Influence of child abuse on adult depression: Moderation by the corticotropin-releasing hormone receptor gene

Rebekah G. Bradley, Elisabeth B. Binder, Michael P. Epstein, Yilang Tang, Hemu P. Nair, Wei Liu, Charles F. Gillespie, Tiina Berg, Mark Evces, D. Jeffrey Newport, Zachary N. Stowe, Christine Marcelle Heim, Charles B. Nemeroff, Ann Schwartz, Joseph F. Cubells, Kerry J. Ressler

Research output: Contribution to journalArticle

449 Citations (Scopus)

Abstract

Context: Genetic inheritance and developmental life stress both contribute to major depressive disorder in adults. Child abuse and trauma alter the endogenous stress response, principally corticotropin-releasing hormone and its downstream effectors, suggesting that a gene x environment interaction at this locus may be important in depression. Objective: To examine whether the effects of child abuse on adult depressive symptoms are moderated by genetic polymorphisms within the corticotropin-releasing hormone type 1 receptor (CRHR1) gene. Design: Association study examining gene x environment interactions between genetic polymorphisms at the CRHR1 locus and measures of child abuse on adult depressive symptoms. Setting: General medical clinics of a large, public, urban hospital and Emory University, Atlanta, Georgia. Participants: The primary participant population was 97.4% African American, of low socioeconomic status, and with high rates of lifetime trauma (n = 422). A supportive independent sample (n = 199) was distinct both ethnically (87.7% Caucasian) and socioeconomically (less impoverished). Main Outcome Measures: Beck Depression Inventory scores and history of major depressive disorder by the Structured Clinical Interview for DSM-IV Axis I Disorders. Results: Fifteen single-nucleotide polymorphisms spanning 57 kilobases of the CRHR1 gene were examined. We found significant gene x environment interactions with multiple individual single-nucleotide polymorphisms (eg, rs110402, P = .008) as well as with a common haplotype spanning intron 1 (P < .001). Specific CRHR1 polymorphisms appeared to moderate the effect of child abuse on the risk for adult depressive symptoms. These protective effects were supported with similar findings in a second independent sample (n = 199). Conclusions: These data support the corticotropin-releasing hormone hypothesis of depression and suggest that a gene x environment interaction is important for the expression of depressive symptoms in adults with CRHR1 risk or protective alleles who have a history of child abuse.

Original languageEnglish (US)
Pages (from-to)190-200
Number of pages11
JournalArchives of General Psychiatry
Volume65
Issue number2
DOIs
StatePublished - Feb 1 2008

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Corticotropin-Releasing Hormone Receptors
Child Abuse
Gene-Environment Interaction
Depression
Genes
Corticotropin-Releasing Hormone
Major Depressive Disorder
Genetic Polymorphisms
Single Nucleotide Polymorphism
Public Hospitals
Urban Hospitals
Wounds and Injuries
Gene
Hormones
Moderation
Psychological Stress
Social Class
Diagnostic and Statistical Manual of Mental Disorders
African Americans
Introns

All Science Journal Classification (ASJC) codes

  • Arts and Humanities (miscellaneous)
  • Psychiatry and Mental health

Cite this

Bradley, R. G., Binder, E. B., Epstein, M. P., Tang, Y., Nair, H. P., Liu, W., ... Ressler, K. J. (2008). Influence of child abuse on adult depression: Moderation by the corticotropin-releasing hormone receptor gene. Archives of General Psychiatry, 65(2), 190-200. https://doi.org/10.1001/archgenpsychiatry.2007.26
Bradley, Rebekah G. ; Binder, Elisabeth B. ; Epstein, Michael P. ; Tang, Yilang ; Nair, Hemu P. ; Liu, Wei ; Gillespie, Charles F. ; Berg, Tiina ; Evces, Mark ; Newport, D. Jeffrey ; Stowe, Zachary N. ; Heim, Christine Marcelle ; Nemeroff, Charles B. ; Schwartz, Ann ; Cubells, Joseph F. ; Ressler, Kerry J. / Influence of child abuse on adult depression : Moderation by the corticotropin-releasing hormone receptor gene. In: Archives of General Psychiatry. 2008 ; Vol. 65, No. 2. pp. 190-200.
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abstract = "Context: Genetic inheritance and developmental life stress both contribute to major depressive disorder in adults. Child abuse and trauma alter the endogenous stress response, principally corticotropin-releasing hormone and its downstream effectors, suggesting that a gene x environment interaction at this locus may be important in depression. Objective: To examine whether the effects of child abuse on adult depressive symptoms are moderated by genetic polymorphisms within the corticotropin-releasing hormone type 1 receptor (CRHR1) gene. Design: Association study examining gene x environment interactions between genetic polymorphisms at the CRHR1 locus and measures of child abuse on adult depressive symptoms. Setting: General medical clinics of a large, public, urban hospital and Emory University, Atlanta, Georgia. Participants: The primary participant population was 97.4{\%} African American, of low socioeconomic status, and with high rates of lifetime trauma (n = 422). A supportive independent sample (n = 199) was distinct both ethnically (87.7{\%} Caucasian) and socioeconomically (less impoverished). Main Outcome Measures: Beck Depression Inventory scores and history of major depressive disorder by the Structured Clinical Interview for DSM-IV Axis I Disorders. Results: Fifteen single-nucleotide polymorphisms spanning 57 kilobases of the CRHR1 gene were examined. We found significant gene x environment interactions with multiple individual single-nucleotide polymorphisms (eg, rs110402, P = .008) as well as with a common haplotype spanning intron 1 (P < .001). Specific CRHR1 polymorphisms appeared to moderate the effect of child abuse on the risk for adult depressive symptoms. These protective effects were supported with similar findings in a second independent sample (n = 199). Conclusions: These data support the corticotropin-releasing hormone hypothesis of depression and suggest that a gene x environment interaction is important for the expression of depressive symptoms in adults with CRHR1 risk or protective alleles who have a history of child abuse.",
author = "Bradley, {Rebekah G.} and Binder, {Elisabeth B.} and Epstein, {Michael P.} and Yilang Tang and Nair, {Hemu P.} and Wei Liu and Gillespie, {Charles F.} and Tiina Berg and Mark Evces and Newport, {D. Jeffrey} and Stowe, {Zachary N.} and Heim, {Christine Marcelle} and Nemeroff, {Charles B.} and Ann Schwartz and Cubells, {Joseph F.} and Ressler, {Kerry J.}",
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Bradley, RG, Binder, EB, Epstein, MP, Tang, Y, Nair, HP, Liu, W, Gillespie, CF, Berg, T, Evces, M, Newport, DJ, Stowe, ZN, Heim, CM, Nemeroff, CB, Schwartz, A, Cubells, JF & Ressler, KJ 2008, 'Influence of child abuse on adult depression: Moderation by the corticotropin-releasing hormone receptor gene', Archives of General Psychiatry, vol. 65, no. 2, pp. 190-200. https://doi.org/10.1001/archgenpsychiatry.2007.26

Influence of child abuse on adult depression : Moderation by the corticotropin-releasing hormone receptor gene. / Bradley, Rebekah G.; Binder, Elisabeth B.; Epstein, Michael P.; Tang, Yilang; Nair, Hemu P.; Liu, Wei; Gillespie, Charles F.; Berg, Tiina; Evces, Mark; Newport, D. Jeffrey; Stowe, Zachary N.; Heim, Christine Marcelle; Nemeroff, Charles B.; Schwartz, Ann; Cubells, Joseph F.; Ressler, Kerry J.

In: Archives of General Psychiatry, Vol. 65, No. 2, 01.02.2008, p. 190-200.

Research output: Contribution to journalArticle

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T1 - Influence of child abuse on adult depression

T2 - Moderation by the corticotropin-releasing hormone receptor gene

AU - Bradley, Rebekah G.

AU - Binder, Elisabeth B.

AU - Epstein, Michael P.

AU - Tang, Yilang

AU - Nair, Hemu P.

AU - Liu, Wei

AU - Gillespie, Charles F.

AU - Berg, Tiina

AU - Evces, Mark

AU - Newport, D. Jeffrey

AU - Stowe, Zachary N.

AU - Heim, Christine Marcelle

AU - Nemeroff, Charles B.

AU - Schwartz, Ann

AU - Cubells, Joseph F.

AU - Ressler, Kerry J.

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N2 - Context: Genetic inheritance and developmental life stress both contribute to major depressive disorder in adults. Child abuse and trauma alter the endogenous stress response, principally corticotropin-releasing hormone and its downstream effectors, suggesting that a gene x environment interaction at this locus may be important in depression. Objective: To examine whether the effects of child abuse on adult depressive symptoms are moderated by genetic polymorphisms within the corticotropin-releasing hormone type 1 receptor (CRHR1) gene. Design: Association study examining gene x environment interactions between genetic polymorphisms at the CRHR1 locus and measures of child abuse on adult depressive symptoms. Setting: General medical clinics of a large, public, urban hospital and Emory University, Atlanta, Georgia. Participants: The primary participant population was 97.4% African American, of low socioeconomic status, and with high rates of lifetime trauma (n = 422). A supportive independent sample (n = 199) was distinct both ethnically (87.7% Caucasian) and socioeconomically (less impoverished). Main Outcome Measures: Beck Depression Inventory scores and history of major depressive disorder by the Structured Clinical Interview for DSM-IV Axis I Disorders. Results: Fifteen single-nucleotide polymorphisms spanning 57 kilobases of the CRHR1 gene were examined. We found significant gene x environment interactions with multiple individual single-nucleotide polymorphisms (eg, rs110402, P = .008) as well as with a common haplotype spanning intron 1 (P < .001). Specific CRHR1 polymorphisms appeared to moderate the effect of child abuse on the risk for adult depressive symptoms. These protective effects were supported with similar findings in a second independent sample (n = 199). Conclusions: These data support the corticotropin-releasing hormone hypothesis of depression and suggest that a gene x environment interaction is important for the expression of depressive symptoms in adults with CRHR1 risk or protective alleles who have a history of child abuse.

AB - Context: Genetic inheritance and developmental life stress both contribute to major depressive disorder in adults. Child abuse and trauma alter the endogenous stress response, principally corticotropin-releasing hormone and its downstream effectors, suggesting that a gene x environment interaction at this locus may be important in depression. Objective: To examine whether the effects of child abuse on adult depressive symptoms are moderated by genetic polymorphisms within the corticotropin-releasing hormone type 1 receptor (CRHR1) gene. Design: Association study examining gene x environment interactions between genetic polymorphisms at the CRHR1 locus and measures of child abuse on adult depressive symptoms. Setting: General medical clinics of a large, public, urban hospital and Emory University, Atlanta, Georgia. Participants: The primary participant population was 97.4% African American, of low socioeconomic status, and with high rates of lifetime trauma (n = 422). A supportive independent sample (n = 199) was distinct both ethnically (87.7% Caucasian) and socioeconomically (less impoverished). Main Outcome Measures: Beck Depression Inventory scores and history of major depressive disorder by the Structured Clinical Interview for DSM-IV Axis I Disorders. Results: Fifteen single-nucleotide polymorphisms spanning 57 kilobases of the CRHR1 gene were examined. We found significant gene x environment interactions with multiple individual single-nucleotide polymorphisms (eg, rs110402, P = .008) as well as with a common haplotype spanning intron 1 (P < .001). Specific CRHR1 polymorphisms appeared to moderate the effect of child abuse on the risk for adult depressive symptoms. These protective effects were supported with similar findings in a second independent sample (n = 199). Conclusions: These data support the corticotropin-releasing hormone hypothesis of depression and suggest that a gene x environment interaction is important for the expression of depressive symptoms in adults with CRHR1 risk or protective alleles who have a history of child abuse.

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