Association between glutamate transporter gene polymorphisms and obsessive-compulsive disorder/trait empathy in a Korean population

Abstract

Accumulating evidence suggests that the glutamatergic system plays a major role in the pathophysiology of obsessive compulsive disorder (OCD) and empathic processing. Particularly, genetic influence of glutamate transporter gene (SLC1A1) on OCD has been frequently replicated in previous studies, but several studies did not replicate the result. Therefore, we aimed to replicate the associations between the SLC1A1 and OCD in a Korean population. In addition, we investigated the influence of SLC1A1 on trait empathy, impairments in which are characteristic of OCD. Six single-nucleotide polymorphisms (SNP) of SLC1A1 were genotyped in 615 patients with OCD and 508 healthy controls. The interpersonal reactivity index (IRI)—which consists of four subscales (perspective taking, PT; fantasy seeking, FS; empathic concern, EC; personal distress, PD)—was assessed from 277 patients with OCD and 395 controls. There were no significant associations between OCD and SNPs or haplotypes of SLC1A1. Patients with OCD exhibited significantly lower PT and higher PD scores than controls. The C-T-G haplotype at rs301430-rs301434-rs3087879 of SLC1A1 was significantly associated with higher PD scores after adjusted for age, sex, and OCD status. Our results suggest that six common SNPs of SLC1A1 may not contribute to the development of OCD, but may contribute to certain aspect of trait empathy such as personal distress. However, insufficient sample size and limited number of SLC1A1 SNPs may have reduced the likelihood of detecting significant associations. Therefore, further studies with larger sample size and more tag SNPs of the SLC1A1 gene were warranted.

Temperament and character influence on depression treatment outcome

“…Similarly, 5-HT2 receptor sensitivity was positively related to HA and negatively associated with SD (Peirson et al, 1999), suggesting that both traits could be regulated by the serotoninergic system, known to influence AD response (Kao et al, 2018, Andrews et al, 2015. Interestingly, common polymorphisms of the glutamate transporter gene were found to contribute to certain aspect of the empathy trait (Kim et al, 2018), a component of the cooperativeness dimension in the TCI. Moreover, schizotypal features, which could be regarded as aspects of low RD, were associated with and imbalance of excitatory glutamate and inhibitory γaminobutyric acid (GABA) concentrations in right and left hemisphere superior temporal (ST)…”

New insights and perspectives on the genetics of obsessive-compulsive disorder

“…Dickel et al (2006) also showed an association of rs378041 in SLC1A1 with early-onset OCD in males, which was replicated by Stewart et al (2007a). Nonetheless, a recent study did not support a role of SLC1A1 in the risk of OCD (Kim et al, 2018) while others reported positive association in males [rs2228622 (Abdolhosseinzadeh et al, 2019);rs301443 (de Salles Andrade et al, 2019)]. Additional glutamate system genes that have been examined include: the glutamate receptor, ionotropic N-methyl D-aspartate (NMDA) 2B (GRIN2B) gene, which has also been reported to have a significant association with the diagnosis of OCD (Arnold et al, 2004); glutamate related synapse (SAPAP/DLGAP family); and NMDA receptor genes (GRIN and GRIK family) with mixed findings.…”

Genetic and pharmacogenetic study of glutamate transporter (SLC1A1) in Iranian patients with obsessive-compulsive disorder

“…Despite mentioned positive reports, there is a recent negative report in which no significant associations were detected between six SNPs (rs2228622, rs3780412, rs301430, rs301434, rs3087879 and rs301443) or haplotypes of SLC1A1 and OCD in a sample of Korean probands and controls …”