Placebo effects in randomized trials of pharmacological and neurostimulation interventions for mental disorders: An umbrella review.

There is a growing literature exploring the placebo response within specific mental disorders, but no overarching quantitative synthesis of this research has analyzed evidence across mental disorders. We carried out an umbrella review of meta-analyses of randomized controlled trials (RCTs) of biological treatments (pharmacotherapy or neurostimulation) for mental disorders. We explored whether placebo effect size differs across distinct disorders, and the correlates of increased placebo effects. Based on a pre-registered protocol, we searched Medline, PsycInfo, EMBASE, and Web of Knowledge up to 23.10.2022 for systematic reviews and/or meta-analyses reporting placebo effect sizes in psychopharmacological or neurostimulation RCTs. Twenty meta-analyses, summarising 1,691 RCTs involving 261,730 patients, were included. Placebo effect size varied, and was large in alcohol use disorder (g = 0.90, 95% CI [0.70, 1.09]), depression (g = 1.10, 95% CI [1.06, 1.15]), restless legs syndrome (g = 1.41, 95% CI [1.25, 1.56]), and generalized anxiety disorder (d = 1.85, 95% CI [1.61, 2.09]). Placebo effect size was small-to-medium in obsessive-compulsive disorder (d = 0.32, 95% CI [0.22, 0.41]), primary insomnia (g = 0.35, 95% CI [0.28, 0.42]), and schizophrenia spectrum disorders (standardized mean change = 0.33, 95% CI [0.22, 0.44]). Correlates of larger placebo response in multiple mental disorders included later publication year (opposite finding for ADHD), younger age, more trial sites, larger sample size, increased baseline severity, and larger active treatment effect size. Most (18 of 20) meta-analyses were judged 'low' quality as per AMSTAR-2. Placebo effect sizes varied substantially across mental disorders. Future research should explore the sources of this variation. We identified important gaps in the literature, with no eligible systematic reviews/meta-analyses of placebo response in stress-related disorders, eating disorders, behavioural addictions, or bipolar mania.

The role of inflammation in anxiety and depression in the European U-BIOPRED asthma cohorts.

BACKGROUND: Growing evidence indicates high comorbid anxiety and depression in patients with asthma. However, the mechanisms underlying this comorbid condition remain unclear. The aim of this study was to investigate the role of inflammation in comorbid anxiety and depression in three asthma patient cohorts of the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) project. METHODS: U-BIOPRED was conducted by a European Union consortium of 16 academic institutions in 11 European countries. A subset dataset from subjects with valid anxiety and depression measures and a large blood biomarker dataset were analysed, including 198 non-smoking patients with severe asthma (SAn), 65 smoking patients with severe asthma (SAs), 61 non-smoking patients with mild-to-moderate asthma (MMA), and 20 healthy non-smokers (HC). The Hospital Anxiety and Depression Scale was used to measure anxiety and depression and a series of inflammatory markers were analysed by the SomaScan v3 platform (SomaLogic, Boulder, Colo). ANOVA and the Kruskal-Wallis test were used for multiple-group comparisons as appropriate. RESULTS: There were significant group effects on anxiety and depression among the four cohort groups (p < 0.05). Anxiety and depression of SAn and SAs groups were significantly higher than that of MMA and HC groups (p < 0.05. There were significant differences in serum IL6, MCP1, CCL18, CCL17, IL8, and Eotaxin among the four groups (p < 0.05). Depression was significantly associated with IL6, MCP1, CCL18 level, and CCL17; whereas anxiety was associated with CCL17 only (p < 0.05). CONCLUSIONS: The current study suggests that severe asthma patients are associated with higher levels of anxiety and depression, and inflammatory responses may underlie this comorbid condition.

An investigation of neuromelanin distribution in substantia nigra and locus coeruleus in patients with Parkinson's disease using neuromelanin-sensitive MRI.

Loss of neuromelanin in the midbrain is known in Parkinson's disease(PD), which can now be directly detected by neuromelanin-sensitive MRI(NM-MRI). This case-control study was to investigate the distribution of neuromelanin in the substantia nigra(SN) and the locus coeruleus(LC) using NM-MRI technique and evaluate its potential as a diagnostic marker for PD. 10 early PD patients(H&Y stage I, II), 11 progressive PD patients(H&Y stage III-V), and 10 healthy controls matched in age and gender were recruited. All participants completed clinical and psychometric assessments as well as NM-MRI scans. Neuromelanin signal intensities in SN and LC were measured by contrast-to-noise ratios(CNRs) derived from NM-MRI scans. There were significant decreases of CNRs in SNpc(including anterior, central, and posterior) and LC in PD patients compared to controls. There were also significant differences of CNR between the left and right sides. CNR in LC had a negative correlation with the Non-Motor Symptoms Scale(NMSS) score in PD patients(|R|=0.49), whereas CNR in SNpc did not correlate with Unified Parkinson Disease Rating Scale(UPDRS) score(|R|<0.3). The receiver operating characteristic(ROC) curves revealed that the CNR in LC had a high diagnostic specificity of 90.1% in progressive patients. This study provides new evidence for the asymmetric distribution of neuromelanin in SN and the LC of patients with PD. The neuromelanin loss is bilateral and more predominately in LC than that in SN. This distinct neuromelanin distribution pattern may offer a potential diagnostic marker and a potential neuropharmacological intervention target for PD patients.

Effect of acceptance and commitment therapy for depressive disorders: a meta-analysis.

OBJECTIVE: To systematically evaluate the effect of Acceptance and Commitment Therapy (ACT) on depressive disorders. METHODS: The electronic databases of Web of Science Core Collection, Pubmed, EMBASE, Cochrane Library, PsycInfo, CNKI, Wanfang and Weipu were used to select relevant publications. Screening, data extraction, and quality assessment were undertaken following PRISMA guidelines for preferred reporting of systematic reviews and meta-analysis. RevMan5.4 was used for meta-analysis. RESULTS: 11 studies with a total of 962 patients were included. Random-effects model analysis showed that ACT could effectively reduce the level of depressive symptoms in patients with depressive disorders (SMD = - 1.05, 95% CI: - 1.43-- 0.66, P < 0.00001), improve psychological flexibility (MD = 4.84, 95% CI: 2.70-6.97, P < 0.00001), and have good maintenance effect (SMD = - 0.70, 95% CI: - 1.15-- 0.25, P = 0.002). All differences were statistically significant. CONCLUSIONS: ACT not only improves depressive symptoms and psychological flexibility, but also has a good maintenance effect, and it is particularly effective in Chinese patients. Large randomized controlled trials are needed to validate the findings from this meta-analysis.

Effects of exercise on obsessive-compulsive disorder symptoms: a systematic review and meta-analysis.

OBJECTIVE: This systematic review and meta-analysis assessed the efficacy of exercise in reducing OCD symptoms. METHODS: We searched PubMed, Cochrane Central Register of Controlled Trials, MEDLINE, Scopus and grey literature until March 2022. The study was preregistered at Prospero (CRD42021283931). We included randomised controlled and pre-post trials assessing physical activity as an intervention for OCD. Risk of bias was assessed using the Cochrane ROBINS-I tool and the RoB2 tool. RESULTS: The analysis included 6 trials (N = 92); 2 were RCTS and 4 were pre-post design studies. A random-effects meta-analysis of pre-post data identified a large reduction of OCD symptoms following exercise (g = 1.33 [95%CI 1.06-1.61]; k = 6). Exercise was also associated with significant pre-post reductions in anxiety (g = 0.71 [95%CI 0.37-1.05; k = 4) and depression (g = 0.57 [95%CI 0.26-0.89]; k = 2). Risk of bias was moderate-high in uncontrolled trials on the ROBINS-I and RCTs showed 'some concerns' on the RoB2. CONCLUSION: Exercise was associated with a large pre-post reduction of OCD symptoms; however, few trials were of robust quality and all were at risk of bias. Further well-powered and better quality RCTs are required to assess the role of exercise as an intervention for OCD.KEY POINTSStudies exploring exercise as an adjunct therapy for OCD have small participant numbers, therefore a systematic review and meta-analysis is needed to estimate potential efficacy.Pre-post analysis shows that exercise was associated with a large reduction of OCD symptomsThe current systematic review and meta-analysis points to the potential for exercise to be beneficial for the treatment for OCD symptoms. However, more well-powered and better controlled RCTs are required to fully assess the benefit of exercise for the treatment of OCD symptoms.

Immune-endocrine biomarkers associated with mental health: A 9-year longitudinal investigation from the Hertfordshire Ageing Study.

BACKGROUND: The study of neural-endocrine-immune system interactions has led to substantial advances in our understanding of neuropsychiatric disorders. Growing evidence reveals the pivotal roles of inflammatory cytokines signalling the brain to produce neurochemical, neuroendocrine, and neuroimmune changes which affect mood and behaviour. Ageing is accompanied by the development of low-grade systemic inflammation which may promote changes in the neural systems predisposing to geriatric depression via the hypothalamic-pituitary-adrenal (HPA) axis. The aim of this study was to investigate the longitudinal associations between baseline values and conditional changes (independent of baseline) in immune-endocrine biomarkers and mental health status in a population-based cohort of older adults. METHODS: Data from 347 subjects (200 men, 147 women) who participated in the Hertfordshire Ageing Study at baseline (1994/5, mean age 67.3 years) and at 9-year follow-up were analysed. Serum samples for analysis of inflammatory and endocrinological measures were collected at baseline and follow-up. At follow-up, depression (Hospital Anxiety and Depression Scale) and mental health (Short Form-36 questionnaire) were assessed. Baseline values and changes in biomarkers in relation to risk of high depression scores (top sex-specific third) and low mental health scores (bottom sex-specific third) were examined using logistic regression. RESULTS: Lower baseline cortisol was related to greater risk of high depression scores; higher baseline cortisol: dehydroepiandrosterone sulphate ratio (men only) and higher baseline C-reactive protein (CRP) (women only) were related to greater risk of poor mental health scores. In addition, greater decline in cortisol was related to increased risk of high depression scores among men. These relationships were robust (p < 0.05) after controlling for sex, age, BMI, smoking, alcohol consumption and number of systems medicated. CONCLUSION: This study provides further evidence of the role of the HPA axis and inflammation in older adults with poor mental health. In addition, the findings highlight sex differences where increased inflammation in women and declines in cortisol in men were linked to poorer mental health. Further research is warranted to confirm these findings. This could lead to the search for potential biomarkers to stratify medications as well as developing novel intervention targets to improve mental health at older age.

Anxiety in asthma: a systematic review and meta-analysis.

BACKGROUND: Background: Growing evidence from observational studies indicates a high prevalence of anxiety in asthma. However, prevalence rates of coexisting anxiety symptoms and comorbid anxiety disorders vary widely across studies. We aimed to evaluate the associations between anxiety and asthma and provide more precise comorbidity estimates. METHODS: We systematically reviewed the literature from case-controlled studies and conducted a meta-analysis to evaluate the pooled prevalence estimates and risks of anxiety symptoms and anxiety disorders in asthma individuals. Screening, data extraction, and quality assessment were undertaken following PRISMA guidelines for preferred reporting of systematic reviews and meta-analysis. A random-effects model was used to calculate pooled prevalence rates. Meta-analysis was conducted using Review Manager 5.3. Multiple databases including PubMed, ScienceDirect, PsychINFO, and PsycARTICLES were searched for publications before 1 December 2019. The review protocol was registered on PROSPERO (ref: CRD42020176028). RESULTS: In total, 19 studies involving 106813 participants were included. The pooled prevalence of anxiety symptoms and anxiety disorders in individuals with asthma was 0.32 (95% CI 0.22-0.43) and 0.24 (95% CI 0.13-0.41), respectively. The risks of coexisting anxiety symptoms and comorbid anxiety disorders were significantly higher in asthma patients than in non-asthma controls indicated by OR 1.89 (95% CI 1.42-2.52; Z = 4.37; p < 0.001) and OR 2.08 (95% CI 1.70-2.56; Z = 6.97; p < 0.001), respectively. Anxiety symptoms and anxiety disorders occur at increased frequency among patients with asthma. CONCLUSIONS: Our findings highlight the need for appropriate assessments for these comorbid conditions, which may help to identify a subgroup of patients who might benefit from interventions designed to reduce anxiety and enhance the quality of life.

Caring for patients in mental health services during COVID-19 outbreak in China.

This article reflects on some radical changes made in mental health services in China which include the implementation of the initial triage system and the special isolation ward, the early screening and testing for both patients and staff, the smaller teams working on rotating shifts on-site, and the adequate provision of PPE. These measures would be of great value as a reference to the effective delivery of mental health services in other countries through this pandemic.

Effects of SSRIs on peripheral inflammatory markers in patients with major depressive disorder: A systematic review and meta-analysis.

INTRODUCTION: Peripheral levels of inflammatory markers are elevated in major depressive disorder (MDD). Selective serotonin reuptake inhibitors (SSRIs) affect levels of inflammatory markers in patients with MDD, but studies have reported inconsistent findings. This systematic review and meta-analysis aims to investigate the effects of SSRI treatment on peripheral levels of a range of inflammatory markers in MDD patients. METHODS: Systematic literature search (Pubmed, Web of Science, Embase, Cochrane) for studies published before November 2018. Studies were included if they used SSRI monotherapy and peripheral levels of interleukin (IL)-1ß, IL-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ were measured before and after treatment in patients with MDD. Meta-analysis was conducted using Comprehensive Meta-analysis (version 2). Effect sizes were calculated using bias-corrected standardized mean difference (Hedges' g) between pre- and post-treatment. Sub-group analyses, meta-regression and publication bias estimates were undertaken; sensitivity analyses were performed using different estimated pre- and post-treatment correlations and after removing poor quality studies. RESULTS: Twenty two eligible studies including 827 MDD patients were included in the meta-analysis: fifteen studies for IL-6; eleven for TNF-α; eight for IL-10; seven for IL-1ß; six for IL-4; five for IL-2; and four for IFN-γ. The pooled effect estimate indicates SSRI treatment decreased levels of pro-inflammatory markers IL-6 (Hedges' g, -0.418; 95%CI, -0.663 to -0.174; I2 = 89.412), TNF-α (Hedges' g, -0.554; 95%CI, -0.990 to -0.118; I2 = 95.438) and IL-1ß (Hedges' g = -0.574; 95%CI, -1.014 to -0.135; I2 = 91.622), and anti-inflammatory marker IL-10 (Hedges' g = -0.615; 95%CI, -0.989 to -0.242; I2 = 90.406). There were no significant treatment effects on levels of IL-2, IL-4, or IFN-γ. There was a high level of heterogeneity between studies. Sensitivity analyses indicated the robustness of the primary analyses. CONCLUSIONS: The current review and meta-analysis indicates moderate immunomodulating effects of SSRI treatment for MDD, which suggests SSRIs may owe some of their therapeutic effect to their anti-inflammatory properties. High heterogeneity across studies may limit interpretation of the findings and larger randomized clinical trials are warranted.

Effects of SSRIs on peripheral inflammatory cytokines in patients with Generalized Anxiety Disorder.

BACKGROUND: Extensive research into psychoneuroimmunology has led to substantial advances in our understanding of the reciprocal interactions between the central nervous system and the immune system in neuropsychiatric disorders. To date, inflammation has been implicated in the pathogenesis of depression and anxiety. The immunomodulating effects of antidepressants on depression have been reported, however, there is no evidence of the similar effects of antidepressants on anxiety. The aim of the study was to investigate the effects of selective serotonin reuptake inhibitors (SSRIs) on peripheral inflammatory cytokines in patients with first episode generalized anxiety disorder (GAD). METHODS: A prospective cohort design was employed: 42 patients with first episode GAD were treated with either escitalopram or sertraline for 12 weeks. Anxiety was measured by the Generalized Anxiety Disorder Scale and the State Trait Anxiety Inventory, serum pro-inflammatory cytokine levels were measured by the enzyme-linked immunosorbent assay (ELISA), and CRP determined by an immunoturbidimetric method before and after SSRIs treatment RESULTS: Baseline levels of anxiety and pro-inflammatory cytokines including IL-1α, IL-6, IL-8, IL-12, IFN-γ, and CRP were significantly reduced after treatment of SSRIs (p < 0.05 in all cases). In addition, the change of anxiety measures co-vary with the change of peripheral cytokine levels (p < 0.05 in all cases). The regression model revealed that log transformed baseline levels of CRP and IL-6 predicted treatment response (p < 0.05 in both cases). CONCLUSIONS: This study is the first to investigate the effects of SSRIs on pro-inflammatory cytokines in patients with first episode GAD. The findings indicate moderate acute anti-inflammatory effects of SSRIs in GAD, and suggest that these anti-inflammatory effects may underlie anxiolytic effects of SSRIs. The study also indicates that serum levels of CRP and IL-6 may predict treatment response. However, data from randomized controlled trials is warranted to confirm these findings.

Peripheral inflammatory cytokines and immune balance in Generalised Anxiety Disorder: Case-controlled study.

INTRODUCTION: Previous investigations have demonstrated that major depression is associated with particular patterns of cytokine signalling. The primary aim of this study was to examine peripheral pro-inflammatory and anti-inflammatory cytokines and immune balance in Generalised Anxiety Disorder (GAD). METHODS: A case-controlled cross-sectional study design was employed: 54 patients with GAD and 64 healthy controls were recruited. Participants completed self-report measures of anxiety and depression. Two pro-inflammatory and two anti-inflammatory cytokines were measured using multiplex technology. RESULTS: Case-control logistic regression analyses revealed significant differences in serum levels of IL-10, TNF-α, and IFN-γ between GAD and control groups after adjusting for age, gender, body mass index, smoking and alcohol consumption: these group differences were independent of the presence or degree of depression. Comparison of pro-inflammatory to anti-inflammatory cytokine ratios indicated that there were significantly higher ratios of TNF-α/IL10, TNF-α/IL4, IFN-γ/IL10, and IFN-γ/IL4 in the GAD group compared to the control group. CONCLUSIONS: This study is the first to investigate both pro- and anti-inflammatory cytokines and their balance in patients with GAD in comparison to healthy controls. The findings indicate a relatively increased pro-inflammatory response and decreased anti-inflammatory response and provide the first demonstration of an altered cytokine balance in GAD. Serum cytokine levels in GAD were independent of the presence of depression.

Effects of antipsychotics on bone mineral density and prolactin levels in patients with schizophrenia: a 12-month prospective study.

OBJECTIVE: Effects of conventional and atypical antipsychotics on bone mineral density (BMD) and serum prolactin levels (PRL) were examined in patients with schizophrenia. METHODS: One hundred and sixty-three first-episode inpatients with schizophrenia were recruited, to whom one of three conventional antipsychotics (perphenazine, sulpiride, and chlorpromazine) or one of three atypical antipsychotics (clozapine, quetiapine, and aripiprazole) was prescribed for 12 months as appropriate. BMD and PRL were tested before and after treatment. Same measures were conducted in 90 matched healthy controls. RESULTS: Baseline BMD of postero-anterior L1-L4 range from 1.04 ± 0.17 to 1.42 ± 1.23, and there was no significant difference between the patients group and healthy control group. However, post-treatment BMD values in patients (ranging from 1.02 ± 0.15 to 1.23 ± 0.10) were significantly lower than that in healthy controls (ranging from 1.15 ± 0.12 to 1.42 ± 1.36). The BMD values after conventional antipsychotics were significantly lower than that after atypical antipsychotics. The PRL level after conventional antipsychotics (53.05 ± 30.25 ng/ml) was significantly higher than that after atypical antipsychotics (32.81 ± 17.42 ng/ml). Conditioned relevance analysis revealed significant negative correlations between the PRL level and the BMD values after conventional antipsychotics. CONCLUSION: The increase of PRL might be an important risk factor leading to a high prevalence of osteoporosis in patients with schizophrenia on long-term conventional antipsychotic medication.

Placebo effects in mental health disorders: protocol for an umbrella review.

INTRODUCTION: Given the high prevalence of mental health disorders and their significant socioeconomic burden, there is a need to develop improved treatments, and to evaluate them through placebo-controlled trials. However, the magnitude of the placebo response in randomised controlled trials to test medications may be substantial, affecting their interpretation. Therefore, improved understanding of the patient, trial and mental disorder factors that influence placebo responses would inform clinical trial design to better detect active treatment effects. There is a growing literature exploring the placebo response within specific mental health disorders, but no overarching synthesis of this research has been produced to date. We present a protocol for an umbrella review of systematic reviews and/or meta-analyses in which we aim to understand the effect size and potential predictors of placebo response within, and across, mental health disorders. METHODS AND ANALYSIS: We will systematically search databases (Medline, PsycINFO, EMBASE+EMBASE Classic, Web of Knowledge) for systematic reviews and/or meta-analyses that report placebo effect size in clinical trials in patients with mental health disorders (initial search date 23 October 2022). Screening of abstracts and full texts will be done in pairs. We will extract data to qualitatively examine how placebo effect size varies across mental health disorders. We also plan to qualitatively summarise predictors of increased placebo response identified either quantitatively (eg, through meta-regression) or qualitatively. Risk of bias will be assessed using the AMSTAR-2 tool. We aim to not only summarise the current literature but also to identify gaps in knowledge and generate further hypotheses. ETHICS AND DISSEMINATION: We do not believe there are any specific ethical considerations relevant to this study. We will publish the results in a peer-reviewed journal.

When a minor head injury results in enduring symptoms: a prospective investigation of risk factors for postconcussional syndrome after mild traumatic brain injury.

OBJECTIVE: A significant proportion (15-30%) of patients with mild traumatic brain injury (MTBI) are at risk of developing postconcussional syndrome (PCS). The aim of this study was to investigate the contributions of cognitive, emotional, behavioural and social factors to the development of PCS and identify early predictors. METHODS: A prospective cohort design was employed. 126 MTBI patients completed baseline questionnaire assessments within 2 weeks of the injury and 107 completed follow-up questionnaire assessments at 3 and 6 months. A series of self-report measures were used to assess cognitive, behavioural and emotional responses to MTBI. The primary outcome was the ICD-10 diagnosis for PCS. Demographic and clinical characteristic variables were compared between PCS cases and non-cases using independent sample t tests and χ(2) tests. Individual and multivariate logistic regression analyses were used to detect predictors of PCS. RESULTS: Of 107 MTBI patients, 24 (22%) met the criteria for PCS at 3 months and 22 (21%) at 6 months. Individual logistic regression analysis indicated that negative MTBI perceptions, stress, anxiety, depression and all-or-nothing behaviour were associated with the risk of PCS. Multivariate analysis revealed that all-or-nothing behaviour was the key predictor for the onset of PCS at 3 months while negative MTBI perceptions predicted PCS at 6 months. CONCLUSIONS: The study provides good support for the proposed cognitive behavioural model. Patients' perceptions of their head injury and their behavioural responses play important roles in the development of PCS, indicating that cognitive and behavioural factors may be potential targets for early preventive interventions.

A neuroimmunological perspective on anxiety disorders.

OBJECTIVE: Research into psychoneuroimmunology has led to substantial advances in our understanding of the reciprocal interactions between the central nervous system and the immune system in neuropsychiatric disorders. To date, the presence of inflammatory responses and the crucial role of cytokines in major depression have been addressed in numerous studies. However, neuroinflammatory hypotheses in anxiety disorders have been studied less extensively than in major depression. There is a high research need for better understanding of both the heterogeneous role of specific cytokines in the control of anxious states and in different anxiety disorders and of the immunomodulating effects of antidepressants on anxiety. METHODS: Relevant literature was identified through a search of MEDLINE via PubMed. We discuss recent research on neuroimmunology in anxiety and make methodological recommendations for future investigation of neuroinflammatory hypotheses in anxiety disorders. RESULTS: Some accumulating evidence has indicated modulatory effects of cytokines on neuronal communication and anxiety; however, research has not revealed consistent reproducible findings. CONCLUSIONS: The availability of inflammatory biomarkers may provide an opportunity to identify patients via specific pathophysiological processes and to monitor therapeutic responses within relevant pathways. Further understanding of the neuroimmunological mechanisms to untangle the reciprocal associations between inflammation and anxiety is warranted.

Locus coeruleus in the pathogenesis of Alzheimer's disease: A systematic review.

The locus coeruleus (LC) is a nucleus in the brain stem producing noradrenaline. While cognitive decline in Alzheimer's disease (AD) has primarily been related to cholinergic depletion, evidence indicates extensive LC degeneration as its earliest pathological marker. The current study aimed to systematically evaluate current evidence investigating the role of the LC in the pathogenesis of AD. A systematic search of the literature was performed on electronic databases including PubMed and Web of Science. Twelve animal, human post mortem, and human imaging studies were included in this review. Screening, data extraction, and quality assessment were undertaken following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for preferred reporting of systematic reviews. Significant associations were identified between LC changes and cognitive decline. Significant reductions in fiber density, neuronal number, and LC volume were seen to correlate with other pathological degenerative markers. Current evidence indicates an important role of the LC in pathogenesis of AD and suggests its potential in both diagnosis and treatment of AD. This systematic review advances our understanding of the role of the LC in AD by synthesizing available evidence, identifying research gaps, highlighting methodological challenges, and making recommendations for future work.

Correlation analysis between D-dimer-to-fibrinogen-ratio and carotid plaque in young patients aged 18-45 with acute cerebral infarction.

BACKGROUND: D-Dimer and fibrinogen were commonly used to detect the coagulation and fibrinolytic function, but D-dimer to fibrinogen ratio (DFR) in carotid plaque in young patients aged 18-45 with acute cerebral infarction (ACI) has not been used clinically. In this work, we focused on the evaluation of the DFR value of this group of patients and analyzed its possible correlation. METHODS: A total of 164 patients with ACI patients aged 18-45 were selected as research subjects after their first admission. They had undergone carotid plaque contrast-enhanced ultrasound (CEUS) and were divided into two groups with carotid plaque (n = 97) and with no carotid plaque (n = 67). According to NIHSS score and carotid plaque grade, the clinical symptoms of patients were judged. Univariate and multivariate analyses were conducted to compare the risk factors of carotid plaque in ACI patients. RESULTS: The DFR value of patients in the carotid plaque group (103.41 ± 20.81) was significantly higher than that of the no carotid plaque control group (88.9 ± 26.51). We also identified DFR X103 was the only independent risk factor (ß = 0.53; 95% CI, 0.914-0.984; P = 0.05). DFR X103 was increased with the severity of the disorder and with the CEUS grades. The area under the DFR curve was 0.673 (95% CI 0.584～0.762). CONCLUSION: The value of the DFR is positively correlated with CEUS carotid plaque grading and NIHSS score, which can predict the severity of carotid plaque in ACI patients aged 18-45. Therefore it is worthy of clinical application.

Prevalence of depressive disorders and associated demographic characteristics in Shandong: An epidemiological investigation.

BACKGROUND: Depression is characterized by debilitating symptoms and high recurrence rates, and there are relatively few large-scale epidemiological surveys of depressive disorders conducted in Shandong since 2005. Data from the largest Epidemiological Survey of Mental Disorders conducted in 2015 in Shandong were collected to investigate the prevalence of depressive disorders and associated demographic characteristics in general adult population. METHODS: A multi-stage stratified cluster sampling method was adopted to select residents and a two-stage screening and assessment process was used to define the prevalence and characteristics of depressive disorders. Respondents were initially screened using the General Health Questionnaire followed by a structured clinical interview using the DSM-IV criteria. RESULTS: Among 27,489 respondents who completed the survey, 1277 respondents met the diagnostic criteria for depressive disorders. The adjusted prevalence in the last month was 4.86%, among which the prevalence of major depressive disorder, dysthymia, and unspecified depressive disorder were 2.32%, 1.78%, and 0.75%, respectively. 40.35% of depression patients had moderate or severe functional impairment and only 10.65% of patients had visited a psychiatric service. Univariate and multivariate analyses revealed that age, gender, occupation, education, marital status, and urban/rural living were associated with the prevalence. LIMITATIONS: The key limitation is that this is a cross-sectional survey therefore cannot draw any causal relationship between risk factors and disease progression. CONCLUSIONS: Findings from this largest epidemiological study reveal current prevalence of depressive disorders and associated demographic factors and offers opportunities for policy makers and health-care professionals to improve mental health provision in Shandong.

External eating, impulsivity and attentional bias to food cues.

Cognitive and behavioural responses to food reward, such as attentional biases and overeating, have been associated with individual differences in reward-responsiveness and impulsivity. This study investigated relationships between external eating, impulsivity and attentional bias to food cues, assessed using the pictorial visual-probe task. As previously reported, attentional bias correlated positively with external eating. Additional novel findings were: (i) attentional bias for food cues was positively related to trait impulsivity, (ii) attentional bias remained related to attention impulsivity after controlling for external eating. Our findings highlight the relationship between the ability to control impulsive responding and selective attention to food cues.

Psychological distress after subarachnoid haemorrhage: A systematic review and meta-analysis.

OBJECTIVE: Psychological distress is a common complication in patients after Subarachnoid haemorrhage (SAH) which often has significant impact on the prognosis. The objective of this study was to determine the pooled prevalence of anxiety symptoms and depressive symptoms in patients after SAH and identify relevant risk factors. METHODS: The study adopted a systematic review and meta-analysis protocol. Multiple databases including EMBASE, Medline, PsychInfo, and Web of Science were searched for publications before 1st January 2020. Screening, data extraction, and quality assessment were undertaken following the PRISMA guidelines for preferred reporting of systematic reviews and meta-analysis. The random-effects model was used to calculate pooled prevalence rates. Meta-analysis was conducted using Comprehensive Meta-analysis software. The review protocol was registered on PROSPERO (CRD42020182594). RESULTS: 42 studies reporting anxiety symptoms and 64 studies reporting depressive symptoms were included. The pooled short term(<3 years) and long term(≥3 years) prevalence rates of anxiety symptoms were 31.4%(95% CI: 23.6%, 40.4%) and 40.4%(95% CI: 31.6%, 49.8%), respectively, whereas the pooled short term and long term prevalence rates of depressive symptoms were 25.2%(95%CI: 17.8%, 34.5%) and 35.8%(95%CI: 28.6%, 43.6%), respectively. Gender and pre-existing psychiatric conditions were identified as potential risk factors. CONCLUSIONS: The high prevalence of anxiety symptoms and depressive symptoms after SAH highlights the need for appropriate assessment and management of psychological stress in patients after SAH. Further research is warranted to explore potential underlying mechanisms and to develop holistic interventions that incorporate understanding of both the biological and psychological impact of SAH.