Aarhus University Seal

Sensitive period-regulating genetic pathways and exposure to adversity shape risk for depression

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Yiwen Zhu, Center for Genomic Medicine
  • ,
  • Min-Jung Wang, Center for Genomic Medicine
  • ,
  • Katherine M Crawford, Center for Genomic Medicine
  • ,
  • Juan Carlos Ramírez-Tapia, Center for Genomic Medicine
  • ,
  • Alexandre A Lussier, Center for Genomic Medicine
  • ,
  • Kathryn A Davis, Center for Genomic Medicine
  • ,
  • Christiaan de Leeuw, Vrije Universiteit Amsterdam
  • ,
  • Anne E Takesian, Harvard University
  • ,
  • Takao K Hensch, Harvard University
  • ,
  • Jordan W Smoller, Center for Genomic Medicine
  • ,
  • Erin C Dunn, Center for Genomic Medicine
  • ,
  • Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium

Animal and human studies have documented the existence of developmental windows (or sensitive periods) when experience can have lasting effects on brain structure or function, behavior, and disease. Although sensitive periods for depression likely arise through a complex interplay of genes and experience, this possibility has not yet been explored in humans. We examined the effect of genetic pathways regulating sensitive periods, alone and in interaction with common childhood adversities, on depression risk. Guided by a translational approach, we: (1) performed association analyses of three gene sets (60 genes) shown in animal studies to regulate sensitive periods using summary data from a genome-wide association study of depression (n = 807,553); (2) evaluated the developmental expression patterns of these genes using data from BrainSpan (n = 31), a transcriptional atlas of postmortem brain samples; and (3) tested gene-by-development interplay (dGxE) by analyzing the combined effect of common variants in sensitive period genes and time-varying exposure to two types of childhood adversity within a population-based birth cohort (n = 6254). The gene set regulating sensitive period opening associated with increased depression risk. Notably, 6 of the 15 genes in this set showed developmentally regulated gene-level expression. We also identified a statistical interaction between caregiver physical or emotional abuse during ages 1-5 years and genetic risk for depression conferred by the opening genes. Genes involved in regulating sensitive periods are differentially expressed across the life course and may be implicated in depression vulnerability. Our findings about gene-by-development interplay motivate further research in large, more diverse samples to further unravel the complexity of depression etiology through a sensitive period lens.

Original languageEnglish
JournalNeuropsychopharmacology
Volume47
Issue2
Pages (from-to)497-506
Number of pages10
ISSN0893-133X
DOIs
Publication statusPublished - Jan 2022

    Research areas

  • BRAIN, CHILDHOOD ADVERSITY, ENVIRONMENT INTERACTION, EXPERIENCE-DEPENDENT PLASTICITY, GENOME-WIDE ASSOCIATION, IDENTIFIES 30, MENTAL-DISORDERS, OXIDATIVE STRESS, SYMPTOMS, VISUAL CORTICAL PLASTICITY

See relations at Aarhus University Citationformats

ID: 227832328