Psychosomatic Approach to Fibromyalgia Syndrome: Concept, Diagnosis and Treatment

Fibromyalgia syndrome (FMS) has chronic widespread pain (CWP) as a core symptom and a variety of associated somatic and psychological symptoms such as fatigue, sleep problems, cognitive disturbances, multiple somatic pain, and depression. FMS is the subject of considerable controversy in the realm of nosology, diagnosis, pathophysiology, and treatment.Moreover, the fact that FMS and mental illness are closely associated with each other might intensify the confusion for the distinction between FMS and mental disorders. This narrative literature review aims to provide the concept, diagnosis, and treatment of FMS from the integrative biopsychosocial and psychosomatic perspective. This article first explains the concepts of FMS as a disease entity of biopsychosocial model, and then summarizes the changes of diagnostic criteria over past three decades, differential diagnosis and comorbidity issue focused on mental illnesses. In addition, an overview of treatment of FMS is presented mainly by arranging the recommendations from the international guidelines which have been developed by four official academic associations.

An Open-Label Clinical Trial of Oral Transmucosal Haloperidol and Olanzapine in the Treatment of Terminal Delirium

Background : The phenomenon of restlessness, agitation, or cognitive disturbances experienced by dying patients is well-known in palliative care; more than half of these patients will experience delirium symptoms at end-of-life. When not identified early and effectively managed, delirium symptoms could lead to caregiver and patient distress and harm. Methods : 80 patients with a prognosis of 3 days or less will be recruited for an open-label randomized control trial. The two arms compare oral-transmucosal haloperidol 2.5mg vs olanzapine 5mg over 72 hours. The severity of agitation, delirium and toxicities of treatments will be compared at the 24 th , 48 th and 72 nd hour after drug administration. Discussion : This trial is the first to compare anti-psychotics in the management of delirium at the dying stage in the home hospice setting using the oral transmucosal route. Ethical considerations, as well as recruitment procedures are discussed. Trial registration : ClinicalTrials.gov, NCT04750395. Registered 11 February 2021, https://clinicaltrials.gov/ct2/show/NCT04750395

Inhibition of 11β-HSD1 Ameliorates Cognition and Molecular Detrimental Changes after Chronic Mild Stress in SAMP8 Mice

Impaired glucocorticoid (GC) signaling is a significant factor in aging, stress, and neurodegenerative diseases such as Alzheimer’s disease. Therefore, the study of GC-mediated stress responses to chronic moderately stressful situations, which occur in daily life, is of huge interest for the design of pharmacological strategies toward the prevention of neurodegeneration. To address this issue, SAMP8 mice were exposed to the chronic mild stress (CMS) paradigm for 4 weeks and treated with RL-118, an 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitor. The inhibition of this enzyme is linked with a reduction in GC levels and cognitive improvement, while CMS exposure has been associated with reduced cognitive performance. The aim of this project was to assess whether RL-118 treatment could reverse the deleterious effects of CMS on cognition and behavioral abilities and to evaluate the molecular mechanisms that compromise healthy aging in SAMP8 mice. First, we confirmed the target engagement between RL-118 and 11β-HSD1. Additionally, we showed that DNA methylation, hydroxymethylation, and histone phosphorylation were decreased by CMS induction, and increased by RL-118 treatment. In addition, CMS exposure caused the accumulation of reactive oxygen species (ROS)-induced damage and increased pro-oxidant enzymes—as well as pro-inflammatory mediators—through the NF-κB pathway and astrogliosis markers, such as GFAP. Of note, these modifications were reversed by 11β-HSD1 inhibition. Remarkably, although CMS altered mTORC1 signaling, autophagy was increased in the SAMP8 RL-118-treated mice. We also showed an increase in amyloidogenic processes and a decrease in synaptic plasticity and neuronal remodeling markers in mice under CMS, which were consequently modified by RL-118 treatment. In conclusion, 11β-HSD1 inhibition through RL-118 ameliorated the detrimental effects induced by CMS, including epigenetic and cognitive disturbances, indicating that GC-excess attenuation shows potential as a therapeutic strategy for age-related cognitive decline and AD.

Bridging the Gap? Altered Thalamocortical Connectivity in Psychotic and Psychedelic States

Psychiatry has a well-established tradition of comparing drug-induced experiences to psychotic symptoms, based on shared phenomena such as altered perceptions. The present review focuses on experiences induced by classic psychedelics, which are substances capable of eliciting powerful psychoactive effects, characterized by distortions/alterations of several neurocognitive processes (e.g., hallucinations). Herein we refer to such experiences as psychedelic states. Psychosis is a clinical syndrome defined by impaired reality testing, also characterized by impaired neurocognitive processes (e.g., hallucinations and delusions). In this review we refer to acute phases of psychotic disorders as psychotic states. Neuropharmacological investigations have begun to characterize the neurobiological mechanisms underpinning the shared and distinct neurophysiological changes observed in psychedelic and psychotic states. Mounting evidence indicates changes in thalamic filtering, along with disturbances in cortico-striato-pallido-thalamo-cortical (CSPTC)-circuitry, in both altered states. Notably, alterations in thalamocortical functional connectivity were reported by functional magnetic resonance imaging (fMRI) studies. Thalamocortical dysconnectivity and its clinical relevance are well-characterized in psychotic states, particularly in schizophrenia research. Specifically, studies report hyperconnectivity between the thalamus and sensorimotor cortices and hypoconnectivity between the thalamus and prefrontal cortices, associated with patients' psychotic symptoms and cognitive disturbances, respectively. Intriguingly, studies also report hyperconnectivity between the thalamus and sensorimotor cortices in psychedelic states, correlating with altered visual and auditory perceptions. Taken together, the two altered states appear to share clinically and functionally relevant dysconnectivity patterns. In this review we discuss recent findings of thalamocortical dysconnectivity, its putative extension to CSPTC circuitry, along with its clinical implications and future directions.

CLINICAL STUDY OF POST COVID SYMPTOMS AFTER 1ST WAVE OF COVID 19, AT A TERTIARY HOSPITAL

Background: Early reports suggest residual effects of SARS-CoV-2 infection, such as fatigue, dyspnea, chest pain, cognitive disturbances, arthralgia and decline in quality of life. In present study we aimed to evaluate post covid symptoms after 1st wave of COVID 19 in COVID 19 recovered patients at a tertiary hospital. Present study was Material and Methods: hospital based, descriptive, cross-sectional, questionnaire-based study conducted in Covid 19 positive patients (RT-PCR or Rapid Antigen positive patients) either hospital admitted or home isolation patients, recovered (either RTPCR negative or completed 14 days isolation and no symptoms) came to post covid OPD for follow up, were studied. In present study 101 post Results: COVID 19 recovered patients were studied. Most of patients were from age group 51-60 years (19.8 %) followed by age group 41-50 years (16.83 %). Male patients (65.35 %) were more than female patients (34.65%), male to female ratio was 1.9 :1. Majority of patients received treatment at hospital (75.25%) & were diagnosed by RTPCR (57.43%). Most of patients had recovered from COVID 61-90 days ago (28.71%) followed by 121-150 days ago (19.8%). During acute COVID-19 pneumonia was diagnosed in 36.63 % cases. Other characteristics were intensive care unit admission (14.85 %), oxygen supplementation (21.78 %), noninvasive ventilation (7.92 %) & mechanical ventilation (2.97 %). Pre-existing comorbidities noted were hypertension (12.87 %), thyroid disease (4.95 %), diabetes (3.96 %), chronic obstructive pulmonary disease (3.96 %), h/o kidney failure (1.98 %), active smoker (8.91 %) & former smoker (14.85 %). No regular physical activity was noted in 83.17 %. Post COVID symptoms noted in present study were cough (14.85 %), fatigue (13.86 %), Breathlessness (8.91 %), headaches (5.94 %), myalgia (3.96 %), palpitation (3.96 %), loss of smell sensation (3.96 %), muscle weakness (2.97 %), loss of taste sensation (2.97 %) & chest pain (1.98 %). Most of the Conclusion: COVID-19 survivors experienced mild post-recovery symptoms such as cough, fatigue, breathlessness, headache, myalgia & palpitation. Raising awareness, recognition, research, and multidisciplinary involvement will be considered the cornerstones to manage long-term sequelae of COVID-19 effectively.

A Randomized Controlled Trial of the Efficacy of Systemic Enzymes and Probiotics in the Resolution of Post-COVID Fatigue

Muscle fatigue and cognitive disturbances persist in patients after recovery from acute COVID-19 disease. However, there are no specific treatments for post-COVID fatigue. Objective: To evaluate the efficacy and safety of the health supplements ImmunoSEB (systemic enzyme complex) and ProbioSEB CSC3 (probiotic complex) in patients suffering from COVID-19 induced fatigue. A randomized, multicentric, double blind, placebo-controlled trial was conducted in 200 patients with a complaint of post-COVID fatigue. The test arm (n = 100) received the oral supplements for 14 days and the control arm (n = 100) received a placebo. Treatment efficacy was compared using the Chalder Fatigue scale (CFQ-11), at various time points from days 1 to 14. The supplemental treatment resulted in resolution of fatigue in a greater percentage of subjects in the test vs. the control arm (91% vs. 15%) on day 14. Subjects in the test arm showed a significantly greater reduction in total as well as physical and mental fatigue scores at all time points vs. the control arm. The supplements were well tolerated with no adverse events reported. This study demonstrates that a 14 days supplementation of ImmunoSEB + ProbioSEB CSC3 resolves post-COVID-19 fatigue and can improve patients’ functional status and quality of life.