Neutrophil/lymphocyte ratio,monocyte/lymphocyte ratio,and mean platelet volume as systemic inflammatory markers in different states of bipolar disorder

Abstract

Background: Currently, increasing evidence supports the hypothesis that alterations in the immune-inflammatory system are critical for the pathophysiology of bipolar disorder (BD). Neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), monocyte/lymphocyte ratio (MLR), and mean platelet volume (MPV) have recently been investigated as inexpensive and simple inflammatory markers.

Aims: The aim of this study is to compare NLR, PLR, MLR, and MPV in depressive, manic, and euthymic patients with BD and healthy controls, and to evaluate whether values of NLR, PLR, MLR, and MPV are possible state or trait biomarkers in BD.

Methods: This retrospective study was conducted with 341 patients with BD (100 patients in a depressive state, 141 patients in a manic state, and 100 patients in a euthymic state) and 114 healthy controls.

Results: We found that patients with BD in manic states had higher levels of MPV, NLR, and MLR, and patients with BD in depressive states had higher levels of MPV than the controls. Moreover, MPV predicted all states of BD, while NLR and MLR predicted the manic state of BD.

Conclusions: NLR, MLR, and MPV obtained from simple and inexpensive blood tests were significantly higher in patients with BD than in healthy controls, which each imply low-grade inflammation. MPV may serve as a possible trait biomarker of BD, while NLR and MLR may both serve as possible state biomarkers of the manic state.     

Evaluation of the neutrophil/lymphocyte ratio,platelet/lymphocyte ratio,and mean platelet volume as inflammatory markers in children with attention‐deficit hyperactivity disorder

Aim

The neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), monocyte/lymphocyte ratio (MLR), and mean platelet volume (MPV) have recently been used as indicators of a systemic inflammatory response. The aim of this study was to investigate the relations of the NLR, PLR, MLR, and MPV with attention‐deficit hyperactivity disorder (ADHD).

Methods

The study group consisting of 82 children diagnosed with ADHD was compared with a healthy control (HC) group of 70 age‐, sex‐, and body‐mass‐index‐matched subjects. The NLR, PLR, MLR, and MPV were measured according to the complete blood count.

Results

The NLR, PLR, MLR, MPV, and neutrophil count of the ADHD group were significantly higher than those of the HC group. The lymphocyte counts of the patients were significantly lower than those of the HC group.

Conclusion

Inflammation might play a role in the etiopathogenesis of ADHD. The NLR, PLR, MLR, and MPV may be potential inflammation markers for ADHD in children.

     

Transition to psychosis in randomized clinical trials of individuals at clinical high risk of psychosis compared to observational cohorts: a systematic review and meta-analysis

BackgroundIndividuals at clinical high risk of psychosis (CHR-P) recruited in randomized clinical trials (RCTs) and observational cohorts may display a different enrichment and hence risk of transition to psychosis. No meta-analysis has ever addressed this issue.Methods“Preferred Reporting Items for Systematic reviews and Meta-Analyses” (PRISMA) and “Meta-analysis Of Observational Studies in Epidemiology” (MOOSE)–compliant meta-analysis. PubMed and Web of Science were searched until November 2020 (PROSPERO:CRD42021229223). We included nonoverlapping longitudinal studies (RCTs-control condition and observational cohorts) reporting the transition to psychosis in CHR-P individuals. The primary effect size measure was the cumulative risk of transition at 0.5, 1, and 2 years follow-up in RCTs compared to observational cohorts. Random effects meta-analyses, heterogeneity assessment, quality assessment, and meta-regressions were conducted.ResultsNinety-four independent studies (24 RCTs, 70 observational cohorts) and 9,243 individuals (mean age = 20.1 ± 3.0 years; 43.7% females) were included. The meta-analytical risk of transitioning to psychosis from a CHR-P stage was 0.091 (95% confidence intervals [CI] = 0.068–0.121) at 0.5 years, 0.140 (95% CI = 0.101–0.191) at 1 year and 0.165 (95% CI = 0.097–0.267) at 2 years follow-up in RCTs, and 0.081 (95% CI = 0.067–0.099) at 0.5 years, 0.138 (95% CI = 0.114–0.167) at 1 year, and 0.174 (95% CI = 0.156–0.193) at 2 years follow-up in observational cohorts. There were no between-group differences in transition risks (p > 0.05). The proportion of CHR-P individuals with substance use disorders (excluding alcohol and cannabis) was higher in observational cohorts (16.8, 95% CI = 13.3–21.0%) than in RCTs (3.4, 95% CI = 0.8–12.7%; p = 0.018).ConclusionsThere is no meta-analytic evidence supporting sampling biases in RCTs of CHR-P individuals. Further RCTs are needed to detect effective interventions to prevent psychosis in this at-risk group.     

Gender and duration of untreated psychosis: a systematic review and meta-analysis

Aim: Duration of untreated psychosis (DUP) can influence the prognosis of schizophrenia. Previous studies have suggested that gender may influence the length of DUP. This study reports the result of the first systematic literature review and meta‐analysis on the role of gender in influencing DUP in first‐episode psychosis. Method: Systematic literature search in PubMed/Medline and Ovid/PsychINFO. Twenty‐seven studies presenting data on 4721 patients diagnosed with psychosis at their first episode (2834 males and 1887 females) were included in the analysis. Results: Samples had a higher proportion of males: odds ratio = 2.5 (95% confidence interval: 1.8–3.3). Mean age at first contact was 25.4 for males and 27.5 for females. Patients from non‐Western countries were older at first contact than patients from Western countries. Average DUP in schizophrenia was 64 weeks and did not differ between genders but was shorter in Western compared with non‐Western countries. Conclusion: Earlier age at first contact and larger incidence in males support the existence of specific gender differences in first‐episode psychosis; however, these are not associated with DUP length.     

Split hand in amyotrophic lateral sclerosis: A systematic review and meta-analysis

ObjectiveTo investigate the frequency of split hand (SI) and its diagnostic performance in amyotrophic lateral sclerosis (ALS).MethodsPubMed, EMBASE, OVID and other databases were searched systematically up to March 2021 for relevant reports about the split hand syndrome. Two reviewers screened and selected the titles and abstracts of the studies independently during the database searches and performed full-text reviews and extracted available data. In our study, AA_CMAP was calculated by AA_CMAP = APB_CMAP/ADM_CMAP and split-hand index (SI) was calculated by SI_CMAP = (APB_CMAP × FDI_CMAP)/ADM_CMAP. The mean differences (MD) in APB/ADM_CMAP and SI_CMAP between patients with ALS and control group were calculated (APB the abductor pollicis brevis muscle; ADM the abductor digiti minimi muscle; CMAP compound muscle action potentials). Meta-analysis was performed to determine summary sensitivity, specificity, and area under the curve (AUC) with 95% confidence intervals (CI) for SI_CMAP.ResultsPooled results of five studies including 339 patients showed that 50% (95%CI: 35%–65%) of patients with ALS presented split hand. APB/ADM_CMAP in patients with ALS was significantly lower than healthy population (MD: −0.38, 95%CI: −0.48, −0.28). SI_CMAP in patients with ALS was significantly lower than healthy controls (MD: −5.87, 95%CI: −6.28, −5.46) and neuromuscular controls (MD: −5.60, 95%CI: −5.78, −5.42). Receiver operating characteristic curve analysis showed that the AUC was 0.860 [95%CI: 0.808, 0.911] for SI_CMAP. The sensitivity and specificity for SI_CMAP were 78% and 81% (cut-off value: 5.2–11.8), respectively.ConclusionHalf of ALS patients might show split hand sign. SI_CMAP could be a potential biomarker in the diagnosis of ALS.     

Rates of homicide during the first episode of psychosis and after treatment: a systematic review and meta-analysis

The observation that almost half of the homicides committed by people with a psychotic illness occur before initial treatment suggests an increased risk of homicide during the first episode of psychosis. The aim of this study was to estimate the rates of homicide during the first episode of psychosis and after treatment. A systematic search located 10 studies that reported details of all the homicide offenders with a psychotic illness within a known population during a specified period and reported the number of people who had received treatment prior to the offense. Meta-analysis of these studies showed that 38.5% (95% confidence interval [CI] = 31.1%-46.5%) of homicides occurred during the first episode of psychosis, prior to initial treatment. Homicides during first-episode psychosis occurred at a rate of 1.59 homicides per 1000 (95% CI = 1.06-2.40), equivalent to 1 in 629 presentations. The annual rate of homicide after treatment for psychosis was 0.11 homicides per 1000 patients (95% CI = 0.07-0.16), equivalent to 1 homicide in 9090 patients with schizophrenia per year. The rate ratio of homicide in the first episode of psychosis in these studies was 15.5 (95% CI = 11.0-21.7) times the annual rate of homicide after treatment for psychosis. Hence, the rate of homicide in the first episode of psychosis appears to be higher than previously recognized, whereas the annual rate of homicide by patients with schizophrenia after treatment is lower than previous estimates. Earlier treatment of first-episode psychosis might prevent some homicides.     

Inflammatory mediators in human epilepsy: A systematic review and meta-analysis

BackgroundAccumulating evidence suggests a role for inflammation in the pathophysiology of epilepsy.MethodsWe performed a systematic review and meta-analysis of studies that investigated inflammatory mediators in human epilepsy. Studies reporting on inflammatory mediators in serum, cerebrospinal fluid or brain tissue of epilepsy patients were included. Studies comparing patients to controls were included in a meta-analysis.Results66 articles reporting on 1934 patients were included. IL-1ra, IL-1β, IL-6, IL-10, IFN-γ and TNF-α were the most extensively investigated proteins. Elevated levels for IL-1ra, IL-1β, IL-6 and CXCL8/IL-8 were reported in several different epilepsy etiologies and media, while other proteins were specifically increased for one etiology. IL-1α, IL-7 and IL-13, as well as the chemokines CCL2-5, −19 and −22, were increased exclusively in brain tissue. In an aggregate meta-analysis, we found significantly different protein levels for serum IL-6, IL-17 and CSF IL-1β and IL-10.ConclusionInflammatory pathways are involved in epilepsy. Future studies may further clarify their role, and prove potential of targeted anti-inflammatory treatment.     

Cognitive motor interference while walking: A systematic review and meta-analysis

Dual-task methodology has been increasingly used to assess cognitive motor interference while walking. However, whether the observed dual-task-related gait changes are systematically related to methodological variations remains unclear and researchers still lack knowledge of what cognitive task to use in different groups for clinical purposes or for research. We systematically reviewed experimental studies that measured gait performance with and without performing concurrent cognitive task. Our results suggest that cognitive tasks that involve internal interfering factors seem to disturb gait performance more than those involving external interfering factors. Meta-analysis results show that the overall effect of different cognitive tasks was prominent in gait speed. In healthy participants, meta-regression analysis suggests strong associations between age and speed reduction under dual-task conditions and between the level of cognitive state and speed reduction under dual-task conditions. Standardizing research methodologies, as well as improving their ecological validity, enables better understanding of dual-task-related gait changes in different populations and improves, in turn, our understanding of neural mechanisms and gait control in general in content.     

Heart rate variability in bipolar disorder: A systematic review and meta-analysis

BackgroundHeart rate variability (HRV) has been suggested reduced in bipolar disorder (BD) compared with healthy individuals (HC). This meta-analysis investigated: HRV differences in BD compared with HC, major depressive disorder or schizophrenia; HRV differences between affective states; HRV changes from mania/depression to euthymia; and HRV changes following interventions.MethodsA systematic review and meta-analysis reported according to the PRISMA guidelines was conducted. MEDLINE, Embase, PsycINFO, The Cochrane Library and Scopus were searched. A total of 15 articles comprising 2534 individuals were included.ResultsHRV was reduced in BD compared to HC (g = -1.77, 95% CI: −2.46; −1.09, P < 0.001, 10 comparisons, n = 1581). More recent publication year, larger study and higher study quality were associated with a smaller difference in HRV. Large between-study heterogeneity, low study quality, and lack of consideration of confounding factors in individual studies were observed.ConclusionsThis first meta-analysis of HRV in BD suggests that HRV is reduced in BD compared to HC. Heterogeneity and methodological issues limit the evidence. Future studies employing strict methodology are warranted.     

Neuropsychological functioning and chronic methadone use: A systematic review and meta-analysis

IntroductionThere is a presumption that neurocognition is commonly impaired in chronic methadone exposed individuals (CM) when compared with healthy controls (HP). Additionally, it remains unclear if short term (<1 year) abstinence (AP) is associated with an altered cognitive profile when compared with CM.MethodA random effect model approach was used on data assembled into the Comprehensive Meta-Analysis programme. Cohen’s d effect sizes and a significance levels of p < 0.01 were calculated for each domain.ResultsData from a total cohort of 1063 CM, 412 AP and 879 HP participants, from 23 independent studies indicate global impairments in neurocognitive function in CM relative to HP participants. The smaller body of evidence comparing CM to AP participants is inconclusive.ConclusionMethodological issues such as small sample sizes, heterogeneity and poor quality limited the interpretation of the results and does not address whether the observed impairments reflect co-morbid functioning, methadone-related sedation and/or other factors. Only higher quality longitudinal studies will permit confident interpretation of the results observed in this meta-analysis.     

Correlation of neutrophil/lymphocyte and platelet/lymphocyte ratios with the severity of idiopathic carpal tunnel syndrome

We performed an observational, natural history study of males with in-frame dystrophin gene deletions causing Becker muscular dystrophy (BMD). A prospective natural history study collected longitudinal medical, strength, and timed function assessments. Eighty-three participants with genetically confirmed BMD were enrolled (age range 5.6–75.4 years). Lower extremity function and the percentage of participants who retained ambulation declined across the age span. The largest single group of participants had in-frame deletions that corresponded to an out-of-frame deletion treated with an exon 45 skip to restore the reading frame. This group of 54 participants showed similarities in baseline motor functional assessments when compared to the group of all others in the study. A prospective natural history cohort with in-frame dystrophin gene deletions offers the potential to contribute to clinical trial readiness for BMD and to analyze therapeutic benefit of exon skipping for Duchenne muscular dystrophy.     

Excessive daytime sleepiness in Parkinson's disease: A systematic review and meta-analysis

ObjectiveTo provide a robust estimate of the prevalence of excessive daytime sleepiness (EDS) and its clinical correlates in patients with Parkinson's disease (PD).MethodWe searched the PubMed and Embase databases for studies investigating the prevalence and clinical correlates of EDS from inception to March 01, 2020. Quality assessment was performed using the Newcastle-Ottawa quality assessment scale. Random-effects models were set to pool the risk estimates. Sensitivity analyses were performed to evaluate the stability of the outcomes.ResultsAfter screening 1367 titles and abstracts, 59 studies involving 12,439 participants were included in the systematic review and meta-analysis. The pooled prevalence of EDS in PD was 35.1%, which was higher in South America, North America, Europe, and Australia than that in Asia. Compared to patients without EDS, patients with EDS had higher effect size on disease duration (0.76 years; 95% CI: 0.16–1.37, I² = 68.8%), Hoehn and Yahr (HY) stage (0.23 grade; 95% CI: 0.11–0.34, I² = 69.1%), Unified PD Rating Scale (UPDRS)-III (3.02 points; 95% CI: 1.53–4.51, I²: 61.2%), levodopa equivalent daily dose (LEDD) (141.46 mg; 95% CI: 64.17–218.77, I² = 86.1%), depression symptoms (Hedges’ g = 0.35; 95% CI: 0.15–0.55, I² = 72.0%) and male sex (OR = 1.50; 95% CI: 1.30–1.72, I² = 0).ConclusionOur results showed that approximately one-third of patients with PD had EDS, which may be associated with the severity of the disease, depression, and male sex, or a combination of neurodegeneration and medication.     

Childhood socioeconomic status and inflammation: A systematic review and meta-analysis

Recent research suggests that risk for chronic diseases of aging including cardiovascular disease, diabetes, and even cancer can be programmed early in the lifespan as a result of exposure to chronic stressors like low socioeconomic status (SES) that are hypothesized to promote a pro-inflammatory response in immune cells that results in chronic, systemic inflammation. The present paper conducted a meta-analysis to establish whether exposure to low (versus higher) SES in childhood and adolescence is associated with higher levels of inflammation (as measured by C-reactive protein, IL-6, and fibrinogen) concurrently and in adulthood. We conducted meta-analyses with both unadjusted bivariate associations between SES and inflammation and with adjusted associations that controlled for a range of covariates including demographic factors, body mass index, smoking, physical activity and current SES. A systematic review of Pubmed and PsycINFO identified a total 35 studies (26 with unadjusted and 31 adjusted effect sizes) to be included in the meta-analysis. Random-effects meta-analysis showed that individuals who were exposed to low SES in childhood and adolescence had significantly higher levels of inflammatory markers (r = −0.07, p < .001, 95% CI = −0.09, −0.05). This association remained significant in adjusted analyses (r = −0.06, p < .001, 95% CI = −0.09, −0.03). However, the relationship between childhood SES and inflammation was non-significant in a meta-analysis with longitudinal studies that all controlled for adulthood SES (r = −0.03, p = .356, 95% CI = −0.08, 0.03). Future longitudinal research should utilize measurement of inflammatory markers at multiple time points to further examine the complex relationships between SES and health both in childhood and adulthood.