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. 2023 Apr 4;24(7):6758.
doi: 10.3390/ijms24076758.

The Impact of BDNF, NTRK2, NGFR, CREB1, GSK3B, AKT, MAPK1, MTOR, PTEN, ARC, and SYN1 Genetic Polymorphisms in Antidepressant Treatment Response Phenotypes

Marlene Santos  1   2 , Luis Lima  3 , Serafim Carvalho  4   5 , Jorge Mota-Pereira  6 , Paulo Pimentel  7 , Dulce Maia  7 , Diana Correia  4 , M Fátima Barroso  8 , Sofia Gomes  4 , Agostinho Cruz  1 , Rui Medeiros  2   9
Affiliations

The Impact of BDNF, NTRK2, NGFR, CREB1, GSK3B, AKT, MAPK1, MTOR, PTEN, ARC, and SYN1 Genetic Polymorphisms in Antidepressant Treatment Response Phenotypes

Marlene Santos et al. Int J Mol Sci. .

Abstract

This study aimed to investigate the influence of genetic variants in neuroplasticity-related genes on antidepressant treatment phenotypes. The BDNF-TrkB signaling pathway, as well as the downstream kinases Akt and ERK and the mTOR pathway, have been implicated in depression and neuroplasticity. However, clinicians still struggle with the unpredictability of antidepressant responses in depressed patients. We genotyped 26 polymorphisms in BDNF, NTRK2, NGFR, CREB1, GSK3B, AKT, MAPK1, MTOR, PTEN, ARC, and SYN1 in 80 patients with major depressive disorder treated according to the Texas Medical Algorithm for 27 months at Hospital Magalhães Lemos, Porto, Portugal. Our results showed that BDNF rs6265, PTEN rs12569998, and SYN1 rs1142636 SNP were associated with treatment-resistant depression (TRD). Additionally, MAPK1 rs6928 and GSK3B rs6438552 gene polymorphisms were associated with relapse. Moreover, we found a link between the rs6928 MAPK1 polymorphism and time to relapse. These findings suggest that the BDNF, PTEN, and SYN1 genes may play a role in the development of TRD, while MAPK1 and GSK3B may be associated with relapse. GO analysis revealed enrichment in synaptic and trans-synaptic transmission pathways and glutamate receptor activity with TRD-associated genes. Genetic variants in these genes could potentially be incorporated into predictive models of antidepressant response.

Keywords: AD; BDNF; GSK3B; MAPK; PTEN; SYN1; genetic polymorphisms; neuroplasticity; treatment-resistant depression.

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Conflict of interest statement

The authors have no financial or proprietary interest in any material discussed in this article. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Effect of MAPK1 rs6928 genotypes in time to relapse in MDD patients. Kaplan–Meier analysis was used to evaluate the association between time to relapse and MAPK1 rs6928 GG and GC + CC carriers. Comparison performed by Log-rank test (p = 0.022).
Figure 2
Figure 2
Bar chart of top enriched terms from the KEGG_2021_Human gene set library. The top 10 enriched terms for the input gene set are displayed based on the -log10 (p-value), with the actual p-value shown next to each term (*). The term at the top has the most significant overlap with the input query gene set.
See this image and copyright information in PMC

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