research published 2026-06-30 · by Hong YM, Kim SJ, Pak K, Yu SB

Brain imaging and behavior · 2026 Jun 30

Abstract

The serotonin transporter gene-linked polymorphic region (5-HTTLPR) has been linked to psychiatric disorders. This meta-analysis aimed to investigate the association between the 5-HTTLPR polymorphism and the availability of the serotonin transporter (SERT) or serotonin 1 A receptor (5-HT1AR), measured by positron emission tomography (PET) or single-photon emission computed tomography (SPECT). A systematic search was conducted to identify studies comparing SERT or 5-HT1AR availability by 5-HTTLPR genotype using PET or SPECT scans in healthy subjects. The standardized mean difference in SERT or 5-HT1AR availability between LL and S-carrier genotypes was calculated for each study in both frequentist and Bayesian meta-analyses. Eleven studies met the inclusion criteria. Pooled analysis showed no differences in SERT availability in the striatum, frontal lobe, brainstem, or thalamus between LL and S carriers of 5-HTTLPR. Similarly, no significant difference was observed in 5-HT1AR availability in the raphe nuclei between two genotypes. Bayesian meta-analysis confirmed that the standardized mean difference in SERT availability between LL and S carriers overlapped substantially with zero. In conclusion, the 5-HTTLPR polymorphism does not appear to affect the availability of SERT or 5-HT1AR in healthy individuals. This suggests that the relationship between 5-HTTLPR polymorphisms and psychiatric disorders is complex and that this polymorphism alone may not fully explain susceptibility.

Neurotransmitters

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