Increased insulin resistance due to long COVID is associated with depressive symptoms and partly predicted by the inflammatory response during acute infection

Objective: Some months after the remission of acute COVID-19, some individuals show depressive symptoms, which are predicted by increased peak body temperature (PBT) and decreased blood oxygen saturation (SpO2). The present study aimed to examine data on whether long COVID is associated with increased insulin resistance (IR) in association with neuroimmune and oxidative (NIO) processes during the acute infectious and long COVID phases. Methods: This case-control, retrospective cohort study used the Homeostasis Model Assessment 2 (HOMA2) calculator© to compute β-cell function (HOMA2%B) and insulin sensitivity (HOMA2%S) and resistance (HOMA2-IR) and administered the Beck Depression Inventory (BDI) and Hamilton Depression Rating Scale (HAMD) to 86 patients with long COVID and 39 controls. Results: Long COVID (3-4 months after the acute infection) is accompanied by increased HOMA2-IR, fasting blood glucose (FBG), and insulin levels; 33.7% of the patients vs. 0% of the controls had HOMA2-IR values > 1.8, suggesting IR. Increased IR was predicted by PBT during acute infection and associated with depressive symptoms above and beyond the effects of NIO pathways (nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing protein 3 [NLRP3] inflammasome, myeloperoxidase [MPO], protein oxidation). There were no significant associations between increased IR and the activated NIO pathways during long COVID. Conclusion: Long COVID is associated with new-onset IR, which may contribute to onset of depressive symptoms due to long COVID by enhancing overall neurotoxicity.

Lowered serum cesium levels in schizophrenia: association with immune-inflammatory biomarkers and cognitive impairments

Objectives: A previous study has shown that schizophrenia (SCZ) is accompanied by lowered levels of trace/metal elements, including cesium. However, it is not clear whether changes in cesium, rubidium, and rhenium are associated with activated immune-inflammatory pathways, cognitive impairments, and the symptomatology of SCZ. Methods: This study measured cesium, rubidium, and rhenium, cognitive impairments (using the Brief Assessment of Cognition in Schizophrenia [BACS]), and the levels of cytokines/chemokines interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and eotaxin (CCL11) in 120 patients with SCZ and 54 healthy controls. Severity of illness was assessed using the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Negative Symptoms (SANS), the Fibromyalgia and Chronic Fatigue Syndrome Rating (FF) Scale, and the Hamilton Depression Rating Scale (HAM-D). Results: Serum cesium was significantly lower in patients with SCZ as compared with controls. Further, serum cesium was significantly and inversely associated with CCL11 and TNF-α, but not IL-1β, in patients with SCZ; significant inverse associations were also noted between serum cesium levels and BPRS, FF, HAM-D, and SANS scores. Finally, cesium was positively correlated with neurocognitive probe results including the Tower of London, Symbol Coding, Controlled Word Association, Category Instances, Digit Sequencing Task, and List Learning tests. Conclusion: The results suggest that lowered serum cesium levels may play a role in the pathophysiology of SCZ, contributing to specific symptom domains including negative, depressive and fatigue symptoms, neurocognitive impairments (spatial working, episodic, and semantic memory and executive functions), and neuroimmune pathways.

Vitamin D deficiency is not associated with increased oxidative stress in chronic kidney disease pre-dialysis patients / A deficiência de vitamina D não está associada ao aumento do estresse oxidativo em pacientes renais crônicos em pré-diálise

Abstract Introduction: The progressive decline in 25-hydroxyvitamin D [25(OH)D] in chronic kidney disease (CKD) limits the kidney ability of synthesizing the vitamin. Vitamin D deficiency as defined by KDIGO (25(OH)D <20 ng/mL) is prevalent in CKD patients and associated to oxidative stress (OS). We studied a possible association between vitamin D deficiency and OS in pre-dialysis patients. Methods: A cross-sectional study with 206 CKD patients was carried out. Laboratory tests for 25(OH)D, 1,25(OH)2D, inflammatory markers, and OS were added to routine tests including creatinine, albumin, calcium, phosphorus, alkaline phosphatase, iPTH, glucose, hemoglobin, uric acid, total cholesterol, LDL, HDL, and triglycerides. Results: Vitamin D deficiency was present in 55 CKD patients and normal vitamin D levels were seen in 149 patients. There was a significant association between vitamin D and estimated glomerular filtration rate (eGRF). Homocysteine levels were best predicted by eGRF, sex, and age; high sensitivity C-reactive protein (hsCRP) by staging and BMI; nitric oxide metabolites (NOx) were increased in late disease; leptin was influenced by BMI and higher in women than man; and adiponectin levels were higher in women. Conclusions: OS biomarkers were not correlated with vitamin D deficiency but increased NOx were seen in stages 4-5 CKD patients. Even though a relatively large number of CKD patients was included and a broad number of OS and inflammatory biomarkers were used in this studied we failed to find an association between vitamin D levels and eGRF. More studies are needed to evaluate the influence of vitamin D status in OS in pre-dialysis CKD patients.

Resumo Introdução: A queda da 25-hidroxivitamina D [25 (OH) D] na doença renal crônica (DRC) limita a capacidade renal de sintetizar a vitamina. A deficiência de vitamina D, (25(OH)D<20 ng/mL), é prevalente em pacientes com DRC e associada ao estresse oxidativo (EO). Avaliamos possível associação entre a deficiência de vitamina D e EO em pacientes pré-dialíticos. Métodos: estudo transversal com 206 pacientes com DRC. Exames para 25(OH)D, 1,25(OH)2D, marcadores inflamatórios e EO foram adicionados àqueles de rotina, incluindo creatinina, albumina, cálcio, fósforo, fosfatase alcalina, iPTH, glicose, hemoglobina, ácido úrico, colesterol total , LDL, HDL e triglicerídeos. Resultados: 55 pacientes com DRC tinham deficiência de vitamina D e os 149 tinham níveis normais da vitamina. Houve uma associação significativa entre a vitamina D e a taxa estimada de filtração glomerular (TFGe). Os níveis de homocisteína foram melhor previstos pela TFGe, gênero e idade; proteína C reativa de alta sensibilidade (hsCRP) por estadiamento e IMC; os metabólitos de óxido nítrico (NOx) aumentaram na doença tardia; a leptina foi influenciada pelo IMC, e mais alta em mulheres, assim como os níveis de adiponectina. Conclusões: biomarcadores do EO não correlacionaram com a deficiência de vitamina D, mas houve aumento de NOx nos estágios 4-5 da DRC. Apesar dos grandes números de pacientes com DRC, de biomarcadores inflamatórios e EO usados neste estudo, não houve associação entre os níveis de vitamina D e a TFGe. Mais estudos são necessários para avaliar a influência do status da vitamina D no EO em pacientes com DRC em pré-diálise.

Personality disorder and functioning in major depressive disorder: a nested study within a randomized controlled trial

Objective: This study aimed to determine if personality disorder (PD) predicted functional outcomes in patients with major depressive disorder (MDD). Methods: Data (n=71) from a double-blind, randomized, placebo-controlled 12-week trial assessing the efficacy of 200 mg/day adjunctive minocycline for MDD were examined. PD was measured using the Standardized Assessment of Personality Abbreviated Scale. Outcome measures included Clinical Global Impression - Improvement (CGI-I), Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), Social and Occupational Functioning Scale (SOFAS), and Range of Impaired Functioning (RIFT). Analysis of covariance was used to examine the impact of PD (dichotomized factor [≥ 3] or continuous measure) on the outcome measures-treatment group correlation. Results: PD was identified in 69% of the sample. After adjusting for age, sex, and baseline scores for each of the outcome measures, there was no significant difference between participants with and without PD on week 12 scores for any of the outcome measures (all p > 0.14). Conclusion: In this secondary analysis of a primary efficacy study, PD was a common comorbidity among those with MDD, but was not a significant predictor of functional outcomes. This study adds to the limited literature on PD in randomized controlled trials for MDD. Clinical trial registration: ACTRN12612000283875.

Psychometric properties of the modified Yale Food Addiction Scale 2 0 in a large Brazilian sample

Objective: The field of food addiction has attracted growing research attention. The modified Yale Food Addiction Scale 2.0 (mYFAS 2.0) is a screening tool based on DSM-5 criteria for substance use disorders. However, there is no validated instrument to assess food addiction. Methods: The mYFAS 2.0 has been transculturally adapted to Brazilian Portuguese. The data for this study was obtained through an anonymous web-based research platform: participants provided sociodemographic data and answered Brazilian versions of the the mYFAS 2.0 and the Barratt Impulsivity Scale (BIS-11). Analysis included an assessment of the Brazilian mYFAS 2.0's internal consistency reliability, factor structure, and convergent validity in relation to BIS-11 scores. Results: Overall, 7,639 participants were included (71.3% females; age: 27.2±7.9 years). The Brazilian mYFAS 2.0 had adequate internal consistency reliability (Cronbach's alpha = 0.89). A single factor solution yielded the best goodness-of-fit parameters for both the continuous and categorical version of the mYFAS 2.0 in confirmatory factor analysis. In addition, mYFAS 2.0 correlated with BIS-11 total scores (Spearman's rho = 0.26, p < 0.001) and subscores. Conclusion: The Brazilian mYFAS 2.0 demonstrated adequate psychometric properties in our sample; however, future studies should further evaluate its discriminant validity.

Paraoxonase 1 (PON1) Q192R genotypes and their interaction with smoking strongly increase atherogenicity and the Framingham risk score

ABSTRACT Objective Paraoxonase 1 (PON1) polymorphisms are associated with an increased susceptibility to cardiovascular disease. PON1 Q192R polymorphism (rs662) partially determine PON1 hydrolytic activity and protect against oxidation of LDL and HDL. This study aimed to delineate the association of PON1 status (functional 192 genotype and plasma activity levels) and atherogenicity in urbans residents aged 40 years or more. Materials and methods Anthropometric data, lipid profiles, the atherogenic index of the plasma (AIP) and Framingham score risk were measured. Three kinetic assays were conducted to assay PON1 status using phenylacetate and 4-(chloromethyl)phenyl acetate as substrates. Results Smoking per se did not significantly impact the AIP but the interaction PON1 genotype by smoking significantly increased the AIP. In subjects with the RR genotype smoking increased the AIP index from (estimated mean ± SEM) -0.038 ± 0.039 to 0.224 ± 0.094. The QR genotype increased the Framingham risk index by around 1.3 points. Smoking by RR genotype carriers significantly increased the Framingham risk score (17.23 ± 2.04) as compared to smoking (13.00 ± 1.06) and non-smoking (7.79 ± 0.70) by QQ+QR genotype carriers. The interaction RR genotype by smoking was a more important predictor (odds ratio = 7.90) of an increased Framingham risk score (> 20) than smoking per se (odds ratio = 2.73). The interaction smoking by RR genotype carriers significantly increased triglycerides and lowered HDL cholesterol. Conclusion Smoking per se has no (AIP) or a mild (Framingham risk score) effect on atherogenicity, while the interaction smoking by PON1 RR genotype has a clinically highly significant impact on atherogenicity.