Article

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: 2.3). 02/2006; 53(1):9-16. DOI: 10.1159/000089916
Source: PubMed

ABSTRACT 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.

Download full-text

Full-text

Available from: Robert Cloninger, Jun 11, 2014
0 Followers
 · 
79 Views
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    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
  • Source
    • "Most of the issues discussed in the context of these studies are relevant to all pharmacogenomics studies of antidepressant induced mania. Several studies have investigated other candidate genes (De Luca et al., 2003; Serretti et al., 2006; Zai et al., 2007). As our knowledge about the mechanism of action of antidepressant drugs and genes that may be involved in this action is limited, the hypothesis free approach of a genome-wide association study (GWAS) may uncover previously unsuspected contributing factors. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Polymorphisms in SNCA, MAPT and LRRK2 genes have recently been confirmed as risk factors for Parkinson's disease (PD), although with small individual attributable risk. Here we investigated the association of PD with interactions between variants of these genes. As part of a previous study of PD susceptibility genes 119 SNCA, MAPT, and LRRK2 haplotype tagging single nucleotide polymorphisms (SNPs) and two variable number tandem repeats (VNTRs) were genotyped in 1098 PD cases from the upper Midwest, USA and 1098 matched controls. Twenty-six of these SNPs were selected for SNP-SNP (or SNP-VNTR or VNTR-VNTR) interaction analysis (256 interaction pairs). Case-control analyses were performed to study association of pairwise SNP interactions with PD susceptibility. Out of the 256 interaction pairs investigated, 10 had uncorrected p-values <0.05. These represented six SNCA-LRRK2 pairs, three SNCA-MAPT pairs, and one MAPT-LRRK2 pair. However, none of these pairwise interactions were significant after correction for multiple testing. Secondary analyses in strata defined by type of control (sibling or unrelated), sex, or age at onset of the case also did not reveal any significant interactions after accounting for multiple testing. This study provides no statistically significant evidence of gene-gene interaction effects for the three confirmed genetic susceptibility loci for PD. However, this does not exclude the possibility that other genomic loci or environmental risk factors interact with these genes.
    Parkinsonism & Related Disorders 08/2011; 17(10):730-6. DOI:10.1016/j.parkreldis.2011.07.001 · 4.13 Impact Factor
  • Source
    • "Most of the issues discussed in the context of these studies are relevant to all pharmacogenomics studies of antidepressant induced mania. Several studies have investigated other candidate genes (De Luca et al., 2003; Serretti et al., 2006; Zai et al., 2007). As our knowledge about the mechanism of action of antidepressant drugs and genes that may be involved in this action is limited, the hypothesis free approach of a genome-wide association study (GWAS) may uncover previously unsuspected contributing factors. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Antidepressants can trigger a rapid mood switch from depression to mania. Identifying genetic risk factors associated with antidepressant induced mania (AIM) may enable individualized treatment strategies for bipolar depression. This review and meta-analysis evaluates the evidence for association between the serotonin transporter gene promoter polymorphism (5HTTLPR) and AIM. Medline up to November 2009 was searched for key words bipolar, antidepressant, serotonin transporter, SLC6A4, switch, and mania. Five studies have evaluated the SLC6A4 promoter polymorphism and AIM in adults (total N=340 AIM+ cases, N=543 AIM- controls). Although a random effects meta-analysis showed weak evidence of association of the S allele with AIM+ status, a test of heterogeneity indicated significant differences in estimated genetic effects between studies. A similar weak association was observed in a meta-analysis based on a subset of three studies that excluded patients on mood stabilizers; however the result was again not statistically significant. Few pharmacogenomic studies of antidepressant treatment of bipolar disorder have been published. The completed studies were underpowered and often lacked important phenotypic information regarding potential confounders such as concurrent use of mood stabilizers or rapid cycling. There is insufficient published data to confirm an association between 5HTTLPR and antidepressant induced mania. Pharmacogenomic studies of antidepressant induced mania have high potential clinical impact provided future studies are of adequate sample size and include rigorously assessed patient characteristics (e.g. ancestry, rapid cycling, concurrent mood stabilization, and length of antidepressant exposure).
    Journal of Affective Disorders 06/2011; 136(1-2):e21-9. DOI:10.1016/j.jad.2011.05.038 · 3.71 Impact Factor
Show more