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 , Luis F.S. Castro-de-Araujo MD, PhD , Madhurbain Singh MBBS , 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.