Cytokines and the Brain: Implications for Clinical Psychiatry (original) (raw)
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Molecular psychiatry, 2002
There is convincing evidence that cytokines are involved in the physiology and pathophysiology of brain function and interact with different neurotransmitter and neuroendocrine pathways. The possible involvement of the immune system in the neurobiological mechanisms that underlie psychiatric disorders has attracted increasing attention in recent years. Thus in the last decade, numerous clinical studies have demonstrated dysregulated immune functions in patients with psychiatric disorders. Such findings formed the basis of the 7th Expert Meeting on Psychiatry and Immunology in Muenster, Germany, where a consensus symposium was held to consider the strengths and weaknesses of current research in psychoneuroimmunology. Following a general overview of the field, the following topics were discussed: (1) methodological problems in laboratory procedures and recruitment of clinical samples; (2) the importance of pre-clinical research and animal models in psychiatric research; (3) the proble...
Journal of Psychiatric Research, 1999
It has been hypothesized that the immune system plays a pathogenetic role in psychiatric disorders, in particular in major depression and schizophrenia. This hypothesis is supported by a number of reports on altered circulating levels and in vitro production of cytokines in these disorders. However, the respective evidence is not consistent. This may be in part due to an incomplete control for numerous confounding in¯uences in earlier studies. We investigated the plasma levels of cytokines and soluble cytokine receptors in psychiatric patients (N = 361) upon hospital admission and compared the results to those obtained in healthy controls (N = 64). By multiple regression analysis we found that circulating levels of interleukin-1 receptor antagonist (IL-1Ra), soluble IL-2 receptor (sIL-2R), tumor necrosis factor-a (TNF-a), soluble TNF receptors (sTNF-R p55, sTNF-R p75) and IL-6 were signi®cantly aected by age, the body mass index (BMI), gender, smoking habits, ongoing or recent infectious diseases, or prior medication. Cytokine or cytokine receptor levels were signi®cantly increased in patients treated with clozapine (sIL-2R, sTNF-R p75), lithium (TNF-a, sTNF-R p75, IL-6) or benzodiazepines (TNF-a, sTNF-R p75). Taking all these confounding factors into account, we found no evidence for disease-related alterations in the levels of IL-1Ra, sIL-2R, sTNF-R p75 and IL-6, whereas levels of TNF-a and sTNF-R p55 in major depression and sTNF-R p55 in schizophrenia were slightly decreased compared to healthy controls. We conclude that, if confounding factors are carefully taken into account, plasma levels of the above mentioned cytokines and cytokine receptors yield little, if any, evidence for immunopathology in schizophrenia or major depression. #
Cytokines dysregulation in schizophrenia: A systematic review of psychoneuroimmune relationship
Introduction: Schizophrenia is a multifactorial psychiatric disease with complex interactions among the brain and the immune system. A psycho-immune relationship underling schizophrenia is supported by several studies and integrates a specific area of knowledge-psychoneuroimmunology. Methods: A systematic review was performed by 2009 Preferred Reporting Items (PRISMA) recommendations. Based on the inclusion/exclusion criteria, publications with relevant information (evaluated by the Joanna Briggs Institute Critical Appraisals tools to quality assessment) were included. Results: In this review, we considered the inflammatory activity promoted by cytokine alterations in schizophre-nia aetiology, which reflects the systemic comprehension of this disease in opposition to the traditional approach focused solely on the brain. We focus on the analysis of several specific outcomes, such as proinflammatory cy-tokines, sample sort, laboratory techniques, diagnosis scales and results of each publication. Conclusion: This systematic review confirms the existence of cytokines abnormalities in schizophrenia disease. Immune imbalances such as increased levels of some cytokines (either at protein level or at mRNA expression), cytokine mRNAs, as well as cytokine gene polymorphisms have been reported with a large support in schizo-phrenia. These findings provide a strong evidence of a concomitant process of inflammatory activity in schizo-phrenia illness course.
Brain, Behavior, and Immunity, 2001
The present paper reviews the results of all publications on in vitro cytokine secretion in patients with schizophrenia, as published by March 2001. The authors supply easy to read tables with respect to the individual cytokines and soluble cytokine receptors investigated, the in vitro methodology used, characterization of the patient samples, and the results on cytokine secretion as stated in these studies. Inconsistent results, e.g., regarding in vitro secretion of IL-2 with 11/18 studies finding decreased secretion, 5/18 finding no change, and 2/18 finding increases, cannot systematically be correlated with any methodological procedures nor any diagnostic subtypes, per se. However, factors such as medication and cigarette smoking are likely to play a role. The authors suggest that more hypothesis-driven research, together with more carefully designed studies, as well as better communication between basic or animal researchers and clinicians might help to answer the question of whether there are meaningful peripheral changes in the immune system related to schizophrenia.
Cytokines in schizophrenia: Hope or hype?
Indian Journal of Psychological Medicine, 2016
Although there is a cumulative evidence for the inflammation pathophysiology in schizophrenia, it has not been conclusively proven yet. One reason for this is the lack of studies that have controlled for major confounding factors such as obesity, smoking, antipsychotic use, and stress. The studies in which the major confounding factors were controlled were done in subjects in acute relapse and in treatment-resistant schizophrenia. To date, no studies have been done in stable outpatients with schizophrenia controlling for major confounding factors. Data on cerebrospinal fluid cytokines in large sample independent of confounding factors are also lacking. The efficacy signal from anti-inflammatory medications in schizophrenia has been modest. In this study, the inconsistent and nonvalidated cytokine findings independent of the confounding factors are discussed.
Molecular Psychiatry, 2016
Schizophrenia, bipolar disorder and major depressive disorder (MDD) have all been associated with aberrant blood cytokine levels; however, neither the pattern of cytokine alterations nor the impact of clinical status have been compared across disorders. We performed a meta-analysis of blood cytokines in acutely and chronically ill patients with these major psychiatric disorders. Articles were identified by searching the PubMed, PsycInfo and Web of Science, and the reference lists of these studies. Sixty-eight studies met the inclusion criteria (40 schizophrenia, 10 bipolar disorder and 18 MDD) for acutely ill patients. Forty-six studies met the inclusion criteria (18 schizophrenia, 16 bipolar disorder and 12 MDD) for chronically ill patients. Levels of two cytokines (interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α)), one soluble cytokine receptor (sIL-2R), and one cytokine receptor antagonist (IL-1RA) were significantly increased in acutely ill patients with schizophrenia, bipolar mania and MDD compared with controls (P < 0.01). Following treatment of the acute illness, IL-6 levels significantly decreased in both schizophrenia and MDD (P < 0.01); sIL-2R levels increased in schizophrenia; and IL-1RA levels in bipolar mania decreased. In chronically ill patients, the levels of IL-6 were significantly increased in schizophrenia, euthymic (but not depressed) bipolar disorder and MDD compared with controls (P < 0.01). The levels of IL-1β and sIL-2R were significantly increased in both chronic schizophrenia and euthymic bipolar disorder. Overall, there were similarities in the pattern of cytokine alterations in schizophrenia, bipolar disorder and MDD during acute and chronic phases of illness, raising the possibility of common underlying pathways for immune dysfunction. Effects of treatment on
Cytokine Imbalance in Schizophrenia. From Research to Clinic: Potential Implications for Treatment
Frontiers in Psychiatry
Cytokines are one of the most important components of the immune system. They orchestrate the brain's response to infectious and other exogenous insults and are crucial mediators of the cross-talk between the nervous and immune systems. Epidemiological studies have demonstrated that severe infections and autoimmune disorders, in addition to genetic predisposition, are risk factors for schizophrenia. Furthermore, maternal infection during pregnancy appears to increase the risk of schizophrenia, and proinflammatory cytokines may be negatively involved in the neurodevelopmental process. A cytokine imbalance has been described in the blood and cerebrospinal fluid of schizophrenia patients, particularly in the T helper type 1 [Th1] and type 2 [Th2] cytokines, albeit the results of such studies appear to be contradictory. Chronic stress, likewise, appears to contribute to a lasting proinflammatory state and likely also promotes the disorder. The aim of this mini-review is to investiga...