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An interaction between early threat exposure and the oxytocin receptor in females: Disorder-specific versus general risk for psychopathology and social–emotional mediators

Published online by Cambridge University Press:  22 July 2020

Amy L. Byrd*
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Irene Tung
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Stephen D. Manuck
Department of Psychology, University of Pittsburgh, Pittsburgh, PA, USA
Vera Vine
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Michelle Horner
Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA
Alison E. Hipwell
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Stephanie D. Stepp
Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Author for correspondence: Amy L. Byrd, Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; E-mail:


Early threat exposure is a transdiagnostic risk factor for psychopathology, and evidence suggests that genetic variation in the oxytocin receptor (OXTR) moderates this association. However, it is unclear if this gene-by-environment (G×E) interaction is tied to unique risk for disorder-specific outcomes or instead increases shared risk for general psychopathology. Moreover, little is known about how this G×E interaction increases risk. The current study utilized a prospective, longitudinal sample of females (n = 2,020) to examine: (a) whether the interaction between early threat exposure and OXTR variation (rs53576, rs2254298) confers risk for disorder-specific outcomes (depression, anxiety, borderline and antisocial personality disorders) and/or general psychopathology in early adulthood; and (b) whether social–emotional deficits (emotion dysregulation, callousness, attachment quality) during adolescence constitute mediating mechanisms. Consistent with hypotheses, the interactive effects of early threat exposure and OXTR variation (rs53576) predicted general psychopathology, with threat-exposed women carrying at least one copy of the rs53576 A-allele at greatest risk. This interaction was mediated via emotional dysregulation in adolescence, with threat-exposed A-allele carriers demonstrating greater emotion dysregulation, and greater emotion dysregulation predicting general psychopathology in early adulthood. Findings suggest that this G×E places women at risk for a broad range of psychopathology via effects on emotion dysregulation.

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Copyright © The Author(s), 2020. Published by Cambridge University Press

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American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (DSM-5®). American Psychiatric Pub.Google Scholar
Anda, R. F., Felitti, V. J., Bremner, J. D., Walker, J. D., Whitfield, C., Perry, B. D., … Giles, W. H. (2006). The enduring effects of abuse and related adverse experiences in childhood. European Archives of Psychiatry Clinical Neuroscience, 256, 174186. doi:10.1007/s00406-005-0624-4CrossRefGoogle ScholarPubMed
Armsden, G. C., & Greenberg, M. T. (1987). The inventory of parent and peer attachment: Individual differences and their relationship to psychological well-being in adolescence. Journal of Youth and Adolescence, 16(5), 427454.CrossRefGoogle ScholarPubMed
Bakermans-Kranenburg, M. J., & Van Ijzendoorn, M. H. (2011). Differential susceptibility to rearing environment depending on dopamine-related genes: New evidence and a meta-analysis. Development and Psychopathology, 23, 3952. doi:10.1017/S0954579410000635CrossRefGoogle ScholarPubMed
Bakermans-Kranenburg, M. J., & van IJzendoorn, M. H. (2014). A sociability gene? Meta-analysis of oxytocin receptor genotype effects in humans. Psychiatric Genetics, 24, 4551. doi:10.1097/YPG.0b013e3283643684CrossRefGoogle ScholarPubMed
Bakermans-Kranenburg, M. J., & Van Ijzendoorn, M. H. (2015). The hidden efficacy of interventions: Gene×environment experiments from a differential susceptibility perspective. Annual Review of Psychology, 66, 381409. doi:10.1146/annurev-psych-010814-015407CrossRefGoogle ScholarPubMed
Barlow, D. H., Allen, L. B., & Choate, M. L. (2004). Toward a unified treatment for emotional disorders. Behavior Therapy, 35, 205230. doi:10.1016/S0005-7894(04)80036-4CrossRefGoogle Scholar
Barnard, K., Johnson, S., Booth, C., & Bee, H. (1994). Difficult life circumstances scale. Seattle, WA: University of Washington.Google Scholar
Blakemore, S. J., & Choudhury, S. (2006). Development of the adolescent brain: Implications for executive function and social cognition. Journal of Child Psychology and Psychiatry, 47, 296312. doi:10.1111/j.1469-7610.2006.01611.xCrossRefGoogle ScholarPubMed
Bogdan, R., Baranger, D. A., & Agrawal, A. (2018). Polygenic risk scores in clinical psychology: Bridging genomic risk to individual differences. Annual Review of Clinical Psychology, 14, 119157. doi:10.1146/annurev-clinpsy-050817-084847CrossRefGoogle ScholarPubMed
Bradley, B., Westen, D., Mercer, K. B., Binder, E. B., Jovanovic, T., Crain, D., … Heim, C. (2011). Association between childhood maltreatment and adult emotional dysregulation in a low-income, urban, African American sample: Moderation by oxytocin receptor gene. Development Psychopathology, 23, 439452. doi:10.1017/S0954579411000162CrossRefGoogle Scholar
Buist, K. L., Deković, M., Meeus, W., & van Aken, M. A. (2004). The reciprocal relationship between early adolescent attachment and internalizing and externalizing problem behaviour. Journal of Adolescence, 27, 251266. doi:10.1016/j.adolescence.2003.11.012CrossRefGoogle ScholarPubMed
Butovskaya, P. R., Lazebny, O. E., Sukhodolskaya, E. M., Vasiliev, V. A., Dronova, D. A., Fedenok, J. N., … Butovskaya, M. L. (2016). Polymorphisms of two loci at the oxytocin receptor gene in populations of Africa, Asia and South Europe. BMC Genetics, 17, 17. doi:10.1186/s12863-015-0323-8CrossRefGoogle Scholar
Byrd, A. L., Hawes, S. W., Loeber, R., & Pardini, D. A. (2018). Interpersonal callousness from childhood to adolescence: Developmental trajectories and early risk factors. Journal of Clinical Child Adolescent Psychology, 47, 467482. doi:10.1080/15374416.2016.1144190CrossRefGoogle ScholarPubMed
Byrd, A. L., Kahn, R. E., & Pardini, D. A. (2013). A validation of the inventory of callous-unemotional traits in a community sample of young adult males. Journal of Psychopathology and Behavioral Assessment, 35, 2034. doi:10.1007/s10862-012-9315-4CrossRefGoogle Scholar
Byrd, A. L., Loeber, R., & Pardini, D. A. (2012). Understanding desisting and persisting forms of delinquency: The unique contributions of disruptive behavior disorders and interpersonal callousness. Journal of Child Psychology and Psychiatry, 53, 371380. doi:10.1111/j.1469-7610.2011.02504.xCrossRefGoogle ScholarPubMed
Byrd, A. L., & Manuck, S. B. (2014). MAOA, childhood maltreatment, and antisocial behavior: Meta-analysis of a gene-environment interaction. Biological Psychiatry, 75, 917. doi:10.1016/j.biopsych.2013.05.004CrossRefGoogle ScholarPubMed
Byrd, A. L., Manuck, S. B., Hawes, S. W., Vebares, T. J., Nimgaonkar, V., Chowdari, K. V., … Stepp, S. D. (2019). The interaction between monoamine oxidase A (MAOA) and childhood maltreatment as a predictor of personality pathology in females: Emotional reactivity as a potential mediating mechanism. Development and Psychopathology, 31, 361377. doi:10.1017/S0954579417001900CrossRefGoogle ScholarPubMed
Carter, C. S. (2003). Developmental consequences of oxytocin. Physiology & Behavior, 79, 383397. doi:10.1016/S0031-9384(03)00151-3CrossRefGoogle ScholarPubMed
Carter, C. S. (2014). Oxytocin pathways and the evolution of human behavior. Annual Review of Psychology, 65, 1739. doi:10.1146/annurev-psych-010213-115110CrossRefGoogle ScholarPubMed
Carter, C. S., Boone, E. M., Pournajafi-Nazarloo, H., & Bales, K. L. (2009). Consequences of early experiences and exposure to oxytocin and vasopressin are sexually dimorphic. Developmental Neuroscience, 31, 332341. doi:10.1159/000216544CrossRefGoogle ScholarPubMed
Casey, B. J., Jones, R. M., & Hare, T. A. (2008). The adolescent brain. Annals of the New York Academy of Sciences, 1124, 111126. doi:10.1196/annals.1440.010CrossRefGoogle ScholarPubMed
Caspi, A., Houts, R. M., Belsky, D. W., Goldman-Mellor, S. J., Harrington, H., Israel, S., … Moffitt, T. E. (2014). The p factor: One general psychopathology factor in the structure of psychiatric disorders? Clinical Psychological Science, 2, 119137. doi:10.1177/2167702613497473CrossRefGoogle Scholar
Chen, F. F., Hayes, A., Carver, C. S., Laurenceau, J. P., & Zhang, Z. (2012). Modeling general and specific variance in multifaceted constructs: A comparison of the bifactor model to other approaches. Journal of Personality, 80, 219251. doi:10.1111/j.1467-6494.2011.00739.xCrossRefGoogle ScholarPubMed
Cicchetti, D. (2013). Annual research review: Resilient functioning in maltreated children–past, present, and future perspectives. Journal of Child Psychology Psychiatry, 54, 402422. doi:10.1111/j.1469-7610.2012.02608.xCrossRefGoogle ScholarPubMed
Cicchetti, D. (2016). Socioemotional, personality, and biological development: Illustrations from a multilevel developmental psychopathology perspective on child maltreatment. Annual Review of Psychology, 67, 187211. doi:10.1146/annurev-psych-122414-033259CrossRefGoogle ScholarPubMed
Cicchetti, D., & Manly, J. T. (2001). Operationalizing child maltreatment: Developmental processes and outcomes. Development Psychopathology, 13, 755757. doi:10.1017/S0954579401004011CrossRefGoogle ScholarPubMed
Cicchetti, D., & Rogosch, F. A. (1996). Equifinality and multifinality in developmental psychopathology. Development and Psychopathology, 8, 597600. doi:10.1017/S0954579400007318CrossRefGoogle Scholar
Cicchetti, D., Rogosch, F. A., Hecht, K. F., Crick, N. R., & Hetzel, S. (2014). Moderation of maltreatment effects on childhood borderline personality symptoms by gender and oxytocin receptor and FK506 binding protein 5 genes. Development Psychopathology, 26, 831849. doi:10.1017/S095457941400042XCrossRefGoogle ScholarPubMed
Cicchetti, D., & Toth, S. L. (2005). Child maltreatment. Annual Review of Clinical Psycholology, 1, 409438. doi:10.1146/annurev.clinpsy.1.102803.144029CrossRefGoogle ScholarPubMed
Cicchetti, D., Toth, S., & Maughan, A.. (2000). An ecological-transactional model of child maltreatment. In Sameroff, A., Lewis, M., & Miller, S. (Eds.), Handbook of developmental psychopathology (pp. 689722). SpringerCrossRefGoogle Scholar
Cole, P. M., Hall, S. E., & Hajal, N. J. (2008). Emotion dysregulation as a risk factor for psychopathology. Child and Adolescent Psychopathology, 341373.Google Scholar
Cole, P. M., Michel, M. K., & Teti, L. O. D. (1994). The development of emotion regulation and dysregulation: A clinical perspective. Monographs of the Society for Research in Child Development, 59, 73102. doi:10.1111/j.1540-5834.1994.tb01278.xCrossRefGoogle ScholarPubMed
Costello, E. J., Compton, S. N., Keeler, G., & Angold, A. (2003). Relationships between poverty and psychopathology: A natural experiment. JAMA, 290, 20232029. doi:10.1001/jama.290.15.2023CrossRefGoogle ScholarPubMed
Cowell, R. A., Cicchetti, D., Rogosch, F. A., & Toth, S. L. (2015). Childhood maltreatment and its effect on neurocognitive functioning: Timing and chronicity matter. Development and Psychopathology, 27, 521533. doi:10.1017/S0954579415000139CrossRefGoogle ScholarPubMed
Creswell, K. G., Wright, A. G., Troxel, W. M., Ferrell, R. E., Flory, J. D., & Manuck, S. B. (2014). OXTR polymorphism predicts social relationships through its effects on social temperament. Social Cognitive Affective Neuroscience, 10, 869876. doi:10.1093/scan/nsu132CrossRefGoogle ScholarPubMed
Crick, N. R., & Dodge, K. A. (1996). Social information-processing mechanisms in reactive and proactive aggression. Child Development, 67, 9931002. doi:10.2307/1131875CrossRefGoogle ScholarPubMed
Dadds, M. R., Moul, C., Cauchi, A., Dobson-Stone, C., Hawes, D. J., Brennan, J., … Ebstein, R. E. (2014). Polymorphisms in the oxytocin receptor gene are associated with the development of psychopathy. Development Psychopathology, 26, 2131. doi:10.1017/S0954579413000485CrossRefGoogle ScholarPubMed
Dick, D. M., Agrawal, A., Keller, M. C., Adkins, A., Aliev, F., Monroe, S., … Sher, K. J. (2015). Candidate gene–environment interaction research: Reflections and recommendations. Perspectives on Psychological Science, 10, 3759. doi:10.1177/1745691614556682CrossRefGoogle ScholarPubMed
Dodge, K. A. (2009). Mechanisms of gene-environment interaction effects in the development of conduct disorder. Perspectives on Psychological Science, 4, 408414. doi:10.1111/j.1745-6924.2009.01147.xCrossRefGoogle ScholarPubMed
Donadon, M. F., Martin-Santos, R., & Osório, F. d. L. (2018). The associations between oxytocin and trauma in humans: A systematic review. Frontiers in Pharmacology, 9, 154. doi:10.3389/fphar.2018.00154CrossRefGoogle ScholarPubMed
Duncan, L. E., & Keller, M. C. (2011). A critical review of the first 10 years of candidate gene-by-environment interaction research in psychiatry. American Journal of Psychiatry, 168, 10411049. doi:10.1176/appi.ajp.2011.11020191CrossRefGoogle Scholar
Eaton, N. R., Krueger, R. F., Keyes, K. M., Skodol, A. E., Markon, K. E., Grant, B. F., & Hasin, D. S. (2011). Borderline personality disorder co-morbidity: Relationship to the internalizing-externalizing structure of common mental disorders. Psychological Medicine, 41, 10411050. doi:10.1017/S0033291710001662CrossRefGoogle ScholarPubMed
Egeland, B., & Sroufe, L. A. (1981). Attachment and early maltreatment. Child Development, 4452. doi:10.2307/1129213CrossRefGoogle ScholarPubMed
Feldman, R. (2012). Oxytocin and social affiliation in humans. Hormones and Behavior, 61, 380391. doi:10.1016/j.yhbeh.2012.01.008CrossRefGoogle ScholarPubMed
Feldman, R., Gordon, I., Influs, M., Gutbir, T., & Ebstein, R. P. (2013). Parental oxytocin and early caregiving jointly shape children's oxytocin response and social reciprocity. Neuropsychopharmacology, 38, 1154. doi:10.1038/npp.2013.22CrossRefGoogle ScholarPubMed
Foa, E. B., Johnson, K. M., Feeny, N. C., & Treadwell, K. R. (2001). The Child PTSD Symptom Scale: A preliminary examination of its psychometric properties. Journal of Clinical Child Psychology, 30, 376384. doi:10.1207/S15374424JCCP3003_9CrossRefGoogle ScholarPubMed
Frick, P. J., & Hare, R. D. (2001). Antisocial process screening device: APSD. Toronto: Multi-Health Systems.Google Scholar
Frick, P. J., Lilienfeld, S. O., Ellis, M., Loney, B., & Silverthorn, P. (1999). The association between anxiety and psychopathy dimensions in children. Journal of Abnormal Child Psychology, 27, 383392. doi:10.1023/A:1021928018403CrossRefGoogle ScholarPubMed
Frick, P. J., & White, S. F. (2008). Research Review: The importance of callous-unemotional traits for developmental models of aggressive and antisocial behavior. Journal of Child Psychology and Psychiatry, 49, 359375. doi:10.1111/j.1469-7610.2007.01862.xCrossRefGoogle ScholarPubMed
Gadow, K. D., Sprafkin, J., & Weiss, M. D. (2004). Adult Self-Report Inventory 4 manual. Stony Brook, NY: Checkmate Plus.Google Scholar
Green, J. G., McLaughlin, K. A., Berglund, P. A., Gruber, M. J., Sampson, N. A., Zaslavsky, A. M., & Kessler, R. C. (2010). Childhood adversities and adult psychiatric disorders in the national comorbidity survey replication I: Associations with first onset of DSM-IV disorders. Archives of General Psychiatry, 67, 113123. doi:10.1001/archgenpsychiatry.2009.186CrossRefGoogle ScholarPubMed
Gullone, E., & Robinson, K. (2005). The inventory of parent and peer attachment—Revised (IPPA-R) for children: A psychometric investigation. Clinical Psychology Psychotherapy: An International Journal of Theory Practice, 12, 6779. doi:10.1002/cpp.433CrossRefGoogle Scholar
Hammen, C., Bower, J. E., & Cole, S. W. (2015). Oxytocin receptor gene variation and differential susceptibility to family environment in predicting youth borderline symptoms. Journal of Personality Disorders, 29, 177192. doi:10.1521/pedi_2014_28_152CrossRefGoogle ScholarPubMed
Hartman, S., Widaman, K. F., & Belsky, J. (2015). Genetic moderation of effects of maternal sensitivity on girl's age of menarche: Replication of the Manuck et al. study. Development and Psychopathology, 27, 747756. doi:10.1017/S0954579414000856CrossRefGoogle ScholarPubMed
Heim, C., & Nemeroff, C. B. (2001). The role of childhood trauma in the neurobiology of mood and anxiety disorders: Preclinical and clinical studies. Biological Psychiatry, 49, 10231039. doi:10.1016/S0006-3223(01)01157-XCrossRefGoogle ScholarPubMed
Heleniak, C., Jenness, J. L., Vander Stoep, A., McCauley, E., & McLaughlin, K. A. (2016). Childhood maltreatment exposure and disruptions in emotion regulation: A transdiagnostic pathway to adolescent internalizing and externalizing psychopathology. Cognitive Therapy and Research, 40, 394415. doi:10.1007/s10608-015-9735-zCrossRefGoogle ScholarPubMed
Hipwell, A. E., Loeber, R., Stouthamer-Loeber, M., Keenan, K., White, H. R., & Kroneman, L. (2002). Characteristics of girls with early onset disruptive and antisocial behaviour. Criminal Behaviour and Mental Health, 12, 99118. doi:10.1002/cbm.489CrossRefGoogle ScholarPubMed
Hipwell, A. E., Murray, J., Xiong, S., Stepp, S. D., & Keenan, K. E. (2016). Effects of adolescent childbearing on maternal depression and problem behaviors: A prospective, population-based study using risk-set propensity scores. PLoS One, 11, e0155641. doi:10.1371/journal.pone.0155641CrossRefGoogle ScholarPubMed
Hipwell, A. E., Pardini, D. A., Loeber, R., Sembower, M., Keenan, K., & Stouthamer-Loeber, M. (2007). Callous-unemotional behaviors in young girls: Shared and unique effects relative to conduct problems. Journal of Clinical Child and Adolescent Psychology, 36, 293304. doi:10.1080/15374410701444165CrossRefGoogle ScholarPubMed
Hostinar, C. E., Cicchetti, D., & Rogosch, F. A. (2014). Oxytocin receptor gene polymorphism, perceived social support, and psychological symptoms in maltreated adolescents. Development and Psychopathology, 26, 465477. doi:10.1017/S0954579414000066CrossRefGoogle ScholarPubMed
Hughes, K., Bellis, M. A., Hardcastle, K. A., Sethi, D., Butchart, A., Mikton, C., … Dunne, M. P. (2017). The effect of multiple adverse childhood experiences on health: A systematic review and meta-analysis. The Lancet Public Health, 2, e356e366. doi:10.1016/S2468-2667(17)30118-4CrossRefGoogle ScholarPubMed
Israel, S., Lerer, E., Shalev, I., Uzefovsky, F., Riebold, M., Laiba, E., … Knafo, A. (2009). The oxytocin receptor (OXTR) contributes to prosocial fund allocations in the dictator game and the social value orientations task. PLoS One, 4, e5535. doi:10.1371/journal.pone.0005535CrossRefGoogle ScholarPubMed
Jaffee, S. R., Caspi, A., Moffitt, T. E., Dodge, K. A., Rutter, M., Taylor, A., & Tully, L. A. (2005). Nature × nurture: Genetic vulnerabilities interact with physical maltreatment to promote conduct problems. Development and Psychopathology, 17, 6784. doi:10.1017/S0954579405050042CrossRefGoogle ScholarPubMed
Jaffee, S. R., Caspi, A., Moffitt, T. E., & Taylor, A. (2004). Physical maltreatment victim to antisocial child: Evidence of an environmentally mediated process. Journal of Abnormal Psychology, 113, 4455. doi:10.1037/0021-843X.113.1.44CrossRefGoogle ScholarPubMed
Jaffee, S. R., & Maikovich-Fong, A. K. (2011). Effects of chronic maltreatment and maltreatment timing on children's behavior and cognitive abilities. Journal of Child Psychology and Psychiatry, 52, 184194. doi:10.1111/j.1469-7610.2010.02304.xCrossRefGoogle ScholarPubMed
Jaffee, S. R., & Price, T. S. (2007). Gene–environment correlations: A review of the evidence and implications for prevention of mental illness. Molecular Psychiatry, 12, 432. doi:10.1038/ ScholarPubMed
Johnson, J. G., Cohen, P., Brown, J., Smailes, E. M., & Bernstein, D. P. (1999). Childhood maltreatment increases risk for personality disorders during early adulthood. Archive General Psychiatry, 56, 600606. doi:10.1001/archpsyc.56.7.600CrossRefGoogle ScholarPubMed
Kessler, R. C., Chiu, W. T., Demler, O., Merikangas, K. R., & Walters, E. E. (2005). Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Archive of General Psychiatry, 62, 617627. doi:10.1001/archpsyc.62.6.617CrossRefGoogle ScholarPubMed
Kessler, R. C., McLaughlin, K. A., Green, J. G., Gruber, M. J., Sampson, N. A., Zaslavsky, A. M., … Angermeyer, M. (2010). Childhood adversities and adult psychopathology in the WHO World Mental Health Surveys. The British Journal of Psychiatry, 197, 378385. doi:10.1192/bjp.bp.110.080499CrossRefGoogle ScholarPubMed
Keyes, K. M., Eaton, N. R., Krueger, R. F., McLaughlin, K. A., Wall, M. M., Grant, B. F., & Hasin, D. S. (2012). Childhood maltreatment and the structure of common psychiatric disorders. The British Journal of Psychiatry, 200, 107115. doi:10.1192/bjp.bp.111.093062CrossRefGoogle ScholarPubMed
Kilpeläinen, T. O., Qi, L., Brage, S., Sharp, S. J., Sonestedt, E., Demerath, E., … Sandholt, C. H. (2011). Physical activity attenuates the influence of FTO variants on obesity risk: A meta-analysis of 218,166 adults and 19,268 children. PLoS Medicine, 8, e1001116. doi:10.1371/journal.pmed.1001116CrossRefGoogle Scholar
Kim, J., & Cicchetti, D. (2010). Longitudinal pathways linking child maltreatment, emotion regulation, peer relations, and psychopathology. Journal of Child Psychology Psychiatry, 51, 706716. doi:10.1111/j.1469-7610.2009.02202.xCrossRefGoogle ScholarPubMed
Kimonis, E. R., Centifanti, L. C., Allen, J. L., & Frick, P. J. (2014). Reciprocal influences between negative life events and callous-unemotional traits. Journal of Abnormal Child Psychology, 42, 12871298. doi:10.1007/s10802-014-9882-9CrossRefGoogle ScholarPubMed
Kimonis, E. R., Fanti, K. A., Isoma, Z., & Donoghue, K. (2013). Maltreatment profiles among incarcerated boys with callous-unemotional traits. Child Maltreatment, 18, 108121. doi:10.1177/1077559513483002CrossRefGoogle ScholarPubMed
Klimes-Dougan, B., Brand, A. E., Zahn-Waxler, C., Usher, B., Hastings, P. D., Kendziora, K., & Garside, R. B. (2007). Parental emotion socialization in adolescence: Differences in sex, age and problem status. Social Development, 16(2), 326342.CrossRefGoogle Scholar
Kline, R. B. (2005). Principles and practice of structural equation modeling. New York: Guilford.Google Scholar
Kotov, R., Krueger, R. F., Watson, D., Achenbach, T. M., Althoff, R. R., Bagby, R. M., … Clark, L. A. (2017). The Hierarchical Taxonomy of Psychopathology (HiTOP): A dimensional alternative to traditional nosologies. Journal of Abnormal Psychology, 126, 454. doi:10.1037/abn0000258CrossRefGoogle ScholarPubMed
Krueger, R. F., & Markon, K. E. (2006). Reinterpreting comorbidity: A model-based approach to understanding and classifying psychopathology. Annual Review of Clinical Psycholology, 2, 111133. doi:10.1146/annurev.clinpsy.2.022305.095213CrossRefGoogle ScholarPubMed
Krueger, F., Parasuraman, R., Iyengar, V., Thornburg, M., Weel, J., Lin, M., … Lipsky, R. (2012). Oxytocin receptor genetic variation promotes human trust behavior. Frontiers in Human Neuroscience, 6, 4.CrossRefGoogle ScholarPubMed
Kumsta, R., & Heinrichs, M. (2013). Oxytocin, stress and social behavior: Neurogenetics of the human oxytocin system. Current Opinion in Neurobiology, 23, 1116. doi:10.1016/j.conb.2012.09.004CrossRefGoogle ScholarPubMed
Laceulle, O. M., Vollebergh, W. A., & Ormel, J. (2015). The structure of psychopathology in adolescence: Replication of a general psychopathology factor in the TRAILS study. Clinical Psychological Science, 3, 850860. doi:10.1177/2167702614560750CrossRefGoogle Scholar
Lahey, B. B., Applegate, B., Hakes, J. K., Zald, D. H., Hariri, A. R., & Rathouz, P. J. (2012). Is there a general factor of prevalent psychopathology during adulthood? Journal of Abnormal Psychology, 121, 971. doi:10.1037/a0028355CrossRefGoogle Scholar
Lahey, B. B., Rathouz, P. J., Keenan, K., Stepp, S. D., Loeber, R., & Hipwell, A. E. (2015). Criterion validity of the general factor of psychopathology in a prospective study of girls. Journal of Child Psychology Psychiatry, 56, 415422. doi:10.1111/jcpp.12300CrossRefGoogle Scholar
Lahey, B. B., Van Hulle, C. A., Singh, A. L., Waldman, I. D., & Rathouz, P. (2011). Higher-order genetic and environmental structure of prevalent forms of child and adolescent psychopathology. Archives of General Psychiatry, 68, 181189. doi:10.1001/archgenpsychiatry.2010.192CrossRefGoogle ScholarPubMed
Lerer, E., Levi, S., Salomon, S., Darvasi, A., Yirmiya, N., & Ebstein, R. (2008). Association between the oxytocin receptor (OXTR) gene and autism: Relationship to Vineland Adaptive Behavior Scales and cognition. Molecular Psychiatry, 13, 980. doi:10.1038/ ScholarPubMed
MacCallum, R. C., Zhang, S., Preacher, K. J., & Rucker, D. D. (2002). On the practice of dichotomization of quantitative variables. Psychological Methods, 7, 19. doi:10.1037/1082-989X.7.1.19CrossRefGoogle ScholarPubMed
Malik, A. I., Zai, C. C., Abu, Z., Nowrouzi, B., & Beitchman, J. H. (2012). The role of oxytocin and oxytocin receptor gene variants in childhood-onset aggression. Genes, Brain and Behavior, 11, 545551. doi:10.1111/j.1601-183X.2012.00776.xCrossRefGoogle ScholarPubMed
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, 759782. doi:10.1017/S0954579401004023CrossRefGoogle ScholarPubMed
Masten, A. S., & Cicchetti, D. (2010). Developmental cascades. Development and Psychopathology, 22(3), 491495.CrossRefGoogle ScholarPubMed
Maughan, A., & Cicchetti, D. (2002). Impact of child maltreatment and interadult violence on children's emotion regulation abilities and socioemotional adjustment. Child Development, 73, 15251542. doi:10.1111/1467-8624.00488CrossRefGoogle ScholarPubMed
McCrory, E. J., De Brito, S. A., Sebastian, C. L., Mechelli, A., Bird, G., Kelly, P. A., & Viding, E. (2011). Heightened neural reactivity to threat in child victims of family violence. Current Biology, 21, 947948. doi:10.1016/j.cub.2011.10.015CrossRefGoogle ScholarPubMed
McDonald, R. P., & Ho, M. R. (2002). Principles and practice in reporting structural equation analyses. Psychological Methods, 7, 6482. doi:10.1037/1082-989X.7.1.64CrossRefGoogle ScholarPubMed
McInnis, O. A., McQuaid, R. J., Matheson, K., & Anisman, H. (2015). The moderating role of an oxytocin receptor gene polymorphism in the relation between unsupportive social interactions and coping profiles: Implications for depression. Frontiers in Psychology, 6, 1133. doi:10.3389/fpsyg.2015.01133CrossRefGoogle ScholarPubMed
McLaughlin, K. A., Green, J. G., Gruber, M. J., Sampson, N. A., Zaslavsky, A. M., & Kessler, R. C. (2012). Childhood adversities and first onset of psychiatric disorders in a national sample of US adolescents. Archives of General Psychiatry, 69, 11511160. doi:10.1001/archgenpsychiatry.2011.2277CrossRefGoogle Scholar
McLaughlin, K. A., Hatzenbuehler, M. L., Mennin, D. S., & Nolen-Hoeksema, S. (2011). Emotion dysregulation and adolescent psychopathology: A prospective study. Behaviour Research and Therapy, 49, 544554. doi:10.1016/j.brat.2011.06.003CrossRefGoogle ScholarPubMed
McLaughlin, K. A., Sheridan, M. A., Alves, S., & Mendes, W. B. (2014a). Child maltreatment and autonomic nervous system reactivity: Identifying dysregulated stress reactivity patterns using the biopsychosocial model of challenge and threat. Psychosomatic Medicine, 76, 538. doi:10.1097/PSY.0000000000000098CrossRefGoogle Scholar
McLaughlin, K. A., Sheridan, M. A., & Lambert, H. K. (2014b). Childhood adversity and neural development: Deprivation and threat as distinct dimensions of early experience. Neuroscience ans Biobehavioral Reviews, 47, 578591. doi:10.1016/j.neubiorev.2014.10.012CrossRefGoogle Scholar
McQuaid, R. J., McInnis, O. A., Abizaid, A., & Anisman, H. (2014). Making room for oxytocin in understanding depression. Journal of Neuroscience and Biobehavioral Reviews, 45, 305322. doi:10.1016/j.neubiorev.2014.07.005CrossRefGoogle ScholarPubMed
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.2013.00128CrossRefGoogle ScholarPubMed
Mersky, J., Topitzes, J., & Reynolds, A. (2013). Impacts of adverse childhood experiences on health, mental health, and substance use in early adulthood: A cohort study of an urban, minority sample in the US. Child Abuse and Neglect, 37, 917925. doi:10.1016/j.chiabu.2013.07.011CrossRefGoogle Scholar
Morey, L. C.. (2007). Personality assessment inventory (PAI): Professional manual. PAR (Psychological Assessment Resources).Google Scholar
Muthén, B. O., & Muthén, L. K. (2012). Mplus user's guide (7th ed.). Los Angeles, CA.Google Scholar
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, 93100. doi:10.1016/j.jpsychires.2014.08.021CrossRefGoogle ScholarPubMed
Neumann, I. D. (2008). Brain oxytocin: A key regulator of emotional and social behaviours in both females and males. Journal of Neuroendocrinology, 20, 858865. doi:10.1111/j.1365-2826.2008.01726.xCrossRefGoogle ScholarPubMed
Nolen-Hoeksema, S., & Watkins, E. R. (2011). A heuristic for developing transdiagnostic models of psychopathology: Explaining multifinality and divergent trajectories. Perspectives on Psychological Science, 6, 589609. doi:10.1177/1745691611419672CrossRefGoogle ScholarPubMed
Pardini, D. A., Lochman, J. E., & Frick, P. J. (2003). Callous-unemotional traits and social-cognitive processes in adjudicated youths. Journal of the American Academy of Child and Adolescent Psychiatry, 42, 364371. doi:10.1097/00004583-200303000-00018CrossRefGoogle ScholarPubMed
Perry, B. D., Pollard, R. A., Blakley, T. L., Baker, W. L., & Vigilante, D. (1995). Childhood trauma, the neurobiology of adaptation, and “use-dependent” development of the brain: How “states” become “traits”. Infant Mental Health Journal, 16, 271291. doi:10.1002/1097-0355(199524)16:4<271::AID-IMHJ2280160404>3.0.CO;2-B3.0.CO;2-B>CrossRefGoogle Scholar
Reyome, N. D. (2010). Childhood emotional maltreatment and later intimate relationships: Themes from the empirical literature. Journal of Aggression, Maltreatment, and Trauma, 19, 224242. doi:10.1080/10926770903539664CrossRefGoogle Scholar
Rodrigues, S. M., Saslow, L. R., Garcia, N., John, O. P., & Keltner, D. (2009). Oxytocin receptor genetic variation relates to empathy and stress reactivity in humans. Proceedings of the National Academy of Sciences, 106, 2143721441. doi:10.1073/pnas.0909579106CrossRefGoogle ScholarPubMed
Rogosch, F. A., & Cicchetti, D. (2005). Child maltreatment, attention networks, and potential precursors to borderline personality disorder. Development and Psychopathology, 17, 10711089. doi:10.1017/S0954579405050509CrossRefGoogle ScholarPubMed
Rutter, M. (2007). Gene–environment interdependence. Developmental Science, 10, 1218. doi:10.1111/j.1467-7687.2007.00557.xCrossRefGoogle ScholarPubMed
Scott, L. N., Whalen, D. J., Zalewski, M., Beeney, J. E., Pilkonis, P. A., Hipwell, A. E., & Stepp, S. D. (2013). Predictors and consequences of developmental changes in adolescent girls’ self-reported quality of attachment to their primary caregiver. Journal of Adolescence, 36, 797806. doi:10.1016/j.adolescence.2013.06.005CrossRefGoogle ScholarPubMed
Seltzer, L. J., Ziegler, T., Connolly, M. J., Prososki, A. R., & Pollak, S. D. (2014). Stress-induced elevation of oxytocin in maltreated children: Evolution, neurodevelopment, and social behavior. Child Development, 85, 501512. doi:10.1111/cdev.12136CrossRefGoogle ScholarPubMed
Shamay-Tsoory, S. G., & Abu-Akel, A. (2016). The social salience hypothesis of oxytocin. Biological Psychiatry, 79, 194202. doi:10.1016/j.biopsych.2015.07.020CrossRefGoogle ScholarPubMed
Sheridan, M. A., & McLaughlin, K. A. (2014). Dimensions of early experience and neural development: Deprivation and threat. Trends in Cognitive Sciences, 18, 580585. doi:10.1016/j.tics.2014.09.001CrossRefGoogle ScholarPubMed
Smearman, E. L., Winiarski, D. A., Brennan, P. A., Najman, J., & Johnson, K. C. (2015). Social stress and the oxytocin receptor gene interact to predict antisocial behavior in an at-risk cohort. Development and Psychopathology, 27, 309318. doi:10.1017/S0954579414000649CrossRefGoogle Scholar
Steele, H., & Siever, L. (2010). An attachment perspective on borderline personality disorder: Advances in gene–environment considerations. Current Psychiatry Reports, 12, 6167. doi:10.1007/s11920-009-0091-0CrossRefGoogle ScholarPubMed
Steinberg, L. (2005). Cognitive and affective development in adolescence. Trends in Cognitive Sciences, 9, 6974. doi:10.1016/j.tics.2004.12.005CrossRefGoogle ScholarPubMed
Steinberg, L., & Morris, A. S. (2001). Adolescent development. Journal of Cognitive Education and Psychology, 2, 5587. doi:10.1891/1945-8959.2.1.55CrossRefGoogle Scholar
Stepp, S. D., Lazarus, S. A. & Byrd, A. L. (2016). A systematic review of risk factors prospectively associated with borderline personality disorder: Taking stock and moving forward. Personality Disorders: Theory, Research, and Treatment, 7, 316-323. doi:10.1037/per0000186CrossRefGoogle ScholarPubMed
Straus, M. A., Hamby, S. L., Boney-McCoy, S., & Sugarman, D. B. (1996). The revised conflict tactics scales (CTS2) development and preliminary psychometric data. Journal of Family Issues, 17, 283316. doi:10.1177/019251396017003001CrossRefGoogle Scholar
Straus, M. A., Hamby, S. L., Finkelhor, D., Moore, D. W., & Runyan, D. (1998). Identification of child maltreatment with the parent-child conflict tactics scales: Development and psychometric data for a national sample of American parents. Child Abuse and Neglect, 22, 249270. doi:10.1016/S0145-2134(97)00174-9CrossRefGoogle ScholarPubMed
Tabak, B. A. (2013). Oxytocin and social salience: A call for gene-environment interaction research. Frontiers in Neuroscience, 7, 199. doi:10.3389/fnins.2013.00199CrossRefGoogle Scholar
Tackett, J. L., Lahey, B. B., Van Hulle, C., Waldman, I., Krueger, R. F., & Rathouz, P. J. (2013). Common genetic influences on negative emotionality and a general psychopathology factor in childhood and adolescence. Journal of Abnormal Psychology, 122(4), 1142.CrossRefGoogle Scholar
Tarullo, A. R., & Gunnar, M. R. (2006). Child maltreatment and the developing HPA axis. Hormones and Behavior, 50, 632639. doi:10.1016/j.yhbeh.2006.06.010CrossRefGoogle ScholarPubMed
Teicher, M. H., Andersen, S. L., Polcari, A., Anderson, C. M., Navalta, C. P., & Kim, D. M. (2003). The neurobiological consequences of early stress and childhood maltreatment. Neuroscience & Biobehavioral Reviews, 27, 3344. doi:10.1016/S0149-7634(03)00007-1CrossRefGoogle ScholarPubMed
Thompson, S. M., Hammen, C., Starr, L. R., & Najman, J. M. (2014). Oxytocin receptor gene polymorphism (rs53576) moderates the intergenerational transmission of depression. Psychoneuroendocrinology, 43, 1119. doi:10.1016/j.psyneuen.2014.01.012CrossRefGoogle ScholarPubMed
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, 144147. doi:10.1016/j.psyneuen.2010.07.003CrossRefGoogle ScholarPubMed
Toepfer, P., Heim, C., Entringer, S., Binder, E., Wadhwa, P., & Buss, C. (2017). Oxytocin pathways in the intergenerational transmission of maternal early life stress. Neuroscience & Biobehavioral Reviews, 73, 293308. doi:10.1016/j.neubiorev.2016.12.026CrossRefGoogle ScholarPubMed
Verona, E., Murphy, B., & Bresin, K. (2018). Oxytocin-related single-nucleotide polymorphisms, family environment, and psychopathic traits. Personality Disorders: Theory, Research, and Treatment, 9, 584. doi:10.1037/per0000290CrossRefGoogle ScholarPubMed
Wald, A. (1943). Tests of statistical hypotheses concerning several parameters when the number of observations is large. Transactions of the American Mathematical society, 54, 426482. doi:10.1090/S0002-9947-1943-0012401-3CrossRefGoogle Scholar
Wang, Q., Shelton, R. C., & Dwivedi, Y. (2018). Interaction between early-life stress and FKBP5 gene variants in major depressive disorder and post-traumatic stress disorder: A systematic review and meta-analysis. Journal of Affective Disorders, 225, 422428. doi:10.1016/j.jad.2017.08.066CrossRefGoogle ScholarPubMed
Zhao, M., Chen, L., Yang, J., Han, D., Fang, D., Qiu, X., … Wang, L. (2018). BDNF Val66Met polymorphism, life stress and depression: A meta-analysis of gene-environment interaction. Journal of Affective Disorders, 227, 226235. doi:10.1016/j.jad.2017.10.024CrossRefGoogle ScholarPubMed
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An interaction between early threat exposure and the oxytocin receptor in females: Disorder-specific versus general risk for psychopathology and social–emotional mediators
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