TPH1 A218C polymorphism and temperament in major depression

BackgroundIn major depression, one of the candidate genes possibly affecting the risk and severity of symptoms has been found to be tryptophan hydroxylase (TPH1). Variation in treatment response to antidepressive agents according to TPH1 genotype has also been found in several studies. However, the relationship between temperament and TPH1 genotype in major depression is poorly understood, as only one study has been published so far. There are no earlier studies on the interaction between temperament traits, antidepressive medication response and TPH1 genotype. This interaction was studied in 97 subjects with major depression treated for six weeks with selective serotonine reuptake inhibitors.MethodsTemperament dimensions Harm Avoidance (HA), Novelty Seeking (NS), Reward Dependence (RD) and Persistence (P) scores at baseline (1) and endpoint (2) were rated with the Temperament and Character Inventory (TCI) and compared between TPH1 A218C genotypes. Multivariate analysis of co-variance (MANCOVA) was used to analyze the interaction between the TPH1 genotype, treatment response and the different temperament dimensions at baseline and endpoint. In the analysis model, treatment response was used as a covariate and TPH1 genotype as a factor. A post hoc analysis for an interaction between remission status and TPH1 A218C genotype at endpoint HA level was also performed.ResultsThe number of TPH1 A-alleles was associated with increasing levels in NS1 and NS2 scores and decreasing levels in HA1 and HA2 scores between TPH1 A218C genotypes. In the MANCOVA model, TPH1 genotype and treatment response had an interactive effect on both HA1 and HA2 scores, and to a lesser degree on NS2 scores. Additionally, an interaction between remission status and TPH1 A218C genotype was found to be associated with endpoint HA score, with a more marked effect of the interaction between CC genotype and remission status compared to A-allele carriers.ConclusionsOur results suggest that in acute depression TPH1 A218C polymorphism and specifically the CC genotype together with the information on remission or treatment response differentiates between different temperament profiles and their changes.

[1]  M. Åsberg,et al.  A New Depression Scale Designed to be Sensitive to Change , 1979, British Journal of Psychiatry.

[2]  C. R. Cloninger,et al.  A psychobiological model of temperament and character. , 1993, Archives of general psychiatry.

[3]  J. Macher,et al.  A dimensional impulsive-aggressive phenotype is associated with the A218C polymorphism of the tryptophan hydroxylase gene: a pilot study in well-characterized impulsive inpatients. , 2002, American journal of medical genetics.

[4]  M. Bader,et al.  A unique central tryptophan hydroxylase isoform. , 2003, Biochemical pharmacology.

[5]  S. Tsai,et al.  Allelic Variants of the Tryptophan Hydroxylase (A218C) and Serotonin 1B Receptor (A-161T) and Personality Traits , 2003, Neuropsychobiology.

[6]  C. Robert Cloninger,et al.  Temperament and Character in Mood Disorders: Influence of DRD4, SERTPR, TPH and MAO-A Polymorphisms , 2006, Neuropsychobiology.

[7]  M. Åsberg,et al.  Haplotype Analysis Reveals Tryptophan Hydroxylase (TPH) 1 Gene Variants Associated with Major Depression , 2006, Biological Psychiatry.

[8]  T. Lehtimäki,et al.  Tryptophan hydroxylase 1 gene haplotypes modify the effect of a hostile childhood environment on adulthood harm avoidance , 2007, Genes, brain, and behavior.

[9]  K. Otani,et al.  No association between the TPH A218C polymorphism and personality traits in Japanese healthy subjects , 2007, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[10]  M. Maj,et al.  Association between A218C polymorphism of the tryptophan-hydroxylase-1 gene, harm avoidance and binge eating behavior in bulimia nervosa , 2007, Neuroscience Letters.

[11]  M. Owen,et al.  Tryptophan hydroxylase and catechol-O-methyltransferase gene polymorphisms: relationships to monoamine metabolite concentrations in CSF of healthy volunteers , 2008, European Archives of Psychiatry and Clinical Neuroscience.

[12]  B. Ham,et al.  Impact of the tryptophan hydroxylase 1 gene A218C polymorphism on amygdala activity in response to affective facial stimuli in patients with major depressive disorder , 2009, Genes, brain, and behavior.

[13]  G. Jenkins,et al.  Resequencing of serotonin-related genes and association of tagging SNPs to citalopram response , 2009, Pharmacogenetics and genomics.

[14]  T. Lehtimäki,et al.  5-HTR1A, 5-HTR2A, 5-HTR6, TPH1 and TPH2 polymorphisms and major depression , 2009, Neuroreport.

[15]  H. Möller,et al.  Predominant expression of tryptophan hydroxylase 1 mRNA in the pituitary: A postmortem study in human brain , 2009, Neuroscience.

[16]  T. Lehtimäki,et al.  TPH1 218A/C polymorphism is associated with major depressive disorder and its treatment response , 2010, Neuroscience Letters.

[17]  O. Andreassen,et al.  Tryptophan hydroxylase gene 1 (TPH1) variants associated with cerebrospinal fluid 5-hydroxyindole acetic acid and homovanillic acid concentrations in healthy volunteers , 2010, Psychiatry Research.

[18]  Janet Best,et al.  Serotonin synthesis, release and reuptake in terminals: a mathematical model , 2010, Theoretical Biology and Medical Modelling.

[19]  A. Serretti,et al.  Review and meta-analysis of antidepressant pharmacogenetic findings in major depressive disorder , 2010, Molecular Psychiatry.

[20]  O. Kampman,et al.  Can onset and recovery in depression be predicted by temperament? A systematic review and meta-analysis. , 2011, Journal of affective disorders.

[21]  A. Illi,et al.  Temperament profiles, major depression, and response to treatment with SSRIs in psychiatric outpatients☆ , 2012, European Psychiatry.