Pathways to self-harm: Biological mechanisms and genetic contribution

自残途径：生物机制和遗传贡献

• 批准号: MR/R004889/1
• 负责人: Becky Mars
• 金额: $ 28.82万
• 依托单位: University of Bristol
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2017
• 资助国家: 英国
• 起止时间: 2017 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FR004889%2F1
• 关键词: Pathways; self; harm; Biological; mechanisms

Self-harm in young people is a major problem. As many as 1-in-6 teenagers have self-harmed at some point in their lives, and self-harm is particularly common between the ages of 10 and 16 years. Young people who self-harm seem to be more likely to do poorly in a number of ways in early adulthood, including being more likely to have a mental health problem, and to use substances like alcohol and drugs. It is also the strongest known risk factor for suicide. Although self-harm is very common in young people, we know little about what causes it. A better understanding of the things that increase the risk for self-harm, and how they work could help us to develop more effective ways to prevent self-harm and support young people when they need it.Research shows that facing bad experiences early in life (such as physical and sexual abuse, and emotional neglect) increases the chances that a young person will self-harm. However we do not yet understand how this works. We know that the social environment (including the occurrence of adversity) can have an impact on the body's internal working, such as inflammation, changes to chemicals around genes, and hormones, and that these things in turn are involved in suicide and self-harm. In this study, we aim to investigate whether early bad experiences are associated with three different biological processes (inflammation, alterations to DNA, and puberty (stage and timing)) and explore whether these factors are, in turn, associated with self-harm in adolescence. Our research will also investigate whether associations between inflammation, alterations to DNA, puberty and self-harm are real, or whether they might be explained by other factors. This research could help to identify potential markers of future self-harm risk, as well as possible targets for treatment for young people who self-harm. We also plan to increase understanding about whether there are clearly distinct types of self-harm. Some researchers have proposed that it may be useful to classify self-harm according to whether or not the person has suicidal ideas, and has self-harmed with the intention of ending their life. However, it can be difficult to judge the extent to which someone wants to end their life and so we are not sure how useful it is to try and judge this in clinical practice. We plan to study whether the genes of young people who self-harm differ according to whether or not they have harmed with suicidal intent. This work will inform future research studies of self-harm, and could help practitioners working with young people who self-harm.In order to take the research forward, we have assembled a team of outstanding scientists from two universities. The proposed research will use data from the Avon Longitudinal Study of Parents and Children (ALSPAC). ALSPAC is a long term study of over 13,000 children born in Bristol and the surrounding area in 1991-1992 who have been followed up since birth with regular questionnaires and research clinics. There are very few studies that have such a large number of people with such detailed questions that were collected in real time. This is important as people's experience can be a strong influence on what they remember. It is also unusual for this kind of study to also have the biological samples that we need to answer the questions about genes, and the body's internal biological processes.

年轻人的自我伤害是一个大问题。多达六分之一的青少年在他们生命中的某个时刻自残过，自残在10岁至16岁之间尤为常见。自我伤害的年轻人似乎更有可能在成年早期的许多方面表现不佳，包括更有可能出现心理健康问题，以及使用酒精和毒品等物质。它也是已知的自杀最大的危险因素。尽管自残在年轻人中很常见，但我们对它的原因知之甚少。更好地了解增加自残风险的事情以及它们是如何工作的，可以帮助我们开发更有效的方法来防止自残，并在年轻人需要时提供支持。研究表明，在生命早期面对不好的经历，（如身体和性虐待，以及情感上的忽视）增加了年轻人自残的机会。然而，我们还不知道这是如何工作的。我们知道，社会环境（包括逆境的发生）会影响身体的内部工作，如炎症，基因周围化学物质的变化，以及激素，而这些事情反过来又与自杀和自残有关。在这项研究中，我们的目的是调查早期的不良经历是否与三种不同的生物学过程（炎症，DNA改变和青春期（阶段和时间））相关，并探索这些因素是否反过来与青春期的自我伤害有关。我们的研究还将调查炎症、DNA改变、青春期和自残之间的联系是否是真实的，或者它们是否可以由其他因素解释。这项研究可以帮助确定未来自残风险的潜在标志，以及自残年轻人的可能治疗目标。我们还计划增加对是否有明显不同类型的自我伤害的理解。一些研究人员提出，根据一个人是否有自杀的想法，以及是否有自残的意图来对自残进行分类可能是有用的。然而，很难判断一个人想要结束生命的程度，所以我们不确定在临床实践中尝试和判断这一点有多有用。我们计划研究自残的年轻人的基因是否根据他们是否有自杀意图而不同。这项工作将为未来的自我伤害研究提供信息，并可以帮助从业者与自我伤害的年轻人一起工作。为了推进研究，我们组建了一个由来自两所大学的杰出科学家组成的团队。这项研究将使用雅芳父母和孩子纵向研究（ALSPAC）的数据。ALSPAC是对1991-1992年出生在布里斯托及周边地区的13,000多名儿童进行的长期研究，这些儿童自出生以来一直接受定期问卷调查和研究诊所的随访。很少有研究能在真实的时间内收集到这么多人的详细问题。这一点很重要，因为人们的经历会对他们的记忆产生很大的影响。这类研究也不寻常，我们需要生物样本来回答基因和身体内部生物过程的问题。

项目成果

An exploration of the genetic epidemiology of non-suicidal self-harm and suicide attempt.

• DOI: 10.1186/s12888-021-03216-z
• 发表时间: 2021-04-23
• 期刊: BMC psychiatry
• 影响因子: 4.4
• 作者: Russell AE;Hemani G;Jones HJ;Ford T;Gunnell D;Heron J;Joinson C;Moran P;Relton C;Suderman M;Watkins S;Mars B
• 通讯作者: Mars B

Childhood adversity, pubertal timing and self-harm: a longitudinal cohort study.

• DOI: 10.1017/s0033291721000611
• 发表时间: 2021-03-08
• 期刊: PSYCHOLOGICAL MEDICINE
• 影响因子: 6.9
• 作者: Russell, Abigail Emma;Joinson, Carol;Roberts, Elystan;Heron, Jon;Ford, Tamsin;Gunnell, David;Moran, Paul;Relton, Caroline;Suderman, Matthew;Mars, Becky
• 通讯作者: Mars, Becky

Suicidal ideation during adolescence: The roles of aggregate genetic liability for suicide attempts and negative life events in the past year.

• DOI: 10.1111/jcpp.13653
• 发表时间: 2022-10
• 期刊: JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY
• 影响因子: 7.6
• 作者: Lannoy, Severine;Mars, Becky;Heron, Jon;Edwards, Alexis C.
• 通讯作者: Edwards, Alexis C.

Investigating evidence for a causal association between inflammation and self-harm: A multivariable Mendelian Randomisation study.

调查炎症与自残之间因果关系的证据：多变量孟德尔随机化研究。

• DOI: 10.17863/cam.52951
• 发表时间: 2020
• 作者: Russell A

Pathways between early-life adversity and adolescent self-harm: the mediating role of inflammation in the Avon Longitudinal Study of Parents and Children.

早期生活逆境与青少年自残之间的途径：雅芳父母和儿童纵向研究中炎症的中介作用。

• DOI: 10.1111/jcpp.13100
• 发表时间: 2019
• 期刊: Journal of child psychology and psychiatry, and allied disciplines
• 作者: Russell AE