Cardiovascular adverse reactions associated with escitalopram in patients with underlying cardiovascular diseases: a systematic review and meta-analysis

BackgroundDespite the anticipated efficacy of escitalopram in treating depression and anxiety in individuals with preexisting cardiovascular conditions, persistent concerns regarding its adverse effects have emerged. In this systematic review, we aimed to evaluate the cardiovascular safety profile of escitalopram compared with that of placebo in patients with underlying cardiovascular disease.MethodsWe used a predefined search strategy in PubMed, Cochrane Central Register of Controlled Trials, Embase, International Clinical Trials Registry Platform, and ClinicalTrials.gov to identify studies evaluating adverse cardiovascular reactions to escitalopram in patients with underlying cardiovascular disease. Randomized controlled trials (RCTs) that provided results on cardiovascular safety outcomes were included. Two independent reviewers screened the abstracts and full texts of the individual studies. The risk of bias was assessed using version 2 of the Cochrane risk-of-bias tool for randomized trials. The certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation approach.ResultsThe primary outcomes were the frequency of major adverse cardiovascular events (MACE), QTc prolongation, and discontinuation of study medication. We identified 5 RCTs with 773 participants who met the inclusion criteria. Escitalopram was not associated with significantly increased risk of MACE (risk ratio [RR] = 1.85; 95% confidence interval [CI] 0.80 to 4.26; I2 0%; 5 RCTs; n = 773, moderate certainty of evidence), discontinuation of study medication (RR = 1.03; 95% CI 0.84–1.26; I2 0%; 5 RCTs; n = 773, low certainty of evidence), and QTc prolongation (RR = 1.20; 95% CI 0.76–1.90; I2 0%; 4 RCTs; n = 646, low certainty of evidence).ConclusionEscitalopram does not significantly increase the risk of cardiovascular adverse reactions compared with placebo in patients with underlying cardiovascular disease. However, the presence of wide CIs and the limited number of included studies highlight the need for further studies with larger sample sizes to enhance the precision and reliability of these findings.Systematic review registration: International Prospective Register of Systematic Reviews [CRD42022298181]

Polycystic Kidney Disease in the Medaka (Oryzias latipes) pc Mutant Caused by a Mutation in the Gli-Similar3 (glis3) Gene

Polycystic kidney disease (PKD) is a common hereditary disease in humans. Recent studies have shown an increasing number of ciliary genes that are involved in the pathogenesis of PKD. In this study, the Gli-similar3 (glis3) gene was identified as the causal gene of the medaka pc mutant, a model of PKD. In the pc mutant, a transposon was found to be inserted into the fourth intron of the pc/glis3 gene, causing aberrant splicing of the pc/glis3 mRNA and thus a putatively truncated protein with a defective zinc finger domain. pc/glis3 mRNA is expressed in the epithelial cells of the renal tubules and ducts of the pronephros and mesonephros, and also in the pancreas. Antisense oligonucleotide-mediated knockdown of pc/glis3 resulted in cyst formation in the pronephric tubules of medaka fry. Although three other glis family members, glis1a, glis1b and glis2, were found in the medaka genome, none were expressed in the embryonic or larval kidney. In the pc mutant, the urine flow rate in the pronephros was significantly reduced, which was considered to be a direct cause of renal cyst formation. The cilia on the surface of the renal tubular epithelium were significantly shorter in the pc mutant than in wild-type, suggesting that shortened cilia resulted in a decrease in driving force and, in turn, a reduction in urine flow rate. Most importantly, EGFP-tagged pc/glis3 protein localized in primary cilia as well as in the nucleus when expressed in mouse renal epithelial cells, indicating a strong connection between pc/glis3 and ciliary function. Unlike human patients with GLIS3 mutations, the medaka pc mutant shows none of the symptoms of a pancreatic phenotype, such as impaired insulin expression and/or diabetes, suggesting that the pc mutant may be suitable for use as a kidney-specific model for human GLIS3 patients

The effect of duration of illness and antipsychotics on subcortical volumes in schizophrenia: Analysis of 778 subjects

BackgroundThe effect of duration of illness and antipsychotic medication on the volumes of subcortical structures in schizophrenia is inconsistent among previous reports. We implemented a large sample analysis utilizing clinical data from 11 institutions in a previous meta-analysis.MethodsImaging and clinical data of 778 schizophrenia subjects were taken from a prospective meta-analysis conducted by the COCORO consortium in Japan. The effect of duration of illness and daily dose and type of antipsychotics were assessed using the linear mixed effect model where the volumes of subcortical structures computed by FreeSurfer were used as a dependent variable and age, sex, duration of illness, daily dose of antipsychotics and intracranial volume were used as independent variables, and the type of protocol was incorporated as a random effect for intercept. The statistical significance of fixed-effect of dependent variable was assessed.ResultsDaily dose of antipsychotics was positively associated with left globus pallidus volume and negatively associated with right hippocampus. It was also positively associated with laterality index of globus pallidus. Duration of illness was positively associated with bilateral globus pallidus volumes. Type of antipsychotics did not have any effect on the subcortical volumes.DiscussionA large sample size, uniform data collection methodology and robust statistical analysis are strengths of the current study. This result suggests that we need special attention to discuss about relationship between subcortical regional brain volumes and pathophysiology of schizophrenia because regional brain volumes may be affected by antipsychotic medication

White matter microstructural alterations across four major psychiatric disorders : mega-analysis study in 2937 individuals

Identifying both the commonalities and differences in brain structures among psychiatric disorders is important for understanding the pathophysiology. Recently, the ENIGMA-Schizophrenia DTI Working Group performed a large-scale meta-analysis and reported widespread white matter microstructural alterations in schizophrenia; however, no similar cross-disorder study has been carried out to date. Here, we conducted mega-analyses comparing white matter microstructural differences between healthy comparison subjects (HCS; N = 1506) and patients with schizophrenia (N = 696), bipolar disorder (N = 211), autism spectrum disorder (N = 126), or major depressive disorder (N = 398; total N = 2937 from 12 sites). In comparison with HCS, we found that schizophrenia, bipolar disorder, and autism spectrum disorder share similar white matter microstructural differences in the body of the corpus callosum; schizophrenia and bipolar disorder featured comparable changes in the limbic system, such as the fornix and cingulum. By comparison, alterations in tracts connecting neocortical areas, such as the uncinate fasciculus, were observed only in schizophrenia. No significant difference was found in major depressive disorder. In a direct comparison between schizophrenia and bipolar disorder, there were no significant differences. Significant differences between schizophrenia/bipolar disorder and major depressive disorder were found in the limbic system, which were similar to the differences in schizophrenia and bipolar disorder relative to HCS. While schizophrenia and bipolar disorder may have similar pathological characteristics, the biological characteristics of major depressive disorder may be close to those of HCS. Our findings provide insights into nosology and encourage further investigations of shared and unique pathophysiology of psychiatric disorders

Long term Aleutian Low dynamics and obliquity-controlled oceanic primary production in the mid-latitude western North Pacific (Core MD01-2421) during the last 145,000 years

We have generated an oceanic primary production record from Core MD01-2421, off central Japan, in the western North Pacific, for the last 145,000 years, in order to examine how the Aleutian Low has responded to orbital-scale climate change. The variation of total organic carbon (TOC) was pronounced with a 41-ky periodicity. High TOC corresponds to a high angle of the Earth's obliquity. The variation of TOC was delayed behind the variation of obliquity by 1 ky and preceded the variation of δ18O of benthic foraminifera Uvigerina by 6 ky. The TOC varied inversely with Polar Circulation Index (Mayewski, P.A., Meeker, L.D., Twickler, M.S., Whitlow, S., Yang, Q., Lyons, B., Prentice, M., 1997. Major features and forcing of high-latitude northern hemisphere atmospheric circulation using a 110,000-year-long glaciochemical series. J. Geophys. Res. 102 (C12), 26345–26366.). Since the primary production in the Kuroshio–Oyashio mixed zone is related to the intensity of the winter Aleutian Low, these correspondences imply that the intensity of the winter Aleutian Low has responded to the obliquity forcing by the atmospheric reorganization in the northern high latitudes. The winter Aleutian Low was stronger when the obliquity was large, implying that the lower insolation in winter presumably increased the temperature contrast between the land and the ocean, deepening the winter Aleutian Low