Exploring Inflammasome/Cytokine/Insulin cascade as converging landscape for AD, Schizophrenia(SCHIZO), and COVID‐19 syndrome: synthesis of evidence and Post‐hoc analysis of Ginsans‐115 RCT in treatment‐resistant‐schizophrenia

Abstract

AbstractBackgroundAmid COVID‐19 pandemic, issue is raised: 1) whether AD and Very‐late‐onset‐schizophrenia‐like psychosis(VLOSL): “dementia praecox” have higher COVID‐19 risk;2)whether dysregulated cross‐talk of immunity and inflammation, in Inflammasome‐Cytokine‐insulin signaling cascade (IFCI) is the missing link for AD, VLOSL and COVID‐19.MethodOur objective is : 1) to conduct Pub‐med search for crucial role of inflammasome‐cytokine‐insulin cascade(IFCI) in AD, VLOSL and COVID‐10 burden; 2a)to examine using RCT data whether in schizophrenia, cognitive impairment correlates with insulin resistance(IR) and cardio‐metabolic risks (CMR);2b)whether Panax Ginseng, as prime executioner of IFCI, modifies IR,CMR in TRS.ResultIn Part1: our Pubmed search concludes Dementia syndrome carries higher mortality risk. A meta‐analysis of 634,338 COVID‐19 patients from 16 studies reveals that schizophrenia, and dementia, significantly increased risk of COVID‐19 mortality and severity. Cardio‐metabolic risk factors modify the link. A large Swedish cohort study and systematic review of 17studies found evidence of VLOSL carries higher risk of dementia. Aberrant IFCI correlated with COVID‐19 severity, but very few data is available for Long‐COVID‐19 syndrome. Effect sizes cannot be calculated due to sample heterogeneity. In Part 2: post‐hoc analysis of Ginsana‐115 (Boehringer‐Ingelheim‐Pharmaton,Switzerland) of 8‐week placebo‐controlled parallel group design in TRS subjects . Log‐IR(insulin resistance) scores significantly correlated with spatial processing (p = 0.017). Framingham‐Risk‐score correlated inversely with visual perception p = 0.040) and spatial processing (p = 0.029) and neurocognitive index (p = 0.090). Systolic blood pressure (sBP) correlated significantly and inversely with visual perception (p = 0.032),speed (p = 0.010),and spatial processing (p = 0.034), HDL correlated with memory score:p = 0.008. Brief‐Psychiatric‐Rating‐Scale:BPRS correlated significantly with executive reasoning (p = 0.047),memory (p = 0.021), and mental inflexibility (p = 0.026). Ginsana‐115 at 100‐mg/200‐mg significantly reduced FRS by 24.1% compared with 16.1%(P<0.05) and systolic blood pressure (P<0.05) and significantly improved lipid profile in raising HDL and lowering LDL. Ginsana‐115 : 100 mg and 200 mg oral dosage, significantly improved negative symptom of apathy akin to AD.ConclusionInflammasome‐Cytokine‐Insulin signaling (IFCI) appears to be the heuristic model integrating COVID‐19 syndrome, late‐onset schizophrenia overlapping with AD. Longitudinal studies are warranted to validate IFCI as the prime driver. The positive findings of Ginsana‐115 in TRS highlight the therapeutic Pandora box of Diet, drug leads and Exercise targeting specifically the IFCI landscape in COVID‐19 syndrome, AD and VLOSL.