Hostname: page-component-5db58dd55d-h5th4 Total loading time: 0 Render date: 2026-06-11T06:07:05.542Z Has data issue: false hasContentIssue false
  • English
  • Français

The interactive effects of child maltreatment and the FK506 binding protein 5 gene (FKBP5) on dissociative symptoms in adolescence

Published online by Cambridge University Press:  20 October 2016

Fatima Tuba Yaylaci ,
Dante Cicchetti ,
Fred A. Rogosch ,
Okan Bulut  and
Susan R. Hetzel
Fatima Tuba Yaylaci*
Affiliation:
University of Minnesota Institute of Child Development
Dante Cicchetti*
Affiliation:
University of Minnesota Institute of Child Development University of Rochester Mt. Hope Family Center
Fred A. Rogosch
Affiliation:
University of Rochester Mt. Hope Family Center
Okan Bulut
Affiliation:
University of Alberta Centre for Research in Applied Measurement and Evaluation
Susan R. Hetzel
Affiliation:
University of Minnesota
*
Address correspondence and reprint requests to: Fatima Tuba Yaylaci, Institute of Child Development, 51 East River Road, Minneapolis, MN 55455; E-mail: yayla003@umn.edu; or Dante Cicchetti, Institute of Child Development, 51 East River Road, Minneapolis, MN 55455; E-mail: cicchett@umn.edu.
Address correspondence and reprint requests to: Fatima Tuba Yaylaci, Institute of Child Development, 51 East River Road, Minneapolis, MN 55455; E-mail: yayla003@umn.edu; or Dante Cicchetti, Institute of Child Development, 51 East River Road, Minneapolis, MN 55455; E-mail: cicchett@umn.edu.
Get access Rights & Permissions [Opens in a new window]

Abstract

The FK506 binding protein 5 gene (FKBP5) has been associated with susceptibility to pathogenic effects of childhood trauma including dissociative symptoms. This study examines the impact of maltreatment on dissociative tendencies in adolescence as moderated by the FKBP5 gene. Dissociative symptoms and variation within FKBP5 were assessed in a high-risk, low socioeconomic status community sample of 279 maltreated and 171 nonmaltreated adolescents. Following the assignment of haplotypes across four single nucleotide polymorphisms (rs3800373, rs9296158, rs1360780, and rs9470080), individuals with one or more copies of the CATT haplotype (N = 230) were grouped together and compared to individuals with zero copies of this haplotype (N = 185). Analyses of covariance were conducted to test hypotheses regarding the effects of developmental timing and the chronicity of maltreatment and the CATT haplotype. We found a significant interactive effect of timing/chronicity of maltreatment and the CATT haplotype on dissociative symptoms. Among adolescents who had no copies of the CATT haplotype, dissociative symptoms were higher for chronically maltreated adolescents who had an infancy onset compared to those who were not maltreated or whose maltreatment experience was either relatively less chronic or not started in infancy. The groups did not differ significantly among subjects who carry one or more copies of the CATT haplotype.

Information

Type
Regular Articles
Information
Development and Psychopathology , Volume 29 , Issue 3 , August 2017 , pp. 1105 - 1117
Copyright
Copyright © Cambridge University Press 2016 

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

Footnotes

This research was supported by funding from the National Institute on Drug Abuse (DA12903) and the Spunk Fund, Inc.

References

American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Arlington, VA: Author.Google Scholar
Amstadter, A. B., Nugent, N. R., Yang, B. Z., Miller, A., Siburian, R., Moorjani, P., … Koenen, K. C. (2011). Corticotrophin-releasing hormone type 1 receptor gene (CRHR1) variants predict posttraumatic stress disorder onset and course in pediatric injury patients. Disease Markers, 30, 89–99.CrossRefGoogle Scholar
Armstrong, J. G., Putnam, F. W., Carlson, E. B., Libero, D. Z., & Smith, S. R. (1997). Development and validation of a measure of adolescent dissociation: The Adolescent Dissociative Experiences Scale. Journal of Nervous and Mental Disease, 185, 491–497.CrossRefGoogle ScholarPubMed
Barnett, D., Manly, J. T., & Cicchetti, D. (1993). Defining child maltreatment: The interface between policy and research. Child Abuse, Child Development, and Social Policy, 8, 7–73.Google Scholar
Becker Blease, K. A., Deater Deckard, K., Eley, T., Freyd, J. J., Stevenson, J., & Plomin, R. (2004). A genetic analysis of individual differences in dissociative behaviors in childhood and adolescence. Journal of Child Psychology and Psychiatry, 45, 522–532.CrossRefGoogle ScholarPubMed
Bevilacqua, L., Carli, V., Sarchiapone, M., George, D. K., Goldman, D., Roy, A., & Enoch, M. A. (2012). Interaction between FKBP5 and childhood trauma and risk of aggressive behavior. Archives of General Psychiatry, 69, 62.CrossRefGoogle ScholarPubMed
Binder, E. B., Bradley, R. G., Liu, W., Epstein, M. P., Deveau, T. C., Mercer, K. B., … Ressler, K. J. (2008). Association of FKBP5 polymorphisms and childhood abuse with risk of posttraumatic stress disorder symptoms in adults. Journal of the American Medical Association, 299, 1291–1305.CrossRefGoogle ScholarPubMed
Binder, E. B., Salyakina, D., Lichtner, P., Wochnik, G. M., Ising, M., Pütz, B., … Muller-Myhsok, B. (2004). Polymorphisms in FKBP5 are associated with increased recurrence of depressive episodes and rapid response to antidepressant treatment. Nature Genetics, 36, 1319–1325.CrossRefGoogle ScholarPubMed
Boscarino, J. A., Erlich, P. M., Hoffman, S. N., & Zhang, X. (2012). Higher FKBP5, COMT, CHRNA5, and CRHR1 allele burdens are associated with PTSD and interact with trauma exposure: Implications for neuropsychiatric research and treatment. Neuropsychiatric Disease and Treatment, 8, 131–139. doi:10.2147/NDT.S29508 CrossRefGoogle ScholarPubMed
Calverley, R. M., Fischer, K. W., & Ayoub, C. (1994). Complex splitting of self-representations in sexually abused adolescent girls. Development and Psychopathology, 6, 195–213.CrossRefGoogle Scholar
Carlson, E. A., Yates, T. M., & Sroufe, L. A. (2009). Dissociation and development of the self. In Dell, P. F., O'Neil, J., & Somer, E. (Eds.), Dissociation and the dissociative disorders: DSM-V and beyond (pp. 39–52). New York: Routledge.Google Scholar
Carlson, E. B., Furby, L., Armstrong, J., & Schlaes, J. (1997). A conceptual framework for the long-term psychological effects of traumatic childhood abuse. Child Maltreatment, 2, 272–295.CrossRefGoogle Scholar
Caspi, A., & Moffitt, T. E. (2006). Gene–environment interactions in psychiatry: Joining forces with neuroscience. Nature Reviews Neuroscience, 7, 583–590.CrossRefGoogle ScholarPubMed
Cicchetti, D., & Banny, A. (2014). A developmental psychopathology perspective on child maltreatment. In Handbook of developmental psychopathology (pp. 723–741). New York: Springer.CrossRefGoogle Scholar
Cicchetti, D., & Manly, J. T. (1990). A personal perspective on conducting research with maltreating families: Problems and solutions. In Brody, G. & Sigel, I. (Eds.), Methods of family research: Families at risk (Vol. 2, pp. 87–133). Hillsdale, NJ: Erlbaum.Google Scholar
Cicchetti, D., & Rogosch, F. A. (1996). Equifinality and multifinality in developmental psychopathology. Development and Psychopathology, 8, 597–600.CrossRefGoogle Scholar
Cicchetti, D., & Rogosch, F. A. (2002). A developmental psychopathology perspective on adolescence. Journal of Consulting and Clinical Psychology, 70, 6.CrossRefGoogle ScholarPubMed
Cicchetti, D., & Toth, S. L. (2009). The past achievements and future promises of developmental psychopathology: The coming of age of a discipline. Journal of Child Psychology and Psychiatry, 50, 16–25.CrossRefGoogle ScholarPubMed
Cicchetti, D., & Toth, S. L. (2015). A multilevel perspective on child maltreatment. In Lamb, M. & Garcia Coll, C. (Eds.), Handbook of child psychology and developmental science: Vol. 3. Socioemotional process (7th ed.). Hoboken, NJ: Wiley.Google Scholar
Cicchetti, D., & Valentino, K. (2006). An ecological-transactional perspective on child maltreatment: Failure of the average expectable environment and its influence on child development. Developmental Psychopathology, 3, 129–201.Google Scholar
Cole, P. M., & Putnam, F. W. (1992). Effect of incest on self and social functioning: A developmental psychopathology perspective. Journal of Consulting and Clinical Psychology, 60, 174–184.CrossRefGoogle ScholarPubMed
Collip, D., Myin-Germeys, I., Wichers, M., Jacobs, N., Derom, C., Thiery, E., … van Winkel, R. (2013). FKBP5 as a possible moderator of the psychosis-inducing effects of childhood trauma. British Journal of Psychiatry, 202, 261–268. doi:10.1192/bjp.bp.112.115972 CrossRefGoogle ScholarPubMed
Cronbach, L. J. (1951). Coefficient alpha and the internal structure of tests. Psychometrika, 16, 297–334.CrossRefGoogle Scholar
Dackis, M. N., Rogosch, F. A., Oshri, A., & Cicchetti, D. (2012). The role of limbic system irritability in linking history of childhood maltreatment and psychiatric outcomes in low-income, high-risk women: Moderation by FK506 binding protein 5 haplotype. Development and Psychopathology, 24, 1237–1252. doi:10.1017/S0954579412000673 CrossRefGoogle Scholar
Dalenberg, C. J., Brand, B. L., Gleaves, D. H., Dorahy, M. J., Loewenstein, R. J., Cardeña, E., … Spiegel, D. (2012). Evaluation of the evidence for the trauma and fantasy models of dissociation. Psychological Bulletin, 138, 550–588.CrossRefGoogle ScholarPubMed
Dell, P. F., & Eisenhower, J. W. (1990). Adolescent multiple personality disorder: A preliminary study of eleven cases. Journal of the American Academy of Child & Adolescent Psychiatry, 29, 359–366.CrossRefGoogle ScholarPubMed
DiTomasso, M. J., & Routh, D. K. (1993). Recall of abuse in childhood and three measures of dissociation. Child Abuse and Neglect, 17, 477–485.CrossRefGoogle ScholarPubMed
Ehlert, U. (2013). Enduring psychobiological effects of childhood adversity. Psychoneuroendocrinology, 38, 1850–1857. doi:10.1016/j.psyneuen.2013.06.007 CrossRefGoogle ScholarPubMed
English, D. J., Upadhyaya, M. P., Litrownik, A. J., Marshall, J. M., Runyan, D. K., Graham, J. C., & Dubowitz, H. (2005). Maltreatment's wake: The relationship of maltreatment dimensions to child outcomes. Child Abuse and Neglect, 29, 597–619.CrossRefGoogle ScholarPubMed
Ethier, L. S., Lemelin, J. P., & Lacharité, C. (2004). A longitudinal study of the effects of chronic maltreatment on children's behavioral and emotional problems. Child Abuse and Neglect, 28, 1265–1278.CrossRefGoogle Scholar
Falush, D., Stephens, M., & Pritchard, J. K. (2003). Inference of population structure using multilocus genotype data: Linked loci and correlated allele frequencies. Genetics, 164, 1567–1587.CrossRefGoogle ScholarPubMed
George, D., & Mallery, P. (2003). SPSS for Windows step by step: A simple guide and reference (4th ed.). Boston: Allyn & Bacon.Google Scholar
Geraerts, E., Merckelbach, H., Jelicic, M., Smeets, E., & van Heerden, J. (2006). Dissociative symptoms and how they relate to fantasy proneness in women reporting repressed or recovered memories. Personality and Individual Differences, 40, 1143–1151.CrossRefGoogle Scholar
Grigorenko, E. L., & Cicchetti, D. (2012). Genomic sciences for developmentalists: The current state of affairs. Development and Psychopathology, 24, 1157–1164.CrossRefGoogle ScholarPubMed
Harter, S. (2012). The construction of the self: A developmental perspective (Vol. 2). New York: Guilford Press.Google Scholar
Hornstein, N. L., & Putnam, F. W. (1992). Clinical phenomenology of child and adolescent dissociative disorders. Journal of the American Academy of Child & Adolescent Psychiatry, 31, 1077–1085.CrossRefGoogle ScholarPubMed
Hubisz, M. J., Falush, D., Stephens, M., & Pritchard, J. K. (2009). Inferring weak population structure with the assistance of sample group information. Molecular Ecology Resources, 9, 1322–1332.CrossRefGoogle Scholar
Hulette, A. C., Fisher, P. A., Kim, H. K., Ganger, W., & Landsverk, J. L. (2008). Dissociation in foster preschoolers: A replication and assessment study. Journal of Trauma and Dissociation, 9, 173–190.CrossRefGoogle ScholarPubMed
Hulette, A. C., Freyd, J. J., & Fisher, P. A. (2011). Dissociation in middle childhood among foster children with early maltreatment experiences. Child Abuse and Neglect, 35, 123–126.CrossRefGoogle ScholarPubMed
Jang, K. L., Paris, J., Zweig-Frank, H., & Livesley, W. J. (1998). Twin study of dissociative experience. Journal of Nervous and Mental Disease, 186, 345–351.CrossRefGoogle ScholarPubMed
Jonson-Reid, M., Kohl, P. L., & Drake, B. (2012). Child and adult outcomes of chronic child maltreatment. Pediatrics, 129, 839–845.CrossRefGoogle ScholarPubMed
Keller, M. C. (2014). Gene × Environment interaction studies have not properly controlled for potential confounders: The problem and the (simple) solution. Biological Psychiatry, 75, 18–24. doi:10.1016/j.biopsych.2013.09.006 CrossRefGoogle Scholar
Klengel, T., Mehta, D., Anacker, C., Rex-Haffner, M., Pruessner, J. C., Pariante, C. M., … Binder, E. B. (2012). Allele-specific FKBP5 DNA demethylation mediates gene–childhood trauma interactions. Nature Neuroscience, 16, 33–41. doi:10.1038/nn.3275 CrossRefGoogle ScholarPubMed
Koenen, K. C., Saxe, G., Purcell, S., Smoller, J. W., Bartholomew, D., Miller, A., Hall, E., Kaplow, J., et al. (2005). Polymorphisms in FKBP5 are associated with peritraumatic dissociation in medically injured children. Molecular Psychiatry, 10, 1058–1059.CrossRefGoogle ScholarPubMed
Kraemer, H. C., Stice, E., Kazdin, A., Offord, D., & Kupfer, D. (2001). How do risk factors work together? Mediators, moderators, and independent, overlapping, and proxy risk factors. American Journal of Psychiatry, 158, 848–856.CrossRefGoogle ScholarPubMed
Lai, C. Q., Tucker, K. L., Choudhry, S., Parnell, L. D., Mattei, J., García-Bailo, B., … Ordovás, J. M. (2009). Population admixture associated with disease prevalence in the Boston Puerto Rican health study. Human Genetics, 125, 199–209.CrossRefGoogle ScholarPubMed
Lekman, M., Laje, G., Charney, D., Rush, A. J., Wilson, A. F., Sorant, A. J., … Paddock, S. (2008). The FKBP5-gene in depression and treatment response—An association study in the sequenced treatment alternatives to relieve depression (STAR* D) cohort. Biological Psychiatry, 63, 1103–1110.CrossRefGoogle ScholarPubMed
Liotti, G. (1992). Disorganized/disoriented attachment in the etiology of the dissociative disorders. Dissociation, 5, 196–204.Google Scholar
Lochner, C., Seedat, S., Hemmings, S. M., Moolman-Smook, J. C., Kidd, M., & Stein, D. J. (2007). Investigating the possible effects of trauma experiences and 5-HTT on the dissociative experiences of patients with OCD using path analysis and multiple regression. Neuropsychobiology, 56, 6–13.CrossRefGoogle ScholarPubMed
Lyons-Ruth, K., Dutra, L., Schuder, M. R., & Bianchi, I. (2006). From infant attachment disorganization to adult dissociation: Relational adaptations or traumatic experiences? Psychiatric Clinics of North America, 29, 63.CrossRefGoogle ScholarPubMed
Macfie, J., Cicchetti, D., & Toth, S. L. (2001). Dissociation in maltreated versus nonmaltreated preschool-aged children. Child Abuse and Neglect, 25, 1253–1267.CrossRefGoogle ScholarPubMed
Manly, J. T. (2005). Advances in research definitions of child maltreatment. Child Abuse and Neglect, 29, 425–439.CrossRefGoogle Scholar
Manly, J. T., Cicchetti, D., & Barnett, D. (1994). The impact of subtype, frequency, chronicity and severity of child maltreatment on social competence and behavior problems. Development and Psychopathology, 6, 121–143.CrossRefGoogle Scholar
Manly, J. T., Kim, J. E., Rogosch, F. A., & Cicchetti, D. (2001). Dimensions of child maltreatment and children's adjustment: Contributions of developmental timing and subtype. Development and Psychopathology, 13, 759–782.CrossRefGoogle ScholarPubMed
Minelli, A., Maffioletti, E., Cloninger, C. R., Magri, C., Sartori, R., Bortolomasi, M., … Gennarelli, M. (2013). Role of allelic variants of Fk506-binding protein 51 (Fkbp5) gene in the development of anxiety disorders: FKBP5 gene and affective disorders. Depression and Anxiety, 30, 1170–1176. doi:10.1002/da.22158 CrossRefGoogle Scholar
Morris, R. W., & Kaplan, N. L. (2002). On the advantage of haplotype analysis in the presence of multiple disease susceptibility alleles. Genetic Epidemiology, 23, 221–233. doi:10.1002/gepi.10200 CrossRefGoogle ScholarPubMed
Ogawa, J. R., Sroufe, L. A., Weinfield, N. S., Carlson, E. A., & Egeland, B. (1997). Development and the fragmented self: Longitudinal study of dissociative symptomatology in a nonclinical sample. Development and Psychopathology, 9, 855–879.CrossRefGoogle Scholar
Pieper, S., Out, D., Bakermans-Kranenburg, M. J., & van IJzendoorn, M. H. (2011). Behavioral and molecular genetics of dissociation: The role of the serotonin transporter gene promoter polymorphism (5-HTTLPR). Journal of Traumatic Stress, 24, 373–380.CrossRefGoogle ScholarPubMed
Putnam, F. W. (1997). Dissociation in children and adolescents: A developmental perspective. New York: Guilford Press.Google Scholar
R Development Core Team. (2015). R: A language and environment for statistical computing. Vienna: R Foundation for Statistical Computing. Retrieved from http://www.R-project.org Google Scholar
Roy, A., Gorodetsky, E., Yuan, Q., Goldman, D., & Enoch, M. A. (2010). Interaction of FKBP5, a stress-related gene, with childhood trauma increases the risk for attempting suicide. Neuropsychopharmacology, 35, 1674–1683.CrossRefGoogle ScholarPubMed
Roy, A., Hodgkinson, C. A., DeLuca, V., Goldman, D., & Enoch, M. A. (2012). Two HPA axis genes, CRHBP and FKBP5, interact with childhood trauma to increase the risk for suicidal behavior. Journal of Psychiatric Research, 46, 72–79.CrossRefGoogle ScholarPubMed
Sanders, B., & Giolas, M. H. (1991). Dissociation and childhood trauma in psychologically disturbed adolescents. American Journal of Psychiatry, 148, 50–54.Google ScholarPubMed
Sinnwell, J. P., & Schaid, D. J. (2012). haplo.stats: Statistical analysis of haplotypes with traits and covariates when linkage phase is ambiguous. R package version 1.5.5 [Computer software]. Retrieved from http://CRAN.R-project.org/package=haplo.stats Google Scholar
Spitzer, C., Klauer, T., Grabe, H. J., Lucht, M., Stieglitz, R. D., Schneider, W., & Freyberger, H. J. (2003). Gender differences in dissociation. Psychopathology, 36, 65–70.CrossRefGoogle ScholarPubMed
Sroufe, L. A. (1989). An organizational perspective on the self. In Cicchetti, D. & Beeghly, M. (Eds.), The self in transition: Infancy to childhood (pp. 281–307). Chicago: University of Chicago Press.Google Scholar
Sroufe, L. A. (1997). Psychopathology as an outcome of development. Development and Psychopathology, 9, 251–268.CrossRefGoogle ScholarPubMed
Szyf, M. (2012). How do environments talk to genes? Nature Neuroscience, 16, 2–4.CrossRefGoogle Scholar
Toth, S. L., & Cicchetti, D. (1998). Remembering, forgetting, and the effects of trauma on memory: A developmental psychopathology perspective. Development and Psychopathology, 10, 589–605.CrossRefGoogle ScholarPubMed
Valentino, K., Cicchetti, D., Rogosch, F. A., & Toth, S. L. (2008). True and false recall and dissociation among maltreated children: The role of self-schema. Development and Psychopathology, 20, 213.CrossRefGoogle ScholarPubMed
Waller, N. G., & Ross, C. A. (1997). The prevalence and biometric structure of pathological dissociation in the general population: Taxometric and behavior genetic findings. Journal of Abnormal Psychology, 106, 499–510.CrossRefGoogle ScholarPubMed
Xie, P., Kranzler, H. R., Poling, J., Stein, M. B., Anton, R. F., Farrer, L. A., & Gelernter, J. (2010). Interaction of FKBP5 with childhood adversity on risk for post-traumatic stress disorder. Neuropsychopharmacology, 35, 1684–1692.CrossRefGoogle ScholarPubMed
Yaeger, R., Avila-Bront, A., Abdul, K., Nolan, P. C., Grann, V. R., Birchette, M. G., … Joe, A. K. (2008). Comparing genetic ancestry and self-described race in African Americans born in the United States and in Africa. Cancer Epidemiology Biomarkers and Prevention, 17, 1329–1338.CrossRefGoogle ScholarPubMed
Yates, T. M., Carlson, E. A., & Egeland, B. (2008). A prospective study of child maltreatment and self-injurious behavior in a community sample. Development and Psychopathology, 20, 651.CrossRefGoogle Scholar
Zannas, A. S., & Binder, E. B. (2013). Gene-environment interactions at the FKBP5 locus: Sensitive periods, mechanisms and pleiotropism: FKBP5 and gene-environment interactions. Genes, Brain and Behavior, 13, 25–37.CrossRefGoogle Scholar
Zimmermann, P., Brückl, T., Nocon, A., Pfister, H., Binder, E. B., Uhr, M., … Ising, M. (2011). Interaction of FKBP5 gene variants and adverse life events in predicting depression onset: Results from a 10-year prospective community study. American Journal of Psychiatry, 168, 1107–1116.CrossRefGoogle ScholarPubMed