Lack of Efficacy of JNJ-18038683 on Cognitive Impairment in Patients With Stable Bipolar Disorder.

BACKGROUND: The serotonin type 7 (5-HT7) receptor is one of 14 5-HT receptors. It has received attention for its possible role in mood disorders and cognition. The 5-HT7 receptor antagonist, JNJ-18038683, has been reported to be effective in rodent models of depression and REM sleep. Also, 5-HT7 receptor blockade has been postulated to be a key component of cognitive enhancement in a number of drugs. Bipolar disorder (BD) usually endures cognitive impairment (CI); however, no treatment for CI in BD has been approved. This study aimed to evaluate the efficacy of JNJ-18038683 to improve the CI of BD compared to a placebo. METHODS: We conducted a placebo-controlled, 8-week trial of JNJ-18038683 in BD patients. Each patient's data were analyzed and reassessed blindly with a comprehensive neuropsychological battery, depression and hypomania ratings, and overall social and work function measures. RESULTS: Of 60 patients, 38 (63%) were female, 43 (72%) had BD type 1, and most patients were Caucasian and married. The overall time effect for the combined group shows statistically significant improvement from baseline to week 8 for most of the neurocognitive battery measures. This indicates a significant improvement in psychopathology and cognition during the study time in both JNJ-18038683 and placebo groups, but no difference between groups. CONCLUSIONS: This study showed no efficacy for the improvement of CIBD or mood symptoms with JNJ-18038683 compared to the placebo.

Association between Alzheimer's disease and Toxocara infection/exposure: a case-control study.

BACKGROUND: Infections may contribute to Alzheimer's disease (AD) risk. Limited evidence suggests Toxocara spp. infection/exposure could influence AD development. METHODS: We investigated Toxocara seropositivity and AD in Iranian adults using a matched case-control study. Our sample included 90 AD cases and 91 healthy older adults. Anti-Toxocara immunoglobulin G (IgG) antibodies were assessed via enzyme-linked immunosorbent assay. We computed the odds ratios (ORs) and 95% confidence intervals (CIs) through univariable and multivariable analyses, adjusting for potential confounders. RESULTS: There were 33/90 (36.67% [95% CI 26.75 to 47.48]) anti-Toxocara IgG seropositive individuals identified among the AD cases and 21/91 (23.07% [95% CI 14.89 to 33.09]) among the healthy controls. In univariable analysis, a significant association was identified between anti-Toxocara IgG seropositivity and AD (OR 1.93 [95% CI 1.01 to 3.69], p<0.001). Moreover, the association remained significant (OR 2.18 [95% CI 1.05 to 4.49], p<0.001) in multivariable analysis after adjustment for covariates. There was no association between anti-Toxocara IgG seropositivity and the severity of AD (OR 0.75 [95% CI 0.21 to 2.61], p=0.47). CONCLUSIONS: Our findings indicated that Toxocara exposure/infection could be a potential risk factor for development of AD. To better understand a real causality between Toxocara exposure/infection and AD and related dementias, follow-up designed and adequately powered studies are needed.

Evaluation and Comparison of the Effectiveness of Atropine Eye Drops, Ipratropium Bromide Nasal Spray, and Amitriptyline Tablet in the Management of Clozapine-Associated Sialorrhea in Patients With Refractory Schizophrenia: A Randomized Clinical Trial.

PURPOSE: Clozapine, a second-generation antipsychotic medication, is mainly indicated for managing treatment-resistant schizophrenia. Among all the nonthreatening adverse effects of clozapine, sialorrhea is a stigmatizing complication occurring in approximately 31.0% to 97.4% of patients. In this study, 2 topical agents (atropine eye drop and ipratropium nasal spray) and a systemic medication (amitriptyline) were compared simultaneously for the management of clozapine-associated sialorrhea. METHODS: We conducted a randomized, single-blinded, non-placebo-controlled clinical trial from June 2022 to January 2023. Eligible patients were randomly allocated into 3 mentioned groups. Patients were monitored for sialorrhea weekly based on scales, including the Toronto Nocturnal Hypersalivation Scale, Clinical Global Impression-Improvement, and Clinical Global Impression-Severity for 1 month. Possible adverse drug reactions and adherence were also recorded. RESULTS: Twenty-four patients, including 6, 10, and 8 individuals in ipratropium bromide nasal spray, atropine eye drop, and amitriptyline groups, completed the study, respectively. The cohort's demographic, baseline clinical, and sociocultural characteristics were comparable among the 3 groups. Within-group comparisons, between times baseline and week 4, demonstrated that significant differences were in groups atropine and amitriptyline based on Toronto Nocturnal Hypersalivation Scale, in 3 groups based on Clinical Global Impression-Improvement, and also in only-atropine group based on Clinical Global Impression-Severity. Likewise, between-group comparisons showed that atropine was significantly more effective in clozapine-associated sialorrhea management than amitriptyline and ipratropium, in the first 2 weeks and second 2 weeks of study, respectively. Regarding safety, the interventions were tolerated relatively well. CONCLUSIONS: Conclusively, atropine is more efficacious than amitriptyline, within the first 2 weeks of study and also relative to ipratropium, overall. As time effect was significant between atropine and amitriptyline, according to analysis of covariance test, further investigation with longer follow-up duration would be prudent. In addition, expanding patient population with larger sample size should be conducted for more precision.

Chlamydia pneumonia infection and risk of multiple sclerosis: A meta-analysis.

BACKGROUND: The role of infectious agents, including Chlamydia pneumoniae (Cpn), in the development of multiple sclerosis (MS), is still a matter of major contention. OBJECTIVE: This meta-analysis study aimed to assess the actual involvement of Cpn in MS development. METHODS: We undertook a search of international scientific databases to identify eligible studies. We used a random-effects meta-analysis model (REM) to generate the pooled odds ratio (OR) and 95% confidence intervals (CIs). Heterogeneity was calculated using the I2 statistic. Sensitivity and subgroup analyses were applied to assess the effects of study characteristics and socio-demographic variables on the pooled OR. RESULTS: We identified 37 studies comprising 51 datasets that satisfied the inclusion criteria. Considering diagnostic methods for Cpn, 26 and 25 datasets used PCR- and serological-based methods, respectively. In PCR-based datasets, REM showed a significant positive association between Cpn infection and the development of MS (OR, 5.29; 95% CI, 3.12-8.97), while a non-significant positive association was achieved in serological-based datasets (OR, 1.34; 95% CI, 0.88-2.03). In subgroup analyses on PCR-based datasets, results were significant for both CSF (OR, 5.70) and serum (OR, 4.84) samples; both healthy (OR, 16.11) and hospital-based (OR, 2.88) controls; and both moderate (OR, 5.14) and high (OR, 5.48) quality studies. In serological-based datasets, only those that used CSF samples yielded significant results (OR, 3.41). CONCLUSIONS: Our findings verify the significant positive relationship between Cpn infection and MS. We advocate prospective cohort studies with lifelong follow-ups and also experimental studies to better understand the role of Cpn in MS development.

Does latent Toxoplasma infection have a protective effect against developing multiple sclerosis? Evidence from an updated meta-analysis.

Previous epidemiologic evidence suggests a protective effect of Toxoplasma gondii infection against multiple sclerosis (MS) development; however, inconsistent findings have been reported in this regard. Therefore, we performed an updated meta-analysis of observational studies to investigate the association of To. gondii infection with MS development. We searched all articles published in PubMed, Scopus, Embase and Web of Science databases as of 20 December 2021. A random effects meta-analysis model was used to generate the pooled OR at 95% CIs. The heterogeneity between studies was assessed using I2 and Cochran's Q statistics. Moreover, the likelihood of publication bias was determined by Egger's regression test. A total of 11 studies were eligible for meta-analysis, including 1172 MS cases and 1802 controls. Our findings indicated that 29.8% (95% CI 22.8 to 37.2%) of MS patients were seropositive for To. gondii infection, compared with 34.2% (95% CI 21.9 to 47.6%) of control subjects. The estimated pooled OR was 0.79 (95% CI 0.49 to 1.26), suggesting a non-significant negative association between To. gondii infection and MS development (p>0.05). The current study does not support the significant protective role of To. gondii infection on MS development. Our findings imply that further well-designed epidemiological and mechanistic studies are warranted to ascertain the possible association between To. gondii infection and MS and to exclude the potential confounders.

Systematic review and meta-analysis of the placebo effect in panic disorder: Implications for research and clinical practice.

OBJECTIVE: This review aimed to measure the degree of placebo response in panic disorder. DATA SOURCES: We searched major databases up to 31 January 2021, for randomized pharmacotherapy trials published in English. STUDY SELECTION: A total of 43 studies met inclusion criteria to be in the analysis (with 174 separate outcome measurements). DATA EXTRACTION: Changes in outcome measures from baseline in the placebo group were used to estimate modified Cohen's d effect size. RESULTS: A total of 43 trials (2392 subjects, 174 outcomes using 27 rating scales) were included in the meta-analysis. Overall placebo effect size was 0.57 (95% confidence interval = [0.50, 0.64]), heterogeneity (I2: 96.3%). Higher placebo effect size was observed among clinician-rated scales compared to patient reports (0.75 vs 0.35) and among general symptom and anxiety scales compared to panic symptoms and depression scales (0.92 and 0.64 vs 0.56 and 0.54, respectively). There was an upward trend in effect size over the publication period (r = 0.02, p = 0.002) that was only significant among clinician-rated scales (r = 0.02, p = 0.011). There was no significant publication bias, Egger's test (p = 0.08). CONCLUSION: We observed a substantial placebo effect size in panic disorder. This effect was more prominent for some aspects of panic disorder psychopathology than for others and was correlated with the source of the assessment and publication year. This finding has implications both for research design, to address the heterogeneity and diversity in placebo responses, and for clinical practice to ensure optimal quality of care. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO, CRD42019125979.