Causal Analyses of Associations Between Brain Structure and Suicide Attempt in Adulthood and Late Childhood

Yi Zhou PhD , Luis F.S. Castro-de-Araujo MD, PhD , Madhurbain Singh MBBS , Michael C. Neale PhD
{"title":"Causal Analyses of Associations Between Brain Structure and Suicide Attempt in Adulthood and Late Childhood","authors":"Yi Zhou PhD ,&nbsp;Luis F.S. Castro-de-Araujo MD, PhD ,&nbsp;Madhurbain Singh MBBS ,&nbsp;Michael C. Neale PhD","doi":"10.1016/j.jaacop.2025.02.005","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><div>Brain markers for suicide risk in adulthood may be detected during childhood and used for earlier detection and initiation of preventive interventions. Genetic instrumental variable analyses were used to determine whether there is evidence of lower brain total cortical surface area and thinner average cortical thickness (ACT) causing increased suicide risk in adults and whether lower measures of similar brain measures can cause increased risk of suicidality and related psychopathology in older children.</div></div><div><h3>Method</h3><div>Two-sample Mendelian randomization (MR) was used with summary statistics from genome-wide association studies for total cortical surface area, ACT, and suicide attempt in adults to test causal hypotheses. In youth ages 9 to 10 years old, a combined MR and twin-based direction-of-causation approach was applied to the European twin sample (199 monozygotic, 257 dizygotic twin pairs), and a hybrid traditional twin direction-of-causation approach was applied to the full twin sample (308 monozygotic, 397 dizygotic twin pairs) from the Adolescent Brain Cognitive Development (ABCD) Study.</div></div><div><h3>Results</h3><div>Two-sample MR analyses found a significant negative causal effect of total cortical surface area on suicide attempt risk in adults. MR–direction-of-causation analyses did not find a significant causal effect of any brain measure on suicidality in older children, but found significant negative causal effects of ACT on depression and internalizing psychopathology, and vice versa.</div></div><div><h3>Conclusion</h3><div>Brain markers of suicide risk may be instantiated differently in adults compared with older children, though lower ACT may be causally related to psychopathology associated with suicidality in these youth.</div></div><div><h3>Plain language summary</h3><div>Using genetic, neuroimaging, and psychiatric measures from adults and older children, we found that lower total brain surface area may be associated with an increased risk of a suicide attempt in adults, but not in older children. Instead, in older children, lower average brain thickness was associated with increased levels of depression and other psychiatric measures known to be associated with suicide risk. These findings suggest that suicide behaviors may be mediated by different brain processes across adults and older children, and thus may require different screening and diagnostic considerations.</div></div>","PeriodicalId":73525,"journal":{"name":"JAACAP open","volume":"3 3","pages":"Pages 455-466"},"PeriodicalIF":0.0000,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"JAACAP open","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S294973292500033X","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

Abstract

Objective

Brain markers for suicide risk in adulthood may be detected during childhood and used for earlier detection and initiation of preventive interventions. Genetic instrumental variable analyses were used to determine whether there is evidence of lower brain total cortical surface area and thinner average cortical thickness (ACT) causing increased suicide risk in adults and whether lower measures of similar brain measures can cause increased risk of suicidality and related psychopathology in older children.

Method

Two-sample Mendelian randomization (MR) was used with summary statistics from genome-wide association studies for total cortical surface area, ACT, and suicide attempt in adults to test causal hypotheses. In youth ages 9 to 10 years old, a combined MR and twin-based direction-of-causation approach was applied to the European twin sample (199 monozygotic, 257 dizygotic twin pairs), and a hybrid traditional twin direction-of-causation approach was applied to the full twin sample (308 monozygotic, 397 dizygotic twin pairs) from the Adolescent Brain Cognitive Development (ABCD) Study.

Results

Two-sample MR analyses found a significant negative causal effect of total cortical surface area on suicide attempt risk in adults. MR–direction-of-causation analyses did not find a significant causal effect of any brain measure on suicidality in older children, but found significant negative causal effects of ACT on depression and internalizing psychopathology, and vice versa.

Conclusion

Brain markers of suicide risk may be instantiated differently in adults compared with older children, though lower ACT may be causally related to psychopathology associated with suicidality in these youth.

Plain language summary

Using genetic, neuroimaging, and psychiatric measures from adults and older children, we found that lower total brain surface area may be associated with an increased risk of a suicide attempt in adults, but not in older children. Instead, in older children, lower average brain thickness was associated with increased levels of depression and other psychiatric measures known to be associated with suicide risk. These findings suggest that suicide behaviors may be mediated by different brain processes across adults and older children, and thus may require different screening and diagnostic considerations.
脑结构与成年期和儿童期晚期自杀企图之间关系的因果分析
目的在儿童时期可以检测到成年期自杀风险的脑标记物,并用于早期发现和启动预防干预。遗传工具变量分析用于确定是否有证据表明较低的大脑总皮质表面积和较薄的平均皮质厚度(ACT)导致成人自杀风险增加,以及较低的类似大脑测量是否会导致较大儿童自杀和相关精神病理风险增加。方法采用两样本孟德尔随机化(MR),并结合全基因组关联研究的汇总统计数据,对成人的总皮质表面积、ACT和自杀企图进行因果假设检验。在9至10岁的青少年中,将MR和基于双胞胎的联合因果关系方法应用于欧洲双胞胎样本(199对同卵双胞胎,257对异卵双胞胎),并将混合传统双胞胎因果关系方法应用于来自青少年大脑认知发展(ABCD)研究的全双胞胎样本(308对同卵双胞胎,397对异卵双胞胎)。结果两样本核磁共振分析发现,总皮质表面积对成人自杀企图风险有显著的负相关影响。mr -因果分析没有发现任何大脑测量对年龄较大的儿童自杀有显著的因果影响,但发现ACT对抑郁和内化精神病理有显著的负因果影响,反之亦然。结论与年龄较大的儿童相比,成人自杀风险的脑标记物可能有不同的实例,尽管较低的ACT可能与这些青少年自杀相关的精神病理有因果关系。通过对成人和年龄较大的儿童的遗传、神经影像学和精神病学测量,我们发现,在成人中,较低的脑表面积可能与自杀企图的风险增加有关,但在年龄较大的儿童中则不然。相反,在年龄较大的儿童中,较低的平均脑厚度与抑郁程度的增加以及其他已知与自杀风险相关的精神指标有关。这些发现表明,自杀行为可能是由不同的大脑过程介导的,因此可能需要不同的筛查和诊断考虑。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
JAACAP open
JAACAP open Psychiatry and Mental Health
自引率
0.00%
发文量
0
审稿时长
16 days
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信