Checkmate Depression – ABCB1 gene
When a king is attacked in a chess game, it is called a check. A checkmate (a.k.a. “mate”) occurs when a king is placed in check and has no legal moves to escape. When a checkmate happens, the game ends immediately, and the player who delivered the checkmate wins.
Checkmate your opponent should be your top priority. This will ensure your victory even if you have less material or a worse position throughout the game.
Unfortunately, many people have a feeling they are playing chess with depression. For decades, the game has started to be exhausting, and they cannot checkmate depression. Undoubtedly, there are numerous gene candidates and other factors for depression, but let’s explore one responsible for a poor response to antidepressant therapy and multiple drug (medication) resistance. In our following blogs, we will discuss others, such as (for example) SLC6A4, MTFHR, DRD2, CYP450 family, and many more.
A possible solution to this problem is pharmacogenomic testing for the ABCB1 gene. Then, your healthcare practitioner will have a much better option for treating your depression. In addition, he/she will approach you with personalized treatment tailored to you, including an integrative and/or holistic approach! So really, it will be checkmate for depression. In addition, there are many commercially available tests such as (for example) https://www.hmnc-brainhealth.com/about-us/our-approach or this one https://genomind.com/providers/abcb1-gene-spotlight/.
What is ABCB1?
According to the scientific literature, so-called ATP-binding cassette – sub-family B (MDR/TAP), member 1 (ABCB1), is a medication transporter protein distributed in the intestine and the blood-brain barrier (Keh-Ming Lin et al., 2011).
Many studies have revealed that P-glycoprotein is involved in the transmembrane transport of many antidepressants. Many antidepressants act as substrates for P-glycoprotein. ABCB1 gene is located on chromosome 7 (humans). As an essential component of the blood-brain barrier and gastrointestinal barrier, it is encoded 1280 amino acid – transporter P-glycoprotein can limit drug infiltration and accumulation in the brain and regulate the effectiveness and toxicity of drugs. Indeed, ABCB1 gene polymorphism may significantly affect the function of P-glycoprotein, changing the concentration of medication in the brain, and with various degrees of impact on the efficacy of antidepressant medications. According to the current research results, ABCB1 gene polymorphism has a specific correlation with the effectiveness of antidepressants. Being known as the multidrug resistance gene, the ABCB1 gene is located at 7q21 and encodes p-glycoprotein. Its primary function includes preventing drugs and foreign substances from entering body tissues, such as antidepressants, anti-tumor drugs, glucocorticoids, and amyloid proteins. Indeed, due to the exogenous effects of P-glycoprotein on exogenous substances and medications, ABCB1 gene polymorphism and different P-glycoprotein expression may lead to diverse populations or individuals with different susceptibility to some diseases, including depression. Previous clinical studies on the relationship between ABCB1 gene mutation and antidepressant efficacy are inconsistent. Through meta-analysis study further explored the relationship between ABCB1 gene polymorphism and the efficacy of antidepressants to provide an etiological basis for individualized treatment in patients suffering from depression (Xiaoying Zheng et al., 2021).
Undoubtedly, P-glycoprotein (P-gp), the gene product of ABCB1, is a drug transporter at the blood-brain barrier and could be a limiting factor for the entrance of antidepressants into the brain, the target site of antidepressant action. Animal studies showed that brain concentrations of many antidepressants depend on P-gp. In humans, ABCB1 genotyping in the treatment of depression rests on the assumption that genetic variations in ABCB1 explain individual differences in antidepressant response via their effects on P-gp expression at the blood-brain barrier. High P-gp expression is hypothesized to lead to lower and often insufficient brain concentrations of P-gp substrate antidepressants (Tanja Maria Brückl, et al., 2016).
The ABCB1 gene contains single nucleotide polymorphisms (SNPs) in the encoding regions. Therefore, variants such as C3435T (rs1045642), G2677T/A (rs2032582), and rs2032583 have been the most commonly studied by many researchers. Most studies indicate that ABCB1 haplotypes, the SNPs rs1045642, rs2032582, and rs2032583 affect the response to treatment with antidepressants (Wei-Wei Xie, et al., 2015).
Polymorphisms in ABCB1 can affect both the function and the expression of the transporter protein P-glycoprotein. Therefore, they may lead to an altered response to many drugs, including antidepressants and antipsychotics. There was a significantly higher frequency of the T allele at positions 1236, 2677, and 3435 among the suicide cases compared with the nonsuicide cases (Samuel Boiso Moreno et al., 2015).
Genetic variation in efflux transporter permeability glycoprotein (P-gp) has recently been associated with completed violent suicides and violent suicide attempts. According to the literature data, as depression is a risk factor for suicide and many antidepressants are P-gp substrates, it has been speculated that inadequate antidepressant treatment response or adverse side effects could be involved (Anna-Liina Rahikainen et al., 2018).
It is time for action, prevention, and precision treatment for depression. Therefore, finding integrative psychiatry healthcare practitioners is beneficial and could lead to more personalized medicine/treatment and finally checkmate depression.
Respectfully,
References
1. Keh-Ming Lin, Yen-Feng Chiu, I-Ju Tsai, Chia-Hui Chen, Winston W Shen, Shu Chih Liu, Shao-Chun Lu, Chia-Yih Liu, Mei-Chun Hsiao, Hwa-Sheng Tang, Shen-Ing Liu, Liang-Huey Chang, Chi-Shin Wu, Hsiao-Hui Tsou, Ming-Hsien Tsai, Chun-Yu Chen, Su-Mei Wang, Hsiang-Wei Kuo, Ya-Ting Hsu, Yu-Li Liu. ABCB1 gene polymorphisms are associated with the severity of major depressive disorder and its response to escitalopram treatment. Pharmacogenet Genomics. 2011 Apr;21(4):163-70.
2. Xiaoying Zheng, Zejuan Fu, Xiaomei Chen, Mingxia Wang, and Rixia Zhu. Effects of ABCB1 gene polymorphism on the efficacy of antidepressant drugs. Medicine (Baltimore). 2021 Jul 16; 100(28): e26411.
3. Tanja Maria Brückl, Manfred Uhr. ABCB1 genotyping in the treatment of depression. Pharmacogenomics. 2016 Dec;17(18):2039-2069.
4. Wei-Wei Xie, Lin Zhang, Ren-Rong Wu, Yan Yu, Jing-Ping Zhao, and Le-Hua Li1. Case-control association study of ABCB1 gene and major depressive disorder in a local Chinese Han population. Neuropsychiatr Dis Treat. 2015; 11: 1967–1971.
5. Samuel Boiso Moreno, Anna-Lena Zackrisson, Ingrid Jakobsen Falk, Louise Karlsson, Björn Carlsson, Andreas Tillmar, Fredrik C Kugelberg, Johan Ahlner, Staffan Hägg, Henrik Gréen. ABCB1 gene polymorphisms are associated with suicide in forensic autopsies. Pharmacogenet Genomics. 2013 Sep;23(9):463-9.
6. Anna-Liina Rahikainen, Jukka U Palo, Jari Haukka, Antti Sajantila. Post-mortem analysis of suicide victims shows ABCB1 haplotype 1236T-2677T-3435T as a candidate predisposing factor behind adverse drug reactions in females. Pharmacogenet Genomics. 2018 Apr;28(4):99-106.