Rising Star Award Research Update – Erin Dunn, ScD, MPH

Assistant Professor of Psychiatry at Massachusetts General Hospital and Harvard Medical School

2018 One Mind Peter Chiarelli Rising Star Collaborative Research Award winner

Exposure to stress and adversity in childhood is a leading risk factor for depression. Experiencing such events as a death in the family, parental divorces, food or financial insecurity, or traumas like the COVID-19 pandemic can all affect a child’s mental health. Studies show that children who are exposed to such events are about twice as likely to develop depression during their lives than that of their peers.

Biologically speaking, it is unknown exactly how stress and adversity leads to depression. Scientists are currently examining four main hypotheses: The first is that exposure itself (compared to no exposure) is what matters most and that people who experience adversity have an elevated risk of depression compared to those who have never been exposed (“Exposure model theory”). The second is that risk for depression increases in a dose response manner as a function of the amount of exposure (“Accumulation of Risk Model”). The third is that risk for depression is elevated in the short-term after exposure and dissipates across time (“Recency Model”). Lastly, the fourth hypothesis is that there are specific times in the course of the lifespan where exposure to adversity is particularly harmful in conferring risk for depression (“Sensitive Period Model”).

Dr. Dunn’s hypothesis is that the effects of stress are time-sensitive (following the Sensitive Period Model above) and that they are most significant during the first five years of life. The support from the $250,000 grant Dr. Dunn earned as a 2018 One Mind Rising Star Awardee is allowing her and her team to test this sensitive period hypothesis in relationship to DNA methylation. More specifically, they hypothesize that exposure to adverse events in the first 5 years of life triggers a set of biological responses that affect how genes are turned on and off. DNA methylation is a well-studied example of how environmental factors can influence gene expression (epigenetics) – including those that are stressful and adverse.

In support of her hypothesis, Dr. Dunn and her team analyzed an existing database (the Avon Longitudinal Study of Parents and Children) and found 40 different DNA methylation marks that were significantly affected in cases with adversity, with more than half of them occurring during the first 3 years of life.

Dr. Dunn’s One Mind funded research is aimed at externally validating this initial finding by analyzing extensive data from a number of different birth cohort studies that are currently ongoing worldwide. After reviewing the types of data collected and reaching out to the researchers conducting these other studies, they have established partnerships with 15 cohorts.

In 2020, which was the second year of their One Mind funded support, Dr. Dunn and her team made substantial progress in their work:

• They continued their collaborations to analyze data from several cohorts, including Generation R (n=500; Netherlands), Fragile Families Childhood Wellbeing Study (n=800; USA), GUSTO (n=812; Singapore), MAVAN I & II (n=363; Canada), and Project Viva (n=609; USA), data to determine if it replicates their previous findings from the ASLPAC cohort (n=1,018; UK).
• They also extended their analysis of data from the ASLPAC cohort to DNA methylation patterns in adolescence, providing an additional layer of replication to their findings that focuses on stability and change in DNA methylation patterns over time.
• They initiated new collaborations with GLAKU (Finland), HELIX (Europe), and the Raine Study (n=812; Australia), which will further inform their replication efforts.

Dr. Dunn and her team continue to work with Dr. Andrew Smith, a biostatistician from University of the West of England, to develop a meta-analytical method for the Structured Life Course Modeling Approach that will help her team investigate time-dependent effects of childhood adversity on DNA methylation across the cohorts.

Looking to the Future:

During 2021, Dr. Dunn and her team will focus on their established collaborations to complete their analyses of the link between developmental adversity and DNA methylation patterns and then harmonize the results of these analyses to ensure they are comparable to each other across both cohort-specific replication and meta-analyses. In parallel, they will continue to establish links to cohorts that have collected depressive symptom data, which will be critical to subsequent NIH grant applications. They also look forward to sharing their preliminary results with the research community this year, and ultimately to the development of targeted and timely interventions to prevent major depression or lessen its effects. One Mind remains highly impressed by the research Dr. Dunn is leading as a Rising Star Award winner because of its potential to positively impact mental health in youth.

You can learn more about Dr. Dunn’s research by watching the presentation she made at the Scientific Symposium of our 2018 Music Festival for Brain Health as well as the April 2020 Brain Waves episode titled Embracing Life in the Age of COVID-19 that Dr. Dunn was a guest on.