Evaluating of Solute Carrier Family 6 Member 4 Gene (SLC6A4) Promoter Polymorphisms with Escitalopram Plasma Levels for Precision Medicine in Major Depressive Disorder

Abstract

Aim and Objective: Escitalopram (SCT) shows an antidepressant effect due to its mechanism of increasing the serotonin level by inhibiting the serotonin transporter protein (5HTT). 5HTT is encoded by solute carrier family 6 member 4 gene (SLC6A4) in the brain. Recognition of SCT plasma level of patients and pharmacodynamics of individuals during SCT treatment will increase the expected response to the treatment and reduce the adverse effects. This study aims to determine the effect of SLC6A4 promoter long/short polymorphism and the SCT plasma level of patients on the response to treatment during the SCT drug therapy. Materials and Methods: Blood and plasma samples of 30 major depressive patients using 20 mg SCT for 8 weeks between the ages of 18 and 65 were analyzed to determine SCT plasma level and SLC6A4 promoter polymorphism. The treatment response level was determined by using the Hamilton Depression Rating Scale at patient files. Results: SCT plasma level of the nine patients with LL polymorphism was found to be in the range of 13.40–63.36 ng/mL. For 13 patients with LS polymorphism, SCT plasma level was found to be in the range of 2.93–57.48 ng/mL. For eight patients with SS polymorphism, the SCT plasma level was found to be in the range of 0.95–49.32 ng/mL. Conclusion: When the association between SCT plasma level and response to the drug treatment was examined, we had significant results to show that SCT level affected the response to treatment, especially in the LS group, as well as the SLC6A4 promoter variation. This study may lead to a more profound understanding of rational drug therapy as well as to a careful application of pharmacogenetics in psychiatry..

Neurobiological Perspective and Personalized Treatment in Schizophrenia

“…The Epidemiological Field Study found more associations between opioid use disorders and SZ than previous studies [5]. The CATIE study, on the other hand, found low levels of opioid abuse or dependence in participants with SZ [27].…”

“…This functional polymorphism has been assigned a unique reference sequence number, rs4680 now. Val allele of rs4680 (guanine allele) is a more active allele than Met allele (adenine allele) and has been accepted as a risk factor for SZ [4][5][6][7]. In summary, the introduction of genetic profile monitoring into routine psychiatric practice in TDM and resistant cases, which is a faster and easier method, seems to be a revolutionary development.…”

“…Alcohol and substance use disorders (ASUD) is a diagnostic group that has been shown to frequently accompany other mental illnesses in many epidemiological studies [5]. One of these mental illnesses is psychotic disorders, and a well-known example is SZ.…”

“…On the other hand, even when nicotine use is excluded, nearly half of SZ patients are diagnosed with a lifelong substance use disorder. The Epidemiological Field Study reports that 34% of patients with SZ have alcohol use disorder and 28% have a substance use disorder [5]. Data from the National Epidemiological Study of Alcohol and Related Conditions revealed that SZ is associated with an increased risk for reuse, especially when cannabis is involved [9].…”