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Differential susceptibility in longitudinal models of gene–environment interaction for adolescent depression

Published online by Cambridge University Press:  08 November 2013

James J. Li ,
Michele S. Berk  and
Steve S. Lee
James J. Li
Affiliation:
University of California, Los Angeles
Michele S. Berk
Affiliation:
University of California, Los Angeles Harbor–UCLA Medical Center
Steve S. Lee*
Affiliation:
University of California, Los Angeles
*
Address correspondence and reprint requests to: Steve S. Lee, Department of Psychology, University of California, Los Angeles, 1285 Franz Hall, Box 951563, Los Angeles, CA 90095-1563; E-mail: [email protected].
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Abstract

Although family support reliably predicts the development of adolescent depression and suicidal behaviors, relatively little is known about the interplay of family support with potential genetic factors. We tested the association of the 44 base pair polymorphism in the serotonin transporter linked promoter region gene (5-HTTLPR), family support (i.e., cohesion, communication, and warmth), and their interaction with self-reported depression symptoms and risk for suicide in 1,030 Caucasian adolescents and young adults from the National Longitudinal Study of Adolescent Health. High-quality family support predicted fewer symptoms of depression and reduced risk for suicidality. There was also a significant interaction between 5-HTTLPR and family support for boys and a marginally significant interaction for girls. Among boys with poor family support, youth with at least one short allele had more symptoms of depression and a higher risk for suicide attempts relative to boys homozygous for the long allele. However, in the presence of high family support, boys with the short allele had the fewest depression symptoms (but not suicide attempts). Results suggest that the short allele may increase reactivity to both negative and positive family influences in the development of depression. We discuss the potential role of interactive exchanges between family support and offspring genotype in the development of adolescent depression and suicidal behaviors.

Type
Regular Articles
Information
Development and Psychopathology , Volume 25 , Issue 4pt1 , November 2013 , pp. 991 - 1003
Copyright
Copyright © Cambridge University Press 2013 

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References

Ansorge, M. S., Zhou, M., Lira, A., Hen, R., & Gingrich, J. A. (2004). Early-life blockade of the 5-HT transporter alters emotional behavior in adult mice. Science, 306, 879–881.CrossRefGoogle ScholarPubMed
Åslund, C., Leppert, J., Comasco, E., Nordquist, N., Oreland, L., & Nilsson, K. W. (2009). Impact of the interaction between the 5HTTLPR polymorphism and maltreatment on adolescent depression: A population-based study. Behavior Genetics, 39, 524–531.Google Scholar
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, 300–304.Google Scholar
Belsky, J., & Pluess, M. (2009). Beyond diathesis stress: Differential susceptibility to environmental influences. Psychological Bulletin, 135, 885–908.Google Scholar
Birmaher, B., Ryan, N. D., Williamson, D. E., Brent, D. A., Kaufman, J., Dahl, R. E., et al. (1996). Childhood and adolescent depression: A review of the past 10 years. Part I. Journal of the American Academy of Child & Adolescent Psychiatry, 35, 1427–1439.CrossRefGoogle ScholarPubMed
Booij, L., Benkelfat, C., Leyton, M., Vitaro, F., Gravel, P., Lévesque, M. L., et al. (2012). Perinatal effects on in vivo measures of human brain serotonin synthesis in adulthood: A 27-year longitudinal study. European Neuropsychopharmacology, 22, 419–423.Google Scholar
Borowsky, I. W., Ireland, M., & Resnick, M. D. (2001). Adolescent suicide attempts: Risks and protectors. Pediatrics, 107, 485–493.Google Scholar
Bouma, E., Ormel, J., Verhulst, F. C., & Oldehinkel, A. J. (2008). Stressful life events and depressive problems in early adolescent boys and girls: The influence of parental depression, temperament and family environment. Journal of Affective Disorders, 105, 185–193.Google Scholar
Branchi, I. (2011). The double-edged sword of neural plasticity: Increasing serotonin levels leads to both greater vulnerability to depression and improved capacity to recover. Psychoneuroendocrinology, 36, 339–351.CrossRefGoogle ScholarPubMed
Brent, D., Perper, J., Moritz, G., Liotus, L., Schweers, J., Balach, L., et al. (1994). Familial risk factors for adolescent suicide: A case control study. Acta Psychiatrica Scandinavica, 89, 52–58.CrossRefGoogle ScholarPubMed
Bridge, J. A., Goldstein, T. R., & Brent, D. A. (2006). Adolescent suicide and suicidal behavior. Journal of Child Psychology and Psychiatry, 47, 372–394.CrossRefGoogle ScholarPubMed
Brown, G. W., & Harris, T. O. (2008). Depression and the serotonin transporter 5-HTTLPR polymorphism: A review and a hypothesis concerning gene–environment interaction. Journal of Affective Disorders, 111, 1–12.Google Scholar
Caspi, A., Hariri, A. R., Holmes, A., Uher, R., & Moffitt, T. E. (2010). Genetic sensitivity to the environment: The case of the serotonin transporter gene and its implications for studying complex diseases and traits. American Journal of Psychiatry, 165, 398–416.Google Scholar
Caspi, A., Sugden, K., Moffitt, T. E., Taylor, A., Craig, I. W., Harrington, H. L., et al. (2003). Influence of life stress on depression: Moderation by a polymorphism in the 5-HTT gene. Science, 301, 386–389.Google Scholar
Clarke, G. M., & Cardon, L. R. (2010). Aspects of observing and claiming allele flips in association studies. Genetic Epidemiology, 34, 266–274.Google Scholar
Collishaw, S., Maughan, B., Goodman, R., & Pickles, A. (2004). Time trends in adolescent mental health. Journal of Child Psychology and Psychiatry, 45, 1350–1362.Google Scholar
Côté, S. M., Boivin, M., Liu, X., Nagin, D. S., Zoccolillo, M., & Tremblay, R. E. (2009). Depression and anxiety symptoms: Onset, developmental course and risk factors during early childhood. Journal of Child Psychology and Psychiatry, 50, 1201–1208.Google Scholar
Cumsille, P. E., & Epstein, N. (1994). Family cohesion, family adaptibility, social support, and adolescent depressive symptoms in outpatient clinic families. Journal of Family Psychology, 8, 202–214.Google Scholar
Cyranowski, J. M., Frank, E., Young, E., & Shear, M. K. (2000). Adolescent onset of the gender difference in lifetime rates of major depression: A theoretical model. Archives of General Psychiatry, 57, 21–27.Google Scholar
Daley, S. E., Hammen, C., Burge, D., Davila, J., Paley, B., Lindberg, N., et al. (1997). Predictors of the generation of episodic stress: A longitudinal study of late adolescent women. Journal of Abnormal Psychology, 106, 251–259.CrossRefGoogle Scholar
Dannlowski, U., Ohrmann, P., Bauer, J., Deckert, J., Hohoff, C., Kugel, H., et al. (2007). 5-HTTLPR biases amygdala activity in response to masked facial expressions in major depression. Neuropsychopharmacology, 33, 418–424.Google Scholar
David-Ferdon, C., & Kaslow, N. (2008). Evidence-based psychosocial treatments for child and adolescent depression. Journal of Clinical Child and Adolescent Psychology, 37, 62–104.CrossRefGoogle ScholarPubMed
Diamond, G. S., Wintersteen, M. B., Brown, G. K., Diamond, G. M., Gallop, R., Shelef, K., et al. (2010). Attachment-based family therapy for adolescents with suicidal ideation: A randomized controlled trial. Journal of the American Academy of Child & Adolescent Psychiatry, 49, 122–131.Google Scholar
Duberstein, P. R., Conwell, Y., Conner, K. R., Eberly, S., & Caine, E. D. (2004). Suicide at 50 years of age and older: Perceived physical illness, family discord and financial strain. Psychological Medicine, 34, 137–146.Google Scholar
Eley, T. C., Sugden, K., Corsico, A., Gregory, A. M., Sham, P., McGuffin, P., et al. (2004). Gene–environment interaction analysis of serotonin system markers with adolescent depression. Molecular Psychiatry, 9, 908–915.Google Scholar
Essex, M. J., Klein, M. H., Miech, R., & Smider, N. A. (2001). Timing of initial exposure to maternal major depression and children's mental health symptoms in kindergarten. British Journal of Psychiatry, 179, 151–156.Google Scholar
Furman, D. J., Hamilton, J. P., Joormann, J., & Gotlib, I. H. (2011). Altered timing of amygdala activation during sad mood elaboration as a function of 5-HTTLPR. Social Cognitive and Affective Neuroscience, 6, 270–276.CrossRefGoogle ScholarPubMed
Garavan, H., Pendergrass, J. C., Ross, T. J., Stein, E. A., & Risinger, R. C. (2001). Amygdala response to both positively and negatively valenced stimuli. NeuroReport, 12, 2779–2783.Google Scholar
Ge, X., Natsuaki, M., & Conger, R. (2006). Trajectories of depressive symptoms and stressful life events among male and female adolescents in divorced and nondivorced families. Development and Psychopathology, 18, 253–273.Google Scholar
Gelernter, J., Cubells, J., Kidd, J., Pakstis, A., & Kidd, K. (1999). Population studies of polymorphisms of the serotonin transporter protein gene. American Journal of Medical Genetics—Neuropsychiatric Genetics, 88, 61–66.Google Scholar
Gibb, B. E., Uhrlass, D. J., Grassia, M., Benas, J. S., & McGeary, J. (2009). Children's inferential styles, 5-HTTLPR genotype, and maternal expressed emotion–criticism: An integrated model for the intergenerational transmission of depression. Journal of Abnormal Psychology, 118, 734–745.Google Scholar
Grunbaum, J. A., Kann, L., Kinchen, S., Ross, J., Hawkins, J., Lowry, R., et al. (2004). Youth risk behavior surveillance—United States, 2003. Morbidity and Mortality Weekly Report. Surveillance Summaries, 53, 1–96.Google Scholar
Hamann, S., & Mao, H. (2002). Positive and negative emotional verbal stimuli elicit activity in the left amygdala. Neuroreport, 13, 15–19.Google Scholar
Hammen, C. (2005). Stress and depression. Annual Review of Clinical Psychology, 1, 293–319.Google Scholar
Hammen, C., Brennan, P. A., Keenan Miller, D., Hazel, N. A., & Najman, J. M. (2010). Chronic and acute stress, gender, and serotonin transporter gene-environment interactions predicting depression symptoms in youth. Journal of Child Psychology and Psychiatry, 51, 180–187.Google Scholar
Hariri, A. R., Mattay, V. S., Tessitore, A., Kolachana, B., Fera, F., Goldman, D., et al. (2002). Serotonin transporter genetic variation and the response of the human amygdala. Science, 297, 400–403.Google Scholar
Harris, K. M. (2008). The National Longitudinal Study of Adolescent Health (Add Health), Waves I & II, 1994–1996; Wave III, 2001–2002 [Computer data file and documentation]. Chapel Hill, NC: University of North Carolina at Chapel Hill, Carolina Population Center.Google Scholar
Harris, T. L., & Molock, S. D. (2000). Cultural orientation, family cohesion, and family support in suicide ideation and depression among African American college students. Suicide and Life-Threatening Behavior, 30, 341–353.Google Scholar
Heils, A., Teufel, A., Petri, S., Stöber, G., Riederer, P., Bengel, D., et al. (1996). Allelic variation of human serotonin transporter gene expression. Journal of Neurochemistry, 66, 2621–2624.Google Scholar
Holroyd, C. B., & Coles, M. G. H. (2002). The neural basis of human error processing: Reinforcement learning, dopamine, and the error-related negativity. Psychological Review, 109, 679–708.Google Scholar
Hu, X. Z., Lipsky, R. H., Zhu, G., Akhtar, L. A., Taubman, J., Greenberg, B. D., et al. (2006). Serotonin transporter promoter gain-of-function genotypes are linked to obsessive-compulsive disorder. American Journal of Human Genetics, 78, 815–826.Google Scholar
Jaffee, S., & Price, T. (2007). Gene–environment correlations: A review of the evidence and implications for prevention of mental illness. Molecular Psychiatry, 12, 432–442.Google Scholar
Kann, L. (2001). The youth risk behavior surveillance system: Measuring health-risk behaviors. American Journal of Health Behaviour, 25, 272–277.Google Scholar
Kaufman, J., Yang, B. Z., Douglas-Palumberi, H., Houshyar, S., Lipschitz, D., Krystal, J. H., et al. (2004). Social supports and serotonin transporter gene moderate depression in maltreated children. Proceedings of the National Academy of Sciences, 101, 17316–17321.Google Scholar
Keenan-Miller, D., Hammen, C. L., & Brennan, P. A. (2007). Health outcomes related to early adolescent depression. Journal of Adolescent Health, 41, 256–262.Google Scholar
Lahey, B. B., Rathouz, P. J., Lee, S. S., Chronis-Tuscano, A., Pelham, W. E., Waldman, I. D., et al. (2011). Interactions between early parenting and a polymorphism of the child's dopamine transporter gene in predicting future child conduct disorder symptoms. Journal of Abnormal Psychology, 120, 33–45.Google Scholar
LeDoux, J. E. (2000). Emotion circuits in the brain. Annual Review Neuroscience, 23, 155–184.Google Scholar
Lee, M. T. Y., Wong, B. P., Chow, B. W. Y., & McBride Chang, C. (2006). Predictors of suicide ideation and depression in Hong Kong adolescents: Perceptions of academic and family climates. Suicide and Life-Threatening Behavior, 36, 82–96.Google Scholar
Lesch, K. P., Bengel, D., Heils, A., Sabol, S. Z., Greenberg, B. D., Petri, S., et al. (1996). Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science, 274, 1527–1531.Google Scholar
Lesch, K. P., & Schmitt, A. (2002). Antidepressants and gene expression profiling: How to SNARE novel drug targets. Journal of Pharmacogenomics, 2, 346–348.Google Scholar
Levinson, D. F. (2006). The genetics of depression: A review. Biological Psychiatry, 60, 84–92.Google Scholar
Lewinsohn, P. M., Rohde, P., & Seeley, J. R. (1996). Adolescent suicidal ideation and attempts: Prevalence, risk factors, and clinical implications. Clinical Psychology: Science and Practice, 3, 25–46.Google Scholar
Lopez, A. D., & Murray, C. (1998). The global burden of disease, 1990–2020. Nature Medicine, 4, 1241–1243.Google Scholar
Luine, V., Beck, K., Bowman, R., Frankfurt, M., & Maclusky, N. (2007). Chronic stress and neural function: Accounting for sex and age. Journal of Neuroendocrinology, 19, 743–751.Google Scholar
Mann, J. J., Huang, Y., Underwood, M. D., Kassir, S. A., Oppenheim, S., Kelly, T. M., et al. (2000). A serotonin transporter gene promoter polymorphism (5-HTTLPR) and prefrontal cortical binding in major depression and suicide. Archives of General Psychiatry, 57, 729–738.Google Scholar
Mannuzza, S., Klein, R. G., Klein, D. F., Bessler, A., & Shrout, P. (2002). Accuracy of adult recall of childhood attention deficit hyperactivity disorder. American Journal of Psychiatry, 159, 1882–1888.CrossRefGoogle ScholarPubMed
Matlin, S. L., Molock, S. D., & Tebes, J. K. (2011). Suicidality and depression among African American adolescents: The role of family and peer support and community connectedness. American Journal of Orthopsychiatry, 81, 108–117.Google Scholar
Matthews, K. A., Gump, B. B., & Owens, J. F. (2001). Chronic stress influences cardiovascular and neuroendocrine responses during acute stress and recovery, especially in men. Health Psychology, 20, 403–410.Google Scholar
Miller, G. E., Chen, E., & Zhou, E. S. (2007). If it goes up, must it come down? Chronic stress and the hypothalamic-pituitary-adrenocortical axis in humans. Psychological Bulletin, 133, 25–45.Google Scholar
Mirenowicz, J., & Schultz, W. (1996). Preferential activation of midbrain dopamine neurons by appetitive rather than aversive stimuli. Nature, 379, 449–451.Google Scholar
Moffitt, T. E. (2005). The new look of behavioral genetics in developmental psychopathology: Gene–environment interplay in antisocial behaviors. Psychological Bulletin, 131, 533–554.Google Scholar
Murphy, D. L., & Lesch, K. P. (2008). Targeting the murine serotonin transporter: Insights into human neurobiology. Nature Reviews Neuroscience, 9, 85–96.Google Scholar
Paton, J. J., Belova, M. A., Morrison, S. E., & Salzman, C. D. (2006). The primate amygdala represents the positive and negative value of visual stimuli during learning. Nature, 439, 865–870.Google Scholar
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, 1070–1074.Google Scholar
Radloff, L. S. (1977). The CES-D Scale: A self-report depression scale for research in the general. Applied Psychological Measurement, 1, 385–401.Google Scholar
Resnick, M. D., Bearman, P. S., Blum, R. W., Bauman, K. E., Harris, K. M., Jones, J., et al. (1997). Protecting adolescents from harm. Journal of the American Medical Association, 278, 823–832.Google Scholar
Rudolph, K. D., & Hammen, C. (1999). Age and gender as determinants of stress exposure, generation, and reactions in youngsters: A transactional perspective. Child Development, 70, 660–677.Google Scholar
Rueger, S. Y., Malecki, C. K., & Demaray, M. K. (2008). Gender differences in the relationship between perceived social support and student adjustment during early adolescence. School Psychology Quarterly, 23, 496–514.Google Scholar
Serretti, A., Kato, M., De Ronchi, D., & Kinoshita, T. (2006). Meta-analysis of serotonin transporter gene promoter polymorphism (5-HTTLPR) association with selective serotonin reuptake inhibitor efficacy in depressed patients. Molecular Psychiatry, 12, 247–257.Google Scholar
Shafer, A. B. (2006). Meta analysis of the factor structures of four depression questionnaires: Beck, CES D, Hamilton, and Zung. Journal of Clinical Psychology, 62, 123–146.Google Scholar
Shahar, G., Cohen, G., Grogan, K. E., Barile, J. P., & Henrich, C. C. (2009). Terrorism-related perceived stress, adolescent depression, and social support from friends. Pediatrics, 124, e235–e240.Google Scholar
Sheeber, L., Hops, H., Alpert, A., Davis, B., & Andrews, J. (1997). Family support and conflict: Prospective relations to adolescent depression. Journal of Abnormal Child Psychology, 25, 333–344.Google Scholar
Sheeber, L., Hops, H., & Davis, B. (2001). Family processes in adolescent depression. Clinical Child and Family Psychology Review, 4, 19–35.Google Scholar
Shih, J. H., Eberhart, N. K., Hammen, C. L., & Brennan, P. A. (2006). Differential exposure and reactivity to interpersonal stress predict sex differences in adolescent depression. Journal of Clinical Child and Adolescent Psychology, 35, 103–115.Google Scholar
Shors, T. J. (2004). Learning during stressful times. Learning and Memory, 11, 137–144.Google Scholar
Silverberg, S. B., & Steinberg, L. (1987). Adolescent autonomy, parent–adolescent conflict, and parental well-being. Journal of Youth and Adolescence, 16, 293–312.Google Scholar
Staley, J. K., Sanacora, G., Tamagnan, G., Maciejewski, P. K., Malison, R. T., Berman, R. M., et al. (2006). Sex differences in diencephalon serotonin transporter availability in major depression. Biological Psychiatry, 59, 40–47.Google Scholar
Stockmeier, C. A. (2003). Involvement of serotonin in depression: Evidence from postmortem and imaging studies of serotonin receptors and the serotonin transporter. Journal of Psychiatric Research, 37, 357–373.Google Scholar
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, 671–676.Google Scholar
Uher, R., Caspi, A., Houts, R., Sugden, K., Williams, B., Poulton, R., et al. (2011). Serotonin transporter gene moderates childhood maltreatment's effects on persistent but not single-episode depression: Replications and implications for resolving inconsistent results. Journal of Affective Disorders, 135, 56–65.Google Scholar
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, 18–22.Google Scholar
Weisz, J. R., McCarty, C. A., & Valeri, S. M. (2006). Effects of psychotherapy for depression in children and adolescents: A meta-analysis. Psychological Bulletin, 132, 132–149.Google Scholar
Wender, P. H., Kety, S. S., Rosenthal, D., & Schulsinger, F. (1986). Psychiatric disorders in the biological and adoptive families of adopted individuals with affective disorders. Archives of General Psychiatry, 43, 923–929.Google Scholar
Whittington, C. J., Kendall, T., Fonagy, P., Cottrell, D., Cotgrove, A., & Boddington, E. (2004). Selective serotonin reuptake inhibitors in childhood depression: Systematic review of published versus unpublished data. Lancet, 363, 1341–1345.Google Scholar
Yap, M. B. H., Whittle, S., Yucel, M., Sheeber, L., Pantelis, C., Simmons, J. G., et al. (2008). Interaction of parenting experiences and brain structure in the prediction of depressive symptoms in adolescents. Archives of General Psychiatry, 65, 1377–1385.Google Scholar
Young, A. F., Powers, J. R., & Bell, S. L. (2006). Attrition in longitudinal studies: Who do you lose? Australian and New Zealand Journal of Public Health, 30, 353–361.Google Scholar
Zammit, S., & Owen, M. J. (2006). Stressful life events, 5-HTT genotype and risk of depression. British Journal of Psychiatry, 188, 199–201.Google Scholar
Zeger, S. L., Liang, K. Y., & Albert, P. S. (1988). Models for longitudinal data: A generalized estimating equation approach. Biometrics, 44, 1049–1060.Google Scholar