ALDH2 Gene: Its Effects on the Neuropsychological Functions in Patients with Opioid Use Disorder Undergoing Methadone Maintenance Treatment

Objective@#Patients with opioid use disorder (OUD) have impaired attention, inhibition control, and memory function. The aldehyde dehydrogenase 2 (ALDH2 ) gene has been associated with OUD and ALDH2 gene polymorphisms may affect aldehyde metabolism and cognitive function in other substance use disorder. Therefore, we aimed to investigate whether ALDH2 genotypes have significant effects on neuropsychological functions in OUD patients undergoing methadone maintenance therapy (MMT). @*Methods@#OUD patients undergoing MMT were investigated and followed-up for 12 weeks. ALDH2 gene polymorphisms were genotyped. Connors’ Continuous Performance Test (CPT) and the Wechsler Memory Scale-Revised (WMS-R) were administered at baseline and after 12 weeks of MMT. Multivariate linear regressions and generalized estimating equations (GEEs) were used to examine the correlation between the ALDH2 genotypes and performance on the CPTs and WMS-R. @*Results@#We enrolled 86 patients at baseline; 61 patients completed the end-of-study assessments. The GEE analysis showed that, after the 12 weeks of MMT, OUD patients with the ALDH2 *1/*2＋*2/*2 (ALDH2 inactive) genotypes had significantly higher commission error T-scores (p = 0.03), significantly lower hit reaction time T-scores (p = 0.04), and significantly lower WMS-R visual memory index scores (p = 0.03) than did patients with the ALDH2 1 */*1 (ALDH2 active) genotype. @*Conclusion@#OUD patients with the ALDH2 inactive genotypes performed worse in cognitive domains of attention, impulse control, and memory than did those with the ALDH2 active genotype. We conclude that the ALDH2 gene is important in OUD and is associated with neuropsychological performance after MMT.

Dextromethorphan Protect the Valproic Acid Induced Downregulation of Neutrophils in Patients with Bipolar Disorder

Objective@#Valproic acid (VPA) is an anticonvulsant and commonly long term used as a mood stabilizer for patients with mood disorders. However its chronic effects on the hematological changes were noticed and need to be further evaluated. In this study, we evaluated, in Taiwanese Han Chinese patients with bipolar disorders (BD), the chronic effects of VPA or VPA plus dextromethorphan (DM) on the hematological molecules (white blood cell [WBCs], red blood cells [RBCs], hemoglobin, hematocrit, and platelets). @*Methods@#In a 12-week, randomized, double-blind study, we randomly assigned BD patients to one of three groups: VPA plus either placebo (VPA＋P, n = 57) or DM (30 mg/day, VPA＋DM30, n = 56) or 60 mg/day (VPA＋DM60, n = 53). The Young Mania Rating Scale and Hamilton Depression Rating Scale were used to evaluate symptom severity, and the hematological molecules were checked. @*Results@#Paired t test showed that the WBC, neutrophils, platelets and RBCs were significantly lowered after 12 weeks of VPA＋P or VPA＋DM30 treatment. VPA＋DM60 represented the protective effects in the WBCs, neutrophils, and RBCs but not in the platelets. We further calculated the changes of each hematological molecules after 12 weeks treatment. We found that combination use of DM60 significantly improved the decline in neutrophils induced by the long-term VPA treatment. @*Conclusion@#Hematological molecule levels were lower after long-term treatment with VPA. VPA＋DM60, which yielded the protective effect in hematological change, especially in the neutrophil counts. Thus, DM might be adjunct therapy for maintaining hematological molecules in VPA treatment.

Increased Readmission Risk and Healthcare Cost for Delirium Patients without Immediate Hospitalization in the Emergency Department

OBJECTIVE: Hospitalization of patients with delirium after visiting the emergency department (ED) is often required. However, the readmission risk after discharge from the ED should also be considered. This study aimed to explore whether (i) immediate hospitalization influences the readmission risk of patients with delirium; (ii) the readmission risk is affected by various risk factors; and (iii) the healthcare cost differs between groups within 28 days of the first ED visit. METHODS: Using the National Health Insurance Research Database, the data of 2,780 subjects presenting with delirium at an ED visit from 2000 to 2008 were examined. The readmission risks of the groups of patients (i.e., patients who were and were not admitted within 24 hours of an ED visit) within 28 days were compared, and the effects of the severities of different comorbidities (using Charlson’s comorbidity index, CCI), age, gender, diagnosis and differences in medical healthcare cost were analyzed. RESULTS: Patients without immediate hospitalization had a higher risk of readmission within 3, 7, 14, or 28 days of discharge from the ED, especially subjects with more severe comorbidities (CCI≥3) or older patients (≥65 years). Subjects with more severe comorbidities or older subjects who were not admitted immediately also incurred a greater healthcare cost for re-hospitalization within the 28-day follow-up period. CONCLUSION: Patients with delirium with a higher CCI or of a greater age should be carefully considered for immediate hospitalization from ED for further examination in order to reduce the risk of re-hospitalization and cost of healthcare.

Decreased Cardiac Vagal Control in Drug-Naive Patients with Posttraumatic Stress Disorder

OBJECTIVE: Decreased cardiac vagal control (CVC) has been proposed in posttraumatic stress disorder (PTSD), but the results are mixed. Analyses with larger sample sizes and better methodology are needed. METHODS: Thirty-two drug-naive survivors with current PTSD, 32 survivors without PTSD and 192 matched controls were recruited for a case-control analysis. We used the PTSD checklist-civilian version (PCL-C) to assess posttraumatic symptoms severity. Cardiac autonomic function was evaluated by measuring heart rate variability (HRV) parameters. Frequency-domain indices of HRV were obtained. The obtained results were evaluated in association with personality traits assessed by the Tridimensional Personality Questionnaire (TPQ). RESULTS: PTSD patients exhibited decreased LF-HRV and HF-HRV as compared to survivors without PTSD and to matched controls. The PTSD symptoms severity was associated with reduced mean RR intervals, Var-HRV, LF-HRV and HF-HRV. The harm avoidance score (which has been suggested to be associated with serotonergic activity) was negatively correlated with Var-HRV, LF-HRV and HF-HRV. CONCLUSION: These data suggest that PTSD is accompanied by decreased CVC, highlighting the importance of assessing HRV in PTSD patients. In view of the increased risk for cardiovascular diseases in these vulnerable individuals, one might consider the treatment to restore their autonomic function while reducing PTSD symptoms.

Generalized Anxiety Disorder, Comorbid Major Depression and Heart Rate Variability: A Case-Control Study in Taiwan

OBJECTIVE: Decreased heart rate variability (HRV) has been reported in generalized anxiety disorder (GAD), but the results are mixed. Little is known about the impact of comorbid major depression (MD) on HRV in GAD patients. Both issues necessitate further investigation. METHODS: Twenty unmedicated, physically healthy GAD patients, 20 GAD patients with a secondary diagnosis of MD, 40 MD patients and 60 matched controls were recruited. We used the Hamilton Anxiety Rating Scale and the Hamilton Depression Rating Scale to assess anxiety and depression severity, respectively. Cardiac autonomic function was evaluated by measuring HRV parameters. Frequency-domain indices of HRV were obtained. RESULTS: Three patient groups had more anxiety and depression symptoms than control subjects, but heart rates (HRs) were significantly elevated only in GAD patients with comorbid depression. Relative to controls, GAD patients had reduced HRV while GAD patients with comorbid depression displayed the greatest reductions in HRV among three patients groups. Correlation analyses revealed anxiety/depression severity significantly associated with HRs, variance, LF-HRV and HF-HRV. However, separately analyzing among individual groups and adjusting for HRV-associated covariables rendered the correlations non-significant. CONCLUSION: Our results suggest that reduction in HRV is a psychophysiological marker of GAD and individuals with comorbid GAD and MD may be distinguished based on psychophysiological correlates (for example, HF-HRV) from non-comorbid GAD patients. Taken into account that comorbid depression may confer increased risks for cardiovascular events in GAD patients, this subgroup of GAD patients may benefit better from cardiovascular risk reduction strategies.