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Keers, Robert; Coleman, Jonathan RI; Lester, Kathryn J; Roberts, Susanna; Breen, Gerome; Thastum, Mikael; Bögels, Susan; Schneider, Silvia; Heiervang, Einar; Meiser-Stedman, Richard; Nauta, Maaike; Creswell, Cathy; Thirlwall, Kerstin; Rapee, Ronald M; Hudson, Jennifer L; Lewis, Cathryn; Plomin, Robert; Eley, Thalia C (2016)
Publisher: Karger
Languages: English
Types: Article
Subjects: Innovations, B, Differential response, Anxiety disorders, Child
Background: The differential susceptibly hypothesis suggests that certain genetic variants moderate the effects of both negative and positive environments on mental health and may therefore be important predictors of response to psychological treatments. Nevertheless, the identification of such variants has so far been limited to preselected candidate genes. In this study we extended the differential susceptibility hypothesis from a candidate gene to a genome-wide approach to test whether a polygenic score of environmental sensitivity predicted response to Cognitive Behavioural Therapy (CBT) in children with anxiety disorders. \ud Methods: We identified variants associated with environmental sensitivity using a novel method in which within-pair variability in emotional problems in 1026 monozygotic (MZ) twin pairs was examined as a function of the pairs’ genotype. We created a polygenic score of environmental sensitivity based on the whole-genome findings and tested the score as a moderator of parenting on emotional problems in 1,406 children and response to individual, group and brief parent-led CBT in 973 children with anxiety disorders.\ud Results: The polygenic score significantly moderated the effects of parenting on emotional problems and the effects of treatment. Individuals with a high score responded significantly better to individual CBT than group CBT or brief parent-led CBT (remission rates: 70.9%, 55.5% and 41.6% respectively).\ud Conclusions: Pending successful replication, our results should be considered exploratory. Nevertheless, if replicated, they suggest that individuals with the greatest environmental sensitivity may be more likely to develop emotional problems in adverse environments, but also benefit more from the most intensive types of treatment.
  • The results below are discovered through our pilot algorithms. Let us know how we are doing!

    • 1 Rapee RM, Schniering CA, Hudson JL: Anxi- 6 Caspi A, Sugden K, Moffitt TE, Taylor A, 10 Kohen R, Cain KC, Buzaitis A, Johnson V, ety disorders during childhood and adoles- Craig IW, Harrington H, McClay J, Mill J, Becker KJ, Teri L, Tirschwell DL, Veith RC, cence: origins and treatment. Annu Rev Clin Martin J, Braithwaite A, Poulton R: Influence Mitchell PH: Response to psychosocial treatPsychol 20095;:311-341. of life stress on depression: moderation by a ment in poststroke depression is associated
    • 2 James AC, James G, Cowdrey FA, Soler A, polymorphism in the 5-HTT gene. Science with serotonin transporter polymorphisms. Choke A: Cognitive behavioural therapy for 2003;301:386-389. Stroke 2011;42:2068-2070. anxiety disorders in children and adoles- 7 Hankin BL, Nederhof E, Oppenheimer CW,11 Drury SS, Gleason MM, Theall KP, Smyke cents. Cochrane Database Syst Rev 2013; Jenness J, Young JF, Abela JR, Smolen A, AT, Nelson CA, Fox NA, Zeanah CH: Genet6:CD004690. Ormel J, Oldehinkel AJ: Differential suscepti- ic sensitivity to the caregiving context: the in-
    • 3 Hudson JL, Lester KJ, Lewis CM, Tropeano bility in youth: evidence that 5-HTTLPR × fluence of 5httlpr and BDNF Val66Met on inM, Creswell C, Collier DA, Cooper P, Lyne- positive parenting is associated with positive discriminate social behavior. Physiol Behav ham HJ, Morris T, Rapee RM, Roberts S, affect 'for better and worse'. Transl Psychiatry 2012;106:728-735. Donald JA, Eley TC: Predicting outcomes fol- 2011;1:e44. 12 Brett ZH, Humphreys KL, Smyke AT, Glealowing cognitive behaviour therapy in chi8ldPluess M, Belsky J, Way BM, Taylor SE: 5- son MM, Nelson CA, Zeanah CH, Fox NA, anxiety disorders: the influence of genetic, de- HTTLPR moderates effects of current life Drury SS: Serotonin transporter linked polymographic and clinical information. J Child events on neuroticism: differential suscepti- morphic region (5-HTTLPR) genotype modPsychol Psychiatry 205143:;1086-1094. bility to environmental influences. Prog Neu- erates the longitudinal impact of early care-
    • 4 Morath J, Moreno-Villanueva M, Hamuni G, ropsychopharmacol Biol Psychiatry 23041:0; giving on externalizing behavior. Dev PsyKolassa S, Ruf-Leuschner M, Schauer M, El- 1070-1074. chopathol 201257;:7-18. bert T, Burkle A, Kolassa IT: Effects of psy- 9 Taylor SE, Way BM, Welch WT, Hilmert CJ, 13 Eley TC, Hudson JL, Creswell C, Tropeano M, chotherapy on DNA strand break accumula- Lehman BJ, Eisenberger NI: Early family en- Lester KJ, Cooper P, Farmer A, Lewis CM, Lytion originating from traumatic stress. Psy- vironment, current adversity, the serotonin neham HJ, Rapee RM, Uher R, Zavos HM, chother Psychosom 208134:2; 89-297. transporter promoter polymorphism, and Collier DA: Therapygenetics: the 5HTTLPR
    • 5 Belsky J, Pluess M: Beyond diathesis stress: depressive symptomatology. Biol Psychiatry and response to psychological therapy. Mol differential susceptibility to environmental 2006;60:671-676. Psychiatry 201127;:236-237. influences. Psychol Bull 200193;5:885-908.
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