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.