PROJECT SUMMARY/ABSTRACT Suicide is the fifth leading cause of death among U.S. children 5 to 12 years, yet limited research on childhood suicide and suicidal behavior (SB) exists. The National Institute of Mental Health (NIMH) has acknowledged this critical gap as a high research priority. A significant risk factor for the early onset of a first suicide attempt (SA) is a parental history of SB. Although the familial transmission of SB is well documented, research examining the specific mechanisms associated with familial risk is limited. Our ongoing NIMH-R21 study (Cohort 1) is investigating factors related to the familial risk of SB in children, 6-9 years, with (PH+; n=100) and without (PH-; n=100) a parental history of SA. This proposed R01 study will continue annual follow-ups for Cohort 1 and add an additional 300 newly enrolled families (Cohort 2; ages 9-11 years; 150 per PH group) for a total sample of 500 parent-child dyads. Youth will be followed for four years from mid/late-childhood through early/mid-adolescence. Using the Research Domain Criteria (RDoC) framework, we will examine the trajectories of neurocognitive function (NF), emotional reactivity/regulation (ERR), non-suicidal self-injury (NSSI), suicidal ideation (SI), and SA in PH+ and PH- youth along with contributions by sex and race. Study participants at first assessment include youth 7-12 years. At last assessment, youth ages will range from 10-15 years. Both groups, PH+ and PH-, will be balanced by sex and race. Two main research aims and one exploratory aim will be tested. Aim 1: Examine longitudinally how PH status is associated with trajectories of NF and ERR constructs measured during mid/late-childhood through early/mid-adolescence. Aim 2: Investigate the potential mediating role of NF and ERR constructs on the association between PH status and offspring NSSI, SI, and SA. Exploratory Aim: Test sex and race as potential moderators of ERR and NF trajectories, and on the association between PH status and offspring NSSI, SI, and SA. This proposal’s central hypotheses are that (1) PH+ status increases vulnerability for developmental trajectories characterized by NF deficits and emotional dysfunction/dysregulation; (2) these trajectories will mediate the association between PH status and youth NSSI, SI, and SA; and (3) these associations between trajectories and SB/NSSI will be moderated by both sex and race. The hypotheses are informed by preliminary findings from the ongoing NIMH- R21 study, where group differences were found for ERR, SB, and NF. The proposed R01 study aligns well with the NIMH 2020 Strategic Plan for Research with emphasis on Goal 2-investigating mental health trajectories and inclusion of diverse samples. Completing the proposed study will assist with the identification of specific mechanisms associated with the familial risk of SB, determine if sex and race moderate the associations between risks and youth SB, and provide direction for targeted prevention strategies for high-risk youth.

Project Narrative The alarming rise in youth suicide rates and attempts creates a tremendous public health burden yet, limited knowledge exists regarding the mechanisms associated with youth suicide in high risk groups which is imperative for primary prevention efforts. A parental history of suicidal behavior (SB) is associated with a 4-to- 6-fold increased risk of offspring SB and a younger age of onset for first suicide attempt. The objective of this study is to fill gaps in our current knowledge through examining, longitudinally, how parental history (PH status) is associated with trajectories of neurocognitive functioning (NF) and emotional reactivity/regulation (ERR), how NF and ERR constructs mediate the association between PH status and offspring SB and non-suicidal self-injury (NSSI), and test sex and race as moderators of the association between NF and ERR trajectories and offspring SB/NSSI.