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: 2.26). 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.

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Available from: Robert Cloninger, Jun 11, 2014
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    • "Since 25 papers did not report raw scores on TPQ/TCI dimensions, an attempt was made to obtain this information from the authors. Unpublished data were gathered this way for seven papers (Goekoop and De Winter, 2011; Harnic et al., 2013; Minaya, 2009; Minelli, 2009; Pawlak et al., 2013; Savitz et al., 2008; Serretti et al., 2006), which were then included in the meta-analysis. "
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    ABSTRACT: Background: Cloninger's psychobiological model of personality has been extensively applied to subjects affected by mood disorders (MOOD). However, most studies are widely heterogeneous in terms of sample size, methods of assessment, and selection of participants. Methods: We conducted a systematic review of literature and a random effects meta-analysis of studies comparing at least two of the following groups: (a) adults with a primary MOOD diagnosis (Bipolar Disorder (BP) or major depressive disorder (MDD)), (b) their unaffected siblings (SIB) or (c) healthy subjects (HS), and reporting quantitative results from the Tridimensional Personality Questionnaire (TPQ) or the Temperament and Character Inventory (TCI). Subgroup, sensitivity and meta-regression analyses were also conducted. Results: High Harm Avoidance and low Self-Directedness were consistently associated with MOOD and SIB samples. BP was characterized by higher scores in Novelty Seeking and Self-Transcendence than HS, SIB and MDD. Age seemed to have a negative effect on Novelty Seeking and a positive effect on Harm Avoidance, Cooperativeness and Self-Transcendence. An euthymic mood state was associated with reduced Harm Avoidance, but increased Reward Dependence, Self-Directedness and Cooperativeness. Limitations: The quality of the included studies varied and was relatively low. Moreover, publication bias and heterogeneity in the distribution of effect sizes may also have limited our results. Conclusion: High Harm Avoidance and Low Self-Directedness may be trait markers for MOOD in general, while high Novelty Seeking and high Self-Transcendence may be specific to BP. Future studies are needed to disentangle the state-trait effect of each personality dimension.
    Full-text · Article · Jan 2016 · Journal of Affective Disorders
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    • "This obsessional pattern involves an exigent effort to strive for order and perfection, associated with harsh self-criticism of failure, and a reduced tolerability for stressful life events, which predisposes people to depression. On the other hand, BP subjects were characterized by higher levels in NS, being apparently more extravagant, impulsive and disorderly than HS, SIB and MDD (Janowsky et al., 1999;Nowakowska et al., 2005;Serretti et al., 2006;Young et al., 1995). However, this finding may require a more complex interpretation, since in our sample NS was significantly moderated by both age (Brändström et al., 2001;Miettunen et al., 2007) and quality of the included studies. "
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    ABSTRACT: Background: Cloninger's psychobiological model of personality has been extensively applied to subjects affected by mood disorders (MOOD). However, most studies are widely heterogeneous in terms of sample size, methods of assessment, and selection of participants. Methods: We conducted a systematic review of literature and a random effects meta-analysis of studies comparing at least two of the following groups: (a) adults with a primary MOOD diagnosis (Bipolar Disorder (BP) or Major Depressive Disorder(MDD)), (b) their unaffected siblings (SIB) or (c) healthy subjects (HS), and reporting quantitative results from the Tridimensional Personality Questionnaire (TPQ) or the Temperament and Character Inventory (TCI). Subgroup, sensitivity and meta-regression analyses were also conducted. Results: High Harm Avoidance and low Self-Directedness were consistently associated with MOOD and SIB samples. BP was characterized by higher scores in Novelty Seeking and Self-Transcendence than HS, SIB and MDD. Age seemed to have a negative effect on Novelty Seeking and a positive effect on Harm Avoidance, Cooperativeness and Self-Transcendence. An euthymic mood state was associated with reduced Harm Avoidance, but increased Reward Dependence, Self-Directedness and Cooperativeness. Limitations: The quality of the included studies varied and was relatively low. Moreover, publication bias and heterogeneity in the distribution of effect sizes may also have limited our results. Conclusion: High Harm Avoidance and Low Self-Directedness may be trait markers for MOOD in general, while high Novelty Seeking and high Self-Transcendence may be specific to BP. Future studies are needed to disentangle the state-trait effect of each personality dimension.
    Full-text · Article · Jan 2016 · Journal of Affective Disorders
    • "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.
    No preview · Article · Oct 2013 · International clinical psychopharmacology
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