Genetics and personality traits in patients with social anxiety disorder: A case-control study in South Africa

MRC Unit on Anxiety and Stress Disorders, Department of Psychiatry, University of Stellenbosch, South Africa.
European Neuropsychopharmacology (Impact Factor: 4.37). 04/2007; 17(5):321-7. DOI: 10.1016/j.euroneuro.2006.06.010
Source: PubMed


Social anxiety disorder (SAD) is among the most common of all psychiatric disorders with lifetime prevalence estimates ranging from 7% to 13%. Although there is evidence that SAD has a strong familial basis, there are few studies of potential candidate genes. In addition to a genetic association, there is also the possibility that temperamental risk factors for the disorder may be genetically transmitted. Against this background, our aims were threefold: i.) to compare patients and controls with respect to personality traits, ii.) to genotype a subgroup of these participants to investigate the role of genes encoding components of serotonergic (5-HT) and dopaminergic (DA) pathways in patients with SAD and iii.) to compare differences in temperament dimensions between carriers of different (dominant vs. recessive) alleles for selected polymorphisms in SAD patients.
Sixty-three patients (n=63; 35 male, 28 female) with a DSM-IV diagnosis of generalized SAD and SPIN-scores >18, and age-matched control participants (n=150; 31 male, 119 female) were included in the study. The Temperament and Character Inventory (TCI) was used to measure behaviours associated with specific personality dimensions (i.e. temperament/character). DNA was extracted and genotyped to investigate the role of select candidate genes encoding components in serotonergic and dopaminergic pathways in mediating the development of SAD. To achieve this, the frequency of variants in 5-HT and DA genes was compared between a Caucasian subset of SAD patients (n=41) and a convenience sample of Caucasian controls (n=88), using case-control association analyses. We also investigated the frequency of variants in 5-HT and DA-related genes across temperament characteristics in SAD patients, using analyses of variance (ANOVA).
Patients scored significantly higher on harm avoidance (p<0.001) but lower on novelty seeking (p=0.04) and self-directedness (p=0.004) compared to controls. In the Caucasian subset, there was a difference between patients and controls in distribution of the 5-HT(2A)T102C polymorphism, with significantly more patients harboring T-containing genotypes (T-containing genotypes: [T/T+T/C] vs. [C/C]) (chi2=7.55; p=0.012). Temperament dimensions did not, however, differ significantly between carriers of different (dominant vs. recessive) alleles for the 5-HT(2A)T102C polymorphism in SAD patients.
The results suggest a possible role for the 5-HT(2A)T102C polymorphism in the development of SAD. To date genetic findings in SAD have been inconsistent; nevertheless, serotonergic variants, and their associations with temperaments (e.g. reward dependence) deserve further exploration, in the hope that endophenotypes relevant to SAD can ultimately be delineated.

Download full-text


Available from: Christer Allgulander,
  • Source
    • "NS is defined as a tendency to respond actively to novel stimuli with frequent exploratory and impulsive activity in response to novelty, and is believed to be regulated by the dopamine system [9]. Numerous studies indicate that SAD is associated with an increase in HA [10] [11] [12] [13] [14] [15] [16] [17] and a decrease in NS [10] [16] [17]. In addition, a recent meta-analysis of temperament in anxiety disorder confirms that increases in the HA dimension has been the most consistent and replicated finding across SAD studies, followed by decreases of the NS dimension [6]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: To study qualitatively different subgroups of social anxiety disorder (SAD) based on harm avoidance (HA) and novelty seeking (NS) dimensions. One hundred and forty-two university students with SAD (SCID-DSM-IV) were included in the study. The temperament dimensions HA and NS from the Cloninger's Temperament and Character Inventory were subjected to cluster analysis to identify meaningful subgroups. The identified subgroups were compared for sociodemographics, SAD severity, substance use, history of suicide and self-harm attempts, early life events, and two serotonin transporter gene polymorphisms (5-HTTLPR and STin2.VNTR). Two subgroups of SAD were identified by cluster analysis: a larger (61% of the sample) inhibited subgroup of subjects with "high-HA/low-NS", and a smaller (39%) atypical impulsive subgroup with high-moderate HA and NS. The two groups did not differ in social anxiety severity, but did differ in history of lifetime impulsive-related-problems. History of suicide attempts and self-harm were as twice as frequent in the impulsive subgroup. Significant differences were observed in the pattern of substance misuse. Whereas subjects in the inhibited subgroup showed a greater use of alcohol (P=0.002), subjects in the impulsive subgroup showed a greater use of substances with a high-sensation-seeking profile (P<0.001). The STin2.VNTR genotype frequency showed an inverse distribution between subgroups (P=0.005). Our study provides further evidence for the presence of qualitatively different SAD subgroups and the propensity of a subset of people with SAD to exhibit impulsive, high-risk behaviors. Copyright © 2014 Elsevier Masson SAS. All rights reserved.
    European Psychiatry 12/2014; 30(1). DOI:10.1016/j.eurpsy.2014.09.418 · 3.44 Impact Factor
  • Source
    • "Other targets for CBT augmentation have also been suggested,12 and this seems an exciting area for future investigation.149 As in the case of other anxiety disorders, there is significant scope for studies that incorporate genetic and imaging methods into pharmacotherapy studies,150,151 aiming ultimately at individualizing treatment approaches in SAD. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Given the enormous contribution of anxiety disorders to the burden of disease, it is key to optimize their prevention and treatment. In this critical review we assess advances in the pharmacotherapy of anxiety disorders, as well as remaining challenges, in recent decades, the field has seen rigorous clinical trial methods to quantify the efficacy and safety of serendipitously discovered agents, more focused development of medications with selective mechanisms of action, and the gradual translation of insights from laboratory research into proof-of-principle clinical trials. On the positive side, a considerable database of studies shows efficacy and relative tolerability of the selective serotonin reuptake inhibitors in the major anxiety disorders, and secondary analyses of such datasets have informed questions such as optimal definition of response and remission, optimal dose and duration, and comparative efficacy of different agents. Significant challenges in the field include barriers to appropriate diagnosis and treatment of anxiety disorders, failure of a significant proportion of patients to respond to first-line pharmacotherapy agents, and a limited database of efficacy or effectiveness studies to guide treatment in such cases.
    Dialogues in clinical neuroscience 12/2011; 13(4):423-37.
  • Source
    • "novelty seeking have also been observed in studies of patients with panic disorder [11] [15] and social phobia [3] [20] [23] [24]. A few studies have found associations between anxiety disorders and the remaining TCI dimensions or their subscales: reward dependence [4] [11] [16] [20], persistence [20], self-directedness [3] [19] [20] [23] [24] [25], cooperativeness [3] [19] [20] [24], and self-transcendence [19] [20] [24]. These associations have primarily been observed in studies of patients with social phobia. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The association between anxiety disorders and different measures of personality has been extensively studied to further the understanding of etiology, course, and treatment, and to possibly prevent the development of anxiety disorders. We have proposed a hierarchical model of bodily anxiety symptoms with 1 second-order severity factor and 5 first-order factors: cardio-respiratory, gastro-intestinal, autonomic, vertigo, and tension. The aim of this study was to investigate whether personality traits were differentially related to distinct symptom subdimensions or exclusively related to the general severity factor. Structural equation modeling of data on 120 patients with a primary diagnosis of social phobia and 207 patients with a primary diagnosis of panic disorder was used to examine the association between anxiety symptom dimensions and the scales of the Temperament and Character Inventory and of the Revised NEO Personality Inventory. When both sets of personality measures were simultaneously modeled as predictors, the Revised NEO Personality Inventory scales, neuroticism and extraversion, remained significantly associated with the severity factor, whereas the association between the Temperament and Character Inventory dimensions, harm avoidance and novelty seeking, and the severity factor became nonsignificant. Harm avoidance was negatively associated with the vertigo first-order factor, whereas neuroticism was negatively associated with the cardio-respiratory first-order factor, indicating that personality factors may be differentially related to specific anxiety subdimensions.
    Comprehensive psychiatry 01/2009; 50(1):38-47. DOI:10.1016/j.comppsych.2008.06.005 · 2.25 Impact Factor
Show more