BACKGROUND: Genetic and environmental factors shape life-long vulnerability to depression, but most gene-environment interaction (G×E) research has focused on cross-sectional assessments rather than life-course phenotypes. This study tests the hypothesis that the G×E involving the length polymorphism in the serotonin-transporter-gene-linked-promoter-region (5-HTTLPR) and childhood maltreatment is specific to depression that runs a persistent course in adulthood. METHODS: The hypothesis is tested in two cohorts. Men and women in the Dunedin Study (N=847), New Zealand, followed to age 32 years with 96% retention and women in the E-Risk Study (N=930), England, followed to age 40 years with 96% retention. Diagnoses of past-year major depressive episode were established at four separate assessments. Depression diagnosed on two or more occasions was considered persistent. RESULTS: In both cohorts, statistical tests of gene-environment interactions showed positive results for persistent depression but not single-episode depression. Individuals with two short 5-HTTLPR alleles and childhood maltreatment had elevated risk of persistent but not single-episode depression. LIMITATIONS: Some cases of recurrent depression may have been misclassified as single-episode due to non-contiguous assessment windows, but this would have a conservative effect on the findings. Chronic and recurrent depression could not be reliably distinguished due to non-contiguous periods of assessment. Therefore, the term persistent depression is used to describe either chronic or recurrent course. CONCLUSIONS: The specific effect on persistent depression increases the significance of this G×E for public health. Research that does not distinguish persistent course may underestimate G×E effects and account for some replication failures in G×E research.
BACKGROUND: Genetic and environmental factors shape life-long vulnerability to depression, but most gene-environment interaction (G×E) research has focused on cross-sectional assessments rather than life-course phenotypes. This study tests the hypothesis that the G×E involving the length polymorphism in the serotonin-transporter-gene-linked-promoter-region (5-HTTLPR) and childhood maltreatment is specific to depression that runs a persistent course in adulthood. METHODS: The hypothesis is tested in two cohorts. Men and women in the Dunedin Study (N=847), New Zealand, followed to age 32 years with 96% retention and women in the E-Risk Study (N=930), England, followed to age 40 years with 96% retention. Diagnoses of past-year major depressive episode were established at four separate assessments. Depression diagnosed on two or more occasions was considered persistent. RESULTS: In both cohorts, statistical tests of gene-environment interactions showed positive results for persistent depression but not single-episode depression. Individuals with two short 5-HTTLPR alleles and childhood maltreatment had elevated risk of persistent but not single-episode depression. LIMITATIONS: Some cases of recurrent depression may have been misclassified as single-episode due to non-contiguous assessment windows, but this would have a conservative effect on the findings. Chronic and recurrent depression could not be reliably distinguished due to non-contiguous periods of assessment. Therefore, the term persistent depression is used to describe either chronic or recurrent course. CONCLUSIONS: The specific effect on persistent depression increases the significance of this G×E for public health. Research that does not distinguish persistent course may underestimate G×E effects and account for some replication failures in G×E research.
Authors: M Aguilera; B Arias; M Wichers; N Barrantes-Vidal; J Moya; H Villa; J van Os; M I Ibáñez; M A Ruipérez; G Ortet; L Fañanás Journal: Psychol Med Date: 2009-02-12 Impact factor: 7.723
Authors: Teri A Manolio; Francis S Collins; Nancy J Cox; David B Goldstein; Lucia A Hindorff; David J Hunter; Mark I McCarthy; Erin M Ramos; Lon R Cardon; Aravinda Chakravarti; Judy H Cho; Alan E Guttmacher; Augustine Kong; Leonid Kruglyak; Elaine Mardis; Charles N Rotimi; Montgomery Slatkin; David Valle; Alice S Whittemore; Michael Boehnke; Andrew G Clark; Evan E Eichler; Greg Gibson; Jonathan L Haines; Trudy F C Mackay; Steven A McCarroll; Peter M Visscher Journal: Nature Date: 2009-10-08 Impact factor: 49.962
Authors: Paul G Surtees; Nicholas W J Wainwright; Saffron A G Willis-Owen; Robert Luben; Nicholas E Day; Jonathan Flint Journal: Biol Psychiatry Date: 2005-09-09 Impact factor: 13.382
Authors: Nis P Suppli; Jens D Bukh; Terrie E Moffitt; Avshalom Caspi; Christoffer Johansen; Anne Tjønneland; Lars V Kessing; Susanne O Dalton Journal: Depress Anxiety Date: 2017-06-07 Impact factor: 6.505
Authors: Helen L Fisher; Sarah Cohen-Woods; Georgina M Hosang; Ania Korszun; Mike Owen; Nick Craddock; Ian W Craig; Anne E Farmer; Peter McGuffin; Rudolf Uher Journal: J Affect Disord Date: 2012-07-25 Impact factor: 4.839