发的理论模型表明，早期逆境暴露与皮质醇对压力的反应减弱有关，并且以更大的冲动行为的形式改变了认知功能，发现证据表明逆境暴露与更冲动的行为风格的发展和更不稳定的情绪调节有关。O’connor等人（2018）提出，更冲动的行为风格的发展以及童年创伤和执行功能受损等前兆可能会增加自杀行为的风险。因此，在童年创伤程度高的个体中，应激反应和休息期间HPA轴活动减弱的发现为Lovallo等人（2013）提出的途径之一提供了证据，并将其模型扩展到自杀行为。然而，在自杀的背景下，童年创伤对压力和皮质醇过程的影响知之甚少。因此，阐明童年创伤、低水平皮质醇和自杀风险之间的确切因果机制，以及弱势个体的执行功能、冲动和自尊之间的联系，是很重要的。Franklin等人（2017）的元分析工作表明，预测自杀想法和行为的能力有限，因为风险因素薄弱且不准确，而且研究通常调查单一风险因素，这进一步限制了预测效用。纳入meta分析的大多数研究随访时间较长（5-10年），但较长的随访时间并不能提高预测能力。因此，作者建议使用微纵向方法来提高预测能力，本文将采用这种方法。这个博士项目旨在了解将童年创伤与慢性压力和自杀联系起来的机制。该项目分为三个部分；首先，通过大规模的网络调查，探讨儿童创伤与自杀意念或企图史的关系，以及与自我报告的压力、执行控制和冲动的关系。一个大规模的调查从来没有包括执行功能的措施，有关童年创伤，自杀和冲动，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