Multimodal Neuroimaging Predictors of Non-Suicidal Self-Injury in the ABCD Study

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PROJECT SUMMARY ABSTRACT Non-suicidal self-injury (NSSI), the deliberate destruction of one’s own body tissue without suicidal intent, is alarmingly common in adolescents, and a risk factor for suicide attempts and deaths. NSSI typically emerges in adolescence, when brain networks supporting self-regulation, such as the cognitive control network, are still maturing, thus dysfunctional brain networks may underlie NSSI risk in adolescents. This project will leverage data from the Adolescent Brain Cognitive Development (ABCD) Study, including baseline MRI data collected when youth are aged 9-10 years, to identify brain network abnormalities in youth who develop NSSI two or more years later. Our analyses will be performed on multimodal MRI data and focus on two major intrinsic functional brain networks. These are the salience network, involved in emotion, and implicated in previous studies of NSSI, and the cognitive control network, important for emotion regulation, yet less comprehensively studied in NSSI. Our central hypothesis is that youth who develop NSSI have enhanced activity and integrity of the salience network and reduced activity and integrity of the cognitive control network compared to a sample of individually matched controls without NSSI. We propose a cross-sectional analysis of MRI data from baseline, in youth who develop NSSI for the first time (and with no history of suicidal ideation or attempt) at year 2 or later. At Year 2, N=141 (68 males) youths met our NSSI criteria. The number of males means this will be the first neuroimaging study with sufficient males to analyze sex differences. Based on community prevalence, we conservatively estimate that 560 youth will meet our NSSI group inclusion criteria by Year 6 (R01 Year 3), for a total sample size of 1120. Aim 1 will investigate fMRI tasks that measure salience network (an emotional N-back task) and cognitive control network (a Stop Signal task) function. We will also study connectivity of these networks during different task conditions using psychophysiological interaction analysis. Aim 2 will investigate the structural integrity of the salience and cognitive control networks by analyzing diffusion imaging to study white matter, and T1-weighted MRI to measure cortical thickness and amygdala shape and volume. Aim 3 will investigate the potential modifying influence of parental history of depression and of school environmental factors on the relationship between brain structure and function, and NSSI risk. An exploratory sub-aim will identify whether earlier age of onset of NSSI is associated with stronger network effects on risk for NSSI. By studying brain networks prior to NSSI onset, this study has promise for identifying biological targets that could be used in experimental therapeutics treatment development, such as pharmacological or neuromodulatory therapeutics. These could reduce the harmful physical and psychological effects of NSSI on individuals and their loved ones, and prevent future deaths by suicide.