Genetic moderation of child maltreatment effects on depression and internalizing symptoms by serotonin transporter linked polymorphic region (5-HTTLPR), brain-derived neurotrophic factor (BDNF), norepinephrine transporter (NET), and corticotropin releasing hormone receptor 1 (CRHR1) genes in African American children
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Genetic moderation of the effects of child maltreatment on depression and internalizing symptoms was investigated in a sample of low-income maltreated and nonmaltreated African American children (N= 1,096). Lifetime child maltreatment experiences were independently coded from Child Protective Services records and maternal report. Child depression and internalizing problems were assessed in the context of a summer research camp by self-report on the Children's Depression Inventory and adult counselor report on the Teacher Report Form. DNA was obtained from buccal cell or saliva samples and genotyped for polymorphisms of the following genes: serotonin transporter linked polymorphic region (5-HTTLPR), brain-derived neurotrophic factor (BDNF), norepinephrine transporter, and corticotropin releasing hormone receptor 1. Analyses of covariance with age and gender as covariates were conducted, with maltreatment status and respective polymorphism as main effects and their Gene × Environment (G × E) interactions. Maltreatment consistently was associated with higher Children's Depression Inventory and Teacher Report Form symptoms. The results for child self-report symptoms indicated a G × E interaction for BDNF and maltreatment. In addition,BDNF and triallelic 5-HTTLPR interacted with child maltreatment in a G × G × E interaction. Analyses for counselor report of child anxiety/depression symptoms on the Teacher Report Form indicated moderation of child maltreatment effects by triallelic 5-HTTLPR. These effects were elaborated based on variation in developmental timing of maltreatment experiences. Norepinephrine transporter was found to further moderate the G × E interaction of 5-HTTLPR and maltreatment status, revealing a G × G × E interaction. This G × G × E was extended by consideration of variation in maltreatment subtype experiences. Finally, G × G × E effects were observed for the co-action of BDNF and the corticotropin releasing hormone receptor 1 haplotype. The findings illustrate the variable influence of specific genotypes in G × E interactions based on variation in maltreatment experiences and the importance of a multigenic approach for understanding influences on depression and internalizing symptoms among African American children.
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BDNF works synergistically with other genes after childhood trauma, such as the 5-HTTLPR, NET and CRHR1 genes, as well as TPH2.
“BDNF works synergistically with other genes after childhood trauma, such as the 5-HTTLPR (182), noradrenaline/norepinephrine transporter (NET) and corticotropin releasing hormone receptor 1 (CRHR1) genes (185), as well as tryptophan hydroxylase (TPH) 2 (186).”
From Epigenetic Modifications in Stress Response Genes Associated With Childhood Trauma (2019) · cites this paper as [185]
The Discussion (page not provided) reports a significant interaction between BDNF, CRHR1, and child maltreatment in predicting anxiety/depression symptoms. It reports NET interacting with 5-HTTLPR and maltreatment, not with BDNF. The separately cited TPH2 claim is outside this citation's scope. (LLM, conf=0.88)
Experimental — accuracy not yet measuredMultiple other genes act in concert with BDNF.
“Besides, as mentioned above, multiple other genes, act in concert with BDNF (185).”
From Epigenetic Modifications in Stress Response Genes Associated With Childhood Trauma (2019) · cites this paper as [185]
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Cites
Inference of Population Structure Using Multilocus Genotype Data
Pritchard, J. K., Stephens, M., & Donnelly, P. (2000) · Genetics · doi:10.1093/genetics/155.2.945 · Cited by 33,871 · see citing works
Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene
Caspi, A., Sugden, K., Moffitt, T. E., Taylor, A., Craig, I. W., Harrington, H., McClay, J., Mill, J., Martin, J., Braithwaite, A., et al. (2003) · Science · doi:10.1126/science.1083968 · Cited by 8,120 · see citing works
Falush, D., Stephens, M., & Pritchard, J. K. (2003) · Genetics · doi:10.1093/genetics/164.4.1567 · Cited by 7,920 · see citing works
Lesch, K.-P., Bengel, D., Heils, A., Sabol, S. Z., Greenberg, B. D., Petri, S., Benjamin, J., Müller, C. R., Hamer, D. H., & Murphy, D. L. (1996) · Science · doi:10.1126/science.274.5292.1527 · Cited by 5,162 · see citing works
Inferring weak population structure with the assistance of sample group information
HUBISZ, M. J., FALUSH, D., STEPHENS, M., & PRITCHARD, J. K. (2009) · Molecular Ecology Resources · doi:10.1111/j.1755-0998.2009.02591.x · Cited by 3,475 · see citing works
Inference of population structure using multilocus genotype data: dominant markers and null alleles
Falush, D., Stephens, M., & Pritchard, J. K. (2007) · Molecular Ecology Notes · doi:10.1111/j.1471-8286.2007.01758.x · Cited by 3,468 · see citing works
Beyond diathesis stress: differential susceptibility to environmental influences
Belsky, J., & Pluess, M. (2009) · Psychological Bulletin · doi:10.1037/a0017376 · Cited by 3,039 · see citing works
Manual for the Teacher's Report Form and 1991 Profile
Achenbach, T. M. (1991) · Medical Entomology and Zoology · Cited by 2,024 · see citing works
Equifinality and multifinality in developmental psychopathology
Cicchetti, D., & Rogosch, F. A. (1996) · Development and Psychopathology · doi:10.1017/s0954579400007318 · Cited by 1,842 · cited 1× · see citing works
“Consistent with the developmental psychopathology principle of multifinality (Cicchetti & Rogosch, 1996), all maltreated children do not develop depression and internalizing problems.”
BackgroundSelf-citationMasten, A. S., & Cicchetti, D. (2010) · Development and Psychopathology · doi:10.1017/s0954579410000222 · Cited by 1,800 · see citing works
Self-citationThe link between childhood trauma and depression: insights from HPA axis studies in humans
Heim, C., Newport, D. J., Mletzko, T., Miller, A. H., & Nemeroff, C. B. (2008) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2008.03.008 · Cited by 1,704 · see citing works
Differential susceptibility to the environment: an evolutionary--neurodevelopmental theory
Ellis, B. J., Boyce, W. T., Belsky, J., Bakermans-Kranenburg, M. J., & van Ijzendoorn, M. H. (2011) · Development and Psychopathology · doi:10.1017/s0954579410000611 · Cited by 1,564 · see citing works
Caspi, A., Hariri, A. R., Holmes, A., Uher, R., & Moffitt, T. E. (2010) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2010.09101452 · Cited by 1,346 · see citing works
Epigenetics and the biological definition of gene×environment interactions
Meaney, M. J. (2010) · Child Development · doi:10.1111/j.1467-8624.2009.01381.x · Cited by 1,239 · see citing works
Spatz Widom, C., DuMont, K., & Czaja, S. J. (2007) · Archives of General Psychiatry · doi:10.1001/archpsyc.64.1.49 · Cited by 1,059 · see citing works
Duncan, L. E., & Keller, M. C. (2011) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2011.11020191 · Cited by 1,032 · see citing works
A Developmental Psychopathology Perspective on Child Abuse and Neglect
Cicchetti, D., & Toth, S. L. (1995) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/00004583-199505000-00008 · Cited by 1,022 · see citing works
Self-citationFourth National Incidence Study of Child Abuse and Neglect (NIS-4): Report to Congress
Sedlak, A. J. (2010) · PsycEXTRA Dataset · Cited by 963 · see citing works
Social supports and serotonin transporter gene moderate depression in maltreated children
Kaufman, J., Yang, B., Douglas-Palumberi, H., Houshyar, S., Lipschitz, D. S., Krystal, J. H., & Gelernter, J. E. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0404376101 · Cited by 801 · see citing works
MANLY, J. T., KIM, J. E., ROGOSCH, F. A., & CICCHETTI, D. (2001) · Development and Psychopathology · doi:10.1017/s0954579401004023 · Cited by 789 · see citing works
Self-citationLevine, M. P., & Smolak, L. (2006) · Psychology Press eBooks · doi:10.4324/9781410613189-11 · Cited by 695 · see citing works
Kaufman, J., Yang, B.-Z., Douglas-Palumberi, H., Grasso, D., Lipschitz, D., Houshyar, S., Krystal, J. H., & Gelernter, J. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.10.026 · Cited by 692 · see citing works
Bradley, R. G., Binder, E. B., Epstein, M. P., Tang, Y., Nair, H. P., Liu, W., Gillespie, C. F., Berg, T., Evces, M., Newport, D. J., et al. (2008) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2007.26 · Cited by 643 · see citing works
Keller, M. C. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.09.006 · Cited by 627 · see citing works
Cicchetti, D., & Toth, S. L. (2008) · Journal of Child Psychology and Psychiatry · doi:10.1111/j.1469-7610.2008.01979.x · Cited by 617 · see citing works
Self-citationDevelopmental Cascades [Special Issue, Part 1]
Masten, A. S., & CICCHETTI, D. V. (2010) · Development and Psychopathology · Cited by 572 · see citing works
Self-citationSedlak, A. J., Mettenburg, J., Basena, M., Petta, I., McPherson, K. S., Greene, A., & Li, S. (2010) · PsycEXTRA Dataset · doi:10.1037/e565022012-001 · Cited by 510 · see citing works
Hu, X., Oroszi, G., Chun, J., Smith, T. L., Goldman, D. A., & Schuckit, M. A. (2005) · Alcoholism Clinical and Experimental Research · doi:10.1097/01.alc.0000150008.68473.62 · Cited by 478 · see citing works
Manly, J. T., Cicchetti, D., & Barnett, D. (1994) · Development and Psychopathology · doi:10.1017/s0954579400005915 · Cited by 470 · see citing works
Self-citationPeer Relationships and Self-Esteem among Children Who Have Been Maltreated
Bolger, K. E., Patterson, C. J., & Kupersmidt, J. B. (1998) · Child Development · doi:10.1111/j.1467-8624.1998.tb06166.x · Cited by 450 · see citing works
Gelernter, J. E., Kranzler, H. R., & Cubells, J. F. (1997) · Human Genetics · doi:10.1007/s004390050624 · Cited by 435 · see citing works
Moffitt, T. E., Caspi, A., & Rutter, M. (2006) · Perspectives on Psychological Science · doi:10.1111/j.1745-6916.2006.00002.x · Cited by 389 · see citing works
Cicchetti, D., Rogosch, F. A., Gunnar, M. R., & Toth, S. L. (2010) · Child Development · doi:10.1111/j.1467-8624.2009.01393.x · Cited by 337 · see citing works
Self-citationMaltreatment's wake: The relationship of maltreatment dimensions to child outcomes
English, D. J., Upadhyaya, M. P., Litrownik, A. J., Marshall, J. M., Runyan, D. K., Graham, J. C., & Dubowitz, H. (2005) · Child Abuse & Neglect · doi:10.1016/j.chiabu.2004.12.008 · Cited by 325 · see citing works
Polanczyk, G., Caspi, A., Williams, B., Price, T. S., Danese, A., Sugden, K., Uher, R., Poulton, R., & Moffitt, T. E. (2009) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2009.114 · Cited by 285 · see citing works
Advances in research definitions of child maltreatment
Manly, J. T. (2005) · Child Abuse & Neglect · doi:10.1016/j.chiabu.2005.04.001 · Cited by 272 · see citing works
Aguilera, M., Arias, B., Wichers, M., Barrantes-Vidal, N., Moya, J., Villa, H., van Os, J., Ibáñez, M. I., Ruipérez, M. A., Ortet, G., et al. (2009) · Psychological Medicine · doi:10.1017/s0033291709005248 · Cited by 265 · see citing works
DNA methylation: A mechanism for embedding early life experiences in the genome
Szyf, M., & Bick, J. (2013) · Child Development · doi:10.1111/j.1467-8624.2012.01793.x · Cited by 251 · see citing works
Editorial: Multiple levels of analysis
Cicchetti, D., & Dawson, G. (2002) · Development and Psychopathology · doi:10.1017/s0954579402003012 · Cited by 251 · see citing works
Self-citationAdverse Childhood Experiences and Suicidal Behavior
Brodsky, B. S., & Stanley, B. (2008) · Psychiatric Clinics of North America · doi:10.1016/j.psc.2008.02.002 · Cited by 238 · see citing works
Child maltreatment and vulnerability to depression
Toth, S. L., Manly, J. T., & Cicchetti, D. (1992) · Development and Psychopathology · doi:10.1017/s0954579400005587 · Cited by 236 · see citing works
Self-citationBolger, K. E., & Patterson, C. J. (2001) · Development and Psychopathology · doi:10.1017/s0954579401004096 · Cited by 234 · see citing works
Bradley, B., Westen, D., Mercer, K. B., Binder, E. B., Jovanovic, T., Crain, D., Wingo, A., & Heim, C. (2011) · Development and Psychopathology · doi:10.1017/s0954579411000162 · Cited by 213 · see citing works
Cicchetti, D., Rogosch, F. A., & Sturge-Apple, M. L. (2007) · Development and Psychopathology · doi:10.1017/s0954579407000600 · Cited by 204 · see citing works
Self-citationYaeger, R., Avila-Bront, A., Abdul, K., Nolan, P. C., Grann, V., Birchette, M. G., Choudhry, S., Burchard, E., Beckman, K., Gorroochurn, P., et al. (2008) · Cancer Epidemiology, Biomarkers and Prevention · doi:10.1158/1055-9965.epi-07-2505 · Cited by 144 · see citing works
Ressler, K. J., Bradley, B., Mercer, K. B., Deveau, T. C., Smith, A. K., Gillespie, C. F., Nemeroff, C. B., Cubells, J. F., & Binder, E. B. (2010) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.31052 · Cited by 140 · see citing works
Uher, R., Mors, O., Rietschel, M., Rajewska-Rager, A., Petrovic, A., Zobel, A., Henigsberg, N., Mendlewicz, J., Aitchison, K., Farmer, A., et al. (2011) · Journal of Clinical Psychiatry · doi:10.4088/jcp.10m06419 · Cited by 139 · see citing works
Duncan, L. E., Pollastri, A. R., & Smoller, J. W. (2014) · American Psychologist · doi:10.1037/a0036320 · Cited by 137 · see citing works
Brody, G. H., Yu, T., Chen, Y., Kogan, S. M., Evans, G. W., Beach, S. R. H., Windle, M. T., Simons, R. L., Gerrard, M., Gibbons, F. X., et al. (2012) · Developmental Psychology · doi:10.1037/a0028847 · Cited by 133 · see citing works
English, D., Lambert, S. F., & Ialongo, N. S. (2014) · Developmental Psychology · doi:10.1037/a0034703 · Cited by 126 · see citing works
CRHR1 genotypes, neural circuits and the diathesis for anxiety and depression
Rogers, J., Raveendran, M., Fawcett, G. L., Fox, A. S., Shelton, S. E., Oler, J. A., Cheverud, J. M., Muzny, D. M., Gibbs, R. A., Davidson, R. J., et al. (2012) · Molecular Psychiatry · doi:10.1038/mp.2012.152 · Cited by 114 · see citing works
Population admixture associated with disease prevalence in the Boston Puerto Rican health study
Lai, C., Tucker, K. L., Choudhry, S., Parnell, L. D., Mattei, J., García‐Bailo, B., Beckman, K. B., Burchard, E. G., & Ordovás, J. M. (2008) · Human Genetics · doi:10.1007/s00439-008-0612-7 · Cited by 112 · see citing works
DeYoung, C. G., Cicchetti, D., & Rogosch, F. A. (2011) · Journal of Child Psychology and Psychiatry · doi:10.1111/j.1469-7610.2011.02404.x · Cited by 84 · cited 2× · see citing works
“DeYoung et al. (2011) found that the CRHR1 TAT haplotype significantly moderated the association of child maltreatment with neuroticism.”
BackgroundSelf-citationCicchetti, D., Rogosch, F. A., Sturge‐Apple, M. L., & Toth, S. L. (2009) · Journal of Pediatric Psychology · doi:10.1093/jpepsy/jsp078 · Cited by 74 · see citing works
Self-citationPredictors for emotionally distressed adolescents to receive mental health care
Kodjo, C. M., & Auinger, P. (2004) · Journal of Adolescent Health · doi:10.1016/j.jadohealth.2003.12.005 · Cited by 72 · see citing works
Harsh parenting and adolescent health: A longitudinal analysis with genetic moderation.
Brody, G. H., Yu, T., Beach, S. R. H., Kogan, S. M., Windle, M. T., & Philibert, R. A. (2013) · Health Psychology · doi:10.1037/a0032686 · Cited by 67 · see citing works
Odgerel, Z., Talati, A., Hamilton, S. P., Levinson, D. F., & Weissman, M. M. (2013) · Translational Psychiatry · doi:10.1038/tp.2013.80 · Cited by 61 · see citing works
Inscoe, A. B., Cicchetti, D., Rogosch, F. A., Oshri, A., & Crick, N. R. (2013) · Development and Psychopathology · doi:10.1017/s0954579413000047 · Cited by 60 · see citing works
Self-citationGunnar, M. R., Wenner, J. A., Thomas, K. M., Glatt, C. E., McKenna, M. C., & Clark, A. G. (2012) · Development and Psychopathology · doi:10.1017/s095457941200065x · Cited by 53 · see citing works
Bringing a developmental perspective to anxiety genetics
McGrath, L. M., Weill, S. R., Robinson, E., Macrae, R., & Smoller, J. W. (2012) · Development and Psychopathology · doi:10.1017/s0954579412000636 · Cited by 52 · see citing works
Predictors for emotionally distressed adolescents to receive mental health care
Kodjo, C. M., & Auinger, P. (2004) · Journal of Adolescent Health · doi:10.1016/s1054-139x(04)00061-8 · Cited by 47 · see citing works
Prevalence of mental health disorders among low-income African American adolescents
Byck, G. R., Bolland, J. M., Dick, D. M., Ashbeck, A., & Mustanski, B. S. (2013) · Social Psychiatry and Psychiatric Epidemiology · doi:10.1007/s00127-013-0657-3 · Cited by 46 · see citing works
Neural plasticity, sensitive periods, and psychopathology
Cicchetti, D. (2015) · Development and Psychopathology · doi:10.1017/s0954579415000012 · Cited by 41 · see citing works
Self-citationCarson, N. J., Cook, B., & Alegria, M. M. (2010) · Journal of Health Care for the Poor and Underserved · doi:10.1353/hpu.0.0297 · Cited by 37 · see citing works
Cutuli, J. J., Raby, K. L., Cicchetti, D., Englund, M. M., & Egeland, B. R. (2012) · Journal of Affective Disorders · doi:10.1016/j.jad.2012.08.011 · Cited by 27 · see citing works
Self-citationGenomic sciences for developmentalists: The current state of affairs
Grigorenko, E. L., & Cicchetti, D. (2012) · Development and Psychopathology · doi:10.1017/s0954579412000612 · Cited by 12 · see citing works
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Research works printed but not linked: 4
- Cicchetti D Lynch M Cicchetti D Cohen DJ Failures in the expectable environment and their impact on individual development: The case of child maltreatment Developmental psychopathology: Risk, disorder, and adaptation 1995 2 New York Wiley 32 71
- Cicchetti D Toth SL Lamb M Garcia Coll C A multilevel perspective on child maltreatment Handbook of child psychology and developmental science, 7th Vol. 3: Socioemotional process New York Wiley (in press).
- Cicchetti D Valentino K Cicchetti D Cohen DJ An ecological transactional perspective on child maltreatment: Failure of the average expectable environment and its influence upon child development Developmental Psychopathology 2006 3 2nd New York Wiley 129 201
- Gottesman II Shields J Schizophrenia and genetics: A twin study vantage point 1972 Oxford, England Academic Press
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Epigenetic Modifications in Stress Response Genes Associated With Childhood Trauma
Jiang, S., Postovit, L., Cattaneo, A., Binder, E. B., & Aitchison, K. J. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.00808 · Cited by 288 · see citing works
Tiwari, A., & Gonzalez, A. (2018) · Clinical Psychology Review · doi:10.1016/j.cpr.2018.01.006 · Cited by 71 · see citing works
- Authors
- Cicchetti, D., & Rogosch, F. A.
- Affiliations
- University of Minnesota (US)
- University of Rochester (US)
- Corresponding author
- Cicchetti, Dante
- Venue
- Development and Psychopathology
- Publisher
- Cambridge University Press (CUP)
- Published
- 2014-11
- Volume
- 26
- Issue
- 4pt2
- Pages
- 1219-1239
- ISSN
- 0954-5794 (ISSN-L)
- 1469-2198
- PMC
- PMC4244663
- OpenAlex
- W2002183332
- Cited by
- 29
- References
- 66
- Citations by year
- 2024: 2 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 3 · 2019: 4 · 2018: 4 · 2017: 1 · 2016: 6 · 2015: 4
- FWCI
- 4.34
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Development and Psychopathology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5r01mh083979-04)
- National Institute of Mental Health (R01‐MH083979)
- National Institute on Drug Abuse (R01DA017741)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
- Social Sciences › Psychology › Clinical Psychology › Child and Adolescent Psychosocial and Emotional Development
- Social Sciences › Safety Research › Child Welfare and Adoption
- Keywords
- child abuse, depression, internalizing problems, gene-environment interaction, 5-HTTLPR, brain-derived neurotrophic factor, norepinephrine transporter, CRHR1, African American children, low-income children, maltreatment subtypes
- MeSH terms
- CRF Receptor, Type 1, Anxiety, Black or African American, Child, Child Abuse, Depression, Female, Humans, Male, Poverty, Receptors, Corticotropin-Releasing Hormone, Brain-Derived Neurotrophic Factor, Norepinephrine Plasma Membrane Transport Proteins, Serotonin Plasma Membrane Transport Proteins, Gene-Environment Interaction
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