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

Yiwen Zhu; Min-Jung Wang; Katherine M Crawford; Juan Carlos Ramírez-Tapia; Alexandre A Lussier; Kathryn A Davis; Christiaan de Leeuw; Anne E Takesian; Takao K Hensch; Jordan W Smoller; Erin C Dunn; Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium

doi:10.1038/s41386-021-01172-6

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

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

Institut for Biomedicin - Forskning og uddannelse, Skou-bygningen

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

10 Citationer (Scopus)

Abstract

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.

Originalsprog	Engelsk
Tidsskrift	Neuropsychopharmacology
Vol/bind	47
Nummer	2
Sider (fra-til)	497-506
Antal sider	10
ISSN	0893-133X
DOI	https://doi.org/10.1038/s41386-021-01172-6
Status	Udgivet - jan. 2022

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10.1038/s41386-021-01172-6

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8674315/pdf/41386_2021_Article_1172.pdf

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Citationsformater

Zhu, Y., Wang, M.-J., Crawford, K. M., Ramírez-Tapia, J. C., Lussier, A. A., Davis, K. A., de Leeuw, C., Takesian, A. E., Hensch, T. K., Smoller, J. W., Dunn, E. C., & Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium (2022). Sensitive period-regulating genetic pathways and exposure to adversity shape risk for depression. Neuropsychopharmacology, 47(2), 497-506. https://doi.org/10.1038/s41386-021-01172-6

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title = "Sensitive period-regulating genetic pathways and exposure to adversity shape risk for depression",

abstract = "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.",

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author = "Yiwen Zhu and Min-Jung Wang and Crawford, {Katherine M} and Ram{\'i}rez-Tapia, {Juan Carlos} and Lussier, {Alexandre A} and Davis, {Kathryn A} and {de Leeuw}, Christiaan and Takesian, {Anne E} and Hensch, {Takao K} and Smoller, {Jordan W} and Dunn, {Erin C} and {Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium} and Christensen, {Jane H.}",

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doi = "10.1038/s41386-021-01172-6",

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Zhu, Y, Wang, M-J, Crawford, KM, Ramírez-Tapia, JC, Lussier, AA, Davis, KA, de Leeuw, C, Takesian, AE, Hensch, TK, Smoller, JW, Dunn, EC & Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium 2022, 'Sensitive period-regulating genetic pathways and exposure to adversity shape risk for depression', Neuropsychopharmacology, bind 47, nr. 2, s. 497-506. https://doi.org/10.1038/s41386-021-01172-6

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T1 - Sensitive period-regulating genetic pathways and exposure to adversity shape risk for depression

AU - Zhu, Yiwen

AU - Wang, Min-Jung

AU - Crawford, Katherine M

AU - Ramírez-Tapia, Juan Carlos

AU - Lussier, Alexandre A

AU - Davis, Kathryn A

AU - de Leeuw, Christiaan

AU - Takesian, Anne E

AU - Hensch, Takao K

AU - Smoller, Jordan W

AU - Dunn, Erin C

AU - Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium

AU - Christensen, Jane H.

PY - 2022/1

Y1 - 2022/1

N2 - 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.

AB - 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.

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KW - CHILDHOOD ADVERSITY

KW - ENVIRONMENT INTERACTION

KW - EXPERIENCE-DEPENDENT PLASTICITY

KW - GENOME-WIDE ASSOCIATION

KW - IDENTIFIES 30

KW - MENTAL-DISORDERS

KW - OXIDATIVE STRESS

KW - SYMPTOMS

KW - VISUAL CORTICAL PLASTICITY

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DO - 10.1038/s41386-021-01172-6

M3 - Journal article

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SN - 0893-133X

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JO - Neuropsychopharmacology

JF - Neuropsychopharmacology

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

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