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Addressing Mental Health in the Second Decade of Life through Translational Lifecourse Research
In this initiative, sponsored by the Harvard Catalyst Child Health Committee, the community was invited to submit applications for pilot grants to foster and enable collaborative research on mental health and the developing brain in the second decade of life across the T1-T4 translational spectrum.
The specific research priority areas represented topics covered as part of the annual Child Health Symposium held in October 2014. Sponsored by Harvard Catalyst’s Child Health Committee, the symposium “Mental Health and the Developing Brain in the Second Decade of Life: Research Challenges and Opportunities” brought together leading scientists from across the nation for a dialog with Harvard’s child health research community on four topics:
- Mood Dysregulation
- Youth Suicide
- Concussion and the Developing Brain
For this initiative, the first two focus areas were consolidated into one research priority area: mood dysregulation and its consequences. Applications in response to this RFA related to this research priority area or to the violence research priority area.
All Harvard University-appointed junior and senior faculty members were encouraged to apply for this funding opportunity, and the principal investigator or a co-investigator must have attended the Child Health Symposium held in October 2014.
Six pilot grants were awarded in amounts of up to $75,000 for each one-year project.
Funding decisions for the Child Mental Health pilot grants were announced in March 2015.
Principal Investigator: Erin Dunn, MPH, ScD, Massachusetts General Hospital
Co-Investigators: Andrea Baccarelli, MD, PhD, Harvard School of Public Health
Takao Hensch, PhD, Boston Children’s Hospital
Jordan Smoller, MD, ScD, Massachusetts General Hospital
We propose to test the overarching hypothesis that epigenetic modification is a central biological mechanism explaining how exposure to childhood adversity (e.g., interpersonal violence, socioeconomic deprivation) gets “under the skin” to increase risk for adolescent-onset depression. We hypothesize that the effects of environmentally-induced epigenetic modification are strongest during sensitive periods in development, or windows of time in the lifespan when the developing human brain is particularly vulnerable or sensitive to experience. This hypothesis will be tested in two aims using secondary data from the Avon Longitudinal Study of Parents and Children (n=1,000), a large birth cohort with repeated epigenetic and phenotypic measures. We focus on DNA methylation, one of the major mechanisms of epigenetic regulation. In Aim 1, we will examine the effect of timing of exposure to childhood adversity on epigenetic modification in “sensitive period” relevant genes, or genes that regulate the timing of high plasticity stages during postnatal brain development. In Aim 2, we will investigate, using statistical mediation models, the extent to which epigenetic modification of sensitive period relevant genes mediates or is directly (or indirectly) on the path between timing of adversity and adolescent-onset depressive symptoms. An interdisciplinary team of junior and senior investigators comprising experts across Harvard will accomplish these aims. Findings generated from the proposed research can help identify periods in the lifespan when interventions could be most effective in preventing adolescent-onset depressive symptoms, biological mechanisms by which adversity increases risk for depression, and possible targets to treat depressive disorders.
Principal Investigator: Elizabeth Goodman, MD, Massachusetts General Hospital
Co-Investigators: Ari Cohen, MD, Massachusetts General Hospital
Timothy Wilens, MD, Massachusetts General Hospital
Suicide is the third leading cause of mortality in 10-24 year olds but we have only a rudimentary ability to predict which adolescents will attempt or complete suicide. Because many adolescents use Emergency Departments (EDs) rather than primary care providers for confidential care and to stay “under the radar” of parents, suicide screening in EDs is not only an opportunity, but a responsibility. This pilot study will perform preliminary testing of a developmentally-based adolescent suicide screening algorithm that incorporates primordial through secondary prevention and can be applied universally within EDs while maintaining high efficiency and clinical acceptability. We will evaluate a new 2-step screening algorithm against the state of the art multi-item suicide screener to detect both occult suicidality and future suicidal behavior over 6 months in a cohort of 350 MGH ED 14-19 year old patients seen for general medical/surgical care. Our algorithm incorporates novel single item screeners derived from current clinical practice thereby maximizing goodness of fit and promoting acceptability among ED clinicians. The study will provide critical pilot data for development of a large R01 application for a multisite study that could transform clinical practice and improve suicide prevention for this vulnerable group.
Principal Investigator: Dina Hirshfeld-Becker, PhD, Massachusetts General Hospital
Co-Investigators: John Gabrieli, PhD, Massachusetts Institute of Technology
Brandon Gibb, PhD, SUNY Binghamton
Jamie Micco, PhD, Massachusetts General Hospital
Benjamin Shapero, MA, Massachusetts General Hospital
Despite growing evidence for atypical brain function in depression, it is uncertain whether these functional differences reflect the clinical state of depression or a trait predisposing to depression. We previously studied a group known to be at elevated risk for depression, offspring of parents with depression. Compared to offspring of controls, healthy 8-14-year-old offspring of parents with depression showed increased activation to fearful versus neutral facial expressions in the amygdala and other brain regions, and decreased activation to happy versus neutral expressions in the anterior cingulate cortex and supramarginal gyrus (N=50). The extensive over-activation to negative expressions and under-activation to positive expressions in at-risk children are consistent with behavioral evidence that vulnerability to depression involves a bias to attend to negative information, and may represent a neural marker of risk for depression. However, prospective follow-up studies are needed to elucidate this issue. We therefore propose a follow-up of these youth, now ages 12-18, to examine whether the neuroimaging data collected previously are associated with three specific forms of cognitive vulnerability to depression: biases to attend to negative information, to interpret ambiguous stimuli negatively, and to explain negative events pessimistically; and whether the neural data predict new emergence of depressed mood and other symptoms of emotional dysregulation. This project will generate pilot data for a larger prospective study examining whether early emerging neural differences identified in children at risk for depression contribute to the development of cognitive biases and onset of disorder and will pave the way for targeted preventive interventions.