Investigating the impact of overnight fasting on intrinsic functional connectivity: a double-blind fMRI study.

The human brain depends mainly on glucose supply from circulating blood as an energy substrate for its metabolism. Most of the energy produced by glucose catabolism in the brain is used to support intrinsic communication purposes in the absence of goal-directed activity. This intrinsic brain function can be detected with fMRI as synchronized fluctuations of the BOLD signal forming functional networks. Here, we report results from a double-blind, placebo controlled, cross-over study addressing changes in intrinsic brain activity in the context of very low, yet physiological, blood glucose levels after overnight fasting. Comparison of four major resting state networks in a fasting state and a state of elevated blood glucose levels after glucagon infusion revealed altered patterns of functional connectivity only in a small region of the posterior default mode network, while the rest of the networks appeared unaffected. Furthermore, low blood glucose was associated with changes in the right frontoparietal network after cognitive effort. Our results suggest that fasting has only limited impact on intrinsic brain activity, while a detrimental impact on a network related to attention is only observable following cognitive effort, which is in line with ego depletion and its reliance on glucose.

Glutamatergic Agents as Add-On Medication for the Treatment of Obsessive-Compulsive Disorder: A Systematic Review and Meta-Analysis.

OBJECTIVE: The aim of the present study was to review the existing literature on clinical trials with glutamatergic agents in adults with obsessive-compulsive disorder (OCD) and to perform a meta-analysis to estimate the overall effect size. DATA SOURCES: We searched in MEDLINE, Embase, and the Cochrane Library for eligible studies, using the following search terms: (glutamate OR glutaminergic OR glutamatergic OR NMDA OR AMPA OR kainate) AND (obsessive-compulsive disorder OR obsessive OR compulsive OR OCD). A separate search was performed for generally known glutamatergic agents. The databases were searched for articles published by May 31, 2015. STUDY SELECTION: Eligible studies were double-blind, randomized controlled trials that tested the efficacy of add-on treatment with a glutamatergic agent in patients with OCD. DATA EXTRACTION: Data were extracted independently by 2 reviewers. We extracted dichotomous data (number of patients with response and remission) to estimate relative risk ratios (RRs), as well as continuous data (scores in Yale-Brown Obsessive Compulsive Scale and Clinical Global Impressions-Severity of Illness and -Improvement scales), which were used to estimate standardized mean differences. Effect sizes were estimated using a random-effects model. RESULTS: Eight randomized controlled trials were identified. The overall ratio for response was RR = 3.71 (95% CI, 2.35-5.83; P < .001). When limited to the studies with treatment-resistant patients, the effect size remained significant (RR = 4.30; 95% CI, 2.19-8.43; P < .001). Secondary outcomes, such as the standardized mean differences for continuous data, showed the statistically significant superiority (P < .001) of glutamatergic agents over placebo. The risk of dropouts was RR = 1.18 (95% CI, 0.83-1.69; P = .361) and the risk of dropouts due to adverse effects was RR = 3.04 (95% CI, 1.57-5.89; P = .001). CONCLUSIONS: Glutamatergic agents are effective as add-on treatment for OCD in general and especially for treatment-refractory OCD.

Effects of overnight fasting on working memory-related brain network: an fMRI study.

Glucose metabolism serves as the central source of energy for the human brain. Little is known about the effects of blood glucose level (BGL) on higher-order cognitive functions within a physiological range (e.g., after overnight fasting). In this randomized, placebo-controlled, double blind study, we assessed the impact of overnight fasting (14 h) on brain activation during a working memory task. We sought to mimic BGLs that occur naturally in healthy humans after overnight fasting. After standardized periods of food restriction, 40 (20 male) healthy participants were randomly assigned to receive either glucagon to balance the BGL or placebo (NaCl). A parametric fMRI paradigm, including 2-back and 0-back tasks, was used. Subclinically low BGL following overnight fasting was found to be linked to reduced involvement of the bilateral dorsal midline thalamus and the bilateral basal ganglia, suggesting high sensitivity of those regions to minimal changes in BGLs. Our results indicate that overnight fasting leads to physiologically low levels of glucose, impacting brain activation during working memory tasks even when there are no differences in cognitive performance.

Antipsychotic-induced elevation of creatine kinase: a systematic review of the literature and recommendations for the clinical practice.

RATIONALE: The primary antipsychotic-induced creatine kinase elevation (i.e., not due to neuroleptic malignant syndrome, extrapyramidal symptoms, etc.) is a poorly studied condition. OBJECTIVES: The aims of the present study were to provide an overview of published cases with antipsychotic-induced creatine kinase elevation and give recommendations for the clinical practice. METHODS: PubMed and EMBASE were searched for eligible trials, case series, and case reports. We set a threshold at ten times the upper normal limit of the creatine kinase value in order to define an elevation as significant. RESULTS: The prevalence of significant creatine kinase elevation ranged between 2 and 7%. We found a total of 42 eligible cases. Men were overrepresented in our sample (81%). Patients with myoglobinuria were more likely to be symptomatic (Fisher's exact test, p = 0.006), whereas neither myoglobinuria (Mann-Whitney test, p > 0.10) nor symptoms (Mann-Whitney test, p = 0.64) were related to the magnitude of the creatine kinase (CK) elevation. In the majority of the cases, the antipsychotic medication was discontinued (86%). Forced diuresis was given in 36% of the patients. Eighty-three percent of the patients had no further complications. Only one case was found with a de novo acute renal failure. CONCLUSIONS: The discontinuation of the antipsychotic medication was a sufficient measure for the CK elevation to subside in the majority of the cases. Cases with myoglobinuria should eventually be treated more aggressively. Further recommendations for the clinical practice are presented.

5-HT2A receptor antagonists for the treatment of neuroleptic-induced akathisia: a systematic review and meta-analysis.

Akathisia is a common and distressing extrapyramidal side-effect, which usually results from the use of antipsychotic medication. Previous reviews and meta-analyses have demonstrated a lack of evidence for the effectiveness of treatment strategies, which are traditionally used against neuroleptic-induced akathisia (NIA), i.e. beta-blockers, anticholinergic agents and benzodiazepines. In the last fifteen years, randomized trials have studied the effect of drugs with antiserotonergic properties on NIA. We conducted a systematic review of randomized control trials and used meta-analytic methods to quantify the overall effect size. PubMed and the Cochrane libraries were searched for eligible trials. Six randomized controlled trials were found, five of which included a placebo control group and qualified for our meta-analysis. The overall effect size in the analysis is RR = 7.10 with 95% CI 3.08-16.40 (p < 0.0001). Our findings suggest that 5-HT(2A) antagonists are effective in the treatment of NIA.

Antidepressants in the treatment of depression/depressive symptoms in cancer patients: a systematic review and meta-analysis.

BACKGROUND: Over the past thirty years a number of studies have suggested that antidepressants can be effective in the treatment of depressive symptoms in patients with cancer. The aim of this paper was to review randomized controlled trials (RCTs) and to perform a meta-analysis in order to quantify their overall effect. METHODS: Pubmed and the Cochrane libraries were searched for the time period between 1980 and 2010. RESULTS: Nine RCTs were identified and reviewed. Six of them (with a total of 563 patients) fulfilled the criteria for meta-analysis, but exhibited an unclear risk for bias. The estimated effect size was 1.56 with 95% CI: 1.07- 2.28 (p= 0.021). There were no differences in discontinuation rates between antidepressants and placebo groups (RR= 0.86 with 95% CI 0.47- 1.56, p=0.62). CONCLUSIONS: This meta-analysis suggests that antidepressants can be effective in treating depressive symptoms beside clinical depression. When considering the risk of side effects and interactions and the heterogeneity among the mostly small studies, a general recommendation cannot be made until well-controlled studies are conducted.