The effect of multigeneration history of suicidality on offspring’s neurodevelopment outcomes: evidence from the Adolescent Brain and Cognitive Development (ABCD) cohort

Background Parent-child transmission of suicidal behaviors has been widely elucidated, while the three-generation family suicide risk paradigm remains to be explored. This longitudinal study aimed to examine the influences of family history of suicidality (FHoS) among two prior generations on offspring’s neurodevelopment. Methods We conducted a retrospective, longitudinal study using the Adolescent Brain Cognitive Development (ABCD) study data collected from 2016 to 2021. Participants were allocated into four groups according to their parents’ (Generation 1 [G1]) and grandparents’ (Generation 2 [G2]) history of suicidality (G1−G2−; G1+G2−; G1−/G2+; G1+/G2+). We estimated adjusted associations between FHoS and offspring’s suicide ideation (SI), psychopathology, impulsivity and brain cortical volumes while controlling for age, sex, parental education, household income and marital status. Findings A total of 11,875 children aged 9-10 years were observed from baseline to 3-year follow-up. Compared to G1-G2-, higher odds of SI were observed for G1-G2+ (OR=1·99, 95% CI [1·54-2·56]) and G1+G2+ (2·25 [1·46-3·47]) by child-report. Higher odds of SI were also observed for G1+G2- (1·54 [1·12-2·12]), G1-G2+ (2·57 [1·89-3·48]) and G1+G2+ (2·70 [1·60-4·56]) by caregiver-report. Higher odds for psychopathology were also observed (1·47 [1·11-1·96]; 3·33 [2·57-4·33]; 5·44 [3·42-8·66]), while higher family suicide risk was associated with high impulsivity (B=1·32 [0·48-2·17]; 2·24 [1·32-3·15]; 2·26 [0·47-4·05]). Offspring in G1+G2-had higher cortical volumes in 12 brain regions, including the bilateral insula, temporal regions and occipital regions, which were also significantly associated with their lifetime SI. Discussion A cumulative risk pattern of FHoS in two prior generations was found for offspring’s neurodevelopmental outcomes. Earlier preventive interventions are warranted to weaken the familial transmission of suicidal risk. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study did not receive any funding ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study used ONLY openly available human data that were originally located at: [http://dx.doi.org/10.15154/1523041][1]. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced are available online at [http://dx.doi.org/10.15154/1523041][1]. [1]: https://dx.doi.org/10.15154/1523041