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The influence of five monoamine genes on trajectories of depressive symptoms across adolescence and young adulthood

  • Daniel E. Adkins (a1), Jonathan K. Daw (a2), Joseph L. McClay (a1) and Edwin J. C. G. van den Oord (a1)

Abstract

The influence of five monoamine candidate genes on depressive symptom trajectories in adolescence and young adulthood were examined in the Add Health genetic sample. Results indicated that, for all respondents, carriers of the dopamine receptor D4 5-repeat allele were characterized by distinct depressive symptom trajectories across adolescence and early adulthood. Similarly, for males, individuals with the monoamine oxidase A 3.5-repeat allele exhibited unique depressive symptom trajectories. Specifically, the trajectories of those with the dopamine receptor D4 5-repeat allele were characterized by rising levels in the transition to adulthood, while their peers were experiencing a normative drop in depressive symptom frequency. Conversely, males with the monoamine oxidase A 3.5-repeat allele were shown to experience increased distress in late adolescence. An empirical method for examining a wide array of allelic combinations was employed, and false discovery rate methods were used to control the risk of false positives due to multiple testing. Special attention was given to thoroughly interrogate the robustness of the putative genetic effects. These results demonstrate the value of combining dynamic developmental perspectives with statistical genetic methods to optimize the search for genetic influences on psychopathology across the life course.

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Corresponding author

Address correspondence and reprint requests to: Daniel E. Adkins, Center for Biomarker Research and Personalized Medicine, Virginia Commonwealth University, McGuire Hall, Room 216A, 1112 East Clay Street, Richmond, VA 23298; E-mail: deadkins@vcu.edu.

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Adkins, D. E., Wang, V., Dupre, M. E., van den Oord, E. J. C. G., & Elder, G. H. (2009). Structure and stress: Trajectories of depression across adolescence and young adulthood. Social Forces, 88, 3160.
Adkins, D. E., Wang, V., & Elder, G. H. (2008). Stress processes and trajectories of depressive symptoms in early life: Gendered development. In Turner, H. A. & Schieman, S. (Eds.), Advances in life course research: Stress processes across the life course (pp. 107134). New York: Elsevier JAI.
Aneshensel, C. S., & Huba, G. J. (1983). Depression, alcohol-use, and smoking over one year—A 4-wave longitudinal causal model. Journal of Abnormal Psychology, 92, 134150.
Anguelova, M., Benkelfat, C., & Turecki, G. (2003). A systematic review of association studies investigating genes coding for serotonin receptors and the serotonin transporter: I. Affective disorders. Molecular Psychiatry, 8, 574591.
Asghari, V., Sanyal, S., Buchwaldt, S., Paterson, A., Jovanovic, V., & Van Tol, H. H. M. (1995). Modulation of intracellular cyclic-AMP levels by different human dopamine D4 receptor variants. Journal of Neurochemistry, 65, 11571165.
Bach, A. W. J., Lan, N. C., Johnson, D. L., Abell, C. W., Bembenek, M. E., Kwan, S. W., et al. (1988). cDNA cloning of human liver monoamine oxidase A and B: Molecular basis of differences in enzymatic properties. Proceedings of the National Academy of Sciences of the United States of America, 85, 49344938.
Barbot, W., Dupressoir, A., Lazar, V., & Heidmann, T. (2002). Epigenetic regulation of an IAP retrotransposon in the aging mouse: Progressive demethylation and de-silencing of the element by its repetitive induction. Nucleic Acids Research, 30, 23652373.
Bergen, S. E., Gardner, C. O., & Kendler, K. S. (2007). Age-related changes in heritability of behavioral phenotypes over adolescence and young adulthood: A meta-analysis. Twin Research and Human Genetics, 10, 423433.
Blazer, D. G., Landerman, L. R., Hays, J. C., Simonsick, E. M., & Saunders, W. B. (1998). Symptoms of depression among community-dwelling elderly African-American and White older adults. Psychological Medicine, 28, 13111320.
Bocchetta, A., Piccardi, M. P., Palmas, M. A., Oi, A., & Del Zompo, M. (1999). Family-based association study between bipolar disorder and DRD2, DRD4, DAT, and SERT in Sardinia. American Journal of Medical Genetics, 88, 522526.
Caspi, A., McClay, J., Moffitt, T. E., Mill, J., Martin, J., Craig, I. W., et al. (2002). Role of genotype in the cycle of violence in maltreated children. Science, 297, 851854.
Caspi, A., Sugden, K., Moffitt, T. E., Taylor, A., Craig, I. W., Harrington, H., et al. (2003). Influence of life stress on depression: Moderation by a polymorphism in the 5-HTT gene. Science, 301, 386389.
Chen, C., Rainnie, D. G., Greene, R. W., & Tonegawa, S. (1994). Abnormal fear response and aggressive behavior in mutant mice deficient for alpha-calcium-calmodulin kinase II. Science, 266, 291294.
Cicchetti, D., & Toth, S. L. (1998). The development of depression in children and adolescents. American Psychologist, 53, 221241.
Colhoun, H. M., McKeigue, P. M., & Smith, G. D. (2003). Problems of reporting genetic associations with complex outcomes. Lancet, 361, 865872.
Costello, E. J., Pine, D. S., Hammen, C., March, J. S., Plotsky, P. M., Weissman, M. A., et al. (2002). Development and natural history of mood disorders. Biological Psychiatry, 52, 529542.
Diggle, P., & Kenward, M. G. (1994). Informative drop-out in longitudinal data-analysis. Applied Statistics—Journal of the Royal Statistical Society Series C, 43, 4993.
Du, L. S., Bakish, D., Ravindran, A., & Hrdina, P. D. (2004). MAO-A gene polymorphisms are associated with major depression and sleep disturbance in males. NeuroReport, 15, 20972101.
Eaves, L., Silberg, J., Foley, D., Bulik, C., Maes, H., Erkanli, A., et al. (2004). Genetic and environmental influences on the relative timing of pubertal change. Twin Research 7, 471481.
Elder, G. H., George, L. K., & Shanahan, M. J. (1996). Psychosocial stress over the life course. In Kaplan, H. B. & Kaplan, B. (Eds.), Psychosocial stress: Perspectives on structure, theory, life course, and methods (pp. 247292). Reading, MA: Academic Press.
Eley, T. C., & Stevenson, J. (1999). Exploring the covariation between anxiety and depression symptoms: A genetic analysis of the effects of age and sex. Journal of Child Psychology and Psychiatry and Allied Disciplines, 40, 12731282.
Elovainio, M., Jokela, M., Kivimaki, M., Pulkki-Raback, L., Lehtimaki, T., Airla, N., et al. (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.
Emilien, G., Maloteaux, J. M., Geurts, M., Hoogenberg, K., & Cragg, S. (1999). Dopamine receptors—Physiological understanding to therapeutic intervention potential. Pharmacology & Therapeutics, 84, 133156.
Ensel, W. (1996). Measuring depression: The CES–D scale. In Lin, N., Dean, A., & Ensel, W. (Eds.), Social support, life events and depression (pp. 5170). Reading, MA: Academic Press.
Fernando, R. L., Nettleton, D., Southey, B. R., Dekkers, J. C. M., Rothschild, M. F., & Soller, M. (2004). Controlling the proportion of false positives in multiple dependent tests. Genetics, 166, 611619.
Fossella, J., Green, A. E., & Fan, J. (2006). Evaluation of a structural polymorphism in the ankyrin repeat and kinase domain containing 1 (ANKK1) gene and the activation of executive attention networks. Cognitive, Affective, & Behavioral Neuroscience, 6, 7178.
Fraga, M. F., Ballestar, E., Paz, M. F., Ropero, S., Setien, F., Ballestart, M. L., et al. (2005). Epigenetic differences arise during the lifetime of monozygotic twins. Proceedings of the National Academy of Sciences of the United States of America, 102, 1060410609.
Freeman, B., Powell, J., Ball, D., Hill, L., Craig, I., & Plomin, R. (1997). DNA by mail: An inexpensive and noninvasive method for collecting DNA samples from widely dispersed populations. Behavior Genetics, 27, 251257.
Ge, X. J., Lorenz, F. O., Conger, R. D., Elder, G. H., & Simons, R. L. (1994). Trajectories of stressful life events and depressive symptoms during adolescence. Developmental Psychology, 30, 467483.
Ge, X. J., Natsuaki, M. N., & Conger, R. D. (2006). Trajectories of depressive symptoms and stressful life events among male and female adolescents in divorced and nondivorced families. Development and Psychopathology, 18, 253273.
Giros, B., Jaber, M., Jones, S. R., Wightman, R. M., & Caron, M. G. (1996). Hyperlocomotion and indifference to cocaine and amphetamine in mice lacking the dopamine transporter. Nature, 379, 606612.
Grant, B. F., & Harford, T. C. (1995). Comorbidity between DSM-IV alcohol-use disorders and major depression—Results of a national survey. Drug and Alcohol Dependence, 39, 197206.
Guo, G., Roettger, M. E., & Cai, T. J. (2008). The integration of genetic propensities into social-control models of delinquency and violence among male youths. American Sociological Review, 73, 543568.
Guo, G., Roettger, M. E., & Shih, J. C. (2007). Contributions of the DAT1 and DRD2 genes to serious and violent delinquency among adolescents and young adults. Human Genetics, 121, 125136.
Haeffel, G. J., Getchell, M., Koposov, R. A., Yrigollen, C. M., DeYoung, C. G., Klinteberg, B.A., et al. (2008). Association between polymorphisms in the dopamine transporter gene and depression—Evidence for a gene–environment interaction in a sample of juvenile detainees. Psychological Science, 19, 6269.
Hankin, B. L., Abramson, L. Y., Moffitt, T. E., Silva, P. A., McGee, R., & Angell, K. E. (1998). Development of depression from preadolescence to young adulthood: Emerging gender differences in a 10-year longitudinal study. Journal of Abnormal Psychology, 107, 128140.
Jansson, M., McCarthy, S., Sullivan, P. F., Dickman, P., Andersson, B., Oreland, L., et al. (2005). MAOA haplotypes associated with thrombocyte-MAO activity. BMC Genetics, 6, 19.
Kelsoe, J. R., Sadovnick, A. D., Kristbjarnarson, H., Bergesch, P., Mroczkowski-Parker, Z., Drennan, M., et al. (1996). Possible locus of bipolar disorder near the dopamine transporter on chromosome 5. American Journal of Medical Genetics, 67, 533540.
Kunugi, H., Ishida, S., Kato, T., Tatsumi, M., Sakai, T., Hattori, M., et al. (1999). A functional polymorphism in the promoter region of monoamine oxidase-A gene and mood disorders. Molecular Psychiatry, 4, 393395.
Lench, N., Stanier, P., & Williamson, R. (1988). Simple non-invasive method to obtain DNA for gene analysis. Lancet, 1, 13561358.
Li, T., Liu, X. H., Sham, P. C., Aitchison, K. J., Cai, G. Q., Arranz, M. J., et al. (1999). Association analysis between dopamine receptor genes and bipolar affective disorder. Psychiatry Research, 86, 193201.
Li, T., Xu, K., Deng, H., Cai, G., Liu, J., Liu, X., et al. (1997). Association analysis of the dopamine D4 gene exon III VNTR and heroin abuse in Chinese subjects. Molecular Psychiatry, 2, 413416.
Lohmueller, K. E., Pearce, C. L., Pike, M., Lander, E. S., & Hirschhorn, J. N. (2003). Meta-analysis of genetic association studies supports a contribution of common variants to susceptibility to common disease. Nature Genetics, 33, 177182.
Lopez, L. S., Croes, E. A., Sayed-Tabatabaei, F. A., Claes, S., Van Broeckhoven, C., & van Duijn, C. M. (2005). The dopamine D4 receptor gene 48-base-pair-repeat polymorphism and mood disorders: A meta-analysis. Biological Psychiatry, 57, 9991003.
Lopez-Leon, S., Janssens, A., Ladd, A., Del-Favero, J., Claes, S. J., Oostra, B. A., et al. (2008). Meta-analyses of genetic studies on major depressive disorder. Molecular Psychiatry, 13, 772785.
Lusher, J. M., Chandler, C., & Ball, D. (2001). Dopamine D4 receptor gene (DRD4) is associated with Novelty Seeking (NS) and substance abuse: The saga continues. Molecular Psychiatry, 6, 497499.
Manki, H., Kanba, S., Muramatsu, T., Higuchi, S., Suzuki, E., Matsushita, S., et al. (1996). Dopamine D2, D3 and D4 receptor and transporter gene polymorphisms and mood disorders. Journal of Affective Disorders, 40, 713.
McClay, J. L., Adkins, D. E., Aberg, K., Stroup, S., Perkins, D. O., Vladimirov, V. I., et al. (2010). Genome-wide pharmacogenomic analysis of response to treatment with antipsychotics. Molecular Psychiatry, 16, 7685.
Meulenbelt, I., Droog, S., Trommelen, G. J. M., Boomsma, D. I., & Slagboom, P. E. (1995). High-yield noninvasive human genomic DNA isolation method for genetic-studies in geographically dispersed families and populations. American Journal of Human Genetics, 57, 12521254.
Meyer-Lindenberg, A., Buckholtz, J. W., Kolachana, B., Hariri, A. R., Pezawas, L., Blasi, G., et al. (2006). Neural mechanisms of genetic risk for impulsivity and violence in humans. Proceedings of the National Academy of Sciences of the United States of America, 103, 62696274.
Muglia, P., Petronis, A., Mundo, E., Lander, S., Cate, T., & Kennedy, J. L. (2002). Dopamine D4 receptor and tyrosine hydroxylase genes in bipolar disorder: Evidence for a role of DRD4. Molecular Psychiatry, 7, 860866.
Muramatsu, T., Higuchi, S., Murayama, M., Matsushita, S., & Hayashida, M. (1996). Association between alcoholism and the dopamine D4 receptor gene. Journal of Medical Genetics, 33, 113115.
Murphy, D. L., Mitchell, P. B., & Potter, W. Z. (1994). Novel pharmacological approaches to the treatment of depression. In Bloom, F. E. & Bloom, D. J. (Eds.), Psychopharmacology. The fourth generation of progress (pp. 11431153). New York: Raven Press.
Natsuaki, M. N., Biehl, M. C., & Ge, X. J. (2009). Trajectories of depressed mood from early adolescence to young adulthood: The effects of pubertal timing and adolescent dating. Journal of Research on Adolescence, 19, 4774.
Nes, R. B., Roysamb, E., Reichborn-Kjennerud, T., Harris, J. R., & Tambs, K. (2007). Symptoms of anxiety and depression in young adults: Genetic and environmental influences on stability and change. Twin Research and Human Genetics, 10, 450461.
Neville, M. J., Johnstone, E. C., & Walton, R. T. (2004). Identification and characterization of ANKK1: A novel kinase gene closely linked to DRD2 on chromosome band 11q23.1. Human Mutation, 23, 540545.
Noble, E. P., Gottschalk, L. A., Fallon, J. H., Ritchie, T. L., & Wu, J. C. (1997). D-2 dopamine receptor polymorphism and brain regional glucose metabolism. American Journal of Medical Genetics, 74, 162166.
Noble, F., & Cox, B. M. (1997). The role of dopaminergic systems in opioid receptor desensitization in nucleus accumbens and caudate putamen of rat after chronic morphine treatment. Journal of Pharmacology and Experimental Therapeutics, 283, 557565.
Oak, J. N., Oldenhof, J., & Van Tol, H. H. M. (2000). The dopamine D-4 receptor: One decade of research. European Journal of Pharmacology, 405, 303327.
Perreira, K. M., Deeb-Sossa, N., Harris, K. M., & Bollen, K. (2005). What are we measuring? An evaluation of the CES-D across race/ethnicity and immigrant generation. Social Forces, 83, 15671601.
Preisig, M., Bellivier, F., Fenton, B. T., Baud, P., Berney, A., Courtet, P., et al. (2000). Association between bipolar disorder and monoamine oxidase A gene polymorphisms: Results of a multicenter study. American Journal of Psychiatry, 157, 948955.
Radloff, L. S. (1977). The Center for Epidemiologic Studies Depression Scale a self report depression scale for research in the general population. Applied Psychological Measurement, 1, 385401.
Radloff, L. S. (1991). The use of the Center for Epidemiologic Studies Depression Scale in adolescents and young-adults. Journal of Youth and Adolescence, 20, 149166.
Reiss, D., & Neiderhiser, J. M. (2000). The interplay of genetic influences and social processes in developmental theory: Specific mechanisms are coming into view. Development and Psychopathology, 12, 357374.
Rutter, M., & Sroufe, L. A. (2000). Developmental psychopathology: Concepts and challenges. Development and Psychopathology, 12, 265296.
Sabatti, C., Service, S., & Freimer, N. (2003). False discovery rate in linkage and association genome screens for complex disorders. Genetics, 164, 829833.
Sabol, S. Z., Hu, S., & Hamer, D. (1998). A functional polymorphism in the monoamine oxidase A gene promoter. Human Genetics, 103, 273279.
Saccone, S. F., Hinrichs, A. L., Saccone, N. L., Chase, G. A., Konvicka, K., Madden, P. A. F., et al. (2007). Cholinergic nicotinic receptor genes implicated in a nicotine dependence association study targeting 348 candidate genes with 3713 SNPs. Human Molecular Genetics, 16, 3649.
Schulze, T. G., Muller, D. J., Krauss, H., Scherk, H., Ohlraun, S., Syagailo, Y. V., et al. (2000). Association between a functional polymorphism in the monoamine oxidase A gene promoter and major depressive disorder. American Journal of Medical Genetics, 96, 801803.
Scourfield, J., Rice, F., Thapar, A., Harold, G. T., Martin, N., & McGuffin, P. (2003). Depressive symptoms in children and adolescents: Changing aetiological influences with development. Journal of Child Psychology and Psychiatry and Allied Disciplines, 44, 968976.
Searle, S. R. (1971). Linear models. New York: Wiley.
Searle, S. R., Casella, G., & McCulloch, C. E. (1992). Variance components. New York: Wiley.
Serretti, A., Cristina, S., Lilli, R., Cusin, C., Lattuada, E., Lorenzi, C., et al. (2002). Family-based association study of 5-HTTLPR, TPH, MAO-A, and DRD4 polymorphisms in mood disorders. American Journal of Medical Genetics, 114, 361369.
Serretti, A., Macciardi, F., Cusin, C., Lattuada, E., Souery, D., Lipp, O., et al. (2000). Linkage of mood disorders with D2, D3 and TH genes: A multicenter study. Journal of Affective Disorders, 58, 5161.
Silberg, J., Pickles, A., Rutter, M., Hewitt, J., Simonoff, E., Maes, H., et al. (1999). The influence of genetic factors and life stress on depression among adolescent girls. Archives of General Psychiatry, 56, 225232.
Silberg, J. L., Rutter, M., & Eaves, L. (2001). Genetic and environmental influences on the temporal association between earlier anxiety and later depression in girls. Biological Psychiatry, 49, 10401049.
Sroufe, L. A., & Rutter, M. (1984). The domain of developmental psychopathology. Child Development, 55, 1729.
Storch, A., Ludolph, A. C., & Schwarz, J. (2004). Dopamine transporter: Involvement in selective dopaminergic neurotoxicity and degeneration. Journal of Neural Transmission, 111, 12671286.
Storey, J. D., & Tibshirani, R. (2003). Statistical significance for genomewide studies. Proceedings of the National Academy of Sciences of the United States of America, 100, 94409445.
Sullivan, P. F., Neale, M. C., & Kendler, K. S. (2000). Genetic epidemiology of major depression: Review and meta-analysis. American Journal of Psychiatry, 157, 15521562.
Surtees, P. G., Wainwright, N. W. J., Willis-Owen, S. A. G., Luben, R., Day, N. E., & Flint, J. (2006). Social adversity, the serotonin transporter (5-HTTLPR) polymorphism and major depressive disorder. Biological Psychiatry, 59, 224229.
Thompson, J., Thomas, N., Singleton, A., Piggott, M., Lloyd, S., Perry, E. K., et al. (1997). D2 dopamine receptor gene (DRD2) Taq1 A polymorphism: reduced dopamine D2 receptor binding in the human striatum associated with the A1 allele. Pharmacogenetics, 7, 479484.
Turner, R., & Wheaton, B. (1995). Checklist measures of stressful life events. In Cohen, S., Kessler, R. C., & Gordon, L. U. (Eds.), Measuring stress: A guide for health and social scientists (pp. 29–58). New York: Oxford University Press.
Vandenbergh, D. J., Persico, A. M., Hawkins, A. L., Griffin, C. A., Li, X., Jabs, E. W., et al. (1992). Human dopamine transporter gene (Dat1) maps to chromosome-5p15.3 and displays a VNTR. Genomics, 14, 11041106.
van den Oord, E. J. C. G. (2005). Controlling false discoveries in candidate gene studies. Molecular Psychiatry, 10, 230231.
van den Oord, E. J. C. G. (2008). Controlling false discoveries in genetic studies. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics147B, 637644.
van den Oord, E. J. C. G., Kuo, P. H., Hartmann, A. M., Webb, B. T., Moller, H. J., Hettema, J. M., et al. (2008). Genomewide association analysis followed by a replication study implicates a novel candidate gene for neuroticism. Archives of General Psychiatry, 65, 10621071.
van den Oord, E. J. C. G., & Sullivan, P. F. (2003). False discoveries and models for gene discovery. Trends in Genetics, 19, 537542.
Van Tol, H. H. M., Wu, C. M., Guan, H. C., Ohara, K., Bunzow, J. R., Civelli, O., et al. (1992). Multiple dopamine-D4 receptor variants in the human-population. Nature, 358, 149152.
Wade, T. J., Cairney, J., & Pevalin, D. J. (2002). Emergence of gender differences in depression during adolescence: National panel results from three countries. Journal of the American Academy of Child & Adolescent Psychiatry 41, 190198.
Waldman, I. D., Robinson, B. F., & Feigon, S. A. (1997). Linkage disequilibrium between the dopamine transporter gene (DAT1) and bipolar disorder: Extending the Transmission Disequilibrium Test (TDT) to examine genetic heterogeneity. Genetic Epidemiology, 14, 699704.
Whitelaw, N. C., & Whitelaw, E. (2006). How lifetimes shape epigenotype within and across generations. Human Molecular Genetics, 15, R131R137.
Wight, R. G., Sepulveda, J. E., & Aneshensel, C. S. (2004). Depressive symptoms: How do adolescents compare with adults? Journal of Adolescent Health, 34, 314323.
Wilhelm, K., Mitchell, P. B., Niven, H., Finch, A., Wedgwood, L., Scimone, A., et al. (2006). Life events, first depression onset and the serotonin transporter gene. British Journal of Psychiatry, 188, 210215.
Willett, J. B., Singer, J. D., & Martin, N. C. (1998). The design and analysis of longitudinal studies of development and psychopathology in context: Statistical models and methodological recommendations. Development and Psychopathology, 10, 395426.
Yu, Y. W. Y., Tsai, S. J., Hong, C. J., Chen, T. J., Chen, M. C., & Yang, C. W. (2005). Association study of a monoamine oxidase A gene promoter polymorphism with major depressive disorder and antidepressant response. Neuropsychopharmacology, 30, 17191723.
Zahn-Waxler, C., Klimes-Dougan, B., & Slattery, M. J. (2000). Internalizing problems of childhood and adolescence: Prospects, pitfalls, and progress in understanding the development of anxiety and depression. Development and Psychopathology, 12, 443466.

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The influence of five monoamine genes on trajectories of depressive symptoms across adolescence and young adulthood

  • Daniel E. Adkins (a1), Jonathan K. Daw (a2), Joseph L. McClay (a1) and Edwin J. C. G. van den Oord (a1)

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