<i>ABCB1</i> gene variants and antidepressant treatment outcome: A meta‐analysis

Breitenstein, Barbara; Brückl, Tanja; Ising, Marcus; Müller‐Myhsok, Bertram; Holsboer, Florian; Czamara, Darina

doi:10.1002/ajmg.b.32309

Cited by 64 publications

(39 citation statements)

References 45 publications

(106 reference statements)

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“…Additionally, we have previously found an influence of CYP2C19 and CYP2B6, but not of ABCB1 , on sertraline pharmacokinetics which was also confirmed in this study. However, other polymorphisms in ABCB1 , such as rs2032583, rs2235040 and rs9282564, but not C3435T , have earlier been linked with remission and side effects of depressive patients treated with sertraline . It is necessary to clarify whether this or other polymorphisms in ABCB1 can affect sertraline disposition and then have an impact on patients' outcome.…”

Section: Discussionmentioning

confidence: 99%

Effect of ABCB1 C3435T Polymorphism on Pharmacokinetics of Antipsychotics and Antidepressants

Saiz‐Rodríguez

Belmonte

Román

et al. 2018

Basic Clin Pharma Tox

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P-glycoprotein, encoded by ABCB1, is an ATP-dependent drug efflux pump which exports substances outside the cell. Some studies described connections between C3435T polymorphism T allele and lower P-glycoprotein expression; therefore, homozygous T/T could show higher plasma levels. Our aim was to evaluate the effect of C3435T on pharmacokinetics of 4 antipsychotics (olanzapine, quetiapine, risperidone and aripiprazole) and 4 antidepressants (trazodone, sertraline, agomelatine and citalopram). The study included 473 healthy volunteers receiving a single oral dose of one of these drugs, genotyped by real-time PCR. Multivariate analysis was performed to adjust the effect of sex and genotype of the main cytochrome P450 enzymes. C3435T polymorphism had an effect on olanzapine pharmacokinetics, as T/T individuals showed lower clearance and volume of distribution. T/T individuals showed lower T of 9-OH-risperidone, but this difference disappeared after multivariate correction. T/T homozygous individuals showed lower dehydro-aripiprazole and trazodone area under the concentration-time curve, along with lower half-life and higher clearance of trazodone. C/T genotype was associated to higher citalopram maximum concentration. C3435T had no effect on quetiapine, sertraline or agomelatine pharmacokinetics. C3435T can affect the elimination of some drugs in different ways. Regarding risperidone, trazodone and dehydro-aripiprazole, we observed enhanced elimination while it was reduced in olanzapine and citalopram. However, in quetiapine, aripiprazole, sertraline and agomelatine, no changes were detected. These results suggest that P-glycoprotein polymorphisms could affect CNS drugs disposition, but the genetic factor that alters its activity is still unknown. This fact leads to consider the analysis of ABCB1 haplotypes instead of individual variants.

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Section: Discussionmentioning

confidence: 99%

Effect of ABCB1 C3435T Polymorphism on Pharmacokinetics of Antipsychotics and Antidepressants

Saiz‐Rodríguez

Belmonte

Román

et al. 2018

Basic Clin Pharma Tox

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“…Previously, a significant association has been reported between a SNP in the gene encoding PGP, (ATP-binding cassette, sub-family B member 1), and MDD [220]. Meta-analysis of 16 pharmacogenetic studies on PGP polymorphisms identified the rs2032583 SNP that was nominally associated (P = 0.035) with anti-depressant treatment outcome [221]. MDD patients undergoing anti-depressant treatment had significantly increased PGP function as measured by positron emission tomography [222].…”

Section: Therapeutic Considerations In Mood Disordersmentioning

confidence: 99%

Blood-brain barrier regulation in psychiatric disorders

Kealy

Greene

Campbell

2020

Neuroscience Letters

200

135

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The blood-brain barrier (BBB) is a dynamic interface between the peripheral blood supply and the cerebral parenchyma, controlling the transport of material to and from the brain. Tight junctions between the endothelial cells of the cerebral microvasculature limit the passage of large, negatively charged molecules via paracellular diffusion whereas transcellular transportation across the endothelial cell is controlled by a number of mechanisms including transporter proteins, endocytosis, and diffusion. Here, we review the evidence that perturbation of these processes may underlie the development of psychiatric disorders including schizophrenia, autism spectrum disorder (ASD), and affective disorders. Increased permeability of the BBB appears to be a common factor in these disorders, leading to increased infiltration of peripheral material into the brain culminating in neuroinflammation and oxidative stress. However, although there is no common mechanism underpinning BBB dysfunction even within each particular disorder, the tight junction protein claudin-5 may be a clinically relevant target given that both clinical and pre-clinical research has linked it to schizophrenia, ASD, and depression. Additionally, we discuss the clinical significance of the BBB in diagnosis (genetic markers, dynamic contrast-enhanced-magnetic resonance imaging, and blood biomarkers) and in treatment (drug delivery).

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“…Multiple studies with conflicting results have been conducted since an association with treatment was reported in 2008 [25]. A recent meta-analysis of 16 pharmacogenetic studies concluded that two SNPs -rs2032583 and rs2235015 are significantly associated with antidepressant treatment outcome for inpatients with depression when treated with antidepressants that are substrates of P-glycoprotein [27]. The C allele of rs2032583 and the T allele of rs2235015 of the ABCB1 gene lead to better rates of remission [28].…”

Section: Abcb1 and Drug Transportmentioning

confidence: 99%

Pharmacogenetics of Antidepressants, A Review of Significant Genetic Variants in Different Populations

Reyes-Barron¹,

Tonarelli²,

Delozier³

et al. 2017

Clin Depress

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Major depressive disorder is a highly prevalent disease that is challenging to treat, often requiring medication and dose adjustments. Genetic factors play an important role in psychotropic medication responses. However, the translation of pharmacogenetics findings to clinical recommendations with regards to antidepressant responses is still in its early stages. We reviewed recent primary research articles, meta-analyses, and reviews on the pharmacogenetics of antidepressant treatment for major depressive disorder in different populations. We identified eight genes with likely associations with treatment responses and summarized genetic variants most likely to influence treatment responses. We determined the frequency of these variants in Caucasian, Asian, Hispanic, and African American populations. The genes are related to functions in drug metabolism, transport, signalling, stress response, and neuroplasticity. Clinical recommendations already exist for CYP2D6 and CYP2C19 cytochrome P450 drug metabolism genes. The other genes are: ABCB1 with single nucleotide polymorphisms (SNPs) rs2032583 and rs2235015; FKBP5 with SNPs rs1360780, rs3800373, and rs4713916; GNB3 with SNP rs5443; BDNF with SNP rs6265; HTR2A with SNPs rs7997012 and rs6313; and SLC6A4 with polymorphisms 5-HTTLPR and STin2. There is significant variability of the frequencies of these polymorphisms in the different populations we reviewed. There is also variability in the antidepressant responses between populations carrying the same polymorphism in some cases, indicating a likely polygenic influence. Future studies in the pharmacogenetics of antidepressants would benefit from including more subjects from underrepresented ethnic groups and stratifying results.

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ABCB1 gene variants and antidepressant treatment outcome: A meta‐analysis

Cited by 64 publications

References 45 publications

Effect of ABCB1 C3435T Polymorphism on Pharmacokinetics of Antipsychotics and Antidepressants

Effect of ABCB1 C3435T Polymorphism on Pharmacokinetics of Antipsychotics and Antidepressants

Blood-brain barrier regulation in psychiatric disorders

Pharmacogenetics of Antidepressants, A Review of Significant Genetic Variants in Different Populations

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