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HPA-axis multilocus genetic variation moderates associations between environmental stress and depressive symptoms among adolescents

  • Lisa R. Starr (a1) and Meghan Huang (a1)

Abstract

Research suggests that genetic variants linked to hypothalamic-pituitary-adrenal (HPA)-axis functioning moderate the association between environmental stressors and depression, but examining gene–environment interactions with single polymorphisms limits power. The current study used a multilocus genetic profile score (MGPS) approach to measuring HPA-axis–related genetic variation and examined interactions with acute stress, chronic stress, and childhood adversity (assessed using contextual threat interview methods) with depressive symptoms as outcomes in an adolescent sample (ages 14–17, N = 241; White subsample n = 192). Additive MGPSs were calculated using 10 single nucleotide polymorphisms within HPA-axis genes (CRHR1, NR3C2, NR3C1, FKBP5). Higher MGPS directly correlated with adolescent depressive symptoms. Moreover, MGPS predicted stronger associations between acute and chronic stress and adolescent depressive symptoms and also moderated the effect of interpersonal, but not noninterpersonal, childhood adversity. Gene–environment interactions individually accounted for 5%–8% of depressive symptom variation. All results were retained following multiple test correction and stratification by race. Results suggest that using MGPSs provides substantial power to examine gene–environmental interactions linked to affective outcomes among adolescents.

Copyright

Corresponding author

Author for correspondence: Lisa Starr, Department of Clinical and Social Sciences in Psychology, 491 Meliora Hall, Box 270266, Rochester, NY 14627; E-mail: lisa.starr@rochester.edu.

References

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Aliev, F., Latendresse, S. J., Bacanu, S.-A., Neale, M. C., & Dick, D. M. (2014). Testing for measured gene-environment interaction: Problems with the use of cross-product terms and a regression model reparameterization solution. Behavior Genetics, 44, 165181.
Appel, K., Schwahn, C., Mahler, J., Schulz, A., Spitzer, C., Fenske, K., … Grabe, H. J. (2011). Moderation of adult depression by a polymorphism in the FKBP5 gene and childhood physical abuse in the general population. Neuropsychopharmacology, 36, 19821991. doi: http://www.nature.com/npp/journal/v36/n10/suppinfo/npp201181s1.html
Avenevoli, S., Swendsen, J., He, J. P., Burstein, M., & Merikangas, K. R. (2015). Major depression in the national comorbidity survey-adolescent supplement: Prevalence, correlates, and treatment. Journal of the American Academy of Child and Adolescent Psychiatry, 54, 3744.e32. doi:10.1016/j.jaac.2014.10.010
Belsky, J., Bakermans-Kranenburg, M. J., & van IJzendoorn, M. H. (2007). For better and for worse. Current Directions in Psychological Science, 16, 300304. doi: 10.1111/j.1467-8721.2007.00525.x
Belsky, J., & Pluess, M. (2009). Beyond diathesis stress: Differential susceptibility to environmental influences. Psychological Bulletin, 135, 885.
Benjamini, Y., & Hochberg, Y. (1995). Controlling the false discovery rate: A practical and powerful approach to multiple testing. Journal of the Royal Statistical Society. Series B (Methodological), 289300.
Bogdan, R., Hyde, L. W., & Hariri, A. R. (2013). A neurogenetics approach to understanding individual differences in brain, behavior, and risk for psychopathology. Molecular Psychiatry, 18, 288299. doi:10.1038/mp.2012.35
Bogdan, R., Salmeron, B. J., Carey, C. E., Agrawal, A., Calhoun, V. D., Garavan, H., … Goldman, D. (2017). Imaging genetics and genomics in psychiatry: A critical review of progress and potential. Biological Psychiatry, 82, 165175. doi: https://doi.org/10.1016/j.biopsych.2016.12.030
Boyle, E. A., Li, Y. I., & Pritchard, J. K. (2017). An expanded view of complex traits: From polygenic to omnigenic. Cell, 169, 11771186. doi: https://doi.org/10.1016/j.cell.2017.05.038
Bradley, R. G., Binder, E. B., Epstein, M. P., Tang, Y., Nair, H. P., Liu, W., … Newport, D. J. (2008). Influence of child abuse on adult depression: Moderation by the corticotropin-releasing hormone receptor gene. Archives of General Psychiatry, 65, 190.
Brown, G. W., & Harris, T. (1978). Social Origins of Depression. New York: Free Press.
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 is implications for studying complex diseases and traits. American Journal of Psychiatry, 167, 509527.
Chida, Y., & Steptoe, A. (2009). Cortisol awakening response and psychosocial factors: A systematic review and meta-analysis. Biological Psychology, 80, 265278. doi: 10.1016/j.biopsycho.2008.10.004
Cicchetti, D., & Rogosch, F. A. (2012). Gene by environment interaction and resilience: Effects of child maltreatment and serotonin, corticotropin releasing hormone, dopamine, and oxytocin genes. Dev Psychopathol, 24, 411427. doi:10.1017/S0954579412000077
Colodro-Conde, L., Couvy-Duchesne, B., Zhu, G., Coventry, W. L., Byrne, E. M., Gordon, S., … Martin, N. G. (2017). A direct test of the diathesis–stress model for depression. Molecular Psychiatry, 23, 15901596. doi:10.1038/mp.2017.130 https://www.nature.com/articles/mp2017130#supplementary-information
Condren, R. M., O'Neill, A., Ryan, M. C. M., Barrett, P., & Thakore, J. H. (2002). HPA axis response to a psychological stressor in generalised social phobia. Psychoneuroendocrinology, 27(6), 693703. doi: http://dx.doi.org/10.1016/S0306-4530(01)00070-1
Converge Consortium (2015). Sparse whole genome sequencing identifies two loci for major depressive disorder. Nature, 523, 588591. doi:10.1038/nature14659
Conway, C. C., Hammen, C., Brennan, P. A., Lind, P. A., & Najman, J. M. (2010). Interaction of chronic stress with serotonin transporter and catechol-O-methyltransferase polymorphisms in predicting youth depression. Depression and Anxiety, 27, 737745. doi:10.1002/da.20715
Cross-Disorder Group of the Psychiatric Genomics Consortium. (2013). Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Nature Genetics, 45, 984994. doi:10.1038/ng.2711
Culverhouse, R. C., Saccone, N. L., Horton, A. C., Ma, Y., Anstey, K. J., Banaschewski, T., … Bierut, L. J. (2017). Collaborative meta-analysis finds no evidence of a strong interaction between stress and 5-HTTLPR genotype contributing to the development of depression. Molecular Psychiatry, 23, 133142. doi:10.1038/mp.2017.44
Davis, C., & Loxton, N. J. (2013). Addictive behaviors and addiction-prone personality traits: Associations with a dopamine multilocus genetic profile. Addictive Behaviors, 38, 23062312. doi: https://doi.org/10.1016/j.addbeh.2013.02.012
Davis, C., Loxton, N. J., Levitan, R. D., Kaplan, A. S., Carter, J. C., & Kennedy, J. L. (2013). ‘Food addiction’ and its association with a dopaminergic multilocus genetic profile. Physiology and Behavior, 118, 6369. doi: https://doi.org/10.1016/j.physbeh.2013.05.014
de Kloet, E. R., Joëls, M., & Holsboer, F. (2005). Stress and the brain: From adaptation to disease. Nature Reviews Neuroscience, 6, 463475. doi: 10.1038/nrn1683
de Vries, Y., Roest, A., Franzen, M., Munafò, M., & Bastiaansen, J. (2016). Citation bias and selective focus on positive findings in the literature on the serotonin transporter gene (5-HTTLPR), life stress and depression. Psychological Medicine, 46, 19.
Di Iorio, C. R., Carey, C. E., Michalski, L. J., Corral-Frias, N. S., Conley, E. D., Hariri, A. R., & Bogdan, R. (2017). Hypothalamic-pituitary-adrenal axis genetic variation and early stress moderates amygdala function. Psychoneuroendocrinology, 80, 170178. doi:10.1016/j.psyneuen.2017.03.016
Dick, D. M., Agrawal, A., Keller, M. C., Adkins, A., Aliev, F., Monroe, S., … Sher, K. J. (2015). Candidate gene–environment interaction research. Perspectives on Psychological Science, 10, 3759. doi:10.1177/1745691614556682
Dickerson, S. S., & Kemeny, M. E. (2004). Acute stressors and cortisol responses: A theoretical integration and synthesis of laboratory research. Psychological Bulletin, 130, 355391. doi:10.1037/0033-2909.130.3.355
Duncan, L. E., & Keller, M. C. (2011). A critical review of the first 10 years of candidate gene-by-environment interaction research in psychiatry. The American Journal of Psychiatry, 168, 10411049. doi:10.1176/appi.ajp.2011.11020191
Eaves, L. J., Silberg, J. L., Meyer, J. M., Maes, H. H., Simonoff, E., Pickles, A., … Truett, K. R. (1997). Genetics and developmental psychopathology: 2. The main effects of genes and environment on behavioral problems in the Virginia Twin Study of Adolescent Behavioral Development. Journal of Child Psychology and Psychiatry, 38, 965980.
Feurer, C., McGeary, J. E., Knopik, V. S., Brick, L. A., Palmer, R. H., & Gibb, B. E. (2017). HPA axis multilocus genetic profile score moderates the impact of interpersonal stress on prospective increases in depressive symptoms for offspring of depressed mothers. Journal of Abnormal Psychology, 126, 10171028.
Gunnar, M. R., & Vazquez, D. (2015). Stress neurobiology and developmental psychopathology. In Cichetti, D. and Cohen, D. J. (Eds), Developmental Psychopathology (pp. 533577). Hoboken, NJ: John Wiley & Sons, Inc.
Gunnar, M. R., Wewerka, S., Frenn, K., Long, J. D., & Griggs, C. (2009). Developmental changes in hypothalamus–pituitary–adrenal activity over the transition to adolescence: Normative changes and associations with puberty. Development and Psychopathology, 21, 6985.
Hames, J. L., Hagan, C. R., & Joiner, T. E. (2013). Interpersonal processes in depression. Annual Review of Clinical Psycholology, 9, 355377. doi:10.1146/annurev-clinpsy-050212-185553
Hammen, C. (1991). Generation of stress in the course of unipolar depression. Journal of Abnormal Psychology, 100, 555.
Hammen, C. (2000). Interpersonal factors in an emerging developmental model of depression. In Johnson, S. L., Hayes, A. M., Field, T. M., Schneiderman, N., & McCabe, P. (Eds.), Stress, Coping and Depression (pp. 7188). Mahwah, NJ: Lawrence Erlbaum Associates.
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.
Harkness, K. L., Bagby, R. M., Stewart, J. G., Larocque, C. L., Mazurka, R., Strauss, J. S., … Kennedy, J. L. (2015). Childhood emotional and sexual maltreatment moderate the relation of the serotonin transporter gene to stress generation. Journal of Abnormal Psychology, 124, 275.
Harkness, K. L., & Monroe, S. M. (2016). The assessment and measurement of adult life stress: Basic premises, operational principles, and design requirements. Journal of Abnormal Psychology, 125, 727745. doi:10.1037/abn0000178
Hayes, A. F. (2013). Introduction to Mediation, Moderation, and Conditional Process Analysis: A Regression-Based Approach. New York: Guilford.
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: http://doi.org/10.1016/S0006-3223(01)01157-X
Insel, T., Cuthbert, B., Garvey, M., Heinssen, R., Pine, D. S., Quinn, K., … Wang, P. (2010). Research Domain Criteria (RDoC): Toward a new classification framework for research on mental disorders. American Journal of Psychiatry, 167, 748751.
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
Kaufman, J., Birmaher, B., Brent, D., Rao, U. M. A., Flynn, C., Moreci, P., … Ryan, N. (1997). Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL): Initial reliability and validity data. Journal of the American Academy of Child and Adolescent Psychiatry, 36, 980988. doi: http://dx.doi.org/10.1097/00004583-199707000-00021
Kendler, K. S., Thornton, L. M., & Gardner, C. O. (2001). Genetic risk, number of previous depressive episodes, and stressful life events in predicting onset of major depression. American Journal of Psychiatry, 158, 582586. doi:10.1176/appi.ajp.158.4.582
Liu, Z., Liu, W., Yao, L., Yang, C., Xiao, L., Wan, Q., … Xiao, Z. (2013). Negative life events and corticotropin-releasing-hormone receptor1 gene in recurrent major depressive disorder. Scientific Reports, 3, 1548. doi:10.1038/srep01548
Lubke, G. H., Hottenga, J. J., Walters, R., Laurin, C., de Geus, E. J. C., Willemsen, G., … Boomsma, D. I. (2012). Estimating the genetic variance of major depressive disorder (MDD) due to all SNPs. Biological Psychiatry, 72, 707709. doi:10.1016/j.biopsych.2012.03.011
Lupien, S. J., Ouellet-Morin, I., Hupbach, A., Tu, M. T., Buss, C., Walker, D., … McEwen, B. S. (2006). Beyond the stress concept: Allostatic load--a developmental biological and cognitive perspective. In Cicchetti, D. & Cohen, D. J. (Eds.), Developmental Psychopathology: Developmental Neuroscience (Vol. 2). Hoboken, NJ: John Wiley & Sons Inc.
Major Depressive Disorder Working Group of the Psychiatric GWAS Consortium. (2013). A mega-analysis of genome-wide association studies for major depressive disorder. Molecular Psychiatry, 18, 497511. doi: http://www.nature.com/mp/journal/v18/n4/suppinfo/mp201221s1.html
McBurnett, K., Lahey, B. B., Capasso, L., & Loeber, R. (1996). Aggressive symptoms and salivary cortisol in clinic-referred boys with conduct disorder. Annals of the New York Academy of Sciences, 794, 169178. doi:10.1111/j.1749-6632.1996.tb32519.x
McBurnett, K., Lahey, B. B., Rathouz, P. J., & Loeber, R. (2000). Low salivary cortisol and persistent aggression in boys referred for disruptive behavior. Archives of General Psychiatry, 57, 3843. doi:10.1001/archpsyc.57.1.38
McEwen, B. S. (1998). Stress, adaptation, and disease: Allostasis and allostatic load. Annals of the New York Academy of Sciences, 840, 3344.
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, 2545.
Monroe, S. M., & Reid, M. W. (2008). Gene-environment interactions in depression research: Genetic polymorphisms and life-stress polyprocedures. Psychological Science, 19, 947956. doi:10.1111/j.1467-9280.2008.02181.x
Moss, H. B., Vanyukov, M. M., & Martin, C. S. (1995). Salivary cortisol responses and the risk for substance abuse in prepubertal boys. Biological Psychiatry, 38, 547555. doi:10.1016/0006-3223(94)00382-D
Mullins, N., Perroud, N., Uher, R., Butler, A. W., Cohen-Woods, S., Rivera, M., … Lewis, C. M. (2014). Genetic relationships between suicide attempts, suicidal ideation and major psychiatric disorders: A genome-wide association and polygenic scoring study. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 165, 428437. doi:10.1002/ajmg.b.32247
Munafò, M. R., Freimer, N. B., Ng, W., Ophoff, R., Veijola, J., Miettunen, J., … Flint, J. (2009). 5-HTTLPR genotype and anxiety-related personality traits: A meta-analysis and new data. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 150B, 271281. doi:10.1002/ajmg.b.30808
Musliner, K. L., Seifuddin, F., Judy, J. A., Pirooznia, M., Goes, F. S., & Zandi, P. P. (2015). Polygenic risk, stressful life events and depressive symptoms in older adults: A polygenic score analysis. Psychological Medicine, 45, 17091720. doi:10.1017/S0033291714002839
Nikolova, Y. S., Ferrell, R. E., Manuck, S. B., & Hariri, A. R. (2011). Multilocus genetic profile for dopamine signaling predicts ventral striatum reactivity. Neuropsychopharmacology, 36, 19401947. doi:10.1038/npp.2011.82
Okbay, A., Baselmans, B. M., De Neve, J.-E., Turley, P., Nivard, M. G., Fontana, M. A., … Derringer, J. (2016). Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses. Nature Genetics, 48, 624633.
Pagliaccio, D., Luby, J. L., Bogdan, R., Agrawal, A., Gaffrey, M. S., Belden, A. C., … Barch, D. M. (2014). Stress-system genes and life stress predict cortisol levels and amygdala and hippocampal volumes in children. Neuropsychopharmacology, 39, 12451253. doi:10.1038/npp.2013.327
Pagliaccio, D., Luby, J. L., Bogdan, R., Agrawal, A., Gaffrey, M. S., Belden, A. C., … Barch, D. M. (2015a). Amygdala functional connectivity, HPA axis genetic variation, and life stress in children and relations to anxiety and emotion regulation. Journal of Abnormal Psychology, 124, 817833. doi:10.1037/abn0000094
Pagliaccio, D., Luby, J. L., Bogdan, R., Agrawal, A., Gaffrey, M. S., Belden, A. C., … Barch, D. M. (2015b). HPA axis genetic variation, pubertal status, and sex interact to predict amygdala and hippocampus responses to negative emotional faces in school-age children. NeuroImage, 109, 111. doi: http://dx.doi.org/10.1016/j.neuroimage.2015.01.017
Pariante, C. M., & Lightman, S. L. (2008). The HPA axis in major depression: Classical theories and new developments. Trends in Neurosciences, 31, 464468.
Pearson-Fuhrhop, K. M., Dunn, E. C., Mortero, S., Devan, W. J., Falcone, G. J., Lee, P., … Cramer, S. C. (2014). Dopamine genetic risk score predicts depressive symptoms in healthy adults and adults with depression. PLoS ONE, 9, e93772. doi: 10.1371/journal.pone.0093772
Petersen, A. C., Crockett, L., Richards, M., & Boxer, A. (1988). A self-report measure of pubertal status: Reliability, validity, and initial norms. Journal of Youth and Adolescence, 17, 117133.
Peyrot, W. J., Milaneschi, Y., Abdellaoui, A., Sullivan, P. F., Hottenga, J. J., Boomsma, D. I., & Penninx, B. W. J. H. (2014). Effect of polygenic risk scores on depression in childhood trauma. British Journal of Psychiatry, 205, 113119. doi:10.1192/bjp.bp.113.143081
Polanczyk, G., Caspi, A., Williams, B., Price, T. S., Danese, A., Sugden, K., … Moffit, T. E. (2009). Protective effect of crhr1 gene variants on the development of adult depression following childhood maltreatment: Replication and extension. Archives of General Psychiatry, 66, 978985. doi:10.1001/archgenpsychiatry.2009.114
Popma, A., Doreleijers, T. A., Jansen, L. M., Van Goozen, S. H., Van Engeland, H., & Vermeiren, R. (2007). The diurnal cortisol cycle in delinquent male adolescents and normal controls. Neuropsychopharmacology, 32, 1622.
Rao, U. M. A., Daley, S. E., & Hammen, C. (2000). Relationship between depression and substance use disorders in adolescent women during the transition to adulthood. Journal of the American Academy of Child and Adolescent Psychiatry, 39, 215222. doi: http://dx.doi.org/10.1097/00004583-200002000-00022
Reuter, M., Markett, S., Melchers, M., & Montag, C. (2012). Interaction of the cholinergic system and the hypothalamic-pituitary-adrenal axis as a risk factor for depression: Evidence from a genetic association study. Neuroreport, 23, 717720. doi:10.1097/WNR.0b013e32835671ba
Rice, F., Harold, G. T., & Thapar, A. (2002). Assessing the effects of age, sex and shared environment on the genetic aetiology of depression in childhood and adolescence. Journal of Child Psychology and Psychiatry, 43, 10391051. doi:10.1111/1469-7610.00231
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. The Journal of the American Medical Association, 301, 24622471. doi:10.1001/jama.2009.878
Romeo, R. D. (2013). The teenage brain: The stress response and the adolescent brain. Current Directions in Psychological Science, 22, 140145. doi:10.1177/0963721413475445
Rosmond, R., & Bjorntorp, P. (2000). The hypothalamic-pituitary-adrenal axis activity as a predictor of cardiovascular disease, type 2 diabetes and stroke. Journal of Internal Medicine, 247, 188197.
Rudolph, K. D. (2002). Gender differences in emotional responses to interpersonal stress during adolescence. Journal of Adolescent Health Care, 30, 313.
Rudolph, K. D., Hammen, C., Burge, D., Lindberg, N., Herzberg, D., & Daley, S. E. (2000). Toward an interpersonal life-stress model of depression: the developmental context of stress generation. Developmental Psychopathology, 12, 215234.
Sheets, E. S., & Craighead, W. E. (2014). Comparing chronic interpersonal and noninterpersonal stress domains as predictors of depression recurrence in emerging adults. Behaviour Research and Therapy, 63, 3642.
Sheikh, H. I., Kryski, K. R., Smith, H. J., Hayden, E. P., & Singh, S. M. (2013). Corticotropin-releasing hormone system polymorphisms are associated with children's cortisol reactivity. Neuroscience, 229, 111. doi:10.1016/j.neuroscience.2012.10.056
Shih, J., Eberhart, N., Hammen, C., & Brennan, P. (2006). Differential exposure and reactivity to interpersonal stress predict sex differences in adolescent depression. Journal of Clinical Child & Adolescent Psychology, 35, 103115. doi:10.1207/s15374424jccp3501_9
Sinha, M., Larkin, E. K., Elston, R. C., & Redline, S. (2006). Self-reported race and genetic admixture. New England Journal of Medicine, 354, 421422. doi:10.1056/NEJMc052515
Starr, L. R., Dienes, K. A., Stroud, C. B., Shaw, Z. A., Li, Y. I., Mlawer, F., & Huang, M. (2017). Childhood adversity moderates the influence of proximal episodic stress on the cortisol awakening response and depressive symptoms in adolescents. Development and Psychopathology, 29, 18771893. doi:10.1017/S0954579417001468
Starr, L. R., Hammen, C., Brennan, P. A., & Najman, J. M. (2012). Serotonin transporter gene as a predictor of stress generation in depression. Journal of Abnormal Psychology, 121, 810818. doi:10.1037/a0027952
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.
Steinberg, S. J., & Davila, J. (2008). Romantic functioning and depressive symptoms among early adolescent girls: The moderating role of parental emotional availability. Journal of Clinical Child and Adolescent Psychology, 37, 350362.
Stroud, C. B., Chen, F. R., Doane, L. D., & Granger, D. A. (2016). Individual differences in early adolescents' latent trait cortisol (LTC): Relation to recent acute and chronic stress. Psychoneuroendocrinology, 70, 3846. doi:10.1016/j.psyneuen.2016.04.015
Sullivan, P. F., Daly, M. J., & O'Donovan, M. (2012). Genetic architectures of psychiatric disorders: The emerging picture and its implications. Nature Reviews. Genetics, 13, 537551. doi:10.1038/nrg3240
Szczepankiewicz, A., Leszczynska-Rodziewicz, A., Pawlak, J., Narozna, B., Rajewska-Rager, A., Wilkosc, M., … Twarowska-Hauser, J. (2014). FKBP5 polymorphism is associated with major depression but not with bipolar disorder. Journal of Affective Disorders, 164, 3337. doi:10.1016/j.jad.2014.04.002
Tully, E. C., Iacono, W. G., & McGue, M. (2010). Changes in genetic and environmental influences on the development of nicotine dependence and major depressive disorder from middle adolescence to early adulthood. Development and Psychopathology, 22, 831848. doi: 10.1017/S0954579410000490
Uher, R., Caspi, A., Houts, R., Sugden, K., Williams, B., Poulton, R., & Moffitt, T. E. (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, 5665. doi: http://dx.doi.org/10.1016/j.jad.2011.03.010
Van Den Oord, E. J., & Sullivan, P. F. (2003). False discoveries and models for gene discovery. Trends in Genetics, 19, 537542.
Vinkers, C. H., Joëls, M., Milaneschi, Y., Gerritsen, L., Kahn, R. S., Penninx, B. W. J. H., & Boks, M. P. M. (2015). Mineralocorticoid receptor haplotypes sex-dependently moderate depression susceptibility following childhood maltreatment. Psychoneuroendocrinology, 54, 90102. doi: https://doi.org/10.1016/j.psyneuen.2015.01.018
Vrshek-Schallhorn, S., Mineka, S., Zinbarg, R. E., Craske, M. G., Griffith, J. W., Sutton, J., … Adam, E. K. (2014). Refining the candidate environment: Interpersonal stress, the serotonin transporter polymorphism, and gene-environment interactions in major depression. Clinical Psychological Science, 2, 235248. doi: 10.1177/2167702613499329
Vrshek-Schallhorn, S., Sapuram, V., & Avery, B. (2017). Letter to the Editor: Bias in the measurement of bias. Letter regarding ‘Citation bias and selective focus on positive findings in the literature on the serotonin transporter gene (5-HTTLPR), life stress and depression’. Psychological Medicine, 47, 187.
Vrshek-Schallhorn, S., Stroud, C. B., Mineka, S., Zinbarg, R. E., Adam, E. K., Redei, E. E., … Craske, M. G. (2015). Additive genetic risk from five serotonin system polymorphisms interacts with interpersonal stress to predict depression. Journal of Abnormal Psychology, 124, 776.
Wray, N. R., & Sullivan, P. F. (2018). Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression. Nature Genetics, 50, 668681. doi:10.1038/s41588-018-0090-3
Yehuda, R., Southwick, S. M., Krystal, J. H., Bremner, D., Charney, D. S., & Mason, J. W. (1993). Enhanced suppression of cortisol following dexamethasone administration in posttraumatic stress disorder. American Journal of Psychiatry, 150, 8386. doi:10.1176/ajp.150.1.83
Yehuda, R., Southwick, S. M., Nussbuam, G., Wahby, V., Giller, E. L. Jr., & Mason, J. W. (1990). Low urinary cortisol excretion in patients with posttraumatic stress disorder. The Journal of Nervous and Mental Disease, 178, 366369.
Zalewski, M., Lengua, L. J., Kiff, C. J., & Fisher, P. A. (2012). Understanding the relation of low income to HPA-axis functioning in preschool children: Cumulative family risk and parenting as pathways to disruptions in cortisol. Child Psychiatry and Human Development, 43, 924942. doi:10.1007/s10578-012-0304-3
Zimmermann, P., Brückl, T., Nocon, A., Pfister, H., Binder, E. B., Uhr, M., … Ising, M. (2011). Interaction of FKBP5 gene variants and adverse life events in predicting depression onset: Results from a 10-year prospective community study. American Journal of Psychiatry, 168, 11071116. doi:10.1176/appi.ajp.2011.10111577

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HPA-axis multilocus genetic variation moderates associations between environmental stress and depressive symptoms among adolescents

  • Lisa R. Starr (a1) and Meghan Huang (a1)

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