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.
Highlights • Depression and frailty are two common and pervasive conditions in older age. • We conducted the first meta-analysis exploring the relationship between these constructs. • In ...cross-sectional studies, participants with frailty had fourfold increased odds of depression. • People with depression were at approximately fourfold increased odds of having frailty. • Pooled data from longitudinal studies confirmed the heighted risk of comorbidity.
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.
Objectives
To investigate whether low‐dose aspirin (<300 mg/d) can influence the onset of cognitive impairment or dementia in observational studies and improve cognitive test scores in randomized ...controlled trials (RCTs) in participants without dementia.
Design
Systematic review and meta‐analysis.
Setting
Observational and interventional studies.
Participants
Individuals with no dementia or cognitive impairment initially.
Measurements
Odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for the maximum number of covariates from each study, were used to summarize data on the incidence of dementia and cognitive impairment in observational studies. Standardized mean differences (SMDs) were used for cognitive test scores in RCTs.
Results
Of 2,341 potentially eligible articles, eight studies were included and provided data for 36,196 participants without dementia or cognitive impairment at baseline (mean age 66, 63% female). After adjusting for a median of three potential confounders over a median follow‐up period of 6 years, chronic use of low‐dose aspirin was not associated with onset of dementia or cognitive impairment (5 studies, N = 26,159; OR = 0.82, 95% CI = 0.55–1.22, P = .33, I2 = 67%). In three RCTs (N = 10,037; median follow‐up 5 years), the use of low‐dose aspirin was not associated with significantly better global cognition (SMD=0.005, 95% CI=–0.04–0.05, P = .84, I2 = 0%) in individuals without dementia. Adherence was lower in participants taking aspirin than in controls, and the incidence of adverse events was higher.
Conclusion
This review found no evidence that low‐dose aspirin buffers against cognitive decline or dementia or improves cognitive test scores in RCTs.
Objective
To compare differences in efficacy during maintenance treatment for bipolar disorder (BD) according to lithium serum levels. A multicenter retrospective cohort study and a dose‐response ...meta‐analysis were conducted.
Methods
The cohort study was conducted in Taiwan from 2001 to 2019 to identify patients with euthymic BD according to different serum levels (<0.4, 0.4–0.8, and 0.8–1.2 mmol/L). We adopted adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) for time to the recurrence of mood episodes having the <0.4 mmol/L group as the reference group. Moreover, we systematically searched for related articles in major databases before January 31, 2021 (PROSPERO: CRD42021235812). We used random‐effects modeling to estimate the dose‐response relationships between lithium serum levels and recurrence of mood episodes, which were depicted as odds ratios (ORs) with 95% CIs.
Results
A total of 1406 participants (cohort: 466; meta‐analysis: 940) were included. In the cohort study, the 0.4–0.8 mmol/L group was associated with a significantly lower risk of recurrences (aHR: 0.75), while the 0.8–1.2 mmol/L group had a lower risk without statistical significance (aHR: 0.77). The dose‐response meta‐analysis showed that with the increase in lithium serum levels, the risk decreased (linear model OR: 0.85, for every 0.1 mmol/L increase; non‐linear model OR: 1.00 at 0.0 mmol/L, 0.42 at 0.4 mmol/L, and 0.27 at 0.8 mmol/L).
Conclusion
Although confounding by indication cannot be excluded, the combined results suggest a significant preventative effect on the recurrence of major affective episodes among those with serum levels of 0.4–0.8 mmol/L.
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