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Background <p>The pharmacological maintenance treatment for bipolar disorder patients depends on mood stabilizers such as lithium and valproate. An association between <i>GRIN2B</i> and <i>NTRK2</i> gene polymorphisms and treatment response to lithium and valproate has been reported. Therefore, we examined the relationship between polymorphisms of <i>GRIN2B</i> and <i>NTRK2</i> and the long-term treatment response to valproate and lithium in bipolar disorder patients.</p> Methods <p>We performed a genetic association study involving bipolar disorder patients treated with valproate and lithium, along with a control group. The long-term treatment response was retrospectively assessed using Alda’s scale. Genotyping of <i>GRIN2B</i> (rs1806201, rs890) and <i>NTRK2</i> (rs2289656) was conducted with allele discrimination TaqMan assays.</p> Results <p>We analyzed 251 bipolar disorder patients, 130 treated with valproate and 121 with lithium, and 300 controls. The analysis, which controlled for sex and age as covariates, observed an association between rs1806201 and BD (<i>p</i> = 0.003). The analysis of treatment response showed an effect of the <i>NTRK2</i>/rs2289656 and treatment response to valproate, with the number of depressive, hypomanic, psychotic, and mixed episodes as covariates (<i>p</i> = 0.043). No association was found between the two genes analyzed and the response to lithium treatment.</p> Conclusions <p>Our findings suggest that <i>GRIN2B</i> and <i>NTRK2</i> may play a crucial role in the cause of bipolar disorder. The analysis of treatment response revealed a link between the <i>NTRK2</i> gene and valproate response in BD patients. However, our results did not reproduce the association of these two genes with lithium response in Mexican patients.</p>

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Genetic variants in GRIN2B and NTRK2 on the etiology and treatment response to valproate and lithium in patients with bipolar disorder

  • 期刊论文

  • 发表日期：

    2025年8月14日

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  • Beatriz Camarena,
  • Marco Antonio Sanabrais-Jiménez,
  • Carlo Esteban Sotelo-Ramírez,
  • Joanna Jiménez-Pavón,
  • Pamela Morales-Cedillo,
  • Hiram Ortega-Ortíz,
  • Claudia Becerra-Palars

摘要

Background

The pharmacological maintenance treatment for bipolar disorder patients depends on mood stabilizers such as lithium and valproate. An association between GRIN2B and NTRK2 gene polymorphisms and treatment response to lithium and valproate has been reported. Therefore, we examined the relationship between polymorphisms of GRIN2B and NTRK2 and the long-term treatment response to valproate and lithium in bipolar disorder patients.

Methods

We performed a genetic association study involving bipolar disorder patients treated with valproate and lithium, along with a control group. The long-term treatment response was retrospectively assessed using Alda’s scale. Genotyping of GRIN2B (rs1806201, rs890) and NTRK2 (rs2289656) was conducted with allele discrimination TaqMan assays.

Results

We analyzed 251 bipolar disorder patients, 130 treated with valproate and 121 with lithium, and 300 controls. The analysis, which controlled for sex and age as covariates, observed an association between rs1806201 and BD (p = 0.003). The analysis of treatment response showed an effect of the NTRK2/rs2289656 and treatment response to valproate, with the number of depressive, hypomanic, psychotic, and mixed episodes as covariates (p = 0.043). No association was found between the two genes analyzed and the response to lithium treatment.

Conclusions

Our findings suggest that GRIN2B and NTRK2 may play a crucial role in the cause of bipolar disorder. The analysis of treatment response revealed a link between the NTRK2 gene and valproate response in BD patients. However, our results did not reproduce the association of these two genes with lithium response in Mexican patients.