Temperament and character in mood disorders: influence of DRD4, SERTPR, TPH and MAO-A polymorphisms. Neuropsychobiology

Washington University in St. Louis, San Luis, Missouri, United States
Neuropsychobiology (Impact Factor: 2.26). 02/2006; 53(1):9-16. DOI: 10.1159/000089916
Source: PubMed


Gene variants exert a complex range of effects on human normal and abnormal behavior. We previously reported the effect of gene variants in serotoninergic and dopaminergic pathways, in a range of clinical features in mood disorders, such as symptomathology, periodicity, social adjustment and treatment response. In this paper we hypothesized that the same gene variants could influence temperamental traits in mood disorders patients. We focused on genes of the serotoninergic and dopaminergic systems (dopamine receptor D4 gene, DRD4; serotonin transporter gene, promoter region SERTPR; tryptophan hydroxylase gene, TPH; monoamine oxidase A gene, MAO-A). Two hundred and seven euthymic subjects, affected by major depressive disorder (n=73) and bipolar disorder (n=134) were assessed by the Cloninger's Temperament and Character Inventory (TCI) and typed using PCR-based analyses. Possible stratification factors such as demographic, clinical and other temperamental factors were also taken into account. We observed that homozygosity for the short SERTPR allele was associated with low novelty-seeking scores (p=0.006) and genotypes containing the DRD4 long allele were marginally associated with low harm avoidance (p=0.05). Finally, the long MAO-A allele was associated with decreased persistence scores among females (p=0.006). Our observation of a pattern of influence on temperamental dimension exerted by serotonergic and dopaminergic genes suggests that the contribution of these polymorphisms to the clinical presentation of mood disorders could be mediated by an influence on personality differences.

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Available from: Robert Cloninger, Jun 11, 2014
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    • "The SLC6A4 gene showed inconsistent associations with impulsivity traits. Although the S variant and S/S genotype were associated with low NS scores in samples of White mood disorder patients (Serretti et al., 2006) and Chinese anxiety-depressive alcohol-dependent patients (Lin et al., 2007), respectively, a large proportion of the studies did not replicate these results. "
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    ABSTRACT: The heritability of human personality traits is by now well established. However, since the first reports on associations between specific genetic variants and personality traits, only modest progress has been made in identifying loci that robustly support these associations. The aim of this study was to provide a summary of literature data on association studies focused on the genetic modulation of personality, according to the Cloninger, Eysenck and Costa and McCrae models. PubMed was searched for papers investigating the association between any gene variant and personality traits, which were grouped into five clusters: (a) anxiety, (b) impulsivity, (c) determination-activity, (d) socialization and (e) spirituality, in healthy individuals, populations and psychiatric patients. A total of 369 studies were included. No clear consensus on the role of any individual gene variant in personality modulation emerged, although SLC6A4 haplotypes and the DRD4 rs1800955 promoter variant seemed to be more reliably related to anxiety and impulsivity-related traits, respectively. Because conflicting results emerged from the literature, plausibly as a result of the combined influence of many loci of small effects on personality, larger sample sizes and more narrow and specific phenotype will be the minimum requirements for future genetic studies on personality. Moreover, gene×gene and gene×environment interaction studies deserve further attention.
    International clinical psychopharmacology 10/2013; 29(1). DOI:10.1097/YIC.0b013e328364590b · 2.46 Impact Factor
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    • "So far only one study has been published on temperament traits and TPH1 A218C polymorphism in major depression; it reports a negative result between HA or NS scores and TPH1 genotypes [5]. The C allele of A218C has been reported to be more common among nonorganic and nonpsychotic inpatients with impulsive behavioral traits [6]. "
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    ABSTRACT: Background In 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. Methods Temperament 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. Results The 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. Conclusions Our 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.
    BMC Psychiatry 04/2013; 13(1):118. DOI:10.1186/1471-244X-13-118 · 2.21 Impact Factor
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    • "A good candidate gene for explaining a rGE for self-control is the 5-HTT gene solute carrier family C6, member 4 (SLC6A4). Many previous studies have found associations between the promoter region insertion/deletion (indel) in this gene (5-HTTLPR) and temperamental tendencies that may be related to self-control, for example, novelty-seeking and risk-taking behaviors (Kuhnen & Chiao, 2009; Serretti et al., 2006), reward dependence (Samochowiec et al., 2004), neuroticism (Munafo, Clark, Roberts, & Johnston, 2006), and fearfulness (Hariri et al., 2002). In addition, a recent metaanalysis associated 5-HTTLPR with selective attention to negative stimuli (Pergamin-Hight, Bakersmans-Kranenburg, van IJzendoorn, & Bar-Haim, 2012), a disposition that may be related to the tendency to inhibit certain behaviors in the face of negative cues. "
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    ABSTRACT: Self-control, involving processes such as delaying gratification, concentrating, planning, following instructions, and adapting emotions and behavior to situational requirements and social norms, may have a profound impact on children's adjustment. The importance of self-control suggests that parents are likely to modify their parenting based on children's ability for self-control. We study the effect of children's self-control, a trait partially molded by genetics, on their mothers' parenting, a process of evocative gene-environment correlation. Israeli 3.5-year-old twins (N = 320) participated in a lab session in which their mothers' parenting was observed. DNA was available from most children (N = 228). Mothers described children's self-control in a questionnaire. Boys were lower in self-control and received less positive parenting from their mothers, in comparison with girls. For boys, and not for girls, the serotonin transporter linked polymorphic region gene predicted mothers' levels of positive parenting, an effect mediated by boys' self-control. The implications of this evocative gene-environment correlation and the observed sex differences are discussed.
    Development and Psychopathology 02/2013; 25(1):151-62. DOI:10.1017/S095457941200096X · 4.89 Impact Factor
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