Associations between impulsivity and fecal microbiota in individuals abstaining from methamphetamine.

INTRODUCTION: Methamphetamine (MA) abuse is a major public problem, and impulsivity is both a prominent risk factor and a consequence of addiction. Hence, clarifying the biological mechanism of impulsivity may facilitate the understanding of addiction to MA. The microbiota-gut-brain axis was suggested to underlie a biological mechanism of impulsivity induced by MA. METHODS: We therefore recruited 62 MA addicts and 50 healthy controls (HCs) to investigate the alterations in impulsivity and fecal microbiota and the associations between them in the MA group. Thereafter, 25 MA abusers who abstained from MA for less than 3 months were followed up for 2 months to investigate the relationship between impulsivity and microbiota as abstinence became longer. 16S rRNA sequencing was conducted for microbiota identification. RESULTS: Elevated impulsivity and dysbiosis characterized by an increase in opportunistic pathogens and a decrease in probiotics were identified in MA abusers, and both the increased impulsivity and disrupted microbiota tended to recover after longer abstinence from MA. Impulsivity was related to microbiota, and the effect of MA abuse on impulsivity was mediated by microbiota. CONCLUSION: Our findings potentially highlighted the importance of abstention and implicated the significant role of the microbiota-gut-brain axis in the interrelationship between microbiota and behaviors, as well as the potential of microbiota as a target for intervention of impulsivity.

The gut microbiota as a potential biomarker for methamphetamine use disorder: evidence from two independent datasets.

Background: Methamphetamine use disorder (MUD) poses a considerable public health threat, and its identification remains challenging due to the subjective nature of the current diagnostic system that relies on self-reported symptoms. Recent studies have suggested that MUD patients may have gut dysbiosis and that gut microbes may be involved in the pathological process of MUD. We aimed to examine gut dysbiosis among MUD patients and generate a machine-learning model utilizing gut microbiota features to facilitate the identification of MUD patients. Method: Fecal samples from 78 MUD patients and 50 sex- and age-matched healthy controls (HCs) were analyzed by 16S rDNA sequencing to identify gut microbial characteristics that could help differentiate MUD patients from HCs. Based on these microbial features, we developed a machine learning model to help identify MUD patients. We also used public data to verify the model; these data were downloaded from a published study conducted in Wuhan, China (with 16 MUD patients and 14 HCs). Furthermore, we explored the gut microbial features of MUD patients within the first three months of withdrawal to identify the withdrawal period of MUD patients based on microbial features. Results: MUD patients exhibited significant gut dysbiosis, including decreased richness and evenness and changes in the abundance of certain microbes, such as Proteobacteria and Firmicutes. Based on the gut microbiota features of MUD patients, we developed a machine learning model that demonstrated exceptional performance with an AUROC of 0.906 for identifying MUD patients. Additionally, when tested using an external and cross-regional dataset, the model achieved an AUROC of 0.830. Moreover, MUD patients within the first three months of withdrawal exhibited specific gut microbiota features, such as the significant enrichment of Actinobacteria. The machine learning model had an AUROC of 0.930 for identifying the withdrawal period of MUD patients. Conclusion: In conclusion, the gut microbiota is a promising biomarker for identifying MUD and thus represents a potential approach to improving the identification of MUD patients. Future longitudinal studies are needed to validate these findings.

Cognitive function and cardiovascular health in the elderly: network analysis based on hypertension, diabetes, cerebrovascular disease, and coronary heart disease.

Introduction: Cognitive decline in the elderly population is a growing concern, and vascular factors, such as hypertension, diabetes, cerebrovascular disease, and coronary heart disease, have been associated with cognitive impairments. This study aims to provide deeper insights into the structure of cognitive function networks under these different vascular factors and explore their potential associations with specific cognitive domains. Methods: Cognitive function was assessed using a modified Chinese version of the mini-mental state examination (MMSE) scale, and intensity centrality and side weights were estimated by network modeling. The network structure of cognitive function was compared across subgroups by including vascular factors as subgroup variables while controlling for comorbidities and confounders. Results: The results revealed that cerebrovascular disease and coronary heart disease had a more significant impact on cognitive function. Cerebrovascular disease was associated with weaker centrality in memory and spatial orientation, and a sparser cognitive network structure. Coronary heart disease was associated with weaker centrality in memory, repetition, executive function, recall, attention, and calculation, as well as a sparser cognitive network structure. The NCT analyses further highlighted significant differences between the cerebrovascular disease and coronary heart disease groups compared to controls in terms of overall network structure and connection strength. Conclusion: Our findings suggest that specific cognitive domains may be more vulnerable to impairments in patients with cerebrovascular disease and coronary heart disease. These insights could be used to improve the accuracy and sensitivity of cognitive screening in these patient populations, inform personalized cognitive intervention strategies, and provide a better understanding of the potential mechanisms underlying cognitive decline in patients with vascular diseases.

Estradiol and raloxifene as adjunctive treatment for women with schizophrenia: A meta-analysis of randomized, double-blind, placebo-controlled trials.

OBJECTIVES: We conducted a comprehensive meta-analysis of all available trials to evaluate the efficacy and safety of estrogen and selective estrogen receptor modulators as adjunctive treatment for women with schizophrenia. METHODS: Multiple databases were searched from the inception until March 2022. Only randomized, double-blind, placebo-controlled studies (randomized controlled trials) were included. Mean differences (MDs) and their 95% confidence intervals (CIs) were calculated using random effects models. RESULTS: The meta-analysis included six estradiol versus placebo studies (n = 724) and seven raloxifene versus placebo studies (n = 419), covering a total of 1143 patients. Adjunctive estradiol outperformed the placebo in terms of the Positive and Negative Syndrome Scale (PANSS) total score (MD = -7.29; 95% CI = -10.67 to -3.91; I2  = 59.1%; p < 0.001; k = 9; N = 858), positive symptom score (MD = -1.54; 95% CI = -3.04 to -0.72; I2  = 45.8%; p < 0.001; k = 7; N = 624), negative symptom score (MD = -1.9; 95% CI = -1.77 to -0.34; I2  = 37.6%; p < 0.05; k = 14; N = 1042), and general psychopathology score (MD = -4.27; 95% CI = -7.14 to -1.41; I2  = 76.3%; p < 0.005; k = 7; N = 624). Adjunctive raloxifene outperformed the placebo in terms of the PANSS total score (MD = -6.83; 95% CI = -11.69 to -1.97; I2  = 67.8%; p = 0.006; k = 8; N = 432) and general psychopathology score (MD = -3.82; 95% CI = -6.36 to -1.28; I2  = 65.3%; p < 0.005; k = 8; N = 432). CONCLUSIONS: Our meta-analysis showed that estradiol and raloxifene are effective and safe adjunctive treatments that improve schizophrenia symptoms in women. Moreover, the effects of estradiol and raloxifene differed in terms of timing and dosage. Both are promising adjunctive treatments that merit further study.

Distinguishing major depressive disorder from bipolar disorder in remission: A brain structural network analysis.

BACKGROUND: It is challenging to differentiate major depressive disorder (MDD) from bipolar disorder (BD) in depression and remission. To exclude the potential influence of depressive episodes, we compared the white matter (WM) network between MDD and BD patients in remission to find disease-specific alterations in MDD and BD, and then distinguish these two affective disorders. METHODS: We recruited 33 patients with remitted MDD (rMDD), 54 patients with remitted BD (rBD), and 60 healthy controls (HCs). Diffusion tensor imaging and high-resolution 3D T1-weighted image were acquired. Global and nodal topological parameters were used to depict the alterations of the whole-brain WM network. RESULTS: We found that rMDD displayed increased global network efficiency (Eglob) and local network efficiency (Eloc) compared with HCs, whereas we found no significance between rBD and HCs. Compared with rBD and HCs, patients in the rMDD group showed increased nodal degree and nodal efficiency, and decreased nodal shortest path length in the four cerebral regions, including the right calcarine fissure (CAL.R), right cuneus (CUN.R), left lingual gyrus (LING.L), and left middle occipital gyrus (MOG.L). We did not find any rBD specific changes of nodal topological metrics. LIMITATIONS: The main limitation is the possible effects of medication and BD subtypes on the results. CONCLUSIONS: Our findings indicate that rMDD exhibited elevated global properties compared with HCs group, and increased nodal properties in the CAL.R, CUN.R, LING.L, and MOG.L specifically compared with rBD and HCs, which may underlie the distinction of the two affective disorders in remission.

Shared Transdiagnostic Neuroanatomical Signatures Across First-episode Patients with Major Psychiatric Diseases and Individuals at Familial Risk.

BACKGROUND: Nowadays, increasing evidence has found transdiagnostic neuroimaging biomarkers across major psychiatric disorders (MPDs). However, it remains to be known whether this transdiagnostic pattern of abnormalities could also be seen in individuals at familial high-risk for MPDs (FHR). We aimed to examine shared neuroanatomical endophenotypes and protective biomarkers for MPDs. METHODS: This study examined brain grey matter volume (GMV) of individuals by voxel-based morphometry method. A total of 287 individuals were included, involving 100 first-episode medication-naive MPDs, 87 FHR, and 110 healthy controls (HC). They all underwent high-resolution structural magnetic resonance imaging (MRI). RESULTS: At the group level, we found MPDs were characterized by decreased GMV in the right fusiform gyrus, the right inferior occipital gyrus, and the left anterior and middle cingulate gyri compared to HC and FHR. Of note, the GMV of the left superior temporal gyrus was increased in FHR relative to MPDs and HC. At the subgroup level, the comparisons within the FHR group did not return any significant difference, and we found GMV difference among subgroups within the MPDs group only in the opercular part of the right inferior frontal gyrus. CONCLUSION: Together, our findings uncover common structural disturbances across MPDs and substantial changes in grey matter that may relate to high hereditary risk across FHR, potentially underscoring the importance of a transdiagnostic way to explore the neurobiological mechanisms of major psychiatric disorders.

The correlation between mental health status, sleep quality, and inflammatory markers, virus negative conversion time among patients confirmed with 2019-nCoV during the COVID-19 outbreak in China: An observational study.

ABSTRACT: The 2019 coronavirus disease (COVID-19) has spread to the whole world. Psychological and sleep problems among confirmed patients have drawn extensive attention which may be highly related to immune function and inflammatory responses of people. The aim of this study is to examine the correlation of mental health status, sleep quality, and inflammatory markers, virus negative conversion time (NCT) among confirmed patients during the COVID-19 outbreak.A cross-sectional survey was conducted in this study. Data from 66 patients assessed with demographic information, anxious symptom, depressive symptom, stress, and sleep quality were collected using a smartphone-based questionnaire platform and then clinical characteristics and laboratory indicators were collected using case review.Nearly 30% of the participants reported depression, anxiety, perceived pressure, and poor sleep quality. Compared with the group without depression, neutrophil count, and ratio of neutrophil count to lymphocyte count (NLR) in the depression disorder group were increased (P = .028, 0.043). There was also a significant difference in NLR and NCT between the anxiety group and the non-anxiety group (P = .021, .024). Similarly, compared with the good sleep quality group, NLR in the poor sleep quality group was increased (P = .011). Correlation analysis indicated that Self-Rating Depression Scale score was positively related to neutrophil count and NLR (r = 0.366, 0.330, P = .016, .031). The total score of Pittsburgh Sleep Quality Index (PSQI) was negatively related to lymphocyte count (r = -0.317, P = .049), and the sleep disturbance as 1 of the 7 dimensions of PSQI scale was positively correlated with NCT and NLR (r = 0.370, 0.340, P = .020, .034).In our study, confirmed patients were prone to have psychological and sleep problems. The level of inflammation in patients with psychological and sleep problems was higher than that in patients without corresponding problems. The inflammatory level increased with the increase of Self-Rating Depression Scale score, and the lymphocyte count decreased with the increase of the PSQI score. NCT was prolonged in the anxiety group and sleep disturbance was positively correlated with NCT.

Is the Long-Term Use of Benzodiazepines Associated With Worse Cognition Performance in Highly Educated Older Adults?

Background: Benzodiazepines (BZD) are common medications for sedative, hypnotic, and anxiolytic that are especially prevalent in older adults. Previous studies have shown that BZD use could impair users' cognition, significantly affecting their quality of life. Past research has shown that higher education might play a protective role in the process of cognitive decline. Very few studies had examined the cognitive effects of BZD on highly educated older adults. The study aimed to explore how cognitive functions would be affected by benzodiazepines among highly educated older adults. Method: 140 older adults with an average education period of 14.8 years were included in this study. The subjects were divided into three separate groups, the long-term BZD users (≥180 days), short-term BZD users (<180 days), and non-users. Demographics and cognitive assessments for the three groups were analyzed using the analysis of variance (ANOVA), the chi-squared test, and the analysis of covariance (ANCOVA). To examine the association between BZD use and cognition a multiple linear aggression approach was used. Result: All three groups were significantly different from each other when looking at executive functioning in the Trail Making Test B (TMT-B). Compared to the control group, short-term BZD users showed significant defects in TMT-B time (p = 0.002) and TMT-B errors (p < 0.001); long-term BZD users showed significant defect on TMT-B time (p = 0.041). Compared to short-term BZD users, long-term BZD users showed significant merit on TMT-B errors (p = 0.001). No significant differences were found in other cognitive tasks that reflected general cognition, verbal memory, language fluency, and visual memory. After adjusting for demographic, increased BZD use over time was positively associated with scores for the revised Brief Visuospatial Memory Test (r = 0.377, p = 0.012). Conclusion: BZD use may be significantly associated with worse executive functioning in highly educated older adults. However, there is no association between the duration of BZD use and increased cognitive deficits in highly educated older adults. This study identified future experimental directions including potential longitudinal studies, within-subject studies comparing mood disorder patients' cognitive performance before and after onset of BZD use, and between-subject studies that directly compare BZD's effect on subjects with the same baseline of cognitive functioning.

The Effects of Benzodiazepine Use and Abuse on Cognition in the Elders: A Systematic Review and Meta-Analysis of Comparative Studies.

OBJECTIVE: Benzodiazepines (BZD) are one of the most frequently prescribed drugs worldwide. However, the cognitive effects of benzodiazepines in the elderly are highly debated. This systematic review and meta-analysis aims to explore the following two questions in the elderly population: (i) Do BZD lead to any impairments in cognitive functions in elderly users? and (ii) Which specific cognitive domains are most affected by BZD use and abuse? METHODS: First, we performed a literature search following the PRISMA guidelines. Electronic databases, including PubMed, PsycINFO, EMBASE, Cochrane Library, and Web of Science were searched until May 14th, 2020. After selecting the relevant articles, we integrated the results of the selected studies with a standardized cognitive classification method. Next, we performed meta-analyses with the random-effects model on the cognitive results. Finally, we specifically examined the cognitive impairments of BZD in the abuse subgroup. RESULTS: Of the included studies, eight of the thirteen had meta-analyzable data. Compared to the controls, elderly BZD users had significantly lower digital symbol test scores (n=253; SMD: -0.61, 95% CI: -0.91 to 0.31, I² = 0%, p < 0.0001). There was no significant difference in Mini-Mental State Examination, Auditory Verbal Learning Test, and Stroop Color and Word Test scores between BZD users and controls. According to the subgroup analyses, BZD abusers performed significantly worse than controls in Mini-Mental State Examination (n=7726; SMD: -0.23, 95% CI: -0.44 to -0.03, I² = 86%, p = 0.02), while there was no significant difference between the regular BZD users and the controls (n=1536; SMD: -0.05, 95% CI: -0.59 to 0.48, I² = 92%, p =0.85). CONCLUSION: In the elderly population, the processing speed (digital symbol test scores) was significantly impaired in BZD users; global cognition (Mini-Mental State Examination scores) was significantly impaired in BZD abusers but not in BZD regular users. This study provides insight into the factors that interact with BZD cognitive effects, such as aging, testing tools, and abuse. Clinicians should be cautious when prescribing BZD for the elderly. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, identifier CRD42019124711.

[Overview of systematic review on acupoint application for bronchial asthma].

OBJECTIVE: To overview the systematic review/meta-analysis on acupoint application for bronchial asthma. METHODS: A computerized retrieval was performed from 6 databases, named CNKI, CBM, VIP, WF, PubMed and Cochrane Library. The time of retrieval was from the establishment of the database to April 1, 2019. According to the inclusion and exclusion criteria, the two researchers independently selected articles and extracted data. In case of disagreement, a third party was adopted to solve it. Using AMSTAR2, PRISMA and GRADE, the literature quality and evidence grade were assessed. RESULTS: A total of 19 articles relevant with systematic evaluation/meta-analysis were included, 16 articles of which were in Chinese and 3 articles in English, published in the period from 2007 to 2018. Forty-two outcome indicators were included. It was found that the quality of methodology was very low, the quality of literature report has some or serious flaws and the quality level of evidence is mostly low or very low. CONCLUSION: Currently, regarding the articles of systematic review/meta-analysis on acupoint application for bronchial asthma, it is quite low in methodological quality and literature report quality and is not high in the grade of outcome indicators. The clinical research should be intensively specified in association with the characteristics of traditional Chinese medicine so as to provide more reliable clinical evidence.