Dataset Information

Cyclooxygenase Inhibition Safety and Efficacy in Inflammation-Based Psychiatric Disorders.

ABSTRACT: According to the World Health Organization, the major psychiatric and neurodevelopmental disorders include major depression, bipolar disorder, schizophrenia, and autism spectrum disorder. The potential role of inflammation in the onset and progression of these disorders is increasingly being studied. The use of non-steroidal anti-inflammatory drugs (NSAIDs), well-known cyclooxygenase (COX) inhibitors, combined with first-choice specific drugs have been long investigated. The adjunctive administration of COX inhibitors to classic clinical treatments seems to improve the prognosis of people who suffer from psychiatric disorders. In this review, a broad overview of the use of COX inhibitors in the treatment of inflammation-based psychiatric disorders is provided. For this purpose, a critical analysis of the use of COX inhibitors in the last ten years of clinical trials of the major psychiatric disorders was carried out.

SUBMITTER: Perrone MG

PROVIDER: S-EPMC7698629 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Cyclooxygenase Inhibition Safety and Efficacy in Inflammation-Based Psychiatric Disorders.

Perrone Maria Grazia MG Centonze Antonella A Miciaccia Morena M Ferorelli Savina S Scilimati Antonio A

Molecules (Basel, Switzerland) 20201118 22

According to the World Health Organization, the major psychiatric and neurodevelopmental disorders include major depression, bipolar disorder, schizophrenia, and autism spectrum disorder. The potential role of inflammation in the onset and progression of these disorders is increasingly being studied. The use of non-steroidal anti-inflammatory drugs (NSAIDs), well-known cyclooxygenase (COX) inhibitors, combined with first-choice specific drugs have been long investigated. The adjunctive administr ...[more]

PMID: 33217958

Similar Datasets

Project description:BackgroundPrimary hypertrophic osteoarthropathy (PHO) is a rare disease involving joint, bone and skin. Two underlying genes responsible for this disease-hydroxyprostaglandin dehydrogenase (HPGD) and solute carrier organic anion transporter family, member 2A1 (SLCO2A1)-are both associated with aberrant accumulation of prostaglandin E2 (PGE2). Cyclooxygenase-2 (COX-2) is a key enzyme in PGE2 synthesis. This study was intended to evaluate the safety and efficacy of COX-2 inhibitor in the treatment of PHO.MethodsWe recruited patients presenting to Peking Union Medical Hospital between January 2009 and December 2016 who were diagnosed with PHO. Participants were given the COX-2 inhibitor etoricoxib (60 mg once daily) and followed up for 9 months. Gene analysis was performed at baseline. The following data were collected at baseline and during treatment: visual analogue score (VAS), volume of the distal middle finger (VDMF), knee joint circumference (KJC), serum and urinary levels of prostaglandin E2 (PGE2) and PGE metabolite (PGE-M) and serum levels of inflammatory markers.ResultsA total of 27 patients were recruited, including seven patients with PHO type I (PHOAR1) carrying HPGD gene mutations and 20 patients with PHO type II (PHOAR2) carrying SLCO2A1 gene mutations. After treatment with etoricoxib, the majority of patients experienced resolution of symptoms including pachydermia (60.9%), joint swelling (100%), digital clubbing (74.1%) and hyperhidrosis (55.0%). In both the PHO subtypes, serum and urinary levels of PGE2 were elevated at baseline and declined sharply upon treatment. For PHOAR1 patients, serum and urinary PGE-M levels were relatively low and demonstrated minimal response to COX-2 inhibition. Among PHOAR2 patients, mean serum and urinary levels of PGE-M presented at a high level at baseline and were normalized after 3 months of treatment. No severe adverse effects were reported during the study period.ConclusionsWe found COX-2 inhibitor to be safe and effective for the treatment of PHO in our cohort.The translational potential of this articleThe underlying genes responsible for PHO suggest COX inhibitor as potential therapy, and our study demonstrates the efficacy and safety of this treatment.

Project description:Lifestyle changes involving high caloric diet, sedentary life, and/or persistent stress appear to play a role in the onset of metabolic syndrome (MetS), which is characterized by hyperglycemia, hyperinsulinemia, dyslipidemia, obesity, and type-2 diabetes. MetS in the long run appears to have cerebrovascular consequences, resulting in neuropsychiatric disorders. However, there is a paucity of molecular studies using relevant animal models of metabolic disorder-induced neuropsychiatric disorders. Here, we tried to model the clinical conditions of MetS by feeding C57bl/6 Ncrl mice a high fructose diet (Hfr) for almost 12 months. Random glucose, fasting glucose, glucose tolerance, and triglycerides did not differ significantly between the Hfr diet and Control diet (Cont) groups even after a year on the Hfr diet, except for the accelerated aging-like phenotype in coat color and shiny texture. However, exposure to chronic stress for a week induced metabolic disorder as reflected in high post-prandial blood glucose in the Hfr group, and subsequently mood disorder (depression and anxiety) (p<0.01) and cognitive disorder (p<0.01) as indicated by the behavioral tests. To uncover the underlying molecular mechanisms in the prefrontal cortex, a transcriptomic study was performed. The data analysis revealed hundreds of differentially expressed genes (DEGs) between the groups (i.e., HfrUST vs CoUST = 348 genes; CoST vs CoUST = 496 genes; HfrST vs HfrUST =226 genes and HfrST vs CoST= 18 genes). The pattern of gene expression was strikingly different in the HfrST group compared to the Ctrl group, thus correlating the phenotype, i.e. MetS induced mood and cognitive disorders. Pathway analysis of the DEGs indicated perturbations in cellular metabolism, inflammation, innate immunity, neurogenesis, vasculogenesis, ion channels, and neuronal signaling. In addition, altered epigenetic regulators appear to mediate the stress-induced precipitation of metabolic and neuropsychiatric disorders. The outcome of our study supports the hypothesis of disease susceptibility due to lifestyle changes involving a high-calorie diet and chronic stress.

Dataset Information

Cyclooxygenase Inhibition Safety and Efficacy in Inflammation-Based Psychiatric Disorders.

Publications

Cyclooxygenase Inhibition Safety and Efficacy in Inflammation-Based Psychiatric Disorders.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets