376 results on '"Maes, Michael"'
Search Results
102. Depressive and anxiety symptoms in the early puerperium are related to increased degradation of tryptophan into kynurenine, a phenomenon which is related to immune activation
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Maes, Michael, Verkerk, Robert, Bonaccorso, Stephania, Ombelet, Willem, Bosmans, Eugene, and Scharpé, Simon
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TRYPTOPHAN , *POSTPARTUM depression , *ANXIETY - Abstract
There is now some evidence that i) the availability of plasma tryptophan, the precursor of serotonin, is significantly lower in pregnant women at the end of term and the first few days after delivery than in nonpregnant women; and ii) both pregnancy and the early puerperium are accompanied by activation of the inflammatory response system. The aims of the present study were to examine the effects of pregnancy and delivery on plasma kynurenine, a major tryptophan catabolite synthesized after induction of indoleamine-2, 3 dioxygenase (IDO) by pro-inflammatory cytokines. We measured plasma kynurenine and tryptophan and immune markers, such as serum interleukin-6 (IL-6), IL-8 and the leukemia inhibitory factor–receptor (LIF-R) in healthy, nonpregnant and pregnant women at the end of term and one and three days after delivery. Plasma kynurenine was significantly lower in pregnant women at the end of term than in nonpregnant women, findings which may be attributed to lower plasma tryptophan at the end of term. The kynurenine/tryptophan (K/T) quotient was significantly higher in the pregnant women at the end of term and in the early puerperium than in nonpregnant women. In the early puerperium there was a significant increase in plasma kynurenine and the K/T quotient. The increases in plasma kynurenine and the K/T quotient were significantly more pronounced in women whose anxiety and depression scores significantly increased in the puerperium. The changes from the end of term to the early puerperium in plasma kynurenine and the K/T quotient were significantly related to those in the immune markers. It is concluded that 1) lower plasma kynurenine at the end of term is the consequence of lower plasma tryptophan; 2) the increased K/T quotient at the end of term and in the early puerperium indicates inflammation-induced degradation of tryptophan along the kynurenine pathway; and 3) that depressive and anxiety symptoms in the early puerperium are (causally) related to an increased catabolism of tryptophan into kynurenine, a phenomenon which probably results from immune activation. [Copyright &y& Elsevier]
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- 2002
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103. Increased serum interleukin-8 and interleukin-10 in schizophrenic patients resistant to treatment with neuroleptics and the stimulatory effects of clozapine on serum leukemia inhibitory factor receptor
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Maes, Michael, Bocchio Chiavetto, Luisella, Bignotti, Stefano, Battisa Tura, Giani-Jean, Pioli, Rosaria, Boin, Francesco, Kenis, Gunter, Bosmans, Eugene, de Jongh, Raf, and Altamura, Carlo A.
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SCHIZOPHRENIA , *CYTOKINES , *INTERLEUKIN-8 , *INTERLEUKIN-10 , *ANTIPSYCHOTIC agents - Abstract
There is now evidence that schizophrenia may be accompanied by an activation of the monocytic and T-helper-2 (Th-2) arms of cell-mediated immunity (CMI) and by various alterations in the Th-1 arm of CMI. There is also evidence that repeated administration of typical and atypical antipsychotics may result in negative immunomodulatory effects. This study was carried out to examine (1) the serum concentrations of interleukin-8 (IL-8), IL-10, the soluble CD8 (sCD8) and the leukemia inhibitory factor receptor (LIF-R) in nonresponders to treatment with typical neuroleptics as compared with normal volunteers and responders to treatment; and (2) the effects of atypical antipsychotics on the above immune variables. The latter were determined in 17 nonresponders to treatment with neuroleptics and in seven normal volunteers and 14 schizophrenic patients who had a good response to treatment with antipsychotic agents. The nonresponders had repeated measurements of the immune variables before, and 2 and 4 months after treatment with clozapine or risperidone. Serum IL-8 and IL-10 were significantly higher in schizophrenic patients than in normal controls. The serum concentrations of the sCD8 were significantly increased 2 months, but not 4 months, after starting treatment with atypical antipsychotics. Serum LIF-R concentrations were significantly increased 2 and 4 months after starting treatment with atypical antipsychotics. It is concluded that: (1) schizophrenia is characterized by an activation of both pro-inflammatory and anti-inflammatory aspects of cell-mediated immunity; (2) prolonged treatment with atypical antipsychotics may increase the anti-inflammatory capacity of the serum in schizophrenic patients by increasing serum LIF-R concentrations; and (3) short-term treatment with clozapine may induce signs of immune activation which disappear upon prolonged treatment. [Copyright &y& Elsevier]
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- 2002
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104. The Prolonged P[sub 300] Latency in Recently Detoxified Alcohol-Dependent Patients Is Related to Activation of the Inflammatory Response System.
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Maes, Michael, van West, Dirk, Nuyten, Dirk, Neels, Hugo, De Vos, Nathalie, De Bruyne, Stephan, and Degroote, Johan
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EVOKED potentials (Electrophysiology) , *ELECTROPHYSIOLOGY , *CYTOKINES , *INFLAMMATION , *IMMUNOLOGY - Abstract
The aims of this study were to examine the late components of the auditory event-related potentials (AERPs), i.e. N[sub 100] , P[sub 200] and P[sub 300] , in recently detoxified alcohol-dependent patients compared to normal controls and to investigate whether there is a relationship between alterations in these AERPs and signs of activation of the inflammatory response system (IRS). The study subjects consisted of 14 healthy volunteers and 14 recently detoxified alcohol-dependent patients. All subjects performed a two-tone auditory discrimination task, using a standard ‘oddball’ paradigm. The alcohol-dependent patients had their blood sampled to examine IRS markers, such as erythrocyte sedimentation rate (ESR), serum copper concentrations and the number of leukocytes. The P[sub 300] latency was significantly greater in recently detoxified alcohol-dependent patients than in normal controls. There were significant correlations between the P[sub 300] latency and the ESR (r = 0.84, p = 0.009), serum copper concentrations (r = 0.73, p = 0.01) and number of monocytes (r = 0.71, p = 0.006). It is concluded that the P[sub 300] latency is prolonged in detoxified, chronic alcohol-dependent patients and is positively related to indicators of IRS activation. It is hypothesized that activation of the IRS may play a role in the delayed P[sub 300] latency in recently detoxified, alcohol-dependent patients.Copyright © 2001 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]
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- 2001
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105. The immunoregulatory effects of antidepressants.
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Maes, Michael
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ANTIDEPRESSANTS , *IMMUNOREGULATION , *CYTOKINES , *MENTAL depression , *INTERLEUKIN-10 - Abstract
There is some evidence that major depression is accompanied by activation of the inflammatory-response system (IRS). It has been hypothesized that increased production of proinflammatory cytokines may play a role in the etiology of major depression. If increased production of proinflammatory cytokines is at all involved in the etiology of depression, one would expect antidepressive treatments to have negative immunoregulatory effects. This paper reviews the effects of antidepressants, such as tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), heterocyclic antidepressants (HCAs), serotonin-noradrenaline reuptake inhibitors (SNRIs), lithium, l-5-hydroxytroptophan (L-5-HTP), reversible inhibitors of MAO-A (RIMA) on the production of proinflammatory cytokines, e.g. interferon-γ (IFNγ), and negative immunoregulatory cytokines and agents, e.g. interleukin-10 (IL-10). In depressed patients, prolonged treatment with antidepressants and mood stabilizers normalizes signs of activation of the IRS, such as increased serum IL-6 and acute phase protein concentrations. In vitro, it has been shown that various types of antidepressive drugs, including TCAs (imipramine; clomipramine); SSRIs (citalopram, fluoxetine, sertraline); lithium; SNRIs (venlafaxine); HCAs (trazodone); RIMAs (moclobemide) and L-5-HTP significantly suppress the ratio of IFNγ/IL-10 production by peripheral blood immunocytes. These antidepressant drugs appear to have a common effect on the IRS, i.e. in vitro they increase the production of IL-10 by peripheral blood leukocytes. Thus, the results suggest that antidepressants have negative immunoregulatory effects. It may be speculated that antidepressants exert some of their antidepressant effects through their negative immunoregulatory capacities. Copyright © 2001 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]
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- 2001
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106. Psychiatric morbidity and comorbidity following accidental man-made traumatic events: incidence and risk factors.
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Maes, Michael, Mylle, Jacques, Delmeire, Laure, and Altamura, Carlo
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MENTAL depression , *BIPOLAR disorder , *ANXIETY - Abstract
Abstract The aims of this study were to examine the incidence and risk factors of major depression, bipolar disorder, psychoactive substance use, psychotic and anxiety disorders in relation to post-traumatic stress disorders (PTSD) in a study group exposed to two different traumatic events, i.e. 128 fire and 55 motor vehicle accident victims. Data have been collected 7-9 months after the traumatic event. The diagnosis of axis-I diagnoses, other than PTSD, was made according to DSM-III-R criteria using the Structured Interview according to the DSM-III-R. The incidence of new-onset major depression was 13.4%, generalised anxiety disorder (GAD) 12.6%, agoraphobia 10.2% and psychoactive substance use disorders 6%. Simple phobia, panic disorder and obsessive compulsive disorder had a much lower incidence (< 2.0%). Fifty-one percent of the victims with PTSD had one or more additional axis-I diagnoses, major depression (26.2%), agoraphobia (21.0%) and generalised anxiety disorder (24.6%) being the most common. Physical injury was the single best predictor for major depression. The best predictors for the development of new-onset anxiety disorders, other than PTSD, were: type and horror of the trauma, the ex tent of physical injury, the loss of control during the traumatic event, contextual stimuli, younger age and female sex. In conclusion: comorbid disorders, such as depression, GAD and agoraphobia, commonly occur within the first few months after man-made accidental traumata. Trauma variables, which are known to be related to the development of PTSD, are also related to the occurrence of these comorbid disorders. [ABSTRACT FROM AUTHOR]
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- 2000
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107. The mast cells - Cytokines axis in Autism Spectrum Disorder.
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Kovacheva, Eleonora, Gevezova, Maria, Maes, Michael, and Sarafian, Victoria
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AUTISM spectrum disorders , *MAST cells , *TRYPTASE , *CYTOKINES , *SOCIAL skills , *MOLECULAR interactions , *KOUNIS syndrome , *CYTOKINE receptors - Abstract
Autism Spectrum Disorder (ASD) is a neurodevelopmental disturbance, diagnosed in early childhood. It is associated with varying degrees of dysfunctional communication and social skills, repetitive and stereotypic behaviors. Regardless of the constant increase in the number of diagnosed patients, there are still no established treatment schemes in global practice. Many children with ASD have allergic symptoms, often in the absence of mast cell (MC) positive tests. Activation of MCs may release molecules related to inflammation and neurotoxicity, which contribute to the pathogenesis of ASD. The aim of the present paper is to enrich the current knowledge regarding the relationship between MCs and ASD by providing PPI network analysis-based data that reveal key molecules and immune pathways associated with MCs in the pathogenesis of autism. Network and enrichment analyzes were performed using receptor information and secreted molecules from activated MCs identified in ASD patients. Our analyses revealed cytokines and key marker molecules for MCs degranulation, molecular pathways of key mediators released during cell degranulation, as well as various receptors. Understanding the relationship between ASD and the activation of MCs, as well as the involved molecules and interactions, is important for elucidating the pathogenesis of ASD and developing effective future treatments for autistic patients by discovering new therapeutic target molecules. • PPI networks of key molecules and immune pathways related to MCs in ASD. • Involvement of receptors for MCs degranulation markers, TPSAB1 and cytokines in ASD. • Novel therapeutic strategies for ASD based on MCs and their molecular interactions. [ABSTRACT FROM AUTHOR]
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- 2024
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108. Reactivation of herpesvirus type 6 and IgA/IgM-mediated responses to activin-A underpin long COVID, including affective symptoms and chronic fatigue syndrome.
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Vojdani, Aristo, Almulla, Abbas F., Zhou, Bo, Al-Hakeim, Hussein K., and Maes, Michael
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POST-acute COVID-19 syndrome , *CORONAVIRUS diseases , *CHRONIC fatigue syndrome - Abstract
Background: Persistent infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), reactivation of dormant viruses, and immune-oxidative responses are involved in long COVID. Objectives: To investigate whether long COVID and depressive, anxiety, and chronic fatigue syndrome (CFS) symptoms are associated with IgA/IgM/IgG to SARS-CoV-2, human herpesvirus type 6 (HHV-6), Epstein-Barr Virus (EBV), and immune-oxidative biomarkers. Methods: We examined 90 long COVID patients and ninety healthy controls. We measured serum IgA/IgM/IgG against HHV-6 and EBV and their deoxyuridine 5′-triphosphate nucleotidohydrolase (duTPase), SARS-CoV-2, and activin-A, C-reactive protein (CRP), advanced oxidation protein products (AOPP), and insulin resistance (HOMA2-IR). Results: Long COVID patients showed significant elevations in IgG/IgM-SARS-CoV-2, IgG/IgM-HHV-6, and HHV-6-duTPase, IgA/IgM-activin-A, CRP, AOPP, and HOMA2-IR. Neural network analysis yielded a highly significant predictive accuracy of 80.6% for the long COVID diagnosis (sensitivity: 78.9%, specificity: 81.8%, area under the ROC curve = 0.876); the topmost predictors were as follows: IGA-activin-A, IgG-HHV-6, IgM-HHV-6-duTPase, IgG-SARS-CoV-2, and IgM-HHV-6 (all positively) and a factor extracted from all IgA levels to all viral antigens (inversely). The top 5 predictors of affective symptoms due to long COVID were IgM-HHV-6-duTPase, IgG-HHV-6, CRP, education, IgA-activin-A (predictive accuracy of r = 0.636). The top 5 predictors of CFS due to long COVID were in descending order: CRP, IgG-HHV-6-duTPase, IgM-activin-A, IgM-SARS-CoV-2, and IgA-activin-A (predictive accuracy: r = 0.709). Conclusion: Reactivation of HHV-6, SARS-CoV-2 persistence, and autoimmune reactions to activin-A combined with activated immune-oxidative pathways play a major role in the pathophysiology of long COVID as well as the severity of its affective symptoms and CFS. [ABSTRACT FROM AUTHOR]
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- 2024
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109. Changes in Platelet Alpha-2-Adrenoceptors in Fibromyalgia: Effects of Treatment with Antidepressants.
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Maes, Michael, Libbrecht, Isabelle, Delmeire, Laure, Lin, Aihua, De Clerck, Luc, Scharpe, Simon, and Janca, Aleksander
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FIBROMYALGIA , *ANTIDEPRESSANTS , *ALPHA adrenoceptors , *ADRENERGIC receptors , *CATECHOLAMINES , *BIOGENIC amines , *MENTAL depression - Abstract
The aim of this study was to determine platelet α[sub 2] -adrenergic receptor (α[sub 2] -AR) binding sites in fibromyalgia both before and after treatment with sertraline or placebo. The maximum number of binding sites (B[sub max] ) and their affinity (K[sub d] ) for [[sup 3] H]rauwolscine, a selective α[sub 2] -AR antagonist, were measured in 13 normal volunteers and 22 fibromyalgia patients. Severity of illness was evaluated by means of the Hamilton Depression Rating Scale (HDRS) and dolorimetric assessments of tenderness at tender points. Fibromyalgia patients had repeated measurements of [[sup 3] H]rauwolscine binding characteristics both before and after subchronic treatment with sertraline or placebo for 12 weeks. [[sup 3] H]rauwolscine binding K[sub d] values were significantly higher in fibromyalgia patients than in normal volunteers. There were significant inverse correlations between [[sup 3] H]rauwolscine binding K[sub d] values and duration of illness, age and lower energy. Significantly higher [[sup 3] H]rauwolscine binding K[sub d] values were found in fibromyalgia patients in an early phase of illness (<3 years) than in fibromyalgia patients with a protracted illness (>3 years). Repeated administration of sertraline had no significant effects on [[sup 3] H]rauwolscine binding B[sub max] or K[sub d] values. The results suggest that fibromyalgia and, in particular, fibromyalgia in an early phase of illness, is accompanied by lowered affinity of platelet α[sub 2] -ARs. [ABSTRACT FROM AUTHOR]
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- 1999
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110. The Effects of Psychological Stress on Leukocyte Subset Distribution in Humans: Evidence of Immune Activation.
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Maes, Michael, Van Bockstaele, Dirk R., Gastel, Ann Van, Song, Cai, Schotte, Chris, Neels, Hugo, DeMeester, Ingrid, Scharpe, Simon, and Janca, Aleksander
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PSYCHOLOGICAL stress , *LEUCOCYTES , *IMMUNOLOGY , *MENTAL health , *CYTOKINES - Abstract
The aim of the present study was to examine the effects of academic examination stress on leukocyte subset distribution in university students. Thirty-eight university students had repeated blood collections for white blood cell differentiation and flow cytometric assay of lymphocytic subsets a few weeks before and after (i.e. two baseline conditions) as well as the day before a difficult academic examination (i.e. stress condition). Flow cytometry was used to determine the number of peripheral blood mononuclear cells (PBMC). In students, who were reactors to psychological stress (criterion based on changes in the Perceived Stress Scale, PSS), but not in stress non-reactors, a significant increase in the number of neutrophils, monocytes, CD8[sup +] , CD2[sup +] CD26[sup +] , and CD2[sup +] HLA-DR[sup +] T cells and CD19[sup +] B cells, and significant reductions in the CD4[sup +] /CD8[sup +] T cell ratio were observed in the stress condition. There were significant and positive relationships between the stress-induced changes in perceived stress (PSS scale) and number of leukocytes, neutrophils, CD2[sup +] , CD2[sup +] CD26[sup +] and CD2[sup +] HLADR[sup +] T cells, and CD19[sup +] B cells. There were significant and negative relationships between the stress-induced changes in the CD4[sup +] /CD8[sup +] ratio and the stress-induced changes in the PSS scale. Female students taking oral contraceptives showed significantly higher stress-induced responses in number of leukocytes, neutrophils and CD19[sup +] B cells than male and female students without use of oral contraceptives. The results suggest that academic examination stress induces changes in the distribution of PBMC, which indicate immune activation and which are probably orchestrated by a stress-induced production of cytokines. [ABSTRACT FROM AUTHOR]
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- 1999
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111. Immune Disturbances in Treatment-Resistant Depression: Modulation by Antidepressive Treatments.
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Maes, Michael, Vandoolaeghe, Eric, Van Hunsel, Fran, Bril, Tania, Demedts, Paul, Wauters, Annick, and Neels, Hugo
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MENTAL depression , *T cells , *B cells , *LEUCOCYTES , *NEUTROPHILS - Abstract
Recently, there were some reports that major depression is accompanied by significant alterations in the percentage and number of peripheral blood mononuclear cells (PBMCs), such as increased number of CD4[sup +] T cells, B cells (e.g. CD19[sup +] , CD21[sup +] ), number of leukocytes, monocytes and neutrophils and an increased CD4[sup +] /CD8[sup +] T-cell ratio. The aims of the present study were to examine the number and percentage of PBMCs in major and treatment-resistant depressed (TRD) patients and the effects of antidepressant treatments on those PBMCs. Major depression was characterized by a significantly higher number of leukocytes and CD4[sup +] T-cells, a higher percentage of CD2[sup +] T cells and CD4[sup +] T cells, and a higher CD4[sup +] /CD8[sup +] T-cell ratio than normal controls. Patients with TRD had a significantly higher percentage of CD4[sup +] T cells and CD4[sup +] /CD8[sup +] T-cell ratio, and a significantly lower percentage of CD8[sup +] T cells than non-TRD patients and normal controls. There were significant negative correlations between the length of the index episode or duration of illness and number or percentage of monocytes. Subchronic treatment with antidepressants significantly reduced the number of leukocytes and neutrophils, but had no effect either on the absolute number of the other PBMCs or on the CD4[sup +] /CD8[sup +] T-cell ratio. The results suggest that (i) the higher CD4[sup +] /CD8[sup +] T-cell ratio in major depression is a trait marker of that illness and of treatment resistance; (ii) the increased numbers of leukocytes and neutrophils are state markers of depression and are reduced by ‘subchronic’ antidepressant therapy; (iii) the number and percentage of monocytes decrease with respect to duration of illness and length of the index depressive episode. © 1997 by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]
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- 1997
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112. Haptoglobin phenotypes and gene frequencies in unipolar major depression.
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Maes, Michael and Delanghe, Joris
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HAPTOGLOBINS , *MENTAL depression genetics - Abstract
Investigates haptoglobin plasma levels and phenotype and gene frequencies in unipolar major depression. Haptoglobin plasma levels and the depressive state; Distribution of haptoglobin phenotypes; Distribution of haptoglobin genotypes; Pitfalls of the study.
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- 1994
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113. Seasonality in violent suicide but not in nonviolent suicide or homicide.
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Maes, Michael and Cosyns, Paul
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SUICIDE , *HOMICIDE - Abstract
Determines seasonality and other significant rhythms in violent and nonviolent suicide, alone and together, and homicide. Analysis of Belgian data on suicide, violent suicide, nonviolent suicide and homicide; Significant seasonality for suicide but not for homicide; Seasonality in violent suicide but not in nonviolent suicide; Relationship of violent suicide with age and prominence among men.
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- 1993
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114. Interleukin-1beta: A putative mediator of HPA axis hyperactivity in major depression?
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Maes, Michael and Bosmans, Eugene
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INTERLEUKIN-1 , *MENTAL depression , *HYPOTHALAMIC-pituitary-adrenal axis - Abstract
Investigates the relationship of interleukin-1beta production to hypothalamic-pituitary-adrenal (HPA) axis activity in depressed subjects. Measurement of subjects' cortisol levels and mitogen-stimulated supernatant interleukin-1beta production; Positive correlations between interleukin-1beta production and post-dexamethasone suppression test (DST) cortisol values.
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- 1993
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115. How to Construct a Bottom-Up Nomothetic Network Model and Disclose Novel Nosological Classes by Integrating Risk Resilience and Adverse Outcome Pathways with the Phenome of Schizophrenia.
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Maes, Michael, Vojdani, Aristo, Galecki, Piotr, and Kanchanatawan, Buranee
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SCHIZOPHRENIA , *COGNITION disorders , *HOSTILITY , *PATTERN recognition systems , *OXIDATIVE stress , *SYMPTOMS - Abstract
Current case definitions of schizophrenia (DSM-5, ICD), made through a consensus among experts, are not cross-validated and lack construct reliability validity. The aim of this paper is to explain how to use bottom-up pattern recognition approaches to construct a reliable and replicable nomothetic network reflecting the direct effects of risk resilience (RR) factors, and direct and mediated effects of both RR and adverse outcome pathways (AOPs) on the schizophrenia phenome. This study was conducted using data from 40 healthy controls and 80 patients with schizophrenia. Using partial least squares (PLS) analysis, we found that 39.7% of the variance in the phenomenome (lowered self-reported quality of life) was explained by the unified effects of AOPs (IgA to tryptophan catabolites, LPS, and the paracellular pathway, cytokines, and oxidative stress biomarkers), the cognitome (memory and executive deficits), and symptomatome (negative symptoms, psychosis, hostility, excitation, mannerism, psychomotor retardation, formal thought disorders); 55.8% of the variance in the symptomatome was explained by a single trait extracted from AOPs and the cognitome; and 22.0% of the variance in the latter was explained by the RR (Q192R polymorphism and CMPAase activity, natural IgM, and IgM levels to zonulin). There were significant total effects (direct + mediated) of RR and AOPs on the symptomatome and the phenomenome. In the current study, we built a reliable nomothetic network that reflects the associations between RR, AOPs, and the phenome of schizophrenia and discovered new diagnostic subclasses of schizophrenia based on unified RR, AOPs, and phenome scores. [ABSTRACT FROM AUTHOR]
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- 2020
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116. Adverse childhood experiences and recent negative events are associated with activated immune and growth factor pathways, the phenome of first episode major depression and suicidal behaviors.
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Almulla, Abbas F., Algon, Ali Abbas Abo, and Maes, Michael
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GROWTH factors , *ADVERSE childhood experiences , *PLATELET-derived growth factor , *MENTAL depression , *SUICIDAL behavior - Abstract
• First episode major depression is accompanied by increased adverse childhood experiences (ACEs) and negative life events (NLEs). • A significant part of the impact of ACEs and NLEs on the major depression phenome is mediated by activated immune and growth factors networks. • ACEs and NLEs are highly significantly correlated with different cytokines/chemokines/growth factors, especially with interleukin (IL)−16, CCL27, stem cell growth factor, and platelet-derived growth factor. This research assessed the effects of adverse childhood experiences (ACEs) and negative life events (NLEs) on forty-eight cytokines/chemokines/growth factors, in 71 FE-MDMD patients and forty heathy controls. ACEs are highly significantly associated with the classical M1 macrophage, T helper (Th)-1, Th-1 polarization, IRS, and neurotoxicity immune profiles, and not with the alternative M2, and Th-2 immune profiles. There are highly significant correlations between ACEs and NLEs and different cytokines/chemokines/growth factors, especially with interleukin (IL)-16, CCL27, stem cell growth factor, and platelet-derived growth factor. Partial Least Squares analysis showed that 62.3 % of the variance in the depression phenome (based on severity of depression, anxiety and suicidal behaviors) was explained by the regression on IL-4 (p = 0.001, inversely), the sum of ACEs + NLEs (p < 0.0001), and a vector extracted from 10 cytokines/chemokines/growth factors (p < 0.0001; both positively associated). The latter partially mediated (p < 0.0001) the effects of ACE + NLEs on the depression phenome. In conclusion, part of the effects of ACEs and NLEs on the depression phenome is mediated via activation of immune and growth factor networks. These pathways have a stronger impact in subjects with lowered activities of the compensatory immune-regulatory system. [ABSTRACT FROM AUTHOR]
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- 2024
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117. Intersections between pneumonia, lowered oxygen saturation percentage and immune activation mediate depression, anxiety, and chronic fatigue syndrome-like symptoms due to COVID-19: A nomothetic network approach.
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Al-Jassas, Hawraa Kadhem, Al-Hakeim, Hussein Kadhem, and Maes, Michael
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OXYGEN saturation , *SYMPTOMS , *COVID-19 , *ANGIOTENSIN converting enzyme , *LUNG diseases , *APATHY , *SOMATOFORM disorders - Abstract
Background: COVID-19 is associated with neuropsychiatric symptoms including increased depressive, anxiety and chronic fatigue-syndrome (CFS)-like and physiosomatic symptoms.Aims: To delineate the associations between affective and CFS-like symptoms in COVID-19 and chest computed tomography scan anomalies (CCTAs), oxygen saturation (SpO2), interleukin (IL)-6, IL-10, C-Reactive Protein (CRP), albumin, calcium, magnesium, soluble angiotensin converting enzyme (ACE2) and soluble advanced glycation products (sRAGEs).Method: The above biomarkers were assessed in 60 COVID-19 patients and 30 healthy controls who had measurements of the Hamilton Depression (HDRS) and Anxiety (HAM-A) and the Fibromyalgia and Chronic Fatigue (FF) Rating Scales.Results: Partial Least Squares-SEM analysis showed that reliable latent vectors could be extracted from a) key depressive and anxiety and physiosomatic symptoms (the physio-affective or PA-core), b) IL-6, IL-10, CRP, albumin, calcium, and sRAGEs (the immune response core); and c) different CCTAs (including ground glass opacities, consolidation, and crazy paving) and lowered SpO2% (lung lesions). PLS showed that 70.0% of the variance in the PA-core was explained by the regression on the immune response and lung lesions latent vectors. One common "infection-immune-inflammatory (III) core" underpins pneumonia-associated CCTAs, lowered SpO2 and immune activation, and this III core explains 70% of the variance in the PA core, and a relevant part of the variance in melancholia, insomnia, and neurocognitive symptoms.Discussion: Acute SARS-CoV-2 infection is accompanied by lung lesions and lowered SpO2 which may cause activated immune-inflammatory pathways, which mediate the effects of the former on the PA-core and other neuropsychiatric symptoms due to SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]- Published
- 2022
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118. A proof-of-concept study of maternal immune activation mediated induction of Toll-like receptor (TLR) and inflammasome pathways leading to neuroprogressive changes and schizophrenia-like behaviours in offspring.
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Talukdar, Pinku Mani, Abdul, Fazal, Maes, Michael, Berk, Michael, Venkatasubramanian, Ganesan, Kutty, Bindu M., and Debnath, Monojit
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MATERNAL immune activation , *INFLAMMASOMES , *TOLL-like receptors , *SPRAGUE Dawley rats , *NEURAL inhibition - Abstract
Infection, particularly prenatal infection, leads to an enhanced risk of schizophrenia in the offspring. Interestingly, few data exist on the pathway(s) such as TLR and inflammasome, primarily involved in sensing the microorganisms and inducing downstream inflammatory responses, apoptosis and neuroprogressive changes that drive prenatal infection-induced risk of schizophrenia. Herein, we aimed to discern whether prenatal infection-induced maternal immune activation (MIA) causes schizophrenia-like behaviours through activation of TLR and inflammasome pathways in the brain of offspring. Sprague Dawley rats (n=15/group) were injected either with poly (I:C) or LPS or saline at gestational day (GD)-12. Significantly elevated plasma levels of IL-6, TNF-α and IL-17A assessed after 24 hours were observed in both the poly (I:C) and LPS-treated rats, while IL-1β was only elevated in LPS-treated rats, indicating MIA. The offspring of poly (I:C)-and LPS-treated dams displayed increased anxiety-like behaviours, deficits in social behaviours and prepulse inhibition. The hippocampus of offspring rats showed increased expression of Tlr3, Tlr4, Nlrp3, Il1b, and Il18 of poly (I:C) and Tlr4, Nlrp3, Cas1, Il1b, and Il18 of LPS-treated dams. Furthermore, Tlr and inflammasome genes were associated with social deficits and impaired prepulse inhibition in offspring rats. The results suggest that MIA due to prenatal infection can trigger TLR and inflammasome pathways and enhances the risk of schizophrenia-like behaviours in the later stages of life of the offspring. [ABSTRACT FROM AUTHOR]
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- 2021
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119. Neuronal damage and inflammatory biomarkers are associated with the affective and chronic fatigue-like symptoms due to end-stage renal disease.
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Al-Hakeim, Hussein Kadhem, Twaij, Basim Abd Al-Raheem, Al-Naqeeb, Tabarek Hadi, Moustafa, Shatha Rouf, and Maes, Michael
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INTERMEDIATE filament proteins , *GLIAL fibrillary acidic protein , *CHRONIC kidney failure , *MYELIN basic protein , *CANCER fatigue , *KIDNEY function tests - Abstract
Many biochemical, immunological, and neuropsychiatric changes are associated with end-stage renal disease (ESRD). Neuronal damage biomarkers such as glial fibrillary acidic protein (GFAP), neurofilament light chain (NFL), S100 calcium-binding protein B (S100B), ionized calcium-binding adaptor molecule-1 (IBA1), and myelin basic protein (MBP) are among the less-studied biomarkers of ESRD. We examined the associations between these neuro-axis biomarkers, inflammatory biomarkers, e.g., C-reactive protein (CRP), interleukin (IL-6), IL-10, and zinc, copper, and neuropsychiatric symptoms due to ERSD. ELISA techniques were used to measure serum levels of neuronal damage biomarkers in 70 ESRD patients, and 46 healthy controls. ESRD patients have higher scores of depression, anxiety, fatigue, and physiosomatic symptoms than healthy controls. Aberrations in kidney function tests and the number of dialysis interventions are associated with the severity of depression, anxiety, fibro-fatigue and physiosomatic symptoms, peripheral inflammation, nestin, and NFL. Serum levels of neuronal damage biomarkers (NFL, MBP, and nestin), CRP, and interleukin (IL)-10 are elevated, and serum zinc is decreased in ESRD patients as compared with controls. The neuronal damage biomarkers NFL, nestin, S100B and MBP are associated with the severity of one or more neuropsychiatric symptom domains. Around 50 % of the variance in the neuropsychiatric symptoms is explained by NFL, nestin, S00B, copper, and an inflammatory index. The severity of renal dysfunction and/or the number of dialysis interventions may induce peripheral inflammation and, consequently, neurotoxicity to intermediate filament proteins, astrocytes, and the blood-brain barrier, leading to the neuropsychiatric symptoms of ESRD. • ESRD patients have higher scores of depression, anxiety, and fatigue. • Kidney function decline and dialysis treatments cause peripheral inflammation. • NFL, MBP, and nestin are associated with the severity of neuropsychiatric symptoms. • Serum levels of NFL, MBP, nestin, CRP, and IL-10 are elevated in ESRD patients. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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120. Effect of early screen media multitasking on behavioural problems in school-age children.
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Srisinghasongkram, Pornchada, Trairatvorakul, Pon, Maes, Michael, and Chonchaiya, Weerasak
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HUMAN multitasking , *BEHAVIOR disorders , *SCREEN time - Abstract
Screen media multitasking (SMM), the act of exposure ≥ 2 screen media simultaneously, is increasing nowadays. Single media use was associated with child's behavioural problems in previous studies. However, the associations between SMM since early childhood and behavioural problems in school-age children had not been elucidated. This study aimed to investigate the association between SMM from age 6 months to 4 years and behavioural problems in 6-year-old children. Two hundred and ninety-one (52.6% girls) healthy children were enrolled since age 6 months and 259 participants were followed-up until age 6 years. SMM was obtained at age 6, 12, 18, 24 months, 3 and 4 years. Behavioural concerns were assessed at age 4 years by the Child Behaviour Checklist and by both the Strengths and Difficulties Questionnaire with the Conners Kiddie Continuous Performance Test at age 6 years. Parenting style, cognitive ability, and baseline characteristics were also ascertained. Partial least squares path modelling was performed to determine both direct and indirect relationships among variables. Results showed that children who had been exposed to SMM for longer duration, specifically at age 18 months, showed more behavioural problems at age 4 and 6 years. Positive parenting during preschool and behavioural concerns at age 4 years were main mediators of those associations. Moreover, SMM in minutes at age 18 months was related to decreased preschool cognition. To minimise behavioural problems in school-age children, SMM should be avoided before 2 years of age so that positive parenting may be successfully implemented since early childhood. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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121. A videotape as introduction for cognitive behavioral therapy with depressed inpatients.
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Schotte, Chris and Maes, Michael
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THERAPEUTICS , *MENTAL depression - Abstract
Reports on the use of the psychoeducational videotape `Depression...the answers' in cognitive behavioral therapy. Introduction, facilitation and clarification of the psychotherapeutic and pharmacological treatment; Didactic advantage of attention; Description of the parts of the videotape; Methodology of study; Recommendation for use in cognitive behavioral treatment programs.
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- 1993
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122. In schizophrenia, immune-inflammatory pathways are strongly associated with depressive and anxiety symptoms, which are part of a latent trait which comprises neurocognitive impairments and schizophrenia symptoms.
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Almulla, Abbas F., Al-Rawi, Khalid F., Maes, Michael, and Al-Hakeim, Hussein Kadhem
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MENTAL depression , *SCHIZOPHRENIA , *COGNITION disorders , *HOSTILITY , *OPIOID receptors , *SEMANTIC memory - Abstract
Background: The aim is to examine whether biomarkers of the immune-inflammatory response (IRS) and endogenous opioid (EOS) systems are associated with affective symptoms in schizophrenia.Methods: We recruited 115 schizophrenia patients and 43 healthy controls and assessed the Hamilton Depression (HDRS) and Anxiety (HAM-A) rating Scale scores as well as serum levels of interleukin (IL)-6, IL-10, eotaxin (CCL11), high mobility group box 1 (HMGB1), Dickkopf-related protein 1 (DKK1), and mu (MOR) and kappa (KOR) opioid receptors.Results: The HDRS and HAM-A scores are significantly and positively correlated with a) psychosis, hostility, excitation, mannerism, negative symptoms, psychomotor retardation, and formal thought disorders; and b) lowered scores on semantic and episodic memory, executive functions, and attention tests as measured with the Brief Assessment of Cognition in Psychiatry. Both HDRS and HAM-A are significantly increased in non-responders to treatment as compared with partial responders. Both affective scores are strongly associated with a latent vector extracted from all symptoms, reflecting overall severity of schizophrenia symptoms (OSOS), and neurocognitive test scores, reflecting a generalized cognitive decline (G-CoDe). The HDRS score was strongly and positively associated with IL-6, HMGB1, KOR, and MOR levels, and the HAM-A score with IL-6, IL-10, CCL11, HMGB1, KOR, and MOR levels. A single latent trait may be extracted from OSOS, G-CoDe, and the HDRS and HAMA scores, and this latent vector score is strongly predicted by HMGB1, MOR, and DKK1.Conclusion: Immune-inflammatory and EOS pathways contribute to the phenome of schizophrenia, which comprises OSOS, affective, and physiosomatic symptoms, and G-CoDe. [ABSTRACT FROM AUTHOR]- Published
- 2021
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123. Exploring Clinical Subgroups of Participants with Major Depressive Disorder that may Benefit from Adjunctive Minocycline Treatment.
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Anmella, Gerard, Meehan, Alcy, Ashton, Melanie, Mohebbi, Mohammadreza, Fico, Giovanna, Ng, Chee H., Maes, Michael, Berk, Lesley, De Prisco, Michele, Singh, Ajeet B., Malhi, Gin S., Berk, Michael, Dodd, Seetal, Hidalgo-Mazzei, Diego, Grande, Iria, Pacchiarotti, Isabella, Murru, Andrea, Vieta, Eduard, and Dean, Olivia M.
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MENTAL depression , *MINOCYCLINE , *COMORBIDITY , *DULOXETINE , *CLINICAL trials - Abstract
Objective: To explore illness-related factors in patients with major depressive disorder (MDD) recipients of adjunctive minocycline (200 mg/day) treatment. The analysis included participants experiencing MDD from a 12-week, double blind, placebo-controlled, randomized clinical trial (RCT). Methods: This is a sub-analysis of a RCT of all 71 participants who took part in the trial. The impact of illness chronicity (illness duration and number of depressive episodes), systemic illness (endocrine, cardiovascular and obesity), adverse effects and minocycline were evaluated as change from baseline to endpoint (12-week) using ANCOVA. Results: There was a consistent but statistically non-significant trend on all outcomes in favour of the use of adjunctive minocycline for participants without systemic illness, less illness chronicity, and fewer adverse effects. Conclusion: Understanding the relationship between MDD and illness chronicity, comorbid systemic illness, and adverse effects, can potentially better characterise those individuals who are more likely to respond to adjunctive anti-inflammatory medications. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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124. The glutathione system in Parkinson's disease and its progression.
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Bjørklund, Geir, Peana, Massimiliano, Maes, Michael, Dadar, Maryam, and Severin, Beatrice
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PARKINSON'S disease , *GLUTATHIONE , *DISEASE progression , *OXIDATIVE stress , *REACTIVE oxygen species - Abstract
• Low GSH metabolism is linked to the pathophysiology of Parkinson's disease (PD). • It is unclear if GSH deficiency is an etiological factor in PD or a consequence of it. • In the future, external modulation of GSH levels may be used in the treatment of PD. • More research is needed on active neuroprotective and anti-neuroinflammatory agents. Redox dysfunctions and neuro-oxidative stress play a major role in the pathophysiology and progression of Parkinson's disease (PD). Glutathione (GSH) and the reduced/oxidized glutathione (GSH/GSSG) ratio are lowered in oxidative stress conditions and may lead to increased oxidative toxicity. GSH is involved not only in neuro-immune and neuro-oxidative processes, including thiol redox signaling, but also in cell proliferation and differentiation and in the regulation of cell death, including apoptotic pathways. Lowered GSH metabolism and a low GSH/GSSG ratio following oxidative stress are associated with mitochondrial dysfunctions and constitute a critical factor in the neuroinflammatory and neurodegenerative processes accompanying PD. This review provides indirect evidence that GSH redox signaling is associated with the pathophysiology of PD. Nevertheless, it has not been delineated whether GSH redox imbalances are a causative factor in PD or whether PD-associated pathways cause the GSH redox imbalances in PD. The results show that antioxidant approaches, including neuroprotective and anti-neuroinflammatory agents, which neutralize reactive oxygen species, may have therapeutic efficacy in the treatment of PD and its progression. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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125. Interactions of Tryptophan and Its Catabolites With Melatonin and the Alpha 7 Nicotinic Receptor in Central Nervous System and Psychiatric Disorders: Role of the Aryl Hydrocarbon Receptor and Direct Mitochondria Regulation.
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Anderson, George and Maes, Michael
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TRYPTOPHAN , *MELATONIN , *CENTRAL nervous system diseases , *PATHOLOGICAL psychology , *ARYL hydrocarbon receptors , *MITOCHONDRIA - Abstract
Recent work indicates an intimate interaction of the tryptophan catabolite (TRYCAT) pathways with the melatonergic pathways, primarily via TRYCAT pathway induction taking tryptophan away from the production of serotonin, which is a necessary precursor for the melatonergic pathways. The alpha 7 nicotinic receptor may be significantly modulated by this interaction, given its inactivation by the TRYCAT, kynurenic acid, and its induction by melatonin. Similarly, the aryl hydrocarbon receptor is activated by both kynurenic acid and kynurenine, leading to CYP1A2 and melatonin metabolism, whereas melatonin may act to inhibit the aryl hydrocarbon receptor. These 2 receptors and pathways may therefore be intimately linked, with relevance to a host of intracellular processes of clinical relevance. In this article, these interactions are reviewed. Interestingly, mitochondria may be a site for direct interactions of these pathways and receptors, suggesting that their differential induction may not only be modulating neuronal, glia, and immune cell processes and activity but also be directly acting to regulate mitochondrial functioning. This is likely to have significant consequences as to how an array of diverse central nervous system and psychiatric conditions are conceptualized and treated. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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126. Immune to happiness - inflammatory process indicators and depressive personality traits.
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Talarowska, Monika E., Kowalczyk, Małgorzata, Maes, Michael, Carvalho, Andre, Su, Kuan-Pin, Szemraj, Janusz, and Gałecki, Piotr
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PERSONALITY , *DYSTHYMIC disorder , *MINNESOTA Multiphasic Personality Inventory , *NITRIC-oxide synthases , *INFLAMMATION , *CYCLOOXYGENASE 2 - Abstract
Introduction: Nowadays, depression is conceptualized as an immune-inflammatory and oxidative stress disorder associated with neuroprogressive changes as a consequence of peripherally activated immune-inflammatory pathways, including peripheral cytokines and immune cells which penetrate into the brain via the blood barrier, as well as nitro-oxidative stress and antioxidant imbalances. The aim of this study was to investigate whether personality traits predisposing to a depressive episode (hypochondria, dysthymic, hysteria) are associated with changes in peripheral gene expression for selected indicators of inflammation and oxidative balance.Material and Methods: One hundred four people meeting the diagnostic criteria specified for a depressive episode took part in the study. Selected scales of the Minnesota Multiphasic Personality Inventory (MMPI-2) were used to measure personality traits. Expression at the mRNA and protein level for manganese superoxide dismutase (MnSOD), myeloperoxidase (MPO), cyclooxygenase 2 (COX-2), inducible nitric oxide synthase (iNOS), and metalloproteinases 2 and 9 (MMP-2, MMP-9) was examined.Results: Scales for the neurotic triad of the MMPI-2 test correlated significantly with the expression at the level of mRNA and protein for MnSOD, MPO and metalloproteinases 2 and 9.Conclusions: The scales specified for the neurotic triad of the MMPI-2 test correspond substantially with the expression of MnSOD, MPO and metalloproteinases 2 and 9 at the mRNA and protein levels in the group of patients suffering from depression. [ABSTRACT FROM AUTHOR]- Published
- 2020
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127. Influence of treatments on cell adhesion molecules in patients with systemic lupus erythematosus and rheumatoid arthritis: a review.
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da Rosa Franchi Santos, Lorena Flor, Costa, Neide Tomimura, Maes, Michael, Simão, Andréa Name Colado, and Dichi, Isaias
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CELL adhesion molecules , *SYSTEMIC lupus erythematosus , *ANTIRHEUMATIC agents , *RHEUMATOID arthritis , *VASCULAR cell adhesion molecule-1 , *CELL adhesion - Abstract
Background: Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are autoimmune diseases characterized by changes in cell adhesion molecules (CAMs). Objective: To review the influence of the main drugs used in the treatment of SLE and RA on CAM levels. Methods: A bibliographic search was performed using electronic databases. The research included human studies, in vivo or in vitro, with an experimental or observational design, and with no limit of publication date or number of subjects. Animal studies and non-standard treatments were not considered. Results: We included 21 studies, 3 on SLE and 18 on RA with monotherapy or combined trials. The most used drugs were cyclophosphamide (CY, in 2 studies) and methylprednisolone pulse (pMP, n = 2) in SLE; and methotrexate (MTX, n = 9) and infliximab (IFX, n = 4) in RA. In addition, the most frequently examined CAMs to predict response to treatment were vascular cell adhesion molecule-1 (VCAM-1, n = 2) in SLE, and intercellular adhesion molecule-1 (ICAM-1, n = 12), VCAM-1 (n = 12), and E-selectin (n = 14) in RA. After treatment, CAM levels were decreased in SLE and RA patients with active disease. Conclusions: It is concluded that the CAM biomarkers may reflect disease activity and the response to treatment in SLE and RA patients. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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128. The Neuroimmune and Neurotoxic Fingerprint of Major Neurocognitive Psychosis or Deficit Schizophrenia: a Supervised Machine Learning Study.
- Author
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Al-Hakeim, Hussein Kadhem, Almulla, Abbas F., and Maes, Michael
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SUPERVISED learning , *MACHINE learning , *SCHIZOPHRENIA , *PSYCHOSES , *BIOMARKERS , *PERITONEAL macrophages , *MACROPHAGES - Abstract
No studies have examined the immune fingerprint of major neurocognitive psychosis (MNP) or deficit schizophrenia using M1 macrophage cytokines in combination with chemokines such as CCL2 and CCL11. The present study delineated the neuroimmune fingerprint of MNP by analyzing plasma levels of IL-1β, sIL-1RA, TNFα, sTNFR1, sTNFR2, CCL2, and CCL11 in 120 MNP versus 54 healthy controls in association with neurocognitive scores (as assessed with the Brief Assessment of Cognition in Schizophrenia) and PHEMN (psychotic, hostility, excitation, mannerism and negative) symptoms. MNP was best predicted by a combination of CCL11, TNFα, IL-1β, and sIL-1RA which yielded a bootstrapped (n = 2000) area under the receiver operating curve of 0.985. Composite scores reflecting M1 macrophage activity and neurotoxic potential including effects of CCL11 and CCL2 were significantly increased in MNP. A large part of the variance in PHEM (38.4–52.6%) and negative (65.8–74.4%) symptoms were explained by combinations of immune markers whereby CCL11 was the most important. The same markers explained a large part of the variance in the Mini-Mental State examination, list learning, digit sequencing task, category instances, controlled word association, symbol coding, and Tower of London. Partial least squares analysis showed that 72.7% of the variance in overall severity of schizophrenia was explained by the regression on IL-1β, sIL-1RA, CCL11, TNFα, and education. It is concluded that the combination of the abovementioned markers defines MNP as a distinct neuroimmune disorder and that increased immune neurotoxicity determines memory and executive impairments and PHEMN symptoms as well. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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129. Serum agrin and talin are increased in major depression while agrin and creatine phosphokinase are associated with chronic fatigue and fibromyalgia symptoms in depression.
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Al-Hakeim, Hussein Kadhem, Al-Issa, Ameer Abdul Razzaq, and Maes, Michael
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CREATINE kinase , *FIBROMYALGIA , *FATIGUE (Physiology) , *MENTAL depression , *HAMILTON Depression Inventory , *BECK Depression Inventory , *MUSCLE proteins - Abstract
Chronic fatigue and fibromyalgia symptoms frequently occur in major depressive disorder (MDD). The pathophysiology of these symptoms may in part, be ascribed to activated immune pathways, although it is unclear whether muscular factors play a role in their onset. The aim of the present study is to examine the role of muscle proteins in major depression in association with symptoms of chronic fatigue and fibromyalgia. We measured serum levels of agrin, talin-2, titin, and creatine phosphokinase (CPK) as well as the FibroFatigue (FF), the Hamilton Depression Rating Scale (HAM-D) and the Beck Depression Inventory (BDI-II) scores in 60 MDD patients and 30 healthy controls. The results show a significant increase in agrin and talin-2 in MDD patients as compared with controls. There were highly significant correlations between agrin and HAM-D, BDI-II and FF scores. Agrin, but not talin or titin, was significantly and positively associated with all 12 items of the FF scale. We found that a large part of the variance in HAM-D (47.4%), BDI-II (43.4%) and FF (43.5%) scores was explained by the regression on agrin, smoking, female sex (positively associated) and education (inversely associated). CPK was significantly and inversely associated with the total FF score and with muscle and gastro-intestinal symptoms, fatigue, a flu-like malaise, headache and memory, autonomic and sleep disturbances. These results suggest that aberrations in neuromuscular (NMJs) and myotendinous junctions play a role in MDD and that the aberrations in NMJs coupled with lowered CPK may play a role in chronic fatigue and fibromyalgia symptoms in MDD. Moreover, the increase of agrin in MDD probably functions as part of the compensatory immune-regulatory system (CIRS). [ABSTRACT FROM AUTHOR]
- Published
- 2020
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130. Increased AGE–RAGE axis stress in methamphetamine abuse and methamphetamine‐induced psychosis: Associations with oxidative stress and increased atherogenicity.
- Author
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Al‐Hakeim, Hussein Kadhem, Altufaili, Mazin Fadhil, Alhaideri, Amer Fadhil, Almulla, Abbas F., Moustafa, Shatha Rouf, and Maes, Michael
- Subjects
- *
METHAMPHETAMINE abuse , *OXIDATIVE stress , *ADVANCED glycation end-products , *PSYCHOSES , *COPPER - Abstract
Methamphetamine (MA)‐induced psychosis (MIP) is associated with increased oxidative toxicity (especially lipid peroxidation) and lowered antioxidant defences. Advanced glycation end products (AGEs) cause oxidative stress upon ligand binding to AGE receptors (RAGEs). There is no data on whether MA use may cause AGE–RAGE stress or whether the latter is associated with MIP. This case–control study recruited 60 patients with MA use disorder and 30 normal controls and measured serum levels of oxidative stress toxicity (OSTOX, lipid peroxidation), antioxidant defences (ANTIOX), magnesium, copper, atherogenicity, AGE and soluble RAGE (sRAGE) and computed a composite reflecting AGE–RAGE axis activity. MA dependence and use were associated with elevated levels of AGE, sRAGE, OSTOX/ANTIOX, Castelli Risk Index 1 and atherogenic index of plasma. Increased sRAGE concentrations were strongly correlated with dependence severity and MA dose. Increased AGE–RAGE stress was correlated with OSTOX, OSTOX/ANTIOX and MA‐induced intoxication symptoms, psychosis, hostility, excitement and formal thought disorders. The regression on AGE–RAGE, the OSTOX/ANTIOX ratio, decreased magnesium and increased copper explained 54.8% of the variance in MIP symptoms, and these biomarkers mediated the effects of increasing MA concentrations on MIP symptoms. OSTOX/ANTIOX, AGE–RAGE and insufficient magnesium were found to explain 36.0% of the variance in the atherogenicity indices. MA causes intertwined increases in AGE–RAGE axis stress and oxidative damage, which together predict the severity of MIP symptoms and increased atherogenicity. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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131. Reverse cholesterol transport and lipid peroxidation biomarkers in major depression and bipolar disorder: A systematic review and meta-analysis.
- Author
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Almulla, Abbas F., Thipakorn, Yanin, Algon, Ali Abbas Abo, Tunvirachaisakul, Chavit, Al-Hakeim, Hussein K., and Maes, Michael
- Subjects
- *
BIPOLAR disorder , *MENTAL depression , *HDL cholesterol , *AFFECTIVE disorders , *UBIQUINONES - Abstract
• Major depression (MDD) and bipolar disorder (BD) are accompanied by significantly reduced reverse cholesterol transport (RCT). • The pathophysiology of MDD and BD involves increased lipid peroxidation and a lowered lipid antioxidant defense system. • There is an increased autoimmune response against neoepitopes formed due to oxidative damage of the lipids. Major depression (MDD) and bipolar disorder (BD) are linked to immune activation, increased oxidative stress, and lower antioxidant defenses. To systematically review and meta -analyze all data concerning biomarkers of reverse cholesterol transport (RCT), lipid-associated antioxidants, lipid peroxidation products, and autoimmune responses to oxidatively modified lipid epitopes in MDD and BD. Databases including PubMed, Google scholar and SciFinder were searched to identify eligible studies from inception to January 10th, 2023. Guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. The current meta -analysis included 176 studies (60 BD and 116 MDD) and examined 34,051 participants, namely 17,094 with affective disorders and 16,957 healthy controls. Patients with MDD and BD showed a) significantly decreased RCT (mainly lowered high-density lipoprotein cholesterol and paraoxonase 1); b) lowered lipid soluble vitamins (including vitamin A, D, and coenzyme Q10); c) increased lipid peroxidation and aldehyde formation, mainly increased malondialdehyde (MDA), 4-hydroxynonenal, peroxides, and 8-isoprostanes; and d) Immunoglobulin (Ig)G responses to oxidized low-density lipoprotein and IgM responses to MDA. The ratio of all lipid peroxidation biomarkers/all lipid-associated antioxidant defenses was significantly increased in MDD (standardized mean difference or SMD = 0.433; 95% confidence intervals (CI): 0.312; 0.554) and BD (SMD = 0.653; CI: 0.501–0.806). This ratio was significantly greater in BD than MDD (p = 0.027). In MDD/BD, lowered RCT, a key antioxidant and anti-inflammatory pathway, may drive increased lipid peroxidation, aldehyde formation, and autoimmune responses to oxidative specific epitopes, which all together cause increased immune-inflammatory responses and neuro-affective toxicity. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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132. Immunoinflammatory and oxidative alterations in subjects with schizophrenia under clozapine: A meta-analysis.
- Author
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Martins, Paulo Levi Bezerra, Moura, Ian Araújo, Mendes, Gabrielle, Ribeiro, Vitória Cristina Almeida Flexa, Arnaud, André, Gama, Clarissa S., Maes, Michael, Macedo, Danielle S., and Pinto, Joel Porfirio
- Subjects
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CLOZAPINE , *FEVER , *ARIPIPRAZOLE , *SCHIZOPHRENIA , *AMISULPRIDE , *INTERLEUKIN-6 - Abstract
Clozapine presents immunoregulatory properties not well understood. To address this issue, we performed this systematic review to evaluate the immune alterations induced by clozapine and its relationship with the drug's clinical response and compare it with other antipsychotics. Our systematic review has selected nineteen studies meeting the inclusion criteria, from which eleven were included in the meta-analysis, totalizing 689 subjects distributed over three different comparisons. The results revealed that clozapine treatment activates the compensatory immune-regulatory system (CIRS) (Hedges's g = +1.049; CI +0.62 – +1.47, p < 0.001) but has no effects on the immune-Inflammatory Response System (IRS) (Hedges's g = -0.27; CI -1.76 – +1.22, p = 0.71), M1 macrophage (Hedges's g= -0.32; CI -1.78 – +1.14, p = 0.65) and Th1 (Hedge's g = 0.86; CI -0.93 – +1.814, p = 0.07) profiles. Comparing clozapine-treated patients with other anti-psychotics-treated, plasma levels of interleukin (IL)-6 were greater in the clozapine group (Hedge's g = 0.75; CI 0.35 - 1.15, p <0.001). In addition, higher IL-6 plasma levels after four weeks of clozapine treatment were related to the development of clozapine-induced fever; however, IL-6 levels recovered to baseline in 6–10 weeks due to an unexplained compensatory mechanism. In conclusion, our results show that clozapine treatment causes a time-dependent mixed immune profile characterized by increased IL-6 levels and CIRS activation, which may contribute to this drug mechanism of action and adverse effects. Future studies must be designed to investigate the relationship between clozapine-induced immune alterations and symptom remission, treatment resistance, and adverse effects, given the importance of this drug for treating resistant schizophrenia. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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133. Paraoxonase 1 status is a major Janus-faced component of mild and moderate acute ischemic stroke and consequent disabilities.
- Author
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Brinholi, Francis F., Michelin, Ana Paula, Matsumoto, Andressa K., de O Semeão, Laura, Almulla, Abbas F., Supasitthumrong, Thitiporn, Tunvirachaisakul, Chavit, Barbosa, Décio S., and Maes, Michael
- Subjects
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ISCHEMIC stroke , *PARAOXONASE , *HIGH density lipoproteins , *HDL cholesterol , *DISABILITIES - Abstract
Aims: This study aims to examine the associations between paraoxonase 1 (PON)1 status and acute ischemic stroke (AIS) and consequent disabilities. Methods: This study recruited 122 patients with AIS and 40 healthy controls and assessed the Q192R gene variants, arylesterase (AREase) and chloromethyl phenylacetate (CMPAase) activities, and high-density lipoprotein cholesterol (HDLc) in baseline conditions. AREase and CMPAase were measured 3 months later. The National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin score (mRS) were assessed at baseline and 3 and 6 months later. Results: Reduced CMPAase and increased AREase activities are significantly associated with AIS and mRS and NIHSS scores (baseline and 3 and 6 months later). The best predictor of AIS/disabilities was a decrease in the z-unit-based composite zCMPAase-zAREase score. Serum high density lipoprotein cholsterol (HDLc) was significantly correlated with CMPAase, but not AREase, activity and a lowered zCMPAase + zHDLc score was the second best predictor of AIS/disabilities. Regression analysis showed that 34.7% of the variance in baseline NIHSS was explained by zCMPAase-zAREase and zCMPAase + zHDLc composites, HDLc, and hypertension. Neural network analysis showed that stroke was differentiated from controls with an area under the ROC curve of 0.975 using both new composite scores, PON1 status, hypertension, dyslipidemia, previous stroke as body mass index. The PON1 Q192R genotype has many significant direct and mediated effects on AIS/disabilities, however, its overall effect was not significant. Discussion: PON1 status and the CMPAase-HDLc complex play key roles in AIS and its disabilities at baseline and 3 and 6 months later. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
134. Chronic fatigue and affective symptoms in acute and long COVID are attributable to immune‐inflammatory pathways.
- Author
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Almulla, Abbas F., Al‐Hakeim, Hussein Kadhem, and Maes, Michael
- Subjects
- *
POST-acute COVID-19 syndrome , *FATIGUE (Physiology) , *COUGH , *SYMPTOMS , *AFFECT (Psychology) , *COVID-19 pandemic - Abstract
The results indicate that the inflammatory response during acute infection and increased nitro-oxidative stress, a mild chronic inflammatory response, decreased antioxidant defenses, and calcium levels are new drug targets to prevent the development of physio-affective symptoms during both the acute and chronic phases. Since immune-inflammatory pathways may mechanistically explain affective symptoms, chronic fatigue, and psychosomatic symptoms,[[6]] it is safe to conclude that the immune-inflammatory response causes the physio-affective phenome of acute infection. Chronic fatigue and affective symptoms in acute and long COVID are attributable to immune-inflammatory pathways. [Extracted from the article]
- Published
- 2023
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135. 771 - Phase-Dependent Alterations in Immune Activation Contribute to Neuroprogression in Bipolar Disorder.
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Maes, Michael, Moreira, Estefânia, Nunes, Sandra, Vargas, Heber, Barbosa, Décio, Siwek, Marcin, Rybakowski, Janusz, and Nowak, Gabriel
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BIPOLAR disorder , *DISEASE progression , *TUMOR necrosis factor receptors , *INTERLEUKINS , *MENTAL depression - Published
- 2017
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136. Novel insights into the mechanisms underlying depression-associated experimental autoimmune encephalomyelitis.
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Duarte-Silva, Eduardo, Macedo, Danielle, Maes, Michael, and Peixoto, Christina Alves
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MENTAL depression , *PREDICTIVE validity , *MULTIPLE sclerosis , *ANIMAL models in research , *OXIDATIVE stress - Abstract
Multiple Sclerosis (MS) is a chronic autoimmune disease characterized by neuroinflammation, demyelination and neuroaxonal degeneration affecting >2 million people around the world. MS is often accompanied by psychiatric comorbidities such as major depressive disorder (MDD), which presents a lifetime prevalence of around 50% in MS patients. Experimental Autoimmune Encephalomyelitis (EAE) is an animal model extensively used to study MS. EAE mimics the autoimmune nature of MS, as well as its inflammatory and demyelinating mechanisms also presenting predictive validity. There are important similarities between EAE and MS-associated depression (MSD). The mechanisms shared by these disorders include peripheral inflammation, neuroinflammation, mitochondrial dysfunctions, oxidative stress, nitrosative stress, lowered antioxidant defenses, increased bacterial translocation into the systemic circulation, and microglial pathology. Although the role of the immune-inflammatory system in MDD has been established in the 1990's, only few studies addressed immune pathways as a major determinant of depressive-like behavior in EAE. Therefore, in the present study we aimed at revising the current literature on EAE as an animal model to investigate the comorbidity between MS and MDD. In this regard, we revised the current literature on behavioral alterations in EAE, the possible mechanisms involved in this comorbidity and the potential and limitations of using this animal model to study depressive-like behavior. • Multiple Sclerosis (MS) and EAE are accompanied by depressive symptoms. • Data show depressive symptoms in EAE mice are similar to depression in MS. • Depression in EAE is due to neuroimmunoendocrine changes. • EAE has translational potential and it provides new insights into depression. • EAE can be used to study depression and depression in MS. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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137. Supervised machine learning to decipher the complex associations between neuro-immune biomarkers and quality of life in schizophrenia.
- Author
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Kanchanatawan, Buranee, Sriswasdi, Sira, and Maes, Michael
- Subjects
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PEOPLE with schizophrenia , *NEUROIMMUNOLOGY , *BIOLOGICAL tags , *QUALITY of life , *MACHINE learning - Abstract
Stable phase schizophrenia is characterized by altered patterning in tryptophan catabolites (TRYCATs) and memory impairments, which are associated with PHEMN (psychosis, hostility, excitation, mannerism and negative) and DAPS (depression, anxiety and physio-somatic) symptoms. This study was carried out to examine the association between TRYCAT patterning, memory impairments, psychopathological features and health-related quality of life (HR-QoL) in schizophrenia. The World Health Organization (WHO) QoL instrument-Abbreviated version (WHO-QoL-BREF), IgA/IgM responses to TRYCATs, cognitive tests, Scale for the Assessment of Negative Symptoms (SANS), Hamilton and Depression (HAMD) and Anxiety (HAMA) Rating Scales and the Fibromyalgia and Chronic Fatigue Syndrome Rating Scale (FF) were measured in 80 schizophrenia patients and 40 controls. Neural Network analysis shows that the total HR-Qol score is best predicted by (in descending order) HAMA, FF, HAMD, and psychosis. Partial least Squares (PLS) analysis shows that 56.7% of the variance in the WHO-QoL scores is explained by PHEMN / DAPS symptoms, while 64.3% of the variance in those symptoms is explained by TRYCAT patterning and episodic/semantic memory impairments. IgA responses to picolinic acid, xanthurenic acid and 3-hydroxy-kynurenine (all negatively) and anthranilic acid (positively) have highly significant indirect effects on WHO-QoL scores, which are completely mediated by cognitive impairments and PHEMN / DAPS symptoms. The results show that lowered HR-Qol in schizophrenia is strongly associated with noxious TRYCATs and that these effects are mediated by impairments in episodic / semantic memory and schizophrenia phenomenology, especially physio-somatic and anxiety symptoms. Mucosal activation of the TRYCAT pathway combined with a deficit in natural IgM isotype antibodies to TRYCATs determine cognitive impairments and DAPS/PHEMN symptoms, which together determine to a large extent lowered HR-QoL in schizophrenia. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
138. Different patterns of alcohol consumption and the incidence and persistence of depressive and anxiety symptoms among older adults in Ireland: A prospective community-based study.
- Author
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Carvalho, Andre F., Stubbs, Brendon, Maes, Michael, Solmi, Marco, Vancampfort, Davy, Kurdyak, Paul A., Brunoni, Andre R., Husain, Muhammad I, and Koyanagi, Ai
- Subjects
- *
MENTAL depression , *ALCOHOL drinking , *DISEASE incidence , *ANXIETY disorders , *OLDER people - Abstract
Background: The associations of different patterns of alcohol consumption and the incidence and persistence of depressive and anxiety symptoms in older age remain unclear.Methods: Data on 6095 adults aged ≥ 50 years old from the Irish Longitudinal Study on Aging (TILDA) was analyzed. Participants completed the CAGE instrument to screen for problematic alcohol use at baseline between October 2009 and February 2011. Outcomes were incident (assessed by the CES-D scale) and anxiety (assessed by the Hospital Anxiety and Depressive scale) symptoms after a two-year follow-up as well as persistence of probable depression and anxiety among those with a positive screen for those disorders at baseline. Associations were adjusted for potential confounders through multivariable models.Results: In the overall sample, problem drinking did not predict incident and persistent depression and anxiety in this sample. Among females, problem drinking increased the risk for incident depression (OR = 2.11; 95%CI = 1.12-4.00) and anxiety (OR = 2.22; 95%CI = 1.01-4.86). In addition, problem drinking increased the risk of persistent depressive symptoms (OR = 2.43; 95%CI = 1.05-5.06) among females.Conclusion: Problem drinking may increase the risk of incident probable depression and anxiety among older females. Furthermore, problem drinking led to a higher likelihood of persistent depressive symptoms in older female participants. Interventions targeting problem drinking among older females may prevent the onset and persistence of depression in this population, while also decreasing the incidence of anxiety symptoms. [ABSTRACT FROM AUTHOR]- Published
- 2018
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139. Mood Symptoms and Chronic Fatigue Syndrome Due to Relapsing-Remitting Multiple Sclerosis Are Associated with Immune Activation and Aberrations in the Erythron.
- Author
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Almulla, Abbas F., Abdul Jaleel, Al-Karrar Kais, Abo Algon, Ali Abbas, Tunvirachaisakul, Chavit, Hassoun, Hayder K., Al-Hakeim, Hussein K., and Maes, Michael
- Subjects
- *
CHRONIC fatigue syndrome , *MULTIPLE sclerosis , *MYELIN sheath diseases , *SYMPTOMS , *PERIPHERAL nervous system , *CENTRAL nervous system diseases - Abstract
Background: Multiple sclerosis (MS) is a chronic autoimmune and neuroinflammatory disease of the central nervous system characterized by peripheral activation of immune-inflammatory pathways which culminate in neurotoxicity causing demyelination of central neurons. Nonetheless, the pathophysiology of relapsing-remitting MS (RRMS)-related chronic fatigue, depression, anxiety, cognitive impairments, and autonomic disturbances is not well understood. Objectives: The current study aims to delineate whether the remitted phase of RRMS is accompanied by activated immune-inflammatory pathways and if the latter, coupled with erythron variables, explain the chronic fatigue and mood symptoms due to RRMS. Material and Methods: We recruited 63 MS patients, 55 in the remitted phase of RRMS and 8 with secondary progressive MS, and 30 healthy controls and assessed erythron variables, and used a bio-plex assay to measure 27 serum cytokines. Results: A significant proportion of the MS patients (46%) displayed activation of the immune-inflammatory response (IRS) and compensatory immune response (CIRS) systems, and T helper (Th)1 and Th17 cytokine profiles. Remitted RRMS patients showed increased chronic fatigue, depression, anxiety, physiosomatic, autonomic, and insomnia scores, which could partly be explained by M1 macrophage, Th1, Th-17, growth factor, and CIRS activation, as well as aberrations in the erythron including lowered hematocrit and hemoglobin levels. Conclusions: Around 50% of remitted RRMS patients show activation of immune-inflammatory pathways in association with mood and chronic-fatigue-like symptoms. IRS and CIRS activation as well as the aberrations in the erythron are new drug targets to treat chronic fatigue and affective symptoms due to MS. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
140. The physio-affective phenome of major depression is strongly associated with biomarkers of astroglial and neuronal projection toxicity which in turn are associated with peripheral inflammation, insulin resistance and lowered calcium.
- Author
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Al-Hakeim, Hussein Kadhem, Al-Naqeeb, Tabarek Hadi, Almulla, Abbas F., and Maes, Michael
- Subjects
- *
PLATELET-derived growth factor receptors , *GLIAL fibrillary acidic protein , *MENTAL depression , *INSULIN resistance , *TAU proteins , *PSYCHONEUROIMMUNOLOGY - Abstract
Major depressive disorder (MDD) is characterized by elevated activity of peripheral neuro-immune and neuro-oxidative pathways, which may cause neuro-affective toxicity by disrupting neuronal circuits in the brain. No study has explored peripheral indicators of neuroaxis damage in MDD in relation to serum inflammatory and insulin resistance (IR) biomarkers, calcium, and the physio-affective phenome consisting of depressive, anxious, chronic fatigue, and physiosomatic symptoms. Serum levels of phosphorylated tau protein 217 (P-tau217), platelet-derived growth factor receptor beta (PDGFR), neurofilament light chain (NF-L), glial fibrillary acidic protein (GFAP), C-reactive protein (CRP), calcium and the HOMA2-insulin resistance (IR) index were measured in 94 MDD patients and 47 controls. 61.1 % of the variance in the physio-affective phenome (conceptualized as a factor extracted from depression, anxiety, fatigue and physiosomatic symptoms) is explained by the regression on GFAP, NF-L, P-tau2017, PDGFRβ and HOMA2-IR (all positively associated), and decreased calcium. In addition, CRP and HOMA2-IR predicted 28.9 % of the variance in the neuroaxis index. We observed significant indirect effects of CRP and calcium on the physio-affective phenome which were partly mediated by the four neuroaxis biomarkers. Annotation and enrichment analysis revealed that the enlarged GFAP, P-tau217, PDGFR, and NF-L network was enriched in glial cell and neuronal projections, the cytoskeleton and axonal transport, including a mitochondrion. Peripheral inflammation and IR may damage the astroglial and neuronal projections thereby interfering with mitochondrial transport. This neurotoxicity, combined with inflammation, IR and lowered calcium, may, at least in part, induce the phenome of MDD. • Major depressive disorder (MDD) is characterized by neuro-immune pathways • Serum biomarkers of astroglial and neuronal injuries are increased in MDD • These injuries are partly explained by insulin resistance and inflammation • Astroglial and neuronal projection toxicity are characteristics of MDD • Projection toxicity, IR and inflammation contribute to the phenome of MDD. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
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141. The Emerging Role of Flavonoids in Autism Spectrum Disorder: A Systematic Review.
- Author
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Savino, Rosa, Medoro, Alessandro, Ali, Sawan, Scapagnini, Giovanni, Maes, Michael, and Davinelli, Sergio
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AUTISM spectrum disorders , *FLAVONOIDS , *SCIENCE databases , *MOTOR ability , *WEB databases - Abstract
Although autism spectrum disorder (ASD) is a multifaceted neurodevelopmental syndrome, accumulating evidence indicates that oxidative stress and inflammation are common features of ASD. Flavonoids, one of the largest and best-investigated classes of plant-derived compounds, are known to exert antioxidant, anti-inflammatory, and neuroprotective effects. This review used a systematic search process to assess the available evidence on the effect of flavonoids on ASD. A comprehensive literature search was carried out in PubMed, Scopus, and Web of Science databases following the PRISMA guidelines. A total of 17 preclinical studies and 4 clinical investigations met our inclusion criteria and were included in the final review. Most findings from animal studies suggest that treatment with flavonoids improves oxidative stress parameters, reduces inflammatory mediators, and promotes pro-neurogenic effects. These studies also showed that flavonoids ameliorate the core symptoms of ASD, such as social deficits, repetitive behavior, learning and memory impairments, and motor coordination. However, there are no randomized placebo-controlled trials that support the clinical efficacy of flavonoids in ASD. We only found open-label studies and case reports/series, using only two flavonoids such as luteolin and quercetin. These preliminary clinical studies indicate that flavonoid administration may improve specific behavioral symptoms of ASD. Overall, this review is the first one to systematically report evidence for the putative beneficial effects of flavonoids on features of ASD. These promising preliminary results may provide the rationale for future randomized controlled trials aimed at confirming these outcomes. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
142. Redefining Autoimmune Disorders' Pathoetiology: Implications for Mood and Psychotic Disorders' Association with Neurodegenerative and Classical Autoimmune Disorders.
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Anderson, George, Almulla, Abbas F., Reiter, Russel J., and Maes, Michael
- Subjects
- *
B cells , *AUTOIMMUNE diseases , *GUT microbiome , *T cell receptors , *PSYCHOSES , *ARYL hydrocarbon receptors , *BRAIN-derived neurotrophic factor , *AFFECTIVE disorders - Abstract
Although previously restricted to a limited number of medical conditions, there is a growing appreciation that 'autoimmune' (or immune-mediated) processes are important aspects of a wide array of diverse medical conditions, including cancers, neurodegenerative diseases and psychiatric disorders. All of these classes of medical conditions are associated with alterations in mitochondrial function across an array of diverse cell types. Accumulating data indicate the presence of the mitochondrial melatonergic pathway in possibly all body cells, with important consequences for pathways crucial in driving CD8+ T cell and B-cell 'autoimmune'-linked processes. Melatonin suppression coupled with the upregulation of oxidative stress suppress PTEN-induced kinase 1 (PINK1)/parkin-driven mitophagy, raising the levels of the major histocompatibility complex (MHC)-1, which underpins the chemoattraction of CD8+ T cells and the activation of antibody-producing B-cells. Many factors and processes closely associated with autoimmunity, including gut microbiome/permeability, circadian rhythms, aging, the aryl hydrocarbon receptor, brain-derived neurotrophic factor (BDNF) and its receptor tyrosine receptor kinase B (TrkB) all interact with the mitochondrial melatonergic pathway. A number of future research directions and novel treatment implications are indicated for this wide collection of poorly conceptualized and treated medical presentations. It is proposed that the etiology of many 'autoimmune'/'immune-mediated' disorders should be conceptualized as significantly determined by mitochondrial dysregulation, with alterations in the mitochondrial melatonergic pathway being an important aspect of these pathoetiologies. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
143. Increased insulin resistance due to long COVID is associated with depressive symptoms and partly predicted by the inflammatory response during acute infection.
- Author
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Al-Hakeim, Hussein Kadhem, Al-Rubaye, Haneen Tahseen, Jubran, Abdulsahib S., Almulla, Abbas F., Moustafa, Shatha Rouf, and Maes, Michael
- Subjects
- *
POST-acute COVID-19 syndrome , *MENTAL depression , *INSULIN resistance , *HAMILTON Depression Inventory , *COVID-19 pandemic - Abstract
Background: 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). No data indicate whether Long COVID is associated with increased insulin resistance (IR) in association with neuroimmune and oxidative (NIO) processes. Methods: This case control and retrospective cohort study used the homeostasis Model Assessment 2 (HOMA2) calculator© to compute β-cell function, insulin sensitivity and resistance (HOMA2-IR) and measured the Beck Depression Inventory (BDI) and the Hamilton Depression Rating Scale (HAMD) in 86 Long COVID patients and 39 controls. Results: Long COVID (3-4 months after the acute infection) is accompanied by increased HOMA2-IR, fasting blood glucose, and insulin levels; 33.7% of the patients versus 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 (NLRP3 inflamasome, myeloperoxidase, 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 the onset of depressive symptoms due to Long COVID by enhancing overall neurotoxicity. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
144. A novel approach of substitution therapy with inhalation of essential oil for the reduction of inhalant craving: A double-blinded randomized controlled trial.
- Author
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Kalayasiri, Rasmon, Maneesang, Wanjaree, and Maes, Michael
- Subjects
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THERAPEUTIC use of essential oils , *INHALANT abuse , *RANDOMIZED controlled trials , *NEUROTOXIC agents , *NEUROTOXICOLOGY , *PREVENTION - Abstract
Inhalants, which are neurotoxic central nervous system (CNS) suppressants, are frequently abused by young adults. Unlike other CNS depressants, including alcohol and opiates, no treatment is currently approved for inhalant dependence. In this report, a novel approach of substitution treatment for inhalant addiction was explored in a double-blinded, randomized, controlled crossover design to examine the effects of inhalation of essential oil and perfume on the reduction of cue-induced craving for inhalant in thirty-four Thai males with inhalant dependence. The craving response was measured by the modified version of Penn Alcohol Craving Score for Inhalants (PACS-inhalants). The participants (mean age ± SE = 27.9 ± 1.4) in this trial had used inhalant for 5.8 ± 1.1 years. Cravings could be induced in all participants by visual cues as assessed by ^50% increases in inhalant craving levels. Generalized estimating equations showed a significant suppressant effect of essential oil, but not perfume, on the craving response as compared with baseline cue-induced craving. Moreover, essential oil, but not perfume, had significant effects on physiological responses including decreasing pulse rate. It is concluded that inhaling essential oil as a substitution treatment for inhalant may be used as part of treatment programs for reducing inhalant craving. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
145. Breastfeeding and the gut-brain axis: is there a role for melatonin?
- Author
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Anderson, George, Vaillancourt, Cathy, Maes, Michael, and Reiter, Russel J.
- Subjects
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BREASTFEEDING , *MELATONIN , *BREAST milk , *MENTAL depression , *OXIDATIVE stress , *CYTOKINES , *KYNURENINE - Abstract
The benefits of breastfeeding over formula feed are widely appreciated. However, for many mothers breastfeeding is not possible, highlighting the need for a significant improvement in the contents of formula feed. In this article, the overlooked role of melatonin and the melatonergic pathways in breast milk and in the regulation of wider breast milk components are reviewed. There is a growing appreciation that the benefits of breastfeeding are mediated by its effects in the infant gut, with consequences for the development of the gut-brain axis and the immune system. The melatonergic pathways are intimately associated with highly researched processes in the gut, gut microbiome and gut-brain axis. As the melatonergic pathways are dependent on the levels of serotonin availability as a necessary precursor, decreased melatonin is linked to depression and depression-associated disorders. The association of breastfeeding and the gut-brain axis with a host of medical conditions may be mediated by their regulation of processes that modulate depression susceptibility. The biological underpinnings of depression include increased levels of pro-inflammatory cytokines, oxidative stress, kynurenine pathway activity and dysregulation of the hypothalamic-pituitary adrenal axis, all of which can decrease melatonergic pathway activity. The inclusion of the melatonergic pathways in the biological interactions of breast milk and gut development has significant theoretical and treatment implications, as well as being important to the prevention of a host of infant-, child- and adult-onset medical conditions. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
146. Lowered oxygen saturation and increased body temperature in acute COVID-19 largely predict chronic fatigue syndrome and affective symptoms due to Long COVID: A precision nomothetic approach.
- Author
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Al-Hadrawi, Dhurgham Shihab, Al-Rubaye, Haneen Tahseen, Almulla, Abbas F., Al-Hakeim, Hussein Kadhem, and Maes, Michael
- Subjects
- *
POST-acute COVID-19 syndrome , *BODY temperature , *CHRONIC fatigue syndrome , *OXYGEN saturation , *HAMILTON Depression Inventory , *GASTROPARESIS , *POSTPOLIOMYELITIS syndrome - Abstract
Background: Long coronavirus disease 2019 (LC) is a chronic sequel of acute COVID-19. The exact pathophysiology of the affective, chronic fatigue and physiosomatic symptoms (labelled as "physio-affective phenome") of LC has remained elusive. Objective: The current study aims to delineate the effects of oxygen saturation (SpO2) and body temperature during the acute phase on the physio-affective phenome of LC. Method: We recruited 120 LC patients and 36 controls. For all participants, we assessed the lowest SpO2 and peak body temperature during acute COVID-19, and the Hamilton Depression and Anxiety Rating Scale (HAMD/HAMA) and Fibro Fatigue (FF) scales 3–4 months later. Results: Lowered SpO2 and increased body temperature during the acute phase and female sex predict 60.7% of the variance in the physio-affective phenome of LC. Using unsupervised learning techniques, we were able to delineate a new endophenotype class, which comprises around 26.7% of the LC patients and is characterised by very low SpO2 and very high body temperature, and depression, anxiety, chronic fatigue, and autonomic and gastro-intestinal symptoms scores. Single latent vectors could be extracted from both biomarkers, depression, anxiety and FF symptoms or from both biomarkers, insomnia, chronic fatigue, gastro-intestinal and autonomic symptoms. Conclusion: The newly constructed endophenotype class and pathway phenotypes indicate that the physio-affective phenome of LC is at least in part the consequence of the pathophysiology of acute COVID-19, namely the combined effects of lowered SpO2, increased body temperature and the associated immune-inflammatory processes and lung lesions. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
147. Persistent SARS-CoV-2 Infection, EBV, HHV-6 and Other Factors May Contribute to Inflammation and Autoimmunity in Long COVID.
- Author
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Vojdani, Aristo, Vojdani, Elroy, Saidara, Evan, and Maes, Michael
- Subjects
- *
POST-acute COVID-19 syndrome , *EPSTEIN-Barr virus , *HERPESVIRUSES , *HUMAN herpesvirus-6 , *VIRAL antibodies , *CHRONIC fatigue syndrome , *AUTOIMMUNITY , *SARS-CoV-2 , *IMMUNOGLOBULINS - Abstract
A novel syndrome called long-haul COVID or long COVID is increasingly recognized in a significant percentage of individuals within a few months after infection with SARS-CoV-2. This disorder is characterized by a wide range of persisting, returning or even new but related symptoms that involve different tissues and organs, including respiratory, cardiac, vascular, gastrointestinal, musculo-skeletal, neurological, endocrine and systemic. Some overlapping symptomatologies exist between long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Very much like with long ME/CFS, infections with herpes family viruses, immune dysregulation, and the persistence of inflammation have been reported as the most common pattern for the development of long COVID. This review describes several factors and determinants of long COVID that have been proposed, elaborating mainly on viral persistence, reactivation of latent viruses such as Epstein–Barr virus and human herpesvirus 6 which are also associated with the pathology of ME/CFS, viral superantigen activation of the immune system, disturbance in the gut microbiome, and multiple tissue damage and autoimmunity. Based on these factors, we propose diagnostic strategies such as the measurement of IgG and IgM antibodies against SARS-CoV-2, EBV, HHV-6, viral superantigens, gut microbiota, and biomarkers of autoimmunity to better understand and manage this multi-factorial disorder that continues to affect millions of people in the world. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
148. Myalgic encephalomyelitis/chronic fatigue syndrome and encephalomyelitis disseminata/multiple sclerosis show remarkable levels of similarity in phenomenology and neuroimmune characteristics.
- Author
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Morris, Gerwyn and Maes, Michael
- Abstract
Background: 'Encephalomyelitis disseminata' (multiple sclerosis) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are both classified as diseases of the central nervous system by the World Health Organization. This review aims to compare the phenomenological and neuroimmune characteristics of MS with those of ME/CFS.Discussion: There are remarkable phenomenological and neuroimmune overlaps between both disorders. Patients with ME/CFS and MS both experience severe levels of disabling fatigue and a worsening of symptoms following exercise and resort to energy conservation strategies in an attempt to meet the energy demands of day-to-day living. Debilitating autonomic symptoms, diminished cardiac responses to exercise, orthostatic intolerance and postural hypotension are experienced by patients with both illnesses. Both disorders show a relapsing-remitting or progressive course, while infections and psychosocial stress play a large part in worsening of fatigue symptoms. Activated immunoinflammatory, oxidative and nitrosative (O+NS) pathways and autoimmunity occur in both illnesses. The consequences of O+NS damage to self-epitopes is evidenced by the almost bewildering and almost identical array of autoantibodies formed against damaged epitopes seen in both illnesses. Mitochondrial dysfunctions, including lowered levels of ATP, decreased phosphocreatine synthesis and impaired oxidative phosphorylation, are heavily involved in the pathophysiology of both MS and ME/CFS. The findings produced by neuroimaging techniques are quite similar in both illnesses and show decreased cerebral blood flow, atrophy, gray matter reduction, white matter hyperintensities, increased cerebral lactate and choline signaling and lowered acetyl-aspartate levels.Summary: This review shows that there are neuroimmune similarities between MS and ME/CFS. This further substantiates the view that ME/CFS is a neuroimmune illness and that patients with MS are immunologically primed to develop symptoms of ME/CFS. [ABSTRACT FROM AUTHOR]- Published
- 2013
- Full Text
- View/download PDF
149. Chronic Fatigue, Depression and Anxiety Symptoms in Long COVID Are Strongly Predicted by Neuroimmune and Neuro-Oxidative Pathways Which Are Caused by the Inflammation during Acute Infection.
- Author
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Al-Hakeim, Hussein Kadhem, Al-Rubaye, Haneen Tahseen, Almulla, Abbas F., Al-Hadrawi, Dhurgham Shihab, and Maes, Michael
- Subjects
- *
POST-acute COVID-19 syndrome , *FATIGUE (Physiology) , *COVID-19 , *MENTAL depression , *OXIDANT status - Abstract
Background: Long-term coronavirus disease 2019 (long COVID) is associated with physio-somatic (chronic fatigue syndrome and somatic symptoms) and affective (depression and anxiety) symptoms. The severity of the long COVID physio-affective phenome is largely predicted by increased peak body temperature (BT) and lowered oxygen saturation (SpO2) during the acute infectious phase. This study aims to delineate whether the association of BT and SpO2 during the acute phase and the long COVID physio-affective phenome is mediated by neurotoxicity (NT) resulting from activated immune-inflammatory and oxidative stress pathways. Methods: We recruited 86 patients with long COVID (3–4 months after the acute phase) and 39 healthy controls and assessed serum C-reactive protein (CRP), caspase 1, interleukin (IL) 1β, IL-18, IL-10, myeloperoxidase (MPO), advanced oxidation protein products (AOPPs), total antioxidant capacity (TAC), and calcium (Ca), as well as peak BT and SpO2 during the acute phase. Results: Cluster analysis revealed that a significant part (34.9%) of long COVID patients (n = 30) show a highly elevated NT index as computed based on IL-1β, IL-18, caspase 1, CRP, MPO, and AOPPs. Partial least squares analysis showed that 61.6% of the variance in the physio-affective phenome of long COVID could be explained by the NT index, lowered Ca, and peak BT/SpO2 in the acute phase and prior vaccinations with AstraZeneca or Pfizer. The most important predictors of the physio-affective phenome are Ca, CRP, IL-1β, AOPPs, and MPO. Conclusion: The infection–immune–inflammatory core of acute COVID-19 strongly predicts the development of physio-affective symptoms 3–4 months later, and these effects are partly mediated by neuro-immune and neuro-oxidative pathways. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
150. Increased Lipid Peroxidation and Lowered Antioxidant Defenses Predict Methamphetamine Induced Psychosis.
- Author
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Al-Hakeim, Hussein Kadhem, Altufaili, Mazin Fadhil, Almulla, Abbas F., Moustafa, Shatha Rouf, and Maes, Michael
- Subjects
- *
METHAMPHETAMINE , *OXIDANT status , *PSYCHOSES , *GLUTATHIONE peroxidase , *ABSTRACT thought , *PEROXIDATION - Abstract
Background: a significant percentage of methamphetamine (MA) dependent patients develop psychosis. The associations between oxidative pathways and MA-induced psychosis (MIP) are not well delineated. Objective: the aim of this study is to delineate whether acute MA intoxication in MA dependent patients is accompanied by increased nitro-oxidative stress and whether the latter is associated with MIP. Method: we recruited 30 healthy younger males and 60 acutely intoxicated males with MA dependence and assessed severity of MA use and dependence and psychotic symptoms during intoxication, and serum oxidative toxicity (OSTOX) biomarkers including oxidized high (oxHDL) and low (oxLDL)-density lipoprotein, myeloperoxidase (MPO), malondialdehyde (MDA), and nitric oxide (NO), and antioxidant defenses (ANTIOX) including HDL-cholesterol, zinc, glutathione peroxidase (GPx), total antioxidant capacity (TAC), and catalase-1. Results: a large part (50%, n = 30) of patients with MA dependence could be allocated to a cluster characterized by high psychosis ratings including delusions, suspiciousness, conceptual disorganization and difficulties abstract thinking and an increased OSTOX/ANTIOX ratio. Partial Least Squares analysis showed that 29.9% of the variance in MIP severity (a first factor extracted from psychosis, hostility, excitation, mannerism, and formal thought disorder scores) was explained by HDL, TAC and zinc (all inversely) and oxLDL (positively). MA dependence and dosing explained together 44.7% of the variance in the OSTOX/ANTIOX ratio. Conclusions: MA dependence and intoxication are associated with increased oxidative stress and lowered antioxidant defenses, both of which increase risk of MIP during acute intoxication. MA dependence is accompanied by increased atherogenicity due to lowered HDL and increased oxLDL and oxHDL. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
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