Author ORCID Identifier
0000-0003-1301-7015
Defense Date
2024
Document Type
Dissertation
Degree Name
Doctor of Philosophy
Department
Integrative Life Sciences
First Advisor
Michael C. Neale
Second Advisor
Alexis Edwards
Third Advisor
Timothy York
Fourth Advisor
Silviu-Alin Bacanu
Fifth Advisor
Liangsuo Ma
Sixth Advisor
Bernard Fuemmeler
Abstract
Background: Identifying risk factors for suicidal thoughts and behaviors, especially causal ones, will be imperative to improving screening and treatment interventions. To identify replicable brain-based risk factors, there is increasing evidence indicating the need for large sample sizes, in the hundreds to thousands, in order to achieve a sufficient level of statistical power to detect them. Furthermore, longitudinal studies of brain and behavioral factors will be essential to understanding how suicide develops, especially the transition from suicide ideation to attempt. While experimental studies may not be feasible or ethical, genetically informed methods for testing evidence for causation are an alternative approach that may reveal critical insights into the mechanisms underlying suicide.
Methods: To replicate previously identified associations between resting-state functional MRI connectivity measures and childhood anhedonia, a significant behavioral risk factor for suicide, we tested these findings in an independent sample from the Adolescent Brain Cognitive Development Study ®, a longitudinal study of adolescent brain and behavioral development. Furthermore, using the same adolescent sample, we applied linear mixed effects modeling and Page 14 of 222 cross-lagged-panel-modeling to investigate differences in brain and behavioral development in those who developed suicide behaviors across the ages of ten to twelve. Finally, using two genetically informed methods, we tested the evidence for a causal relationship between brain structure and suicide risk using data derived from both adults and youths.
Results: We found replicable hypoconnectivity in two new resting-state functional MRI connectivity measures in children reporting anhedonia compared to controls. Youths reporting suicide behaviors exhibited accelerated rates of total cortical volume decline, the greatest increases in DSM5-depression scores, and slower declines in levels of Behavioral Activation System-fun-seeking scores compared to other groups. Finally, we found evidence of negative causal effects of total cortical brain structures on suicide attempt risk in adults and internalizing psychopathology in youths.
Conclusions: Hypoconnectivity in resting-state function MRI measures may be a marker of childhood anhedonia. Specific changes in brain total cortical gray matter development is associated with suicide behaviors in youths and may underlie a common causal mechanism between youth and adult suicidality.
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
6-9-2024
Included in
Behavior and Behavior Mechanisms Commons, Mental Disorders Commons, Other Genetics and Genomics Commons, Other Neuroscience and Neurobiology Commons