The importance of tryptophan as a precursor for neuroactive compounds has long been acknowledged. The metabolism of tryptophan along the kynurenine pathway and its involvement in mental disorders is ...an emerging area in psychiatry. We performed a meta-analysis to examine the differences in kynurenine metabolites in major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SZ). Electronic databases were searched for studies that assessed metabolites involved in the kynurenine pathway (tryptophan, kynurenine, kynurenic acid, quinolinic acid, 3-hydroxykynurenine, and their associate ratios) in people with MDD, SZ, or BD, compared to controls. We computed the difference in metabolite concentrations between people with MDD, BD, or SZ, and controls, presented as Hedges' g with 95% confidence intervals. A total of 101 studies with 10,912 participants were included. Tryptophan and kynurenine are decreased across MDD, BD, and SZ; kynurenic acid and the kynurenic acid to quinolinic acid ratio are decreased in mood disorders (i.e., MDD and BD), whereas kynurenic acid is not altered in SZ; kynurenic acid to 3-hydroxykynurenine ratio is decreased in MDD but not SZ. Kynurenic acid to kynurenine ratio is decreased in MDD and SZ, and the kynurenine to tryptophan ratio is increased in MDD and SZ. Our results suggest that there is a shift in the tryptophan metabolism from serotonin to the kynurenine pathway, across these psychiatric disorders. In addition, a differential pattern exists between mood disorders and SZ, with a preferential metabolism of kynurenine to the potentially neurotoxic quinolinic acid instead of the neuroprotective kynurenic acid in mood disorders but not in SZ.
We conducted a systematic review and meta-analysis to investigate whether the use of statins could be associated with the risk of all-caused dementia, Alzheimer's disease (AD), vascular dementia ...(VaD), and mild cognitive impairment (MCI). Major electronic databases were searched until December 27
, 2017 for studies investigating use of statins and incident cognitive decline in adults. Random-effects meta-analyses calculating relative risks (RRs) were conducted to synthesize effect sizes of individual studies. Twenty-five studies met eligibility criteria. Use of statins was significantly associated with a reduced risk of all-caused dementia (k = 16 studies, adjusted RR (aRR) = 0.849, 95% CI = 0.787-0.916, p = 0.000), AD (k = 14, aRR = 0.719, 95% CI = 0.576-0.899, p = 0.004), and MCI (k = 6, aRR = 0.737, 95% CI = 0.556-0.976, p = 0.033), but no meaningful effects on incident VaD (k = 3, aRR = 1.012, 95% CI = 0.620-1.652, p = 0.961). Subgroup analysis suggested that hydrophilic statins were associated with reduced risk of all-caused dementia (aRR = 0.877; CI = 0.818-0.940; p = 0.000) and possibly lower AD risk (aRR = 0.619; CI = 0.383-1.000; p = 0.050). Lipophilic statins were associated with reduced risk of AD (aRR = 0.639; CI = 0.449-0.908; p = 0.013) but not all-caused dementia (aRR = 0.738; CI = 0.475-1.146; p = 0.176). In conclusion, our meta-analysis suggests that the use of statins may reduce the risk of all-type dementia, AD, and MCI, but not of incident VaD.
Within recent years, there has been a seismic shift in smoking rates from high-income to low- and middle-income countries (LMICs). Evidence indicates that perceived stress may comprise a barrier for ...smoking cessation, but little is known about the association of perceived stress and smoking in LMICs. We conducted a cross-sectional, community-based study comprising 217,561 people mean age 38.5 (SD = 16.1) years, 49.4% males. A perceived stress score range 2 (lowest-stress) 10 (highest-stress) was computed from the Perceived Stress Scale. Multivariable logistic regression analyses were conducted. In the overall sample, a one-unit increase in perceived-stress resulted in a 5% increased odds of smoking (OR = 1.05; 95%CI = 1.03-1.06). Increased stress was associated with smoking in Africa (OR = 1.06; 95%CI = 1.04-1.09), Americas (OR = 1.03; 95%CI = 1.01-1.05), and Asia (OR = 1.06; 95%CI = 1.04-1.08), but not Europe (OR = 0.99; 95%CI = 0.95-1.02). Increasing levels of perceived stress were significantly associated with heavy smoking (≥30 cigarettes per day) among daily smokers (OR = 1.08; 95%CI = 1.02-1.15). A country-wide meta-analysis showed that perceived stress is associated with daily smoking in most countries. Prospective studies are warranted to confirm/refute this relationship, which may have meaningful public health implications.
Evidence has indicated an association between depression and low dietary intake of omega-3 polyunsaturated fatty acids (PUFAs). However, clinical trials examining the therapeutic benefit of omega-3 ...PUFAs in depression showed inconsistent results. The goal of this study is to systematically evaluate the antidepressant efficacy of omega-3 PUFAs by using meta-analytic method.
MEDLINE, Embase, and PsycINFO databases were searched from 1966 through August 2006 using the key words (depression OR depressive disorder OR mood disorder) AND (omega-3 OR EPA OR DHA OR poly-unsaturated fatty acid OR fish oil). The search was limited to literature in English and clinical trials.
Ten double-blind, placebo-controlled studies in patients with mood disorders receiving omega-3 PUFAs with the treatment period lasting 4 weeks or longer were included.
Effect size (ES) of each individual study was derived by computing the standardized mean difference. A random-effects model was used to pool the ESs of all included studies.
When pooling the results of 10 included studies (N = 329), we found a significant antidepressant effect of omega-3 PUFAs (ES = 0.61, p = .003). Likewise, omega-3 PUFAs significantly improved depression in patients with clearly defined depression (ES = 0.69, p = .002) or with bipolar disorder (ES = 0.69, p = .0009). The dosage of eicosapentaenoic acid (EPA) did not change the antidepressant efficacy significantly. However, significant heterogeneity among these studies and publication bias were noted.
Although our meta-analysis showed significant antidepressant efficacy of omega-3 PUFAs, it is still premature to validate this finding due to publication bias and heterogeneity. More large-scale, well-controlled trials are needed to find out the favorable target subjects, therapeutic dose of EPA, and the composition of omega-3 PUFAs in treating depression.
Omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are widely recommended for health promotion. Over the last decade, prescription omega-3 fatty acid products (RxOME3FAs) ...have been approved for medical indications. Nonetheless, there is no comprehensive analysis of safety and tolerability of RxOME3FAs so far.
A systematic review of randomized controlled trials (RCTs) was carried out based on searches in six electronic databases. The studies involving marketed RxOME3FA products were included, and adverse-effect data were extracted for meta-analysis. Subgroup analysis and meta-regression were conducted to explore the sources of potential heterogeneity.
Among the 21 included RCTs (total 24,460 participants; 12,750 from RxOME3FA treatment cohort and 11,710 from control cohort), there was no definite evidence of any RxOME3FA-emerging serious adverse event. Compared with the control group, RxOME3FAs were associated with more treatment-related dysgeusia (fishy taste; p = 0.011) and skin abnormalities (eruption, itching, exanthema, or eczema; p < 0.001). Besides, RxOME3FAs had mild adverse effects upon some non-lipid laboratory measurements elevated fasting blood sugar (p = 0.005); elevated alanine transaminase (p = 0.022); elevated blood urea nitrogen (p = 0.047); decreased hemoglobin (p = 0.002); decreased hematocrit (p = 0.009). Subgroup analysis revealed that EPA/DHA combination products were associated with more treatment-related gastrointestinal adverse events eructation (belching; p = 0.010); nausea (p = 0.044) and low-density lipoprotein cholesterol elevation (p = 0.009; difference in means = 4.106mg/dL).
RxOME3FAs are generally safe and well tolerated but not free of adverse effects. Post-marketing surveillance and observational studies are still necessary to identify long-term adverse effects and to confirm the safety and tolerability profiles of RxOME3FAs.
•Among the 21 included RCTs, there was no definite evidence of any RxOME3FA-emerging serious adverse event.•RxOME3FAs were associated with mild adverse events and minor changes upon laboratory measurements.•The two subgroups of RxOME3FAs,EPA/DHA combinations and EPA-only products, may have slightly different adverse-effect profiles.
Background and aims
Nicotine is a highly addictive substance in tobacco products that dysregulates several neurotransmitters in the brain and impairs executive function. Non‐invasive brain ...stimulation (NIBS) methods such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are promising treatments for nicotine dependence. We investigated the efficacy and acceptability of NIBS in managing smoking cessation through a systematic review and network meta‐analysis (NMA).
Methods
We conducted a systematic review to identify randomized controlled trials (RCTs) that investigated the efficacy of NIBS for smoking cessation. All pairwise meta‐analyses and NMA procedures were conducted using random‐effects and frequentist models. The co‐primary outcomes were (1) the change in number of cigarettes smoked per day (change in frequency of smoking) in patients with nicotine dependence after NIBS and (2) acceptability (the dropout rate). The effect sizes for co‐primary outcomes of change in frequency of smoking and acceptability were assessed according to standardized mean difference (SMD) and odds ratio, respectively.
Results
Twelve RCTs with 710 participants (mean age: 44.2 years, 31.2% female) were included. Compared with the sham control, 10‐Hz rTMS over the left dorsolateral prefrontal cortex (DLPFC) was associated with the largest changes in smoking frequency SMD = −1.22, 95% confidence interval (95% CI) = −1.77 to −0.66. The 2‐mA bifrontal tDCS (SMD = −0.97, 95% CI = −1.32 to −0.62) and 10‐Hz deep rTMS over the bilateral DLPFC with cue provocation (SMD = −0.77, 95% CI = −1.20 to −0.34) were associated with a significantly larger decrease in smoking frequency versus the sham. None of the investigated NIBSs was associated with dropout rates significantly different from those of the sham control groups.
Conclusion
Prefrontal non‐invasive brain stimulation interventions appear to reduce the number of cigarettes smoked with good acceptability.
Although hypofunction of N-methyl-D-aspartate (NMDA) receptor-mediated neurotransmission is proposed to play an important role in the pathophysiology of schizophrenia, results of the clinical trials ...of small molecules that enhance the NMDA function are inconsistent. A meta-analysis of all the double-blind, placebo-controlled studies in patients with schizophrenia was performed to examine their efficacy on different symptom domains, the dose-response, the effects of concomitant antipsychotics, and their side effects. About eight hundred subjects from 26 studies were included in current meta-analysis. Overall, the NMDA-enhancing molecules are effective in most schizophrenic symptom domains with the effect size (ES) of total psychopathology of 0.40 (p<1 x 10(-4)). The ES of clinical efficacy of the symptom domains were in the order of depressive (0.40, p=3 x 10(-4)), negative (0.38, p<1 x 10(-4)), cognitive (0.28, p=2 x 10(-3)), positive symptom (0.26, p=0.0006), and general psychopathology (0.26, p=0.006). Glycine, D-serine, and sarcosine treatments significantly improved multiple symptom domains, whereas D-cycloserine did not improve any symptom domain. Moderator analysis revealed that glycine, D-serine and sarcosine are better than D-cycloserine in improving the overall psychopathology. Patients receiving risperidone or olanzapine, but not clozapine, improved. No significant side effect or safety concern was noted. In addition to testing more lead compounds, long-term trials are required to determine their functional improvement capacity. Other drug targets that may enhance NMDA neurotransmission more than the molecules tested so far need to be explored.
Background On the basis of evidence from studies showing the antidepressant effects of omega-3 polyunsaturated fatty acids and the inverse relation between fish consumption and the prevalence of ...depression, the phospholipid hypothesis seems promising in ascertaining the etiology and treatment of depression. Although several studies have shown lower levels of omega-3 (n-3) polyunsaturated fatty acids in depressive patients, the results of individual polyunsaturated fatty acids, including docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and the omega-6 (n-6) polyunsaturated fatty acid arachidonic acid (AA), were inconsistent. Methods We conducted the meta-analyses of 14 studies comparing the levels of polyunsaturated fatty acids between depressive patients and control subjects. The effect size of each study was synthesized by using a random effects model. Results Compared with control subjects, the levels of EPA, DHA, and total n-3 polyunsaturated fatty acids were significantly lower in depressive patients. There was no significant change in AA or total n-6 polyunsaturated fatty acids. Conclusions The results showed lower levels of EPA, DHA, and total n-3 polyunsaturated fatty acids in patients with depression, thus implying that n-3 polyunsaturated fatty acids play a role in the pathogenesis of depression. Our findings provide further support to the phospholipid hypothesis of depression and a rationale for using n-3 polyunsaturated fatty acids as an alternative treatment for depression. With these results, future studies examining specific roles of DHA and EPA in different clusters of depressive symptoms are warranted.
Urinary tract infections (UTIs) with pathogenic strain resistance leading to a high recurrence rate affect health quality and have become a high-priority issue due to the economic burden on the ...health care system.
This study aimed to investigate the supportive benefits of traditional herbal medicines (THMs) for the treatment and prevention of recurrent UTIs through a meta-analysis of randomized controlled trials.
Systematic searches of databases, including PubMed/Medline, the Cochrane Library, and China National Knowledge Infrastructure (CNKI), were conducted to collect eligible studies for meta-analysis. The inclusion criteria were randomized controlled trials that investigated UTI recurrence using THM treatment.
The results of 22 studies showed that THM treatment led to significantly fewer UTI events in the experimental group than in the control group (OR = 0.348; 95% confidence interval CI = 0.257 to 0.473; p < 0.001). Seventeen studies reported UTI events during the follow-up period, and the recurrence rate was lower in the experimental group than in the control group (OR, 0.326; 95% CI, 0.245-0.434; p < 0.01). Subgroup analysis further showed that compared to antibiotics alone, treatment with THM plus antibiotics significantly reduced UTI events in the acute phase (OR = 0.301; 95% CI = 0.201 to 0.431; p < 0.001) as well as in the follow-up period (OR = 0.347; 95% CI = 0.241 to 0.498; p < 0.001). However, THM treatment alone was not superior to antibiotics in the acute treatment phase (OR = 0.540; 95% CI = 0.250 to 1.166; p = 0.117) or in the follow-up period (OR = 0.464; 95% CI = 0.111 to 1.951; p = 0.295). Herbal ingredients for recurrent UTI events also showed benefits compared to placebo treatment in the acute phase (OR = 0.337; 95% CI = 0.158 to 0.717; p = 0.005) and during follow-up (OR = 0.238; 95% CI = 0.139 to 0.409; p < 0.001).
THM combined with antibiotics is helpful for people with acute UTIs and for reinfection prevention. THMs alone, although less effective for recurrent UTIs, could be considered a therapeutic alternative to antibiotics.
Abstract Background Accelerated telomere shortening is associated with stress-related cell damage and aging. Patients with depression have been shown to have shortened life expectancy and to be ...associated with multiple age-related systemic diseases. Previous studies have examined leukocyte telomere length (LTL) in patients with depression, but have shown inconsistent results. Methods We conducted meta-analyses by pooling relevant results strictly from all eligible case-control studies for cross-sectional comparison of LTL between depressive patients and control subjects (16 studies involving 7207 subjects). The effect sizes (shown as Hedges’s g ) of each individual study were synthesized by using a random effects model. Results Our analysis revealed telomere length is significantly shorter in subjects with depression in comparison to healthy controls (Hedges’ g =-0.42, p =1*10-5 , corresponding to r =-0.21). Significant heterogeneity among studies examining LTL in subjects with depression was found (Q=116.07, df = 16, I 2 = 86.21%, p <1*10-8 ), which can possibly be explained by methods used in measuring telomere length (Q=18.42, df =2, p =1*10-4 ). There was no significant publication bias, nor moderating effect of age, female percentage, or illness duration of depression on synthesized results. Conclusions Our results support the hypothesis that depression is associated with accelerated cell aging. Future studies are required to clarify whether the association is mediated through environmental stress, and whether effective treatment can halt cell aging.
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