scholarly journals Adrenergic Attenuation of Immune Activity is Associated with Anhedonia in Adolescents

2021 ◽  
Author(s):  
Tram N. B. Nguyen ◽  
Benjamin A Ely ◽  
Seunghee Kim-Schulze ◽  
Vilma Gabbay
Keyword(s):  
Psychiatric Symptoms ◽  
Ex Vivo ◽  
Nonparametric Tests ◽  
Promising Agent ◽  
Cytokine Levels ◽  
Sympathetic Modulation ◽  
Psychiatric Conditions ◽  
Consummatory Anhedonia ◽  
Symptom Measures

While inflammation has been implicated in the manifestation of psychiatric symptoms, the role of immune attenuation via sympathetic modulation in psychopathology remains unclear. Here, this study aimed to assess β2-agonist clenbuterol (CBL) as a promising agent to model adrenergic-induced immune response following ex vivo immune activation with lipopolysaccharide (LPS). Relationships between CBL-modulated cytokine levels and symptom measures were then explored. Adolescents were evaluated with semi-structure interviews and self-reported depression, anxiety, and anhedonia levels. Fasting whole-blood samples were collected and stimulated with LPS in the presence and absence of CBL for 6 hours, with supernatants being subjected to Luminex multiplex assay for 41 cytokines. Cytokine levels between conditions were compared using Bonferroni-corrected nonparametric tests. Exploratory factor analysis reduced 41 cytokines into fewer factors in each experimental condition, and their relationships with psychiatric symptoms were examined with Spearman correlations controlling for age, sex, and BMI. Data from 130 participants (15.25 ± 2.16 years old, 59% female) were analyzed. 10 cytokines were significantly affected by CBL treatment compared to LPS alone. LPS+CBL factor 3 significantly correlated with both anticipatory (rho = -0.39, p = 7.4 × 10-5) and consummatory anhedonia (rho = -0.36, p = 3.3 × 10-4), and these correlations remained significant when controlling additionally for depression. There were no significant associations between immune factors with depression or anxiety severity. Findings support our hypothesis that clenbuterol attenuates inflammatory effects thought to underlie psychiatric conditions in youth. Using a data-driven analytic method, distinctive relationships between CBL-affected cytokines and dimensional anhedonia were reported, further elucidating the role of β2-agonism in adolescent affective symptomatology.

scholarly journals Neuroinflammation and cognition across psychiatric conditions

CNS Spectrums ◽  
2019 ◽  
Vol 24 (1) ◽  
pp. 4-15 ◽  
Author(s):  
Célia Fourrier ◽  
Gaurav Singhal ◽  
Bernhard T. Baune
Keyword(s):  
Psychiatric Disorders ◽  
Cognitive Impairments ◽  
Kynurenine Pathway ◽  
Homeostatic Plasticity ◽  
Cytokine Levels ◽  
Inflammatory Processes ◽  
Psychiatric Conditions ◽  
First Time

Cognitive impairments reported across psychiatric conditions (ie, major depressive disorder, bipolar disorder, schizophrenia, and posttraumatic stress disorder) strongly impair the quality of life of patients and the recovery of those conditions. There is therefore a great need for consideration for cognitive dysfunction in the management of psychiatric disorders. The redundant pattern of cognitive impairments across such conditions suggests possible shared mechanisms potentially leading to their development. Here, we review for the first time the possible role of inflammation in cognitive dysfunctions across psychiatric disorders. Raised inflammatory processes (microglia activation and elevated cytokine levels) across diagnoses could therefore disrupt neurobiological mechanisms regulating cognition, including Hebbian and homeostatic plasticity, neurogenesis, neurotrophic factor, the HPA axis, and the kynurenine pathway. This redundant association between elevated inflammation and cognitive alterations across psychiatric disorders hence suggests that a cross-disorder approach using pharmacological and nonpharmacological (ie, physical activity and nutrition) anti-inflammatory/immunomodulatory strategies should be considered in the management of cognition in psychiatry.

Psychiatry and the Frontal Lobes

1990 ◽  
Vol 24 (1) ◽  
pp. 113-132 ◽  
Author(s):  
Janice D. Russell ◽  
Milton G. Roxanas
Keyword(s):  
Frontal Lobe ◽  
Psychiatric Symptoms ◽  
Brain Area ◽  
Neuropsychological Testing ◽  
Frontal Lobes ◽  
Biological Data ◽  
Frontal Lobe Damage ◽  
Psychiatric Conditions ◽  
The Brain

The frontal lobes of the brain have long been regarded as enigmatic in their function and perhaps should be considered even more so in states of dysfunction. Observed associations between structural lesions and psychiatric symptoms and the demonstration of disturbed function and morphology in the frontal lobes of individuals suffering from major psychiatric disorders have led to increased interest in this brain area. Psychiatrists have been particularly concerned with seeking the aetiogenesis of common diagnostic entities and this article attempts to synthesize the available facts. A brief overview of relevant biological data precedes a description of methods of neuropsychological testing and the clinical features arising from frontal lobe damage. A discussion of the role of the frontal lobes in some aspects of personality function follows. Neuropsychiatric features associated with known frontal lobe pathology are described, prefacing a discussion of those psychiatric conditions where an aetiological role for frontal lobe dysfunction has been proposed.

The Role of Polyphenols in the Modulation of Plasma Non-Enzymatic Antioxidant Capacity (NEAC)

2012 ◽  
Vol 82 (3) ◽  
pp. 228-232 ◽  
Author(s):  
Mauro Serafini ◽  
Giuseppa Morabito
Keyword(s):  
Antioxidant Capacity ◽  
Dietary Intervention ◽  
Ex Vivo ◽  
The Body ◽  
Dietary Polyphenols ◽  
Enzymatic Antioxidant ◽  
Endogenous Antioxidant

Dietary polyphenols have been shown to scavenge free radicals, modulating cellular redox transcription factors in different in vitro and ex vivo models. Dietary intervention studies have shown that consumption of plant foods modulates plasma Non-Enzymatic Antioxidant Capacity (NEAC), a biomarker of the endogenous antioxidant network, in human subjects. However, the identification of the molecules responsible for this effect are yet to be obtained and evidences of an antioxidant in vivo action of polyphenols are conflicting. There is a clear discrepancy between polyphenols (PP) concentration in body fluids and the extent of increase of plasma NEAC. The low degree of absorption and the extensive metabolism of PP within the body have raised questions about their contribution to the endogenous antioxidant network. This work will discuss the role of polyphenols from galenic preparation, food extracts, and selected dietary sources as modulators of plasma NEAC in humans.

EMDR as therapy for conditions other than PTSD: a systematic review.

2020 ◽  
Author(s):  
Charles Scelles ◽  
LUIS CARLO BULNES
Keyword(s):  
Mood Disorders ◽  
Obsessive Compulsive ◽  
Treatment As Usual ◽  
Compulsive Disorder ◽  
Adult Personality ◽  
Post Traumatic ◽  
Psychiatric Conditions ◽  
Research Criteria ◽  
Positive Effect

Eye Movement Desensitization and Reprocessing (EMDR) is a treatment for post-traumatic stressdisorder (PTSD). The technique is known to stimulate the capacity to reprocess maladaptive memoriesthat are thought to be central to this pathology. Here we investigate if EMDR therapy can be used in otherconditions than PTSD. We conducted a systematic literature search on PubMed, ScienceDirect, Scopus, and Web of Science. Wesearched for published empirical findings on EMDR, excluding those centred on trauma and PTSD,published up to 2020. The results were classified by psychiatric categories.   Ninety articles met our research criteria. A positive effect was reported in addictions, somatoformdisorders, sexual dysfunction, eating disorder, disorders of adult personality, mood disorders, reaction tosevere stress, anxiety disorders, performance anxiety, Obsessive-Compulsive Disorder (OCD), pain,neurodegenerative disorders, paedopsychiatry and sleep. The evidence was more consistent in pain, OCD,mood disorders, and reaction to severe stress.EMDR’s efficiency across numerous pathological situations, highlighted the central role of affectivememory in several psychiatric and non-psychiatric conditions. Furthermore, EMDR seems to besuccessful in usually uncooperative (e.g. Dementia) or unproductive cases (e.g. aphasia). Moreover, insome severe medical situations were psychologic distress was an obstacle, EMDR allowed thecontinuation of treatment-as-usual. Our review suggests that it is a safe and economical therapeuticoption, and its effect in non-pathological situations opens new avenues for translational research. Overallmore methodologically rigorous studies are needed.

Peripheral Immunity, Immunoaging and Neuroinflammation in Parkinson’s Disease

2019 ◽  
Vol 26 (20) ◽  
pp. 3719-3753 ◽  
Author(s):  
Natasa Kustrimovic ◽  
Franca Marino ◽  
Marco Cosentino
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Immune System ◽  
Neurodegenerative Disorder ◽  
Neurodegenerative Process ◽  
Progressive Degeneration ◽  
Cytokine Levels ◽  
Inflammatory Phenotype ◽  
Immune Challenges

:Parkinson’s disease (PD) is the second most common neurodegenerative disorder among elderly population, characterized by the progressive degeneration of dopaminergic neurons in the midbrain. To date, exact cause remains unknown and the mechanism of neurons death uncertain. It is typically considered as a disease of central nervous system (CNS). Nevertheless, numerous evidence has been accumulated in several past years testifying undoubtedly about the principal role of neuroinflammation in progression of PD. Neuroinflammation is mainly associated with presence of activated microglia in brain and elevated levels of cytokine levels in CNS. Nevertheless, active participation of immune system as well has been noted, such as, elevated levels of cytokine levels in blood, the presence of auto antibodies, and the infiltration of T cell in CNS. Moreover, infiltration and reactivation of those T cells could exacerbate neuroinflammation to greater neurotoxic levels. Hence, peripheral inflammation is able to prime microglia into pro-inflammatory phenotype, which can trigger stronger response in CNS further perpetuating the on-going neurodegenerative process.:In the present review, the interplay between neuroinflammation and the peripheral immune response in the pathobiology of PD will be discussed. First of all, an overview of regulation of microglial activation and neuroinflammation is summarized and discussed. Afterwards, we try to collectively analyze changes that occurs in peripheral immune system of PD patients, suggesting that these peripheral immune challenges can exacerbate the process of neuroinflammation and hence the symptoms of the disease. In the end, we summarize some of proposed immunotherapies for treatment of PD.

The Level of Cytokines in the Vitreous Body of Severe Proliferative Diabetic Retinopathy Patients Undergoing Posterior Vitrectomy

2018 ◽  
Vol 24 (27) ◽  
pp. 3276-3281 ◽  
Author(s):  
Dorota Raczyńska ◽  
Katarzyna A. Lisowska ◽  
Krzysztof Pietruczuk ◽  
Joanna Borucka ◽  
Mateusz Ślizień ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Proliferative Diabetic Retinopathy ◽  
Vitreous Body ◽  
Control Group ◽  
Slit Lamp ◽  
Corrected Visual Acuity ◽  
Cytokine Levels ◽  
Pars Plana ◽  
Eye Examination

Objective: The objective of the study was to compare cytokine levels in the vitreous body of patients with proliferative diabetic retinopathy (PDR) undergoing posterior vitrectomy. Patients and methods: The study included 39 patients (39 eyes) undergoing pars plana vitrectomy (PPV). Patients were divided into three groups: patients with proliferative diabetic retinopathy (PDR) without aflibercept injection prior to the surgery, PDR patients administered aflibercept injection prior to the surgery, and patients without diabetes mellitus (control group). All patients underwent a comprehensive eye examination one day before and 3 weeks after the surgery, including measurements of: best-corrected visual acuity (BVCA) and intraocular pressure (IOP), slit-lamp examination and spectral domain optical coherence tomography (SOCT). Concentrations of cytokines: IL-6, IL-8, IL-12p70, TNF, IL-10, IL-1β were measured in the vitreous body of patients with BD™ Cytometric Bead Array (CBA) Human Inflammatory Cytokines Kit. Results: PDR patients who received pretreatment with aflibercept injection showed significantly lower concentrations of IL-12p70, TNF, IL-10 and IL-1β in the vitreous body compared to the control group. Meanwhile, patients without prior aflibercept injection had a significantly higher concentration of IL-8. There was also a significant positive correlation between IOP before PPV and IL-8 concentration in both PDR patients’ groups. Conclusion: Findings of our study suggest an important role of IL-8 in the development of severe PDR. Aflibercept administration on the day before elective vitrectomy facilitated the surgery.

Hepatoprotective Role of Berberine on Doxorubicin Induced Hepatotoxicity - Involvement of Cyp

2020 ◽  
Vol 21 (7) ◽  
pp. 541-547
Author(s):  
Bao Sun ◽  
Yue Yang ◽  
Mengzi He ◽  
Yanan Jin ◽  
Xiaoyu Cao ◽  
...  
Keyword(s):  
Drug Metabolism ◽  
Cardiac Tissue ◽  
Liver Toxicity ◽  
Elevated Serum ◽  
Similar Response ◽  
Wide Range ◽  
Cytokine Levels ◽  
Major Organ ◽  
Anti Oxidant

Background: The liver is one of the major organ involved in drug metabolism. Cytochrome P450s are predominantly involved in drug metabolism. A wide range of CYPs have been reported in the liver which have been involved in its normal as well as in diseased conditions. Doxorubicin, one of the most potent chemotherapeutic drugs, although highly efficacious, also has adverse side effects, with its targets being liver and cardiac tissue. Objective: The study aims to evaluate the reversal potentials of berberine on Doxorubicin induced cyp conversion. Methodology: In the present study, the interplay between anti-oxidants, cytochrome and inflammatory markers in DOX induced liver toxicity and its possible reversal by berberine was ascertained. Results: DOX administration significantly elevated serum as well as tissue stress, which was reverted by berberine treatment. A similar response was observed in tissue inflammatory mediators as well as in serum cytokine levels. Most profound reduction in the cytochrome expression was found in Cyp 2B1, 2B2, and 2E1. However, 2C1, 2C6, and 3A1 although showed a decline, but it did not revert the expression back to control levels. Conclusion: It could be concluded that berberine may be an efficient anti-oxidant and immune modulator. It possesses low to moderate cytochrome modulatory potentials.

scholarly journals Evaluating Targeted Therapies in Ovarian Cancer Metabolism: Novel Role for PCSK9 and Second Generation mTOR Inhibitors

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3727
Author(s):  
Dafne Jacome Sanz ◽  
Juuli Raivola ◽  
Hanna Karvonen ◽  
Mariliina Arjama ◽  
Harlan Barker ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Lipid Metabolism ◽  
Cell Survival ◽  
Drug Testing ◽  
Cancer Metabolism ◽  
Ex Vivo ◽  
Specific Inhibitor ◽  
Low Grade ◽  
Serous Ovarian Cancer

Background: Dysregulated lipid metabolism is emerging as a hallmark in several malignancies, including ovarian cancer (OC). Specifically, metastatic OC is highly dependent on lipid-rich omentum. We aimed to investigate the therapeutic value of targeting lipid metabolism in OC. For this purpose, we studied the role of PCSK9, a cholesterol-regulating enzyme, in OC cell survival and its downstream signaling. We also investigated the cytotoxic efficacy of a small library of metabolic (n = 11) and mTOR (n = 10) inhibitors using OC cell lines (n = 8) and ex vivo patient-derived cell cultures (PDCs, n = 5) to identify clinically suitable drug vulnerabilities. Targeting PCSK9 expression with siRNA or PCSK9 specific inhibitor (PF-06446846) impaired OC cell survival. In addition, overexpression of PCSK9 induced robust AKT phosphorylation along with increased expression of ERK1/2 and MEK1/2, suggesting a pro-survival role of PCSK9 in OC cells. Moreover, our drug testing revealed marked differences in cytotoxic responses to drugs targeting metabolic pathways of high-grade serous ovarian cancer (HGSOC) and low-grade serous ovarian cancer (LGSOC) PDCs. Our results show that targeting PCSK9 expression could impair OC cell survival, which warrants further investigation to address the dependency of this cancer on lipogenesis and omental metastasis. Moreover, the differences in metabolic gene expression and drug responses of OC PDCs indicate the existence of a metabolic heterogeneity within OC subtypes, which should be further explored for therapeutic improvements.

scholarly journals Role and Regulation of Adipokines during Zymosan-Induced Peritoneal Inflammation in Mice

Endocrinology ◽  
2008 ◽  
Vol 149 (8) ◽  
pp. 4080-4085 ◽  
Author(s):  
Maria Pini ◽  
Melissa E. Gove ◽  
Joseph A. Sennello ◽  
Jantine W. P. M. van Baal ◽  
Lawrence Chan ◽  
...  
Keyword(s):  
Inflammatory Infiltrate ◽  
Peritoneal Lavage ◽  
Lavage Fluid ◽  
Wild Type ◽  
Cellular Infiltrate ◽  
Peritoneal Lavage Fluid ◽  
Peritoneal Inflammation ◽  
Leptin Deficiency ◽  
Cytokine Levels

Adipokines, cytokines mainly produced by adipocytes, are active participants in the regulation of inflammation. Administration of zymosan (ZY) was used to investigate the regulation and role of adipokines during peritonitis in mice. Injection of ZY led to a significant increase in leptin levels in both serum and peritoneal lavage fluid, whereas a differential trend in local vs. systemic levels was observed for both resistin and adiponectin. The role of leptin in ZY-induced peritonitis was investigated using leptin-deficient ob/ob mice, with and without reconstitution with exogenous leptin. Leptin deficiency was associated with delayed resolution of peritoneal inflammation induced by ZY, because ob/ob mice had a more pronounced cellular infiltrate in the peritoneum as well as higher and prolonged local and systemic levels of IL-6, TNFα, IL-10, and chemokine (C-X-C motif) ligand 2 compared with wild-type mice. Reconstitution with exogenous leptin exacerbated the inflammatory infiltrate and systemic IL-6 levels in ob/ob mice while inhibiting production of TNFα, IL-10, and chemokine (C-X-C motif) ligand 2. In contrast with the important role of leptin in regulating each aspect of ZY-induced peritonitis, adiponectin deficiency was associated only with a decreased inflammatory infiltrate, without affecting cytokine levels. These findings point to a complex role for adipokines in ZY-induced peritonitis and further emphasize the interplay between obesity and inflammation.

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