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A Polymorphism in the Serotonin Receptor 3A (HTR3A) Gene and Its Association With Harm Avoidance in Women
Jonas Melke, PhD;
Lars Westberg, BSc;
Staffan Nilsson, PhD;
Mikael Landén, MD, PhD;
Henrik Soderstrom, MD, PhD;
Fariba Baghaei, MD;
Roland Rosmond, MD, PhD;
Göran Holm, MD, PhD;
Per Björntorp, MD, PhD;
Lars-Göran Nilsson, PhD;
Rolf Adolfsson, MD, PhD;
Elias Eriksson, PhD
Arch Gen Psychiatry. 2003;60:1017-1023.
Background The brain neurotransmitter serotonin is known to affect various aspects of human behavior, including personality traits. Serotonin receptor type 3 is a ligand-gated channel encoded by 2 different subunit genes, HTR3A and HTR3B. A polymorphism (C178T) in the 5' region of the HTR3A gene has recently been identified and suggested to be of functional importance.
Objective To elucidate the possible association between the C178T polymorphism in the HTR3A gene and personality traits in women.
Design Two independent samples of 35- to 45-year-old Swedish women were recruited using the population register. Sample 1 (n = 195) was assessed via the Karolinska Scales of Personality and the Temperament and Character Inventory; sample 2 (n = 175) was assessed using the latter only. Both samples were genotyped with respect to the C178T polymorphism in the HTR3A gene. The A1596G polymorphism in the same gene was also investigated.
Results A significant association between C178T genotype and the Temperament and Character Inventory factor harm avoidance was observed in sample 1 (corrected for multiple comparisons P = .04); this finding was subsequently replicated in sample 2 (P = .004) (pooled populations: P<.001). In the pooled sample, all harm avoidance subscales were found to be significantly associated with the C178T polymorphism: anticipatory worry (P = .001), fear of uncertainty (P<.001), shyness (P<.001), and fatigability and asthenia (P = .008). In addition, a significant association was found in sample 1 between the C178T polymorphism and the Karolinska Scales of Personality nonconformity factor (corrected P = .002), including the subscales of social desirability (P<.001), indirect aggression (P = .002), verbal aggression (P = .05), and irritability (P<.001). Participants homozygous for the less common T allele (<4%) differed from the remaining women by displaying lower ratings on harm avoidance and nonconformity.
Conclusion The C178T polymorphism in the HTR3A gene may affect the personality trait of harm avoidance in women.
From the Departments of Pharmacology (Drs Melke and Eriksson and Mr Westberg), Clinical Genetics (Dr S. Nilsson), Child and Adolescent Psychiatry (Dr Soderstrom), and Heart and Lung Diseases (Drs Baghaei, Rosmond, Holm, and Björntorp), the Section of Psychiatry (Dr Landén), and the Institute of Clinical Neuroscience (Dr Soderstrom), Göteborg University, Göteborg; the Department of Mathematical Statistics, Chalmers University of Technology, Göteborg (Dr S. Nilsson); the National Board of Forensic Medicine, Göteborg (Dr Soderstrom); the Department of Psychology, Stockholm University, Stockholm (Dr L.-G. Nilsson); and the Department of Psychiatry, Umeå University, Umeå (Dr Adolfsson), Sweden.
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