Variant GADL1 and response to lithium therapy in bipolar I disorder.

BACKGROUND: Lithium has been a first-line choice for maintenance treatment of bipolar disorders to prevent relapse of mania and depression, but many patients do not have a response to lithium treatment. METHODS: We selected subgroups from a sample of 1761 patients of Han Chinese descent with bipolar I disorder who were recruited by the Taiwan Bipolar Consortium. We assessed their response to lithium treatment using the Alda scale and performed a genomewide association study on samples from one subgroup of 294 patients with bipolar I disorder who were receiving lithium treatment. We then tested the single-nucleotide polymorphisms (SNPs) that showed the strongest association with a response to lithium for association in a replication sample of 100 patients and tested them further in a follow-up sample of 24 patients. We sequenced the exons, exon-intron boundaries, and part of the promoter of the gene encoding glutamate decarboxylase-like protein 1 (GADL1) in 94 patients who had a response to lithium and in 94 patients who did not have a response in the genomewide association sample. RESULTS: Two SNPs in high linkage disequilibrium, rs17026688 and rs17026651, that are located in the introns of GADL1 showed the strongest associations in the genomewide association study (P=5.50×10(-37) and P=2.52×10(-37), respectively) and in the replication sample of 100 patients (P=9.19×10(-15) for each SNP). These two SNPs had a sensitivity of 93% for predicting a response to lithium and differentiated between patients with a good response and those with a poor response in the follow-up cohort. Resequencing of GADL1 revealed a novel variant, IVS8+48delG, which lies in intron 8 of the gene, is in complete linkage disequilibrium with rs17026688 and is predicted to affect splicing. CONCLUSIONS: Genetic variations in GADL1 are associated with the response to lithium maintenance treatment for bipolar I disorder in patients of Han Chinese descent. (Funded by Academia Sinica and others.).

Development of a chinese version of the Yale-Brown obsessive compulsive scale for heavy drinking.

BACKGROUND: Measurement of craving is an important component in the investigation of the etiology and clinical pictures of alcoholism and dependence of other substances in different cultures. The aim of this study was to develop a Chinese version of the Yale-Brown Obsessive Compulsive Scale for heavy drinking (YBOCS-hd-C), the instrument most frequently used in assessing the severity of alcohol craving in Taiwan. METHODS: Four hundred twenty Han Chinese (220 with alcohol use disorders) and 218 Bunun aborigines (150 with alcohol use disorders) in Taiwan were interviewed by mental health professionals with the YBOCS-hd-C and a Chinese version of the World Health Organization Schedules for Clinical Assessment in Neuropsychiatry to establish the psychiatric diagnosis. Validity and reliability of the YBOCS-hd-C were examined. RESULTS: The YBOCS-hd-C was found to have acceptable interrater reliability (intraclass correlation, 0.89-0.96), internal consistency (Cronbach's alpha = 0.99), construct validity, concurrent validity, and cross-cultural validity. The correlations between 10 items of the YBOCS-hd-C and 11 items of the World Health Organization Schedules for Clinical Assessment in Neuropsychiatry adjusted for age, gender, and ethnicity ranged from 0.39 to 1.00. The YBOCS-hd-C also discriminated effectively among individuals with alcohol dependence, alcohol abusers, and normal drinkers. CONCLUSIONS: This study demonstrated that the YBOCS-hd-C is a reliable and valid instrument for assessing the extent of craving for alcohol in Taiwanese Han and Bunun individuals.