scholarly journals Сellular and Molecular Mechanisms of Proinflammatory Monocytes Participation in the Pathogenesis of Mental Disorders. Part 2

Psychiatry ◽  
2020 ◽  
Vol 18 (4) ◽  
pp. 81-92
Author(s):  
E. F. Vasilyeva ◽  
O. S. Brusov
Keyword(s):  
Mental Disorders ◽  
Proinflammatory Cytokines ◽  
Molecular Mechanisms ◽  
Psychotic Disorders ◽  
Bipolar Affective Disorder ◽  
Research Data ◽  
Scientific Publications ◽  
Somatic Comorbidity ◽  
Immune Inflammation

Introduction: at the end of the last century, the macrophage-T-lymphocyte theory of the development of mental disorders was formulated. It underlines the important role of monocytes/macrophages and cytokines produced by them in the pathogenesis of schizophrenia, bipolar affective disorder (BAD) and depression. The first part of our review is dedicated to the analysis of the mechanisms of cellular and molecular interactions of activated monocytes/macrophages synthesizing proinflammatory CD16 receptors with endothelial cells, platelets, and microglia cells in the pathogenesis of systemic immune inflammation, including CNS as a result of violation of the integrity of the blood-brain barrier (BBB), activate microglia and cause the development of neuroinflammation in patients.The aim of work: to analyze and summarize the results of the main scientific publications for the role of cell-molecular mechanisms of the monocyte-macrophage immunity link activation in the pathogenesis of schizophrenia, BAD and depression. Material and methods: keywords “proinflammatory monocytes, cytokines, chemokines, molecules of cell adhesion, microglia, neuroinflammation, mental disorders” were used to search for data published over the past 20 years in domestic and foreign studies in PubMed, eLIBRARY, Science direct and EMBASE.Conclusion: the present review is dedicated to the analysis of the latest research data concerning an increase in the number of active circulating monocytes/macrophages and an increased level of proinflammatory cytokines, chemokines and receptors for them produced by monocytes in patients with schizophrenia, BAD and depression, what allows to associate these disorders with systemic immune inflammation. The data reasearches on cellular and molecular mechanisms of proinflammatory monocytes/macrophages interaction with microglia cells that initiate neuroinflammation in the CNS and lead to destabilization of brain function and the development of psychotic disorders are presented. The association of high levels of proinflammatory cytokines with somatic comorbidity, including metabolic syndrome, diabetes, atherosclerosis and other systemic diseases is shown in patients with mental disorders.Findings: the presented review of the research data allows us to better understand the cellular and molecular aspects of activation of the monocyte-macrophage immunity link in the development of neuroinflammation and cognitive decline in the pathogenesis of mental disorders, as well as helps in the search for informative biomarkers of the positive treatment of these disorders and the new approaches in the treatment of patients, based on the complex use of psychotropic and anti-inflammatory drugs.

scholarly journals The Role of Monocytes Cellular and Molecular Mechanisms in the Development of Systemic Immune Inflammation. Part 1

Psychiatry ◽  
2020 ◽  
Vol 18 (3) ◽  
pp. 76-85
Author(s):  
E. F. Vasilyeva ◽  
O. S. Brusov
Keyword(s):  
Mental Disorders ◽  
Molecular Mechanisms ◽  
Vascular Endothelial Cells ◽  
Cognitive Disorders ◽  
Research Data ◽  
Vascular Endothelial ◽  
Platelet Aggregates ◽  
Immune Inflammation ◽  
The Brain

Introduction: the important role of monocytes /macrophages, as well as cytokines produced by them was determined in the pathogenesis of mental disorders, as a macrophage-T-lymphocyte theory of bipolar disorder, schizophrenia and depression. According to this theory, there is an increase in the number of active circulating monocytes, macrophages and T-cells in patients with mental disorders. These cells migrate to the CNS as a result of the blood-brain barrier breach, destabilize the brain and lead to worsening of mental disorders.The aim of work: to review research data on the role of proinflammator monocytes in the development of immune inflammation in the pathogenesis of a number of systemic diseases and to examine the molecular mechanisms mediating the interaction of proinflammatory monocytes with other cells involved in immune inflammation.Material and methods: keywords “proinflammatory monocyte CD16+”, “cytokines”, “molecules of cell adhesion”, “monocyte-platelet aggregates”, “microglia”, “psychiatriс disorders”, are used to search for data published over the past 20 years in domestic and foreign studies in PubMed and e-Library.Conclusion: in the first part of the review, the research data concerning the studies of the functional characteristics of a monocytes subpopulation that express on their surface an increased level of CD16 receptors when activated were analyzed. Most of researchers associate the proinflammatory functions of monocytes with this subpopulation. Molecular mechanisms of monocytes activation, which include increased secretion of CD16 receptors, cytokines, chemokines and receptors for them involved in their interaction with vascular endothelial cells, with neurons in the CNS and also with platelets in the development of systemic inflammation, are considered. Analysis of these mechanisms allows us to better understand the immune aspects of inflammation in the brain mediated by the interaction of CD16+ monocytes with neuronal cells, which results in cognitive disorders in patients with mental disorders, as well as to identify related new approaches to the treatment of cognitive decline in these patients. Studies of the monocyte unit of immunity in patients with mental disorders will be covered in the second part of the review.

scholarly journals The role of rumination in illness trajectories in youth: linking trans-diagnostic processes with clinical staging models

2016 ◽  
Vol 46 (12) ◽  
pp. 2467-2484 ◽  
Author(s):  
A. B. Grierson ◽  
I. B. Hickie ◽  
S. L. Naismith ◽  
J. Scott
Keyword(s):  
Mental Disorders ◽  
Emotional Regulation ◽  
Potential Role ◽  
Psychotic Disorders ◽  
Developmental Trajectory ◽  
Clinical Staging ◽  
Neurocognitive Deficits ◽  
Illness Onset ◽  
Co Morbidity

Research in developmental psychopathology and clinical staging models has increasingly sought to identify trans-diagnostic biomarkers or neurocognitive deficits that may play a role in the onset and trajectory of mental disorders and could represent modifiable treatment targets. Less attention has been directed at the potential role of cognitive-emotional regulation processes such as ruminative response style. Maladaptive rumination (toxic brooding) is a known mediator of the association between gender and internalizing disorders in adolescents and is increased in individuals with a history of early adversity. Furthermore, rumination shows moderate levels of genetic heritability and is linked to abnormalities in neural networks associated with emotional regulation and executive functioning. This review explores the potential role of rumination in exacerbating the symptoms of alcohol and substance misuse, and bipolar and psychotic disorders during the peak age range for illness onset. Evidence shows that rumination not only amplifies levels of distress and suicidal ideation, but also extends physiological responses to stress, which may partly explain the high prevalence of physical and mental co-morbidity in youth presenting to mental health services. In summary, the normative developmental trajectory of rumination and its role in the evolution of mental disorders and physical illness demonstrates that rumination presents a detectable, modifiable trans-diagnostic risk factor in youth.

Сellular and Molecular Mechanisms of Proinflammatory Monocytes Participation in the Pathogenesis of Mental Disorders. Part 3

Psychiatry ◽  
2021 ◽  
Vol 19 (4) ◽  
pp. 125-134
Author(s):  
E. F. Vasilyeva ◽  
O. S. Brusov
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Mental Disorders ◽  
Molecular Mechanisms ◽  
Microglial Cells ◽  
Inflammatory Reactions ◽  
Mental Diseases ◽  
The Central Nervous System ◽  
The Brain

Background: at present, the important role of the monocyte-macrophage link of immunity in the pathogenesis of mental diseases has been determined. In the first and second parts of our review, the cellular and molecular mechanisms of activation of monocytes/macrophages, which secreting proinflammatory CD16 receptors, cytokines, chemokines and receptors to them, in the development of systemic immune inflammation in the pathogenesis of somatic diseases and mental disorders, including schizophrenia, bipolar affective disorder (BAD) and depression were analyzed. The association of high levels of proinflammatory activity of monocytes/macrophages in patients with mental disorders with somatic comorbidity, including immune system diseases, is shown. It is known that proinflammatory monocytes of peripheral blood, as a result of violation of the integrity of the hematoencephalic barrier can migrate to the central nervous system and activate the resident brain cells — microglia, causing its activation. Activation of microglia can lead to the development of neuroinammation and neurodegenerative processes in the brain and, as a result, to cognitive disorders. The aim of review: to analyze the results of the main scientific studies concerning the role of cellular and molecular mechanisms of peripheral blood monocytes interaction with microglial cells and platelets in the development of neuroinflammation in the pathogenesis of mental disorders, including Alzheimer’s disease (AD). Material and methods: keywords “mental disorders, AD, proinflammatory monocytes, microglia, neuroinflammation, cytokines, chemokines, cell adhesion molecules, platelets, microvesicles” were used to search for articles of domestic and foreign authors published over the past 30 years in the databases PubMed, eLibrary, Science Direct and EMBASE. Conclusion: this review analyzes the results of studies which show that monocytes/macrophages and microglia have similar gene expression profiles in schizophrenia, BAD, depression, and AD and also perform similar functions: phagocytosis and inflammatory responses. Monocytes recruited to the central nervous system stimulate the increased production of proinflammatory cytokines IL-1, IL-6, tumor necrosis factor alpha (TNF-α), chemokines, for example, MCP-1 (Monocyte chemotactic protein-1) by microglial cells. This promotes the recruitment of microglial cells to the sites of neuronal damage, and also enhances the formation of the brain protein beta-amyloid (Aβ). The results of modern studies are presented, indicating that platelets are involved in systemic inflammatory reactions, where they interact with monocytes to form monocyte-platelet aggregates (MTA), which induce the activation of monocytes with a pro inflammatory phenotype. In the last decade, it has been established that activated platelets and other cells of the immune system, including monocytes, detached microvesicles (MV) from the membrane. It has been shown that MV are involved as messengers in the transport of biologically active lipids, cytokines, complement, and other molecules that can cause exacerbation of systemic inflammatory reactions. The presented review allows us to expand our knowledge about the cellular and molecular aspects of the interaction of monocytes/macrophages with microglial cells and platelets in the development of neuroinflammation and cognitive decline in the pathogenesis of mental diseases and in AD, and also helps in the search for specific biomarkers of the clinical severity of mental disorder in patients and the prospects for their response to treatment.

scholarly journals Anti-Inflammatory Cytokines: Important Immunoregulatory Factors Contributing to Chemotherapy-Induced Gastrointestinal Mucositis

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Masooma Sultani ◽  
Andrea M. Stringer ◽  
Joanne M. Bowen ◽  
Rachel J. Gibson
Keyword(s):  
Inflammatory Cytokines ◽  
Proinflammatory Cytokines ◽  
Molecular Mechanisms ◽  
Tissue Injury ◽  
Financial Burden ◽  
Interleukin 1 ◽  
Treatment Strategies ◽  
Inflammatory Reactions ◽  
Anti Inflammatory

“Mucositis” is the clinical term used to describe ulceration and damage of the mucous membranes of the entire gastrointestinal tract (GIT) following cytotoxic cancer chemotherapy and radiation therapy common symptoms include abdominal pain, bloating, diarrhoea, vomiting, and constipation resulting in both a significant clinical and financial burden. Chemotherapeutic drugs cause upregulation of stress response genes including NFκB, that in turn upregulate the production of proinflammatory cytokines such as interleukin-1β (IL-1β), Interleukin-6 (IL-6), and tumour necrosis factor-α (TNF-α). These proinflammatory cytokines are responsible for initiating inflammation in response to tissue injury. Anti-inflammatory cytokines and specific cytokine inhibitors are also released to limit the sustained or excessive inflammatory reactions. In the past decade, intensive research has determined the role of proinflammatory cytokines in development of mucositis. However, a large gap remains in the knowledge of the role of anti-inflammatory cytokines in the setting of chemotherapy-induced mucositis. This critical paper will highlight current literature available relating to what is known regarding the development of mucositis, including the molecular mechanisms involved in inducing inflammation particularly with respect to the role of proinflammatory cytokines, as well as provide a detailed discussion of why it is essential to consider extensive research in the role of anti-inflammatory cytokines in chemotherapy-induced mucositis so that effective targeted treatment strategies can be developed.

Psychotic experiences as precursors in schizophrenia? Findings from a population-based sample in Germany (DEGS1-MH)

2016 ◽  
Vol 33 (S1) ◽  
pp. S48-S48
Author(s):  
C. Schmidt-Kraepelin
Keyword(s):  
Mental Health ◽  
Mental Disorders ◽  
Psychotic Disorders ◽  
Age Groups ◽  
Population Based ◽  
Care Utilization ◽  
Psychotic Experiences ◽  
German Health ◽  
Wide Range

There are only a few studies that have studied the prevalence of psychotic experiences (PEs) in a representative population-based sample and a broad range of age. The association and predictive role of PEs in the context of psychotic and other mental disorders remains a subject of discussion. The Mental Health Module of the German Health Interview and Examination Survey for Adults is the first wave of a German health monitoring survey describing:– the distribution and frequency, the severity and the impairments of a wide range of mental disorders;– risk factors as well as patterns of help-seeking and health care utilization;– associations between mental and somatic disorders.A total of 4483 participants participated in the mental health section of the survey. The Composite International Diagnostic Interview, the Launay-Slade Hallucination Scale and the Peter's Delusion Inventory were used to assess PEs by clinically experienced interviewers. We can confirm and extend previous findings for younger age groups that PEs are very frequent psychopathological expressions in the general population across genders and all age groups. PEs rates were elevated among those with other mental disorders, particularly among possible psychotic disorders, PTSD and affective disorders. This points to the relevant role of PEs as a marker for psychopathology and mental disorders. Future prospective studies will have to focus on specific properties of psychotic experiences such as their appraisal or underlying social influences to determine their significance for the prediction of psychotic and other mental disorders.Disclosure of interestThe author has not supplied his declaration of competing interest.

scholarly journals Praecox-Gefühl in Classical and Modern Researches

Psychiatry ◽  
2020 ◽  
Vol 18 (3) ◽  
pp. 58-64
Author(s):  
I. D. Gornushenkov ◽  
I. V. Pluzhnikov
Keyword(s):  
Mental Disorders ◽  
Interpersonal Communication ◽  
Diagnostic Technique ◽  
Diagnostic Tools ◽  
Diagnostic Process ◽  
Patient Relationship ◽  
Doctor Patient Relationship ◽  
Scientific Publications ◽  
Intersubjective Experience

Background: The introduction of modern classifications of mental disorders has caused a number of significant changes in the diagnostic process. Recently, both domestic and foreign authors began to pay more attention to the analysis of the “weaknesses” of the operational approach in the diagnosis of mental disorders. One of the “lacunae” that arose due to its distribution, which is hardly discussed in modern classifications, is the problems of the role of intersubjective experience in the doctor–patient relationship and the diagnostic process. The diagnostic technique based on the Praecox-Gefühl phenomenon is one of the most striking examples of the utility of such an experience.The aim was to present and discuss modern and classic Praecox-Gefühl studies in the context of analyzing the role of intersubjective experience in psychiatric diagnosis.Material and method: Modern and classic scientific publications were selected by using the keywords “Praecox-Gefühl” or “Praecox-feeling” in the databases of Web of Science, PubMed and in the other sources.Conclusion: the professional use of intersubjective experience arising in a doctor–patient relationship can be one of the diagnostic tools for identifying schizophrenia, including the early stages of the disease. Modern psychological studies indirectly confirm this statement by revealing an impairment of functions that provide interpersonal communication among patients with schizophrenia.

Pharmacotherapy of acute psychotic states: The reason for benzodiazepines and valproic acid augmentation

2016 ◽  
Vol 33 (S1) ◽  
pp. S612-S612
Author(s):  
A. Veraksa ◽  
A. Egorov
Keyword(s):  
Valproic Acid ◽  
Mental Disorders ◽  
Mental State ◽  
Schizoaffective Disorder ◽  
Affective Disorders ◽  
Psychotic Disorders ◽  
Bipolar Affective Disorder ◽  
Schizophrenia Spectrum ◽  
Icd 10 ◽  
Competing Interest

Acute psychotic states (APS) usually are diagnosed as schizophrenia spectrum and affective disorders and make up about 45% of cases. The goal of the study was to elucidate the effect of benzodiazepines (BDZ) and valproic acid augmentation in the APS pharmacotherapy. The study was carried out on 102 inpatients diagnosed up to ICD-10 as schizophrenia (n = 24), acute and transient psychotic disorders (n = 40), other mental disorders due to brain damage and dysfunction and to physical disease (n = 17), schizoaffective disorder (n = 12), bipolar affective disorder (n = 9). Patients were randomized into four therapeutic groups:– benzodiazepines (BDZ);– one neuroleptic or combination of one neuroleptic and one BDZ (NBDZ);– combination of valproic acid with BDZ or neuroleptic (VBDZN);– polypragmasy (PP): from two drugs of one group up to four and more drugs at the same time.The mental state of the patients was evaluated daily and estimated before, weekly and after APS termination by BPRS and CGI scale. The APS in all groups lasted from 1 to 50 days (mean 11.4). The shortest duration of APS was In BDZ group – 4.7 days; in VBDZN and NBDZ, the duration was 7.0 and 7.4 days (P < 0.05); in PP group, the treatment lasted 24.5 days (P < 0.001). Before therapy, average BPRS rate was 43.5 ± 8.1, CGI – 6.2 ± 0.8; after APS, BPRS was 18.9 ± 2.1, CGI – 1.1 ± 0.3. All rates did not differ among subgroups. APS therapy by BDZ and its combination with neuroleptics and valproic acid was effective compared to the polypragmasy.Disclosure of interestThe authors have not supplied their declaration of competing interest.

P02 - 362 - Schizencephaly and psychosis

2011 ◽  
Vol 26 (S2) ◽  
pp. 958-958
Author(s):  
P. Tibrewal ◽  
L. English ◽  
E. Foo ◽  
R.S. Dhillon
Keyword(s):  
Psychotic Disorders ◽  
Bipolar Affective Disorder ◽  
Bipolar Disorders ◽  
Interesting Case ◽  
Motor Deficits ◽  
Mesh Terms ◽  
Pubmed Search ◽  
Neurodevelopmental Abnormalities ◽  
Intrauterine Infections

Schizencephaly is an uncommon congenital disorder of cerebral cortical development, defined as a gray matter-lined cleft extending from the pial surface to the ventricle. It is a neuronal migration anomaly, caused by insults to migrating neuroblasts during 3rd to 5th gestational months.Ischemia, germline mutations, intrauterine infections and exposure to drugs have been implicated in its etiology. The outcome relates with the severity of pathology. Unilateral closed lip schizencephaly has the mildest clinical picture and bilateral open lip the most severe. The most prominent manifestations are motor deficits and seizures.Schizencephaly has been related with psychosis. However, there is paucity of literature exploring this relation. Pubmed search with “Schizencephaly AND Psychotic disorders OR Bipolar Disorders” as Mesh terms resulted in 9 results. Of these four discussed Schizencephaly. Rest five reports were related to other disorders of cortical malformation. We present an interesting case of schizencephaly associated with psychosis and congenital hemiparesis. We also present a review of literature available for this rare association.This case points towards the role of neurodevelopmental abnormalities in the manifestation of psychosis and bipolar affective disorder. It indicates that presence of neurodevelopmental anomalies may have pathoplastic effects on the presentation of psychosis and may also influence treatment response adversely. A possible mechanism explaining the development of psychosis in schizencephaly is the disruption in intracortical connections. There is also a possibility of underlying ictal phenomenon leading to psychosis. The above case provides support to the neurodevelopmental theory of Schizophrenia.

scholarly journals Inhibition of Neddylation Represses Lipopolysaccharide-induced Proinflammatory Cytokine Production in Macrophage Cells

2012 ◽  
Vol 287 (42) ◽  
pp. 35756-35767 ◽  
Author(s):  
Fang-Mei Chang ◽  
Sara M. Reyna ◽  
Jose C. Granados ◽  
Sung-Jen Wei ◽  
Wendy Innis-Whitehouse ◽  
...  
Keyword(s):  
Proinflammatory Cytokines ◽  
Molecular Mechanisms ◽  
Nuclear Translocation ◽  
Transcriptional Level ◽  
E3 Ligases ◽  
Target Proteins ◽  
Molecular Process ◽  
Tnf Α ◽  
Ring E3 Ligases

Cullin-RING E3 ligases (CRLs) are a class of ubiquitin ligases that control the proteasomal degradation of numerous target proteins, including IκB, and the activity of these CRLs are positively regulated by conjugation of a Nedd8 polypeptide onto Cullin proteins in a process called neddylation. CRL-mediated degradation of IκB, which normally interacts with and retains NF-κB in the cytoplasm, permits nuclear translocation and transactivation of the NF-κB transcription factor. Neddylation occurs through a multistep enzymatic process involving Nedd8 activating enzymes, and recent studies have shown that the pharmacological agent, MLN4924, can potently inhibit Nedd8 activating enzymes, thereby preventing neddylation of Cullin proteins and preventing the degradation of CRL target proteins. In macrophages, regulation of NF-κB signaling functions as a primary pathway by which infectious agents such as lipopolysaccharides (LPSs) cause the up-regulation of proinflammatory cytokines. Here we have analyzed the effects of MLN4924, and compared the effects of MLN4924 with a known anti-inflammatory agent (dexamethasone), on certain proinflammatory cytokines (TNF-α and IL-6) and the NF-κB signaling pathway in LPS-stimulated macrophages. We also used siRNA to block neddylation to assess the role of this molecular process during LPS-induced cytokine responsiveness. Our results demonstrate that blocking neddylation, either pharmacologically or using siRNA, abrogates the increase in certain proinflammatory cytokines secreted from macrophages in response to LPS. In addition, we have shown that MLN4924 and dexamethasone inhibit LPS-induced cytokine up-regulation at the transcriptional level, albeit through different molecular mechanisms. Thus, neddylation represents a novel molecular process in macrophages that can be targeted to prevent and/or treat the LPS-induced up-regulation of proinflammatory cytokines and the disease processes associated with their up-regulation.

scholarly journals Role of SIRT1 in regulation of LPS- or two ethanol metabolites-induced TNF-α production in cultured macrophage cell lines

2009 ◽  
Vol 296 (5) ◽  
pp. G1047-G1053 ◽  
Author(s):  
Zheng Shen ◽  
Joanne M. Ajmo ◽  
Christopher Q. Rogers ◽  
Xiaomei Liang ◽  
Lisa Le ◽  
...  
Keyword(s):  
Cell Lines ◽  
Proinflammatory Cytokines ◽  
Molecular Mechanisms ◽  
Sirtuin 1 ◽  
Class Iii ◽  
Macrophage Cell ◽  
Tnf Α ◽  
Sirt1 Inhibitor ◽  
Factor Α

Dysregulation of proinflammatory cytokines such as tumor necrosis factor-α (TNF-α) has been implicated in the pathogenesis of alcoholic liver injury. Sirtuin 1 (SIRT1) is an NAD+-dependent class III protein deacetylase that is known to be involved in regulating production of proinflammatory cytokines including TNF-α. In the present study, we examined the role of SIRT1 signaling in TNF-α generation stimulated by either lipopolysaccharide (LPS), acetaldehyde (AcH), or acetate (two major metabolites of ethanol) in two cultured macrophage cell lines. In both rat Kupffer cell line 1 (RKC1) and murine RAW 264.7 macrophages, treatment with either LPS, AcH, or acetate caused significant decreases in SIRT1 transcription, translation, and activation, which essentially demonstrated an inverse relationship with TNF-α levels. LPS, AcH, and acetate each provoked the release of TNF-α from RKC1 cells, whereas coincubation with resveratrol (a potent SIRT1 agonist) inhibited this effect. Conversely, addition of sirtinol (a known SIRT1 inhibitor) or knocking down SIRT1 by the small silencing SIRT1 plasmid (SIRT1shRNA) augmented TNF-α release, suggesting that impairment of SIRT1 may contribute to TNF-α secretion. Further mechanistic studies revealed that inhibition of SIRT1 by LPS, AcH, or acetate was associated with a marked increase in the acetylation of the RelA/p65 subunit of nuclear transcription factor (NF-κB) and promotion of NF-κB transcriptional activity. Taken together, our findings suggest that SIRT1-NF-κB signaling is involved in regulating LPS- and metabolites-of-ethanol-mediated TNF-α production in rat Kupffer cells and in murine macrophages. Our study provides new insights into understanding the molecular mechanisms underlying the development of alcoholic steatohepatitis.

Sign in / Sign up

Export Citation Format

Share Document