Hostname: page-component-76d6cb85b7-lrvh5 Total loading time: 0 Render date: 2026-07-26T02:47:11.834Z Has data issue: false hasContentIssue false
  • English
  • Français

Early adversity and 5-HTT/BDNF genes: new evidence of gene–environment interactions on depressive symptoms in a general population

Published online by Cambridge University Press:  12 February 2009

M. Aguilera ,
B. Arias ,
M. Wichers ,
N. Barrantes-Vidal ,
J. Moya ,
H. Villa ,
J. van Os ,
M. I. Ibáñez ,
M. A. Ruipérez  and
G. Ortet
...Show all authors
M. Aguilera
Affiliation:
Unitat d'Antropologia, Departament Biologia Animal, Facultat de Biologia, Universitat de Barcelona and Institut de Biomedicina de la Universitat de Barcelona (IBUB) and CIBER de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Spain
B. Arias
Affiliation:
Unitat d'Antropologia, Departament Biologia Animal, Facultat de Biologia, Universitat de Barcelona and Institut de Biomedicina de la Universitat de Barcelona (IBUB) and CIBER de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Spain
M. Wichers
Affiliation:
Department of Psychiatry and Neuropsychology, South Limburg Mental Health Research and Teaching Network, EURON, Maastricht University, Maastricht, The Netherlands
N. Barrantes-Vidal
Affiliation:
Departament de Psicologia Clínica i de la Salut, Facultat de Psicologia, Universitat Autònoma de Barcelona and CIBER Salud Mental, Instituto de Salud Carlos III, Barcelona, Spain
J. Moya
Affiliation:
Departament de Psicologia Bàsica, Clínica i Psicobiologia, Facultat de Ciències Humanes i Socials, Universitat Jaume I, Spain
H. Villa
Affiliation:
Departament de Psicologia Bàsica, Clínica i Psicobiologia, Facultat de Ciències Humanes i Socials, Universitat Jaume I, Spain
J. van Os
Affiliation:
Department of Psychiatry and Neuropsychology, South Limburg Mental Health Research and Teaching Network, EURON, Maastricht University, Maastricht, The Netherlands
M. I. Ibáñez
Affiliation:
Departament de Psicologia Bàsica, Clínica i Psicobiologia, Facultat de Ciències Humanes i Socials, Universitat Jaume I, Spain
M. A. Ruipérez
Affiliation:
Departament de Psicologia Bàsica, Clínica i Psicobiologia, Facultat de Ciències Humanes i Socials, Universitat Jaume I, Spain
G. Ortet
Affiliation:
Departament de Psicologia Bàsica, Clínica i Psicobiologia, Facultat de Ciències Humanes i Socials, Universitat Jaume I, Spain
L. Fañanás*
Affiliation:
Unitat d'Antropologia, Departament Biologia Animal, Facultat de Biologia, Universitat de Barcelona and Institut de Biomedicina de la Universitat de Barcelona (IBUB) and CIBER de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Spain
*
*Address for correspondence: Dr L. Fañanás, Unitat d'Antropologia, Departament Biologia Animal, Facultat Biologia, Universitat de Barcelona, Av. Diagonal 645, 08028 Barcelona, Spain. (Email: lfananas@ub.edu)
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

Adverse childhood experiences have been described as one of the major environmental risk factors for depressive disorder. Similarly, the deleterious impact of early traumatic experiences on depression seems to be moderated by individual genetic variability. Serotonin transporter (5-HTT) and brain-derived neurotrophic factor (BDNF) modulate the effect of childhood adversity on adult depression, although inconsistencies across studies have been found. Moreover, the gene×environment (G×E) interaction concerning the different types of childhood adversity remains poorly understood. The aim of this study was to analyse the putative interaction between the 5-HTT gene (5-HTTLPR polymorphism), the BDNF gene (Val66Met polymorphism) and childhood adversity in accounting for adult depressive symptoms.

Method

A sample of 534 healthy individuals filled in self-report questionnaires of depressive symptomatology [the Symptom Check List 90 Revised (SCL-90-R)] and different types of childhood adversities [the Childhood Trauma Questionnaire (CTQ)]. The 5-HTTLPR polymorphism (5-HTT gene) and the Val66Met polymorphism (BDNF gene) were genotyped in the whole sample.

Results

Total childhood adversity (β=0.27, p<0.001), childhood sexual abuse (CSA; β=0.17, p<0.001), childhood emotional abuse (β=0.27, p<0.001) and childhood emotional neglect (β=0.22, p<0.001) had an impact on adult depressive symptoms. CSA had a greater impact on depressive symptoms in Met allele carriers of the BDNF gene than in the Val/Val group (F=5.87, p<0.0001), and in S carriers of the 5-HTTLPR polymorphism (5-HTT gene) (F=5.80, p<0.0001).

Conclusions

Childhood adversity per se predicted higher levels of adult depressive symptoms. In addition, BDNF Val66Met and 5-HTTLPR polymorphisms seemed to moderate the effect of CSA on adult depressive symptoms.

Keywords

BDNF Val66Metchildhood adversitydepressionG×E interaction5-HTTLPR

Information

Type
Original Articles
Information
Psychological Medicine , Volume 39 , Issue 9 , September 2009 , pp. 1425 - 1432
Copyright
Copyright © 2009 Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Article purchase

Temporarily unavailable

References

Akiskal, HS, Judd, LL, Gillin, JC, Lemmi, H (1997). Subthreshold depressions: clinical and polysomnographic validation of dysthymic, residual and masked forms. Journal of Affective Disorders 45, 53–63.Google Scholar
Anda, RF, Felitti, VJ, Bremner, JD, Walker, JD, Whitfield, C, Perry, BD, Dube, SHR, Giles, WH (2006). The enduring effects of abuse and related adverse experiences in childhood: a convergence of evidence from neurobiology and epidemiology. European Archives of Psychiatry and Clinical Neuroscience 256, 174–186.Google Scholar
Angelucci, F, Brene, S, Mathe, AA (2005). BDNF in schizophrenia, depression and corresponding animal models. Molecular Psychiatry 10, 345–352.CrossRefGoogle ScholarPubMed
Bernstein, DP, Fink, L (1998). Childhood Trauma Questionnaire: A Retrospective Self-report. The Psychological Corporation: San Antonio.Google Scholar
Bernstein, DP, Fink, L, Handelsman, L, Foote, J, Lovejoy, M, Wenzel, K, Sapareto, E, Ruggiero, J (1994). Initial reliability and validity of a new retrospective measure of child abuse and neglect. American Journal of Psychiatry 151, 1132–1136.Google ScholarPubMed
Bernstein, DP, Stein, JA, Newcomb, MD, Walker, E, Pogge, D, Ahluvalia, T, Stokes, J, Handelsman, L, Medrano, M, Desmond, D, Zule, W (2003). Development and validation of a brief screening version of the Childhood Trauma Questionnaire. Child Abuse and Neglect 27, 169–190.CrossRefGoogle ScholarPubMed
Brown, GW, Harris, TO (2008). Depression and the serotonin transporter 5-HTTLPR polymorphism: a review and a hypothesis concerning gene–environment interaction. Journal of Affective Disorders 111, 1–12.Google Scholar
Calafell, F, Bertranpetit, J (1994). Principal component analysis of gene frequencies and the origin of Basques. American Journal of Physical Anthropology 93, 201–215.Google Scholar
Caspi, A, Sugden, K, Moffitt, TE, Taylor, A, Craig, IW, Harrington, H, McClay, J, Mill, J, Martin, J, Braithwaite, A, Poulton, R (2003). Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science 301, 386–389.CrossRefGoogle ScholarPubMed
Chapman, DP, Whitfield, CL, Felitti, VJ, Dube, SR, Edwards, VJ, Anda, RF (2004). Adverse childhood experiences and the risk of depressive disorders in adulthood. Journal of Affective Disorders 82, 217–225.Google Scholar
Cotter, PA (1998). Sexual abuse is not the only childhood adversity that may lead to later depression. British Medical Journal 316, 1244.CrossRefGoogle Scholar
Derogatis, LR, Melisaratos, N (1983). The Brief Symptom Inventory: an introductory report. Psychological Medicine 13, 595–605.CrossRefGoogle ScholarPubMed
Dong, M, Anda, RF, Dube, SR, Giles, WH, Felitti, VJ (2003). The relationship of exposure to childhood sexual abuse to other forms of abuse, neglect, and household dysfunction during childhood. Child Abuse and Neglect 27, 625–639.Google Scholar
Dong, M, Anda, RF, Felitti, VJ, Dube, SR, Williamson, DF, Thompson, TJ, Loo, CM, Giles, WH (2004). The interrelatedness of multiple forms of childhood abuse, neglect, and household dysfunction. Child Abuse and Neglect 28, 771–784.CrossRefGoogle ScholarPubMed
Duman, RS (2002). Synaptic plasticity and mood disorders. Molecular Psychiatry 7 (Suppl. 1), S29–S34.CrossRefGoogle ScholarPubMed
Egan, MF, Kojima, M, Callicott, JH, Goldberg, TE, Kolachana, BS, Bertolino, A, Zaitsev, E, Gold, B, Goldman, D, Dean, M, Lu, B, Weinberger, DR (2003). The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell 112, 257–269.CrossRefGoogle ScholarPubMed
Fink, LA, Bernstein, D, Handelsman, L, Foote, J, Lovejoy, M (1995). Initial reliability and validity of the childhood trauma interview: a new multidimensional measure of childhood interpersonal trauma. American Journal of Psychiatry 152, 1329–1335.Google ScholarPubMed
Finkelhor, D (1994). The international epidemiology of child sexual abuse. Child Abuse and Neglect 18, 409–417.CrossRefGoogle ScholarPubMed
Freedman, ML, Reich, D, Penney, KL, McDonald, GJ, Mignault, AA, Patterson, N, Gabriel, SB, Topol, EJ, Smoller, JW, Pato, CN, Pato, MT, Petryshen, TL, Kolonel, LN, Lander, ES, Sklar, P, Henderson, B, Hirschhorn, JN, Altshuler, D (2004). Assessing the impact of population stratification on genetic association studies. Nature Genetics 36, 388–393.CrossRefGoogle ScholarPubMed
Gibb, BE, McGeary, JE, Beevers, CG, Miller, IW (2006). Serotonin transporter (5-HTTLPR) genotype, childhood abuse, and suicide attempts in adult psychiatric inpatients. Suicide and Life-Threatening Behavior 36, 687–693.CrossRefGoogle ScholarPubMed
Gratacos, M, Gonzalez, JR, Mercader, JM, De Cid, R, Urretavizcaya, M, Estivill, X (2007). Brain-derived neurotrophic factor Val66Met and psychiatric disorders: meta-analysis of case-control studies confirm association to substance-related disorders, eating disorders, and schizophrenia. Biological Psychiatry 61, 911–922.CrossRefGoogle ScholarPubMed
Heils, A, Mossner, R, Lesch, KP (1997). The human serotonin transporter gene polymorphism: basic research and clinical implications. Journal of Neural Transmission 104, 1005–1014.Google Scholar
Heim, C, Nemeroff, CB (2001). The role of childhood trauma in the neurobiology of mood and anxiety disorders: preclinical and clinical studies. Biological Psychiatry 49, 1023–1039.CrossRefGoogle ScholarPubMed
Heim, C, Nemeroff, CB (2002). Neurobiology of early life stress: clinical studies. Seminars in Clinical Neuropsychiatry 7, 147–159.Google Scholar
Hill, J, Davis, R, Byatt, M, Burnside, E, Rollinson, L, Fear, S (2000). Childhood sexual abuse and affective symptoms in women: a general population study. Psychological Medicine 30, 1283–1291.CrossRefGoogle ScholarPubMed
Hu, XZ, Lipsky, RH, Zhu, G, Akhtar, LA, Taubman, J, Greenberg, BD, Xu, K, Arnold, PD, Richter, MA, Kennedy, JL, Murphy, DL, Goldman, D (2006). Serotonin transporter promoter gain-of-function genotypes are linked to obsessive-compulsive disorder. American Journal of Human Genetics 78, 815–826.CrossRefGoogle ScholarPubMed
Karege, F, Perret, G, Bondolfi, G, Schwald, M, Bertschy, G, Aubry, JM (2002). Decreased serum brain-derived neurotrophic factor levels in major depressed patients. Psychiatry Research 109, 143–148.CrossRefGoogle ScholarPubMed
Kaufman, J, Yang, BZ, Douglas-Palumberi, H, Grasso, D, Lipschitz, D, Houshyar, S, Krystal, JH, Gelernter, J (2006). Brain-derived neurotrophic factor-5–HTTLPR gene interactions and environmental modifiers of depression in children. Biological Psychiatry 59, 673–680.CrossRefGoogle ScholarPubMed
Kendler, KS, Kessler, RC, Neale, MC, Heath, AC, Eaves, LJ (1993). The prediction of major depression in women: toward an integrated etiologic model. American Journal of Psychiatry 150, 1139–1148.Google ScholarPubMed
Kendler, KS, Kuhn, JW, Prescott, CA (2004). Childhood sexual abuse, stressful life events and risk for major depression in women. Psychological Medicine 34, 1475–1482.CrossRefGoogle ScholarPubMed
Kendler, KS, Kuhn, JW, Vittum, J, Prescott, CA, Riley, B (2005). The interaction of stressful life events and a serotonin transporter polymorphism in the prediction of episodes of major depression: a replication. Archives of General Psychiatry 62, 529–535.Google Scholar
Kessler, RC, Magee, WJ (1993). Childhood adversities and adult depression: basic patterns of association in a US national survey. Psychological Medicine 23, 679–690.CrossRefGoogle Scholar
Kim, JM, Stewart, R, Kim, SW, Yang, SJ, Shin, IS, Kim, YH, Yoon, JS (2007). Interactions between life stressors and susceptibility genes (5-HTTLPR and BDNF) on depression in Korean elders. Biological Psychiatry 62, 423–428.Google Scholar
Lenroot, RK, Giedd, JN (2006). Brain development in children and adolescents: insights from anatomical magnetic resonance imaging. Neuroscience and Biobehavioral Reviews 30, 718–729.Google Scholar
Lesch, KP, Bengel, D, Heils, A, Sabol, SZ, Greenberg, BD, Petri, S, Benjamin, J, Muller, CR, Hamer, DH, Murphy, DL (1996). Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 274, 1527–1531.Google Scholar
Levinson, DF (2006). The genetics of depression: a review. Biological Psychiatry 60, 84–92.Google Scholar
Martinowich, K, Lu, B (2008). Interaction between BDNF and serotonin: role in mood disorders. Neuropsychopharmacology 33, 73–83.CrossRefGoogle ScholarPubMed
Mattson, MP, Maudsley, S, Martin, B (2004). BDNF and 5-HT: a dynamic duo in age-related neuronal plasticity and neurodegenerative disorders. Trends in Neurosciences 27, 589–594.Google Scholar
May-Chahal, C, Cawson, P (2005). Measuring child maltreatment in the United Kingdom: a study of the prevalence of child abuse and neglect. Child Abuse and Neglect 29, 969–984.CrossRefGoogle ScholarPubMed
McCutcheon, VV, Heath, AC, Nelson, EC, Bucholz, KK, Madden, PA, Martin, NG (2008). Accumulation of trauma over time and risk for depression in a twin sample. Psychological Medicine. Published online: 4 June 2008. doi:10.1017/S0033291708003759.Google Scholar
Nemeroff, CB (2004). Neurobiological consequences of childhood trauma. Journal of Clinical Psychiatry 65 (Suppl. 1), 18–28.Google ScholarPubMed
Nestler, EJ, Barrot, M, Dileone, RJ, Eisch, AJ, Gold, SJ, Monteggia, LM (2002). Neurobiology of depression. Neuron 34, 13–25.Google Scholar
Owens, MJ, Nemeroff, CB (1998). The serotonin transporter and depression. Depression and Anxiety 8 (Suppl. 1), 5–12.3.0.CO;2-I>CrossRefGoogle ScholarPubMed
Pak, CS (2006). Types of gene–environment interplay and their statistical properties. In Beyond Nature and Nurture in Psychiatry: Genes, Environment and their Interplay (ed. MacCabe, J., O'Daly, O., Murray, M. R., McGuffin, P. and Wright, P.), pp. 11–17. Informa Healthcare: London.Google Scholar
Perroud, N, Courtet, P, Vincze, I, Jaussent, I, Jollant, F, Bellivier, F, Leboyer, M, Baud, P, Buresi, C, Malafosse, A (2008). Interaction between BDNF Val66Met and childhood trauma on adult's violent suicide attempt. Genes, Brain and Behaviour 7, 314–322.CrossRefGoogle ScholarPubMed
Roy, A, Hu, XZ, Janal, MN, Goldman, D (2007). Interaction between childhood trauma and serotonin transporter gene variation in suicide. Neuropsychopharmacology 32, 2046–2052.CrossRefGoogle ScholarPubMed
StataCorp (2005). STATA Statistical Software: Release 9.1. Stata Corporation, College Station, TX.Google Scholar
Stein, MB, Schork, NJ, Gelernter, J (2008). Gene-by-environment (serotonin transporter and childhood maltreatment) interaction for anxiety sensitivity, an intermediate phenotype for anxiety disorders. Neuropsychopharmacology 33, 312–319.CrossRefGoogle ScholarPubMed
Teicher, MH, Andersen, SL, Polcari, A, Anderson, CM, Navalta, CP (2002). Developmental neurobiology of childhood stress and trauma. Psychiatric Clinics of North America 25, 397–426, vii–viii.Google Scholar
UCLA: Academic Technology Services (2008). How can I understand a categorical by continuous interaction? (www.ats.ucla.edu/stat/stata/faq/catcon.htm). Accessed 1 June 2008.Google Scholar
Uher, R, McGuffin, P (2008). The moderation by the serotonin transporter gene of environmental adversity in the aetiology of mental illness: review and methodological analysis. Molecular Psychiatry 13, 131–146.Google Scholar
Wichers, M, Kenis, G, Jacobs, N, Mengelers, R, Derom, C, Vlietinck, R, Van Os, J (2008). The BDNF Val66Met×5-HTTLR×child adversity interaction and depressive symptoms: an attempt at replication. American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics 141, 120–123.CrossRefGoogle Scholar