interleukin-8 and Bipolar-Disorder

Alcohol use disorder (AUD) is a highly prevalent comorbid disorder in patients with bipolar disorder (BD). Both BD and AUD were found to be associated with inflammation and cognitive deficits, but few study has been done on BD comorbid with AUD (BD+AUD). We aimed to investigate the impacts of comorbid AUD and BD on cognitive function, inflammatory and neurotrophic markers.. We recruited 641 BD patients, 150 patients with BD+AUD, and 185 healthy controls (HC). Neuropsychological tests [Wisconsin card sorting test (WCST), continuous performance test (CPT), and Wechsler memory scale - third edition (WMS-III)] and cytokine plasma levels [tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), interleukin-8 (IL-8), transforming growth factor-β1 (TGF-β1), and brain-derived neurotrophic factor (BDNF)] were assessed.. BD+AUD patients had worse cognitive performance than those without AUD. There was a significant difference in the plasma levels of TNF-α, IL-8, and BDNF (P < 0.001, <0.001, and 0.01, respectively) between the patients and the HC groups. Post hoc analysis showed that BD+AUD patients had higher levels of TNF-α and IL-8 than BD-only patients (P < 0.001). Additionally, plasma IL-8 levels were negatively associated with number of completed categories in WCST (P = 0.02), and TNF-α levels were negatively associated with visual immediate index in WMS-III (P = 0.05).. Our results suggest that comorbid AUD and BD might worsen cognitive impairments and inflammatory processes. Further longitudinal studies on BD+AUD may be needed.

Topics: Alcoholism; Bipolar Disorder; Brain-Derived Neurotrophic Factor; Humans; Interleukin-8; Tumor Necrosis Factor-alpha

Immune system dysregulation plays a key role in the physiopathology of bipolar disorder (BD) and major depressive disorder (MDD). However, whether interleukins might be biomarkers to distinguish these 2 affective disorders is unclear. Here, we assessed the differences in serum levels of interleukin 6 (IL-6) and interleukin 8 (IL-8) as well as C-reactive protein (CRP) in patients with MDD and BD. In total, we enrolled 21 MDD patients, 26 BD patients, and 20 healthy controls. We collected a total of 35 samples from BD patients in 3 different phases, depression phase, manic phase, and remission stage, and 27 samples from MDD patients in acute and remission phases. Serum IL-6 and IL-8 levels were assessed with solid phase sandwich ELISA-based quantitative arrays, and CRP levels were determined with an automatic analyzer. Both serum IL-6 and IL-8 levels were elevated in BD patients but not MDD patients. Subgroup analysis indicated elevated serum IL-6 in both the depression and manic phases in BD patients. The serum CRP levels did not change in either BD or MDD patients. However, sex differences in CRP concentrations were observed in healthy controls. Furthermore, there were linear correlations between the CRP levels and Bech-Rafaelsen Mania Rating Scale (BRMS) scores in BD patients. IL-6 and IL-8 levels may serve as biomarkers to differentiate between MDD and BD patients, even when the clinical manifestations are atypical. IL-6 may be used for the differential diagnosis of MDD and depressive episodes in BD.

Topics: Adult; Biomarkers; Bipolar Disorder; C-Reactive Protein; Case-Control Studies; Depressive Disorder, Major; Female; Humans; Interleukin-6; Interleukin-8; Longitudinal Studies; Male; Retrospective Studies; Sex Factors

The role of immune response dysregulation has been previously noticed in the pathogenesis of bipolar disorder (BD).. In the current investigation, we compared expression levels of eight cytokines and a chemokine (CXCL8) in the peripheral blood of BD patients and healthy subjects. All BD patients were in euthymic phase.. We found higher expression of IL-1B, IL-10, IFN-G, TNF-a, TGF-B and IL-2 in male patients compared with male controls (ExR=3.44, P<0.0001, ExR=2.54, P<0.0001; ExR=2.39, P<0.0001; ExR=2.74, P<0.0001; ExR=2.32, P<0.0001; ExR=1.87, P = 0.04 respectively). For these cytokines, no significant differences were found between female patients and female controls. While expression of IL-6 was higher in male patients compared with male controls (ExR=2.07, P = 0.006), in female subjects the opposite trend was detected (ExR=0.44, P = 0.02). However, no significant difference was detected between female subjects. Expression levels of IL-17 were not different between patients and controls or between any subgroups of them. We found significant correlations between expression of IFN-G and age at disease onset (R = 0.25, P = 0.04) as well as expression of CXCL8 and both age of patients and age at disease onset (R = 0.26, P = 0.03; R = 0.25, P = 0.04). Moreover, inverse correlation was detected between expression of TNF-a and age in control group (R=-0.34, P = 0.008).. Combination of transcript levels of six genes could differentiate BD patients from healthy subjects with diagnostic power of 0.85 (Sensitivity=78%, Specificity=80% and P<0.0001). The current investigation highlights the role of cytokine coding genes in the pathogenesis of BD and potentiates them as diagnostic biomarkers.

Topics: Adult; Bipolar Disorder; Cyclothymic Disorder; Cytokines; Female; Humans; Interferon-gamma; Interleukin-10; Interleukin-17; Interleukin-1beta; Interleukin-2; Interleukin-6; Interleukin-8; Male; Sensitivity and Specificity; Tumor Necrosis Factor-alpha; 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

Emerging evidence suggests that inflammation and neurodegeneration underlies bipolar disorder. To investigate biological markers of cytokines and brain-derived neurotrophic factor between bipolar I, bipolar II, and other specified bipolar disorder with short duration hypomania may support the association with inflammatory dysregulation and bipolar disorder and, more specifically, provide evidence for other specified bipolar disorder with short duration hypomania patients were similar to bipolar II disorder patients from a biological marker perspective.. We enrolled patients with bipolar I disorder (n=234), bipolar II disorder (n=260), other specified bipolar disorder with short duration hypomania (n=243), and healthy controls (n=140). Their clinical symptoms were rated using the Hamilton Depression Rating Scale and Young Mania Rating Scale. Inflammatory cytokine (tumor necrosis factor-α, C-reactive protein, transforming growth factor-β1, and interleukin-8) and brain-derived neurotrophic factor levels were measured in each group. Multivariate analysis of covariance and linear regression controlled for possible confounders were used to compare cytokine and brain-derived neurotrophic factor levels among the groups.. Multivariate analysis of covariance adjusted for age and sex and a main effect of diagnosis was significant (P<.001). Three of the 5 measured biomarkers (tumor necrosis factor-α, transforming growth factor-β1, and interleukin-8) were significantly (P=.006, .01, and <.001) higher in all bipolar disorder patients than in controls. Moreover, covarying for multiple associated confounders showed that bipolar I disorder patients had significantly higher IL-8 levels than did bipolar II disorder and other specified bipolar disorder with short duration hypomania patients in multivariate analysis of covariance (P=.03) and linear regression (P=.02) analyses. Biomarkers differences between bipolar II disorder and other specified bipolar disorder with short duration hypomania patients were nonsignificant.. The immunological disturbance along the bipolar spectrum was most severe in bipolar I disorder patients. Other specified bipolar disorder with short duration hypomania patients and bipolar II disorder patients did not differ in these biological markers.

Topics: Adult; Biomarkers; Bipolar Disorder; Brain-Derived Neurotrophic Factor; C-Reactive Protein; Case-Control Studies; Female; Humans; Interleukin-8; Male; Transforming Growth Factors; Tumor Necrosis Factor-alpha; Young Adult

Peripheral blood brain-derived neurotrophic factor (BDNF) and inflammatory markers may reflect key pathophysiological mechanisms in bipolar disorder in relation to disease activity and neuroprogression.. To investigate whether neutrophins and inflammatory marker vary with mood states and are increased in patients with bipolar disorder type I during euthymia as well as in all affective states as a group, compared to levels in healthy control subjects.. In a prospective 6-12 months follow-up study, we investigated state specific, intra-individual alterations in levels of BDNF, hsCRP, IL-1β, IL-6, IL-8, IL-18 and TNF-α in 60 patients with bipolar I disorder with an acute severe manic index episode and in subsequent euthymic and depressive and manic states and compared with repeated measurements in healthy control subjects. Data were analysed with linear mixed effects model and with adjustment for gender, age, BMI, alcohol intake and smoking.. From inclusion to end of the 6-12 months follow-up, samples of blood were drawn from the 60 patients during a total of 180 affective states, comprising 57 manic, 11 mixed, 23 depressive and 89 states of euthymia. Further, 69 blood samples were drawn from 35 healthy control subjects with three months apart. In unadjusted mixed-model analysis, levels of IL-6 and IL-8 were increased 64% (b=1.64, 95% CI: 1.31-2.05, p=<0.0001) and 24% (b=1.24, 95% CI: 1.05-1.47, p=0.013), respectively in patients with bipolar disorder overall compared with healthy control subjects. However, in adjusted models, no statistically significant differences were found in any measure between patients and control individuals. Levels of hsCRP in depressive states were decreased with 40% (95% CI: 5-62%, p=0.029) compared with euthymia and with 48% (95% CI: 17-66%, p=0.006) when compared with hypomanic/manic states after adjustment. BDNF and the other inflammatory markers did not vary according to affective state in adjusted mixed models.. Patients were all medicated, specifically with high doses of atypical antipsychotics during the manic index episodes.. In a sample recruited during hospitalization for acute mania, levels of hsCRP varied according to affective state with higher levels during manic states compared with depressive states.

Topics: Adult; Biomarkers; Bipolar Disorder; Body Mass Index; Brain-Derived Neurotrophic Factor; C-Reactive Protein; Depression; Female; Follow-Up Studies; Humans; Interleukin-18; Interleukin-1beta; Interleukin-6; Interleukin-8; Interleukins; Male; Middle Aged; Prospective Studies; Smoking; Tumor Necrosis Factor-alpha

Inflammation has been linked to the pathophysiology of bipolar disorder based on studies of inflammation markers, such as cytokine concentrations, in plasma and serum samples from cases and controls. However, peripheral measurements of cytokines do not readily translate to immunological activity in the brain. The aim of the present study was to study brain immune and inflammatory activity. To this end, we analyzed cytokines in cerebrospinal fluid from 121 euthymic bipolar disorder patients and 71 age and sex matched control subjects. Concentrations of 11 different cytokines were determined using immunoassays. Cerebrospinal fluid IL-8 concentrations were significantly higher in patients as compared to controls. The other cytokines measured were only detectable in part of the sample. IL-8 concentrations were positively associated to lithium- and antipsychotic treatment. The findings might reflect immune aberrations in bipolar disorder, or be due to the effects of medication.

Topics: Adult; Antimanic Agents; Antipsychotic Agents; Bipolar Disorder; Female; Humans; Interleukin-8; Lithium; Male; Middle Aged

Bipolar disorder carries a substantive morbidity and mortality burden, particularly related to cardiovascular disease. Abnormalities in peripheral inflammatory markers, which have been commonly reported in case-control studies, potentially link these co-morbidities. However, it is not clear whether inflammatory markers change episodically in response to mood states or are indicative of chronic pro-inflammatory activity, regardless of mood, in bipolar disorder.. Investigations focused on comparing concentrations of specific inflammatory cytokines associated with immune activation status (primary outcome=tumor necrosis factor alpha (TNF-α)) in 37 participants with bipolar disorder across 3 mood states (mania N=15, depression N=9, normal mood N=13) and 29 controls without a psychiatric disorder (total N=66). Cytokine levels were also compared to T1ρ, a potential neuroimaging marker for inflammation, in select brain regions in a subsample (N=39).. Participants with bipolar disorder and healthy controls did not differ significantly in inflammatory cytokine concentrations. However, compared to cases with normal mood, cases with abnormal mood states (mania and depression) had significantly elevated levels of TNF-α, its soluble receptors (sTNFR1/sTNFR2), other macrophage-derived cytokines (interleukin 1β (IL-1β), IL-6, IL-10, and IL-18) in addition to IL-4, interferon-γ, monocyte chemotactic protein-1, fibroblast growth factor β, and vascular endothelial growth factor. Cytokine levels were not correlated with signals from T1ρ imaging in selected structures (amygdalae, hippocampi, hypothalamus, anterior cingulate gyrus, and middle frontal gyrus).. Participants were not followed prospectively across mood states.. Activation of inflammatory markers was found in abnormal mood states of bipolar disorder. Longitudinal study of individuals with mood disorders is needed to confirm these findings and to elucidate the time course of any such changes.

Topics: Adult; Affect; Bipolar Disorder; Case-Control Studies; Cytokines; Female; Humans; Inflammation Mediators; Interleukin-10; Interleukin-6; Interleukin-8; Male; Middle Aged; Psychiatric Status Rating Scales; Reference Values; Tumor Necrosis Factor-alpha

The role of the immune system in mood disorders is predominately supported by studies in unipolar major depression. However activation of the immune system has also been demonstrated in bipolar mania. Our study examines pro-inflammatory and anti-inflammatory cytokines in both phases of bipolar affective disorder (BPAD).. Plasma concentrations of IL-6, IL-8, IL-10, TNF-alpha and sIL-6R were measured with enzyme linked immunosorbent assays (ELISA) in patients with BPAD who were depressed, or manic and in healthy controls.. Bipolar depression had significantly higher production of the pro-inflammatory cytokines, IL-8 (p < 0.001) and TNF-alpha (p < 0.05) compared to healthy subjects. The manic group also had increased production of IL-8 (p < 0.05) and TNF-alpha (p < 0.001) as compared to healthy subjects. Anti-inflammatory cytokine levels did not differ across the 3 groups.. A small sample size was studied. All patients remained on medication for this study.. BPAD is associated with increased production of pro-inflammatory cytokines both in the manic and in the depressed phase as compared to healthy subjects. This is the first study, which examined both mania and bipolar depression.

Topics: Adolescent; Adult; Affect; Bipolar Disorder; Cytokines; Female; Humans; Inflammation Mediators; Interleukin-10; Interleukin-6; Interleukin-8; Male; Middle Aged; Personality Inventory; Psychiatric Status Rating Scales; Reference Values; Statistics as Topic; Tumor Necrosis Factor-alpha