Depression is among the most prevalent of all psychiatric disorders. Consistent with the NIH objectives of promoting discovery in the brain and behavioral sciences to fuel research on the causes of mental disorders and charting mental illness trajectories to determine when, where, and how to intervene, a critical public health priority is the development of methods for identifying and altering factors and mechanisms that increase individuals'vulnerability to depression. Offspring of depressed parents are known to be at elevated risk for developing depression;consequently, assessing these children has been an important strategy for elucidating factors associated with the increased risk for psychiatric disorder. To date, however, few studies have gone beyond documenting the magnitude of this risk to examine specific mechanisms that might underlie the intergenerational transmission of risk for depression. Over the last four years we have worked hard to recruit and test a large, carefully diagnosed, sample of 10- to 14-year-old never-disordered girls at either high or low familial risk for depression. Each girl has a biological mother who either has experienced recurrent episodes of Major Depressive Disorder (MDD) during her daughter's lifetime (high risk) or has never experienced an episode of any Axis-I disorder (low risk). Although the high-risk girls are asymptomatic, we have found that they nevertheless already exhibit characteristics of MDD, including selective attention to sad faces, higher and more prolonged cortisol secretion in response to a laboratory stressor, higher levels of awakening cortisol, smaller hippocampi, and anomalous neural functioning both in response to reward and punishment and while experiencing and regulating a sad mood. Because we began recruiting the girls in this study at this young age only four years ago, we have not yet been able to examine fully whether these difficulties predict the subsequent onset of a first episode of MDD. Therefore, we propose to conduct a 54-month follow-up diagnostic session with this sample and to add a second fMRI scan to assess differences in the stability of neural structure and function between high-risk girls who do, and who do not, develop MDD. We also propose to recruit a new sample of high-risk daughters, to teach them either through attentional bias training or through real-time neurofeedback training to alter mechanisms that we posit underlie the development of MDD, and to assess both short- and long-term effects of modulating these mechanisms. We propose to examine immediate changes in stress reactivity, cognitive biases, and reward processing as a function of training. We also propose to conduct an 18-month follow-up assessment to examine longer-term effects of training on specific clinical constructs, such as levels of depressive symptoms, coping strategies, and the onset of MDD. This project will yield new insights concerning psychological and biological risk factors for MDD, and will provide important information that can be used to develop innovative and effective approaches to the prevention of depression.

Public Health Relevance

This project promises to improve our understanding of psychological and biological mechanisms that increase risk for depression, a devastating psychiatric condition that affects one-quarter of the world's population, that starts early in life and frequently becomes chronic and unrelenting. Understanding these mechanisms will help us to develop more effective approaches to the prevention of clinical depression.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Study Section
Biobehavioral Mechanisms of Emotion, Stress and Health Study Section (MESH)
Program Officer
Garriock, Holly A
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Stanford University
Schools of Arts and Sciences
United States
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Davis, Elena Goetz; Keller, Jennifer; Hallmayer, Joachim et al. (2018) Corticotropin-releasing factor 1 receptor haplotype and cognitive features of major depression. Transl Psychiatry 8:5
Manczak, Erika M; Gotlib, Ian H (2018) Relational Victimization and Telomere Length in Adolescent Girls. J Res Adolesc :
Ellwood-Lowe, Monica E; Humphreys, Kathryn L; Ordaz, Sarah J et al. (2018) Time-varying effects of income on hippocampal volume trajectories in adolescent girls. Dev Cogn Neurosci 30:41-50
Waugh, Christian E; Running, Kristin E; Reynolds, Olivia C et al. (2018) People are better at maintaining positive than negative emotional states. Emotion :
Colich, Natalie L; Ho, Tiffany C; Ellwood-Lowe, Monica E et al. (2017) Like mother like daughter: putamen activation as a mechanism underlying intergenerational risk for depression. Soc Cogn Affect Neurosci 12:1480-1489
Davis, E G; Humphreys, K L; McEwen, L M et al. (2017) Accelerated DNA methylation age in adolescent girls: associations with elevated diurnal cortisol and reduced hippocampal volume. Transl Psychiatry 7:e1223
Pagliaccio, David; Luking, Katherine R; Anokhin, Andrey P et al. (2016) Revising the BIS/BAS Scale to study development: Measurement invariance and normative effects of age and sex from childhood through adulthood. Psychol Assess 28:429-42
Sacchet, Matthew D; Gotlib, Ian H (2016) Neurofeedback training for major depressive disorder: recent developments and future directions. Expert Rev Neurother 16:1003-5
LeMoult, Joelle; Joormann, Jutta; Kircanski, Katharina et al. (2016) Attentional bias training in girls at risk for depression. J Child Psychol Psychiatry 57:1326-1333
Foland-Ross, Lara C; Behzadian, Negin; LeMoult, Joelle et al. (2016) Concordant Patterns of Brain Structure in Mothers with Recurrent Depression and Their Never-Depressed Daughters. Dev Neurosci 38:115-23

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