ABSTRACT
OBJECTIVE: To assess factors associated with emotional changes and Hyperactivity/Inattention (HI) motivated by COVID-19 quarantine in adolescents with immunocompromising diseases. METHODS: A cross-sectional study included 343 adolescents with immunocompromising diseases and 108 healthy adolescents. Online questionnaires were answered including socio-demographic data and self-rated healthcare routine during COVID-19 quarantine and validated surveys: Strengths and Difficulties Questionnaire (SDQ), Pittsburgh Sleep Quality Index (PSQI), Pediatric Quality of Life Inventory 4.0 (PedsQL4.0). RESULTS: The frequencies of abnormal emotional SDQ scores from adolescents with chronic diseases were similar to those of healthy subjects (110/343 [32%] vs. 38/108 [35%], p = 0.548), as well as abnormal hyperactivity/inattention SDQ scores (79/343 [23%] vs. 29/108 [27%], p = 0.417). Logistic regression analysis of independent variables associated with abnormal emotional scores from adolescents with chronic diseases showed: female sex (Odds Ratio [OR = 3.76]; 95% Confidence Interval (95% CI) 2.00â7.05; p < 0.001), poor sleep quality (OR = 2.05; 95% CI 1.08â3.88; p = 0.028) and intrafamilial violence during pandemic (OR = 2.17; 95% CI 1.12â4.19; p = 0.021) as independently associated with abnormal emotional scores, whereas total PedsQL score was inversely associated with abnormal emotional scores (OR = 0.95; 95% CI 0.93â0.96; p < 0.0001). Logistic regression analysis associated with abnormal HI scores from patients evidenced that total PedsQL score (OR = 0.97; 95% CI 0.95â0.99; p = 0.010], changes in medical appointments during the pandemic (OR = 0.39; 95% CI 0.19-0.79; p = 0.021), and reliable COVID-19 information (OR = 0.35; 95% CI 0.16â0.77; p = 0.026) remained inversely associated with abnormal HI scores. CONCLUSION: The present study showed emotional and HI disturbances in adolescents with chronic immunosuppressive diseases during the COVID-19 pandemic. It reinforces the need to promptly implement a longitudinal program to protect the mental health of adolescents with and without chronic illnesses during future pandemics.
Subject(s)
Attention , COVID-19 , Immune System Diseases , Mental Disorders , Adolescent , Child , Female , Humans , Cross-Sectional Studies , Mental Disorders/epidemiology , Pandemics , Quality of Life , Surveys and Questionnaires , Emotions , Immune System Diseases/psychology , Chronic DiseaseABSTRACT
Importance: Recent estimates suggest that more than 50% of all deaths worldwide are currently attributable to inflammation-related diseases. Psychosocial interventions may represent a potentially useful strategy for addressing this global public health problem, but which types of interventions reliably improve immune system function, under what conditions, and for whom are unknown. Objective: To address this issue, we conducted a systematic review and meta-analysis of randomized clinical trials (RCTs) in which we estimated associations between 8 different psychosocial interventions and 7 markers of immune system function, and examined 9 potential moderating factors. Data Sources: PubMed, Scopus, PsycInfo, and ClinicalTrials.gov databases were systematically searched from February 1, 2017, to December 31, 2018, for all relevant RCTs published through December 31, 2018. Study Selection: Eligible RCTs included a psychosocial intervention, immune outcome, and preintervention and postintervention immunologic assessments. Studies were independently examined by 2 investigators. Of 4621 studies identified, 62 were eligible and 56 included. Data Extraction and Synthesis: Data were extracted and analyzed from January 1, 2019, to July 29, 2019. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guideline was followed. Data were extracted by 2 investigators who were blind to study hypotheses and analyses, and were then analyzed using robust variance estimation. Analysis included 8 psychosocial interventions (behavior therapy, cognitive therapy, cognitive behavior therapy [CBT], CBT plus additive treatment or mode of delivery that augmented the CBT, bereavement or supportive therapy, multiple or combined interventions, other psychotherapy, and psychoeducation), 7 immune outcomes (proinflammatory cytokine or marker levels, anti-inflammatory cytokine levels, antibody levels, immune cell counts, natural killer cell activity, viral load, and other immune outcomes), and 9 moderating factors (intervention type, intervention format, intervention length, immune marker type, basal vs stimulated markers, immune marker measurement timing, disease state or reason for treatment, age, and sex). Main Outcomes and Measures: The primary a priori outcomes were pretest-posttest-control (ppc) group effect sizes (ppc g) for the 7 immunologic outcomes investigated. Results: Across 56 RCTs and 4060 participants, psychosocial interventions were associated with enhanced immune system function (ppc g = 0.30, 95% CI, 0.21-0.40; t50.9 = 6.22; P < .001). Overall, being randomly assigned to a psychosocial intervention condition vs a control condition was associated with a 14.7% (95% CI, 5.7%-23.8%) improvement in beneficial immune system function and an 18.0% (95% CI, 7.2%-28.8%) decrease in harmful immune system function over time. These associations persisted for at least 6 months following treatment and were robust across age, sex, and intervention duration. These associations were most reliable for CBT (ppc g = 0.33, 95% CI, 0.19-0.47; t27.2 = 4.82; P < .001) and multiple or combined interventions (ppc g = 0.52, 95% CI, 0.17-0.88; t5.7 = 3.63; P = .01), and for studies that assessed proinflammatory cytokines or markers (ppc g = 0.33, 95% CI, 0.19-0.48; t25.6 = 4.70; P < .001). Conclusions and Relevance: These findings suggest that psychosocial interventions are reliably associated with enhanced immune system function and may therefore represent a viable strategy for improving immune-related health.
Subject(s)
Immune System Diseases/therapy , Immune System/immunology , Psychosocial Intervention/methods , Biomarkers/blood , Cognitive Behavioral Therapy , Combined Modality Therapy , Correlation of Data , Hospice Care , Immune System Diseases/immunology , Immune System Diseases/psychology , Patient Education as Topic , Psychosocial Support Systems , Psychotherapy , Randomized Controlled Trials as TopicABSTRACT
PROBLEM: Autism spectrum disorder (ASD)-like phenotypes in murine models are linked to elevated pro-inflammatory cytokine profiles caused by maternal immune activation (MIA), but whether MIA alters the immune response in the offspring remains unclear. METHOD OF STUDY: Polyinosinic:polycytidylic acid (poly:[IC]) was used to induce MIA in immunocompetent and control TLR3-deficient pregnant mice, and cytokine levels were measured in maternal and foetal organs. Furthermore, cytokines and behaviour responses were tested after challenge with lipopolysaccharide in 7-day-old and adult mice. RESULTS: MIA induced on E12 resulted in changes in the cytokine expression profile in maternal and foetal organs and correlated with TNFα and IL-18 dysregulation in immune organs and brains from neonatal mice born to MIA-induced dams. Such changes further correlated with altered behavioural responses in adulthood. CONCLUSION: MIA induced by pathogens during pregnancy can interfere with the development of the foetal immune and nervous systems leading to dysfunctional immune responses and behaviour in offspring.
Subject(s)
Autism Spectrum Disorder/immunology , Immune System Diseases/immunology , Poly I-C/immunology , Pregnancy/immunology , Prenatal Exposure Delayed Effects/immunology , Virus Diseases/immunology , Animals , Autism Spectrum Disorder/psychology , Behavior, Animal , Child of Impaired Parents , Disease Models, Animal , Female , Humans , Immune System Diseases/psychology , Immunity , Immunity, Maternally-Acquired , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Prenatal Exposure Delayed Effects/psychology , Toll-Like Receptor 3/genetics , Transcriptome/immunology , Virus Diseases/psychologyABSTRACT
Immune mediated inflammatory diseases (IMIDs) have similarities in pathophysiology and treatment. Not much is known, however, about health-related quality of life (HR-QoL) in IMIDs. We assessed and compared HR-QoL, using the validated EuroQoL 5-dimensions 5-levels questionnaire, in an observational cohort comprising 530 patients (67.5% female, mean age 49 years (95% CI 35.9-50.9), mean disease duration 31.0 months (95% CI 27.2-34.8)), with the following IMIDs: connective tissue diseases (32.6%), uveitis (20.8%), inflammatory arthritis (17.7%), psoriasis (15.5%), vasculitis (6.2%), primary antiphospholipid syndrome (4.2%), and autoinflammatory diseases (2.8%). Patients used either no anti-inflammatory therapy (31.5%), monotherapy (28.7%), or a combination of anti-inflammatory drugs (39.8%). The mean HR-QoL utility score was 0.75 (95% CI 0.72-0.78). Multinominal logistic regression analysis showed a statistically significant association between a very low HR-QoL (utility score (<0.70)) and female sex, rheumatological IMID or psoriasis, smoking or having smoked in the past, and current biological disease modifying anti-rheumatic drugs use.
Subject(s)
Immune System Diseases/psychology , Inflammation/psychology , Quality of Life , Adolescent , Adult , Aged , Aged, 80 and over , Alcohol Drinking/epidemiology , Antirheumatic Agents/adverse effects , Antirheumatic Agents/therapeutic use , Autoimmune Diseases/drug therapy , Autoimmune Diseases/epidemiology , Autoimmune Diseases/immunology , Autoimmune Diseases/psychology , Comorbidity , Cross-Sectional Studies , Female , Humans , Immune System Diseases/drug therapy , Immune System Diseases/epidemiology , Inflammation/drug therapy , Inflammation/epidemiology , Inflammation/immunology , Male , Medicine , Middle Aged , Netherlands/epidemiology , Obesity/epidemiology , Patient Care Team , Prospective Studies , Referral and Consultation , Smoking/epidemiology , Smoking/psychology , Young AdultABSTRACT
PURPOSE OF REVIEW: Immune dysregulation has been suggested as a pathophysiological pathway in schizophrenia. MRI could aid in investigating this pathological process in more detail. This review aims to provide an overview of recent MRI findings of immune dysregulation in schizophrenia. In addition, we discuss the potential of more recently developed MRI techniques. RECENT FINDINGS: Subtle and indirect signs of immune dysregulation are detected in schizophrenia, particularly in the early stages of the disease. In recently diagnosed schizophrenia patients, findings based on conventional and novel MRI techniques suggest increased glutamate levels and increases in extracellular free water that may be associated with glial activation. As the disease progresses, reductions in white matter, myelin and grey matter seem present, that may point to neurodegeneration. SUMMARY: These MRI findings support the notion of immune dysregulation in early psychosis, which may result in neurodegeneration in later stages. However, these findings are not unequivocal. Therefore, we recommend multimodal MRI studies to further elucidate the role of different immune-related processes in schizophrenia. Future studies should consider inter-individual variability in immune dysregulation, for example, by focusing on recent-onset psychosis and/or by using stratification based on central or peripheral immune markers.
Subject(s)
Brain/diagnostic imaging , Immune System Diseases , Magnetic Resonance Imaging/methods , Schizophrenia , Disease Progression , Humans , Immune System Diseases/diagnosis , Immune System Diseases/psychology , Schizophrenia/diagnosis , Schizophrenia/immunologyABSTRACT
Affect and emotion are defined as "an essential part of the process of an organism's interaction with stimuli." Similar to affect, the immune response is the "tool" the body uses to interact with the external environment. Thanks to the emotional and immunological response, we learn to distinguish between what we like and what we do not like, to counteract a broad range of challenges, and to adjust to the environment we are living in. Recent compelling evidence has shown that the emotional and immunological systems share more than a similarity of functions. This review article will discuss the crosstalk between these two systems and the need for a new scientific area of research called affective immunology. Research in this field will allow a better understanding and appreciation of the immunological basis of mental disorders and the emotional side of immune diseases.
Afecto y emoción son definidos como "una parte esencial del proceso de interaccíon de un organismo con un estímulo". Similar al afecto, la respuesta inmune es la "herramienta" que emplea el cuerpo para interactuar con el ambiente externo. Gracias a la respuesta emocional e inmune, aprendemos a distinguir entre lo que queremos y no queremos, a contrarrestar una amplia gama de desafíos, y a adaptarnos con el ambiente donde estamos viviendo. Evidencias recientes y convincentes han mostrado que los sistemas emocional e inmunológico comparten más de una semejanza de funciones. Este artículo de revisión discutirá las alteraciones de la comunicación entre estos sistemas y la necesidad de una nueva área de investigación científica denominada inmunología afectiva. La investigación en este campo permitirá una mejor comprensión y apreciación de las bases inmunológicas de los trastornos mentales y del aspecto emocional de las enfermedades inmunes.
L'affect et l'émotion se définissent comme « une part essentielle du processus d'interaction d'un organisme avec les stimuli ¼. Similaire à l'affect, la réponse immunitaire est « l'outil ¼ utilisé par le corps pour interagir avec l'environnement extérieur. Grâce aux réponses émotionnelle et immunologique, nous apprenons à distinguer ce que nous aimons de ce que nous n'aimons pas, pour affronter un large éventail de défis, et pour nous adapter à l'environnement dans lequel nous vivons. Des données récentes ont montré que les systèmes émotionnels et immunologiques partagent plus qu'une similarité de fonctions. Cet article de synthèse analyse les interactions entre ces deux systèmes et la nécessité de définir un nouveau domaine de recherche appelé immunologie affective. La recherche dans ce domaine permettra une meilleure compréhension et une meilleure appréciation de la base immunologique des troubles mentaux et du côté émotionnel des maladies immunitaires.
Subject(s)
Emotions/physiology , Immune System Diseases/psychology , Mood Disorders/immunology , Receptor Cross-Talk/immunology , Humans , Immune System Diseases/immunology , ImmunityABSTRACT
INTRODUCTION: Depression can suppress immune function, leading to lower resistance against infection and longer healing times in depressed individuals. Sexuality may also influence immune function, with evidence that sexual activity is associated with lowered immune function in women and mixed results in men. Immune mediators like immunoglobulin A (IgA) are immediately relevant to sexual health, since they are the first line of defense against pathogens at mucous membranes like the vagina. AIM: This study aims to determine if and how depression, sexual activity, and their interaction impact salivary IgA (SIgA) in men and women. METHODS: In Study 1, a community-based sample of 84 women and 88 men provided saliva samples and completed questionnaires on their demographic background, level of depression, and frequency of partnered and solitary sexual activity. Study 2, conducted separately in an undergraduate student sample of 54 women and 52 men, had similar methods. MAIN OUTCOME MEASURES: The main outcome measures were scores on the General Well-Being Schedule depression subscale, reported frequency of sexual activity, and SIgA levels as measured by enzyme immunoassay. RESULTS: Across studies, higher levels of partnered sexual activity were associated with lower SIgA for women with high depression scores, but not for women with low depression scores. In contrast, higher levels of partnered sexual activity were associated with higherâ SIgA for men with high depression scores, but not for men with low depression scores. CONCLUSION: Our results show that partnered sexual activity is a risk factor for lowered immunity in women with depressive symptoms but a possible resilience factor for men with depressive symptoms. This suggests a role for sexual activity in determining the impact of depression on physical health parameters.
Subject(s)
Depressive Disorder/immunology , Immune System Diseases/psychology , Sexual Behavior/psychology , Adolescent , Depressive Disorder/psychology , Female , Humans , Immunoglobulin A/metabolism , Male , Risk Factors , Saliva/chemistry , Sexual Behavior/physiology , Sexual Behavior/statistics & numerical data , Sexual Partners , Surveys and Questionnaires , Young AdultABSTRACT
An increasing body of evidence reported in the literature indicates a possible role for post-traumatic stress disorder (PTSD) as a cause for cardiovascular disease (CVD). However, mechanistic evidence on the progression of adverse cardiac outcomes in PTSD is lacking. In this review, we examine the potential paths by which CVD could occur in those with PTSD. Dysregulation of the hypothalamic-pituitary-adrenal axis and autonomic nervous dysfunction are commonly observed in PTSD, which in turn leads to a variety of physiological changes potentially damaging to the heart. Increased inflammation, dysfunction of the vascular endothelium, hypercoagulability, and cardiac hyperreactivity all have been noted in patients with PTSD. Altered neurochemistry, most notably increased arginine vasopressin, as well as an increased prevalence of the metabolic syndrome, may also contribute to adverse cardiac outcomes. Although the association between PTSD and physical disease is often complicated by health risk behaviors or comorbid psychiatric conditions, the evidence for a link between PTSD and CVD is substantial. In our examination, we attempt to identify potential cardiac biomarkers that may be useful in detecting increased cardiac risk in patients with PTSD. As research in this area is exceedingly limited, we hope to inspire further research, as there is great potential value in identifying prognostically useful cardiac biomarkers so as to predict and prevent the onset of CVD in patients with PTSD.
Subject(s)
Biomarkers/blood , Cardiovascular Diseases/psychology , Stress Disorders, Post-Traumatic/complications , Autonomic Nervous System Diseases/psychology , Cardiovascular Diseases/physiopathology , Endothelium, Vascular/physiology , Forecasting , Humans , Hypothalamo-Hypophyseal System/physiology , Immune System Diseases/psychology , Metabolic Diseases/psychology , Pituitary-Adrenal System/physiology , Risk Factors , Stress Disorders, Post-Traumatic/physiopathologyABSTRACT
Since oophorectomy in healthy women predates the commercialization of BRCA mutations screens, genomics cannot explain entirely why physicians and cancer specialists recommend this procedure for women at risk. Rather, one must situate the development of reproductive cancer genomics within a broader sociocultural context in which researchers bring to bear habits of mind about women, reproduction and motherhood. (Happe, 2006, p. 173)
Subject(s)
Gender Identity , Ovariectomy/psychology , Ovariectomy/statistics & numerical data , Ovary/surgery , Self Concept , Adult , Breast Neoplasms/epidemiology , Breast Neoplasms/genetics , Breast Neoplasms/prevention & control , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/psychology , Cognition Disorders/epidemiology , Cognition Disorders/psychology , Female , Genes, BRCA1 , Humans , Immune System Diseases/epidemiology , Immune System Diseases/psychology , Male , Menopause/psychology , Middle Aged , Mothers/psychology , Osteoporosis/epidemiology , Osteoporosis/psychology , Ovarian Neoplasms/epidemiology , Ovarian Neoplasms/prevention & control , Risk Factors , Sleep Wake Disorders/epidemiology , Sleep Wake Disorders/psychologyABSTRACT
This article explores the concept of allostatic load and its utility as an integrative framework for thinking about the impact of chronic stress on children and adolescents. Allostatic load refers to the failure or exhaustion of normal physiologic processes that occurs in response to severe, frequent, or chronic stressors. This persistent physiologic dysregulation may lead to secondary health problems such as immunosuppression, obesity, atherosclerosis, and hypertension. Allostatic load can be measured and followed as a composite index of a group of physiologic parameters which fall outside of a normal range. Although research regarding allostatic load in children is limited, this article explores relevant studies and identifies ways in which the concept of allostatic load can be used to broaden approaches to assessment, case formulation, and treatment in children. The concept of allostatic load may be of particular interest to psychodynamic psychiatrists in recognizing the ways in which chronic stress and adverse childhood experiences lead not only to negative psychological sequelae but also to long-term health consequences including the possibility of premature death. It underscores the importance of monitoring patients' physical as well as psychological health and thinking about the complex interrelations between the two.
Subject(s)
Allostasis , Stress, Psychological/physiopathology , Stress, Psychological/psychology , Adaptation, Psychological , Adolescent , Atherosclerosis/complications , Atherosclerosis/physiopathology , Atherosclerosis/psychology , Child , Chronic Disease , Humans , Hypertension/complications , Hypertension/physiopathology , Hypertension/psychology , Immune System Diseases/complications , Immune System Diseases/physiopathology , Immune System Diseases/psychology , Obesity/complications , Obesity/physiopathology , Obesity/psychology , Stress, Psychological/complicationsABSTRACT
Recent studies have implicated physiological and metabolic abnormalities in autism spectrum disorders (ASD) and other psychiatric disorders, particularly immune dysregulation or inflammation, oxidative stress, mitochondrial dysfunction and environmental toxicant exposures ('four major areas'). The aim of this study was to determine trends in the literature on these topics with respect to ASD. A comprehensive literature search from 1971 to 2010 was performed in these four major areas in ASD with three objectives. First, publications were divided by several criteria, including whether or not they implicated an association between the physiological abnormality and ASD. A large percentage of publications implicated an association between ASD and immune dysregulation/inflammation (416 out of 437 publications, 95%), oxidative stress (all 115), mitochondrial dysfunction (145 of 153, 95%) and toxicant exposures (170 of 190, 89%). Second, the strength of evidence for publications in each area was computed using a validated scale. The strongest evidence was for immune dysregulation/inflammation and oxidative stress, followed by toxicant exposures and mitochondrial dysfunction. In all areas, at least 45% of the publications were rated as providing strong evidence for an association between the physiological abnormalities and ASD. Third, the time trends in the four major areas were compared with trends in neuroimaging, neuropathology, theory of mind and genetics ('four comparison areas'). The number of publications per 5-year block in all eight areas was calculated in order to identify significant changes in trends. Prior to 1986, only 12 publications were identified in the four major areas and 51 in the four comparison areas (42 for genetics). For each 5-year period, the total number of publications in the eight combined areas increased progressively. Most publications (552 of 895, 62%) in the four major areas were published in the last 5 years (2006-2010). Evaluation of trends between the four major areas and the four comparison areas demonstrated that the largest relative growth was in immune dysregulation/inflammation, oxidative stress, toxicant exposures, genetics and neuroimaging. Research on mitochondrial dysfunction started growing in the last 5 years. Theory of mind and neuropathology research has declined in recent years. Although most publications implicated an association between the four major areas and ASD, publication bias may have led to an overestimation of this association. Further research into these physiological areas may provide insight into general or subset-specific processes that could contribute to the development of ASD and other psychiatric disorders.
Subject(s)
Child Development Disorders, Pervasive/etiology , Child Development Disorders, Pervasive/metabolism , Hazardous Substances/adverse effects , Immune System Diseases/psychology , Mitochondrial Diseases/psychology , Oxidative Stress/physiology , Publication Bias/trends , Child , Child Development Disorders, Pervasive/complications , Child Development Disorders, Pervasive/immunology , Humans , Immune System Diseases/complications , Mitochondrial Diseases/complicationsABSTRACT
AIMS: Patients with intractable disease require long-term treatment and experience repeated bouts of progressive symptoms and resolutions, which cause them severe suffering. The aim of this study was to elucidate the concepts of self-transcendence and subjective well-being in patients with intractable disease. METHODS: Forty-four patients with intractable disease (men/women: 22/22) participated. The diseases of the participants were classified into five systems: (i) neural/muscle system; (ii) digestive system; (iii) immunity/blood system; (iv) visual system; and (v) bone/joint system. The controls were 1854 healthy individuals (men/women: 935/869). Participants completed the Self-Transcendence Scale (STS) and the Japanese version of the World Health Organization-Subjective Inventory. The Japanese version of the Mini-International Neuropsychiatric Interview was also used for the intractable disease group. RESULTS: Analysis of covariance found a significant increase in STS score among the intractable disease group (P < 0.001). Multiple regression analysis showed that the positive affect measured by the World Health Organization-Subjective Inventory showed the greatest effect on the STS score for the intractable disease group (ß = 0.539, P < 0.001). CONCLUSION: As a life-changing experience, an intractable disease may influence an increase in self-transcendence. The results also showed that there was a strong correlation between self-transcendence and respondents' subjective well-being. Our results suggest that patients with life-changing intractable disease can have a high level of self-transcendence, which may lead them to regain mental well-being, and increase their psychological health even in situations that cause physical and mental suffering.
Subject(s)
Adaptation, Psychological , Chronic Disease/psychology , Spirituality , Adult , Bone Diseases/psychology , Digestive System Diseases/psychology , Female , Hematologic Diseases/psychology , Humans , Immune System Diseases/psychology , Japan , Joint Diseases/psychology , Life Change Events , Male , Middle Aged , Neuromuscular Diseases/psychology , Personal Satisfaction , Vision Disorders/psychologyABSTRACT
Psycho- and immunomodulator activity of GABA(B)-mimetic drug baclofen was studied on Wistar-line rats with the cyclophosphamide-induced immunosuppression and lypopolysaccharide-induced immune stress. It was established that the stimulation of GABA(B) receptors in animals with the immune system hypofunction favors regeneration of the cellular and humoral components of immune response. At the same time, under the conditions of immune hyperreactivity, the modulating effect of baclofen appears only in respect of the cell-mediated immune reaction. Moreover, it was shown that baclofen suppresses psychoemotional disorders that develop under the conditions of cyclophosphamide- and lipopolysaccharide-induced immunopathology. The results obtained in this study confirm that GABA(B) receptors participate in the processes of psycho- and immunomodulation.
Subject(s)
Baclofen/therapeutic use , Behavior, Animal/drug effects , GABA-B Receptor Agonists/therapeutic use , Immune System Diseases/drug therapy , Immune System Diseases/psychology , Immunologic Factors/therapeutic use , Animals , Baclofen/administration & dosage , Baclofen/pharmacology , Cyclophosphamide/pharmacology , Exploratory Behavior/drug effects , GABA-B Receptor Agonists/administration & dosage , GABA-B Receptor Agonists/pharmacology , Immune System Diseases/chemically induced , Immunity, Cellular/drug effects , Immunity, Humoral/drug effects , Immunologic Factors/administration & dosage , Immunologic Factors/pharmacology , Lipopolysaccharides/pharmacology , Maze Learning/drug effects , Motor Activity/drug effects , Rats , Rats, WistarABSTRACT
Huntington's disease (HD) is a devastating and incurable neurodegenerative disorder characterized by progressive cognitive, psychiatric and motor impairments. Although the disease has been seen as a disorder purely of the brain, there is now emerging evidence that abnormalities outside the central nervous system are commonly seen in HD. Indeed, the mutant huntingtin (mHtt) coded for by the abnormal gene in HD is found in every cell type where its presence has been sought. In particular, there are a number of recent observations in HD patients that mHtt interacts with the immune system with accumulating evidence that changes in the immune system may critically contribute to the pathology of HD. However, the nature of this contribution remains unclear, to the extent that it is not even known whether the immune system has a beneficial or detrimental role in HD patients. In this review, we attempt to bring a novel understanding to the interaction of the immune system to HD pathology, thereby shedding light on its potential pathogenic role. As part of this discussion, we revisit the clinical data on the anti-inflammatory drug trials in HD and propose new experimental approaches to interrogate the role of immunity in this currently incurable disorder.
Subject(s)
Huntington Disease/immunology , Immune System Diseases/psychology , Immunity/genetics , Animals , Anti-Inflammatory Agents/therapeutic use , Humans , Huntingtin Protein , Huntington Disease/complications , Huntington Disease/drug therapy , Huntington Disease/genetics , Immune System Diseases/complications , Immune System Diseases/genetics , Inflammation/metabolism , Models, Immunological , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Nuclear Proteins/genetics , Nuclear Proteins/metabolismABSTRACT
The molecular basis for psychosocial-distress mediated immune-dysregulation is not well understood. The purpose of this study was to determine whether peripheral blood mononuclear cell (PBMC) epigenetic pattern associates with this form of immune dysregulation. Women newly diagnosed with early stage breast cancer were enrolled into the study and psychosocial, immunological and epigenetic assessments were made at diagnosis and four months later, after completion of cancer treatment. At diagnosis women reported increased perceived stress, anxiety, and mood disturbance and the PBMC of these women exhibited reduced natural killer cell activity and reduced production of interferon gamma, which contrasted with results, obtained after completion of treatment. At the epigenetic level, a PBMC subset derived from women at diagnosis exhibited a distinct epigenetic pattern, with reduced nuclear acetylation of histone residues H4-K8 and H4-K12, as well as reduced phosphorylation of H3-S10, when compared to similar cells derived after the completion of treatment. Natural killer cell activity and interferon-gamma production were associated with nuclear acetylation and phosphorylation status of these histone residues. These findings demonstrate associations among nuclear epigenetic pattern and the immune dysregulation that accompanies psychosocial distress.
Subject(s)
Epigenesis, Genetic/immunology , Immune System Diseases/psychology , Stress, Psychological/immunology , Adult , Aged , Breast Neoplasms/genetics , Breast Neoplasms/immunology , Breast Neoplasms/psychology , Carcinoma, Intraductal, Noninfiltrating/genetics , Carcinoma, Intraductal, Noninfiltrating/immunology , Carcinoma, Intraductal, Noninfiltrating/psychology , Cytokines/immunology , Cytokines/physiology , Epigenesis, Genetic/genetics , Female , Flow Cytometry , Humans , Immune System Diseases/genetics , Immune System Diseases/immunology , Interferon-gamma/immunology , Interferon-gamma/physiology , Killer Cells, Natural/immunology , Killer Cells, Natural/physiology , Lymphocytes/immunology , Lymphocytes/physiology , Middle Aged , Psychological Tests , Stress, Psychological/geneticsABSTRACT
Serotonin (5-hydroxytryptamine; 5-HT) has an important role in mood regulation, and its dysfunction in the central nervous system (CNS) is associated with depression. Reports of mood and immune disorder co-morbidities indicate that immune-5-HT interactions may mediate depression present in immune compromised disease states including HIV/AIDS, multiple sclerosis, and Parkinson's disease. Chemokines, immune proteins that induce chemotaxis and cellular adhesion, and their G-protein coupled receptors distribute throughout the CNS, regulate neuronal patterning, and mediate neuropathology. The purpose of this study is to investigate the neuroanatomical and neurophysiological relationship between the chemokine fractalkine/CX3CL1 and its receptor CX3CR1 with 5-HT neurons in the rat midbrain raphe nuclei (RN). Immunohistochemistry was used to examine the colocalization of CX3CL1 or CX3CR1 with 5-HT in the RN, and whole-cell patch-clamp recordings in rat brain slices were used to determine the functional impact of CX3CL1 on 5-HT dorsal raphe nucleus (DRN) neurons. Greater than 70% of 5-HT neurons colocalize with CX3CL1 and CX3CR1 in the RN. CX3CL1 localizes as discrete puncta throughout the cytoplasm, whereas CX3CR1 concentrates to the perinuclear region of 5-HT neurons and exhibits microglial expression. CX3CL1 and CX3CR1 also colocalize with one another on individual RN cells. Electrophysiology studies indicate a CX3CL1-mediated enhancement of spontaneous inhibitory postsynaptic current (sIPSC) amplitude and dose-dependent increase of evoked IPSC (eIPSC) amplitude without affecting eIPSC paired-pulse ratio, a finding observed selectively in 5-HT neurons. CX3CL1's effect on eIPSC amplitude is blocked by pretreatment with an anti-CX3CL1 neutralizing antibody. Thus, CX3CL1 enhances postsynaptic GABA receptor number or sensitivity on 5-HT DRN neurons under conditions of both spontaneous and synaptically-evoked GABA release. CX3CL1 may indirectly inhibit 5-HT neurotransmission by increasing the sensitivity of 5-HT DRN neurons to GABA inputs. Therapies targeting CX3CL1 may treat serotonin related mood disorders, including depression experienced by patients with compromised immune systems.
Subject(s)
Chemokine CX3CL1/metabolism , Mesencephalon/metabolism , Neurons/metabolism , Raphe Nuclei/metabolism , Serotonin/metabolism , gamma-Aminobutyric Acid/metabolism , Animals , Chemokine CX3CL1/pharmacology , Depressive Disorder/drug therapy , Depressive Disorder/immunology , Depressive Disorder/physiopathology , Immune System Diseases/complications , Immune System Diseases/physiopathology , Immune System Diseases/psychology , Male , Mesencephalon/cytology , Neural Inhibition/drug effects , Neural Inhibition/immunology , Neurons/drug effects , Raphe Nuclei/cytology , Rats , Rats, Sprague-Dawley , Synaptic Transmission/drug effects , Synaptic Transmission/immunology , Up-Regulation/drug effects , Up-Regulation/immunologyABSTRACT
BACKGROUND: Immune thrombocytopenic purpura (ITP), a condition characterized by autoimmune-mediated platelet destruction and suboptimal platelet production, is associated with symptoms such as bruising, epistaxis, menorrhagia, mucosal bleeding from the gastrointestinal and urinary tracts and, rarely central nervous system bleeding. The aim of this research is to develop a conceptual model to describe the impact of ITP and its treatment on patients' health-related quality of life (HRQoL). METHODS: A literature search and focus groups with adult ITP patients were conducted to identify areas of HRQoL affected by ITP. Published literature was reviewed to identify key HRQoL issues and existing questionnaires used to assess HRQoL. Focus group transcripts were reviewed, and common themes were extracted by grouping conceptual categories that described the impact on HRQoL. RESULTS: The literature synthesis and themes from the focus group data suggest that decreased platelet counts, disease symptoms, and treatment side effects influence multiple domains of HRQoL for ITP patients. Key areas affected by ITP and its treatments include emotional and functional health, work life, social and leisure activities, and reproductive health. CONCLUSION: ITP affects various areas of HRQoL. This conceptual model will help inform the evaluation of therapeutic strategies for ITP.
Subject(s)
Health Status , Purpura, Thrombocytopenic , Quality of Life , Adolescent , Adult , California , Chronic Disease , Female , Focus Groups , Hospitals, Teaching , Humans , Immune System Diseases/psychology , Male , Models, Theoretical , New York City , Oklahoma , Psychometrics/methods , Purpura, Thrombocytopenic/physiopathology , Purpura, Thrombocytopenic/psychology , Reproducibility of Results , Social Behavior , Surveys and QuestionnairesABSTRACT
For many years, anecdotal evidence and clinical observations have suggested that exposure to psychosocial stress can affect disease outcomes in immune-related disorders such as viral infections, chronic autoimmune diseases and tumors. Experimental evidence in humans supporting these observations was, however, lacking. Studies published in the last 2 decades in Brain, Behavior and Immunity and other journals have demonstrated that acute and chronic psychological stress can induce pronounced changes in innate and adaptive immune responses and that these changes are predominantly mediated via neuroendocrine mediators from the hypothalamic-pituitary-adrenal axis and the sympathetic-adrenal axis. In addition, psychological stress has predicted disease outcomes using sophisticated models such as viral challenge, response to vaccination, tracking of herpesvirus latency, exploration of tumor metastasis and healing of experimental wounds, as well as epidemiological investigations of disease progression and mortality. These studies have contributed significantly to our understanding that the neuroendocrine-immune interaction is disturbed in many pathophysiological conditions, that stress can contribute to this disturbance, and that malfunction in these communication pathways can play a significant role in the progression of disease processes. There are, however, significant gaps in the extant literature. In the coming decade(s), it will be essential to further analyze neuroendocrine-immune communication during disease states and to define the specific pathways linking the central nervous system to the molecular events that control important disease-relevant processes. This knowledge will provide the basis for new therapeutic pharmacological and non-pharmacological behavioral approaches to the treatment of chronic diseases via specific modulation of nervous system-immune system communication.