Oxytocin Receptor Genetic and Epigenetic Variations: Association With Child Abuse and Adult Psychiatric Symptoms

Child Development

Volumn 87, Issue 1, 2016, Pages 122-134

  Smearman, Erica L ^a   Almli, Lynn M ^b   Conneely, Karen N ^b   Brody, Gene H ^a,c   Sales, Jessica M ^a,c   Bradley, Bekh ^b,d   Ressler, Kerry J ^a,e   Smith, Alicia K ^b  

^a EMORY UNIVERSITY   (United States)

^b EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c UNIVERSITY OF GEORGIA   (United States)

^d VETERANS AFFAIRS MEDICAL CENTER   (United States)

^e MCLEAN HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

OXTR PROTEIN, HUMAN; OXYTOCIN RECEPTOR;

ADOLESCENT; ADULT; AFRICAN AMERICAN; AGED; ANXIETY; CHILD ABUSE SURVIVOR; CPG ISLAND; DEPRESSION; DNA METHYLATION; FEMALE; GENETIC EPIGENESIS; GENETICS; GENOTYPE; HUMAN; MALE; MIDDLE AGED; PSYCHOLOGY; SINGLE NUCLEOTIDE POLYMORPHISM; YOUNG ADULT;

ADOLESCENT; ADULT; ADULT SURVIVORS OF CHILD ABUSE; AFRICAN AMERICANS; AGED; ANXIETY; CPG ISLANDS; DEPRESSION; DNA METHYLATION; EPIGENESIS, GENETIC; FEMALE; GENOTYPE; HUMANS; MALE; MIDDLE AGED; POLYMORPHISM, SINGLE NUCLEOTIDE; RECEPTORS, OXYTOCIN; YOUNG ADULT;

EID: 85000399021     PISSN: 00093920     EISSN: 14678624     Source Type: Journal    
DOI: 10.1111/cdev.12493     Document Type: Article

References (48)

1. Almli, L. M., Duncan, R., Feng, H., Ghosh, D., Binder, E., Bradley, B., ... Epstein, M. P. (2014). Correcting systematic inflation in genetic association tests that consider interaction effects: Application to a genome-wide association study of post-traumatic stress disorder. JAMA Psychiatry, 71, 1392-1399. doi:10.1001/jamapsychiatry.2014.1339
2. Barfield, R. T., Kilaru, V., Smith, A. K., & Conneely, K. N. (2012). CpGassoc: An R function for analysis of DNA methylation microarray data. Bioinformatics, 28, 1280-1281. doi:10.1093/bioinformatics/bts124
3. Bartz, J. A., Zaki, J., Bolger, N., & Ochsner, K. N. (2011). Social effects of oxytocin in humans: Context and person matter. Trends in Cognitive Sciences, 15, 301-309. doi:10.1016/j.tics.2011.05.002
4. Beck, A. T., Ward, C. H., Mendelson, M., Mock, J., & Erbaugh, J. (1961). An inventory for measuring depression. Archives of General Psychiatry, 4, 561-571.
5. Bell, J. T., Tsai, P. C., Yang, T. P., Pidsley, R., Nisbet, J., & Glass, D. (2012). Epigenome-wide scans identify differentially methylated regions for age and age-related phenotypes in a healthy ageing population. PLoS Genetics, 8, e1002629. doi:10.1371/journal.pgen.1002629
6. Belsky, J., Jonassaint, C., Pluess, M., Stanton, M., Brummett, B., & Williams, R. (2009). Vulnerability genes or plasticity genes? Molecular Psychiatry, 14, 746-754. doi:10.1038/mp.2009.44
7. Bernstein, D. P., & Fink, L. (1998). Childhood Trauma Questionnaire manual. San Antonio, TX: Psychological Corporation.
8. Bernstein, D. P., Stein, J. A., Newcomb, M. D., & Walker, E. (2003). Development and validation of a brief screening version of the Childhood Trauma Questionnaire. Child Abuse & Neglect, 27, 169-190. doi:10.1016/S0145-2134(02)00541-0
9. Binder, E. B., Bradley, R. G., Liu, W., & Epstein, M. P. (2008). Association of FKBP5 polymorphisms and childhood abuse with risk of posttraumatic stress disorder symptoms in adults. JAMA, 299, 1291-1305. doi:10.1001/jama.299.11.1291
10. Bird, A. (2002). DNA methylation patterns and epigenetic memory. Genes & Development., 16, 6-21. doi:10.1101/gad.947102
11. Bradley, R. G., Binder, E. B., & Epstein, M. P. (2008). Influence of child abuse on adult depression: Moderation by the corticotropin-releasing hormone receptor gene. Archives of General Psychiatry, 65, 190-200. doi:10.1001/archgenpsychiatry.2007.26
12. Brown, J., Cohen, P., Johnson, J. G., & Smailes, E. M. (1999). Childhood abuse and neglect: Specificity of effects on adolescent and young adult depression and suicidality. Journal of the American Academy of Child & Adolescent Psychiatry, 38, 1490-1496. doi:10.1097/00004583-199912000-00009
13. Campbell, D. B., Datta, D., Jones, S. T., Batey Lee, E., Sutcliffe, J. S., Hammock, E. A. D., & Levitt, P. (2011). Association of oxytocin receptor (OXTR) gene variants with multiple phenotype domains of autism spectrum disorder. Journal of Neurodevelopmental Disorders, 3, 101-112. doi:10.1007/s11689-010-9071-2
14. Chen, Y., Lemire, M., Choufani, S., & Butcher, D. T. (2013). Discovery of cross-reactive probes and polymorphic CpGs in the Illumina Infinium HumanMethylation450 microarray. Epigenetics, 8, 203. doi:10.4161/epi.23470
15. Costa, B., Pini, S., Gabelloni, P., Abelli, M., Lari, L., Cardini, A., ... Martini, C. (2009). Oxytocin receptor polymorphisms and adult attachment style in patients with depression. Psychoneuroendocrinology, 34, 1506-1514. doi:10.1016/j.psyneuen.2009.05.006
16. Dadds, M. R., Moul, C., Cauchi, A., Dobson-Stone, C., Hawes, D. J., Brennan, J., & Ebstein, R. E. (2014). Methylation of the oxytocin receptor gene and oxytocin blood levels in the development of psychopathy. Development and Psychopathology, 26, 33-40. doi:10.1017/S0954579413000497
17. Francis, D. D., Champagne, F. C., & Meaney, M. J. (2000). Variations in maternal behaviour are associated with differences in oxytocin receptor levels in the rat. Journal of Neuroendocrinology, 12, 1145-1148. doi:10.1046/j.1365-2826.2000.00599.x
18. Gillespie, C. F., Bradley, B., Mercer, K., Smith, A. K., Conneely, K., Gapen, M., ... Ressler, K. J. (2009). Trauma exposure and stress-related disorders in inner city primary care patients. General Hospital Psychiatry, 31, 505-514. doi:10.1016/j.genhosppsych.2009.05.003
19. Gregory, S. G., Connelly, J. J., Towers, A. J., Johnson, J., Biscocho, D., Markunas, C. A., ... Pericak-Vance, M. A. (2009). Genomic and epigenetic evidence for oxytocin receptor deficiency in autism. BMC Medicine, 7, 62. doi:10.1186/1741-7015-7-62
20. Harony-Nicolas, H., Mamrut, S., Brodsky, L., Shahar-Gold, H., Barki-Harrington, L., & Wagner, S. (2014). Brain region-specific methylation in the promoter of the murine oxytocin receptor gene is involved in its expression regulation. Psychoneuroendocrinology, 39, 121-131. doi:10.1016/j.psyneuen.2013.10.004
21. Heim, C., Young, L. J., Newport, D. J., & Mletzko, T. (2008). Lower CSF oxytocin concentrations in women with a history of childhood abuse. Molecular Psychiatry, 14, 954-958. doi:10.1038/mp.2008.112
22. Houseman, E. A., Accomando, W. P., Koestler, D. C., Christensen, B. C., Marsit, C. J., Nelson, H. H., ... Kelsey, K. T. (2012). DNA methylation arrays as surrogate measures of cell mixture distribution: Supplementary material. BMC Bioinformatics, 13, 86. doi:10.1186/1471-2105-13-86
23. Insel, T. R., & Young, L. J. (2001). The neurobiology of attachment. Nature Reviews Neuroscience, 2, 129-136. doi:10.1038/35053579
24. Klose, R. J., & Bird, A. P. (2006). Genomic DNA methylation: The mark and its mediators. Trends in Biochemical Sciences, 31, 89-97. doi:10.1016/j.tibs.2005.12.008
25. Koestler, D. C., Christensen, B., Karagas, M. R., Marsit, C. J., Langevin, S. M., Kelsey, K. T., ... Houseman, E. A. (2013). Blood-based profiles of DNA methylation predict the underlying distribution of cell types: A validation analysis. Epigenetics, 8, 816-826. doi:10.4161/epi.25430
26. Krueger, F., Parasuraman, R., Iyengar, V., Thornburg, M., Weel, J., Lin, M., ... Lipsky, R. H. (2012). Oxytocin receptor genetic variation promotes human trust behavior. Frontiers in Human Neuroscience, 6. doi:10.3389/fnhum.2012.00004
27. Kumsta, R., Hummel, E., Chen, F. S., & Heinrichs, M. (2013). Epigenetic regulation of the oxytocin receptor gene: Implications for behavioral neuroscience. 7. Frontiers in Neuroscience, 7. doi:10.3389/fnins.2013.00083
28. Loth, E., Poline, J.-B., Thyreau, B., Jia, T., Tao, C., Lourdusamy, A., ... IMAGEN, Consortium. (2014). Oxytocin receptor genotype modulates ventral striatal activity to social cues and response to stressful life events. Biological Psychiatry, 76, 367-376. doi:10.1016/j.biopsych.2013.07.043
29. Maier, W., Buller, R., Philipp, M., & Heuser, I. (1988). The Hamilton Anxiety Scale: Reliability, validity and sensitivity to change in anxiety and depressive disorders. Journal of Affective Disorders, 14, 61-68. doi:10.1016/0165-0327(88)90072-9
30. Mamrut, S., Harony, H., Sood, R., Shahar-Gold, H., Gainer, H., Shi, Y.-J., ... Wagner, S. (2013). DNA methylation of specific CpG sites in the promoter region regulates the transcription of the mouse oxytocin receptor. PLoS ONE, 8, e56869. doi:10.1371/journal.pone.0056869
31. Mancini, C., Van Ameringen, M., & MacMillan, H. (1995). Relationship of childhood sexual and physical abuse to anxiety disorders. Journal of Nervous and Mental Disease, 183, 309-314.
32. Maunakea, A. K., Nagarajan, R. P., Bilenky, M., Ballinger, T. J., D'Souza, C., Fouse, S. D., ... Delaney, A. (2010). Conserved role of intragenic DNA methylation in regulating alternative promoters. Nature, 466, 253-257. doi:10.1038/nature09165
33. McGowan, P. O., Sasaki, A., D'Alessio, A. C., Dymov, S., Labonté, B., Szyf, M., ... Meaney, M. J. (2009). Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nature Neuroscience, 12, 342-348. doi:10.1038/nn.2270
34. McQuaid, R. J., McInnis, O. A., Stead, J. D., Matheson, K., & Anisman, H. (2013). A paradoxical association of an oxytocin receptor gene polymorphism: Early-life adversity and vulnerability to depression. Frontiers in Neuroscience, 7, 128. doi:10.3389/fnins.2013.00128
35. Meaney, M. J. (2010). Epigenetics and the biological definition of Gene × Environment interactions. Child Development, 81, 41-79. doi:10.1111/j.1467-8624.2009.01381.x
36. Mizumoto, Y., Kimura, T., & Ivell, R. (1997). A genomic element within the third intron of the human oxytocin receptor gene may be involved in transcriptional suppression. Molecular and Cellular Endocrinology, 135, 129-138. doi:10.1016/S0303-7207(97)00195-0
37. Myers, A. J., Williams, L., Gatt, J. M., McAuley-Clark, E. Z., Dobson-Stone, C., Schofield, P. R., & Nemeroff, C. B. (2014). Variation in the oxytocin receptor gene is associated with increased risk for anxiety, stress and depression in individuals with a history of exposure to early life stress. Journal of Psychiatric Research, 59, 93-100. doi:10.1016/j.jpsychires.2014.08.021
38. Schwartz, A. C., Bradley, R. L., & Sexton, M. (2005). Posttraumatic stress disorder among African Americans in an inner city mental health clinic. Psychiatric Services, 56, 212-215. doi:10.1176/appi.ps.56.2.212
39. Shonkoff, J. P. (2010). Building a new biodevelopmental framework to guide the future of early childhood policy. Child Development, 81, 357-367. doi:10.1111/j.1467-8624.2009.01399.x
40. Smith, A. K., Kilaru, V., Klengel, T., Mercer, K. B., Bradley, B., Conneely, K. N., ... Binder, E. B. (2015). DNA extracted from saliva for methylation studies of psychiatric traits: Evidence tissue specificity and relatedness to brain. American Journal of Medical Genetics, 168, 36-44. doi:10.1002/ajmg.b.32278
41. Smith, A. K., Kilaru, V., Kocak, M., Almli, L. M., Mercer, K. B., Ressler, K. J., ... Conneely, K. N. (2014). Methylation quantitative trait loci (meQTLs) are consistently detected across ancestry, developmental stage, and tissue type. BMC Genomics, 15, 145. doi:10.1186/1471-2164-15-145
42. Sun, Y. V., Smith, A. K., Conneely, K. N., Chang, Q., Li, W., Lazarus, A., ... Kardia, S. L. (2013). Epigenomic association analysis identifies smoking-related DNA methylation sites in African Americans. Human Genetics, 132, 1027-1037. doi:10.1007/s00439-013-1311-6
43. Szyf, M., & Bick, J. (2012). DNA methylation: A mechanism for embedding early life experiences in the genome. Child Development, 84, 49-57. doi:10.1111/j.1467-8624.2012.01793.x
44. Thompson, R. J., Parker, K. J., Hallmayer, J. F., Waugh, C. E., & Gotlib, I. H. (2011). Oxytocin receptor gene polymorphism (rs2254298) interacts with familial risk for psychopathology to predict symptoms of depression and anxiety in adolescent girls. Psychoneuroendocrinology, 36, 144-147. doi:10.1016/j.psyneuen.2010.07.003
45. Unternaehrer, E., Luers, P., Mill, J., Dempster, E., Meyer, A. H., Staehli, S., ... Meinschmidt, G. (2012). Dynamic changes in DNA methylation of stress-associated genes (OXTR, BDNF) after acute psychosocial stress. Translational Psychiatry, 2, e150. doi:10.1038/tp.2012.77
46. Voorman, A., Lumley, T., McKnight, B., & Rice, K. (2011). Behavior of QQ-plots and genomic control in studies of gene-environment interaction. PLoS ONE, 6, e19416. doi:10.1371/journal.pone.0019416
47. Wu, N., Li, Z., & Su, Y. (2012). The association between oxytocin receptor gene polymorphism (OXTR) and trait empathy. Journal of Affective Disorders, 138, 468-472. doi:10.1016/j.jad.2012.01.009
48. Zeileis, A. (2004). Econometric computing with HC and HAC covariance matrix estimators. Journal of Statistical Software, 11, 1-17. Retrieved from http://www.jstatsoft.org/v11/i10/