Interaction among childhood trauma and functional polymorphisms in the serotonin pathway moderate the risk of depressive disorders

详细信息    查看全文

• 作者：Sandra Van der Auwera ; Deborah Janowitz…
• 关键词：Gene–gene–environment interaction ; TPH2 ; 5 ; HTTLPR ; Abuse ; Serotonin
• 刊名：European Archives of Psychiatry and Clinical Neuroscience
• 出版年：2014
• 出版时间：November 2014
• 年：2014
• 卷：264
• 期：1-supp
• 页码：45-54
• 全文大小：266 KB
• 参考文献：1. Wittchen, HU, Jacobi, F, Rehm, J, Gustavsson, A, Svensson, M, J?nsson, B, Olesen, J, Allgulander, C, Alonso, J, Faravelli, C, Fratiglioni, L, Jennum, P, Lieb, R, Maercker, A, vanOs, J, Preisig, M, Salvador-Carulla, L, Simon, R, Steinhausen, HC (2011) The size and burden of mental disorders and other disorders of the brain in Europe 2010. Eur Neuropsychopharmacol 21: pp. 655-679 CrossRef
  2. Sullivan, PF, Neale, MC, Kendler, KS (2000) Genetic epidemiology of major depression: review and meta-analysis. Am J Psychiatry 157: pp. 1552-1562 CrossRef
  A mega-analysis of genome-wide association studies for major depressive disorder. Mol Psychiatry 18: pp. 497-511
  3. Hek, K, Demirkan, A, Lahti, J, Terracciano, A, Teumer, A (2013) A genome-wide association study of depressive symptoms. Biol Psychiatry 73: pp. 667-678 CrossRef
  4. Zill, P, Baghai, TC, Zwanzger, P, Schüle, C, Eser, D, Rupprecht, R, M?ller, HJ, Bondy, B, Ackenheil, M (2004) SNP and haplotype analysis of a novel tryptophan hydroxylase isoform (TPH2) gene provide evidence for association with major depression. Mol Psychiatry 9: pp. 1030-1036 CrossRef
  5. Gao, J, Pan, Z, Jiao, Z, Li, F, Zhao, G, Wei, Q, Pan, F, Evangelou, E (2012) TPH2 gene polymorphisms and major depression-a meta-analysis. PLoS One.
  6. Walther, DJ, Peter, JU, Bashammakh, S, H?rtnagl, H, Voits, M, Fink, H, Bader, M (2003) Synthesis of serotonin by a second tryptophan hydroxylase isoform. Science 299: pp. 76 CrossRef
  7. Jacobsen, JPR, Medvedev, IO, Caron, MG (2012) The 5-HT deficiency theory of depression: perspectives from a naturalistic 5-HT deficiency model, the tryptophan hydroxylase 2Arg 439Hisknockin mouse. Phil Trans Soc B 367: pp. 2444-2459 CrossRef
  8. Widom, CS, DuMont, K, Czaja, SJ (2007) A prospective investigation of major depressive disorder and comorbidity in abused and neglected children grownup. Arch Gen Psychiatry 64: pp. 49-56 CrossRef
  9. Heim, C, Binder, EB (2012) Current research trends in early life stress and depression: Review of human studies on sensitive periods, gene-environment interactions, and epigenetics. Exp Neurol 233: pp. 102-111 CrossRef
  10. Edwards, VJ, Holden, GW, Felitti, VJ, Anda, RF (2003) Relationship between multiple forms of childhood maltreatment and adult mental health in community respondents: results from the adverse childhood experiences study. Am J Psychiatry 160: pp. 1453-1460 CrossRef
  11. Chapman, DP, Whitfield, CL, Felitti, VJ, Dube, SR, Edwards, VJ, Anda, RF (2004) Adverse childhood experiences and the risk of depressive disorders in adulthood. J Affect Disord 82: pp. 217-225 CrossRef
  12. Kendler, KS, Eaves, LJ (1986) Models for the joint effect of genotype and environment on liability to psychiatric illness. Am J Psychiatry 143: pp. 279-289
  13. Cadoret, RJ, Yates, WR, Troughton, E, Woodworth, G, Stewart, MA (1995) Genetic-environmental interaction in the genesis of aggressivity and conduct disorders. Arch Gen Psychiatry 52: pp. 916-924 CrossRef
  14. Caspi, A, Sugden, K, Moffitt, TE, Taylor, A, Craig, IW, Harrington, H, McClay, J, Mill, J, Martin, J, Braithwaite, A, Poulton, R (2004) Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science 301: pp. 386-389 CrossRef
  15. Grabe, HJ, Schwahn, C, Mahler, J, Schulz, A, Spitzer, C, Fenske, K, Appel, K, Barnov, S, Nauck, M, Schomerus, G, Rosskopf, D, Biffar, R, John, U, V?lzke, H, Freyberger, HJ (2012) Moderation of adult depressi
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Psychiatry
  Neurosciences
  Neurology
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1433-8491

文摘

Depressive disorders are influenced by a complex interplay between genetic and environmental factors. Multiple studies support a role of serotonergic pathways in the pathophysiology of depressive disorders. As a rate-limiting enzyme of serotonin synthesis in the brain, tryptophan hydroxylase 2 (TPH2) represents a plausible candidate gene. This also applies to the serotonin reuptake transporter (5-HTTLPR) regulating the availability of serotonin in the synaptic gap. We hypothesize that functional polymorphisms (TPH2: rs7305115, 5-HTTLPR and rs25531) within both genes contribute to the risk of depressive disorders after childhood abuse in adult life. To confirm our results, we investigated two independent samples of Caucasian subjects from the study of health in Pomerania (SHIP–LEGEND: n?=?2,029 and SHIP–TREND-0: n?=?2,475). Depression severity was assessed by the Beck depression inventory (BDI-II) for LEGEND and the patient health questionnaire (PHQ-9) for TREND-0. Childhood abuse was assessed by the childhood trauma questionnaire. Rs7305115 (TPH2) revealed significant effects in SNP?×?abuse and SNP?×?SNP as well as in the three-way interaction. This three-way interaction among abuse, TPH2 and 5-HTTLPR showed a significant effect on depression score (p?=?0.023). The SS genotype of 5-HTTLPR was associated with increased depression scores after childhood abuse only in carriers of the low-expression TPH2 GG genotype, whereas the TPH2 AA genotype reversed this effect. Our results support the role of interaction effects of genetic variants within serotonergic pathways. Genetic variants that may decrease the presynaptic serotonin concentration were associated with increased adult depressive symptoms in subjects with childhood abuse.