| 1 | Bipolar Disord 2004 Apr 6: 150-5 |
|---|---|
| PMID | 15005754 |
| Title | von Willebrand's disease and psychotic disorders: co-segregation and genetic associations. |
| Abstract | To evaluate co-segregation and genetic associations between von Willebrand's disease (vWD) and psychotic disorders. The study was initiated following ascertainment of a nuclear family in which four members were diagnosed with vWD and psychotic/mood disorders. As co-segregation was uncertain in the extended pedigree, we also investigated population-based linkage and association using polymorphisms of VWF, the gene conferring susceptibility to vWD. Three common VWF polymorphisms were investigated among 194 patients with psychotic disorders (bipolar I disorder, BD I; schizoaffective disorder, SZA and schizophrenia, SZ) and their parents. The cases were also compared with unrelated population-based controls (n = 183). The transmission disequilibrium test and related analyses suggested nominally significant transmission distortion of one allele and related haplotypes to the probands from their parents. The most significant results were obtained among patients with BD I, and similar trends were also evident in the SZ sample. Comparisons between the cases and population-based controls did not reveal associations, though marginally significant case-control differences were obtained in the BD I sample. These studies are consistent with association and linkage between VWF and BD I. However, given the relatively small sample, stochastic variation is an alternative explanation. |
| SCZ Keywords | schizophrenia |
| 2 | Bipolar Disord 2009 Nov 11: 726-34 |
| PMID | 19839997 |
| Title | Similar immune profile in bipolar disorder and schizophrenia: selective increase in soluble tumor necrosis factor receptor I and von Willebrand factor. |
| Abstract | Alterations in the inflammatory system have been associated with schizophrenia and major depression, while bipolar disorder has been less studied. Most previous studies examined small samples, and the literature is inconsistent with regard to specific underlying immune mechanisms. In the present study, we examined markers representing different inflammatory pathways, and the aim was to investigate whether the levels of inflammatory parameters in a representative sample of bipolar disorder and schizophrenia are elevated compared to healthy controls, and to investigate whether the inflammatory profile is different between the groups. Plasma levels of soluble tumor necrosis factor receptor 1 (sTNF-R1), interleukin-1 receptor antagonist (IL-1Ra), interleukin-6 (IL-6), high-sensitivity CRP (hs-CRP), soluble CD40L ligand (sCD40L), and von Willebrand factor (VWF) were measured with ELISA techniques in a catchment area based sample of consecutively referred patients with severe mental disorders [N = 311, comprising bipolar disorder (n = 125) and schizophrenia (n = 186)] and in healthy volunteers (n = 244). Plasma levels of sTNF-R1 and VWF were statistically significantly increased in both bipolar disorder and schizophrenia compared to controls (p < 0.00001), and were also increased in unmedicated patients, but there were no major differences between the two diagnostic groups. Controlling for age, gender, ethnicity, cardiovascular disorders, kidney and liver function, and other confounders did not affect the results. There were no differences in other inflammation factors between the groups. The present results indicate specific alterations of endothelium-related inflammation processes in both bipolar disorder and schizophrenia. |
| SCZ Keywords | schizophrenia |
| 3 | J Psychiatr Res 2011 Dec 45: 1608-16 |
| PMID | 21889167 |
| Title | Affective symptoms are associated with markers of inflammation and immune activation in bipolar disorders but not in schizophrenia. |
| Abstract | Elevated levels of inflammation are reported in bipolar disorders (BP), but how this relates to affective symptoms is unclear. We aimed to determine if immune markers that consistently have been reported elevated in BP were associated with depressive and manic symptoms, and if this was specific for BP. From a catchment area, 112 BP patients were included together with 153 schizophrenia (SCZ) patients and 239 healthy controls. Depression and mania were assessed and the patients were grouped into depressed, neutral, and elevated mood. We measured the immune markers tumor necrosis factor receptor 1 (sTNF-R1), interleukin 1 receptor antagonist (IL-1Ra), interleukin 6 (IL-6), high sensitive C-reactive protein (hsCRP), osteoprotegerin (OPG) and von Willebrand factor (VWF) which have been found increased in severe mental disorders. In BP all inflammatory markers were lowest in depressed state, with significant group differences after control for confounders with respect to TNF-R1 (p = 0.04), IL-1Ra (p = 0.02), OPG (p = 0.004) and IL-6 (p = 0.005). STNF-R1 was positively correlated with the item elevated mood (p = 0.02) whereas sad mood was negatively correlated with OPG (p = 0.0003), IL-1Ra (p = 0.001) and IL-6 (p = 0.006). Compared to controls the neutral mood group had significantly higher levels of OPG (p = 0.0003) and IL-6 (p = 0.005), and the elevated mood group had higher levels of TNF-R1 (p = 0.000005) and VWF (p = 0.002). There were no significant associations between affective states orsymptoms in SCZ. The current associations between inflammatory markers and affective symptomatology in BP and not SCZ suggest that immune related mechanisms are associated with core psychopathology of BP. |
| SCZ Keywords | schizophrenia |
| 4 | Schizophr. Res. 2012 Sep 140: 169-74 |
| PMID | 22817875 |
| Title | Cardiovascular risk factors during second generation antipsychotic treatment are associated with increased C-reactive protein. |
| Abstract | Severe mental disorder and cardiovascular disease (CVD) are often associated, and inflammation is implicated in both disorders. We investigated whether there is a relationship between CVD risk factors and inflammation in schizophrenia or bipolar disorder, and if second generation antipsychotics (SGA) interact. We included 361 patients in a naturalistic cross-sectional study, 235 subjects on current SGA treatment and 126 subjects not treated with SGA as controls. Cardiovascular parameters were measured and current medication recorded. Fasting plasma levels of the following cytokines were measured: high sensitivity CRP (hsCRP), soluble tumor necrosis factor receptor 1 (sTNF-R1), osteoprotegerin (OPG), soluble CD40 ligand (sCD40L), interleukin-1 receptor antagonist (IL-1Ra), von Willebrand factor (VWF) and interleukin-6 (IL-6). In this relatively young sample of patients with a mean age of 33.3years, the following CVD risk factors were associated with elevated inflammation markers after adjusting for confounders: BMI, triglycerides and glucose with hsCRP (p=0.041-0.001), HDL-cholesterol and triglycerides with sTNF-R1 (p=0.009-0.001) and triglycerides with VWF (p=0.004). In patients treated with SGA, elevated hsCRP was significantly associated with high BMI (p=0.012), and with high glucose levels (p=0.003). Several CVD risk factors are associated with elevated levels of inflammation markers in young patients with severe mental illness. The interaction between SGA and CVD risk factors on hsCRP levels might indicate a specific inflammatory activation related to SGA induced overweight and hyperglycemia. This suggests that hsCRP could be a valuable marker for future cardiovascular events, particularly in patients treated with SGA. |
| SCZ Keywords | schizophrenia |
| 5 | Schizophr. Res. 2013 Apr 145: 36-42 |
| PMID | 23403415 |
| Title | Interleukin 1 receptor antagonist and soluble tumor necrosis factor receptor 1 are associated with general severity and psychotic symptoms in schizophrenia and bipolar disorder. |
| Abstract | Previous studies suggest elevated inflammation in schizophrenia and bipolar disorder, with increased activity of the Interleukin 1 (IL-1), interleukin 6 (IL-6), tumor necrosis factor (TNF)-alpha, von Willebrand factor (VWF) and osteoprotegerin (OPG). It is unclear how immune activation is involved in the psychopathology. We investigated if elevated inflammation was associated with disease severity (trait) or current symptom level (state), comparing psychotic with general characteristics. Plasma levels of sTNF receptor 1 (sTNF-R1), IL-1 receptor antagonist (IL-1Ra), IL-6, VWF and OPG were measured with ELISA techniques in 322 patients with schizophrenia spectrum and bipolar disorder. Current symptom level (state) was measured with Global Assessment of Functioning (GAF) and Positive and Negative Syndrome Scale (PANSS). Disease severity (trait) was measured with premorbid adjustment scale (PAS), age at onset, number of psychotic episodes and number and length of hospitalizations. After controlling for confounders, IL-1Ra and TNF-R1 were independently associated with GAF, and significantly correlated with PANSS negative and positive, respectively. In addition, Il-1Ra was associated with PAS, and sTNF-R1 with number of hospitalizations and psychotic episodes. VWF was significantly correlated with psychotic episodes, OPG with hospitalizations and IL-6 with history of psychosis. Linear regression analysis showed that GAF remained associated with sTNF-R1 and IL-1Ra with PANSS, after controlling for the other clinical measures. This supports that inflammatory markers, particularly IL-1Ra and sTNF-R1 are associated with both general disease severity and psychotic features. This supports a role of immune activation in the core pathological mechanisms of severe mental disorders. |
| SCZ Keywords | schizophrenia |
| 6 | Biomark Insights 2015 -1 10: 47-54 |
| PMID | 26052224 |
| Title | Immunomodulatory Effects of Probiotic Supplementation in Schizophrenia Patients: A Randomized, Placebo-Controlled Trial. |
| Abstract | Although peripheral immune system abnormalities have been linked to schizophrenia pathophysiology, standard antipsychotic drugs show limited immunological effects. Thus, more effective treatment approaches are required. Probiotics are microorganisms that modulate the immune response of the host and, therefore, may be beneficial to schizophrenia patients. The aim of this study was to examine the possible immunomodulatory effects of probiotic supplementation in chronic schizophrenia patients. The concentrations of 47 immune-related serum proteins were measured using multiplexed immunoassays in samples collected from patients before and after 14 weeks of adjuvant treatment with probiotics (Lactobacillus rhamnosus strain GG and Bifidobacterium animalis subsp. lactis strain Bb12; n = 31) or placebo (n = 27). Probiotic add-on treatment significantly reduced levels of von Willebrand factor (VWF) and increased levels of monocyte chemotactic protein-1 (MCP-1), brain-derived neurotrophic factor (BDNF), RANTES, and macrophage inflammatory protein-1 beta (MIP-1) beta with borderline significance (P ? 0.08). In silico pathway analysis revealed that probiotic-induced alterations are related to regulation of immune and intestinal epithelial cells through the IL-17 family of cytokines. We hypothesize that supplementation of probiotics to schizophrenia patients may improve control of gastrointestinal leakage. |
| SCZ Keywords | schizophrenia |
| 7 | Schizophr. Res. 2015 Feb 161: 222-8 |
| PMID | 25433965 |
| Title | Association between altered brain morphology and elevated peripheral endothelial markers--implications for psychotic disorders. |
| Abstract | Increased inflammation, endothelial dysfunction, and structural brain abnormalities have been reported in both schizophrenia and bipolar disorder, but the relationships between these factors are unknown. We aimed to identify associations between markers of inflammatory and endothelial activation and structural brain variation in psychotic disorders. We measured von Willebrand factor (VWF) as a marker of endothelial cell activation and six inflammatory markers (tumor necrosis factor-receptor 1, osteoprotegerin, interleukin-1-receptor antagonist, interleukin-6, C-reactive protein, CD40 ligand) in plasma and 16 brain structures obtained from MRI scans of 356 individuals (schizophrenia spectrum; n=121, affective spectrum; n=95, healthy control subjects; n=140). The relationship between the inflammatory and endothelial markers and brain measurements were investigated across groups. There was a positive association (p=2.5×10(-4)) between plasma levels of VWF and total volume of the basal ganglia which remained significant after correction for multiple testing. Treatment with first generation antipsychotics was associated with basal ganglia volume only (p=0.009). After adjusting for diagnosis and antipsychotic medication, VWF remained significantly associated with increased basal ganglia volume (p=0.008), in particular the right globus pallidus (p=3.7×10(-4)). The relationship between VWF and basal ganglia volume was linear in all groups, but the intercept was significantly higher in the schizophrenia group (df=2, F=8.2, p=3.4×10(-4)). Our results show a strong positive correlation between VWF levels and basal ganglia volume, in particular globus pallidus, independent of diagnosis. VWF levels were significantly higher in schizophrenia, which could indicate a link between endothelial cell activation and basal ganglia morphology in schizophrenia patients. |
| SCZ Keywords | schizophrenia |
| 8 | Psychoneuroendocrinology 2016 May 67: 189-97 |
| PMID | 26923849 |
| Title | Inflammatory evidence for the psychosis continuum model. |
| Abstract | Inflammation and immune activation have been implicated in the pathophysiology of severe mental disorders. Previous studies of inflammatory markers, however, have been limited with somewhat inconsistent results. We aimed to determine the effect sizes of inflammatory marker alterations across diagnostic groups of the psychosis continuum and investigate association to antipsychotic medications. Plasma levels of soluble tumor necrosis factor receptor 1 (sTNF-R1), interleukin 1 receptor antagonist (IL-1Ra), osteoprotegerin (OPG), and von Willebrand factor (VWF) were measured in patients (n=992) with schizophrenia spectrum (SCZ, n=584), schizoaffective disorder (SA, n=93), affective spectrum disorders (AFF, n=315), and healthy controls (HC, n=638). Levels of sTNF-R1 (p=1.8×10(-8), d=0.23) and IL-1Ra (p=0.002, d=0.16) were increased in patients compared to HC. The SCZ group had higher levels of sTNF-R1 (p=8.5×10(-8), d=0.27) and IL-1Ra (p=5.9×10(-5), d=0.25) compared to HC, and for sTNF-R1 this was also seen in the SA group (p=0.01, d=0.3) and in the AFF group (p=0.002, d=0.12). Further, IL-1Ra (p=0.004, d=0.25) and VWF (p=0.02, d=0.21) were increased in the SCZ compared to the AFF group. There was no significant association between inflammatory markers and use of antipsychotic medication. We demonstrate a small increase in sTNF-R1 and IL-1Ra in patients with severe mental disorders supporting a role of inflammatory mechanisms in disease pathophysiology. The increase was more pronounced in SCZ compared to AFF supporting a continuum psychosis model related to immune factors. |
| SCZ Keywords | schizophrenia |