TPH-2 Polymorphisms Interact with Early Life Stress to Influence Response to Treatment with Antidepressant Drugs

Int J Neuropsychopharmacol. 2016 Nov 1;19(11):pyw070. doi: 10.1093/ijnp/pyw070. Print 2016 Nov.

Abstract

Background: Variation in genes implicated in monoamine neurotransmission may interact with environmental factors to influence antidepressant response. We aimed to determine how a range of single nucleotide polymorphisms in monoaminergic genes influence this response to treatment and how they interact with childhood trauma and recent life stress in a Chinese sample. An initial study of monoaminergic coding region single nucleotide polymorphisms identified significant associations of TPH2 and HTR1B single nucleotide polymorphisms with treatment response that showed interactions with childhood and recent life stress, respectively (Xu et al., 2012).

Methods: A total of 47 further single nucleotide polymorphisms in 17 candidate monoaminergic genes were genotyped in 281 Chinese Han patients with major depressive disorder. Response to 6 weeks' antidepressant treatment was determined by change in the 17-item Hamilton Depression Rating Scale score, and previous stressful events were evaluated by the Life Events Scale and Childhood Trauma Questionnaire-Short Form.

Results: Three TPH2 single nucleotide polymorphisms (rs11178998, rs7963717, and rs2171363) were significantly associated with antidepressant response in this Chinese sample, as was a haplotype in TPH2 (rs2171363 and rs1487278). One of these, rs2171363, showed a significant interaction with childhood adversity in its association with antidepressant response.

Conclusions: These findings provide further evidence that variation in TPH2 is associated with antidepressant response and may also interact with childhood trauma to influence outcome of antidepressant treatment.

Keywords: TPH2; antidepressive agents; depression; polymorphism; single nucleotide; stress.

Publication types

  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Affect / drug effects*
  • Age Factors
  • Antidepressive Agents / therapeutic use*
  • Asian People / genetics
  • China
  • Depressive Disorder, Major / drug therapy*
  • Depressive Disorder, Major / ethnology
  • Depressive Disorder, Major / genetics
  • Depressive Disorder, Major / psychology
  • Female
  • Gene Frequency
  • Gene-Environment Interaction*
  • Haplotypes
  • Humans
  • Male
  • Middle Aged
  • Pharmacogenetics
  • Pharmacogenomic Variants*
  • Polymorphism, Single Nucleotide*
  • Remission Induction
  • Risk Factors
  • Stress, Psychological*
  • Surveys and Questionnaires
  • Time Factors
  • Treatment Outcome
  • Tryptophan Hydroxylase / genetics*
  • Young Adult

Substances

  • Antidepressive Agents
  • TPH2 protein, human
  • Tryptophan Hydroxylase