title: Genetics and personality traits in patients with social anxiety disorder: a case-control study in South Africa.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: MRC Unit on Anxiety and Stress Disorders, Department of Psychiatry, University of Stellenbosch, South Africa. cl2@sun.ac.za
authors.forename: Christine
authors.initials: C
authors.lastname: Lochner
authors.forename: Sian
authors.initials: S
authors.lastname: Hemmings
authors.forename: Soraya
authors.initials: S
authors.lastname: Seedat
authors.forename: Craig
authors.initials: C
authors.lastname: Kinnear
authors.forename: Renata
authors.initials: R
authors.lastname: Schoeman
authors.forename: Kristina
authors.initials: K
authors.lastname: Annerbrink
authors.forename: Marie
authors.initials: M
authors.lastname: Olsson
authors.forename: Elias
authors.initials: E
authors.lastname: Eriksson
authors.forename: Johanna
authors.initials: J
authors.lastname: Moolman-Smook
authors.forename: Christer
authors.initials: C
authors.lastname: Allgulander
authors.forename: Dan J
authors.initials: DJ
authors.lastname: Stein
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D015897:Comorbidity; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010551:Personality; D010555:Personality Inventory; D010698:Phobic Disorders / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology* / Q000523:psychology; D011110:Polymorphism, Genetic; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics*; D013019:South Africa / Q000453:epidemiology
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D044402:Receptor, Serotonin, 5-HT2A