Serotonin receptor 1A promoter polymorphism, rs 6295, modulates human anxiety levels via altering parasympathetic nervous activity

• Published in: Acta psychiatrica Scandinavica Vol. 137; no. 3; pp. 263 - 272
• Main Authors: Huang, J.‐H., Chang, H.‐A., Fang, W.‐H., Ho, P.‐S., Liu, Y.‐P., Wan, F.‐J., Tzeng, N.‐S., Shyu, J.‐F., Chang, C.‐C.
• Format: Journal Article
• Language: English
• Published: 01.03.2018
• ISSN: 0001-690X; 1600-0447
• DOI: 10.1111/acps.12853

Objective The G‐allele of the ‐1019C/G ( rs 6295) promoter polymorphism of the serotonin receptor 1A ( HTR 1A ) gene has been implicated in anxiety; however, the underlying neurophysiological processes are still not fully understood. Recent evidence indicates that low parasympathetic (vagal) tone is predictive of anxiety. We thus conducted a structural equation model ( SEM ) to examine whether the HTR 1A rs 6295 variant can affect anxiety by altering parasympathetic nervous activity. Method A sample of 1141 drug‐free healthy Han Chinese was recruited for HTR 1A genotyping. Autonomic nervous function was assessed by short‐term spectral analysis of heart rate variability ( HRV ). Anxiety and stress levels were evaluated by the Beck Anxiety Inventory ( BAI ) and the Perceived Stress Scale ( PSS ) respectively. Results The number of the HTR 1A G allele was inversely correlated with high‐frequency power ( HF ), a parasympathetic index of HRV . The HF index was negatively associated with BAI scores. Furthermore, the good‐fitting SEM , adjusting for confounding variables (e.g., age and PSS levels), revealed a significant pathway linking rs 6295 variant to BAI scores via HF index modulation. Conclusion These results are the first to show that HTR 1A ‐1019C/G polymorphism influences anxiety levels by modulating parasympathetic tone, providing a neurophysiological insight into the role of  HTR 1A in human anxiety.