Diabetes mellitus type 2 as an underlying, comorbid or consequent state of mental disorders.

Somatic disturbances that occur in parallel with psychiatric diseases are a major challenge in clinical practice. Various factors contribute to the development of mental and somatic disorders. Type 2 diabetes mellitus (T2DM) is a significant health burden worldwide, and the prevalence of diabetes in adults is increasing. The comorbidity of diabetes and mental disorders is very common. By sharing a bidirectional link, both T2DM and mental disorders influence each other in various manners, but the exact mechanisms underlying this link are not yet elucidated. The potential mechanisms of both mental disorders and T2DM are related to immune and inflammatory system dysfunction, oxidative stress, endothelial dysfunction, and metabolic disturbances. Moreover, diabetes is also a risk factor for cognitive dysfunction that can range from subtle diabetes-associated cognitive decline to pre-dementia and dementia. A complex re-lationship between the gut and the brain also represents a new therapeutic approach since gut-brain signalling pathways regulate food intake and hepatic glucose production. The aim of this minireview is to summarize and present the latest data on mutual pathogenic pathways in these disorders, emphasizing their complexity and interweaving. We also focused on the cognitive performances and changes in neurodegenerative disorders. The importance of implementing integrated approaches in treating both of these states is highlighted, along with the need for individual therapeutic strategies.

Neuroimmune, clinical and treatment challenges in multiple sclerosis-related psychoses.

In recent years, epidemiological and genetic studies have shown an association between autoimmune diseases and psychosis. The question arises whether patients with schizophrenia are more likely to develop multiple sclerosis (MS) later in life. It is well known that the immune system plays an important role in the etiopathogenesis of both disorders. Immune disturbances may be similar or very different in terms of different types of immune responses, disturbed myelination, and/or immunogenetic predispositions. A psychotic symptom may be a consequence of the MS diagnosis itself or a separate entity. In this review article, we discussed the timing of onset of psychotic symptoms and MS and whether the use of corticosteroids as therapy for acute relapses in MS is unfairly neglected in patients with psychiatric comorbidities. In addition, we discussed that the anti-inflammatory potential of antipsychotics could be useful and should be considered, especially in the treatment of psychosis that coexists with MS. Autoimmune disorders could precipitate psychotic symptoms, and in this context, autoimmune psychosis must be considered as a persistent symptomatology that requires continuous and specific treatment.

Targeting Underlying Inflammation in Carcinoma Is Essential for the Resolution of Depressiveness.

In modern clinical practice and research on behavioral changes in patients with oncological problems, there are several one-sided approaches to these problems. Strategies for early detection of behavioral changes are considered, but they must take into account the specifics of the localization and phase in the course and treatment of somatic oncological disease. Behavioral changes, in particular, may correlate with systemic proinflammatory changes. In the up-to-date literature, there are a lot of useful pointers on the relationship between carcinoma and inflammation and between depression and inflammation. This review is intended to provide an overview of these similar underlying inflammatory disturbances in both oncological disease and depression. The specificities of acute and chronic inflammation are considered as a basis for causal current and future therapies. Modern therapeutic oncology protocols may also cause transient behavioral changes, so assessment of the quality, quantity, and duration of behavioral symptoms is necessary to prescribe adequate therapy. Conversely, antidepressant properties could be used to ameliorate inflammation. We will attempt to provide some impetus and present some unconventional potential treatment targets related to inflammation. It is certain that only an integrative oncology approach is justifiable in modern patient treatment.

VALIDATION OF THE BRIEF INTERNATIONAL COGNITIVE ASSESSMENT FOR MULTIPLE SCLEROSIS (BICAMS) IN A LARGE COHORT OF RELAPSING-REMITTING MS PATIENTS.

Cognitive impairment is one of the most frequently reported symptoms in persons with multiple sclerosis (MS). The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) has been recommended as a standardized international screening and monitoring tool for brief cognitive assessment. The aim of our study was to assess the reliability and validity of the Serbian version of the BICAMS. A total of 500 relapsing-remitting MS (RRMS) patients and 69 age-, gender- and education-matched healthy control (HC) subjects were examined. All participants performed the BICAMS test battery, which includes the oral version of the Symbol Digit Modalities Test (SDMT), California Verbal Learning Test second edition (CVLT-II), and Brief Visuospatial Memory Test Revised (BVMTR). A randomly selected subset of patients were retested one to three weeks after baseline. Statistically significant differences between patients and HCs were evident on the SDMT and BVMTR (p<0.001). HCs had higher CVLT-II scores but this difference did not reach statistical significance (p=0.063). Cognitive impairment, defined as an abnormal test score on ≥1 subtest, was found in 62.9% of MS patients. There were statistically significant correlations between BICAMS scores and age, education, EDSS and disease duration in patient sample. Test-retest reliability was confirmed with Pearson correlation coefficient of 0.70 in all measures. This study supported the reliability and validity of the Serbian BICAMS, although the CVLT-II version tested here lacked sensitivity to detect MS compared to healthy volunteers.

Admission Predictors of Mortality in Hospitalized COVID-19 Patients-A Serbian Cohort Study.

Background: Early prediction of COVID-19 patients' mortality risk may be beneficial in adequate triage and risk assessment. Therefore, we aimed to single out the independent morality predictors of hospitalized COVID-19 patients among parameters available on hospital admission. Methods: An observational, retrospective−prospective cohort study was conducted on 703 consecutive COVID-19 patients hospitalized in the University Clinical Center Kragujevac between September and December 2021. Patients were followed during the hospitalization, and in-hospital mortality was observed as a primary end-point. Within 24 h of admission, patients were sampled for blood gas and laboratory analysis, including complete blood cell count, inflammation biomarkers and other biochemistry, coagulation parameters, and cardiac biomarkers. Socio-demographic and medical history data were obtained using patients' medical records. Results: The overall prevalence of mortality was 28.4% (n = 199). After performing multiple regression analysis on 20 parameters, according to the initial univariate analysis, only four independent variables gave statistically significant contributions to the model: SaO2 < 88.5 % (aOR 3.075), IL-6 > 74.6 pg/mL (aOR 2.389), LDH > 804.5 U/L (aOR 2.069) and age > 69.5 years (aOR 1.786). The C-index of the predicted probability calculated using this multivariate logistic model was 0.740 (p < 0.001). Conclusions: Parameters available on hospital admission can be beneficial in predicting COVID-19 mortality.

Galectin-3 Involvement in Cognitive Processes for New Therapeutic Considerations.

Cognitive impairment may be a consequence of the normal aging process, but it may also be the hallmark of various neurodegenerative and psychiatric diseases. Early identification of individuals at particular risk for cognitive decline is critical, as it is imperative to maintain a cognitive reserve in these neuropsychiatric entities. In recent years, galectin-3 (Gal-3), a member of the galectin family, has received considerable attention with respect to aspects of neuroinflammation and neurodegeneration. The mechanisms behind the putative relationship between Gal-3 and cognitive impairment are not yet clear. Intrigued by this versatile molecule and its unique modular architecture, the latest data on this relationship are presented here. This mini-review summarizes recent findings on the mechanisms by which Gal-3 affects cognitive functioning in both animal and human models. Particular emphasis is placed on the role of Gal-3 in modulating the inflammatory response as a fine-tuner of microglia morphology and phenotype. A review of recent literature on the utility of Gal-3 as a biomarker is provided, and approaches to strategically exploit Gal-3 activities with therapeutic intentions in neuropsychiatric diseases are outlined.

The Influence of Serum Uric Acid on the Brain and Cognitive Dysfunction.

Uric acid is commonly known for its bad reputation. However, it has been shown that uric acid may be actively involved in neurotoxicity and/or neuroprotection. These effects could be caused by oxidative stress or inflammatory processes localized in the central nervous system, but also by other somatic diseases or systemic conditions. Our interest was to summarize and link the current data on the possible role of uric acid in cognitive functioning. We also focused on the two putative molecular mechanisms related to the pathological effects of uric acid-oxidative stress and inflammatory processes. The hippocampus is a prominent anatomic localization included in expressing uric acid's potential impact on cognitive functioning. In neurodegenerative and mental disorders, uric acid could be involved in a variety of ways in etiopathogenesis and clinical presentation. Hyperuricemia is non-specifically observed more frequently in the general population and after various somatic illnesses. There is increasing evidence to support the hypothesis that hyperuricemia may be beneficial for cognitive functioning because of its antioxidant effects but may also be a potential risk factor for cognitive dysfunction, in part because of increased inflammatory activity. In this context, gender specificities must also be considered.

Breast cancer in schizophrenia could be interleukin-33-mediated.

Recent epidemiological and genetic studies have revealed an interconnection between schizophrenia and breast cancer. The mutual underlying pathophysiological mechanisms may be immunologically driven. A new cluster of molecules called alarmins may be involved in sterile brain inflammation, and we have already reported the potential impact of interleukin-33 (IL-33) on positive symptoms onset and the role of its soluble trans-membranes full length receptor (sST2) on amelioration of negative symptoms in schizophrenia genesis. Furthermore, these molecules have already been shown to be involved in breast cancer etiopathogenesis. In this review article, we aim to describe the IL-33/suppressor of tumorigenicity 2 (ST2) axis as a crossroad in schizophrenia-breast cancer comorbidity. Considering that raloxifene could be tissue-specific and improve cognition and that tamoxifen resistance in breast carcinoma could be improved by strategies targeting IL-33, these selective estrogen receptor modulators could be useful in complementary treatment. These observations could guide further somatic, as well as psychiatric therapeutical protocols by incorporating what is known about immunity in schizophrenia.

Galectin-3 possible involvement in antipsychotic-induced metabolic changes of schizophrenia: A minireview.

Recently, specific immunometabolic profiles have been postulated in patients with schizophrenia, even before full-blown disease and independent of antipsychotic treatment. Proteomic profiling studies offer a promising potential for elucidating the cellular and molecular pathways that may be involved in the onset and progression of schizophrenia symptoms, and co-occurrent metabolic changes. In view of all this, we were intrigued to explore galectin-3 (Gal-3) as a glycan, and in our previous study, we measured its elevated levels in remission of schizophrenia. The finding may be a consequence of antipsychotic treatment and may have an impact on the onset of inflammation, the development of obesity, and the presumed cognitive changes in schizophrenia. In the animal study, it was shown that downregulation of Gal-3 was beneficial in insulin regulation of obesity and cognitive preservation. Strategies involving plasma exchange are discussed in this review, particularly in the context of Gal-3 elimination.

Uric Acid Potential Role in Systemic Inflammation and Negative Symptoms After Acute Antipsychotic Treatment in Schizophrenia.

Uric acid (UA) has been shown to have neuroprotective or neurotoxic properties, in relation to specific tissues and diseases that have been studied. Previous studies provided contradictory results on the role of UA in schizophrenia as a neurodegenerative disorder. The aim of this brief report was an additional analysis of UA sera levels in different phases of schizophrenia. Here, 86 patients with first-episode psychosis (FEP) vs. 45 patients with schizophrenia in relapse (SC in relapse) vs. 35 healthy control subjects (HC) were studied before and 1 month after antipsychotic therapy. Further, we aimed to explore the possible correlation of UA with scores presenting clinical features and with serum concentrations of the proinflammatory cytokines interleukin (IL)-6 and IL-17. When comparing the data between all three groups, we did not find significant differences in UA levels, either before or after the applied therapy. Also, comparing sera concentrations of UA in every single group, the analysis did not reveal statistically significant differences between FEP patients, but statistically, a significant difference was found in SC in relapse before and after treatment (334.71 ± 116.84 vs. 289.37 ± 109.15 µmol/L, p = 0.05). Uric acid serum levels correlated with negative sub-score (p = 0.001, r = 0.306), general sub-score (p = 0.015, r = 0.236), and total PANSS score (p = 0.009, r = 0.3) after 1 month of therapy. We have established a statistically significant positive correlation between serum concentrations of UA and IL-6 in exacerbation (p = 0.01, r = 0.220) and with IL-17 after treatment and in the stabilization of psychosis (p = 0.01, r = 0.34), suggesting potential cascades in different phases of schizophrenia that potentiate inflammation.

Impact of epilepsy duration, seizure control and EEG abnormalities on cognitive impairment in drug-resistant epilepsy patients.

Cognitive impairment frequently occurs in epilepsy patients. Patients with drug-resistant epilepsy (DRE) have poor drug responsivity and higher seizure frequency which consequently lead to brain damage and may have implications on cognitive status. In the present study, we assessed a frequency and degree of cognitive impairment in 52 patients with drug-sensitive epilepsy (DSE) and 103 DRE patients at three time points (baseline, after 12 and 18 months). Degree of cognitive decline was assessed with Montreal Cognitive Assessment (MoCA) scale. We examined the possible correlation between demographic and clinical characteristics and cognitive deterioration in epilepsy patients. Patients in the DRE group had significantly lower MoCA score than patients in the DSE group at baseline (28.83 ± 2.05 vs. 29.69 ± 0.61, p = 0.003), after 12 months (27.36 ± 2.40 vs. 29.58 ± 1.22, p = 0.000) and 18 months (26.86 ± 2.73 vs. 29.33 ± 1.47, p = 0.000). Patients with DRF epilepsy had significantly lower MoCA score than patients with DSF epilepsy at three time points (28.71 ± 2.48 vs. 29.86 ± 0.35, p = 0.015; 27.22 ± 2.72 vs. 29.52 ± 1.37, p = 0.000; 26.80 ± 2.99 vs. 29.31 ± 1.56, p = 0.000). After 12 and 18 months of follow-up, patients with DRG epilepsy had significantly lower MoCA score than patients with DSG epilepsy (27.52 ± 2.01 vs. 29.65 ± 1.02, p = 0.000; 26.94 ± 2.43 vs. 29.35 ± 1.40, p = 0.000). Illness duration negatively correlated with cognitive status (p = 0.005); seizure control and EEG findings positively correlated with MoCA score (p = 0.000). Illness duration, seizure control, drug responsivity, and EEG findings are significant predictors of MoCA score (p < 0.05). Clinicians have to pay attention to patients with drug-resistant epilepsy and concepts of aggressive treatment to minimize the adverse effects of epilepsy on cognition.