BACKGROUND: There is ongoing interest in the possible interaction of the serotonin-transporter-linked polymorphic region (5-HTTLPR) with environmental factors in determining Major Depressive Disorder (MDD). The current study contributes to this research area by comprehensively examining the interaction-effects and direct-effects of 5-HTTLPR and five environmental factors on MDD prevalence and course in a well-characterized longitudinal sample. METHODS: The sample consisted of 1625 patients with a CIDI-confirmed diagnosis of MDD and 1698 screened controls from the Netherlands. Four MDD outcomes were studied as dependent variables: one main MDD prevalence-outcome (all MDD), two more severe MDD prevalence-outcomes (suicidal and chronic MDD), and one MDD course outcome (chronic versus non-chronic MDD). Because SNP rs25531 modifies the effect of 5-HTTLPR, haplotypes of 5-HTTLPR and rs25531 were measured. For the four MDD outcome measures, we examined the direct effects of 5-HTTLPR/rs25531-haplotypes, five environmental factors (lifetime and recent stressful life-events, sexual abuse, low educational attainment, and childhood trauma) and their interaction in logistic regression models. RESULTS: The environmental factors had large and consistent effects on all four MDD outcomes, including course of MDD. The 5-HTTLPR/rs25531-haplotype had a suggestive effect on course of MDD, but not on presence of MDD. Gene-by-environment interaction was significant (<0.05) for one of the 20 tests performed, which is not more than expected by chance. LIMITATIONS: Environmental factors were not assessed before the onset of MDD. CONCLUSIONS: Environmental factors had a strong impact on the presence and course of MDD, but no evidence for gene-by-environment interaction was found.
BACKGROUND: There is ongoing interest in the possible interaction of the serotonin-transporter-linked polymorphic region (5-HTTLPR) with environmental factors in determining Major Depressive Disorder (MDD). The current study contributes to this research area by comprehensively examining the interaction-effects and direct-effects of 5-HTTLPR and five environmental factors on MDD prevalence and course in a well-characterized longitudinal sample. METHODS: The sample consisted of 1625 patients with a CIDI-confirmed diagnosis of MDD and 1698 screened controls from the Netherlands. Four MDD outcomes were studied as dependent variables: one main MDD prevalence-outcome (all MDD), two more severe MDD prevalence-outcomes (suicidal and chronic MDD), and one MDD course outcome (chronic versus non-chronic MDD). Because SNP rs25531 modifies the effect of 5-HTTLPR, haplotypes of 5-HTTLPR and rs25531 were measured. For the four MDD outcome measures, we examined the direct effects of 5-HTTLPR/rs25531-haplotypes, five environmental factors (lifetime and recent stressful life-events, sexual abuse, low educational attainment, and childhood trauma) and their interaction in logistic regression models. RESULTS: The environmental factors had large and consistent effects on all four MDD outcomes, including course of MDD. The 5-HTTLPR/rs25531-haplotype had a suggestive effect on course of MDD, but not on presence of MDD. Gene-by-environment interaction was significant (<0.05) for one of the 20 tests performed, which is not more than expected by chance. LIMITATIONS: Environmental factors were not assessed before the onset of MDD. CONCLUSIONS: Environmental factors had a strong impact on the presence and course of MDD, but no evidence for gene-by-environment interaction was found.
Authors: Janos Bokor; Sandor Krause; Dora Torok; Nora Eszlari; Sara Sutori; Zsofia Gal; Peter Petschner; Ian M Anderson; Bill Deakin; Gyorgy Bagdy; Gabriella Juhasz; Xenia Gonda Journal: Front Psychiatry Date: 2020-06-25 Impact factor: 4.157
Authors: Thalida E Arpawong; Jinkook Lee; Drystan F Phillips; Eileen M Crimmins; Morgan E Levine; Carol A Prescott Journal: Behav Genet Date: 2015-09-02 Impact factor: 2.805
Authors: Marieke S Tollenaar; Marc L Molendijk; Brenda W J H Penninx; Yuri Milaneschi; Niki Antypa Journal: Eur Arch Psychiatry Clin Neurosci Date: 2017-03-28 Impact factor: 5.270
Authors: Dávid Kovacs; Xénia Gonda; Péter Petschner; Andrea Edes; Nóra Eszlari; György Bagdy; Gabriella Juhasz Journal: Ann Gen Psychiatry Date: 2014-06-13 Impact factor: 3.455
Authors: R C Culverhouse; N L Saccone; A C Horton; Y Ma; K J Anstey; T Banaschewski; M Burmeister; S Cohen-Woods; B Etain; H L Fisher; N Goldman; S Guillaume; J Horwood; G Juhasz; K J Lester; L Mandelli; C M Middeldorp; E Olié; S Villafuerte; T M Air; R Araya; L Bowes; R Burns; E M Byrne; C Coffey; W L Coventry; K A B Gawronski; D Glei; A Hatzimanolis; J-J Hottenga; I Jaussent; C Jawahar; C Jennen-Steinmetz; J R Kramer; M Lajnef; K Little; H M Zu Schwabedissen; M Nauck; E Nederhof; P Petschner; W J Peyrot; C Schwahn; G Sinnamon; D Stacey; Y Tian; C Toben; S Van der Auwera; N Wainwright; J-C Wang; G Willemsen; I M Anderson; V Arolt; C Åslund; G Bagdy; B T Baune; F Bellivier; D I Boomsma; P Courtet; U Dannlowski; E J C de Geus; J F W Deakin; S Easteal; T Eley; D M Fergusson; A M Goate; X Gonda; H J Grabe; C Holzman; E O Johnson; M Kennedy; M Laucht; N G Martin; M R Munafò; K W Nilsson; A J Oldehinkel; C A Olsson; J Ormel; C Otte; G C Patton; B W J H Penninx; K Ritchie; M Sarchiapone; J M Scheid; A Serretti; J H Smit; N C Stefanis; P G Surtees; H Völzke; M Weinstein; M Whooley; J I Nurnberger; N Breslau; L J Bierut Journal: Mol Psychiatry Date: 2017-04-04 Impact factor: 15.992