Current work in our group focuses on three primary areas.
1. Identifying individuals most at risk for depression. Experts have known for decades that exposure to stress is one of the biggest risk factors for depression. However, not everyone who experiences stress or adversity goes on to experience mental health problems, and we don’t yet know which individuals might be more susceptible to, or at risk for, developing depression following a stressful event. Given that depression is known to be partially genetically determined, we are studying the role of genetic variation in shaping risk for depression, by asking which genes confer an increased susceptibility to the effects of stress. Through our involvement in the Psychiatric Genomics Consortium (PGC), a massive collaborative effort to understand the genetic basis of psychiatric disorders, we’re working to identify the full spectrum of genetic variants underlying risk for depression. Using prospective data gathered over many years from large birth cohorts, we’re also exploring the genomic predictors of depressive symptom trajectories from childhood to adolescence. Finally, recognizing that non-European populations are dramatically underrepresented in genetics research, we are also working to complete genome-wide association study (GWAS) with more diverse racial/ethnic samples.
2. Understanding how stress gets biologically embedded. Although we know that people are more likely to develop depression after experiencing a stressor, we don’t yet know how stress “gets under the skin”, or causes biological changes to create this long-term vulnerability. We’re working to understand the mechanisms linking stress to depression risk by identifying biomarkers, such as epigenetic signatures, that do not alter the sequence of the genome, but rather shape how genes are expressed. Our currently funded work in this area is exploring how early exposure to stressors—including poverty, maltreatment, and other adversities—can leave epigenetic marks known as DNA methylation (DNAm) changes, which in turn can increase risk for depression in childhood, adolescence, and even adulthood. Understanding the biological pathways connecting stress to depression can help us better understand the etiology of depression and therefore focus our interventions on potentially modifiable biological targets.
3. Determining sensitive periods in development, or periods of heightened plasticity. There is a growing body of evidence from our research group and others to suggest that the impact of certain exposures on mental health outcomes might also depend on whether those exposures occur during “sensitive periods” in development. Sensitive periods are high-risk/high-reward stages in the course of the lifespan when the brain is highly plastic and when experience, whether exposure to adversity on the one hand or health-promoting interventions on the other, can have lasting impacts on brain health. Using large-scale epidemiological samples, we’re working to identify when these sensitive periods occur and how they shape risk across multiple different domains—spanning social-emotional skills (e.g., emotion recognition, social cognition), biological processes (e.g., epigenetic changes), and risk for depression. We’re also actively exploring the use of teeth and other tissue types as novel biomarkers of past stress exposure, the timing of those exposures, and future mental health risk. Teeth in particular represent a promising new tool for identifying sensitive periods because they preserve a kind of “fossil record” of their growth and disruptions to that growth, like rings in a tree marking its age. After determining when these sensitive periods occur, our ultimate goal is to design interventions that not only promote brain health across the lifespan, but are also uniquely timed to minimize the consequences of stress exposure and prevent depression years before it onsets.