Association between the BDNF Val66Met polymorphism and major depressive disorder: a systematic review and meta-analysis.

Study objectives: This meta-analysis analytically reviewed recent studies concerning the potential associations between the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism and susceptibility to major depressive disorder (MDD), with subgroup analyses for race and age. Methods: Relevant case-control studies were systematically searched for in PubMed, Embase, the Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang, and Sinomed databases. A total of 24 studies were finally identified to have reported outcomes including alleles, dominant genes, recessive genes, homozygosity, and heterozygosity. Subgroup meta-analyses were performed based on participant age and ethnicity. Publication bias was represented by funnel plots. All meta-analyses of the randomized controlled trials included for evaluation were performed using RevMan5.3 software. Results: The findings revealed no significant association between BDNF Val66Met polymorphism and MDD. However, the Met allele was found to be associated with genetic susceptibility to MDD among white populations on subgroup analysis (OR = 1.25, 95% CI: 1.05-1.48, P = 0.01). In the genetic model, dominant (OR = 1.40, 95% CI: 1.18-1.66, P = 0.0001), recessive (OR = 1.70, 95% CI: 1.05-2.78, P = 0.03), and homozygous (OR = 1.77, 95% CI: 1.08-2.88, P = 0.02) genes were all associated with MDD. Conclusions: Despite the outcome limitations, this meta-analysis confirmed that the BDNF Val66Met polymorphism is a susceptibility factor for MDD in white populations.

Regulatory Molecules of Synaptic Plasticity in Anxiety Disorder.

Synaptic plasticity is the capacity of synaptic transmission between neurons to be strengthened or weakened. There are many signal molecules accumulated in the presynaptic and postsynaptic membranes that can lead to the regulation of synaptic plasticity and involvement in numerous of neurological and psychiatric diseases, including anxiety disorder. However, the regulatory mechanisms of synaptic plasticity in the development of anxiety disorder have not been well summarized. This review mainly aims to discuss the biological functions and mechanisms of synaptic plasticity-related molecules in anxiety disorder, with a particular focus on the metabotropic glutamate receptors, brain-derived neurotrophic factor, hyperpolarization-activated cyclic nucleotide-gated channels, and postsynaptic density 95. The summarized functions and mechanisms of synaptic plasticity-related molecules in anxiety will provide insight into novel neuroplasticity modifications for targeted therapy for anxiety.

Efficacy and Safety of Acupuncture Combined with Yishen Granule in Elderly Adults with Mild Cognitive Impairment: A Multicenter, Randomized Controlled Trial.

Objective: Mild cognitive impairment (MCI) is a clinical disease that is prevalent in the elderly. Traditional Chinese herbs (TCHs) and acupuncture are valuable therapeutic options for MCI. This study aimed to assess the efficacy and safety of acupuncture and Yishen Granule (YSG) in restoring cognitive function in elderly patients with MCI. Methods: A multicenter, randomized, double-blind, parallel-group, controlled trial (8-week intervention) was conducted at two tertiary hospitals in Shanghai, China. A total of 120 participants were randomly divided into four groups (n = 30 per group): A, acupuncture with YSG; B, acupuncture with placebo herbal medicine; C, sham acupuncture with YSG; D, sham acupuncture with placebo herbal medicine. The primary outcome was a change in Montreal Cognitive Assessment (MoCA), while the secondary outcome was to evaluate improvement in the Mini-Mental State Examination (MMSE). Assessments were conducted at baseline and weeks 4 and 8. Results: Of the 120 patients (69.17 ± 6.57 years; 71 women [59.17%] and 49 men [40.83%]) included in the study, 106 (88.33%) completed the study. Two-way repeated measures ANOVA showed that the MoCA and MMSE scores in group A were significantly different from those in group D at week 4 (P < .05). At week 8, the MoCA and MMSE scores in groups A, B, and C were significantly improved compared with those in group D (P < .001 for all), and the delayed recall score in group A was significantly greater than those in groups B and C (P < .05). Acupuncture and YSG were well tolerated and safe, and no serious adverse events were reported. Conclusions: Acupuncture, YSG, and the combination of both improved cognitive function, with the combined therapy being the most effective, which can be beneficial in preventing dementia and improving the quality of life of the elderly.

Efficacy and safety of Yi Shen Fang granules in elderly people with MCI: study protocol for a multicentre, randomized, double-blind, parallel-group, controlled trial.

BACKGROUND: Mild cognitive impairment (MCI) is a transitional state between normal ageing and dementia. Most MCI patients will progress to dementia within 5 years; therefore, early intervention for MCI is important for delaying the occurrence and progression of dementia. Yi Shen Fang (YSF) granules are a promising traditional Chinese medicine (TCM) treatment that shows great neuroprotective potential against cognitive impairment, as evidenced in clinical and basic studies. This trial aims to systematically evaluate the efficacy and safety of YSF granules in elderly people with MCI. METHODS: This study is a multicentre, randomized, double-blind, parallel-group, controlled trial. Based on the results of previous clinical trials, 280 elderly patients with MCI will be randomly divided into a treatment group (n = 140) and control group (n = 140). The study will last 33 weeks, including 1 week of screening, 8 weeks of intervention, and 24 weeks of follow-up. The primary outcomes will be the changes in Montreal Cognitive Assessment (MoCA) and Memory and Executive Screening (MES) scores before and after the intervention. The secondary outcome measures will be homocysteine (HCY) levels, Functional Assessment Questionnaire (FAQ) scores and event-related potential (ERP) detection in typical cases. The TCM symptom scale is a combined measure of syndrome differentiation and treatment. During this study, the classifications and characteristics of adverse events, the times of occurrence and disappearance, the measures of treatment, their impact on the primary disease, and outcomes will be reported truthfully. DISCUSSION: This study will provide valuable clinical evidence that YSF can help to improve the cognitive function of elderly people with MCI, and the results will be disseminated via conferences and publications. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000036807. Registered on August 25, 2020.

Possible Neuropathology of Sleep Disturbance Linking to Alzheimer's Disease: Astrocytic and Microglial Roles.

Sleep disturbances not only deteriorate Alzheimer's disease (AD) progress by affecting cognitive states but also accelerate the neuropathological changes of AD. Astrocytes and microglia are the principal players in the regulation of both sleep and AD. We proposed that possible astrocyte-mediated and microglia-mediated neuropathological changes of sleep disturbances linked to AD, such as astrocytic adenosinergic A1, A2, and A3 regulation; astrocytic dopamine and serotonin; astrocyte-mediated proinflammatory status (TNFα); sleep disturbance-attenuated microglial CX3CR1 and P2Y12; microglial Iba-1 and astrocytic glial fibrillary acidic protein (GFAP); and microglia-mediated proinflammatory status (IL-1b, IL-6, IL-10, and TNFα). Furthermore, astrocytic and microglial amyloid beta (Aß) and tau in AD were reviewed, such as astrocytic Aß interaction in AD; astrocyte-mediated proinflammation in AD; astrocytic interaction with Aß in the central nervous system (CNS); astrocytic apolipoprotein E (ApoE)-induced Aß clearance in AD, as well as microglial Aß clearance and aggregation in AD; proinflammation-induced microglial Aß aggregation in AD; microglial-accumulated tau in AD; and microglial ApoE and TREM2 in AD. We reviewed astrocytic and microglial roles in AD and sleep, such as astrocyte/microglial-mediated proinflammation in AD and sleep; astrocytic ApoE in sleep and AD; and accumulated Aß-triggered synaptic abnormalities in sleep disturbance. This review will provide a possible astrocytic and microglial mechanism of sleep disturbance linked to AD.

The efficacy and safety of 'antianxiety granule' for anxiety disorder: a multicentre, randomized, double-blind, placebo-controlled, parallel-group trial.

BACKGROUND: Anxiety disorders are the most prevalent class of lifetime disorders in China, and generalized anxiety disorder (GAD) is one of the most common but frequently overlooked anxiety disorders. Conventional pharmacological treatments for GAD have varying degrees of side effects, dependency, and/or withdrawal syndromes. Traditional Chinese medicine (TCM) is considered a valuable therapeutic option for anxiety disorders and a potentially effective technique to reduce the side effects associated with antipsychotic drugs. This trial aimed to evaluate the clinical efficacy and safety of Antianxiety Granule, a granular Chinese medicine compound, for treatment of GAD. METHODS/DESIGN: The current work is a multicentre, randomized, double-blind, placebo-controlled, parallel-group clinical trial with a 6-week treatment schedule. The study consists of three periods: a 1-7-day screening period, a 6-week primary treatment period, and a 1-week follow-up period. Follow-up assessments will be conducted 1 week after the last visit with a face-to-face interview or by telephone. The clinical efficacy of Antianxiety Granule for the treatment of GAD will be evaluated by examining the change in the Hamilton anxiety scale (HAMA) score, state-trait anxiety inventory (STAI) score, and TCM symptom scale in patients with GAD who receive daily TCM treatment. Moreover, an intention-to-treat (ITT) analysis will also be used in this randomized controlled trial (RCT). DISCUSSION: Our study is a multicentre, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the safety and efficacy of Antianxiety Granule for the treatment of GAD. The results of this trial will provide valuable clinical evidence for the treatment of GAD. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1800016039. Registered on 8 May 2018.