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Genes involved in stress response influence lithium efficacy in bipolar patients.

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  • معلومة اضافية
    • المصدر:
      Publisher: Wiley-Blackwell Munksgaard Country of Publication: Denmark NLM ID: 100883596 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1399-5618 (Electronic) Linking ISSN: 13985647 NLM ISO Abbreviation: Bipolar Disord Subsets: MEDLINE
    • بيانات النشر:
      Publication: Copenhagen : Wiley-Blackwell Munksgaard
      Original Publication: Copenhagen, Denmark : Munksgaard, 1999-
    • الموضوع:
      Bipolar Disorder/*drug therapy ; Bipolar Disorder/*genetics ; Lithium Carbonate/*therapeutic use ; Stress, Psychological/*genetics; Adult ; Aged ; Aged, 80 and over ; Female ; Gene Expression ; Haplotypes ; Humans ; Hypothalamo-Hypophyseal System/drug effects ; Linkage Disequilibrium ; Male ; Middle Aged ; Mood Disorders/genetics ; Pituitary-Adrenal System/drug effects ; Polymorphism, Single Nucleotide
    • نبذة مختصرة :
      Objectives: In mood disorders, chronic stimulation with stress results in aberrant regulation of the hypothalamic-pituitary-adrenal (HPA) axis. Lithium was shown to influence HPA axis function. The underlying genetic background as well as environmental context may influence the stress response, and therefore lithium efficacy. The aim of the present study was to analyze if genetic variants located in genes involved in HPA axis regulation affect the response to long-term lithium treatment in bipolar patients.
      Methods: We included 93 patients with bipolar disorder (32 males and 61 females), aged 31-80 years. The patients had been treated with lithium carbonate for at least 5 years. The magnitude of the lithium response was assessed using the Alda scale. Genotyping was performed for 28 polymorphisms in the genes encoding the following proteins involved in HPA axis regulation: corticotropin-releasing hormone receptor 1 (CRHR1), arginine vasopressin receptor 1B (AVPR1b), FK506 binding protein (FKBP) 5, FKBP4, BCL2-associated athanogene 1 (BAG1), stress induced phosphoprotein 1 (STIP1), glucocorticoid-induced transcript 1 (GLCC1), dual specificity phosphatase 1 (DUSP1) serine and arginine rich splicing factor (SRSF) 3, SRSF9, SRSF5, and acid phosphatase 1 (ACP1). Linkage disequilibrium and haplotype analysis were then performed, followed by statistical analysis (Statistica v.12; Stasoft, Krakow, Poland).
      Results: We found a correlation between stressful life events at first episode and worse response to lithium (P=.019). In single marker analysis, we observed a significant association between three FKBP5 polymorphisms (rs1360780, rs7748266 and rs9296158), one ACP1 variant (rs300774) and one glucocorticoid-induced transcript 1 gene (GLCC1) variant (rs37972) and the degree of lithium response. Five out of seven FKBP5 polymorphisms showed strong linkage with one haplotype demonstrating an association with lithium efficacy (P=.008). No relationship was found between the other analyzed polymorphisms and lithium response.
      Conclusion: The response to lithium may depend on the variants of genes regulating the HPA axis and stressful life events in bipolar patients.
      (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
    • Contributed Indexing:
      Keywords: gene; hypothalamus-pituitary-adrenal axis; polymorphism; stress
    • الرقم المعرف:
      2BMD2GNA4V (Lithium Carbonate)
    • الموضوع:
      Date Created: 20180327 Date Completed: 20190510 Latest Revision: 20190510
    • الموضوع:
      20221213
    • الرقم المعرف:
      10.1111/bdi.12639
    • الرقم المعرف:
      29578315