By Yiwen Zhu and Erin C. Dunn

Developmental scientists have long been interested in the idea that timing – or when things happen in development – matters for our short- and long-term health. As a result, many developmental scientists have been on the hunt to identify sensitive periods in development, or age windows when our life experiences can have more lasting effects. However, two key questions remain: (1) how exactly do sensitive periods arise for a specific disorder, like depression? And (2) how might genetic risks and exposure to early life stress interact to affect people’s susceptibility of depression?

In the current study, focused on people’s risk for depression, we examined in humans the effect of genes previously shown to influence the timing of sensitive periods in animals. We also investigated the interplay between these genetic factors and exposure to commonly occurring childhood adversities on depression risk. Specifically, we tested three hypotheses (see schematic): (1) Genes regulating sensitive periods would associate with depression risk; (2) Expression of these genes would vary over the course of development; (3) Children with greater genetic risk who were exposed to childhood adversity during a sensitive period in development would have the greatest risk for depression.

Our results found support for all three hypotheses. Genes implicated in altering the timing of sensitive period onset were linked to increased depression risk in the population. Six out of the 15 genes in one specific pathway were developmentally regulated (meaning varied in their expression by age) specifically within a region of the brain called the medial prefrontal cortex.

Variation in the genetic regulation of sensitive period onsets exerted little or no influence on depression risk among children living in typical environments. However, for children exposed to physical or emotional abuse by their caregivers, genetic risk for dysregulated sensitive period timing was associated with heightened levels of depressive symptoms.

Systematic approach to examining the role of sensitive period-regulating genes, alone and in interaction with exposure to adversity, on risk for depression.

Overall, these findings motivate future studies to examine the trajectories of genes involved in sensitive period regulation and the interplay between these genetic factors and experience over the course of development in larger, more diverse samples. With these inquiries, the complexity of what causes depression can be unraveled and novel targets for prevention or intervention can be identified.

Yiwen Zhu is currently a doctoral student in the Department of Epidemiology at the Harvard T.H. Chan School of Public Health. The work featured here was completed when she was a data analyst in Dr. Erin Dunn’s research group at the Massachusetts General Hospital (http://www.thedunnlab.com). 

Learn more in the original research article:
Sensitive period-regulating genetic pathways and exposure to adversity shape risk for depression.
Zhu Y, Wang MJ, Crawford KM, Ramírez-Tapia JC, Lussier AA, Davis KA, de Leeuw C, Takesian AE; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Hensch TK, Smoller JW, Dunn EC. Neuropsychopharmacology. 2022 Jan;47(2):497-506. doi: 10.1038/s41386-021-01172-6. Epub 2021 Oct 23