Inflammation in psychotic disorders: A population-based study
Introduction
Inflammation and immunity may be involved in the etiology and pathogenesis of schizophrenia and major mood disorders (Ganguli et al., 1994, Miller et al., 2009, Drexhage et al., 2010). There is evidence of both proinflammatory activation of the innate immune system and an activation of the T-cells of the adaptive immune system in both schizophrenia and bipolar disorder (Drexhage et al., 2010). This activation is reflected in alterations in circulating inflammatory cytokines (Potvin et al., 2008, Brietzke et al., 2009, Miller et al., 2009).
Elevated cytokine levels might lead to psychiatric symptoms through several mechanisms. Cytokines are involved in neuronal cell survival (de Araujo et al., 2009), neural stem cell renewal, differentiation and brain repair (Bauer, 2009), and in monoamine neurotransmitter metabolism (Miller et al., 2009). Some cytokines have stressor-like effects on CNS, including changes in tryptophan metabolism, hypothalamo–pituitary–adrenocortical axis, and brain-derived neurotrophic factor expression (Dantzer et al., 2008, Miller et al., 2009).
However, elevated cytokine levels might also reflect general medical comorbidity and lifestyle-related factors in psychotic disorders. Schizophrenia and other psychotic disorders are associated with high prevalence of type 2 diabetes (Suvisaari et al., 2008), metabolic syndrome (Suvisaari et al., 2007), and obesity (Saarni et al., 2009), all diseases in which inflammation has a key role (Pradhan et al., 2001, Hajer et al., 2008). Lifestyle-related factors that could be related to the association between psychotic disorders and both inflammation and medical comorbidity include smoking (Sopori, 2002), alcohol use (Cook, 1998), and poor physical condition and low muscle strength (Schrager et al., 2007, Ruiz et al., 2008).
The objectives of the current study were to investigate the role of inflammation in different psychotic disorders, and its association with metabolic comorbidity, antipsychotic medication, smoking and alcohol use, physical fitness, and mood in a general population-based sample of people with psychotic disorders and matched controls. We analyzed five cytokines or cytokine receptors most strongly associated with schizophrenia in a recent meta-analysis (Potvin et al., 2008): tumor necrosis factor alpha (TNF-α), interleukin-1 receptor antagonist (IL-1RA), interleukin-2 (IL-2) and its soluble receptor's alpha subunit (sIL-2Rα), and interleukin-6 (IL-6), and sensitive C-reactive protein (CRP) as another inflammatory marker.
Section snippets
Study population
The Health 2000 survey was based on a nationally representative sample of 8028 persons aged 30 years or over from Finland. A two-stage stratified cluster sampling procedure was used. The field work took place between September 2000 and June 2001, and consisted of an interview and a comprehensive health examination. The Health 2000 study and the accompanying Psychoses in Finland (PIF) study were approved by the Ethics Committees of the National Public Health Institute (since 2009 the National
Clinical and metabolic characteristics
When each diagnostic group was compared with its matched controls, persons with schizophrenia had significantly higher glucose, insulin, triglyceride, and CRP levels and lower HDL level, as well as higher BDI score, larger waist circumference and higher prevalence of type 2 diabetes than their controls. Persons with ONAP had significantly higher triglyceride and CRP levels, larger waist circumference and higher BDI score than their controls. Persons with affective psychosis had higher BDI score
Discussion
Elevated soluble IL-2-receptor's alpha subunit (sIL-2Rα) concentration in persons with schizophrenia is consistent with previous research (Rapaport et al., 1993, Potvin et al., 2008), and since activated T-cells express a high level of IL-2Rα (Malek and Bayer, 2004), the results suggest that persons with schizophrenia have increased T-cell activity. It has been suggested that the T-cell activation in schizophrenia would be related to regulatory T-cell (Treg) activity rather than a high effector
Acknowledgments
This study was supported by the NARSAD Maltz Investigator Award and the Academy of Finland grant (129434).
References (52)
- et al.
Comparison of cytokine levels in depressed, manic, and euthymic patients with bipolar disorder
Journal of Affective Disorders
(2009) - et al.
Coagulation and inflammation markers during atypical or typical antipsychotic treatment in schizophrenia patients and drug-free first-degree relatives
Schizophrenia Research
(2008) - et al.
The relationship between blood pressure and C-reactive protein in the Multi-Ethnic Study of Atherosclerosis (MESA)
Journal of the American College of Cardiology
(2005) - et al.
Genetic variation of the interleukin-1 family and nongenetic factors determining the interleukin-1 receptor antagonist phenotypes
Metabolism
(2010) - et al.
Inflammatory markers in schizophrenia: comparing antipsychotic effects in Phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness Study
Biological Psychiatry
(2009) - et al.
Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression
Biological Psychiatry
(2009) - et al.
The wolf in sheep's clothing: the role of interleukin-6 in immunity, inflammation and cancer
Trends in Molecular Medicine
(2008) Regulatory T cells in health and disease
Cytokine
(2008)- et al.
Inflammatory cytokine alterations in schizophrenia: a systematic quantitative review
Biological Psychiatry
(2008) - et al.
Reduction in C-reactive protein and LDL cholesterol and cardiovascular event rates after initiation of rosuvastatin: a prospective study of the JUPITER trial
Lancet
(2009)
Activation of indices of cell-mediated immunity in bipolar mania
Biological Psychiatry
Is autoimmune thyroiditis part of the genetic vulnerability (or an endophenotype) for bipolar disorder?
Biological Psychiatry
Cytokine control of adult neural stem cells. Chronic versus acute exposure
Annals of the New York Academy of Science
The TNF-α system: functional aspects in depression, narcolepsy, and psychopharmacology
Current Neuropharmacology
Learning Bayesian networks with mixed variables
DEAL: a package for learning Bayesian networks
Journal of Statistical Software
Accelerated increase in serum interleukin-1 receptor antagonist starts 6 years before diagnosis of type 2 diabetes: Whitehall II prospective cohort study
Diabetes
Increased plasma interleukin-1 receptor antagonist levels in men with visceral obesity
Annals of Medicine
Alcohol abuse, alcoholism, and damage to the immune system — a review
Alcoholism, Clinical and Experimental Research
From inflammation to sickness and depression: when the immune system subjugates the brain
Nature Reviews Neuroscience
Neuronal cell survival: the role of interleukins
Annals of the New York Academy of Science
The mononuclear phagocyte system and its cytokine networks in schizophrenia and bipolar disorder
Expert Review of Neurotherapeutics
Autoimmune diseases, bipolar disorder, and non-affective psychosis
Bipolar Disorders
C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis
Lancet
Inflammation and cardiovascular disease: role of the interleukin-1 receptor antagonist
Circulation
Cited by (58)
Cortisol and cytokines in schizophrenia: A scoping review
2023, Comprehensive PsychoneuroendocrinologyImmune response to vaccination in adults with mental disorders: A systematic review
2022, Journal of Affective DisordersThe aetiology of social deficits within mental health disorders: The role of the immune system and endogenous opioids
2020, Brain, Behavior, and Immunity - HealthRelation of inflammatory markers with symptoms of psychotic disorders: a large cohort study
2018, Progress in Neuro-Psychopharmacology and Biological PsychiatryExcess mortality in severe mental illness: more questions than answers
2018, The Lancet PsychiatryCytokines dysregulation in schizophrenia: A systematic review of psychoneuroimmune relationship
2018, Schizophrenia Research