Cytokines and the Brain: Implications for Clinical Psychiatry

Kronfol, Ziad

doi:10.1176/appi.ajp.157.5.683

Cited by 676 publications

(420 citation statements)

References 88 publications

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“…Some biological explanations are possible: cytokines play a critical role in the pathogenesis of allergic diseases. 33,34 Besides acting as chemical messengers between immune cells, cytokines can serve as mediators between the immune system and the brain. 33,35 In atopic states, there exists a shift from T helper (Th) 1 to Th2 responses from Th lymphocyte precursors.…”

Section: Discussionmentioning

confidence: 99%

“…33,34 Besides acting as chemical messengers between immune cells, cytokines can serve as mediators between the immune system and the brain. 33,35 In atopic states, there exists a shift from T helper (Th) 1 to Th2 responses from Th lymphocyte precursors. 36 Of the cytokines produced by Th2 cells, 33,34 interleukin-4 (IL-4) is an essential mediator of immediate hypersensitivity favoring the production of immunoglobulin E. 37 IL-4 has, furthermore, been shown to have an effect on the serotonin (5-HT) metabolism, but different regulatory effects on different serotonin transporter (5-HTT) genotypes.…”

Section: Discussionmentioning

confidence: 99%

“…33,35 In atopic states, there exists a shift from T helper (Th) 1 to Th2 responses from Th lymphocyte precursors. 36 Of the cytokines produced by Th2 cells, 33,34 interleukin-4 (IL-4) is an essential mediator of immediate hypersensitivity favoring the production of immunoglobulin E. 37 IL-4 has, furthermore, been shown to have an effect on the serotonin (5-HT) metabolism, but different regulatory effects on different serotonin transporter (5-HTT) genotypes. 12 Because 5-HT is an important mediator of bidirectional interactions between the nervous and the immune systems, 12,38 and because the genetic polymorphism in the 5-HTT gene promoter has been found to be associated with depression, 39 our findings might be explained by an altered 5-HT metabolism in the brain because of some immunological reactions during atopy.…”

Section: Discussionmentioning

confidence: 99%

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Atopy and depression: results from the Northern Finland 1966 Birth Cohort Study

et al. 2003

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Several studies have suggested an association between IgE-mediated atopic allergies and depression. The present study extends our understanding about putative gender differences of this association and provides further epidemiological evidence for our previous finding that the association between atopy and depression may be characteristic for females only. In order to clearly determine the presence of atopic disorders and depression, we used more valid tools than had been employed earlier and we had access to a database (the Northern Finland 1966 Birth Cohort), in which individuals were followed up prospectively until the age of 31 years. The information on allergic symptoms, verified by skin-prick tests and comprising data of 5518 individuals, was used to ascertain the presence of atopy. Depression was assessed with the help of Hopkins' Symptom Checklist-25 and self-reported doctor-diagnosed depression. After adjusting for a father's social class, mother's parity, and place of residence, logistic regression analyses showed that the risk of developing depression increased in parallel with the increasing severity of depression and, when compared with nonatopic subjects, was 3.0 to 4.7-fold up in atopic females and statistically significant. In atopic males, the association between atopy and depression was statistically significant only in the highest depression scores, the odds ratio being 6.3-fold. The results indicate that females suffering from atopic diseases might possess an elevated risk of developing depression already during early adulthood. In males, the association between these two disorders is evident only among the most severe manifestations of depression. Possible background theories, that is, genetic abnormalities in serotonin metabolism, HPA-axis dysfunction, and histamine theory are discussed.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Atopy and depression: results from the Northern Finland 1966 Birth Cohort Study

et al. 2003

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“…Peripheral mononuclear cells may reflect molecular processes in the CNS of schizophrenic patients and have been used to study various substances including cytokines (e.g., interleukins IL-6, IL-10, and IL-2), receptors for major neurotransmitters (e.g., dopamine, serotonin, and GABA A ), and G-protein subunits that regulate intracellular signal transduction. [53][54][55][56][57][58][59][60][61] Chertkow et al 62 used microarrays to examine the gene expression profile of peripheral mononuclear cells in schizophrenia patients on steady antipsychotic treatment before and 3 and 6 weeks after addition of fluvoxamine and found changes in transcripts related to Gprotein coupled receptors. Using customized cDNA array and real-time RT-PCR, they also found significant downregulation of chemokine receptors IL8RA and CCR1, and of RGS7 mRNA.…”

Section: Clinical Relevancementioning

confidence: 99%

Multifunctional Pharmacotherapy: What Can We Learn from Study of Selective Serotonin Reuptake Inhibitor Augmentation of Antipsychotics in Negative-Symptom Schizophrenia?

et al. 2009

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Summary: Many patients suffering from major psychiatric disorders do not respond adequately to monotherapy and require additional drugs. To date, there are no objective guidelines for deciding which combination may be effective, and the choice is based on previous clinical experience and on trial and error. Even when combination drugs are effective, the biochemical mechanisms responsible for the value-added effect are unknown. Understanding the mechanism of such synergism may provide a rational basis for choosing drug combinations and for developing more effective drugs. In schizophrenia, negative symptoms respond poorly to antipsychotics, but may improve when these are augmented with selective serotonin reuptake inhibitors (SSRI). This augmenting effect cannot be explained by summating the pharmacological effects of the individual drugs. We proposed that the study of SSRI augmentation can serve as a window to understanding the biochemical mechanisms of clinically effective drug synergism. In a series of studies we identified unique biochemical effects of the combination, different from each individual drug, and proposed that some of these are involved in mediating the clinical effect. Here we review some of the findings and propose that the mechanism of action involves regionally selective modulation of the GABA system. The evidence indicates that the SSRI antidepressant-antipsychotic combination may be a useful paradigm for studying therapeutically effective synergistic drug interactions in schizophrenia. Although as yet limited in scope, the findings of definable molecular targets for synergistic SSRIantipsychotic interaction provide new directions to inform future research and provide novel bio-molecular targets for drug development.

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“…Tolerance-promoting behavioural and physiological responses can arise when immunoregulatory cytokines interact with the endocrine system, and cause downstream release of glucocorticoids and sickness behaviours [8,[10][11][12]. Indeed, enhanced glucocorticoid production in response to experimental infection from parasites has been documented in domestic animals [13], laboratory amphibians [14] and fish [15,16].…”

Section: Introductionmentioning

confidence: 99%

Changes in physiological stress and behaviour in semi-free-ranging red-capped mangabeys ( Cercocebus torquatus ) following antiparasitic treatment

2016

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Parasites are ubiquitous in wildlife populations, but physiological and behavioural responses of hosts to infection are difficult to measure. We experimentally treated semi-free-ranging red-capped mangabeys (Cercocebus torquatus) in Nigeria with antiparasitic drugs and examined subsequent changes in glucocorticoid production and individual behaviour. Because both parasites and stress impact energy balance and health, we measured (i) behavioural time re-allocation via activity budgets, (ii) social relationships (e.g. social connectivity and dominance hierarchy stability) and (iii) body condition. We collected triplicate faecal samples (n ¼ 441) from 49 individuals prior to and following treatment. Cortisol levels fluctuated in parallel with parasite abundance. Elevations in cortisol, but not parasitism, were related to reduced body condition. Behaviour also shifted according to infection status, with uninfected individuals spending more time foraging and less time resting and vigilant compared with when they were infected. Time spent feeding, travelling or socializing did not differ between pre-and posttreatment time periods. Group cohesion, but not dominance stability, changed following treatment, suggesting parasite-induced social avoidance. Together, these findings show a coordinated response to infection that promotes host tolerance through stress and energy conservation, reduces transmission risk and increases protection when infected hosts are vulnerable.

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Cytokines and the Brain: Implications for Clinical Psychiatry

Abstract: A better understanding of the role of cytokines in various brain activities will enhance knowledge of specific psychobiological mechanisms in health and disease and provide opportunities for novel treatment interventions.

Cited by 676 publications

References 88 publications

Atopy and depression: results from the Northern Finland 1966 Birth Cohort Study

Atopy and depression: results from the Northern Finland 1966 Birth Cohort Study

Multifunctional Pharmacotherapy: What Can We Learn from Study of Selective Serotonin Reuptake Inhibitor Augmentation of Antipsychotics in Negative-Symptom Schizophrenia?

Changes in physiological stress and behaviour in semi-free-ranging red-capped mangabeys ( Cercocebus torquatus ) following antiparasitic treatment

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