Psychiatric Comorbidities of Inflammatory Bowel Disease: It Is a Matter of Microglia's Gut Feeling.

Inflammatory bowel disease (IBD), a common term for Crohn's disease and ulcerative colitis, is a chronic, relapse-remitting condition of the gastrointestinal tract that is increasing worldwide. Psychiatric comorbidities, including depression and anxiety, are more prevalent in IBD patients than in healthy individuals. Evidence suggests that varying levels of neuroinflammation might underlie these states in IBD patients. Within this context, microglia are the crucial non-neural cells in the brain responsible for innate immune responses following inflammatory insults. Alterations in microglia's functions, such as secretory profile, phagocytic activity, and synaptic pruning, might play significant roles in mediating psychiatric manifestations of IBD. In this review, we discuss the role played by microglia in IBD-associated comorbidities.

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.

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.

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.

Contrasting Roles of the Galectin-3 in the Schizophrenia Onset, Clinical Presentation, and Somatic Comorbidity.

The role of the Galectin-3 (Gal-3) has already been explored in various somatic diseases, considering its engagement in infection, acute and chronic inflammation, and autoimmunity. Additionally, it has been recognized that Gal-3 is included in neuroinflammation and neurodegeneration, so we presented the possibility for its involvement in neuroprogression in schizophrenia. Gal-3 possibly participates in the early life programming of schizophrenia, also in the specific response to viral infections as a "second hit" later in life, and as a part of a unique systemic somatic dysfunction leading to the specific mental changes. In this review, we would like to put all these previous observations of Gal-3 properties in the context of schizophrenia onset, clinical symptoms presentation, frequent somatic comorbid states, and future options for Gal-3 centered treatment in schizophrenia.

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.