Article

Lithium response and Val66Met polymorphism of the brain-derived neurotrophic factor gene in Japanese patients with bipolar disorder

Department of Psychiatry, Fujita Health University, Nagoya, Aichi, Japan
Psychiatric Genetics (Impact Factor: 2.27). 05/2006; 16(2):49-50. DOI: 10.1097/01.ypg.0000180680.72922.57
Source: PubMed

ABSTRACT Lithium is a first-line agent for the treatment of bipolar disorder. A significant association between the Val66Met polymorphism of the brain-derived neurotrophic factor gene and bipolar disorder has been reported. We investigated whether this polymorphism is associated with the response to lithium treatment in Japanese patients with bipolar disorder. Patients had been treated with lithium carbonate for more than 1 year, and the response was retrospectively evaluated. No significant differences were found in the genotype distribution or allele frequency between responders and non-responders. Our results suggested that the brain-derived neurotrophic factor Val66Met polymorphism might not greatly contribute to the efficacy of lithium in bipolar disorder.

0 Followers
 · 
80 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Bipolar disorder (BD) is a psychiatric illness defined by pathological alterations between the mood states of mania and depression, causing disability, imposing healthcare costs and elevating the risk of suicide. Although effective treatments for BD exist, variability in outcomes leads to a large number of treatment failures, typically followed by a trial and error process of medication switches that can take years. Pharmacogenetic testing (PGT), by tailoring drug choice to an individual, may personalize and expedite treatment so as to identify more rapidly medications well suited to individual BD patients.
    BMC Medicine 01/2014; 12(1):90. DOI:10.1186/1741-7015-12-90 · 7.28 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: El objetivo de nuestro metaanálisis fue evaluar la asociación entre el polimorfismo BDNF Val66Met y la respuesta al tratamiento en pacientes con trastorno depresivo mayor (TDM). Se identificaron 8 estudios que incluían datos de 1.115 individuos. Estudiamos 2 fenotipos: tasa de respuesta y tasa de remisión. Se utilizó la OR como medida del efecto de la asociación en un modelo de efectos fijos/aleatorios. Se realizó un metaanálisis para los genotipos Met/Met frente a Val/Val, Val/Met frente a Val/Val, Met/Met frente a Val/Met, Val/Met + Met/Met frente a Val/Val, Met/Met frente a Val/Val + Val/Met, y alelo Met frente a alelo Val. Al combinar todos los grupos, se observó una asociación significativa del genotipo Val/Met con un aumento de la tasa de respuesta en comparación con el Val/Val en la población global (OR = 1,66, IC del 95% = 1,07-2,57, p = 0,02). En el análisis de subgrupos se obtuvieron resultados similares para la población asiática (OR = 1,83, IC del 95%, 1,03-3,26, p = 0,04), pero no para la población caucásica. No observamos una asociación significativa del polimorfismo BDNF Val66Met con la tasa de remisión. Este metaanálisis pone de manifiesto la asociación entre el polimorfismo BDNF Val66Met y la respuesta al tratamiento en pacientes con TDM, y que los pacientes heterocigotos para Val66Met tienen una tasa de respuesta superior a la de los pacientes homocigotos Val/Val, especialmente en la población asiática.
    10/2012; 19(4):100-109. DOI:10.1016/j.psiq.2012.07.003
  • [Show abstract] [Hide abstract]
    ABSTRACT: The use of lithium is a cornerstone for preventing recurrences in bipolar disorder (BD). The response of patients with bipolar disorder to lithium has different levels of magnitude. About one third of lithium-treated patients are excellent lithium responders (ELR), showing total prevention of the episodes. A number of clinical characteristic were delineated in patients with favorable response to lithium as regards to clinical course, family history of mood disorders, and psychiatric co-morbidity. We have also demonstrated that temperamental features of hypomania (a hyperthymic temperament) and a lack of cognitive disorganization, predict the best results of lithium prophylaxis. A degree of prevention against manic and depressive episodes has been regarded as an endophenotype for pharmacogenetic studies. The majority of data have been gathered from so called "candidate" gene studies. The candidates were selected on the basis of neurobiology of bipolar disorder and mechanisms of lithium action including, among others, neurotransmission, intracellular signaling, neuroprotection or circadian rhythms. We demonstrated that response to lithium has been connected with the genotype of BDNF gene and serum BDNF levels and have shown that ELR have normal cognitive functions and serum BDNF levels, even after long-term duration of the illness. A number of genome-wide association studies (GWAS) of BD have been also performed in recent years, some of which also focused on lithium response. The Consortium on Lithium Genetics (ConLiGen) has established the large sample for performing the genome-wide association study (GWAS) of lithium response in BD and the first results have already been published.
    ACS Chemical Neuroscience 03/2014; 5(6). DOI:10.1021/cn5000277 · 4.21 Impact Factor