interleukin-8 and Psychotic-Disorders

Immune parameters are elevated in psychosis, but it is unclear whether alterations are homogenous across patients or heterogeneity exists, consistent with the hypothesis that immune alterations are specific to a subgroup of patients. To address this, we examine whether antipsychotic-naïve first-episode psychosis patients exhibit greater variability in blood cytokines, C-reactive protein, and white cell counts compared with controls, and if group mean differences persist after adjusting for skewed data and potential confounds. Databases were searched for studies reporting levels of peripheral immune parameters. Means and variances were extracted and analyzed using multivariate meta-analysis of mean and variability of differences. Outcomes were (1) variability in patients relative to controls, indexed by variability ratio (VR) and coefficient of variation ratio (CVR); (2) mean differences indexed by Hedges g; (3) Modal distribution of raw immune parameter data using Hartigan's unimodality dip test. Thirty-five studies reporting on 1263 patients and 1470 controls were included. Variability of interleukin-6 (IL6) (VR = 0.19), tumor necrosis factor-α (TNFα) (VR = 0.36), interleukin-1β (VR = 0.35), interleukin-4 (VR = 0.55), and interleukin-8 (VR = 0.28) was reduced in patients. Results persisted for IL6 and IL8 after mean-scaling. Ninety-four percent and one hundred percent of raw data were unimodally distributed in psychosis and controls, respectively. Mean levels of IL6 (g = 0.62), TNFα (g = 0.56), interferon-γ (IFNγ) (g = 0.32), transforming growth factor-β (g = 0.53), and interleukin-17 (IL17) (g = 0.48) were elevated in psychosis. Sensitivity analyses indicated this is unlikely explained by confounders for IL6, IFNγ, and IL17. These findings show elevated cytokines in psychosis after accounting for confounds, and that the hypothesis of an immune subgroup is not supported by the variability or modal distribution.

Topics: C-Reactive Protein; Case-Control Studies; Cytokines; Humans; Interferon-gamma; Interleukin-17; Interleukin-1beta; Interleukin-4; Interleukin-6; Interleukin-8; Leukocyte Count; Lymphocyte Count; Models, Statistical; Prodromal Symptoms; Psychotic Disorders; Schizophrenia; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha

Considering Acute and Transient psychotic disorders (ATPDs) to be a close entity to Schizophrenia (SZ) with a completely different course and outcome, studies evaluating the immunological abnormalities are scarce in ATPDs. We analysed immune-mediated inflammatory marker levels [Interleukin-2 (IL-2), Interleukin-4 (IL-4), Interleukin-6 (IL-6), Interleukin-8 (IL-8), Interleukin-17 (IL-17) and Tumour necrosis factor-alpha (TNF-α)] in patients with ATPDs (in the acute phase and after remission), and compared these with patients with SZ in remission and with healthy controls.. Ninteen subjects with ATPDs in acute phase of illness were age-/gender-matched with healthy controls and patients with schizophrenia in remission; recruited through purposive sampling. Clinical assessment and immune-marker levels were carried out in all the three groups. Follow -up repeat immune-marker levels assessment in the ATPD group was conducted after remission status was ensured. Immune-marker levels were compared across the three groups.. Patients with ATPDs had elevated levels of the pro-inflammatory cytokines IL-6 and IL-17 and low levels of IL-8 in the acute phase and low levels of IL-6 and elevated levels of IL-8 during the remission phase. Compared to patients with SZ in remission, patients with ATPD in remission had low levels of all the three pro-inflammatory cytokines (with significantly low IL-6 levels and non-significant, yet low levels of IL-8 and IL-17) and had significantly low and high levels of IL-6 and IL-8 respectively than healthy controls.. These findings suggest that there existed immunological abnormalities in the acute and remission phase of illness in patients with ATPDs compared to both patients with SZ in remission and healthy controls.

Topics: Biomarkers; Cytokines; Humans; Interleukin-17; Interleukin-6; Interleukin-8; Psychotic Disorders; Schizophrenia

There are studies to support association between immune function and cognition in patients with schizophrenia (SZ). However, there are no such study which had tried to explore the same in patients with Acute and transient psychotic disorders (ATPDs), which is considered to similar in presentation to SZ.. This is an extended analysis of the study published in which we had recruited 19 subjects with ATPDs in acute phase of illness were age-/gender-matched with patients schizophrenia in remission. Clinical assessment and immune-marker levels (IL-6,IL-8,IL-17) were carried out along with follow -up repeat immune-marker levels assessment in the ATPD group was conducted after remission status was ensured (at least 3 months after resolution of acute phase). Cognitive assessment was done on Montreal Cognitive Assessment Scale (MoCA) in both the groups (ATPD in both phases and in SZ).. The mean MoCA total score was 12.05 (SD-5.0) in the acute phase and 27.05 (SD-2.46) in the remission phase in the ATPD group which was statistically significant. When compared with patients with SZ in remission, patients with ATPD in remission performed better in all domains of MoCA, however only statistically significant differences in the total MoCA score and in the visuospatial domain scores of MoCA. No significant association between any of the immune marker levels (IL-6, Il-8 and IL-17) with any domains of the MoCA in patients with ATPD neither in the acute phase nor in the remission phase was found. Additionally, no significant association between the cognitive scores in the MoCA domains of the patients with schizophrenia and immune marker levels was found too.. To conclude, the present study's findings suggested that there existed definite cognitive deficits in patients with ATPDs in both acute and remission phase and in patients with SZ. However, the study could not establish any relationship/association between cognitive deficits/scores in patients with ATPDs in both phases as well as in patients with SZ with immune marker levels.

Topics: Biomarkers; Cognition; Cognitive Dysfunction; Humans; Interleukin-17; Interleukin-6; Interleukin-8; Neuropsychological Tests; Pilot Projects; Psychotic Disorders

Though many previous studies have indicated immunological alterations in psychotic disorders, the role and prevalence of neuroinflammation is still unknown. Studies previously investigating immune related biomarkers in the cerebrospinal fluid (CSF) of these patients are mainly small studies on few markers, and many have not compared patients to healthy controls.. We will conduct a large case-control study including at least 100 patients with recent onset psychotic disorders and 100 sex- and age matched healthy controls. The cases will include patients diagnosed with a psychotic disorder according to ICD-10 (F20/F22-29) within a year prior to inclusion. We will collect both CSF, blood and fecal samples, to gain insight into possible immunological alterations. The psychopathology of all participants will thoroughly be evaluated using the SCAN interview, and multiple rating scales covering different symptom groups. All participants will partake in a detailed neurological examination, including the Neurological Evaluation Scale assessing neurological soft signs. Additionally, we will assess cognitive functioning, evaluate quality of life and level of functioning, and collect data on a broad array of possible confounders. Our primary outcomes will include CSF leucocytes, CSF/serum albumin ratio, CSF total protein, IgG index, CSF levels of IL-6 and IL-8, and presence of antineuronal autoantibodies in CSF and blood. For our secondary outcomes, exploratory analyses will be performed on a broader panel of neuroimmunological markers. All participants will be invited for a follow-up visit to assess longitudinal changes. The current study is part of a larger CSF biobank build-up for severe mental disorders (PSYCH-FLAME).. This study will represent the largest investigation of CSF in patients with psychotic disorders compared to healthy controls to date. We expect the study to contribute with new, important knowledge on pathophysiological mechanisms, and to help pave the way for future investigations of individualized treatment options.. The study is approved by The Regional Committee on Health Research Ethics (Capital Region, j.no: H-16030985) and The Danish Data Protection Agency (j.no: RHP-2016-020, I-Suite no.: 04945).

Topics: Adult; Age of Onset; Antibodies, Antinuclear; Biomarkers; Case-Control Studies; Female; Humans; Interleukin-6; Interleukin-8; Leukocytes; Male; Middle Aged; Prospective Studies; Psychotic Disorders; Quality of Life; Serum Albumin, Human; Young Adult

Emerging evidence suggests a possible role for immune system dysregulation in the pathogenesis of postpartum psychosis (PP) but the evidence is limited. The current study sought to determine the serum cytokines/ chemokine changes associated with first-onset PP.. Women with first onset PP were recruited as cases and the cytokines/ chemokine changes were compared against healthy postpartum (HP) and healthy non-postpartum (HNP) women.There were 20 subjects in each of the three groups. Levels of serum cytokines and Monocyte Chemoattractant Protein-1 (MCP-1) were estimated with a cytometric beadarray assay.. HP group showed significantly elevated levels of interleukin (IL)-6 as compared to HNP group. Whereas, the first onset PP group showed significantly elevated levels of both IL-6 and IL-8 as compared to HNP group.. Postpartum period appears to be a state of altered immune functioning considering the elevated level of IL-6 in both HP and PP group. Additionally, IL-8 appears to play a role in the manifestation of PP. Our study highlights the immune alterations associated with first-onset PP.

Topics: Adult; Cytokines; Female; Humans; Interleukin-6; Interleukin-8; Psychotic Disorders; Puerperal Disorders; Young Adult

Several observations indicate that cytokine concentrations might also relate to the severity of the psychosis. In this study we assessed whether inflammatory and anti-inflammatory cytokine concentrations are associated with the degree of the psychotic manifestations. A group of 41 patients with schizophrenia suffering from an acute psychosis leading to hospitalization in a psychiatric ward were assessed for the intensity of their psychotic manifestations by the PANSS score. Serum IL-2R, IL-6, IL-8, IL-10 were analyzed by commercial ELISA kits. These patients were compared to controls without schizophrenia. At the univariate analysis, statistically significant elevated levels of the cytokines IL-6, IL-2R and IL-8 were detected in the sera of the patients with schizophrenia compared to controls. At the multivariate analysis, statistically significance held only for IL-2R concentration. Furthermore, positive correlation was found between symptom severity as measured by the PANSS and IL-6 levels as well as IL-2R levels. In Conclusion, our data indicate that elevated serum concentrations of IL-6, IL-8 and IL-2R are associated with severe clinical symptoms measured by the total, general, negative and positive scores of the PANSS scale.

Topics: Adolescent; Adult; Aged; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-10; Interleukin-6; Interleukin-8; Male; Middle Aged; Psychotic Disorders; Receptors, Interleukin-2; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Young Adult

Neuroimmune mechanisms have been linked to the pathophysiology of bipolar disorder based on studies of biomarkers in plasma, cerebrospinal fluid (CSF), and postmortem brain tissue. There are, however, no longitudinal studies investigating if CSF markers of neuroinflammation and neuronal injury predict clinical outcomes in patients with bipolar disorder. We have in previous studies found higher CSF concentrations of interleukin-8 (IL-8), monocyte chemoattractant protein 1 (MCP-1/CCL-2), chitinase-3-like protein 1 (CHI3L1/YKL-40), and neurofilament light chain (NF-L) in euthymic patients with bipolar disorder compared with controls. Here, we investigated the relationship of these CSF markers of neuroinflammation and neuronal injury with clinical outcomes in a prospective study. 77 patients with CSF analyzed at baseline were followed for 6-7years. Associations of baseline biomarkers with clinical outcomes (manic/hypomanic and depressive episodes, suicide attempts, psychotic symptoms, inpatient care, GAF score change) were investigated. Baseline MCP-1 concentrations were positively associated with manic/hypomanic episodes and inpatient care during follow-up. YKL-40 concentrations were negatively associated with manic/hypomanic episodes and with occurrence of psychotic symptoms. The prospective negative association between YKL-40 and manic/hypomanic episodes survived multiple testing correction. Concentrations of IL-8 and NF-L were not associated with clinical outcomes. High concentrations of these selected CSF markers of neuroinflammation and neuronal injury at baseline were not consistently associated with poor clinical outcomes in this prospective study. The assessed proteins may be involved in adaptive immune processes or reflect a state of vulnerability for bipolar disorder rather than being of predictive value for disease progression.

Topics: Adult; Biomarkers; Bipolar Disorder; Chemokine CCL2; Chitinase-3-Like Protein 1; Cytokines; Female; Humans; Interleukin-8; Longitudinal Studies; Male; Middle Aged; Neurofilament Proteins; Neuroimmunomodulation; Neurons; Prognosis; Prospective Studies; Psychotic Disorders; Treatment Outcome

Increased cytokines and kynurenic acid (KYNA) levels in cerebrospinal fluid (CSF) have been reported in patients with schizophrenia and bipolar disorder. The aim of the present study was to investigate cytokines and kynurenines in the CSF of twin pairs discordant for schizophrenia or bipolar disorder and to study these CSF markers in relation to psychotic symptoms and personality traits. CSF levels of tryptophan (TRP), KYNA, quinolinic acid (QUIN), interleukin (IL)-6, IL-8 and tumor necrosis factor-alpha (TNF-α) were analyzed in 23 twins with schizophrenia or bipolar disorder, and in their not affected co-twins. Ratings of psychotic symptoms and personality traits were made using the Scales for Assessment of Negative and Positive symptoms, the Structured Clinical Interview for DSM-IV - Axis II Disorders, and the Schizotypal Personality Questionnaire - Brief. A total score for psychotic symptoms and personality traits was constructed for analysis. CSF KYNA was associated with the score for psychotic symptom and personality traits. TNF-α and IL-8 were associated, and the intra-pair differences scores of TNF-α and IL-8 were highly correlated. Intraclass correlations indicated genetic influences on CSF KYNA, TRP, IL-8 and TNF-α. The association between KYNA and psychotic symptoms further supports a role of KYNA in psychotic disorders.

Topics: Bipolar Disorder; Female; Humans; Interleukin-6; Interleukin-8; Kynurenic Acid; Male; Middle Aged; Personality; Psychotic Disorders; Quinolinic Acid; Schizophrenia; Schizophrenic Psychology; Tryptophan; Tumor Necrosis Factor-alpha; Twins

Increasing evidence indicates that childhood trauma is a risk factor for schizophrenia and patients with this syndrome have a pro-inflammatory phenotype. We tested the hypothesis that the pro-inflammatory phenotype in schizophrenia is associated with childhood trauma and that patients without a history of such trauma have a similar immune profile to healthy controls.. We recruited 40 schizophrenia patients and 40 controls, all of whom completed the Childhood Trauma Questionnaire (CTQ). Using enzyme-linked immunosorbent assay (ELISA) techniques, we measured peripheral levels of interleukin (IL)-1β, IL-6, IL-8 and tumour necrosis factor (TNF)-α. These immune parameters were compared in schizophrenia with childhood trauma, schizophrenia without childhood trauma and healthy controls.. Patients with childhood trauma had higher levels of IL-6 and TNF-α than patients without trauma and healthy controls, and TNF-α levels correlated with the extent of the trauma. Patients with no trauma had similar immune profiles to controls.. Childhood trauma drives changes, possibly epigenetic, that generate a pro-inflammatory phenotype.

Topics: Adult; Case-Control Studies; Child; Child Abuse; Enzyme-Linked Immunosorbent Assay; Female; Humans; Inflammation; Inflammation Mediators; Interleukin-1beta; Interleukin-6; Interleukin-8; Male; Middle Aged; Parental Death; Phenotype; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology; Stress, Psychological; Tumor Necrosis Factor-alpha

Symptoms originating from the central nervous system (CNS) occur frequently in patients with systemic lupus erythematosus (SLE), and CNS involvement in lupus is associated with increased morbidity and mortality. We recently showed that neurones and astrocytes are continuously damaged during the course of CNS lupus. The matrix metalloproteinases (MMPs) are a group of tissue degrading enzymes that may be involved in this ongoing brain destruction. The aim of this study was to examine endogenous levels of free, enzymatically active MMP-2 and MMP-9 in cerebrospinal fluid from patients with SLE. A total of 123 patients with SLE were evaluated clinically, with magnetic resonance imaging of brain and cerebrospinal fluid (CSF) analyses. Levels of free MMP-2 and MMP-9 were determined in CSF using an enzymatic activity assay. CSF samples from another 22 cerebrally healthy individuals were used as a control. Intrathecal MMP-9 levels were significantly increased in patients with neuropsychiatric SLE as compared with SLE patients without CNS involvement (P < 0.05) and healthy control individuals (P = 0.0012). Interestingly, significant correlations between MMP-9 and intrathecal levels of neuronal and glial degradation products were noted, indicating ongoing intrathecal degeneration in the brains of lupus patients expressing MMP-9. In addition, intrathecal levels of IL-6 and IL-8--two cytokines that are known to upregulate MMP-9--both exhibited significant correlation with MMP-9 levels in CSF (P < 0.0001), suggesting a potential MMP-9 activation pathway. Our findings suggest that proinflammatory cytokine induced MMP-9 production leads to brain damage in patients with CNS lupus.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Brain; Central Nervous System Diseases; Cerebrospinal Fluid Proteins; Enzyme Induction; Female; Glial Fibrillary Acidic Protein; Humans; Interleukin-6; Interleukin-8; Leukocytosis; Lupus Erythematosus, Systemic; Magnetic Resonance Imaging; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Meningitis, Aseptic; Middle Aged; Myelitis, Transverse; Nerve Tissue Proteins; Psychotic Disorders; Seizures; tau Proteins

We investigated levels of maternal cytokines in late pregnancy in relation to the subsequent development of adult schizophrenia and other psychoses in their offspring. The sample included the mothers of 27 adults with schizophrenia and other psychotic illnesses and 50 matched unaffected controls from the Providence cohort of the Collaborative Perinatal Project. Serum samples were analyzed for interleukin 1 beta (IL-1-beta), interleukin 2 (IL-2), interleukin 6 (IL-6), interleukin 8 (IL-8), and tumor necrosis factor alpha (TNF-alpha) by enzyme immunoassay. Maternal levels of TNF-alpha were significantly elevated among the case series (t = 2.22, p =.04), with evidence of increasing odds of psychosis in relation to higher cytokine levels. We did not find significant differences between case and control mothers in the serum levels of IL-1, IL-2, IL-6, or IL-8. These data support previous clinical investigations reporting maternal infections during pregnancy as a potential risk factor for psychotic illness among offspring.

Topics: Adult; Case-Control Studies; Cohort Studies; Cytokines; Female; Humans; Interleukin-1; Interleukin-2; Interleukin-6; Interleukin-8; Male; Pregnancy; Pregnancy Complications, Infectious; Psychotic Disorders; Risk Factors; Tumor Necrosis Factor-alpha