Gene–environment interactions predict cortisol responses after acute stress: implications for the etiology of depression

Alexander, Nina; Kuepper, Yvonne; Schmitz, Anja; Osinsky, Roman; Kozyra, Eva; Hennig, Juergen

doi:10.1016/j.psyneuen.2009.03.017

Cited by 171Stress Responses and CortisolNeurotransmitter Receptor Influence on BehaviorGenetic Associations and Epidemiology

Gene–environment interactions predict cortisol responses after acute stress: implications for the etiology of depression

Alexander, Nina, Kuepper, Yvonne, Schmitz, Anja, Osinsky, Roman, Kozyra, Eva, Hennig, Juergen·2009·Psychoneuroendocrinology

DOI 10.1016/j.psyneuen.2009.03.017

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Abstract

Background Growing evidence suggests that the serotonin transporter polymorphism (5-HTTLPR) interacts with adverse environmental influences to produce an increased risk for the development of depression while the underlying mechanisms of this association remain largely unexplored. As one potential intermediate phenotype, we investigated alterations of hypothalamic-pituitary-adrenal (HPA) axis responses to stress in individuals with no history of psychopathology depending on both 5-HTTLPR and stressful life events.Methods Healthy male adults (N=100) were genotyped and completed a questionnaire on severe stressful life events (Life Events Checklist). To test for gene-by-environment interactions on endocrine stress reactivity, subjects were exposed to a standardized laboratory stress task (Public Speaking). Saliva cortisol levels were obtained at 6 time points prior to the stressor and during an extended recovery period.Results Subjects homozygous for the s-allele with a significant history of stressful life events exhibited markedly elevated cortisol secretions in response to the stressor compared to all other groups, indicating a significant gene-by-environment interaction on endocrine stress reactivity. No main effect of either 5-HTTLPR (biallelic and triallelic) or stressful life events on cortisol secretion patterns appeared.Conclusion This is the first study reporting that 5-HTTLPR and stressful life events interact to predict endocrine stress reactivity in a non-clinical sample. Our results underpin the potential moderating role of HPA-axis hyper-reactivity as a premorbid risk factor to increase the vulnerability for depression in subjects with low serotonin transporter efficiency and a history of severe life events.

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The s′ allele of 5-HTTLPR has been associated with an exaggerated cortisol response to a standardized psychosocial stressor in children and adults.
“Consistent with this, the s′ allele of 5-HTTLPR has been associated with an exaggerated cortisol response to a standardized psychosocial stressor in children and adults (Alexander et al. 2009; Gotlib et al. 2008).”
From Gene–environment interactions: early life stress and risk for depressive and anxiety disorders (2011) · cites this paper as Alexander et al. 2009

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The Adaptive Calibration Model of stress responsivity
Del Giudice, M., Ellis, B. J., & Shirtcliff, E. A. (2011) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2010.11.007 · Cited by 1,373 · see citing works
Genetic Sensitivity to the Environment: The Case of the Serotonin Transporter Gene and Its Implications for Studying Complex Diseases and Traits
Caspi, A., Hariri, A. R., Holmes, A., Uher, R., & Moffitt, T. E. (2010) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2010.09101452 · Cited by 1,346 · see citing works
Vantage sensitivity: Individual differences in response to positive experiences.
Pluess, M., & Belsky, J. (2012) · Psychological Bulletin · doi:10.1037/a0030196 · Cited by 577 · see citing works
Individual Differences in Environmental Sensitivity
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Child maltreatment and risk for psychopathology in childhood and adulthood
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Inflammation as a psychophysiological biomarker in chronic psychosocial stress
Hänsel, A., Hong, S., Cámara, R. J. A., & von Känel, R. (2009) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2009.12.012 · Cited by 458 · see citing works
Human hypothalamus–pituitary–adrenal axis responses to acute psychosocial stress in laboratory settings
Foley, P., & Kirschbaum, C. (2010) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2010.01.010 · Cited by 455 · see citing works
Looking on the Bright Side of Serotonin Transporter Gene Variation
Homberg, J. R., & Lesch, K. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.09.024 · Cited by 437 · see citing works
Sexual selection and sex differences in the prevalence of childhood externalizing and adolescent internalizing disorders.
Martel, M. M. (2013) · Psychological Bulletin · doi:10.1037/a0032247 · Cited by 329 · see citing works
High anxiety trait: A vulnerable phenotype for stress‐induced depression
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Gene–environment interactions: early life stress and risk for depressive and anxiety disorders
Nugent, N. R., Tyrka, A. R., Carpenter, L. L., & Price, L. H. (2011) · Psychopharmacology · doi:10.1007/s00213-010-2151-x · Cited by 269 · see citing works
“Consistent with this, the s′ allele of 5-HTTLPR has been associated with an exaggerated cortisol response to a standardized psychosocial stressor in children and adults (Alexander et al. 2009; Gotlib et al. 2008).”
Background
The neurobiology of depression in later-life: Clinical, neuropsychological, neuroimaging and pathophysiological features
Naismith, S. L., Norrie, L. M., Mowszowski, L., & Hickie, I. B. (2012) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2012.05.009 · Cited by 269 · see citing works
Genetic Gating of Human Fear Learning and Extinction
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Early adversity and adult health outcomes
Taylor, S. E., Way, B. M., & Seeman, T. E. (2011) · Development and Psychopathology · doi:10.1017/s0954579411000411 · Cited by 235 · see citing works
Sensitivity to the depressogenic effect of stress and HPA-axis reactivity in adolescence: a review of gender differences
Oldehinkel, A. J., & Bouma, E. M. C. (2011) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2010.10.013 · Cited by 225 · see citing works
Gene × Environment Interactions: From Molecular Mechanisms to Behavior
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Increased serotonin transporter gene ( <i>SERT</i> ) DNA methylation is associated with bullying victimization and blunted cortisol response to stress in childhood: a longitudinal study of discordant monozygotic twins
Ouellet-Morin, I., Wong, C. C. Y., Danese, A., Pariante, C. M., Papadopoulos, A. S., Mill, J., & Arseneault, L. (2013) · Psychological Medicine · doi:10.1017/s0033291712002784 · Cited by 207 · see citing works
Oxytocin buffers cortisol responses to stress in individuals with impaired emotion regulation abilities
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Interaction between early-life stress and FKBP5 gene variants in major depressive disorder and post-traumatic stress disorder: A systematic review and meta-analysis
Wang, Q., Shelton, R. C., & Dwivedi, Y. (2018) · Journal of Affective Disorders · doi:10.1016/j.jad.2017.08.066 · Cited by 201 · see citing works
Stress and protective factors in individuals at ultra-high risk for psychosis, first episode psychosis and healthy controls
Pruessner, M., Iyer, S. N., Faridi, K., Joober, R., & MALLA, A. K. (2011) · Schizophrenia Research · doi:10.1016/j.schres.2011.03.022 · Cited by 188 · see citing works
The serotonin transporter gene-linked polymorphic region (5-HTTLPR) and cortisol stress reactivity: a meta-analysis
Miller, R. E., Wankerl, M., Tobias Stalder, A., Kirschbaum, C., & Alexander, N. (2012) · Molecular Psychiatry · doi:10.1038/mp.2012.124 · Cited by 177 · see citing works
Self-citation
Impact of early adversity on glucocorticoid regulation and later mental disorders
Strüber, N., Strüber, D., & Roth, G. (2014) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2013.10.015 · Cited by 173 · see citing works
HPA axis responses to psychological challenge linking stress and disease: What do we know on sources of intra- and interindividual variability?
Zänkert, S., Bellingrath, S., Wüst, S., & Kudielka, B. (2019) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2018.10.027 · Cited by 124 · see citing works
Major depression, cognitive dysfunction and Alzheimer's disease: Is there a link?
Sierksma, A. S. R., van den Hove, D. L. A., Steinbusch, H. W. M., & Prickaerts, J. (2010) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2009.10.021 · Cited by 139 · see citing works
Heritability and genetic correlation of hair cortisol in vervet monkeys in low and higher stress environments
Fairbanks, L. A., Jorgensen, M. J., Bailey, J. N., Breidenthal, S. E., Grzywa, R. L., & Laudenslager, M. L. (2011) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2011.02.013 · Cited by 135 · see citing works
From nature versus nurture, via nature and nurture, to gene × environment interaction in mental disorders
Wermter, A., Laucht, M., SCHIMMELMANN, B. G., Banaschewski, T., Sonuga-Barke, E. J. S., Rietschel, M., & Becker, K. (2009) · European Child & Adolescent Psychiatry · doi:10.1007/s00787-009-0082-z · Cited by 132 · see citing works
Cortisol secretion in depressed, and at-risk adults
Dienes, K. A., Hazel, N. A., & Hammen, C. L. (2013) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2012.09.019 · Cited by 128 · see citing works
Influence of life stress, 5-HTTLPR genotype, and SLC6A4 methylation on gene expression and stress response in healthy Caucasian males
Duman, E. A., & Canli, T. (2015) · Biology of Mood & Anxiety Disorders · doi:10.1186/s13587-015-0017-x · Cited by 128 · see citing works
Childhood trauma in mood disorders: Neurobiological mechanisms and implications for treatment
Jaworska-Andryszewska, P., & RYBAKOWSKI, J. K. (2018) · Pharmacological Reports · doi:10.1016/j.pharep.2018.10.004 · Cited by 128 · see citing works
Effects of genetic and early environmental risk factors for depression on serotonin transporter expression and methylation profiles
Wankerl, M., Miller, R. E., Kirschbaum, C., Hennig, J., Stalder, T., & Alexander, N. (2014) · Translational Psychiatry · doi:10.1038/tp.2014.37 · Cited by 124 · see citing works
Self-citation
Early life experiences and social cognition in major psychiatric disorders: A systematic review
Rokita, K., Dauvermann, M. R., & Donohoe, G. J. (2018) · European Psychiatry · doi:10.1016/j.eurpsy.2018.06.006 · Cited by 122 · see citing works
Molecular actions and clinical pharmacogenetics of lithium therapy
Can, A., Schulze, T. G., & Gould, T. D. (2014) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2014.02.004 · Cited by 121 · see citing works
Genetic sensitivity to the caregiving context: The influence of 5httlpr and BDNF val66met on indiscriminate social behavior
Drury, S. S., Gleason, M. M., Theall, K. P., Smyke, A. T., Nelson, C. A., Fox, N. A., & Zeanah, C. H. (2011) · Physiology & Behavior · doi:10.1016/j.physbeh.2011.11.014 · Cited by 115 · see citing works
Stress and animal models of inflammatory bowel disease—An update on the role of the hypothalamo–pituitary–adrenal axis
Reber, S. O. (2011) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2011.05.014 · Cited by 115 · see citing works
Gene—Environment Interactions in Major Depressive Disorder
Klengel, T., & Binder, E. B. (2013) · The Canadian Journal of Psychiatry · doi:10.1177/070674371305800203 · Cited by 113 · see citing works
Prenatal stress and genetic risk: How prenatal stress interacts with genetics to alter risk for psychiatric illness
Abbott, P. W., Gumusoglu, S. B., Bittle, J., Beversdorf, D. Q., & Stevens, H. E. (2018) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2018.01.019 · Cited by 109 · see citing works
The BDNF Val66Met polymorphism affects HPA-axis reactivity to acute stress
Alexander, N., Osinsky, R., Schmitz, A. P., Mueller, E., Kuepper, Y., & Hennig, J. (2010) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2009.12.008 · Cited by 106 · see citing works
Self-citation
The other allele: Exploring the long allele of the serotonin transporter gene as a potential risk factor for psychopathy: A review of the parallels in findings
Glenn, A. L. (2010) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2010.07.005 · Cited by 101 · see citing works
Toward Psychoinformatics: Computer Science Meets Psychology
Montag, C., Duke, É., & Markowetz, A. (2016) · Computational and Mathematical Methods in Medicine · doi:10.1155/2016/2983685 · Cited by 97 · see citing works
DNA methylation profiles within the serotonin transporter gene moderate the association of 5-HTTLPR and cortisol stress reactivity
Alexander, N., Wankerl, M., Hennig, J., Miller, R., Zänkert, S., Steudte-Schmiedgen, S., Stalder, T., & Kirschbaum, C. (2014) · Translational Psychiatry · doi:10.1038/tp.2014.88 · Cited by 95 · see citing works
Self-citation
Maternal depression and anxiety are associated with altered gene expression in the human placenta without modification by antidepressant use: Implications for fetal programming
Ponder, K. L., Salisbury, A. L., McGonnigal, B., Laliberte, A., Lester, B. M., & Padbury, J. F. (2011) · Developmental Psychobiology · doi:10.1002/dev.20549 · Cited by 89 · see citing works
Interaction of Serotonin Transporter Gene-Linked Polymorphic Region and Stressful Life Events Predicts Cortisol Stress Response
Mueller‐Alcazar, A., Armbruster, D., Moser, D., Canli, T., Lesch, K., Brocke, B., & Kirschbaum, C. (2011) · Neuropsychopharmacology · doi:10.1038/npp.2011.11 · Cited by 89 · see citing works
Reflections on the interaction of psychogenic stress systems in humans: The stress coherence/compensation model
Andrews, J., Ali, N., & Pruessner, J. C. (2013) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2013.02.010 · Cited by 87 · see citing works
Childhood adversity and allostatic overload of the hypothalamic–pituitary–adrenal axis: A vulnerability model for depressive disorders
Wilkinson, P. O., & Goodyer, I. M. (2011) · Development and Psychopathology · doi:10.1017/s0954579411000472 · Cited by 86 · see citing works
Early-life stress and recurrent psychological distress over the lifecourse predict divergent cortisol reactivity patterns in adulthood
Goldman-Mellor, S. J., Hamer, M., & Steptoe, A. (2012) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2012.03.010 · Cited by 85 · see citing works
The role of the serotonin transporter polymorphism for the endocrine stress response in newborns
Mueller‐Alcazar, A., Brocke, B., Fries, E., Lesch, K., & Kirschbaum, C. (2009) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2009.07.002 · Cited by 83 · see citing works
Gene–Environment Interactions and Intermediate Phenotypes: Early Trauma and Depression
Hornung, O., & Heim, C. M. (2013) · Frontiers in Endocrinology · doi:10.3389/fendo.2014.00014 · Cited by 86 · see citing works
Genetic Sensitivity to the Environment: The Case of the Serotonin Transporter Gene and Its Implications for Studying Complex Diseases and Traits
Caspi, A., Hariri, A. R., Holmes, A., Uher, R., & Moffitt, T. E. (2010) · FOCUS The Journal of Lifelong Learning in Psychiatry · doi:10.1176/foc.8.3.foc398 · Cited by 79 · see citing works
5-HTTLPR and BDNF Val66Met polymorphisms moderate effects of stress on rumination
Clasen, P. C., Wells, T. T., Knopik, V. S., McGeary, J. E., & Beevers, C. G. (2011) · Genes Brain & Behavior · doi:10.1111/j.1601-183x.2011.00715.x · Cited by 78 · see citing works
Social Influences on Health: Is Serotonin a Critical Mediator?
Way, B. M., & Taylor, S. E. (2010) · Psychosomatic Medicine · doi:10.1097/psy.0b013e3181ce6a7d · Cited by 75 · see citing works
Systematic review, structural analysis, and new theoretical perspectives on the role of serotonin and associated genes in the etiology of psychopathy and sociopathy
Yildirim, B. O., & Derksen, J. J. L. (2013) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2013.04.009 · Cited by 75 · see citing works
Serotonin Transporter Gene Polymorphism, Childhood Trauma, and Cognition in Patients With Psychotic Disorders
Aas, M., Djurovic, S., Athanasiu, L., Steen, N. E., Agartz, I., Lorentzen, S., Sundet, K. S., Andreassen, O. A., & Melle, I. S. (2011) · Schizophrenia Bulletin · doi:10.1093/schbul/sbr113 · Cited by 70 · see citing works
Genetics of emotion
Bevilacqua, L. M., & Goldman, D. A. (2011) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2011.07.009 · Cited by 67 · see citing works
Epigenetic and epistatic interactions between serotonin transporter and brain-derived neurotrophic factor genetic polymorphism: insights in depression
Ignácio, Z. M., Réus, G. Z., Abelaira, H. M., & Quevedo, J. (2014) · Neuroscience · doi:10.1016/j.neuroscience.2014.06.036 · Cited by 65 · see citing works
Interaction between 5-HTTLPR and BDNF Val66Met polymorphisms on HPA axis reactivity in preschoolers
Dougherty, L. R., Klein, D. N., Congdon, E. L., Canli, T., & Hayden, E. P. (2009) · Biological Psychology · doi:10.1016/j.biopsycho.2009.10.009 · Cited by 64 · see citing works
Stress impairs retrieval of socially relevant information.
Merz, C. J., Wolf, O. T., & Hennig, J. (2010) · Behavioral Neuroscience · doi:10.1037/a0018942 · Cited by 63 · see citing works
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Interaction of the Serotonin Transporter-Linked Polymorphic Region and Environmental Adversity: Increased Amygdala-Hypothalamus Connectivity as a Potential Mechanism Linking Neural and Endocrine Hyperreactivity
Alexander, N., Klucken, T., Koppe, G., Osinsky, R., Walter, B., Vaitl, D., Sammer, G., Stark, R. M., & Hennig, J. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.01.030 · Cited by 62 · see citing works
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Functional Gene Polymorphisms in the Serotonin System and Traumatic Life Events Modulate the Neural Basis of Fear Acquisition and Extinction
Hermann, A., Kuepper, Y., Schmitz, A., Walter, B., Vaitl, D., Hennig, J., Stark, R. M., & Tabbert, K. (2012) · PLoS ONE · doi:10.1371/journal.pone.0044352 · Cited by 59 · see citing works
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Individual differences in neural correlates of fear conditioning as a function of 5-HTTLPR and stressful life events
Klucken, T., Alexander, N., Schweckendiek, J., Merz, C. J., Kagerer, S., Osinsky, R., Walter, B., Vaitl, D., Hennig, J., & Stark, R. M. (2012) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nss005 · Cited by 56 · see citing works
Self-citation
Early life adversity and serotonin transporter gene variation interact to affect DNA methylation of the corticotropin-releasing factor gene promoter region in the adult rat brain
van der Doelen, R. H. A., Arnoldussen, I. A. C., Ghareh, H., van Och, L., Homberg, J. R., & Kozicz, T. (2015) · Development and Psychopathology · doi:10.1017/s0954579414001345 · Cited by 53 · see citing works
Drug withdrawal-induced depression: Serotonergic and plasticity changes in animal models
Renoir, T., Pang, T. Y., & Lanfumey, L. (2011) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2011.10.003 · Cited by 52 · see citing works
The serotonin transporter gene and functional and pathological adaptation to environmental variation across the life span
Homberg, J. R., & van den Hove, D. (2012) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2012.08.003 · Cited by 51 · see citing works
Maternal postnatal depression predicts altered offspring biological stress reactivity in adulthood
Barry, T. J., Murray, L., Fearon, P. R. M., Moutsiana, C., Cooper, P., Goodyer, I. M., Herbert, J., & Halligan, S. L. (2014) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2014.12.003 · Cited by 51 · see citing works
The 5-HTTLPR polymorphism is associated with altered hemodynamic responses during appetitive conditioning
Klucken, T., Wehrum‐Osinsky, S., Schweckendiek, J., Merz, C. J., Hennig, J., Vaitl, D., & Stark, R. M. (2012) · Human Brain Mapping · doi:10.1002/hbm.22085 · Cited by 50 · see citing works
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Genetic variants within the dopaminergic system interact to modulate endocrine stress reactivity and recovery
Alexander, N., Osinsky, R., Mueller, E., Schmitz, A., Günthert, S. J., Kuepper, Y., & Hennig, J. (2010) · Behavioural Brain Research · doi:10.1016/j.bbr.2010.07.003 · Cited by 50 · see citing works
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Serotonin contracts the rat mesenteric artery by inhibiting 4-aminopyridine-sensitive Kv channels via the 5-HT2A receptor and Src tyrosine kinase
Sung, D. J., Noh, H. J., Kim, J. G., Park, S. W., Kim, B., Cho, H., & Bae, Y. M. (2013) · Experimental & Molecular Medicine · doi:10.1038/emm.2013.116 · Cited by 49 · see citing works
Toward an integration of cognitive and genetic models of risk for depression
Gibb, B. E., Beevers, C. G., & McGeary, J. E. (2012) · Cognition & Emotion · doi:10.1080/02699931.2012.712950 · Cited by 49 · see citing works
Affective and neuroendocrine stress reactivity to an academic examination: Influence of the 5-HTTLPR genotype and trait neuroticism
Verschoor, E., & Markus, C. R. (2011) · Biological Psychology · doi:10.1016/j.biopsycho.2011.06.001 · Cited by 48 · see citing works
Supportive family environments, genes that confer sensitivity, and allostatic load among rural african american emerging adults: A prospective analysis.
Brody, G. H., Yu, T., Chen, Y., Kogan, S. M., Evans, G. W., Windle, M. T., Gerrard, M., Gibbons, F. X., Simons, R. L., & Philibert, R. A. (2012) · Journal of Family Psychology · doi:10.1037/a0027829 · Cited by 47 · see citing works
Early life adversity and serotonin transporter gene variation interact at the level of the adrenal gland to affect the adult hypothalamo-pituitary-adrenal axis
van der Doelen, R. H. A., Deschamps, W., D'Annibale, C., Peeters, D. G. A., Wevers, R. A., Zelena, D., Homberg, J. R., & Kozicz, T. (2014) · Translational Psychiatry · doi:10.1038/tp.2014.57 · Cited by 46 · see citing works
Relative frontal brain asymmetry and cortisol release after social stress: The role of action orientation
Düsing, R., Mattie Tops, A., Radtke, E. L., Kühl, J., & Quirin, M. (2016) · Biological Psychology · doi:10.1016/j.biopsycho.2016.01.012 · Cited by 46 · see citing works
The association between the 5-HTTLPR and neural correlates of fear conditioning and connectivity
Klucken, T., Schweckendiek, J., Blecker, C. R., Walter, B., Kuepper, Y., Hennig, J., & Stark, R. M. (2014) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nsu108 · Cited by 45 · see citing works
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The burden of conscientiousness? Examining brain activation and cortisol response during social evaluative stress
Dahm, A.-S., Schmierer, P., Veer, I. M., Streit, F., Görgen, A., Kruschwitz, J., Wüst, S., Kirsch, P., Walter, H., & Erk, S. (2017) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2017.01.019 · Cited by 45 · see citing works
5‐HTTLPR S‐allele: a genetic plasticity factor regarding the effects of life events on personality?
Kuepper, Y., Wielpuetz, C., Alexander, N., Mueller, E., Grant, P. S., & Hennig, J. (2012) · Genes Brain & Behavior · doi:10.1111/j.1601-183x.2012.00783.x · Cited by 42 · see citing works
Self-citation
Interplay between stress response genes associated with attention‐deficit hyperactivity disorder and brain volume
van der Meer, D., Hoekstra, P. J., Bralten, J., van Donkelaar, M. M. J., Heslenfeld, D. J., Oosterlaan, J., Faraone, S. V., Franke, B., Buitelaar, J. K., & Hartman, C. A. (2016) · Genes Brain & Behavior · doi:10.1111/gbb.12307 · Cited by 40 · see citing works
Prefrontal serotonin transporter availability is positively associated with the cortisol awakening response
Frøkjær, V. G., Erritzøe, D., Holst, K. K., Jensen, P. S., Rasmussen, P. M., Fisher, P. M., Baaré, W. F. C., Madsen, K. S., Madsen, J., Svarer, C., et al. (2012) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2012.05.013 · Cited by 39 · see citing works
Stressful Life Events Prior to Depression Onset and the Cortisol Response to Stress in Youth with First Onset Versus Recurrent Depression
Mazurka, R., Wynne‐Edwards, K. E., & Harkness, K. L. (2015) · Research on Child and Adolescent Psychopathology · doi:10.1007/s10802-015-0103-y · Cited by 35 · see citing works
Attentional bias to negative information and 5-HTTLPR genotype interactively predict students' emotional reactivity to first university semester.
Osinsky, R., Lösch, A., Hennig, J., Alexander, N., & MacLeod, C. (2012) · Emotion · doi:10.1037/a0026674 · Cited by 34 · see citing works
Self-citation
Gene × environment interactions in the prediction of response to antidepressant treatment
Klengel, T., & Binder, E. B. (2012) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145712001459 · Cited by 34 · see citing works
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Authors: Alexander, N., Kuepper, Y., Schmitz, A., Osinsky, R., Kozyra, E., & Hennig, J.
Affiliations: Justus-Liebig-Universität Gießen (DE)
Corresponding author: Alexander, Nina
ORCID: Alexander, Nina
Kuepper, Yvonne
Osinsky, Roman
Hennig, Juergen
Venue: Psychoneuroendocrinology
Publisher: Elsevier BV
Published: 2009-10
Volume: 34
Issue: 9
Pages: 1294-1303
ISSN: 0306-4530 (ISSN-L)
DOI: 10.1016/j.psyneuen.2009.03.017
OpenAlex: W2043334194
Cited by: 171
References: 90
Citations by year: 2026: 1 · 2025: 2 · 2022: 2 · 2021: 3 · 2020: 3 · 2019: 6 · 2018: 13 · 2017: 10 · 2016: 11 · 2015: 14 · 2014: 19 · 2013: 13 · 2012: 26
FWCI: 9.25
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Psychoneuroendocrinology (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Keywords: gene-environment interaction, 5-HTTLPR, serotonin transporter polymorphism, cortisol, acute stress, life events, depression risk, salivary cortisol, premorbid risk factors
MeSH terms: Adult, Depression, Genotype, Humans, Hydrocortisone, Hypothalamo-Hypophyseal System, Life Change Events, Male, Pituitary-Adrenal System, Saliva, Speech, Stress, Psychological, Serotonin Plasma Membrane Transport Proteins

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Gene–environment interactions predict cortisol responses after acute stress: implications for the etiology of depression

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