Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Influence of Life Stress on Depression: Moderation by a Polymorphism in the 5-HTT Gene
Avshalom Caspi,1,2Karen Sugden,1Terrie E. Moffitt,1,2*Alan Taylor,1Ian W. Craig,1HonaLee Harrington,2Joseph McClay,1Jonathan Mill,1Judy Martin,3Antony Braithwaite,4Richie Poulton3
In a prospective-longitudinal study of a representative birthcohort, we tested why stressful experiences lead to depressionin some people but not in others. A functional polymorphismin the promoter region of the serotonin transporter (5-HT T)gene was found to moderate the influence of stressful life eventson depression. Individuals with one or two copies of the shortallele of the 5-HT T promoter polymorphism exhibited more depressivesymptoms, diagnosable depression, and suicidality in relationto stressful life events than individuals homozygous for thelong allele. This epidemiological study thus provides evidenceof a gene-by-environment interaction, in which an individual'sresponse to environmental insults is moderated by his or hergenetic makeup.
1 Medical Research Council Social, Genetic, and Developmental Psychiatry Research Centre, Institute of Psychiatry, King's College London, PO80 De Crespigny Park, London, SE5 8AF, UK. 2 Department of Psychology, University of Wisconsin, Madison, WI 53706, USA. 3 Dunedin School of Medicine, 4 Department of Pathology, University of Otago, Dunedin, New Zealand.
* To whom correspondence should be addressed. E-mail: t.moffitt{at}iop.kcl.ac.uk
Human neuronal acetylcholine receptor A5-A3-B4 haplotypes are associated with multiple nicotine dependence phenotypes.
T. B. Baker, R. B. Weiss, D. Bolt, A. von Niederhausern, M. C. Fiore, D. M. Dunn, M. E. Piper, N. Matsunami, S. S. Smith, H. Coon, et al. (2009)
Nicotine Tob Res
11, 785-796
|Abstract »|Full Text »|PDF »
Serotonin transporter genotype, morning cortisol and subsequent depression in adolescents.
I. M. Goodyer, A. Bacon, M. Ban, T. Croudace, and J. Herbert (2009)
The British Journal of Psychiatry
195, 39-45
|Abstract »|Full Text »|PDF »
Serotonin shapes risky decision making in monkeys.
Interaction Between the Serotonin Transporter Gene (5-HTTLPR), Stressful Life Events, and Risk of Depression: A Meta-analysis.
N. Risch, R. Herrell, T. Lehner, K.-Y. Liang, L. Eaves, J. Hoh, A. Griem, M. Kovacs, J. Ott, and K. R. Merikangas (2009)
JAMA
301, 2462-2471
|Abstract »|Full Text »|PDF »
Neuroscience, Molecular Biology, and the Childhood Roots of Health Disparities: Building a New Framework for Health Promotion and Disease Prevention.
Environmental Adversity and Increasing Genetic Risk for Externalizing Disorders.
B. M. Hicks, S. C. South, A. C. DiRago, W. G. Iacono, and M. McGue (2009)
Arch Gen Psychiatry
66, 640-648
|Abstract »|Full Text »|PDF »
Role of GABRA2 in Trajectories of Externalizing Behavior Across Development and Evidence of Moderation by Parental Monitoring.
D. M. Dick, S. J. Latendresse, J. E. Lansford, J. P. Budde, A. Goate, K. A. Dodge, G. S. Pettit, and J. E. Bates (2009)
Arch Gen Psychiatry
66, 649-657
|Abstract »|Full Text »|PDF »
Depression and Suicide in Children and Adolescents.
L. M. Prager (2009)
Pediatr. Rev.
30, 199-206
|Full Text »|PDF »
Looking on the bright side: biased attention and the human serotonin transporter gene.
Frontal-Limbic White Matter Pathway Associations with the Serotonin Transporter Gene Promoter Region (5-HTTLPR) Polymorphism.
J. Pacheco, C. G. Beevers, C. Benavides, J. McGeary, E. Stice, and D. M. Schnyer (2009)
J. Neurosci.
29, 6229-6233
|Abstract »|Full Text »|PDF »
A Genetically Mediated Bias in Decision Making Driven by Failure of Amygdala Control.
J. P. Roiser, B. de Martino, G. C. Y. Tan, D. Kumaran, B. Seymour, N. W. Wood, and R. J. Dolan (2009)
J. Neurosci.
29, 5985-5991
|Abstract »|Full Text »|PDF »
Social Ecology, Genomics, and African American Health: A Nonlinear Dynamical Perspective.
S. Madhere, J. Harrell, and C. D. M. Royal (2009)
Journal of Black Psychology
35, 154-179
|Abstract »|PDF »
Genetic architecture of quantitative traits in mice, flies, and humans.
The Antecedents of Schizophrenia: A Review of Birth Cohort Studies.
J. Welham, M. Isohanni, P. Jones, and J. McGrath (2009)
Schizophr Bull
35, 603-623
|Abstract »|Full Text »|PDF »
Issues concerning feedback about genetic testing and risk of depression.
K. Wilhelm, B. Meiser, P. B. Mitchell, A. W. Finch, J. E. Siegel, G. Parker, and P. R. Schofield (2009)
The British Journal of Psychiatry
194, 404-410
|Abstract »|Full Text »|PDF »
Cortical thinning in persons at increased familial risk for major depression.
B. S. Peterson, V. Warner, R. Bansal, H. Zhu, X. Hao, J. Liu, K. Durkin, P. B. Adams, P. Wickramaratne, and M. M. Weissman (2009)
PNAS
106, 6273-6278
|Abstract »|Full Text »|PDF »
Posttraumatic Stress Disorder: A State-of-the-Science Review.
C. B. Nemeroff, J. D. Bremner, E. B. Foa, H. S. Mayberg, C. S. North, and M. B. Stein (2009)
Focus
7, 254-273
|Abstract »|Full Text »|PDF »
Treatment of Depression After Coronary Artery Bypass Surgery: A Randomized Controlled Trial.
K. E. Freedland, J. A. Skala, R. M. Carney, E. H. Rubin, P. J. Lustman, V. G. Davila-Roman, B. C. Steinmeyer, and C. W. Hogue Jr (2009)
Arch Gen Psychiatry
66, 387-396
|Abstract »|Full Text »|PDF »
Political Science, Biometric Theory, and Twin Studies: A Methodological Introduction.
Neurobiological mechanisms in major depressive disorder.
M. aan het Rot PhD, S. J. Mathew MD, and D. S. Charney MD (2009)
Can. Med. Assoc. J.
180, 305-313
|Full Text »|PDF »
The Rebirth of Neuroscience in Psychosomatic Medicine, Part I: Historical Context, Methods, and Relevant Basic Science.
R. D. Lane, S. R. Waldstein, M. A. Chesney, J. R. Jennings, W. R. Lovallo, P. J. Kozel, R. M. Rose, D. A. Drossman, N. Schneiderman, J. F. Thayer, et al. (2009)
Psychosom Med
71, 117-134
|Abstract »|Full Text »|PDF »
Enhanced activity of human serotonin transporter variants associated with autism.
H. C Prasad, J. A Steiner, J. S Sutcliffe, and R. D Blakely (2009)
Phil Trans R Soc B
364, 163-173
|Abstract »|Full Text »|PDF »
Psychosocial stress reversibly disrupts prefrontal processing and attentional control.
Depression and heart disease: What do we know, and where are we headed?.
L. POZUELO, G. TESAR, J. ZHANG, M. PENN, K. FRANCO, and W. JIANG (2009)
Cleveland Clinic Journal of Medicine
76, 59-70
|Abstract »|Full Text »|PDF »
Influence of Functional Variant of Neuronal Nitric Oxide Synthase on Impulsive Behaviors in Humans.
A. Reif, C. P. Jacob, D. Rujescu, S. Herterich, S. Lang, L. Gutknecht, C. G. Baehne, A. Strobel, C. M. Freitag, I. Giegling, et al. (2009)
Arch Gen Psychiatry
66, 41-50
|Abstract »|Full Text »|PDF »
Consequences of chronic social stress on behaviour and vasopressin gene expression in the PVN of DBA/2OlaHsd mice--influence of treatment with the CRHR1-antagonist R121919/NBI 30775.
A. Erhardt, M. Muller, A. Rodel, T. Welt, F. Ohl, F. Holsboer, and M. Keck (2009)
J Psychopharmacol
23, 31-39
|Abstract »|PDF »
Core Components of Therapy in Youth: Do We Know what to Disseminate?.
V. R. Weersing, M. Rozenman, and A. Gonzalez (2009)
Behav Modif
33, 24-47
|Abstract »|PDF »
Relationship of Genetic Variability and Depressive Symptoms to Adverse Events After Coronary Artery Bypass Graft Surgery.
B. Phillips-Bute, J. P. Mathew, J. A. Blumenthal, R. W. Morris, M. V. Podgoreanu, M. Smith, M. Stafford-Smith, H. P. Grocott, D. A. Schwinn, M. F. Newman, et al. (2008)
Psychosom Med
70, 953-959
|Abstract »|Full Text »|PDF »
Suicide and Suicidal Behavior.
M. K. Nock, G. Borges, E. J. Bromet, C. B. Cha, R. C. Kessler, and S. Lee (2008)
Epidemiol. Rev.
30, 133-154
|Abstract »|Full Text »|PDF »
Association of Serotonin Transporter Gene Polymorphisms With Poststroke Depression.
R. Kohen, K. C. Cain, P. H. Mitchell, K. Becker, A. Buzaitis, S. P. Millard, G. P. Navaja, L. Teri, D. Tirschwell, and R. Veith (2008)
Arch Gen Psychiatry
65, 1296-1302
|Abstract »|Full Text »|PDF »
Gene-Environment Interactions in Schizophrenia: Review of Epidemiological Findings and Future Directions.
J. van Os, B. P. Rutten, and R. Poulton (2008)
Schizophr Bull
34, 1066-1082
|Abstract »|Full Text »|PDF »
Mood changes after delivery: role of the serotonin transporter gene.
J. Sanjuan, R. Martin-Santos, L. Garcia-Esteve, J. M. Carot, R. Guillamat, A. Gutierrez-Zotes, I. Gornemann, F. Canellas, E. Baca-Garcia, M. Jover, et al. (2008)
The British Journal of Psychiatry
193, 383-388
|Abstract »|Full Text »|PDF »
Resilience and depression: perspectives from primary care.
C. Dowrick, R. Kokanovic, K. Hegarty, F. Griffiths, and J. Gunn (2008)
Health (London)
12, 439-452
|Abstract »|PDF »
The Economics and Psychology of Personality Traits.
L. Borghans, A. L. Duckworth, J. J. Heckman, and B. t. Weel (2008)
J. Human Resources
43, 972-1059
|Abstract »|PDF »
Depression during menopausal transition: a review of treatment strategies and pathophysiological correlates.
Preliminary Evidence for Sensitive Periods in the Effect of Childhood Sexual Abuse on Regional Brain Development.
S. L. Andersen, A. Tomada, E. S. Vincow, E. Valente, A. Polcari, and M. H. Teicher (2008)
J Neuropsychiatry Clin Neurosci
20, 292-301
|Abstract »|Full Text »|PDF »
Effect of Bright Light and Melatonin on Cognitive and Noncognitive Function in Elderly Residents of Group Care Facilities: A Randomized Controlled Trial.
R. F. Riemersma-van der Lek, D. F. Swaab, J. Twisk, E. M. Hol, W. J. G. Hoogendijk, and E. J. W. Van Someren (2008)
JAMA
299, 2642-2655
|Abstract »|Full Text »|PDF »
Understanding the Agreements and Controversies Surrounding Childhood Psychopharmacology.
Population-Based Study of First Onset and Chronicity in Major Depressive Disorder.
W. W. Eaton, H. Shao, G. Nestadt, B. H. Lee, O. J. Bienvenu, and P. Zandi (2008)
Arch Gen Psychiatry
65, 513-520
|Abstract »|Full Text »|PDF »
Lasting Syndrome of Depression Produced by Reduction in Serotonin Uptake during Postnatal Development: Evidence from Sleep, Stress, and Behavior.
D. Popa, C. Lena, C. Alexandre, and J. Adrien (2008)
J. Neurosci.
28, 3546-3554
|Abstract »|Full Text »|PDF »
Major depression, 5HTTLPR genotype, suicide and antidepressant influences on thalamic volume.
K. A. Young, W. L. Bonkale, L. A. Holcomb, P. B. Hicks, and D. C. German (2008)
The British Journal of Psychiatry
192, 285-289
|Abstract »|Full Text »|PDF »
Gene-Environment Interactions, Not Neonatal Growth Hormone Deficiency, Time Puberty in Female Rhesus Monkeys.
Association of FKBP5 Polymorphisms and Childhood Abuse With Risk of Posttraumatic Stress Disorder Symptoms in Adults.
E. B. Binder, R. G. Bradley, W. Liu, M. P. Epstein, T. C. Deveau, K. B. Mercer, Y. Tang, C. F. Gillespie, C. M. Heim, C. B. Nemeroff, et al. (2008)
JAMA
299, 1291-1305
|Abstract »|Full Text »|PDF »
Epigenetics: what is it and why is it important to mental disease?.
Neuroendocrine-Immune Mechanisms of Behavioral Comorbidities in Patients With Cancer.
A. H. Miller, S. Ancoli-Israel, J. E. Bower, L. Capuron, and M. R. Irwin (2008)
J. Clin. Oncol.
26, 971-982
|Abstract »|Full Text »|PDF »
Hippocampal Morphology and Distinguishing Late-Onset From Early-Onset Elderly Depression.
M. Ballmaier, K. L. Narr, A. W. Toga, V. Elderkin-Thompson, P. M. Thompson, L. Hamilton, E. Haroon, D. Pham, A. Heinz, and A. Kumar (2008)
Am J Psychiatry
165, 229-237
|Abstract »|Full Text »|PDF »
Macrolevel Stressors, Terrorism, and Mental Health Outcomes: Broadening the Stress Paradigm.
J. A. Richman, L. Cloninger, and K. M. Rospenda (2008)
Am J Public Health
98, 323-329
|Abstract »|Full Text »|PDF »
Influence of Child Abuse on Adult Depression: Moderation by the Corticotropin-Releasing Hormone Receptor Gene.
R. G. Bradley, E. B. Binder, M. P. Epstein, Y. Tang, H. P. Nair, W. Liu, C. F. Gillespie, T. Berg, M. Evces, D. J. Newport, et al. (2008)
Arch Gen Psychiatry
65, 190-200
|Abstract »|Full Text »|PDF »
Variations in Heritability of Cortisol Reactivity to Stress as a Function of Early Familial Adversity Among 19-Month-Old Twins.
I. Ouellet-Morin, M. Boivin, G. Dionne, S. J. Lupien, L. Arsenault, R. G. Barr, D. Perusse, and R. E. Tremblay (2008)
Arch Gen Psychiatry
65, 211-218
|Abstract »|Full Text »|PDF »
Major Depressive Disorder.
R.H. Belmaker and G. Agam (2008)
N. Engl. J. Med.
358, 55-68
|Full Text »|PDF »
Recent Findings in the Pathophysiology of Depression.
Deep Brain Stimulation for Treatment-Resistant Depression.
H. S. Mayberg, A. M. Lozano, V. Voon, H. E. McNeely, D. Seminowicz, C. Hamani, J. M. Schwalb, and S. H. Kennedy (2008)
Focus
6, 143-154
|Abstract »|Full Text »|PDF »
Amygdala and Nucleus Accumbens Activation to Emotional Facial Expressions in Children and Adolescents at Risk for Major Depression.
C. S. Monk, R. G. Klein, E. H. Telzer, E. A. Schroth, S. Mannuzza, J. L. Moulton III, M. Guardino, C. L. Masten, E. B. McClure-Tone, S. Fromm, et al. (2008)
Am J Psychiatry
165, 90-98
|Abstract »|Full Text »|PDF »
Family-Based Association Study of Lithium-Related and Other Candidate Genes in Bipolar Disorder.
R. H. Perlis, S. Purcell, J. Fagerness, A. Kirby, T. L. Petryshen, J. Fan, and P. Sklar (2008)
Arch Gen Psychiatry
65, 53-61
|Abstract »|Full Text »|PDF »
Childhood Socioeconomic Status and Serotonin Transporter Gene Polymorphism Enhance Cardiovascular Reactivity to Mental Stress.
R. B. Williams, D. A. Marchuk, I. C. Siegler, J. C. Barefoot, M. J. Helms, B. H. Brummett, R. S. Surwit, J. D. Lane, C. M. Kuhn, K. M. Gadde, et al. (2008)
Psychosom Med
70, 32-39
|Abstract »|Full Text »|PDF »
Biology is psychiatry's new dawn.
J. W. Hill (2008)
The British Journal of Psychiatry
192, 70-71
|Full Text »|PDF »
Differential effects of tryptophan depletion on emotion processing according to face direction.
J. H. G. Williams, D. I. Perrett, G. D. Waiter, and S. Pechey (2007)
Soc Cogn Affect Neurosci
2, 264-273
|Abstract »|Full Text »|PDF »
Alcohol Consumption and Posttraumatic Stress After Exposure to Terrorism: Effects of Proximity, Loss, and Psychiatric History.
D. S. Hasin, K. M. Keyes, M. L. Hatzenbuehler, E. A. Aharonovich, and D. Alderson (2007)
Am J Public Health
97, 2268-2275
|Abstract »|Full Text »|PDF »
Moderation of breastfeeding effects on the IQ by genetic variation in fatty acid metabolism.
A. Caspi, B. Williams, J. Kim-Cohen, I. W. Craig, B. J. Milne, R. Poulton, L. C. Schalkwyk, A. Taylor, H. Werts, and T. E. Moffitt (2007)
PNAS
104, 18860-18865
|Abstract »|Full Text »|PDF »
Depressive Symptoms in Adults Separated from Their Parents as Children: A Natural Experiment during World War II.
A.-K. Pesonen, K. Raikkonen, K. Heinonen, E. Kajantie, T. Forsen, and J. G. Eriksson (2007)
Am. J. Epidemiol.
166, 1126-1133
|Abstract »|Full Text »|PDF »
Genetic Configurations of Political Phenomena: New Theories, New Methods.
I. H. Carmen (2007)
The ANNALS of the American Academy of Political and Social Science
614, 34-55
|Abstract »|PDF »
The Serotonin Transporter Genotype and Social Support and Moderation of Posttraumatic Stress Disorder and Depression in Hurricane-Exposed Adults.
D. G. Kilpatrick, K. C. Koenen, K. J. Ruggiero, R. Acierno, S. Galea, H. S. Resnick, J. Roitzsch, J. Boyle, and J. Gelernter (2007)
Am J Psychiatry
164, 1693-1699
|Abstract »|Full Text »|PDF »
Relationship of SERT Polymorphisms to Depressive and Anxiety Symptoms in Irritable Bowel Syndrome.
M. E. Jarrett, R. Kohen, K. C. Cain, R. L. Burr, A. Poppe, G. P. Navaja, and M. M. Heitkemper (2007)
Biol Res Nurs
9, 161-169
|Abstract »|PDF »
Genes and Environment in Suicidality.
E. S. Gershon (2007)
Am J Psychiatry
164, 1460-1461
|Full Text »|PDF »
13-cis-Retinoic Acid Alters Intracellular Serotonin, Increases 5-HT1A Receptor, and Serotonin Reuptake Transporter Levels In Vitro.
K. C. O'Reilly, S. Trent, S. J. Bailey, and M. A. Lane (2007)
Experimental Biology and Medicine
232, 1195-1203
|Abstract »|Full Text »|PDF »
Serotonin Transporter Gene Polymorphism (5-HTTLPR) and Anxiety Reactivity in Daily Life: A Daily Process Approach to Gene-Environment Interaction.
K. C. Gunthert, T. S. Conner, S. Armeli, H. Tennen, J. Covault, and H. R. Kranzler (2007)
Psychosom Med
69, 762-768
|Abstract »|Full Text »|PDF »
History of childhood maltreatment is associated with comorbid depression in women with migraine.
G. E. Tietjen, J. L. Brandes, K. B. Digre, S. Baggaley, V. T. Martin, A. Recober, L. O. Geweke, F. Hafeez, S. K. Aurora, N. A. Herial, et al. (2007)
Neurology
69, 959-968
|Abstract »|Full Text »|PDF »
Association of a Serotonin Transporter Polymorphism (5-HTTLPR) With Depression, Perceived Stress, and Norepinephrine in Patients With Coronary Disease: The Heart and Soul Study.
C. Otte, J. McCaffery, S. Ali, and M. A. Whooley (2007)
Am J Psychiatry
164, 1379-1384
|Abstract »|Full Text »|PDF »
Designing Multidisciplinary Longitudinal Studies of Human Development: Analyzing Past Research to Inform Methodology.
B. Shulruf, S. Morton, F. Goodyear-Smith, C. O'Loughlin, and R. Dixon (2007)
Eval Health Prof
30, 207-228
|Abstract »|PDF »
Sleep Quality Varies as a Function of 5-HTTLPR Genotype and Stress.
B. H. Brummett, A. D. Krystal, A. Ashley-Koch, C. M. Kuhn, S. Zuchner, I. C. Siegler, J. C. Barefoot, E. L. Ballard, L. P. Gwyther, and R. B. Williams (2007)
Psychosom Med
69, 621-624
|Abstract »|Full Text »|PDF »
The Long and the Short of It: Associations Between 5-HTT Genotypes and Coping With Stress.
K. Wilhelm, J. E. Siegel, A. W. Finch, D. Hadzi-Pavlovic, P. B. Mitchell, G. Parker, and P. R. Schofield (2007)
Psychosom Med
69, 614-620
|Abstract »|Full Text »|PDF »