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Childhood quality influences genetic sensitivity to environmental influences across adulthood: A life-course Gene × Environment interaction study

  • Robert Keers (a1) and Michael Pluess (a1)
Abstract

While environmental adversity has been shown to increase risk for psychopathology, individuals differ in their sensitivity to these effects. Both genes and childhood experiences are thought to influence sensitivity to the environment, and these factors may operate synergistically such that the effects of childhood experiences on later sensitivity are greater in individuals who are more genetically sensitive. In line with this hypothesis, several recent studies have reported a significant three-way interaction (Gene × Environment × Environment) between two candidate genes and childhood and adult environment on adult psychopathology. We aimed to replicate and extend these findings in a large, prospective multiwave longitudinal study using a polygenic score of environmental sensitivity and objectively measured childhood and adult material environmental quality. We found evidence for both Environment × Environment and Gene × Environment × Environment effects on psychological distress. Children with a poor-quality material environment were more sensitive to the negative effects of a poor environment as adults, reporting significantly higher psychological distress scores. These effects were further moderated by a polygenic score of environmental sensitivity. Genetically sensitive children were more vulnerable to adversity as adults, if they had experienced a poor childhood environment but were significantly less vulnerable if their childhood environment was positive. These findings are in line with the differential susceptibility hypothesis and suggest that a life course approach is necessary to elucidate the role of Gene × Environment in the development of mental illnesses.

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Corresponding author
Address correspondence and reprint requests to: Michael Pluess, Department of Biological and Experimental Psychology, School of Biological and Chemical Sciences, Queen Mary University of London, Mile End Road, London E1 4NS, UK; E-mail: m.pluess@qmul.ac.uk.
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This work made use of data and samples generated by the 1958 Birth Cohort (National Child Development Study), which is managed by the Centre for Longitudinal Studies at the University College London Institute of Education, funded by Economic and Social Research Council Grant ES/M001660/1. Access to these resources was enabled via the 58READIE Project funded by Wellcome Trust and Medical Research Council Grant WT095219MA and G1001799. A full list of the financial, institutional, and personal contributions to the development of the 1958 Birth Cohort Biomedical resource is available at http://www2.le.ac.uk/projects/birthcohort/1958bc/about/contributors-funders. Genotyping was undertaken as part of the Wellcome Trust Case-Control Consortium under Wellcome Trust Award 076113, and a full list of the investigators who contributed to the generation of the data is available at http://www.wtccc.org.uk. Dr. Keers was supported by MRC Population Health Scientist Award MR/K021281/1. We are grateful to the Centre for Longitudinal Studies, Institute of Education, for the use of these data and to the UK Data Service for making them available. However, neither Centre for Longitudinal Studies nor the UK Data Service bears any responsibility for the analysis or interpretation of these data.

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References
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Amato, P. R. (2010). Research on divorce: Continuing trends and new developments. Journal of Marriage and Family, 72, 650666. doi:10.1111/j.1741-3737.2010.00723.x
Amone-P'Olak, K., Burger, H., Ormel, J., Huisman, M., Verhulst, F. C., & Oldehinkel, A. J. (2009). Socioeconomic position and mental health problems in pre- and early-adolescents: The TRAILS study. Social Psychiatry and Psychiatric Epidemiology, 44, 231238. doi:10.1007/s00127-008-0424-z
Amstadter, A. B., Myers, J. M., & Kendler, K. S. (2014). Psychiatric resilience: Longitudinal twin study. British Journal of Psychiatry, 205, 275280. doi:10.1192/bjp.bp.113.130906
Aron, E. N., & Aron, A. (1997). Sensory-processing sensitivity and its relation to introversion and emotionality. Journal of Personality and Social Psychology, 73, 345368.
Aron, E. N., Aron, A., & Jagiellowicz, J. (2012). Sensory processing sensitivity: A review in the light of the evolution of biological responsivity. Personality and Social Psychology Review, 16, 262282. doi:10.1177/1088868311434213
Assary, E., Zavos, H. M., Krapohl, E., Keers, R., & Pluess, M. (2017). Sensitivity to the environment is a heritable personality trait. Manuscript submitted for publication.
Belsky, J. (1997). Variation in susceptibility to rearing influences: An evolutionary argument. Psychological Inquiry, 8, 182186.
Belsky, J. (2005). Differential susceptibility to rearing influences: An evolutionary hypothesis and some evidence. In Ellis, B. & Bjorklund, D. (Eds.), Origins of the social mind: Evolutionary psychology and child development (pp. 139163). New York: Guilford Press.
Belsky, J., Bakermans-Kranenburg, M. J., & van IJzendoorn, M. H. (2007). For better and for worse: Differential susceptibility to environmental influences. Current Directions in Psychological Science, 16, 300304. doi.10.1111/j.1467-8721.2007.00525.x
Belsky, J., & Beaver, K. M. (2011). Cumulative-genetic plasticity, parenting and adolescent self-regulation. Journal of Child Psychology and Psychiatry, and Allied Disciplines, 52, 619626. doi:10.1111/j.1469-7610.2010.02327.x
Belsky, J., & Pluess, M. (2009). Beyond diathesis stress: Differential susceptibility to environmental influences. Psychological Bulletin, 135, 885908. doi:10.1037/a0017376
Belsky, J., & Pluess, M. (2013). Beyond risk, resilience, and dysregulation: Phenotypic plasticity and human development. Development and Psychopathology, 25, 12431261. doi:10.1017/S095457941300059X
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, 12911305. doi:10.1001/jama.299.11.1291
Bogdan, R., Williamson, D. E., & Hariri, A. R. (2012). Mineralocorticoid receptor Iso/Val (rs5522) genotype moderates the association between previous childhood emotional neglect and amygdala reactivity. American Journal of Psychiatry, 169, 515522. doi:10.1176/appi.ajp.2011.11060855
Boyce, W. T., & Ellis, B. J. (2005). Biological sensitivity to context: I. An evolutionary–developmental theory of the origins and functions of stress reactivity. Development and Psychopathology, 17, 271301.
Brett, Z. H., Humphreys, K. L., Smyke, A. T., Gleason, M. M., Nelson, C. A., Zeanah, C. H., … Drury, S. S. (2015). Serotonin transporter linked polymorphic region (5-HTTLPR) genotype moderates the longitudinal impact of early caregiving on externalizing behavior. Development and Psychopathology, 27, 718. doi:10.1017/S0954579414001266
Brown, G. W., Craig, T. K., & Harris, T. O. (2008). Parental maltreatment and proximal risk factors using the Childhood Experience of Care & Abuse (CECA) instrument: A life-course study of adult chronic depression—5. Journal of Affective Disorders, 110, 222233. doi:10.1016/j.jad.2008.01.016
Brown, G. W., & Harris, T. O. (1978). Social origins of depression: A study of psychiatric disorder in women. New York: Free Press.
Caspi, A., Sugden, K., Moffitt, T. E., Taylor, A., Craig, I. W., Harrington, H., … Poulton, R. (2003). Influence of life stress on depression: Moderation by a polymorphism in the 5-HTT gene. Science, 301, 386389. doi:10.1126/science.1083968
Cicchetti, D. (2013). Annual research review: Resilient functioning in maltreated children—Past, present, and future perspectives. Journal of Child Psychology and Psychiatry, 54, 402422. doi:10.1111/j.1469-7610.2012.02608.x
Cicchetti, D., & Rogosch, F. A. (2012). Gene × Environment interaction and resilience: Effects of child maltreatment and serotonin, corticotropin releasing hormone, dopamine, and oxytocin genes. Development and Psychopathology, 24, 411427. doi:10.1017/S0954579412000077
Cicchetti, D., Rogosch, F. A., & Oshri, A. (2011). Interactive effects of corticotropin releasing hormone receptor 1, serotonin transporter linked polymorphic region, and child maltreatment on diurnal cortisol regulation and internalizing symptomatology. Development and Psychopathology, 23, 11251138. doi:10.1017/s0954579411000599
Covault, J., Tennen, H., Armeli, S., Conner, T. S., Herman, A. I., Cillesson, A. H., & Kranzler, H. R. (2007). Interactive effects of the serotonin transporter 5-HTTLPR polymorphism and stressful life events on college student drinking and drug use. Biological Psychiatry, 61, 609616. doi:10.1016/j.biopsych.2006.05.018
Daskalakis, N. P., Bagot, R. C., Parker, K. J., Vinkers, C. H., & de Kloet, E. R. (2013). The three-hit concept of vulnerability and resilience: Toward understanding adaptation to early-life adversity outcome. Psychoneuroendocrinology, 38, 18581873. doi:10.1016/j.psyneuen.2013.06.008
DeYoung, C. G., Cicchetti, D., & Rogosch, F. A. (2011). Moderation of the association between childhood maltreatment and neuroticism by the corticotropin-releasing hormone receptor 1 gene. Journal of Child Psychology and Psychiatry, and Allied Disciplines, 52, 898906. doi:10.1111/j.1469-7610.2011.02404.x
Dougherty, L. R., Klein, D. N., & Davila, J. (2004). A growth curve analysis of the course of dysthymic disorder: The effects of chronic stress and moderation by adverse parent-child relationships and family history. Journal of Consulting and Clinical Psychology, 72, 10121021. doi:10.1037/0022-006X.72.6.1012
Drury, S. S., Gleason, M. M., Theall, K. P., Smyke, A. T., Nelson, C. A., Fox, N. A., & Zeanah, C. H. (2012). Genetic sensitivity to the caregiving context: The influence of 5HTTLPR and BDNF val66met on indiscriminate social behavior. Physiology & Behavior, 106, 728735. doi:10.1016/j.physbeh.2011.11.014
Drury, S. S., Theall, K. P., Smyke, A. T., Keats, B. J., Egger, H. L., Nelson, C. A., … Zeanah, C. H. (2010). Modification of depression by COMT val 158 met polymorphism in children exposed to early severe psychosocial deprivation. Child Abuse and Neglect, 34, 387395. doi:10.1016/j.chiabu.2009.09.021
Eley, T. C., Hudson, J. L., Creswell, C., Tropeano, M., Lester, K. J., Cooper, P., … Collier, D. A. (2012). Therapygenetics: The 5HTTLPR and response to psychological therapy. Molecular Psychiatry, 17, 236241. doi:10.1038/mp.2011.132
Ellis, B. J., & Boyce, W. T. (2008). Biological sensitivity to context. Current Directions in Psychological Science, 17, 183187.
Ellis, B. J., Boyce, W. T., Belsky, J., Bakermans-Kranenburg, M. J., & van IJzendoorn, M. H. (2011). Differential susceptibility to the environment: An evolutionary–neurodevelopmental theory. Development and Psychopathology, 23, 728. doi:10.1017/S0954579410000611
Elovainio, M., Jokela, M., Kivimaki, M., Pulkki-Raback, L., Lehtimaki, T., Airla, N., & Keltikangas-Jarvinen, L. (2007). Genetic variants in the DRD2 gene moderate the relationship between stressful life events and depressive symptoms in adults: Cardiovascular risk in young Finns study. Psychosomatic Medicine, 69, 391395. doi:10.1097/psy.0b013e31806bf365
Fergusson, D. M., Horwood, L. J., Miller, A. L., & Kennedy, M. A. (2011). Life stress, 5-HTTLPR and mental disorder: Findings from a 30-year longitudinal study. British Journal of Psychiatry, 198, 129135. doi:10.1192/bjp.bp.110.085993
Forssman, L., Peltola, M. J., Yrttiaho, S., Puura, K., Mononen, N., Lehtimaki, T., & Leppanen, J. M. (2014). Regulatory variant of the TPH2 gene and early life stress are associated with heightened attention to social signals of fear in infants. Journal of Child Psychology and Psychiatry, and Allied Disciplines, 55, 793801. doi:10.1111/jcpp.12181
Frodl, T., Reinhold, E., Koutsouleris, N., Donohoe, G., Bondy, B., Reiser, M., … Meisenzahl, E. M. (2010). Childhood stress, serotonin transporter gene and brain structures in major depression. Neuropsychopharmacology, 35, 13831390. doi:10.1038/npp.2010.8
Gatt, J. M., Nemeroff, C. B., Dobson-Stone, C., Paul, R. H., Bryant, R. A., Schofield, P. R., … Williams, L. M. (2009). Interactions between BDNF Val66Met polymorphism and early life stress predict brain and arousal pathways to syndromal depression and anxiety. Molecular Psychiatry, 14, 681695. doi:10.1038/mp.2008.143
Grabe, H. J., Schwahn, C., Mahler, J., Schulz, A., Spitzer, C., Fenske, K., … Freyberger, H. J. (2012). Moderation of adult depression by the serotonin transporter promoter variant (5-HTTLPR), childhood abuse and adult traumatic events in a general population sample. American Journal of Medical Genetics, 159 B, 298309. doi:10.1002/ajmg.b.32027
Hammen, C. (2005). Stress and depression. Annual Review of Clinical Psychology, 1, 293319. doi:10.1146/annurev.clinpsy.1.102803.143938
Hammen, C., Henry, R., & Daley, S. E. (2000). Depression and sensitization to stressors among young women as a function of childhood adversity. Journal of Consulting and Clinical Psychology, 68, 782787.
Hankin, B. L., Nederhof, E., Oppenheimer, C. W., Jenness, J., Young, J. F., Abela, J. R. Z., … Oldehinkel, A. J. (2011). Differential susceptibility in youth: Evidence that 5-HTTLPR × Positive Parenting is associated with positive affect “for better and worse.Translational Psychiatry, 1, e44. doi:10.1038/tp.2011.44
Harkness, K. L., Bruce, A. E., & Lumley, M. N. (2006). The role of childhood abuse and neglect in the sensitization to stressful life events in adolescent depression. Journal of Abnormal Psychology, 115, 730741. doi:10.1037/0021-843X.115.4.730
Heim, C., Bradley, B., Mletzko, T. C., Deveau, T. C., Musselman, D. L., Nemeroff, C. B., … Binder, E. B. (2009). Effect of childhood trauma on adult depression and neuroendocrine function: Sex-specific moderation by CRH receptor 1 gene. Frontiers in Behavioral Neuroscience, 3, 41. doi:10.3389/neuro.08.041.2009
Hosang, G. M., Uher, R., Keers, R., Cohen-Woods, S., Craig, I., Korszun, A., … Farmer, A. E. (2010). Stressful life events and the brain-derived neurotrophic factor gene in bipolar disorder. Journal of Affective Disorders, 125, 345349. doi:10.1016/j.jad.2010.01.071
Johansson, A., Bergman, H., Corander, J., Waldman, I. D., Karrani, N., Salo, B., … Westberg, L. (2012). Alcohol and aggressive behavior in men—Moderating effects of oxytocin receptor gene (OXTR) polymorphisms. Genes, Brain and Behavior, 11, 214221. doi:10.1111/j.1601-183X.2011.00744.x
Jokela, M., Keltikangas-Jarvinen, L., Kivimaki, M., Puttonen, S., Elovainio, M., Rontu, R., & Lehtimaki, T. (2007). Serotonin receptor 2A gene and the influence of childhood maternal nurturance on adulthood depressive symptoms. Archives of General Psychiatry, 64, 356360. doi:10.1001/archpsyc.64.3.356
Karg, K., Burmeister, M., Shedden, K., & Sen, S. (2011). The serotonin transporter promoter variant (5-HTTLPR), stress, and depression meta-analysis revisited: Evidence of genetic moderation. Archives of General Psychiatry, 68, 444454. doi:10.1001/archgenpsychiatry.2010.189
Keers, R., Coleman, J. R. I., Lester, K. J., Roberts, S., Breen, G., Thastum, M., … Eley, T. C. (2016). A genome-wide test of the differential susceptibility hypothesis reveals a genetic predictor of differential response to psychological treatments for child anxiety disorders. Psychotherapy and Psychosomatics. Advance online publication. doi:10.1159/000444023
Keltikangas-Jarvinen, L., Puttonen, S., Kivimaki, M., Elovainio, M., Rontu, R., & Lehtimaki, T. (2007). Tryptophan hydroxylase 1 gene haplotypes modify the effect of a hostile childhood environment on adulthood harm avoidance. Genes, Brain and Behavior, 6, 305313. doi:10.1111/j.1601-183X.2006.00255.x
Kendler, K. S., Hettema, J. M., Butera, F., Gardner, C. O., & Prescott, C. A. (2003). Life event dimensions of loss, humiliation, entrapment, and danger in the prediction of onsets of major depression and generalized anxiety. Archives of General Psychiatry, 60, 789796. doi:10.1001/archpsyc.60.8.789
Kendler, K. S., Kuhn, J. W., & Prescott, C. A. (2004). Childhood sexual abuse, stressful life events and risk for major depression in women. Psychological Medicine, 34, 14751482.
Kohen, R., Cain, K. C., Buzaitis, A., Johnson, V., Becker, K. J., Teri, L., … Mitchell, P. H. (2011). Response to psychosocial treatment in poststroke depression is associated with serotonin transporter polymorphisms. Stroke, 42, 20682070.
Kumsta, R., Stevens, S., Brookes, K., Schlotz, W., Castle, J., Beckett, C., … Sonuga-Barke, E. (2010). 5HTT genotype moderates the influence of early institutional deprivation on emotional problems in adolescence: Evidence from the English and Romanian Adoptee (ERA) study. Journal of Child Psychology and Psychiatry, and Allied Disciplines, 51, 755762. doi:10.1111/j.1469-7610.2010.02249.x
Lester, K., Hudson, J. L., Tropeano, M., Creswell, C., Collier, D., Farmer, A., … Eley, T. (2012). Neurotrophic gene polymorphisms and response to psychological therapy. Translational Psychiatry, 2, e108. doi:10.1038/tp.2012.33
McCrory, E., De Brito, S. A., & Viding, E. (2010). Research review: The neurobiology and genetics of maltreatment and adversity. Journal of Child Psychology and Psychiatry, 51, 10791095. doi:10.1111/j.1469-7610.2010.02271.x
McLaughlin, K. A., Conron, K. J., Koenen, K. C., & Gilman, S. E. (2010). Childhood adversity, adult stressful life events, and risk of past-year psychiatric disorder: A test of the stress sensitization hypothesis in a population-based sample of adults. Psychological Medicine, 40, 16471658. doi:10.1017/S0033291709992121
Monroe, S. M., & Simons, A. D. (1991). Diathesis-stress theories in the context of life stress research: Implications for the depressive disorders. Psychological Bulletin, 110, 406.
Munafo, M. R., Durrant, C., Lewis, G., & Flint, J. (2009). Gene × Environment interactions at the serotonin transporter locus. Biological Psychiatry, 65, 211219. doi:10.1016/j.biopsych.2008.06.009
Pluess, M. (2015). Individual differences in environmental sensitivity. Child Development Perspectives, 9, 138143. doi:10.1111/cdep.12120
Pluess, M., & Belsky, J. (2011). Prenatal programming of postnatal plasticity? Development and Psychopathology, 23, 2938. doi:10.1017/S0954579410000623
Pluess, M., & Belsky, J. (2013). Vantage sensitivity: Individual differences in response to positive experiences. Psychological Bulletin, 139, 901916. doi:10.1037/a0030196
Pluess, M., Belsky, J., Way, B. M., & Taylor, S. E. (2010). 5-HTTLPR moderates effects of current life events on neuroticism: Differential susceptibility to environmental influences. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 34, 10701704. doi:10.1016/j.pnpbp.2010.05.028
Pluess, M., Stevens, S., & Belsky, J. (2013). Differential susceptibility: Developmental and evolutionary mechanisms of gene-environment interactions. In Legerstee, M., Haley, D. W., & Bornstein, M. H. (Eds.), The infant mind: Origins of the social brain (pp. 7796). New York: Guilford Press.
Power, C., & Elliott, J. (2006). Cohort profile: 1958 British birth cohort (National Child Development Study). International Journal of Epidemiology, 35, 3441. doi:10.1093/ije/dyi183
Power, R. A., Lecky-Thompson, L., Fisher, H. L., Cohen-Woods, S., Hosang, G. M., Uher, R., … McGuffin, P. (2013). The interaction between child maltreatment, adult stressful life events and the 5-HTTLPR in major depression. Journal of Psychiatric Research, 47, 10321035. doi:10.1016/j.jpsychires.2013.03.017
Risch, N., Herrell, R., Lehner, T., Liang, K.-Y., Eaves, L., Hoh, J., … Merikangas, K. R. (2009). Interaction between the serotonin transporter gene (5-HTTLPR), stressful life events, and risk of depression: A meta-analysis. Journal of the American Medical Association, 301, 24622471.
Rutter, M., Tizard, J., & Whitmore, K. (1970). Malaise Inventory. In Rutter, M., Tizard, J., & Whitmore, K. (Eds.), Education, health and behaviour (pp. 339340). London: Longman.
Shapero, B. G., Black, S. K., Liu, R. T., Klugman, J., Bender, R. E., Abramson, L. Y., & Alloy, L. B. (2014). Stressful life events and depression symptoms: The effect of childhood emotional abuse on stress reactivity. Journal of Clinical Psychology, 70, 209223. doi:10.1002/jclp.22011
Shepherd, P. (2012). 1958 National Child Development Study ethical review and consent. London: Institute of Education.
Slavich, G. M., Thornton, T., Torres, L. D., Monroe, S. M., & Gotlib, I. H. (2009). Targeted rejection predicts hastened onset of major depression. Journal of Social and Clinical Psychology, 28, 223243. doi:10.1521/jscp.2009.28.2.223
Starr, L. R., Hammen, C., Conway, C. C., Raposa, E., & Brennan, P. A. (2014). Sensitizing effect of early adversity on depressive reactions to later proximal stress: Moderation by polymorphisms in serotonin transporter and corticotropin releasing hormone receptor genes in a 20-year longitudinal study. Development and Psychopathology, 26, 12411254. doi:10.1017/S0954579414000996
StataCorp. (2011). Stata statistical software: Release 12. College Station, TX: Author.
Taylor, S. E., Way, B. M., Welch, W. T., Hilmert, C. J., Lehman, B. J., & Eisenberger, N. I. (2006). Early family environment, current adversity, the serotonin transporter promoter polymorphism, and depressive symptomatology. Biological Psychiatry, 60, 671676. doi:10.1016/j.biopsych.2006.04.019
Troisi, A., Frazzetto, G., Carola, V., Di Lorenzo, G., Coviello, M., Siracusano, A., & Gross, C. (2012). Variation in the μ-opioid receptor gene (OPRM1) moderates the influence of early maternal care on fearful attachment. Social Cognitive and Affective Neuroscience, 7, 542547. doi:10.1093/scan/nsr037
Tyrka, A. R., Price, L. H., Gelernter, J., Schepker, C., Anderson, G. M., & Carpenter, L. L. (2009). Interaction of childhood maltreatment with the corticotropin-releasing hormone receptor gene: Effects on hypothalamic-pituitary-adrenal axis reactivity. Biological Psychiatry, 66, 681685. doi:10.1016/j.biopsych.2009.05.012
Uher, R. (2008). The implications of gene-environment interactions in depression: Will cause inform cure? Molecular Psychiatry, 13, 10701078. doi:10.1038/mp.2008.92
Uher, R. (2014). Gene–environment interactions in common mental disorders: An update and strategy for a genome-wide search. Social Psychiatry and Psychiatric Epidemiology, 49, 314. doi:10.1007/s00127-013-0801-0
Uher, R., & McGuffin, P. (2010). The moderation by the serotonin transporter gene of environmental adversity in the etiology of depression: 2009 update. Molecular Psychiatry, 15, 1822. doi:10.1038/mp.2009.123
van IJzendoorn, M. H., & Bakermans-Kranenburg, M. J. (2015). Genetic differential susceptibility on trial: Meta-analytic support from randomized controlled experiments. Development and Psychopathology, 27, 151162. doi:10.1017/S0954579414001369
Zannas, A. S., & Binder, E. B. (2014). Gene-environment interactions at the FKBP5 locus: Sensitive periods, mechanisms and pleiotropism. Genes, Brain and Behavior, 13, 2537. doi:10.1111/gbb.12104
Zuckerman, M. (1999). Diathesis-stress models. In Zuckerman, M. (Ed.), Vulnerability to psychopathology: A biosocial model. Washington, DC: American Psychological Association.
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