Evaluation of the interaction between genetic variants of GAD1 and miRNA in bipolar disorders.

BACKGROUND: Glutamic acid dehydrogenase 1 (GAD1) serves as the rate-limiting enzyme for synthesizing GABA, and is reported to be associated with several psychiatric disorders. The present study examined the effects of GAD1 genetic variants on bipolar disorder (BD) and its subtypes. Moreover, we investigated functional interactions between genetic variants and miRNAs via algorithm prediction and experimental validation. METHODS: A case-control study was conducted with 280 BD patients and 200 healthy controls. Eight tag SNPs in GAD1 were genotyped. For associated markers, we performed in silico prediction for their potential functions through SNP-miRNA interactions by establishing a scoring system to combine information from several miRNA predictive algorithms. We then tested allelic expression differences using Dual-Glo luciferase reporter assays for the selected SNP-miRNA pair. Lastly, we examined the associations of the GAD1 gene and BD in two additional independent datasets with a few thousand samples for replication. RESULTS: Marker rs3749034 was associated with BD, in particular the BD-II subtype. According to our scoring system, several candidate miRNAs were predicted to interact with rs3749034, and hsa-miR-504 had the highest score. Findings from an in vitro experiment revealed a non-statistically significant trend for lower gene expression level with the A allele of rs3749034 compared with the G allele. The association between rs3749034 and BD was not replicated in either of the independent datasets. Instead, other rarer genetic variants in GAD1 showed suggestive signals (e.g. rs575441409, p-value = 3.8*10-4, D' = 1 with rs3749034) with BD in the Taiwanese dataset. LIMITATIONS: The present study considered common genetic variants only. In addition, we only used a 293T cell-line in conducting luciferase reporter assays, as no primary cell-lines from patient samples were available to differentiate the effects between BD subtypes. CONCLUSIONS: Our results demonstrate a weak effect of the GAD1 gene on the risk of bipolar illness, and the associated marker might represent a proxy for real signals of rare variants.

Initiating long-acting injectable antipsychotics during acute admission for patients with schizophrenia--A 3-year follow-up.

BACKGROUND/PURPOSE: The debate on whether long-acting injectable antipsychotic (LAIA) medication is superior to oral medication, in preventing rehospitalization of patients with schizophrenia, remains inconclusive. We compared rehospitalization rates over 3 years following discharge from an acute admission, in which patients either began using LAIAs regularly for the first time, or continued to use oral antipsychotics. METHODS: A retrospective observational study of 92 inpatients with schizophrenia from a university-based medical center during 2004-2008. The primary outcome measure is the rehospitalization rates between groups, as estimated by Kaplan-Meier survival analysis. RESULTS: Eighteen of 47 (38.3%) LAIA patients, and 16 of 45 (35.6%) oral medication patients were rehospitalized (average time to rehospitalization, 378 ± 262 vs. 378 ± 340 days; p = 0.997). The estimated cumulative rates of rehospitalization were similar between groups. The overall odds comparing the LAIA to the oral medication group were 1.085 ± 0.373 (95% confidence interval: 0.553-2.13, p = 0.813). Compared to the oral medication group, the LAIA group had fewer coded with sufficient previous treatment response (32% vs. 69%, p < 0.001), more poorly compliant (91% vs. 56%, p < 0.001), and a slightly longer length of stay at index admission (32.7 ± 11.3vs. 27.6 ± 12.1, p = 0.04). CONCLUSION: Initiating LAIAs during admission for an acute psychotic episode, to a group of patients with an inadequate previous treatment response and poorer compliance, might keep their rehospitalization rates to the level of their oral antipsychotic medication treated counterparts.

Detoxification of high-dose zolpidem using cross-titration with an adequate equivalent dose of diazepam.

BACKGROUND: There have been numerous case reports of zolpidem abuse and dependence in the recent decade, giving rise to a focus on adverse withdrawal events such as seizure. No standard detoxification regimen has been proposed to date, despite the similarity of effects of zolpidem and benzodiazepines at high doses. CASE DESCRIPTIONS: We describe the results, in a 53-year-old female patient, of undergoing three different zolpidem detoxification programs. CONCLUSIONS: Because of her experiences, we recommend using the cross-titration strategy with an adequate equivalent dose of diazepam.