A role of Yueju in fast-onset antidepressant action on major depressive disorder and serum BDNF expression: a randomly double-blind, fluoxetine-adjunct, placebo-controlled, pilot clinical study.

INTRODUCTION: Conventional antidepressants, including fluoxetine, have a major disadvantage in delayed onset of efficacy. Yueju, an herbal medicine used to treat mood disorders was recently found to exhibit rapid antidepressant effects. The present study was conducted to evaluate the role of Yueju in rapidly acting on major depressive disorder (MDD). METHODS: Participants were MDD patients with scores of 24-item Hamilton Depression Rating Scale (HDRS-24) ≥20 and without history of antidepressant use. They randomly received daily oral doses of Yueju (23 g/day) plus fluoxetine (20 mg/day) (experimental group) or placebo plus fluoxetine (control group) for 7 days. HDRS-24 was used as the primary outcome measurement at baseline, and on days 1, 3, 5, and 7. Concentrations of serum brain-derived neurotrophic factor (BDNF) were assessed at baseline and on days 1 and 7. RESULTS: In all, 18 participants met the criteria for data analysis. Compared to baseline level, only experimental group showed significant decrease of HDRS-24 score from day 3 to day 7 (P<0.05). Experimental group also showed significant improvement compared with control group from day 3 to day 7 (P<0.05). No correlation between treatment outcomes with serum BDNF levels was observed. However, experimental group showed significant correlation for serum BDNF level on day 1 with day 7 (r=0.721, P=0.028), whereas the control group did not. CONCLUSION: Yueju likely contributes to fast-onset antidepressant effects on MDD. Further investigation is necessary to firmly establish the ancient formula as a safe, efficacious, and rapidly acting alternative medicine for MDD treatment.

Effects of zinc supplementation on efficacy of antidepressant therapy, inflammatory cytokines, and brain-derived neurotrophic factor in patients with major depression.

OBJECTIVE: Zinc is found in abundance in the human brain. Patients with depression may have decreased consumption of food sources rich in zinc, and zinc supplementation may have a potential influence on depressive symptoms. However, clinical trials on the effect of zinc supplementation in depression are limited. The objective of the present study was to determine the effect of zinc supplementation on efficacy of antidepressant therapy. Furthermore, the effect of zinc on plasma levels of interleukin-6 (IL-6), tumor necrosis factor (TNF-α), and brain-derived neurotrophic factor-a (BDNF-a) were assessed. DESIGN: A single-center, randomized, double-blind, placebo-controlled trial of zinc supplementation was conducted in patients with DSM-IV major depression. Forty-four patients of both sexes aged 18-55 years were recruited for this study from a university hospital. The zinc-supplemented group received zinc sulfate (25 mg elemental Zn/day) orally in addition to their selective serotonin reuptake inhibitor antidepressants for 12 weeks. Symptoms were evaluated using the Hamilton Depression Rating Scale (HDRS) on arrival, weeks 6 and 12. Plasma levels of IL-6, TNF-α and BDNF-a were measured at baseline and at the end of study. RESULTS: Twenty patients in zinc group and 17 patients in placebo groups completed the study. At baseline, there were no significant differences in any variable between the patients allocated to receive placebo and those taking zinc supplement. Zinc supplementation significantly reduced HDRS compared to placebo (P < 0.01 at 12th week). No significant differences were observed in plasma levels of IL-6, TNF-α, and BDNF-a between zinc-supplemented and placebo-supplemented group. CONCLUSION: Zinc supplementation in conjunction with antidepressant drugs might be beneficial for reducing depressive symptoms. However, its effect does not appear to be mediated through impact of zinc on inflammatory processes.

Morphometric brain characterization of refractory obsessive-compulsive disorder: diffeomorphic anatomic registration using exponentiated Lie algebra.

BACKGROUND: Few studies have used neuroimaging to characterize treatment-refractory obsessive-compulsive disorder (OCD). This study sought to explore gray matter structure in patients with treatment-refractory OCD and compare it with that of healthy controls. METHODS: A total of 18 subjects with treatment-refractory OCD and 26 healthy volunteers were analyzed by MRI using a 3.0-T scanner and voxel-based morphometry (VBM). Diffeomorphic anatomical registration using exponentiated Lie algebra (DARTEL) was used to identify structural changes in gray matter associated with treatment-refractory OCD. A partial correlation model was used to analyze whether morphometric changes were associated with Yale-Brown Obsessive-Compulsive Scale scores and illness duration. RESULTS: Gray matter volume did not differ significantly between the two groups. Treatment-refractory OCD patients showed significantly lower gray matter density than healthy subjects in the left posterior cingulate cortex (PCC) and mediodorsal thalamus (MD) and significantly higher gray matter density in the left dorsal striatum (putamen). These changes did not correlate with symptom severity or illness duration. CONCLUSIONS: Our findings provide new evidence of deficits in gray matter density in treatment-refractory OCD patients. These patients may show characteristic density abnormalities in the left PCC, MD and dorsal striatum (putamen), which should be verified in longitudinal studies.

Surgery for psychiatric disorders.

Surgery in psychiatric disorders has a long history and has regained momentum in the past few decades with deep brain stimulation (DBS). DBS is an adjustable and reversible neurosurgical intervention using implanted electrodes to deliver controlled electrical pulses to targeted areas of the brain. It holds great promise for therapy-refractory obsessive-compulsive disorder. Several double-blind controlled and open trials have been conducted and the response rate is estimated around 54%. Open trials have shown encouraging results with DBS for therapy-refractory depression and case reports have shown potential effects of DBS on addiction. Another promising indication is Tourette syndrome, where potential efficacy of DBS is shown by several case series and a few controlled trials. Further research should focus on optimizing DBS with respect to target location and increasing the number of controlled double-blinded trials. In addition, new indications for DBS and new target options should be explored in preclinical research.