Project Title: Investigation of the Neural Correlates of the Acquired Capability for Suicide in Child and Adult Brains.
Abstract:
Few studies have investigated the potential neural correlates underlying the acquired capability for suicide (ACS) as part of the Interpersonal Theory of Suicide (ITP) and other related theoretical models. While there have been many neuroimaging studies of suicidality, most have been cross-sectional and none have explored how transitioning from suicide ideation (SI) to suicide attempt (SA) is related to changes in brain structure and function associated with the ACS directly in individuals with suicidal thoughts and behaviors (STBs), to our knowledge.
Research Aims: In this project, we propose to 1) in children from the ABCD study who develop SA at 2-year follow-up, quantify the changes in the functional connectivity of brain networks, including those specifically associated with the ACS and 2) using a genetic epidemiological method called mendelian randomization (MR) to evaluate the evidence for the causal relationships between brain structure and function associated with the ACS and SA.
Sample: In total, there are 71 individuals who go on to develop SA at 2-year follow-up who previously did not report SA at baseline. These consist of individuals who previously did not endorse any STBs (STB naïve) and those who only endorsed SI at baseline. Furthermore, we will include a group of 290 individuals who develop suicide ideation at 2-year follow-up who were STB naive at baseline. Finally, we will also include 5995 individuals who remain STB naive at 2-year follow-up.
Measures: In the ABCD study, there are in total, 443 resting state functional MRI (rsfMRI) connectivity measures that we will use in our longitudinal analyses. Additionally, we will use pre-processed rsfMRI temporal variance measures from 19 brain regions previously identified to be associated with the ACS. For our MR analyses, we will be using genome wide association study (GWAS) summary statistics from brain imaging measures obtained from the UK Biobank, which were analyzed using brain scans from around 43,000 healthy adults. As well, we will be using GWAS summary statistics from a recent study of suicide attempt that utilized 29,782 suicide attempt cases and 519,961 controls
Procedures: For each of the pre-processed major rsfMRI connectivity measures, we will use mixed effects modeling to analyze the changes in rsfMRI connectivity from baseline to 2-year follow-up, while controlling for the random effects of subjects. Additionally, we will perform longitudinal factor analysis using 19 rsfMRI measures from brain regions previously associated with the ACS. Finally, we will perform 2-step MR analyses with brain imaging measures as our exposure/risk factor and SA as our outcome measure.
Potential Impact: Findings from our study may help us understand and identify biomarkers of the transition from SI to SA and provide specific targets for intervention to prevent SA.
Next Steps: Our next seps are to begin data preparation to carry out the analyses outlined in our specific aims.
