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Parkinson's disease (PD) is second most prevalent neurodegenerative disorder following Alzheimer's disease. Parkinson's disease is hypothesized to be caused by a multifaceted interplay between genetic and environmental factors. Herein, and for the first time, we describe the integration of metabolomics and epigenetics (genome-wide DNA methylation; epimetabolomics) to profile the frontal lobe from people who died from PD and compared them with age-, and sex-matched controls. We identified 48 metabolites to be at significantly different concentrations (FDR q < 0.05), 4,313 differentially methylated sites [5'-C-phosphate-G-3' (CpGs)] (FDR q < 0.05) and increased DNA methylation age in the primary motor cortex of people who died from PD. We identified Primary bile acid biosynthesis as the major biochemical pathway to be perturbed in the frontal lobe of PD sufferers, and the metabolite taurine (p-value = 5.91E-06) as being positively correlated with CpG cg14286187 (SLC25A27; CYP39A1) (FDR q = 0.002), highlighting previously unreported biochemical changes associated with PD pathogenesis. In this novel multi-omics study, we identify regulatory mechanisms which we believe warrant future translational investigation and central biomarkers of PD which require further validation in more accessible biomatrices.

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This review is intended to provide an updated summary of, but not limited to, classification, etiopathogenesis, diagnosis, and treatment strategies for insomnia disorder. The severity of insomnia symptoms irrespective of co-existing primary medical condition/s in the studied patients classified insomnia as 'insomnia disorder' to prioritize the clinical attention on insomnia (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition). The frequency and duration of symptoms further divided insomnia into chronic, short-term, and other insomnia disorder (International Classification of Sleep Disorders, Third Edition). This disorder is a phenomenal state of hyperarousal developed and perpetuated by environmental, behavioral, cognitive, genetic, socioeconomic, preexisting medical factors. Overarching physiological, cortical, behavioral, and cognition changes in hyperarousal manifest insomnia disorder. It, sometimes, leads to the co-occurrence of other chronic medical condition/s. The contemporary diagnosis of insomnia disorder needs to consider modified diagnostic criteria, growing evidence on insomnia disorder symptoms, associated factors, co-existing medical condition/s (if any) to identify the subjective severity of insomnia disorder and design a treatment plan. The recommended treatment strategies include cognitive-behavioral therapy for insomnia (CBTI) and pharmacotherapy. However, CBTI lacks accessibility, qualified facilitators, and pharmacotherapy has limitations like side effects, physiological tolerance/dependence. The investigation of phytocompounds subdued these drawbacks of existing treatments as some compounds showed anti-insomniac potential. Furthermore, complementary alternative medicines (CAMs) like mindfulness-based practices, acupuncture, listening to music, Yogasanas, Pranayama, digital cognitive behavioral therapy for insomnia (dCBTI) during bedtime proved supportive in insomnia disorder treatment.

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The authors have compiled the available references on the use of risperidone in 'non-psychotic conditions', not including schizophrenia and bipolar disorders. In addition, information was gathered on the mechanism of action of risperidone in this diverse disorders. Atypical antipsychotics are known to have fewer adverse effects seen with typical antipsychotics, such as tardive dyskinesia (TD), neuroleptic malignant syndrome (NMS), and cognitive disturbances, and they possess a 'broad range of therapeutic efficacy.' The broad psychotropic effects, apart from the antipsychotic action, of risperidone are attributed to their particular pharmacological properties, which differ greatly from those of typical antipsychotics. Risperidone has a greater affinity for the dopamine D2 receptor than for the D1 receptor, but its D2/5-HT2 affinity ratio is low. This fixed D2/5-HT2 ratio may bring about significantly different clinical effects depending on the dosage. The dose-dependent pharmacologic properties of risperidone, in the form of the effects of blocking the 5-HT2 receptors, which are observed at smaller doses, and the effects of D2 blockade, which are manifested progressively with increasing dosage, may be the basis of the efficacy of risperidones in non-psychotic conditions at smaller doses than in psychoses. The authors have also ascertained that risperidone may be of efficacy in the treatment of non-psychotic conditions other than the major psychoses. The authors consider the different dosages depending on the diagnoses to be reflective of differences in the etiopathophysiology between the conditions. In addition, the authors have noted that risperidone, at small doses, shows efficacy in the treatment of a wide variety of disorders other than psychotic disorders, including obsessive symptoms, anxiety. This also demonstrates the greater range of therapeutic efficacy of risperidone other than typical antipsychotics. Despite the fact that risperidone possesses such various therapeutic actions, the first-line drugs in the treatment of non-psychotic conditions are and should be non-antipsychotic psychotropics;risperidone is still an antipsychotic drug, with all the entailing characteristics, and it is not completely free of the side effects common in typical antipsychotics, such as EPS. Wisdom is called for in the appropriate application of risperidone in the treatment regimen of suitable patients following treatment with other non-antipsychotic psychotropics. It seem to review all non-psychotic psychiatric disorders via the clinical applications of risperidone. Through expansion of the indications for risperidone, further insight will be gained on its previously unknown psychotropic effects and the etiopathophysiology of the indicated conditions.

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