•Publication Date：01/15/2014
•Source： Taiwan Today
Taiwan scientists from the Institute of Biomedical Sciences at Taipei City-based Academia Sinica, together with psychiatrists from 44 local hospitals, identified a gene that can predict response to lithium therapy in Han Chinese sufferers of bipolar disorder, the institute said Jan. 15.
The findings will help in the design and development of new drugs to treat the disorder, as well as clinical testing kits, Academia Sinica said. The research was published Jan. 9 in The New England Journal of Medicine.
The study found three genetic variants in the gene encoding glutamate decarboxylase-like protein 1 (GADL1) can predict response to lithium maintenance treatment in bipolar I disorder sufferers of Asian ancestry, Academia Sinica said. These variants are rare in persons of Caucasian and African ancestry, but it is possible that other GADL1 alleles, or genetic variants, specific to these populations could also be linked to lithium efficacy.
Bipolar disorder, commonly known as manic depression, is a mood disorder characterized by episodes of mania and depression, with a high risk of suicide in some patients.
Lithium has been the first-line drug of choice for maintenance treatment of bipolar disorder for almost 50 years, with about 30 percent of patients showing complete symptom remission and 80 percent a partial response in Caucasian populations, the institute said. However, many patients have a poor or no response to lithium, and this study is the first to find genetic markers that can be used to select alternative treatment regimes.
Patient recruitment and lithium efficacy assessment were conducted by a team led by Andrew Cheng at Academia Sinica and Lee Chau-shoun at the Department of Psychiatry, Mackay Memorial Hospital in Taipei. Genomewide association study, genotyping and sequencing were conducted by a team led by Chen Yuan-tsong and including Chen Chien-hsiun, Michael Lee Ming-ta and Wu Jer-yuarn at Academia Sinica.
According to Academia Sinica, little is known about the physiological function of GADL1, but it may be similar to that of glutamate decarboxylase, which is involved in the decarboxylation of glutamate and other amino acids and is also a key enzyme in the biosynthesis of gamma-aminobutyric acid (GABA).
Glutamate acts as the primary excitatory neurotransmitter and GABA is a major inhibitory neurotransmitter in the human brain. The research suggests the importance of the glutamate pathway in bipolar disorder and the possibility that lithium may affect glutamate-based neurotransmission.
A total of 47.2 percent of the 1,761 bipolar patients in this study carried the response allele T in one variant of GADL1, a prevalence similar to that in the general Han Chinese population, suggesting that approximately half the patients with bipolar I disorder in Taiwan may benefit from lithium therapy, but that alternative treatments may be more appropriate for the other half.
