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Dr. Erin Dunn – How Stress and Adversity Leads to Depression

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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

 

Erin Dunn Research UpdateExposure 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 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 ensuring replicability of this initial finding by analyzing extensive data from up to 39 different birth cohort studies that are currently ongoing worldwide.

In 2019, which was the first year of their One Mind funded support, Dr. Dunn and her team

made substantial progress in their work:

  • They solidified their research team by hiring key staff, including a postdoctoral research fellow named Alexandre Lussier who has extensive epigenetic analyses experience.
  • They initiated collaborations with cohorts that have collected childhood adversity and DNA methylation data and created documents and analytical plans to promote the collaborative nature of this project (see details below).

Creating Documents and Analytical Plans to Promote Collaboration:

Dr. Dunn and her team have compiled the contact information and cohort data for 30 cohorts that will be relevant to the present study, which will help initiate collaborations and streamline data harmonization. They have also taken several steps to facilitate the collaborative process between their lab and the different cohorts. Such actions include creating a public repository on a website called GitHub to share the data analysis scripts and analytical protocols that will be used to generate the results for the project; creating a “Standard Operating Procedures” (SOP) document that can be shared with current and prospective collaborators, which streamline the sharing of data and completion of analyses, and working closely with a biostatistician, Dr. Andrew Smith (University of the West of England), to develop a meta-analytical method for testing their hypotheses. Dr. Smith’s contributions are instrumental to their project, as his efforts will allow them to identify time-dependent effects of exposure to childhood adversity on DNA methylation across cohorts.

Some of the cohorts Dr. Dunn and her team have begun collaborations with include: 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). They have also initiated contacts with the Raine Study (n=812; Australia). Dr. Dunn’s team prioritized these studies because they are among the largest and have collected repeated measures of postnatal adversity, which they will use to first replicate their findings from a previous publication using data from the ALSPAC cohort (n=1,018; UK) (Dunn et al., 2019).

Looking to the Future:

Dr. Dunn and her team are excited about their second year of One Mind funded support that will happen in 2020, during which they will begin analyzing the results from the replication analyses, including both cohort-specific replication and meta-analyses across cohorts of the effects of childhood adversity on DNA methylation patterns. 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 hopeful and energized by the research Dr. Dunn is leading and are proud to have her as a Rising Star Award winner.

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.