Date of Award

Fall 1-1-2024

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Interdepartmental Neuroscience Program

First Advisor

Gee, Dylan

Abstract

Family history of depression is a robust predictor of early-onset depression (Elsayed, Fields et al. 2019, Ho, Shah et al. 2022) as well as other types of psychopathology (van Santvoort, Hosman et al. 2015, van Dijk, Murphy et al. 2021) among youth. Youth are at especially high risk when the family members with depression are their parents; youth whose parents have depression are at a 3- to 5-fold increased risk for developing depression themselves (Lieb, Isensee et al. 2002, Williamson, Birmaher et al. 2004). Prior work has indicated that risk may be conferred through alterations in neurodevelopment that precede the onset of psychopathology among child and adolescent samples (Gotlib, Hamilton et al. 2010, Clasen, Beevers et al. 2014, Chai, Hirshfeld-Becker et al. 2015, Frost Bellgowan, Molfese et al. 2015, Chai, Hirshfeld-Becker et al. 2016, Posner, Cha et al. 2016, Singh, Leslie et al. 2018, Morgan, Silk et al. 2019, Shapero, Chai et al. 2019, Fischer, Holt-Gosselin et al. 2022, Holt- Gosselin, Keding et al. 2023). Heightened risk may also be partly due to environmental factors, particularly within the family, such as family conflict, which has been shown to be elevated in youth at high (versus low) familial risk for depression (Pilowsky, Wickramaratne et al. 2006, Silk, Shaw et al. 2011, Gong, Rolls et al. 2021). However, the field currently lacks knowledge in three key areas. First, it is unclear which specific neurodevelopmental patterns during childhood, prior to the onset of psychopathology, represent early neural markers of familial risk for depression. Second, further research is needed to elucidate whether these childhood neural markers of familial risk predict the later development of psychopathology during adolescence. Finally, no studies to our knowledge have investigated the complex interactions among familial risk for depression, child neurodevelopment, and the family environment in predicting the onset of future psychopathology during adolescence. It is essential to address these knowledge gaps to help improve early detection, diagnosis, and treatment for youth at elevated risk for psychopathology. In the longer term, neural markers of vulnerability could potentially serve as targets for future prevention or intervention efforts. Here, I present three empirical studies utilizing neuroimaging, surveys, and clinical interviews collected from a well-powered longitudinal dataset from the ongoing Adolescent Brain Cognitive Development (ABCD) Study® (Casey, Cannonier et al. 2018), which recruited over 11,000 children (9-10 years old at baseline) who are being followed over 10 years. In the introductory chapter, I briefly review extant literature on familial risk for depression along with limitations of this existing work. In Study 1, I investigate emotion- and reward-related neural markers of familial risk for depression at 9-10 years old. In Study 2, I examine whether emotion- and reward-related neural markers of familial risk for depression at 9-10 years old predict the later onset of depression symptoms at 11-12 years old. In Study 3, I utilize an exploratory approach to identify large-scale neural circuit markers of familial risk for depression at 9-10 years oldand examine whether neural circuitry interacts with familial risk status and family conflict to predict psychopathology at ages 12-13 years. In the final chapter, I discuss interpretations of the dissertation findings along with future directions. Taken together, this dissertation contributes to our knowledge of the neurobiological and environmental factors and their interactions that may contribute to the development of psychopathology among youth at elevated risk for poor mental health outcomes. In the long term, this research has the potential to improve detection, diagnosis, and treatment of mental health problems among vulnerable youth.

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