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Thesis Format

Integrated Article


Doctor of Philosophy




Hayden, Elizabeth P.


Children of mothers with a history of depression are at significantly higher risk for developing depression themselves. Although numerous mechanisms explaining this relationship have been proposed (Goodman & Gotlib, 1999), relatively little is known about the neural substrates of never-depressed children’s depression risk. Of the few studies that have used neuroimaging techniques to characterize risk-based differences in children’s neural structure, function, and functional connectivity, most have used samples that include participants with a personal history of depression or older samples (i.e., past the typical age of onset for depressive disorders). These approaches limit what can be determined regarding whether findings are true markers of risk (and potential etiological mechanisms) or better reflect resilience to depression or brain-based sequelae of depression. There is a clear need to better characterize children’s neuroimaging-based markers of depression risk by focusing on samples with clear statistical risk (i.e., a maternal history of depression or early emerging depression symptoms) prior to their own onset of disorder. This dissertation addresses this gap in the literature by characterizing the association between a sample (Ns = 80-85) of never-depressed children’s risk for depression and magnetic resonance imaging (MRI) markers of children’s brain structure (Study 1), functional response to maternal feedback (Study 2), and resting-state functional connectivity (Study 3). Main findings included never-depressed children’s self-reported depression symptoms being negatively associated with grey matter volume in regions relevant to reward processing (i.e., orbitofrontal cortex; Study 1), functional activity in salience processing regions (i.e., anterior insula) and reward processing (i.e., putamen) during critical maternal feedback (Study 2), and resting-state functional connectivity within the Central Executive Network and Salience Network (Study 3). I also demonstrated that children with high maternal risk for depression (i.e., a maternal history of depression) had significantly increased resting-state functional connectivity within the default mode network. Results indicate that brain-based associates of depression risk (i.e., maternal history of depression and children’s depression symptoms) pre-exist the development of depression, potentially contributing to the etiology of depression. Future directions for the emerging field of neuroimaging children’s risk for depression are discussed.

Summary for Lay Audience

Depression is among the most common mental health problems and one of the leading causes of disability worldwide. In addition, it is often associated with profoundly negative outcomes at the level of the individual (i.e., relationship and occupational impairment, poor quality of life, early death). Although there are many factors which are associated with an increased risk for depression (e.g., familial history, female sex, certain cognitive styles, etc.), little is known about the mechanisms that cause depression. Differences in the structure, function (i.e., activity), and connectivity of the brain are thought to contribute to the development of depression. Previous research has found that people with depression have differences in brain structure, function, and connectivity; however, as participants in these studies have already experienced depression, it is unclear whether brain-based associations contributed to the development of depression or were a consequence of depression. Using magnetic resonance imaging (MRI) techniques with a sample of never-depressed children, I investigated the associations between depression risk (i.e., a maternal history of depression, and both self- and maternal-reports of children’s depression symptoms) and brain structure (Study 1), function during exposure to maternal praise and criticism (Study 2), and connectivity at rest (Study 3). Across all studies I found evidence that early emerging depression symptoms were associated with differences in never-depressed children’s brains. Further, I found evidence that a maternal history of depression was associated with differences in brain connectivity at rest. These results have implications for our understanding of the neural mechanisms that contribute to the development of depression.

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Creative Commons Attribution-Noncommercial 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 4.0 License.