1Eur. J. Clin. Pharmacol. 2001 Dec 57: 705-8
PMID11829199
TitleEffect of influenza vaccination on serum clozapine and its main metabolite concentrations in patients with schizophrenia.
AbstractTo study the effect of influenza vaccine on serum clozapine, N-desmethylclozapine and clozapine-N-oxide steady-state concentrations in patients with schizophrenia.
This was an open-label study in 14 schizophrenic inpatients (with 2 drop-outs) using clozapine. Serum trough concentrations of clozapine. N-desmethylclozapine and clozapine-N-oxide, as well as the concentration of c-reactive protein (CRP), were measured immediately before conventional trivalent influenza vaccination and 2, 4, 7 and 14 days after the vaccination.
Influenza vaccination had no significant effect on serum concentrations of clozapine, N-desmethylclozapine or clozapine-N-oxide. No changes in the clinical effects of clozapine were observed after vaccination. Influenza vaccination did not increase CRP. However, two drop-out patients who developed upper respiratory and abdominal symptoms had increased and elevated serum concentrations of clozapine, compared with the baseline.
Influenza vaccination using conventional trivalent influenza vaccine does not affect serum concentrations of clozapine or its main metabolites. However, an infection-related increase in CRP may be associated with increased serum concentration of clozapine.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
2Eur. J. Clin. Pharmacol. 2001 Dec 57: 705-8
PMID11829199
TitleEffect of influenza vaccination on serum clozapine and its main metabolite concentrations in patients with schizophrenia.
AbstractTo study the effect of influenza vaccine on serum clozapine, N-desmethylclozapine and clozapine-N-oxide steady-state concentrations in patients with schizophrenia.
This was an open-label study in 14 schizophrenic inpatients (with 2 drop-outs) using clozapine. Serum trough concentrations of clozapine. N-desmethylclozapine and clozapine-N-oxide, as well as the concentration of c-reactive protein (CRP), were measured immediately before conventional trivalent influenza vaccination and 2, 4, 7 and 14 days after the vaccination.
Influenza vaccination had no significant effect on serum concentrations of clozapine, N-desmethylclozapine or clozapine-N-oxide. No changes in the clinical effects of clozapine were observed after vaccination. Influenza vaccination did not increase CRP. However, two drop-out patients who developed upper respiratory and abdominal symptoms had increased and elevated serum concentrations of clozapine, compared with the baseline.
Influenza vaccination using conventional trivalent influenza vaccine does not affect serum concentrations of clozapine or its main metabolites. However, an infection-related increase in CRP may be associated with increased serum concentration of clozapine.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
3Zh Nevrol Psikhiatr Im S S Korsakova 2005 -1 105: 45-9
PMID16329635
Title[A state of innate and adaptive immunity in children with schizophrenia and in the high-risk group for the disease].
AbstractLeukocyte elastase (LE) activity, alpha1-proteinase inhibitor (alpha1-PI), C-reactive protein (CRP) as the indices of innate immunity and the level of autoantibodies to nerve growth factor (Aab-NGF) and to basic myelin protein (Aab-BMP) as the indices of adaptive immunity have been studied in the blood serum of 40 children at high risk for schizophrenia and in 32 children with schizophrenia. In the high-risk group, an increase both of the LE activity, CRP content and variance of alpha1-PI concentrations, indicating the activation of innate immunity, was found. LE activity correlated with severity of schizotypal diathesis. The development of schizophrenic process is accompanied by generalization of the immune response: along with activation of the innate immunity, there was activation of immunity acquired as an increase of the level of autoantibodies to neuroantigenes. It is suggested that activation of innate and adaptive immunity is related to the processes determining the disturbances of the nervous system development.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
4Zh Nevrol Psikhiatr Im S S Korsakova 2005 -1 105: 45-9
PMID16329635
Title[A state of innate and adaptive immunity in children with schizophrenia and in the high-risk group for the disease].
AbstractLeukocyte elastase (LE) activity, alpha1-proteinase inhibitor (alpha1-PI), C-reactive protein (CRP) as the indices of innate immunity and the level of autoantibodies to nerve growth factor (Aab-NGF) and to basic myelin protein (Aab-BMP) as the indices of adaptive immunity have been studied in the blood serum of 40 children at high risk for schizophrenia and in 32 children with schizophrenia. In the high-risk group, an increase both of the LE activity, CRP content and variance of alpha1-PI concentrations, indicating the activation of innate immunity, was found. LE activity correlated with severity of schizotypal diathesis. The development of schizophrenic process is accompanied by generalization of the immune response: along with activation of the innate immunity, there was activation of immunity acquired as an increase of the level of autoantibodies to neuroantigenes. It is suggested that activation of innate and adaptive immunity is related to the processes determining the disturbances of the nervous system development.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
5Zh Nevrol Psikhiatr Im S S Korsakova 2005 -1 105: 45-9
PMID16329635
Title[A state of innate and adaptive immunity in children with schizophrenia and in the high-risk group for the disease].
AbstractLeukocyte elastase (LE) activity, alpha1-proteinase inhibitor (alpha1-PI), C-reactive protein (CRP) as the indices of innate immunity and the level of autoantibodies to nerve growth factor (Aab-NGF) and to basic myelin protein (Aab-BMP) as the indices of adaptive immunity have been studied in the blood serum of 40 children at high risk for schizophrenia and in 32 children with schizophrenia. In the high-risk group, an increase both of the LE activity, CRP content and variance of alpha1-PI concentrations, indicating the activation of innate immunity, was found. LE activity correlated with severity of schizotypal diathesis. The development of schizophrenic process is accompanied by generalization of the immune response: along with activation of the innate immunity, there was activation of immunity acquired as an increase of the level of autoantibodies to neuroantigenes. It is suggested that activation of innate and adaptive immunity is related to the processes determining the disturbances of the nervous system development.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
6Schizophr. Res. 2007 Jul 93: 261-5
PMID17490859
TitleC-reactive protein is associated with the severity of cognitive impairment but not of psychiatric symptoms in individuals with schizophrenia.
AbstractWe investigated the association between serum levels of C-reactive protein (CRP), a marker of inflammation, and the severity of psychopathology and cognitive impairment in schizophrenia.
We measured the levels of CRP in N=413 individuals with schizophrenia. Symptom severity was evaluated with the Positive and Negative Syndrome Scale (PANSS) and cognitive functioning with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).
The individuals with CRP >or=5.0 mg/microl had significantly lower RBANS cognitive scores than those with CRP <5.0 mg/microl (F=8.07, p<.005). However the CRP groups did not differ in the severity of positive, negative, or general PANSS symptoms (all p>.2).
Elevated serum levels of C-reactive protein in schizophrenia are associated with the severity of cognitive impairment but not of psychiatric symptoms. The long term consequences of elevated levels of CRP require further investigation.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
7Psychiatry Res 2007 Jan 149: 267-71
PMID17112596
TitleElevated serum levels of C-reactive protein are associated with more severe psychopathology in a subgroup of patients with schizophrenia.
AbstractThe present study examined the hypothesis that elevated serum levels of C-reactive protein (CRP) would be associated with more severe clinical symptoms in patients with schizophrenia. Twenty-six inpatients with schizophrenia or schizoaffective disorder were enrolled. Serum levels of CRP were measured, and each patient was assessed with the Positive and Negative Syndrome Scale (PANSS). Subjects with CRP levels above the normal range (CRP>0.50 mg/dl, elevated CRP group, N=5) scored significantly higher than those with CRP levels in the normal range (CRPCRP group, N=21) on the PANSS total score, negative symptom subscale score and general psychopathology subscale score. There was no significant difference between the two groups on the PANSS positive symptom subscale score. An inflammatory process, as reflected by elevated serum levels of CRP, might be associated with more severe psychopathology in a subgroup of patients with schizophrenia.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
8Altern Med Rev 2007 Sep 12: 207-27
PMID18072818
TitleOmega-3 DHA and EPA for cognition, behavior, and mood: clinical findings and structural-functional synergies with cell membrane phospholipids.
AbstractThe omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are orthomolecular, conditionally essential nutrients that enhance quality of life and lower the risk of premature death. They function exclusively via cell membranes, in which they are anchored by phospholipid molecules. DHA is proven essential to pre- and postnatal brain development, whereas EPA seems more influential on behavior and mood. Both DHA and EPA generate neuroprotective metabolites. In double-blind, randomized, controlled trials, DHA and EPA combinations have been shown to benefit attention deficit/hyperactivity disorder (AD/HD), autism, dyspraxia, dyslexia, and aggression. For the affective disorders, meta-analyses confirm benefits in major depressive disorder (MDD) and bipolar disorder, with promising results in schizophrenia and initial benefit for borderline personality disorder. Accelerated cognitive decline and mild cognitive impairment (MCI) correlate with lowered tissue levels of DHA/EPA, and supplementation has improved cognitive function. Huntington disease has responded to EPA. Omega-3 phospholipid supplements that combine DHA/EPA and phospholipids into the same molecule have shown marked promise in early clinical trials. Phosphatidylserine with DHA/EPA attached (Omega-3 PS) has been shown to alleviate AD/HD symptoms. Krill omega-3 phospholipids, containing mostly phosphatidylcholine (PC) with DHA/EPA attached, markedly outperformed conventional fish oil DHA/EPA triglycerides in double-blind trials for premenstrual syndrome/dysmenorrhea and for normalizing blood lipid profiles. Krill omega-3 phospholipids demonstrated anti-inflammatory activity, lowering C-reactive protein (CRP) levels in a double-blind trial. Utilizing DHA and EPA together with phospholipids and membrane antioxidants to achieve a triple cell membrane synergy may further diversify their currently wide range of clinical applications.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
9Int Clin Psychopharmacol 2007 Jul 22: 205-11
PMID17519643
TitleSimilar frequency of abnormal correlation between serum leptin levels and BMI before and after olanzapine treatment in schizophrenia.
AbstractMelkersson proposed leptin dysregulation as a factor in the olanzapine-induced metabolic dysfunction. Their suggestion was based on the absence of the expected positive correlation between serum leptin levels and the BMI, and the loss of the sex-dependent difference in leptin levels, which are higher in women. Although subsequent studies did not confirm that proposal, few of them assessed basal leptin levels and corrected for body fat percentage. Along with these variables, we added a precise definition of participants out of the expected positive correlation in a large sample of schizophrenia patients. Sixty patients (26 women and 34 men) with severe schizophrenia undergoing chronic hospitalization and conventional antipsychotic treatment were switched to olanzapine (10-20 mg/day). We assessed at baseline, and at weeks 8 and 16 of treatment, the percentage of participants with abnormal correlation (out of the 95% confidence interval in the regression line) between leptin levels and the BMI, and the correlation between leptin and insulin, glucose, the insulin resistance index, c-reactive protein (CRP) and treatment response. Leptin levels were higher in women than in men (P<0.01). The positive correlation between leptin levels, BMI and percentage of fat were preserved. After olanzapine, 3.8% of women and 2.9-5.8% of men were out the 95% confidence interval, and the proportion was similar at baseline. Glucose, insulin, the insulin resistance index and the CRP levels significantly increased after olanzapine. The impact of olanzapine on leptin regulation appears discrete and limited to a small number of participants. Additional studies must clarify the features that render them to metabolic dysregulation.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
10J. Neurosci. Res. 2007 May 85: 1373-80
PMID17348038
TitleS100B in neuropathologic states: the CRP of the brain?
AbstractIn recent years there has been a proliferation of interest in the brain-specific protein S100B, its many physiologic roles, and its behaviour in various neuropathologic conditions. Since the mid-1960s, its wide variety of intracellular and extracellular activities has been elucidated, and it has also been implicated in an increasing number of central nervous system (CNS) disorders. S100B is part of a superfamily of proteins, some of which (including S100B) have been implicated as calcium-dependent regulatory proteins that modulate the activity of effector proteins or cells. S100B is primarily an astrocytic protein. Within cells, it may have a role in signal transduction, and it is involved in calcium homeostasis. Information about the functional implication of S100B secretion by astrocytes into the extracellular space is scant but there is substantial evidence that secreted glial S100B exerts trophic or toxic effects depending on its concentration. This review summarises the historic development and current knowledge of S100B, including recent interesting findings relating S100B to a diversity of CNS pathologies such as traumatic brain injury, Alzheimer's disease, Down's syndrome, schizophrenia, and Tourette's syndrome. These broad implications have led some workers to describe S100B as 'the CRP (C-reactive protein) of the brain.' This review also examines S100B's potential role as a neurologic screening tool, or biomarker of CNS injury, analogous to the role of CRP as a marker of systemic inflammation.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
11Biol. Psychiatry 2008 Dec 64: 1019-23
PMID18760403
TitleEndogenous retrovirus type W GAG and envelope protein antigenemia in serum of schizophrenic patients.
AbstractRecent and independent molecular studies have shown an association between human endogenous retroviruses type "W" family (HERV-W) and schizophrenia, mostly by polymerase chain reaction studies, but none has yet addressed specific antigen detection in living patients.
Forty-nine schizophrenic patients and an equivalent number of healthy control subjects were included in the present exploratory study. The HERV-W GAG and envelope (ENV) proteins were quantified in the serum with a dedicated immunoassay set-up with specific monoclonal antibodies to either antigen.
In schizophrenic patients, positive antigenemia for ENV was found in 23 of 49 (47%) and for GAG in 24 of 49 (49%). Only 1 of 30 (3%) for ENV and 2 of 49 (4%) for GAG were positive in blood donors (p < .01 for ENV; p < .001 for GAG). Interestingly, bioclinical data analyses revealed significant correlation between GAG or ENV antigenemia (a protein causing dysimmune inflammatory effects) and C-reactive protein (CRP) levels (a systemic inflammation biomarker).
Frequently elevated CRP has previously been described in schizophrenic patients and has been shown to match with an evolution toward cognitive deficit and neuronal loss. Elsewhere viruses such as influenza, long-associated with risk for schizophrenia through perinatal infections, have been shown to activate HERV-W elements in human cells. We therefore discuss a relationship between environment factors long-associated with early risk, genetic factors represented by this endogenous family, the production of its pro-inflammatory ENV protein and known "inflammation-mediated" neurotoxicity, as a possible hypothesis for a pathogenic cascade in association with HERV-W. Our present results thus confirm that HERV-W studies have opened a novel avenue of research in schizophrenia.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
12Schizophr. Res. 2008 Aug 103: 83-93
PMID18436434
TitleCoagulation and inflammation markers during atypical or typical antipsychotic treatment in schizophrenia patients and drug-free first-degree relatives.
AbstractClinical studies suggest that the second generation antipsychotics (APs) clozapine and olanzapine and to a lesser extent the typical antipsychotics may be associated with a procoagulant and proinflammatory state that promotes venous thromboembolism. We evaluated here several blood factors associated with coagulation and inflammation in AP-treated schizophrenia patients and their first-degree relatives.
Procoagulant factors (fibrinogen and plasminogen activator inhibitor [PAI-1]), the anticoagulant factor antithrombin III [AT-III], and inflammation-related factors (C-reactive protein [CRP] and leptin) were assessed in patients chronically treated with clozapine (n=29), olanzapine (n=29), typical APs (n=30) and first degree relatives of clozapine (n=23) and olanzapine subjects (n=11).
The typical AP group had the highest CRP level (p=0.013) in spite of having the lowest body mass index (BMI). Patients as a single group had higher CRP levels than relatives (p=0.003). The typical AP group also had the highest AT-III levels (p=0.021). Fibrinogen levels did not differ between the groups (p=0.13). Olanzapine patients displayed the highest PAI-1 and leptin levels among the drug-treated subjects, but values were similar to those observed in their relatives, and were significantly correlated with the BMI.
A homogeneous negative profile of high inflammation and procoagulant factors along with low levels of anticoagulants was not detected in any group. While preliminary, our results suggest that the observed abnormalities were not related to a direct drug effect, but to elevated BMI (high PAI-1 and leptin in olanzapine-treated patients). We speculate that the high CRP in the typical AP group might be related to poor lifestyle habits, but this must we confirmed in future studies.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
13Biol. Psychiatry 2008 Dec 64: 1019-23
PMID18760403
TitleEndogenous retrovirus type W GAG and envelope protein antigenemia in serum of schizophrenic patients.
AbstractRecent and independent molecular studies have shown an association between human endogenous retroviruses type "W" family (HERV-W) and schizophrenia, mostly by polymerase chain reaction studies, but none has yet addressed specific antigen detection in living patients.
Forty-nine schizophrenic patients and an equivalent number of healthy control subjects were included in the present exploratory study. The HERV-W GAG and envelope (ENV) proteins were quantified in the serum with a dedicated immunoassay set-up with specific monoclonal antibodies to either antigen.
In schizophrenic patients, positive antigenemia for ENV was found in 23 of 49 (47%) and for GAG in 24 of 49 (49%). Only 1 of 30 (3%) for ENV and 2 of 49 (4%) for GAG were positive in blood donors (p < .01 for ENV; p < .001 for GAG). Interestingly, bioclinical data analyses revealed significant correlation between GAG or ENV antigenemia (a protein causing dysimmune inflammatory effects) and C-reactive protein (CRP) levels (a systemic inflammation biomarker).
Frequently elevated CRP has previously been described in schizophrenic patients and has been shown to match with an evolution toward cognitive deficit and neuronal loss. Elsewhere viruses such as influenza, long-associated with risk for schizophrenia through perinatal infections, have been shown to activate HERV-W elements in human cells. We therefore discuss a relationship between environment factors long-associated with early risk, genetic factors represented by this endogenous family, the production of its pro-inflammatory ENV protein and known "inflammation-mediated" neurotoxicity, as a possible hypothesis for a pathogenic cascade in association with HERV-W. Our present results thus confirm that HERV-W studies have opened a novel avenue of research in schizophrenia.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
14J Neural Transm (Vienna) 2009 Feb 116: 213-20
PMID19082523
TitleDifferentiating nicotine- versus schizophrenia-associated decreases of the alpha7 nicotinic acetylcholine receptor transcript, CHRFAM7A, in peripheral blood lymphocytes.
AbstractNicotine addiction is prevalent in individuals with schizophrenia. Nicotine activation of nicotinic receptors (nAChRs) is time- and dose-dependent, but gene expression analyses often rely on qualitative self- or family-reported measures of smoking. We sought lymphocyte surrogates for cerebral alpha7-nAChR activity and tested if receptor transcription correlated with concurrently measured serum biomarkers for smoking [cotinine, C-reactive protein (CRP)]. PCR surveys to detect lymphocytic alpha7-related isoforms identified CHRFAM7A as the only consistently amplifiable transcript. In 20 smoking-matched people (n = 10 schizophrenia, n = 10 controls), we found significantly lower CHRFAM7A in cotinine and self-reported smokers versus nonsmokers (p CRP in any bi- or multi-variate analysis. Smoking-related CRP elevations only occurred in cotinine-based comparisons (p
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
15Bipolar Disord 2009 Nov 11: 726-34
PMID19839997
TitleSimilar immune profile in bipolar disorder and schizophrenia: selective increase in soluble tumor necrosis factor receptor I and von Willebrand factor.
AbstractAlterations 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 Keywordsschizophrenia, schizophrenic, schizotypal
16Biol. Psychiatry 2009 Dec 66: 1013-22
PMID19640511
TitleInflammatory markers in schizophrenia: comparing antipsychotic effects in phase 1 of the clinical antipsychotic trials of intervention effectiveness study.
AbstractC-reactive protein (CRP), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin are systemic inflammatory markers (IM) that positively correlate with cardiovascular (CV) risk. Despite the known CV effects of atypical antipsychotics, there is limited prospective data on IM changes during treatment.
The IM outcomes were compared between antipsychotic treatment groups in the CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) schizophrenia trial phase 1 with subjects with laboratory assessments at baseline and 3 months (n = 789).
There were significant treatment differences in CRP, E-selectin, and ICAM-1 at 3 months, with a differential impact of baseline values on the CRP and ICAM-1 results. In overall comparisons, quetiapine and olanzapine had the highest median levels for CRP, and olanzapine for E-selectin and ICAM-1. Olanzapine was significantly different after baseline adjustment than perphenazine (p = .001) for E-selectin, and in those with low baseline CRP (<1 mg/L), olanzapine was significantly different than perphenazine (p < .001), risperidone (p < .001), and ziprasidone (p = .002) for CRP. Perphenazine had the lowest 3-month ICAM-1 levels in subjects with baseline ICAM-1 above the median, but the differences were not statistically significant versus olanzapine (p = .010), quetiapine (p = .010), and risperidone (p = .006) after controlling for multiple comparisons. The 18-month repeated measures CRP analysis confirmed the significantly higher values for olanzapine in those with low baseline CRP.
This analysis provides further evidence for differential antipsychotic metabolic liabilities as measured by changes in systemic inflammation. C-reactive protein might emerge as a useful target for CV risk outcomes in schizophrenia patients.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
17Psychiatry Res 2009 Aug 169: 56-61
PMID19619902
TitleAssociation of blood levels of C-reactive protein with clinical phenotypes in Arab schizophrenic patients.
Abstractschizophrenia may be associated with inflammatory reactions and C-reactive protein (CRP) is a nonspecific serum protein marker for persisting inflammatory states. This study aimed to assess concentrations of high sensitivity CRP (hsCRP) in schizophrenic Arab patients and evaluate the relationships of hsCRP levels with aspects of clinical phenotypes of the disease. Two age-matched groups of subjects were studied: (1) healthy controls, HC, n=165; (2) patients with schizophrenia, SZ: n=207. Each subject was evaluated with a standard questionnaire for age at disease onset, family history, disease severity and outcome. Serum hsCRP levels were measured by immunoassay. The two groups of subjects were similar in age, ethnic composition and socioeconomic status. Those with SZ had significantly greater serum concentrations of hsCRP. There were significant associations between hsCRP and (i) age in both groups; (ii) body mass index (BMI) in HC but not in SZ. In the latter, hsCRP levels were: (a) marginally higher in women with later age of disease onset; (ii) highest with remission and with catatonic features; and (iii) lower with family history of psychosis. The study concludes that serum levels of hsCRP are increased in clinically stable Arab patients with schizophrenia and appear related to the disorder's clinical expression. It is suggested that there may be an inflammatory component to schizophrenia which is associated with aspects of its clinical phenotype.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
18Psychiatry Res 2009 Aug 169: 56-61
PMID19619902
TitleAssociation of blood levels of C-reactive protein with clinical phenotypes in Arab schizophrenic patients.
Abstractschizophrenia may be associated with inflammatory reactions and C-reactive protein (CRP) is a nonspecific serum protein marker for persisting inflammatory states. This study aimed to assess concentrations of high sensitivity CRP (hsCRP) in schizophrenic Arab patients and evaluate the relationships of hsCRP levels with aspects of clinical phenotypes of the disease. Two age-matched groups of subjects were studied: (1) healthy controls, HC, n=165; (2) patients with schizophrenia, SZ: n=207. Each subject was evaluated with a standard questionnaire for age at disease onset, family history, disease severity and outcome. Serum hsCRP levels were measured by immunoassay. The two groups of subjects were similar in age, ethnic composition and socioeconomic status. Those with SZ had significantly greater serum concentrations of hsCRP. There were significant associations between hsCRP and (i) age in both groups; (ii) body mass index (BMI) in HC but not in SZ. In the latter, hsCRP levels were: (a) marginally higher in women with later age of disease onset; (ii) highest with remission and with catatonic features; and (iii) lower with family history of psychosis. The study concludes that serum levels of hsCRP are increased in clinically stable Arab patients with schizophrenia and appear related to the disorder's clinical expression. It is suggested that there may be an inflammatory component to schizophrenia which is associated with aspects of its clinical phenotype.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
19Int. J. Immunogenet. 2010 Oct 37: 407-10
PMID21182750
TitleGenetic variants of the inflammatory C-reactive protein and schizophrenia in Armenian population: a pilot study.
AbstractC-reactive protein (CRP) is an inflammation marker implicated in the pathogenesis of schizophrenia. To investigate association of the CRP rs1417938, rs1800947, rs1205 variants with susceptibility to schizophrenia 208 unrelated Armenians (103 patients and 105 healthy controls) were genotyped. In this pilot study, none of studied variants was associated with schizophrenia.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
20Psychiatr Danub 2010 Jun 22: 275-7
PMID20562761
TitleC-reactive protein and metabolic syndrome in patients with bipolar disorder compared to patients with schizophrenia.
AbstractInfectious and inflammatory processes could potentially play an important role in the etiology and pathogenesis of psychotic disorders. The aim was to investigate is there any differences in CRP levels in patients with bipolar disorder compared to patients with schizophrenia and if there is an association between increased CRP levels and the presence of MS in these two groups of patients.
Patients with bipolar disorder (N=60; 32 males and 28 females) and schizophrenia (N=63, 33 males and 30 females). MS was defined according to NCEP ATP III criteria. The cut-off point for elevated CRP was set at 5 mg /L.
The prevalence of the MS was 31% in bipolar group compared to the 37% in schizophrenia group. No statistically significant differences in mean CRP values was observed between bipolar and schizophrenia group. CRP >5 mg /l was significantly associated with the presence of MS.
Measurement of serum inflammatory parameters in psychiatric patients may be beneficial in order to obtain a better assessment of their metabolic risk profile.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
21Folia Parasitol. 2010 Jun 57: 129-35
PMID20608475
TitleThe diagnosis of a personality disorder increases the likelihood for seropositivity to Toxoplasma gondii in psychiatric patients.
AbstractIndividuals serologically positive for the chronic infection with the parasite Toxoplasma gondii (TG) display certain personality traits differently from uninfected individuals. Experimental data in mice demonstrate that TG infection modulates behaviour. However, psychiatric patients with a personality disorder have not yet been investigated systematically. In our sample containing 896 psychiatric inpatients with the primary diagnoses of schizophrenia, major depression, schizoaffective or bipolar disorder and 214 psychiatrically unaffected controls (same geographic region, sampled during same time period) we analysed for effects of the additional diagnosis of a personality disorder in the patients. Psychiatrically, a patient can meet the criteria of a personality disorder additionally to any of the mentioned primary diagnoses. We applied logistic regression and cross-table statistics, separated groups by the presence/absence of a personality disorder (ICD-10) and adjusted for age between groups. We found that among all patients the additional diagnosis of a personality disorder was significantly associated with TG infection. Furthermore, only in the patients with an additional personality disorder medium titre responses (1:16-1:64) were associated with chronic course and high C-reactive protein (CRP) levels whereas high titre response (>1:64) was associated with a more acute recurrent clinical course. In the older individuals only there was a preponderance of medium titre responses (1:16-1:64) among the patients with personality disorder compared to those without and controls. We conclude that TG infection and the host's response to it make a difference for the diagnosis of a personality disorder. Our data support that TG infection can modulate human behaviour and personality traits.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
22Rinsho Shinkeigaku 2010 Feb 50: 103-7
PMID20196492
Title[Anti-NMDA receptor encephalitis during pregnancy].
AbstractA 19-year-old female in her 2nd trimester (17 weeks) of pregnancy became irritable a few days before admission. She became unable to open her mouth and could not talk. She was admitted to the psychiatric hospital due to a rapid change in behavior and a consciousness disturbance. She was diagnosed as having schizophrenia by a psychiatrist. Her EEG showed diffuse high voltage and slow waves. Acute encephalitis was then suspected. Her past and family histories were not suggestive of viral infection. On physical examination, she had a low grade fever. She had hyperhidrosis, autophagia, and repeated oral dyskinesia. Her consciousness level fluctuated from somnolence to stupor. Although her blood CRP level was mildly elevated and she had mild pleocytosis, HSV-PCR was negative in the cerebrospinal fluid (CSF). Abdominal ultrasound examination and MRI showed no ovarian teratoma. Computed tomography (CT) and magnetic resonance imaging (MRI) showed no brain abnormalities. Before analysis for specific nervous system antibodies, the initial diagnosis was non-herpetic limbic encephalitis. She was twice treated with a 6-day course of methylprednisolone (500 mg/day) infusion. She was also given phenobarbital since she had a tonic-clonic seizure about 1 month after admission. Finally, she had a normal delivery at 37 weeks. The baby was healthy, and the patient was discharged without sequelae. We concluded that her diagnosis was anti-N-methyl-D-aspartate (NMDA) receptor (anti-NMDAR) encephalitis based on the presence of anti-NMDAR antibody in the CSF. This report is the first description of a patient with anti-NMDAR antibody encephalitis. The precise mechanism of this encephalitis is not clear, although there have been several reports of autoimmune encephalitis during pregnancy. The patient's CSF anti-NMDAR antibody titer during treatment was measured. Before treatment, the CSF anti-NMDAR antibody titer was strongly positive, but it decreased during treatment and then disappeared after delivery. We hypothesized that the presence of the embryo or placenta may have triggered an antigenic signal and/or antibody through inappropriate immunological modulation.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
23Psychiatry Res 2011 Sep 189: 305-11
PMID21798602
TitleInflammation in psychotic disorders: a population-based study.
AbstractWe investigated inflammatory markers in psychotic disorders and their association with metabolic comorbidity, antipsychotic medication, smoking, alcohol use, physical condition, and mood. From the population-based Finnish Health 2000 study, we identified all persons with schizophrenia (n=45), other nonaffective psychosis (ONAP) (n=57), affective psychosis (n=37) and chose controls matched by age, sex, and region of residence. We found that persons with schizophrenia had significantly higher sIL-2R?, IL-1RA and C-reactive protein (CRP), persons with ONAP significantly higher IL-1RA and CRP and persons with affective psychosis almost significantly higher TNF-? compared to their matched controls. Current antipsychotic use was associated with elevated IL-1RA and CRP. After taking metabolic and lifestyle-related variables that associated with inflammatory markers into account, only antipsychotic medication remained associated with elevated IL-1RA and TNF-? which are markers related to the activation of innate immune system. CRP was influenced by both antipsychotic medication and nonaffective psychosis. sIL-2R?, a marker of T-cell activation, was associated with depressive symptoms, schizophrenia, and affective psychosis. We conclude that in persons with psychotic disorders, activation of mononuclear phagocyte system was mostly related to metabolic comorbidity and antipsychotic medication use, whereas T-cell activation had a more direct relationship with both psychotic disorders and depressive symptoms.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
24Psychiatry Res 2011 Nov 190: 91-7
PMID21621854
TitleC-reactive protein serum level in drug-free male Egyptian patients with schizophrenia.
AbstractDespite the growing research interest in the role of immunological markers in schizophrenia, few studies, with conflicting results, have focused on the association between high sensitivity C-reactive protein (hs-CRP) levels and clinical characteristics in schizophrenia. In this cross-sectional case-control study, a sample of 200 antipsychotic-free male Egyptian schizophrenia patients was assessed by the Positive and Negative Syndrome Scale (PANSS) and compared with 200 healthy controls as regards serum hs-CRP level using an immunoturbidimetric method. CRP level for patients (geometric mean=3.3 mg/L) was significantly (P=0.000) higher than that for controls (geometric mean=1.4 mg/L). PANSS scores and patients' data, which significantly correlated with serum hs-CRP level, were entered into a stepwise multiple regression analysis. Results of this analysis showed that PANSS negative symptom score was second only to the waist circumference, with which they explained 54.7 % of the variation in serum hs-CRP. Comparable results were obtained when patients, controls and the relevant confounders were included in one multivariate analysis. We concluded that in Egyptian men, waist circumference and schizophrenia diagnosis are strong predictors of raised CRP level independent of a number of potentially confounding variables. In antipsychotic-free patients, CRP level is higher than in healthy controls and is positively correlated with the severity of the psychopathology as measured by PANSS. This relationship is especially notable in negative, but not positive symptoms.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
25Schizophr. Res. 2012 Sep 140: 169-74
PMID22817875
TitleCardiovascular risk factors during second generation antipsychotic treatment are associated with increased C-reactive protein.
AbstractSevere 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 Keywordsschizophrenia, schizophrenic, schizotypal
26Case Rep Psychiatry 2012 -1 2012: 592784
PMID22934219
TitleThe Value of Desmethylclozapine and Serum CRP in Clozapine Toxicity: A Case Report.
AbstractClozapine, an atypical antipsychotic, has proved to be superior to other antipsychotics in treating patients with refractory schizophrenia. An increased plasma clozapine level above the therapeutic window may be associated with serious adverse events including paralytic ileus. Clozapine toxicity may occur in association with infection or after drug overdose. In a medical emergency situation, differentiating between a toxic clozapine ingestion and an infection-induced toxicity might be hindered by associated CNS changes and by the clozapine modulation of the inflammatory process. This may delay prompt initiation of a tailored treatment strategy. Here, we report a case of paralytic ileus developed within the context of clozapine toxicity. Although the underlying cause of toxicity was not clinically obvious, giving antimicrobial therapy resulted in an improvement in the patient's clinical condition. This report indicates the value of serum levels of C-reactive protein and desmethylclozapine, major metabolite of clozapine, in the treatment of aetiologically unclear clozapine toxicity.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
27Schizophr. Res. 2012 Jan 134: 83-8
PMID22048011
TitleAdditive effects of elevated C-reactive protein and exposure to Herpes Simplex Virus type 1 on cognitive impairment in individuals with schizophrenia.
AbstractWe investigated the effect of elevated levels of C-reactive protein (CRP) and exposure to Herpes simplex virus type 1 (HSV-1) on the severity of cognitive impairment in individuals with schizophrenia.
We measured the levels of CRP and of antibodies to HSV-1 in serum samples from 588 individuals with schizophrenia by enzyme immunoassay tests. Cognitive functioning was measured with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and psychiatric symptoms with the Positive and Negative Syndrome Scale (PANSS). The effects of HSV1 and CRP on cognitive functioning were analyzed with linear and logistic regression analyses adjusting for demographic and clinical variables.
The individuals with elevated CRP levels and HSV-1 seropositivity had lower RBANS cognitive scores. The strongest effect was found in individuals who had both serological evidence of HSV-1 exposure and elevated levels of CRP. These individuals had odds of 2.35 to have an RBANS Total score<=60 as compared to individuals who were HSV-1 seronegative and who did not have elevated levels of CRP (p=.002). The risks of decreased cognitive functioning associated with HSV-1 exposure and elevated levels of CRP were independent and additive. There was no effect of HSV-1 exposure and CRP levels on the severity of symptoms as measured by the PANSS (all p>.5).
Elevated levels of CRP and exposure to HSV-1 are associated with the severity of cognitive impairment in schizophrenia. These findings indicate that infection and inflammation may play a major role in the cognitive deficits associated with schizophrenia.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
28Prog. Neuropsychopharmacol. Biol. Psychiatry 2013 Aug 45: 92-9
PMID23685202
TitleObesity and psychiatric disorders: commonalities in dysregulated biological pathways and their implications for treatment.
AbstractRates of obesity are higher than normal across a range of psychiatric disorders, including major depressive disorder, bipolar disorder, schizophrenia and anxiety disorders. While the problem of obesity is generally acknowledged in mental health research and treatment, an understanding of their bi-directional relationship is still developing. In this review the association between obesity and psychiatric disorders is summarised, with a specific emphasis on similarities in their disturbed biological pathways; namely neurotransmitter imbalances, hypothalamus-pituitary-adrenal axis disturbances, dysregulated inflammatory pathways, increased oxidative and nitrosative stress, mitochondrial disturbances, and neuroprogression. The applicability and effectiveness of weight-loss interventions in psychiatric populations are reviewed along with their potential efficacy in ameliorating disturbed biological pathways, particularly those mediating inflammation and oxidative stress. It is proposed that weight loss may not only be an effective intervention to enhance physical health but may also improve mental health outcomes and slow the rate of neuroprogressive disturbances in psychiatric disorders. Areas of future research to help expand our understanding of the relationship between obesity and psychiatric disorders are also outlined.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
29Schizophr. Res. 2013 Aug 148: 130-7
PMID23746484
TitleDiscordant patterns of bacterial translocation markers and implications for innate immune imbalances in schizophrenia.
AbstractThe origin of inflammation in psychiatric disorders is not well understood. The translocation of commensal microbiota across the gastrointestinal barrier can result in a persistent state of low-grade immune activation and/or inflammation. We measured serological surrogate markers of bacterial translocation (soluble CD14 (sCD14) and lipopolysaccharide binding protein (LBP)) in two psychiatric cohorts and compared these levels to C-reactive protein (CRP), body mass index (BMI), and food-related and autoimmune antibodies. The two cohorts were composed of the following: (1) n=141 schizophrenia, n=75 bipolar disorder, n=78 controls; (2) n=78 antipsychotic-naïve first-episode schizophrenia, n=38 medicated first-episode schizophrenia. sCD14 seropositivity conferred a 3.1-fold increased odds of association with schizophrenia (multivariate regressions, OR=3.09, p<0.0001) compared to controls. Case-control differences in sCD14 were not matched by LBP. Quantitative levels of LBP, but not sCD14, correlated with BMI in schizophrenia (R(2)=0.21, p<0.0001). sCD14 and LBP also exhibited some congruency in schizophrenia with both significantly correlated with CRP (R(2)=0.26-0.27, p<0.0001) and elevated in females compared to males (p<0.01). Antipsychotic treatment generally did not impact sCD14 or LBP levels except for significant correlations, especially sCD14, with gluten antibodies in antipsychotic-naïve schizophrenia (R(2)=0.27, p<0.0001). In bipolar disorder, sCD14 levels were significantly correlated with anti-tissue transglutaminase IgG (R(2)=0.37, p<0.001). In conclusion, these bacterial translocation markers produced discordant and complex patterns of activity, a finding that may reflect an imbalanced, activated innate immune state. Whereas both markers may upregulate following systemic exposure to Gram-negative bacteria, non-lipopolysaccharide-based monocyte activation, autoimmunity and metabolic dysfunction may also contribute to the observed marker profiles.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
30J Clin Diagn Res 2013 Dec 7: 2694-6
PMID24551615
TitleCardiovascular disease risk in schizophrenia patients: a case control study.
AbstractThe schizophrenia patients are at higher risk for cardiovascular morbidity and mortality. The aim of this case-control study is to measure Cardiovascular Disease (CVD) risk parameters in patient group and compare it with normal population.
We recruited 45 cases of schizophrenia diagnosed by diagnostic and statistical manual of mental disorders (DSM-IV) criteria and 41 healthy controls from general population. The body mass index, metabolic syndrome parameters, lipid parameters and high sensitive C-reactive protein were measured in both groups. Metabolic syndrome and dyslipidemia prevalence were assessed based on National Cholesterol Education Programme (NCEP) Adult Treatment Panel III (ATP III) guidelines.
The schizophrenia subjects showed statistically significant high waist circumference, increased triglycerides and decreased HDL cholesterol values. The subjects also showed statistically significant increased hs-CRP values. The prevalence of metabolic syndrome and laboratory dyslipidemia were 28.8% and 51.1% respectively, which were higher compared to control group.
The schizophrenia subjects are at higher risk for cardiovascular disease events due to high prevalence of metabolic syndrome and dyslipidemia. These patients should be regularly monitored for CVD risk factors and timely referred to physician for further management.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
31Asia Pac Psychiatry 2013 Jun 5: E58-63
PMID23857813
TitleIncreased high-sensitivity C-reactive protein levels in Taiwanese schizophrenic patients.
Abstractschizophrenia is associated with the activation of the immune/inflammatory system. C-reactive protein (CRP), a positive acute phase protein, may be associated with schizophrenia and antipsychotic treatment.
The serum high-sensitivity CRP (hsCRP) levels of 36 schizophrenic patients undergoing clozapine, olanzapine or risperidone treatment and 36 sex-matched healthy subjects were collected. The difference in hsCRP levels between the schizophrenic and the control groups was estimated using ancova. anova was performed to examine the differences in the hsCRP levels between three antipsychotic groups (clozapine, olanzapine and risperidone).
ancova adjusted for age and body mass index (BMI) revealed a significant increase in the hsCRP levels in the schizophrenic group (1.4 mg/L, SD =1.5 mg/L) in comparison with the control group (0.9 mg/L, SD = 1.4 mg/L) (P = 0.013). anova revealed no statistical difference of age, BMI and hsCRP in three antipsychotic groups (P = 0.83, 0.90 and 0.71, respectively).
The elevation of CRP level is seen in chronic schizophrenia under antipsychotic treatment; however, studies with a larger sample size are required to confirm these results.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
32Asia Pac Psychiatry 2013 Jun 5: E58-63
PMID23857813
TitleIncreased high-sensitivity C-reactive protein levels in Taiwanese schizophrenic patients.
Abstractschizophrenia is associated with the activation of the immune/inflammatory system. C-reactive protein (CRP), a positive acute phase protein, may be associated with schizophrenia and antipsychotic treatment.
The serum high-sensitivity CRP (hsCRP) levels of 36 schizophrenic patients undergoing clozapine, olanzapine or risperidone treatment and 36 sex-matched healthy subjects were collected. The difference in hsCRP levels between the schizophrenic and the control groups was estimated using ancova. anova was performed to examine the differences in the hsCRP levels between three antipsychotic groups (clozapine, olanzapine and risperidone).
ancova adjusted for age and body mass index (BMI) revealed a significant increase in the hsCRP levels in the schizophrenic group (1.4 mg/L, SD =1.5 mg/L) in comparison with the control group (0.9 mg/L, SD = 1.4 mg/L) (P = 0.013). anova revealed no statistical difference of age, BMI and hsCRP in three antipsychotic groups (P = 0.83, 0.90 and 0.71, respectively).
The elevation of CRP level is seen in chronic schizophrenia under antipsychotic treatment; however, studies with a larger sample size are required to confirm these results.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
33BMC Psychiatry 2013 -1 13: 176
PMID23805859
TitleInvestigating the safety and efficacy of naltrexone for anti-psychotic induced weight gain in severe mental illness: study protocol of a double-blind, randomized, placebo-controlled trial.
AbstractObesity is a growing health problem leading to high rates of mortality and morbidity in patients with severe mental illness (SMI). The increased rate of obesity is largely attributed to antipsychotic use. The effect of antipsychotic medications on H1 and 5HT2 receptors has been associated with weight gain, but there is also a substantial amount of evidence showing that D2 receptor blockade may be responsible for weight gain by interacting with the dopamine-opioid system. Unfortunately, current available medications for weight loss have limited efficacy in this population. Naltrexone, an opioid receptor antagonist, may be a promising agent to reduce antipsychotic induced weight gain by decreasing food cravings. We aim to investigate the safety and efficacy of two doses of naltrexone (25 mg & 50 mg) versus placebo for weight and health risk reduction in overweight and obese individuals (BMI ? 28) with SMI, who gained weight while being treated with antipsychotics.
One hundred and forty four patients will be recruited throughout the greater New Haven area. The participants will be randomized to naltrexone 25 mg/day, naltrexone 50 mg/day, or placebo in a 1:1:1 ratio. Participants will be on the study medication for 52 weeks, and assessed weekly for the first 4 weeks and bi-weekly thereafter. The primary outcome measurements are weight reduction and percentage achieving clinically significant weight loss (5% of total body weight). Waist circumference, body mass index, serum lipid profile, fasting glucose, and glycosylated hemoglobin are the secondary outcome measures. The effect of naltrexone on other outcome measurements such as schizophrenia symptoms, depression, dietary consumption, quality of life, cognitive functioning, physical activity, metabolism/inflammation markers, serum leptin, ghrelin, peptide YY, adinopectin, high sensitivity CRP, interleukin 6, interleukin-1B, interleukin-18, and tumor necrosis factor alpha (TNF-?) will be evaluated. The data will be analyzed by applying linear mixed effect models.
This is the first large scale study investigating the safety and efficacy of naltrexone in antipsychotic induced weight gain; and hopefully, this may lead to a novel pharmacological option for management of this major health problem.
This trial is registered in http://www.clinicaltrials.gov as NCT01866098.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
34Trials 2013 -1 14: 101
PMID23782463
TitleOndansetron and simvastatin added to treatment as usual in patients with schizophrenia: study protocol for a randomized controlled trial.
AbstractNegative symptoms and cognitive deficits are two partially-related features of schizophrenia which have a major negative impact on social function and objective quality of life. Standard drug treatments have little impact on either. There is some evidence that anti-inflammatory treatment may have beneficial effects in schizophrenia and major depression. Statins are cholesterol-lowering agents that have been found to be anti-inflammatory agents and are also known to decrease C-reactive protein (CRP). Ondansetron is a serotonin (5-HT3) receptor antagonist widely used to prevent nausea and vomiting in patients receiving chemotherapy for cancer. Small studies have suggested that ondansetron is effective as an adjunct drug in improving the symptoms of schizophrenia.
This is a two center, six-month, double-blind placebo controlled, factorial design study of ondansetron and/or simvastatin added to treatment as usual for patients suffering from schizophrenia, schizoaffective disorder, psychosis not otherwise specified or schizophreniform disorder. This will be a 2 × 2 design, with 54 patients in each cell, giving a total of 216 patients over three years. There will be a screening, a randomization and seven follow-up visits. Full clinical and neurocognitive assessments will be carried out at baseline (randomization), 14 weeks and at 26 weeks, while the positive and negative syndrome scale (PANSS), pill count and side effects checklist will be carried out at every visit. Simvastatin will be started at 20 mg once daily (OD), this will be increased to 40 mg after four weeks. Ondansetron will be administered in an 8 mg dose.
Anti-inflammatory treatments have been shown to have some beneficial effects in schizophrenia. Both simvastatin and ondansetron provide some evidence of a reduction in symptoms compared to treatment as usual. The aim of this study is to establish the degree of improvement in negative symptoms with the addition of ondansetron and/or simvastatin to treatment as usual.
[corrected] ClinicalTrails.gov NCT01602029.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
35J Affect Disord 2013 Sep 150: 456-9
PMID23684514
TitleElevated C-reactive protein and cognitive deficits in individuals with bipolar disorder.
AbstractSome individuals with bipolar disorder have cognitive deficits even when euthymic. In previous studies, we found an association between elevated levels of C-reactive protein (CRP), a marker of inflammation, and reduced cognitive functioning in schizophrenia. This issue has not been examined in bipolar disorder.
We measured the levels of high sensitivity CRP in serum samples from 107 individuals with bipolar disorder. Cognitive functioning was measured with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Trail Making Test Part A and WAIS Information and Letter Number Sequencing. We estimated the odds of RBANS scores <=70 for participants whose CRP levels were above the 75th and the 90th percentile of the level of non-psychiatric controls. We also examined the association between cognitive scores and CRP levels. Covariates included demographic factors, mood symptom severity, cigarette smoking status, and body mass index.
There was a significantly increased odds of low RBANS total score for individuals who had a CRP level higher than the 90th percentile (OR=4.32, p=.018) and the 75th percentile (OR=3.07, p=.04)) of the control group. There was an inverse relationship between CRP levels and performance on RBANS total (t=-2.48, p=.015); RBANS immediate memory (t=-2.16, p=.033); RBANS attention (t=-2.18, p=.032); RBANS language (t=-2.13, p=.036); Trail Making A (t=-2.39, p=.019).
Factors which we did not measure such as diet, allergen exposure, and underlying autoimmune disorders may contribute to CRP levels.
Inflammation may play a major role in the cognitive deficits associated with bipolar disorder.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
36Nord J Psychiatry 2013 Oct 67: 320-5
PMID23228159
TitleAssociation between C-reactive protein and homocysteine with the subcomponents of metabolic syndrome in stable patients with bipolar disorder and schizophrenia.
AbstractPrevious studies revealed high prevalence of metabolic syndrome (MetS) in patients with bipolar disorder and schizophrenia. C-Reactive protein (CRP) and homocysteine have also both emerged as independent risk factors for the development of cardiovascular disease (CVD) but are less investigated in psychiatric disorders.
The aim of this study was to ascertain which specific subcomponents of MetS are associated with levels of CRP and homocysteine in patients with bipolar disorder and schizophrenia.
Our sample consisted of patient group (n = 122) (60 bipolar and 62 schizophrenic patients) treated with second-generation antipsychotics (SGA) and healthy controls (n = 59). MetS was defined according to NCEP ATP-III criteria; the cut-off point for elevated CRP was set up at 5 mg/l and for hyperhomocysteinemia at 15 ?mol/l.
In the patient group, homocysteine was correlated with waist circumference, systolic and diastolic blood pressure, triglycerides and blood glucose, while CRP was correlated with waist circumference and diastolic blood pressure. Patients with hyperhomocysteinemia had an 8.442 times higher chance to have met the criteria for MetS while elevated CRP was not a significant predictor of MetS.
There is a complex association between CRP and homocysteine with specific subcomponents of MetS in patients with bipolar disorder and schizophrenia. Given the high risk of cardiovascular disorders in psychiatric patients, these relationships deserve further investigation. Clinically, it could be useful to include the measurement of homocysteine and CRP levels in routine psychiatric diagnostic procedures.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
37Schizophr. Res. 2013 Jan 143: 198-202
PMID23218564
TitleC-reactive protein is elevated in schizophrenia.
AbstractIncreased levels of inflammatory markers have been reported in schizophrenia, but few studies have examined levels of high sensitivity C-reactive protein (CRP), a non-specific inflammatory marker.
Levels of high sensitivity CRP were measured in individuals with schizophrenia, bipolar disorder, and non-psychiatric controls. Linear regression analyses were used to compare the CRP levels among the three groups adjusting for demographic and clinical variables. Logistic regression analyses were used to determine the odds ratios associated with elevated levels of CRP, defined as >=75th and 90th percentile in the controls.
The sample consisted of 715 individuals: 295 with schizophrenia, 192 with bipolar disorder, and 228 without a psychiatric disorder. The levels of CRP in the schizophrenia group, but not in the bipolar disorder group, were significantly increased compared to controls adjusting for age, gender, race, maternal education, smoking status, and Body Mass Index (BMI) (t=3.78, p=<.001). The individuals with schizophrenia had significantly increased odds of having elevated levels of CRP relative to both the 75th and 90th percentile levels of the controls adjusting for the same covariates (OR 1.79, 95% CI 1.14, 2.82; p=.012; OR 2.76, 95% CI 1.58, 4.83, p=<.001). In the multivariate linear and logistic regression analyses, levels of CRP were also associated with BMI and female gender.
Individuals with schizophrenia may be at risk for the adverse health consequences associated with elevated CRP in the overall population. Trials of interventions directed at lowering the level of CRP and other inflammatory markers are indicated.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
38Eur. Psychiatry 2013 Mar 28: 161-7
PMID21964485
TitleC-reactive protein as a marker of cardiovascular disease in patients with a schizophrenia spectrum disorder treated in routine medical practice.
AbstractInterest in cardiovascular diseases (CVD) in schizophrenia has grown recently due to documented incremental mortality. C-reactive protein (CRP) has been assessed as a marker in individuals with CVD and/or at high risk of developing it. However, its role in schizophrenia patients is unknown. The goal of this research was thus to explore the use of CRP as a marker of CVD risk in patients with schizophrenia.
A cross-sectional analysis of the Badalona Serveis Assistencials (BSA) administrative claims database was conducted including all subjects aged>18 years with a diagnosis of schizophrenia spectrum disorder. CRP measurement, sociodemographics, medical history, 10-year CVD risk (Framingham function) and clinical chemistry data were extracted for analysis.
Seven hundred and five patients (53.0% men, 48.2 [15.8] years, 78.7% on atypicals) met criteria for analysis. Mean 10-year CVD risk was high; 11.9±5.7% and mean CRP levels were 2.6±2.5 mg/L with 30.4% showing above-normative levels (>3 mg/L). After adjusting for age, gender, smoking and presence of neoplasm or inflammatory diseases, CRP was linearly associated with 10-year CVD risk stratified by risk (low, moderate, high/very high): respectively, 2.3 (95% CI: 2.1-2.5), 3.1 (2.6-3.5) and 3.7 (3.2-4.1) mg/L; F=13.5, P<0.001. Patients with known CVD also showed higher CRP levels: 3.7 (2.9-4.5) vs. 2.5 (2.4-2.7) mg/L, P=0.008; and higher probability of above-normal values; odds ratio=4.71 (2.01-11.04), P<0.001.
High CRP levels above normative were associated with both known CVD and high/very high 10-year risk of a CVD event in patients with schizophrenia, suggesting CRP could be a marker of CVD in this psychiatric disorder.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
39Nord J Psychiatry 2013 Oct 67: 320-5
PMID23228159
TitleAssociation between C-reactive protein and homocysteine with the subcomponents of metabolic syndrome in stable patients with bipolar disorder and schizophrenia.
AbstractPrevious studies revealed high prevalence of metabolic syndrome (MetS) in patients with bipolar disorder and schizophrenia. C-Reactive protein (CRP) and homocysteine have also both emerged as independent risk factors for the development of cardiovascular disease (CVD) but are less investigated in psychiatric disorders.
The aim of this study was to ascertain which specific subcomponents of MetS are associated with levels of CRP and homocysteine in patients with bipolar disorder and schizophrenia.
Our sample consisted of patient group (n = 122) (60 bipolar and 62 schizophrenic patients) treated with second-generation antipsychotics (SGA) and healthy controls (n = 59). MetS was defined according to NCEP ATP-III criteria; the cut-off point for elevated CRP was set up at 5 mg/l and for hyperhomocysteinemia at 15 ?mol/l.
In the patient group, homocysteine was correlated with waist circumference, systolic and diastolic blood pressure, triglycerides and blood glucose, while CRP was correlated with waist circumference and diastolic blood pressure. Patients with hyperhomocysteinemia had an 8.442 times higher chance to have met the criteria for MetS while elevated CRP was not a significant predictor of MetS.
There is a complex association between CRP and homocysteine with specific subcomponents of MetS in patients with bipolar disorder and schizophrenia. Given the high risk of cardiovascular disorders in psychiatric patients, these relationships deserve further investigation. Clinically, it could be useful to include the measurement of homocysteine and CRP levels in routine psychiatric diagnostic procedures.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
40Prog. Neuropsychopharmacol. Biol. Psychiatry 2014 Jan 48: 287-94
PMID23085507
TitleImmune system and glucose metabolism interaction in schizophrenia: a chicken-egg dilemma.
AbstractImpaired glucose metabolism and the development of metabolic syndrome contribute to a reduction in the average life expectancy of individuals with schizophrenia. It is unclear whether this association simply reflects an unhealthy lifestyle or whether weight gain and impaired glucose tolerance in patients with schizophrenia are directly attributable to the side effects of atypical antipsychotic medications or disease-inherent derangements. In addition, numerous previous studies have highlighted alterations in the immune system of patients with schizophrenia. Increased concentrations of interleukin (IL)-1, IL-6, and transforming growth factor-beta (TGF-?) appear to be state markers, whereas IL-12, interferon-gamma (IFN-?), tumor necrosis factor-alpha (TNF-?), and soluble IL-2 receptor (sIL-2R) appear to be trait markers of schizophrenia. Moreover, the mononuclear phagocyte system (MPS) and microglial activation are involved in the early course of the disease. This review illustrates a "chicken-egg dilemma", as it is currently unclear whether impaired cerebral glucose utilization leads to secondary disturbances in peripheral glucose metabolism, an increased risk of cardiovascular complications, and accompanying pro-inflammatory changes in patients with schizophrenia or whether immune mechanisms may be involved in the initial pathogenesis of schizophrenia, which leads to disturbances in glucose metabolism such as metabolic syndrome. Alternatively, shared underlying factors may be responsible for the co-occurrence of immune system and glucose metabolism disturbances in schizophrenia.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
41Prog. Neuropsychopharmacol. Biol. Psychiatry 2014 Jan 48: 295-303
PMID23313563
TitleIs there an association between peripheral immune markers and structural/functional neuroimaging findings?
AbstractThere is mounting evidence that inflammatory processes play a key role in emotional as well as cognitive dysfunctions. In this context, research employing magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MR spectroscopy) suggests a possible link between structural/functional anomalies in the brain and an increase of circulating inflammation markers. The present paper reviews this research, with particular focus on major depressive disorder (MDD), cognitive impairment in older adults, Alzheimer's disease (AD) and schizophrenia.
In MDD, cognitive impairment and AD, inflammatory processes have been found to be associated with both structural and functional anomalies, perhaps under the influence of environmental stress. Not enough research can suggest similar considerations in schizophrenia, although studies in mice and non-human primates support the belief that inflammatory responses generated during pregnancy can affect brain development and contribute to the etiology of schizophrenia.
The present review suggests a link between inflammatory processes and MRI detected anomalies in the brain of individuals with MDD, older adults with cognitive impairment as well as of individuals with AD and schizophrenia.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
42Psychiatry Res 2014 May 216: 277-85
PMID24565000
TitleRole of C-reactive protein in schizophrenia: an overview.
AbstractOver the years, schizophrenia is speculated to be associated with immune or inflammatory reactions mediated by cytokines. It is proposed that chronic inflammation might damage the micro-vascular system of brain and hamper cerebral blood flow. Scientific evidence suggests that an increase of stress hormone like norepinephrine may activate the inflammatory arm of the immune system and trigger the expression of genes that cause chronic, low-grade inflammation. Thus, studies were conducted to decipher the potentiality of CRP as a marker for inflammation in schizophrenia. This article reviews the findings of CRP in schizophrenia, and the limitations of the previous studies have been discussed. The importance of simultaneous study of CRP modulating cytokines and CRP gene polymorphism in the study of serum or plasma level of CRP has been emphasized.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
43Clin Schizophr Relat Psychoses 2014 Jan 7: 223-30
PMID23428789
TitleC-reactive protein levels in schizophrenia: a review and meta-analysis.
AbstractThere is an impression in the literature that schizophrenia is associated with increased inflammation, including abnormal blood levels of the acute phase reactant C-reactive protein (CRP). We performed a meta-analysis of blood CRP levels to estimate the overall effect size, as well as a pooled analysis of the prevalence of an elevated CRP level in patients with schizophrenia and related disorders. We identified articles by searching PubMed, PsycInfo, and ISI, and the reference lists of identified studies. Eight studies met the inclusion criteria for the meta-analysis, and five studies were included in the pooled analysis. CRP levels were significantly increased in patients compared to controls (effect size=0.45, 95% confidence interval 0.34-0.55, p<0.001). There was a 28% prevalence of an elevated CRP level in patients with schizophrenia and related disorders. Our results support a growing body of literature that schizophrenia is associated with increased inflammation, although many studies did not control for potential confounding factors such as BMI and smoking. Given the high prevalence of elevated CRP, metabolic syndrome, and premature cardiovascular mortality, our findings also suggest that measurement of blood CRP levels may be germane to the clinical care of patients with schizophrenia and related disorders.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
44Schizophr. Res. 2014 Nov 159: 395-403
PMID25261882
TitleA randomized placebo-controlled pilot study of pravastatin as an adjunctive therapy in schizophrenia patients: effect on inflammation, psychopathology, cognition and lipid metabolism.
AbstractThe aim of this study was to investigate the role of pravastatin, as an adjunctive therapy, on inflammatory markers, lipid and glucose metabolism, psychopathology, and cognition in subjects with schizophrenia and schizoaffective disorder.
schizophrenia or schizoaffective subjects (N=60) were randomized to receive either a 12-week supply of pravastatin 40 mg/day or placebo treatment. Anthropometric measures, lipids and glucose metabolism, inflammatory markers, psychopathology and cognitive performance were assessed at baseline, 6 weeks and 12 weeks.
Pravastatin use was associated with a significant decrease in total cholesterol, low density lipoprotein (LDL) cholesterol and LDL particle number levels, but was not associated with any significant changes in cognition or psychopathology in the participants, except a significant decrease in the Positive and Negative Syndrome Scale (PANSS) positive symptom score from baseline to week 6. However, this decrease failed to remain significant at 12 weeks. Interestingly, triglycerides, LDL-cholesterol, total cholesterol, LDL particle number, small LDL particle number, large very low density lipoprotein (VLDL) particle number and C-reactive protein (CRP) followed a similar pattern at 6 and 12 weeks as psychopathology.
These results suggest that a randomized trial with a larger sample size and a higher dosage of pravastatin would be helpful in further evaluating the anti-inflammatory properties of pravastatin, its association with improvements in cognitive symptoms, and its potential to reduce positive and negative symptoms associated with schizophrenia or schizoaffective disorders.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
45JAMA Psychiatry 2014 Oct 71: 1121-8
PMID25133871
TitleAssociation of serum interleukin 6 and C-reactive protein in childhood with depression and psychosis in young adult life: a population-based longitudinal study.
AbstractLongitudinal studies have linked the systemic inflammatory markers interleukin 6 (IL-6) and C-reactive protein (CRP) with the risk of developing heart disease and diabetes mellitus, which are common comorbidities for depression and psychosis. Recent meta-analyses of cross-sectional studies have reported increased serum levels of these inflammatory markers in depression, first-episode psychosis, and acute psychotic relapse; however, the direction of the association has been unclear.
To test the hypothesis that higher serum levels of IL-6 and CRP in childhood would increase future risks for depression and psychosis.
The Avon Longitudinal Study of Parents and Children (ALSPAC)is a prospective general population birth cohort study based in Avon County, England. We have studied a subsample of approximately 4500 individuals from the cohort with data on childhood IL-6 and CRP levels and later psychiatric assessments.
Levels of IL-6 and CRP were measured in nonfasting blood samples obtained in participants at age 9 years.
Participants were assessed at age 18 years. Depression was measured using the Clinical Interview Schedule-Revised (CIS-R) and Mood and Feelings Questionnaire (MFQ), thus allowing internal replication; psychotic experiences (PEs) and psychotic disorder were measured by a semistructured interview.
After adjusting for sex, age, body mass index, ethnicity, social class, past psychological and behavioral problems, and maternal postpartum depression, participants in the top third of IL-6 values compared with the bottom third at age 9 years were more likely to be depressed (CIS-R) at age 18 years (adjusted odds ratio [OR], 1.55; 95% CI, 1.13-2.14). Results using the MFQ were similar. Risks of PEs and of psychotic disorder at age 18 years were also increased with higher IL-6 levels at baseline (adjusted OR, 1.81; 95% CI, 1.01-3.28; and adjusted OR, 2.40; 95% CI, 0.88-6.22, respectively). Higher IL-6 levels in childhood were associated with subsequent risks of depression and PEs in a dose-dependent manner.
Higher levels of the systemic inflammatory marker IL-6 in childhood are associated with an increased risk of developing depression and psychosis in young adulthood. Inflammatory pathways may provide important new intervention and prevention targets for these disorders. Inflammation might explain the high comorbidity between heart disease, diabetes mellitus, depression, and schizophrenia.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
46Ther Adv Psychopharmacol 2014 Jun 4: 110-6
PMID25057343
TitleAdd-on clinical effects of simvastatin and ondansetron in patients with schizophrenia stabilized on antipsychotic treatment: pilot study.
AbstractThere is some evidence that anti-inflammatory treatment may have beneficial effects in schizophrenia and major depression. Statins are cholesterol-lowering agents but have been found to be anti-inflammatory and also decrease C-reactive protein (CRP). Ondansetron is a serotonin (5-HT3) receptor antagonist widely used to prevent nausea and vomiting in patients receiving chemotherapy for cancer. Small studies have suggested that adjunctive ondansetron is efficacious against schizophrenia symptoms. We carried out a feasibility study in schizophrenia patients (within 5 years of first diagnosis) to explore the adjunctive use of simvastatin and ondansetron on positive, negative and general psychopathology.
This was a 12-week rater-blind placebo-controlled study. A total of 36 patients with DSM-IV diagnosis of schizophrenia were recruited, 12 in each arm. Patients were assessed at baseline and at 12 weeks using Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression (CGI) scale, Global Assessment of Functioning (GAF) and Abnormal Involuntary Movement Scale (AIMS).
Both simvastatin and ondansetron provide some evidence of a reduction in symptoms compared with treatment as usual (TAU) on PANSS total score, although this was not statistically significant. In the secondary analyses, no significant differences were seen on CGI, GAF and AIMS.
Anti-inflammatory treatments have been shown to have some beneficial effects in schizophrenia. Both simvastatin and ondansetron provide some evidence of a reduction in symptoms compared with TAU. This study has led to a larger Stanley Medical Research Institute (SMRI)-funded, double-blind, randomized control trial.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
47Psychiatry Res 2014 Aug 218: 277-83
PMID24837425
TitleCytokine and adipokine alterations in patients with schizophrenia treated with clozapine.
AbstractMetabolic syndrome is associated with both schizophrenia and antipsychotic medication, especially clozapine, with alterations in inflammatory cytokines and adipokines. However, the data in this field is heterogeneous and the sample sizes of the patients are limited. In this study we assessed the serum levels of cytokines/adipokines IL-6, IL-1Ra, hs-CRP and adiponectin, and components of metabolic syndrome in 190 patients with treatment resistant schizophrenia treated with clozapine. Substantial metabolic comorbidity was found in this patient group; overweight/obesity, smoking, hypertriglyceridemia, low HDL-cholesterol, high HOMA-IR, low adiponectin levels, elevated hs-CRP levels and elevated IL-1Ra levels. Elevated IL-1Ra levels are associated with insulin resistance, obesity and hypertriglyceridemia. Low adiponectin levels were associated with hypertriglyceridemia, low HDL cholesterol and high glucose, and in male patients also with obesity and high IL-1Ra levels. After controlling for confounding factors age and smoking, levels of IL-1Ra and hs-CRP associated with obesity, and the levels of IL-6 associated with obesity in female patients. We conclude that there are partly gender dependent cytokine and adipokine alterations in patients with schizophrenia on clozapine treatment associated with metabolic comorbidity. The genetic background of these cytokine alterations needs to be further investigated.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
48Psychoneuroendocrinology 2014 Mar 41: 23-32
PMID24495605
TitleIncreased serum interleukin-6 levels in early stages of psychosis: associations with at-risk mental states and the severity of psychotic symptoms.
Abstractschizophrenia patients experience activated inflammatory responses, but little is known about the presence of such inflammatory processes at or prior to disease onset. We measured interleukin-6 (IL-6) and C-reactive protein (CRP) serum levels and plasma fibrinogen in 17 at-risk mental state (ARMS) subjects, 77 patients with psychotic disorder (PD) and 25 healthy control subjects (HC). ARMS subjects were followed-up, and transition to psychosis was registered. IL6 rs1800795 SNP was genotyped, as IL-6 levels may be influenced by this genetic variant. We did not observe significant differences in the IL6 rs1800795 SNP genotype frequencies between the groups. ARMS subjects exhibited significantly higher IL-6 levels than did controls (p=0.019). In subjects not taking cannabis, we found that patients diagnosed with ARMS or PD exhibited increased IL-6 levels when compared with HC (p=0.004). In both ARMS and PD subjects, IL-6 levels were positively associated with negative symptoms. However, with respect to positive psychotic symptoms, a different relationship was observed in the ARMS and PD groups (positive relationship in ARMS; negative relationship in PD). These findings could not be attributed to confounding variables, including gender, body mass index (BMI), tobacco consumption or the rs1800795 genotype. Six of 17 ARMS subjects (35%) exhibited a transition to psychosis during the follow-up period of 26 months. ARMS subjects who developed psychosis exhibited increased median IL-6 levels compared with those who did not transition (0.61 vs. 0.35pg/mL). However, this difference was not statistically significant, which could be explained by a lack of statistical power due to the small sample size. Our results suggest that IL-6 may be a biomarker for early psychotic symptoms; however, further studies in larger samples are needed to confirm this result.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
49Schizophr. Res. 2014 Jan 152: 139-45
PMID24268471
TitleA population-based study of atopic disorders and inflammatory markers in childhood before psychotic experiences in adolescence.
Abstractschizophrenia is associated with atopy and increased inflammatory markers. We report a population-based longitudinal study of the associations between childhood atopic disorders, subsequent serum inflammatory markers, interleukin 6 (IL-6) and C-reactive protein (CRP), and the risk of psychotic experiences (PEs).
PEs were assessed at age 13 years (n=6785). Presence of clinician-diagnosed atopic disorders (asthma and eczema) was determined from parent-completed questionnaires at age 10 years (n=7814). Serum IL-6 and CRP were measured at age 9 years (n=5076). Logistic regression examined the association between (1) atopy and PEs, (2) inflammatory markers and PEs, and (3) mediating effects of inflammatory markers on the atopy-PEs association. Linear regression examined the association between atopy and inflammatory markers. Age, gender, social class, ethnicity and body mass index were included as potential confounders.
At age 10 years, about 14% of the sample was reported to have asthma, 12% eczema, and 7% both asthma and eczema. Compared with children with no atopy, risk of PEs at age 13 years was increased for all of these groups; adjusted odds ratios (95% CI) were, respectively, 1.39 (1.10-1.77), 1.33 (1.04-1.69), and 1.44 (1.06-1.94). Atopy was associated with increased serum IL-6 and CRP; however, this did not mediate association between atopy and PEs. Inflammatory markers were not associated with later PEs.
Childhood atopic disorders increase the risk of psychotic experiences in adolescence. Follow-up of these individuals will be useful to determine the effect of atopy and inflammation on different trajectories of early-life PEs.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
50Schizophr Bull 2014 Sep 40: 1117-27
PMID23996346
TitleElevated C-reactive protein associated with late- and very-late-onset schizophrenia in the general population: a prospective study.
AbstractIndividuals with autoimmune diseases and severe infections have persistent or acutely elevated inflammatory biomarkers and increased risk of schizophrenia. We tested the hypothesis that baseline elevated plasma levels of the inflammatory biomarker, C-reactive protein (CRP), associate with increased risk of late- and very-late-onset schizophrenia in the general population, and if such an association possibly is causal.
We analyzed data from 78 810 men and women, aged 20-100 years, from 2 large population studies. Endpoints were hospitalization with schizophrenia and schizophrenia and schizophrenia-like psychosis combined. We performed prospective and cross-sectional analyses adjusted for potential confounders with up to 20 years of follow-up. Furthermore, we used genetic variants influencing plasma CRP levels to perform a Mendelian randomization study.
Age- and gender-adjusted hazard ratios vs individuals in the first quartile of CRP were 1.7 (95% CI: 0.3-8.9) for second quartile, 2.1 (0.4-10) for third quartile, and 11 (2.8-40) for fourth quartile individuals. The corresponding hazard ratio for fourth quartile individuals after multifactorial adjustment was 5.9 (1.4-24). Furthermore, individuals with vs without schizophrenia had 63% increased plasma levels of CRP (P = 1 × 10(-4)). Finally, when CRP was on a continuous scale, a doubling in CRP yielded an age- and gender-adjusted observational OR of 1.5 (1.3-1.8) and a corresponding causal OR of 1.4 (0.5-4.3) (observed vs causal: P = .89).
Baseline elevated plasma CRP is associated with a 6- to 11-fold increased risk of late- and very-late-onset schizophrenia in the general population. We cannot exclude that this is a causal association. These are novel findings.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
51Prog. Neuropsychopharmacol. Biol. Psychiatry 2014 Jan 48: 277-86
PMID23123365
TitleThe role of pro-inflammatory cytokines in the neuroinflammation and neurogenesis of schizophrenia.
Abstractschizophrenia is a serious mental illness with chronic symptoms and significant impairment in psychosocial functioning. Although novel antipsychotics have been developed, the negative and cognitive symptoms of schizophrenia are still unresponsive to pharmacotherapy. The high level of social impairment and a chronic deteriorating course suggest that schizophrenia likely has neurodegenerative characteristics. Inflammatory markers such as pro-inflammatory cytokines are well-known etiological factors for psychiatric disorders, including schizophrenia. Inflammation in the central nervous system is closely related to neurodegeneration. In addition to pro-inflammatory cytokines, microglia also play an important role in the inflammatory process in the CNS. Uncontrolled activity of pro-inflammatory cytokines and microglia can induce schizophrenia in tandem with genetic vulnerability and glutamatergic neurotransmitters. Several studies have investigated the possible effects of antipsychotics on inflammation and neurogenesis. Additionally, anti-inflammatory adjuvant therapy has been under investigation as a treatment option for schizophrenia. Further studies should consider the confounding effects of systemic factors such as metabolic syndrome and smoking. In addition, the unique mechanisms by which pro-inflammatory cytokines are involved in the etiopathology of schizophrenia should be investigated. In this article, we aimed to review (1) major findings regarding neuroinflammation and pro-inflammatory cytokine alterations in schizophrenia, (2) interactions between neuroinflammation and neurogenesis as possible neural substrates for schizophrenia, and (3) novel pharmacological approaches.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
52Psychiatry Res 2015 Feb 225: 501-8
PMID25529262
TitleEffect of Ramadan fasting on anthropometric, metabolic, inflammatory and psychopathology status of Egyptian male patients with schizophrenia.
AbstractRamadan fasting is believed to be beneficial. We assessed a random sample of 100 Egyptian male schizophrenia outpatients using the Positive and Negative Syndrome Scale (PANSS) and dietary, anthropometric, clinical, and laboratory measures at baseline (T1) before Ramadan of 2014 and during the fourth week of Ramadan (T2). The metabolic syndrome was identified in 31 patients and these showed a reduction of high-density lipoprotein cholesterol (HDLc) and brain-derived neurotrophic factor (BDNF) concentrations and increase in the levels of dietary intakes, body mass index (BMI), waste circumference, systolic and diastolic blood pressure, all PANSS subscales, glucose, insulin, HOMA-IR, total cholesterol, triglycerides, low-density lipoprotein-cholesterol (LDL-c), white blood cells, granulocytes, lymphocytes, monocytes, fibrinogen and high-sensitivity C-reactive protein (hs-CRP). In a multiple regression analysis, total energy intake and body mass index (BMI) emerged as the main independent predictors of deterioration in most inflammatory and psychopathology parameters. These findings did not support our hypothesis but suggested that Ramadan fasting has a negative impact on schizophrenia patients, especially those with metabolic syndrome. This could draw attention to the need in the psycho-education management of such patients to focus more on nutrition education for safe fasting.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
53Schizophr. Res. 2015 Oct 168: 461-4
PMID26189077
TitleSedentary behaviour is associated with elevated C-reactive protein levels in people with psychosis.
AbstractPsychosis is associated with elevated inflammatory markers including C-reactive protein (CRP), a marker of cardiovascular disease (CVD) risk. Using a cross sectional design, 250 participants with established psychosis (48.2years (SD 10.2), 39.2% female) were classified as having normal (<5.0mg/?l, N=159) or high CRP levels (>5.0mg/?l, N=91). Regression analysis demonstrated that higher sedentary behaviour was associated with elevated CRP levels (?=.155, p=.01) after adjustment for confounding variables. Female gender (?=.229, p=.001), waist circumference (?=.205, p=.003) and non-white ethnicity (?=.181, p=.005) were also associated with elevated CRP. Sedentary behaviour is modifiable and increasing physical activity may reduce CRP levels.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
54Psychiatry Res 2015 Aug 228: 565-70
PMID26106052
TitleHigh levels of vitamin D in relation to reduced risk of schizophrenia with elevated C-reactive protein.
AbstractThere is growing evidence on the novel role of vitamin D in reducing inflammation. This study aimed to examine the hypothesis that vitamin D is inversely associated with C-reactive protein (CRP) in patients with schizophrenia, and high levels of vitamin D may be linked to reduced risk of schizophrenia with elevated CRP. Ninety-three patients with schizophrenia and 93 family-matched controls were recruited in this cross-sectional study. Plasma concentrations of CRP and 25-hydroxyvitamin D [25(OH)D] were measured using commercial kits. Information about demographic characteristics and clinic data were obtained by interviews or medical records. Mean levels of CRP and 25(OH)D were 43.3% higher and 26.7% lower for patients compared to controls, respectively. 25(OH)D were inversely associated with CRP in the patients, but not in the controls. The proportions of patients significantly increased with increasing quartiles of CRP, while significantly decreased with increasing quartiles of 25(OH)D. Among individuals with high CRP, participants with high 25(OH)D have significantly lower proportion (adjusted OR =0.217, 95% CI 0.063, 0.751) of schizophrenia compared to those with low 25(OH)D. The evidence suggested that high levels of vitamin D may be linked to reduced risk of schizophrenia with elevated CRP.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
55Sci Rep 2015 -1 5: 10793
PMID26041435
TitleQuality of life is associated with chronic inflammation in schizophrenia: a cross-sectional study.
AbstractInflammation may play a crucial role in the pathogenesis of schizophrenia. However, the association between chronic inflammation and health outcomes in schizophrenia remains unclear, particularly for patient-reported outcomes. The aim of this study was to investigate the relationship between quality of life (QoL) and chronic inflammation assessed using C -Reactive Protein (CRP) in patients with schizophrenia. Two hundred and fifty six patients with schizophrenia were enrolled in this study. After adjusting for key socio-demographic and clinical confounding factors, patients with high levels of CRP (>3.0 mg/l) had a lower QoL than patients with normal CRP levels (OR = 0.97, 95% CI = 0.94-0.99). An investigation of the dimensions of QoL revealed that psychological well-being, physical well-being and sentimental life were the most salient features of QoL associated with CRP. Significant associations were found between lower educational level (OR = 4.15, 95% CI = 1.55-11.07), higher body mass index (OR = 1.16, 95% CI = 1.06-1.28), higher Fagerström score (OR = 1.22, 95% CI = 1.01-1.47) and high levels of CRP. After replications with longitudinal approaches, the association between QoL and chronic inflammation may offer interesting interventional prospects to act both on inflammation and QoL in patients with schizophrenia.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
56Schizophr. Res. 2015 Jun 165: 94-6
PMID25864954
TitleElevated C-reactive protein is associated with sensory gating deficit in schizophrenia.
AbstractSensory and cognitive impairments and inflammatory processes are contributing factors to the pathogenesis of schizophrenia. A previous study found that an elevated CRP level (?5mg/L) was associated with higher cognitive impairments in schizophrenia. We aimed to investigate the association between an elevated CRP level and sensory impairments defined by a sensory gating deficit (abnormal P50 suppression) in 55 outpatients. Fifteen patients (27.3%) had an elevated CRP level that was associated with higher rate of sensory gating deficit (60% vs. 12.5%, p<0.001). This is the first study suggesting a relationship between sensory gating deficit and inflammatory processes in schizophrenia.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
57Pharmacol Rep 2015 Apr 67: 353-9
PMID25712663
TitleTherapeutic effect of aripiprazole in chronic schizophrenia is accompanied by anti-inflammatory activity.
AbstractWeight gain and metabolic abnormalities occur in chronic schizophrenia patients treated with atypical antipsychotics. The purpose of the study was to evaluate changes in serum levels of C-reactive protein (CRP), insulin and cytokines (IL-6, TNF-?, IL-1?, IFN-?, sTNF-R1, IL-12, IL-23, IL-1Ra, TGF-?1, IL-4, and IL-10) after switching to aripiprazole.
Cytokine, hsCRP and insulin measurements were performed in patients (n=17) on day 0 and day 28 of the study using standard ELISA assays. The psychopathological status was assessed using PANSS. WC and BMI were measured and calculated, respectively.
We observed high clinical efficacy in aripiprazole linked to a 2.7% weight loss. There were statistically significant reductions in PANSS scores and body parameters (p<0.001). After 28 days we detected a significant reduction in hsCRP (p<0.001), insulin (p<0.001), IL-1?, IL-6, TNF-?, sTNF-R1, IL-12, IL-23, IL-1Ra, TGF-?1, IL-4 (p<0.001), IFN-? (p<0.05) and a significant elevation of IL-10 (p<0.001). There was a significant negative correlation between IL-10 levels and PANSS positive, negative and total scores after the study (p=0.022, p=0.003, p=0.008, respectively).
Aripiprazole limits inflammatory processes by enhancing anti-inflammatory signaling. Aripiprazole also reduces the risk of metabolic abnormalities.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
58Vojnosanit Pregl 2015 Dec 72: 1085-92
PMID26898032
TitleThe effect of antipsychotic drugs on nonspecific inflammation markers in the first episode of schizophrenia.
AbstractImmune system disorder, including inflammation, takes a significant place when considering still unclear etiology of schizophrenia. The aim of this study was to determine the blood levels of nonspecific inflammation markers in the first episode of schizophrenia and their relation to the therapy response.
In this study we determined the blood levels of nonspecific inflammation markers: white blood cells count (WBC), C-reactive protein (CRP), erythrocytes sedimentation rate (ESR) and the elements of differential white blood cell counts (or the leukocyte formula): granulocytes (Gra), lymphocytes (Lym) and monocytes (Mon), in the first episode of schizofrenia, in 78 patients hospitalized at the Clinic for Psychiatric Disorders "Dr Laza Lazarevi?" in Belgrade. The levels were measured at admission to the clinic, as well as after 4 weeks of antipsychotic treatment. The Positive and negative syndrome scale for schizophrenia (PANSS) was applied to measure the severity of psychopathology and response to the treatment.
During the first episode of schizophrenia, before initiation of antipsychotic treatment, the frequency of abnormal values was high (? 25% of the patients) for the following non-specific inflammation markers: WBC, CRP, ESR and Gra, in the leukocyte formula, but dropped after 4 weeks of antipsychotic treatment at the level of high statistical significance for WBC and Gra (p < 0.001). The ESR remained unchanged in as many as 50% of the patients even after 4-week antipsychotic treatment, at the level of statistical significance in the non-responders compared to the responders (p = 0.045).
The obtained results indicate that in the first episode of schizophrenia the blood levels of non-specific inflammation markers (WBS, CRP, ESR and Gra from the leukocyte formula) were high in the subpopulation of patients with the tendency towards normalization of inflammation parameters after a 4-week antipsychotic treatment.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
59Schizophr. Res. 2015 Dec 169: 30-5
PMID26475215
TitleTotal and differential white blood cell counts, inflammatory markers, adipokines, and the metabolic syndrome in phase 1 of the clinical antipsychotic trials of intervention effectiveness study.
AbstractThe metabolic syndrome is highly prevalent in patients with schizophrenia, and is associated with a state of chronic, low-grade inflammation. We investigated relationships between total and differential white blood cell (WBC) counts, inflammatory markers, adipokines and the metabolic syndrome in patients with schizophrenia.
For subjects with available data from the baseline/screening visit of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia trial, WBC counts, inflammatory markers, and adipokines were investigated as predictors of the metabolic syndrome (and its components), using linear and binary logistic regression models, controlling for potential confounding effects of age, sex, race, smoking, fasting status, alcohol, and illicit drug use.
After controlling for potential confounders, blood CRP, interleukin-6, and leptin were significant predictors of all five individual components of the metabolic syndrome (as both continuous and categorical outcome measures). Furthermore, total WBC (OR=2.31, 95% CI 1.58-3.41, p<0.01) and lymphocyte (OR=2.51, 95% CI 1.75-3.60, p<0.01) counts were the strongest predictors of current metabolic syndrome.
Our findings provide the strongest evidence to date that measurement of total and differential WBC counts are germane to the clinical care of patients with schizophrenia, and that inflammation and adipokines are associated with metabolic disturbance in these patients.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
60Schizophr. Res. 2015 Oct 168: 456-60
PMID26341579
TitleAssociations of high sensitivity C-reactive protein levels in schizophrenia and comparison groups.
Abstractschizophrenia is characterized by physical (mainly metabolic and cardiovascular) comorbidity and shortened lifespan. High sensitivity C-reactive protein (hs-CRP), an inflammatory marker of hepatic origin linked to metabolic and cardiovascular diseases and mortality in the general population, has been reported to be elevated in people with schizophrenia. However, the relationship of hs-CRP to psychiatric and medical risk factors, after controlling for potentially confounding variables such as smoking, is not well established in schizophrenia. We assessed hs-CRP levels along with various demographic, psychiatric, and metabolic measures in 88 clinically stable outpatients with schizophrenia or schizoaffective disorder and 71 age epoch-matched comparison subjects with no history of a major psychiatric illness. hs-CRP levels were significantly higher in individuals with schizophrenia than in comparison subjects. Higher hs-CRP levels in the schizophrenia group were associated with female gender, more severe negative symptoms, greater medical comorbidity, and worse metabolic risk factors including BMI, fasting glucose, and hemoglobin A1c levels. hs-CRP was not related to age, race, education, smoking status, antipsychotic dosage, or cognitive impairment. Longitudinal studies are needed to investigate the relationship between hs-CRP and long-term health outcomes including metabolic syndrome, cardiovascular disease, and mortality in schizophrenia.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
61J Affect Disord 2015 Aug 182: 106-14
PMID25985379
TitleIL-6, IL-18, sIL-2R, and TNF? proinflammatory markers in depression and schizophrenia patients who are free of overt inflammation.
AbstractMajor depressive disorder (MDD) and schizophrenia are associated with inflammatory processes. Studies have shown that these disorders exhibit increase in the level of one or more proinflammatory markers. However, these studies did not exclude patients with obvious inflammation (i.e., CRP>6mg/L). Therefore, a comprehensive study should include those inflammatory disorders. In the present study, the inflammatory natures of MDD and schizophrenia were investigated. To achieve this goal, serum levels of interleukin-6 (IL-6), interleukin-18 (IL-18), tumor necrosis factor alpha (TNF?), and soluble interleukin 2 receptor (sIL-2R) in depressed and schizophrenic patients were obtained and compared with those of the control group. Results showed a significant increase (p<0.05) in serum levels of IL-6, IL-18, TNF?, and sIL-2R in MDD and schizophrenic patients compared with the control group. Also patients with schizophrenia group showed higher levels of the inflammatory markers than MDD and control groups. The current study concluded that the immunological response in the MDD and schizophrenic patients groups was significantly stimulated. These disorders may be considered an inflammatory disorder because of elevated levels of proinflammatory cytokines in spite of lacking an overt inflammation. Furthermore results of this study suggested the possibility of the use of anti-inflammatory drugs as adjuvant therapy in schizophrenic and depressive disorders.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
62J Affect Disord 2015 Aug 182: 106-14
PMID25985379
TitleIL-6, IL-18, sIL-2R, and TNF? proinflammatory markers in depression and schizophrenia patients who are free of overt inflammation.
AbstractMajor depressive disorder (MDD) and schizophrenia are associated with inflammatory processes. Studies have shown that these disorders exhibit increase in the level of one or more proinflammatory markers. However, these studies did not exclude patients with obvious inflammation (i.e., CRP>6mg/L). Therefore, a comprehensive study should include those inflammatory disorders. In the present study, the inflammatory natures of MDD and schizophrenia were investigated. To achieve this goal, serum levels of interleukin-6 (IL-6), interleukin-18 (IL-18), tumor necrosis factor alpha (TNF?), and soluble interleukin 2 receptor (sIL-2R) in depressed and schizophrenic patients were obtained and compared with those of the control group. Results showed a significant increase (p<0.05) in serum levels of IL-6, IL-18, TNF?, and sIL-2R in MDD and schizophrenic patients compared with the control group. Also patients with schizophrenia group showed higher levels of the inflammatory markers than MDD and control groups. The current study concluded that the immunological response in the MDD and schizophrenic patients groups was significantly stimulated. These disorders may be considered an inflammatory disorder because of elevated levels of proinflammatory cytokines in spite of lacking an overt inflammation. Furthermore results of this study suggested the possibility of the use of anti-inflammatory drugs as adjuvant therapy in schizophrenic and depressive disorders.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
63PLoS ONE 2015 -1 10: e0116696
PMID25781172
TitleInfection and inflammation in schizophrenia and bipolar disorder: a genome wide study for interactions with genetic variation.
AbstractInflammation and maternal or fetal infections have been suggested as risk factors for schizophrenia (SZ) and bipolar disorder (BP). It is likely that such environmental effects are contingent on genetic background. Here, in a genome-wide approach, we test the hypothesis that such exposures increase the risk for SZ and BP and that the increase is dependent on genetic variants. We use genome-wide genotype data, plasma IgG antibody measurements against Toxoplasma gondii, Herpes simplex virus type 1, Cytomegalovirus, Human Herpes Virus 6 and the food antigen gliadin as well as measurements of C-reactive protein (CRP), a peripheral marker of inflammation. The subjects are SZ cases, BP cases, parents of cases and screened controls. We look for higher levels of our immunity/infection variables and interactions between them and common genetic variation genome-wide. We find many of the antibody measurements higher in both disorders. While individual tests do not withstand correction for multiple comparisons, the number of nominally significant tests and the comparisons showing the expected direction are in significant excess (permutation p=0.019 and 0.004 respectively). We also find CRP levels highly elevated in SZ, BP and the mothers of BP cases, in agreement with existing literature, but possibly confounded by our inability to correct for smoking or body mass index. In our genome-wide interaction analysis no signal reached genome-wide significance, yet many plausible candidate genes emerged. In a hypothesis driven test, we found multiple interactions among SZ-associated SNPs in the HLA region on chromosome 6 and replicated an interaction between CMV infection and genotypes near the CTNNA3 gene reported by a recent GWAS. Our results support that inflammatory processes and infection may modify the risk for psychosis and suggest that the genotype at SZ-associated HLA loci modifies the effect of these variables on the risk to develop SZ.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
64Nord J Psychiatry 2015 Jul 69: 346-53
PMID25495587
TitleLevels of C-reactive protein (CRP) in patients with schizophrenia, unipolar depression and bipolar disorder.
AbstractC-reactive protein (CRP) is the major acute-phase plasma protein. Studies show that patients with various mental disorders have elevated levels of CRP. The aim of the study was to determine differences in CRP serum level in patients with acute schizophrenia, unipolar depression, bipolar depression and bipolar mania.
Serum level of CRP was measured in 950 Caucasian inpatients (589 women, 62.0%; mean age 50.3 years).
Mean concentration of CRP in study groups was: schizophrenia (n = 485) 5.30 mg/l, unipolar depression (n = 319) 5.61 mg/l, bipolar disorder (n = 146) 4.65 mg/l, bipolar depression (n = 114) 3.82 mg/l and bipolar mania (n = 32) 7.36 mg/l. There was no difference for CRP levels between patients with schizophrenia, unipolar depression, bipolar depression and bipolar mania (P = 0.58). The overall rate of being above the high level of CRP (set at 3.0 mg/l) was 35.7% for schizophrenia, 38.6% for unipolar depression, 40.4% for bipolar disorder, 40.4% for bipolar depression and 40.6% for bipolar mania. There were no significant differences in the risk of having high level of CRP between the clinical groups. The rate of patients being above high level was higher in women. We also found that in whole study group CRP level was positively correlated with age (P = 0.002).
Although there is no statistically significant difference in CRP serum level between patients with schizophrenia, unipolar depression, bipolar depression and bipolar mania, our results show that more than one-third (37.4%) of all subjects had CRP level > 3 mg/l, which is the cut-off point for high cardiovascular risk.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
65Schizophr. Res. 2015 Jan 161: 119-25
PMID25449712
TitleDifferential susceptibility of white matter tracts to inflammatory mediators in schizophrenia: an integrated DTI study.
AbstractThe pathophysiological underpinnings of impaired anatomical and functional connectivity are not precisely known. Emerging data suggest that immune mediators may underlie such dysconnectivity. We examined anatomical brain connections using diffusion tensor imaging (DTI) data in relation to interleukin-6 (IL-6) and C-reactive protein (CRP) levels among early-course clinically stable schizophrenia subjects compared to healthy controls (HC).
DTI data were acquired in 30 directions with 2 averages. Fractional anisotropy (FA) and radial diffusivity (RD) maps were separately processed using FSL4.1.9 and Tract-Based Spatial Statistics (TBSS). Threshold free cluster enhancements (TFCE) were examined employing familywise error (FWE) corrections for multiple testing within linear regression models including age, sex and socioeconomic status as covariates. IL-6 and CRP were assayed using highly sensitive and specific sandwich immunosorbent assays.
The groups did not differ in age and sex as well as in the IL-6 and CRP levels. IL-6 levels were negatively correlated with the FA and positively correlated with RD among schizophrenia subjects but not HC. The voxel clusters that showed significant correlations were localized to the forceps major, the inferior longitudinal fasciculus and the inferior fronto-occipital fasciculus. CRP levels showed similar pattern except for lack of correlation with RD on any cluster that corresponded to the forceps major.
Our results suggest that the IL-6 and CRP contribute to impaired anisotropy of water diffusion in selected pathways that have been previously associated with schizophrenia suggesting differential susceptibility of selected neural pathways to immune mediators.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
66Eur. Psychiatry 2015 Feb 30: 296-302
PMID25284335
TitleAssociation study of the HTR2C, leptin and adiponectin genes and serum marker analyses in clozapine treated long-term patients with schizophrenia.
AbstractClozapine treatment is associated with weight gain and cardio-metabolic consequences among patients with schizophrenia. Polymorphisms of leptin, serotonin receptor HTR2C and adiponectin genes have been associated with antipsychotic-induced weight gain and metabolic comorbidity. However, the results of the studies so far are inconclusive. The aim of the present study was first to test for a possible role of serum leptin and adiponectin levels as a marker of weight gain in association with inflammatory cytokines/adipokines (IL-6, IL-1Ra, hs-CRP and adipsin), and second to study associations between SNPs LEP rs7799039 (-2548 A/G), ADIPOQ rs1501299 and HTR2C rs1414334 and weight gain and levels of leptin and adiponectin, in 190 patients with schizophrenia on clozapine treatment, with retrospectively assessed weight change and cross-sectionally measured cytokine levels. A strong association was found between serum levels of leptin and weight gain and cytokines/adipokines related to metabolic comorbidity, especially among female patients (in women leptin vs. weight gain, IL-6 and IL-1Ra, P<0.001; in men leptin vs. weight gain, P=0.026, leptin vs. IL-1Ra, P<0.001). In male patients low adiponectin level was a more specific marker of clozapine-induced weight gain (P=0.037). The results of the present study do not support a major role of SNPs LEP rs7799039, ADIPOQ rs1501299 and HTR2C rs1414334 in the regulation of weight gain or association of serum levels of leptin and adiponectin and corresponding studied SNPs in patients with schizophrenia on clozapine treatment.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
67Ann. Hum. Genet. 2016 Jan 80: 38-49
PMID26474449
TitlePractical Experience of the Application of a Weighted Burden Test to Whole Exome Sequence Data for Obesity and Schizophrenia.
AbstractFor biological and statistical reasons it makes sense to combine information from variants at the level of the gene. One may wish to give more weight to variants which are rare and those that are more likely to affect function. A combined weighting scheme, implemented in the SCOREASSOC program, was applied to whole exome sequence data for 1392 subjects with schizophrenia and 982 with obesity from the UK10K project. Results conformed fairly well with null hypothesis expectations and no individual gene was strongly implicated. However, a number of the higher ranked genes appear plausible candidates as being involved in one or other phenotype and may warrant further investigation. These include MC4R, NLGN2, CRP, DONSON, GTF3A, IL36B, ADCYAP1R1, ARSA, DLG1, SIK2, SLAIN1, UBE2Q2, ZNF507, CRHR1, MUSK, NSF, SNORD115, GDF3 and HIBADH. Some individual variants in these genes have different frequencies between cohorts and could be genotyped in additional subjects. For other genes, there is a general excess of variants at many different sites so attempts at replication would be more difficult. Overall, the weighted burden test provides a convenient method for using sequence data to highlight genes of interest.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
68Sci Rep 2016 -1 6: 26105
PMID27193331
TitleA significant causal association between C-reactive protein levels and schizophrenia.
AbstractMany observational studies have shown elevated blood CRP levels in schizophrenia compared with controls, and one population-based prospective study has reported that elevated plasma CRP levels were associated with late- and very-late-onset schizophrenia. Furthermore, several clinical studies have reported the efficacy of anti-inflammatory drugs on the symptoms in patients with schizophrenia. However, whether elevated CRP levels are causally related to schizophrenia is not still established because of confounding factors and reverse causality. In the present study, we demonstrated that serum CRP levels were significantly higher in patients with schizophrenia than in the controls by conducting a case-control study and a meta-analysis of case-control studies between schizophrenia and serum CRP levels. Furthermore, we provided evidence for a causal association between elevated CRP levels and increased schizophrenia risk by conducting a Mendelian randomization analysis. Our findings suggest that elevated CRP itself may be a causal risk factor for schizophrenia.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
69Schizophr. Res. 2016 May -1: -1
PMID27211515
TitleAdiposity-independent hypoadiponectinemia as a potential marker of insulin resistance and inflammation in schizophrenia patients treated with second generation antipsychotics.
AbstractThe purpose of this study was to explore body fat independent effect of second generation antipsychotics (SGAs) on measures of glucose and adipokine homeostasis, and markers of inflammation.
Eight non-diabetic men with schizophrenia (age: 55±3years, BMI: 29.7±1.2kg/m(2)) on SGAs were studied after an overnight fast. DXA and single-cut CT of abdomen were respectively used for the assessment of total body and abdominal fat. Blood samples were collected for measurements of glucose, insulin, leptin, adiponectin, C-reactive protein (CRP), and TNF-?. Data in schizophrenic subjects were compared to eight age (55±2.8years) and BMI (29.6±1.1kg/m(2)) matched healthy men.
The results were significant for markedly decreased serum adiponectin in schizophrenia patients (4.6±0.9 vs 11.1±1.5ng/mL, p=0.001). Lower levels of adiponectin in schizophrenia men were associated with significant increases in insulin resistance (4.2±0.7 vs 1.7±0.4, p=0.004), CRP (3.5±1.2 vs 1.2±0.3, p=0.037), and leptin (12±1.4 vs 8.5±1.4ng/mL, p=0.05). Various measures of adiposity, including fat mass index (FMI) and abdominal fat were not different in the two study groups.
These findings in the context of comparable age and total body/abdominal fat mass are assumed to be either disease specific, and/or treatment inflicted. The definitive invoking etiology and a presumptive role of hypoadiponectinemia in the development of insulin resistance and increased risk of inflammation warrant future investigation.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
70Schizophr. Res. 2016 May -1: -1
PMID27211515
TitleAdiposity-independent hypoadiponectinemia as a potential marker of insulin resistance and inflammation in schizophrenia patients treated with second generation antipsychotics.
AbstractThe purpose of this study was to explore body fat independent effect of second generation antipsychotics (SGAs) on measures of glucose and adipokine homeostasis, and markers of inflammation.
Eight non-diabetic men with schizophrenia (age: 55±3years, BMI: 29.7±1.2kg/m(2)) on SGAs were studied after an overnight fast. DXA and single-cut CT of abdomen were respectively used for the assessment of total body and abdominal fat. Blood samples were collected for measurements of glucose, insulin, leptin, adiponectin, C-reactive protein (CRP), and TNF-?. Data in schizophrenic subjects were compared to eight age (55±2.8years) and BMI (29.6±1.1kg/m(2)) matched healthy men.
The results were significant for markedly decreased serum adiponectin in schizophrenia patients (4.6±0.9 vs 11.1±1.5ng/mL, p=0.001). Lower levels of adiponectin in schizophrenia men were associated with significant increases in insulin resistance (4.2±0.7 vs 1.7±0.4, p=0.004), CRP (3.5±1.2 vs 1.2±0.3, p=0.037), and leptin (12±1.4 vs 8.5±1.4ng/mL, p=0.05). Various measures of adiposity, including fat mass index (FMI) and abdominal fat were not different in the two study groups.
These findings in the context of comparable age and total body/abdominal fat mass are assumed to be either disease specific, and/or treatment inflicted. The definitive invoking etiology and a presumptive role of hypoadiponectinemia in the development of insulin resistance and increased risk of inflammation warrant future investigation.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
71Clin. Lab. 2016 -1 62: 337-42
PMID27156321
TitleAltered Adipocytokine Levels and Heart Rate Variability in Schizophrenic Patients with Risk of Metabolic Syndrome.
AbstractThe aim of this study was to investigate changes in the levels of high-sensitivity C-reactive protein (Hs-CRP), tumor necrosis factor ? (TNF-?), myocardial fibrosis, and long-term heart rate variability (HRV) in schizophrenic patients at risk of developing metabolic syndrome (MS).
45 subjects without schizophrenia or MS were recruited into the control group (group A), 45 schizophrenic patients not at risk for developing MS constituted group B, and 45 schizophrenic patients at risk of MS constituted group C. Serum levels of TNF-? and Hs-CRP were examined by enzyme linked immunosorbent assay (ELISA). Ultrasonic acoustic densitometry (AD) analysis was performed to assess myocardial fibrosis, and 24 hours dynamic electrocardiography was conducted to determine HRV time-domain index.
Compared with the control group, schizophrenic patients at risk of MS displayed a reduced HRV (p < 0.05). The AD parameter CAI increased in schizophrenic patients with MS risk as compared to the control group (p < 0.05), whereas CVIB was significantly lowered (p > 0.05). Moreover, serum levels of TNF-? and Hs-CRP in the schizophrenic patients with MS risk were elevated compared with the control group (p <0.05).
Due to the influence of such factors as high glucose levels, hypertension and obesity, schizophrenic patients at risk of MS exhibited elevated levels of TNF-? and Hs-CRP, enhanced ventricular myocardial fibrosis, and reduced HRV, which might have resulted from structural changes and autonomic nervous dysfunction in cardiac tissues.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
72Clin. Lab. 2016 -1 62: 337-42
PMID27156321
TitleAltered Adipocytokine Levels and Heart Rate Variability in Schizophrenic Patients with Risk of Metabolic Syndrome.
AbstractThe aim of this study was to investigate changes in the levels of high-sensitivity C-reactive protein (Hs-CRP), tumor necrosis factor ? (TNF-?), myocardial fibrosis, and long-term heart rate variability (HRV) in schizophrenic patients at risk of developing metabolic syndrome (MS).
45 subjects without schizophrenia or MS were recruited into the control group (group A), 45 schizophrenic patients not at risk for developing MS constituted group B, and 45 schizophrenic patients at risk of MS constituted group C. Serum levels of TNF-? and Hs-CRP were examined by enzyme linked immunosorbent assay (ELISA). Ultrasonic acoustic densitometry (AD) analysis was performed to assess myocardial fibrosis, and 24 hours dynamic electrocardiography was conducted to determine HRV time-domain index.
Compared with the control group, schizophrenic patients at risk of MS displayed a reduced HRV (p < 0.05). The AD parameter CAI increased in schizophrenic patients with MS risk as compared to the control group (p < 0.05), whereas CVIB was significantly lowered (p > 0.05). Moreover, serum levels of TNF-? and Hs-CRP in the schizophrenic patients with MS risk were elevated compared with the control group (p <0.05).
Due to the influence of such factors as high glucose levels, hypertension and obesity, schizophrenic patients at risk of MS exhibited elevated levels of TNF-? and Hs-CRP, enhanced ventricular myocardial fibrosis, and reduced HRV, which might have resulted from structural changes and autonomic nervous dysfunction in cardiac tissues.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
73Schizophr Bull 2016 May -1: -1
PMID27143795
TitleChronic Peripheral Inflammation is Associated With Cognitive Impairment in Schizophrenia: Results From the Multicentric FACE-SZ Dataset.
AbstractInflammation, measured by abnormal blood C-reactive protein (CRP) level, has been described in schizophrenia (SZ), being inconsistently related to impaired cognitive functions. The aim of the present study is to investigate cognitive impairment associated with abnormal CRP levels in a large multi-centric sample of community-dwelling SZ patients, using a comprehensive neuropsychological battery.
Three hundred sixty-nine community-dwelling stable SZ subjects (76.2% men, mean age 32.7 y) were included and tested with a comprehensive battery of neuropsychological tests. Abnormal CRP level was defined as >3mg/L.
Multiple factor analysis revealed that abnormal CRP levels, found in 104 patients (28.2%), were associated with impaired General Intellectual Ability and Abstract Reasoning (aOR = 0.56, 95% CI 0.35-0.90, P = .014), independently of age, sex, education level, psychotic symptomatology, treatments, and addiction comorbidities. Abnormal CRP levels were also associated with the decline of all components of working memory (respectively effect size [ES] = 0.25, P = .033; ES = 0.27, P = .04; ES = 0.33, P = .006; and ES = 0.38, P = .004) and a wide range of other impaired cognitive functions, including memory (ES = 0.26, P = .026), learning abilities (ES = 0.28, P = .035), semantic memory (ES = 0.26, P = .026), mental flexibility (ES = 0.26, P = .044), visual attention (ES = 0.23, P = .004) and speed of processing (ES = 0.23, P = .043).
Our results suggest that abnormal CRP level is associated with cognitive impairment in SZ. Evaluating the effectiveness of neuroprotective anti-inflammatory strategies is needed in order to prevent cognitive impairment in SZ.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
74BMC Psychiatry 2016 -1 16: 76
PMID27000113
TitleClinical correlates of vitamin D deficiency in established psychosis.
AbstractSuboptimal vitamin D levels have been identified in populations with psychotic disorders. We sought to explore the relationship between vitamin D deficiency, clinical characteristics and cardiovascular disease risk factors among people with established psychosis.
Vitamin D levels were measured in 324 community dwelling individuals in England with established psychotic disorders, along with measures of mental health, cardiovascular risk and lifestyle choices. Vitamin D deficiency was defined as serum 25-hydroxyvitamin D (25-OHD) levels below 10 ng/ml (equivalent to <25 nmol/L) and "sufficient" Vitamin D as above 30 ng/ml (>50 nmol/L).
The mean 25-OHD serum level was 12.4 (SD 7.3) ng/ml, (range 4.0-51.7 ng/ml). Forty nine percent (n?=?158) were vitamin D deficient, with only 14 % (n?=?45) meeting criteria for sufficiency. Accounting for age, gender, ethnicity and season of sampling, serum 25-OHD levels were negatively correlated with waist circumference (r?=?-0.220, p?CRP levels (r?=?-0.211, p?=?0.003) and were linked to the presence of metabolic syndrome.
This is the largest cross sectional study of serum 25-OHD levels in community dwelling individuals with established psychosis, indicating a high level of vitamin D deficiency. Lower vitamin D levels are associated with increased cardiovascular disease risk factors and in particular metabolic syndrome. Further research is needed to define appropriate protocols for vitamin D testing and supplementation in practice to see if this can improve cardiovascular disease risk.
ISRCTN number is ISRCTN58667926 Date of registration: 23/04/2010.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
75BMC Psychiatry 2016 -1 16: 60
PMID26973142
TitleThe serum level of C-reactive protein (CRP) is associated with cognitive performance in acute phase psychosis.
AbstractInflammatory processes have been implicated in the etiology of schizophrenia and related psychoses, in which cognitive deficits represent core symptoms. The aim of the present study was to investigate possible associations between the level of the inflammation marker C-reactive protein (CRP) and cognitive performance in patients through the acute phase of psychosis.
A total of 124 patients were assessed at admittance to hospital and 62 patients were retested at discharge or after 6 weeks at the latest, with measurements of the CRP levels and alternative forms of the Repeatable Battery for the Assessment of Neuropsychological Status.
There was an inverse relationship between overall cognitive performance and CRP level at admittance. The association increased in sub-analyses including only patients with schizophrenia. In cognitive subdomain analyses statistically significant inverse associations were found between the CRP level and Delayed memory and Attention, respectively. No associations were found between CRP level and other measures of psychopathology including psychosis symptoms, depression, or functioning. At follow-up the association between CRP level and cognition was no longer present. There was a significant increase in cognitive performance between baseline and follow-up. There was a stronger increase in overall cognition scores in patients with higher baseline CRP levels.
The findings indicate that signs of inflammation may serve as a state-dependent marker of cognitive dysfunctions in acute psychosis.
ClinicalTrials.gov ID; NCT00932529 , registration date: 02.07.2009.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
76J Affect Disord 2016 Feb 191: 209-15
PMID26674214
TitlePeripheral sub-inflammation is associated with antidepressant consumption in schizophrenia. Results from the multi-center FACE-SZ data set.
AbstractThe relation between C-Reactive Protein (CRP), depression and antidepressant consumption has been well explored in major depressive disorders but not in schizophrenia, which has a high rate of depression comorbidity. The objectives of this study were: (i) to determine the prevalence of abnormal CRP levels, depression and antidepressant consumption in a multicenter community-dwelling sample of subjects with schizophrenia (ii) to determine the association between abnormal CRP levels, depression and antidepressant consumption in schizophrenia.
219 stable patients with schizophrenia (mean age=31.6 years, 75.3% male gender) were systematically included in the multicentre network of FondaMental Expert Center for schizophrenia (FACE-SZ) and assessed with a dedicated electronic medical record including the Structured Clinical Interview for DSM-IV Axis I Disorders and Calgary Depression Scale for depression. High sensitivity CRP (hs-CRP) was measured with an assay using nephelometry (Dade Behring). Abnormal CRP level was defined by levels >3mg/L. Current medication was recorded.
Overall, 63 subjects (28.8%) were found to have abnormal CRP levels, 43 (20.1%) received a diagnosis of comorbid current depression, and 51 (31.9%) had ongoing antidepressant treatment. In univariate analysis, abnormal CRP levels were found to be significantly associated with body mass index (BMI) (p<0.0001), hypertriglyceridemia (p=0.0015), high waist circumference (p<0.0001), metabolic syndrome (p=0.0011), abdominal obesity (p<0.0001) and with antidepressant consumption (p=0.01), while depression, psychotic symptomatology, age of onset, illness duration, sociodemographic characteristics, current tobacco or cannabis status, hypertension or high fasting glucose were not (all p>0.05). In a multivariate model, abnormal CRP was associated with antidepressant consumption independently of other confounding variables (adjusted Odds Ratio=2.8, 95% confidence interval 1.22-6.62). Metabolic syndrome was also independently associated with abnormal CRP (adjusted Odds Ratio=2.6, 95% confidence interval 1.01-6.71).
Abnormal CRP levels in schizophrenia were found to be associated with antidepressant consumption, but not with depression. The potential mechanisms were discussed. Antidepressant consumption should be systematically recorded in future studies exploring inflammation in schizophrenia. Future clinical trials of interventions directed at lowering the level of CRP and other inflammatory markers are discussed.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
77Eur. Psychiatry 2016 Jan 31: 8-12
PMID26657596
TitleElevated C-reactive protein levels in schizophrenia inpatients is associated with aggressive behavior.
AbstractAn association between inflammation and behavioral domains of mental disorders is of growing interest. Recent studies reported an association between aggression and inflammation. In this study, we investigated the association between aggressive behavior and inflammatory markers in schizophrenia inpatients.
Adult schizophrenia inpatients without affective symptoms (n=213) were retrospectively identified and categorized according to their C-reactive protein measurement at admission as either elevated (CRP>1 mg/dL; n=57) or normal (CRP<1 mg/dL; n=156). The following indicators of aggression were compared: PANSS excitement component (PANSS-EC), restraints and suicidal behavior during hospitalization. Univariate comparisons between elevated and normal CRP levels were performed and multivariate analysis was conducted to control for relevant covariates.
CRP levels significantly correlated with other laboratory markers indicating increased inflammation including leukocyte count and neutrophil to lymphocyte ratio (r=0.387, P<0.0001 and r=0.356, P<0.0001) respectively. Inpatients with elevated C-reactive protein displayed increased aggressive behavior compared to patients with normal CRP levels (<1 mg/dL). This was manifested by higher rates of restraint during hospitalization (?(2)=5.22, P=0.031) and increased PANSS-EC score (U=5410.5, P=0.012). Elevated CRP levels were not associated with suicidal behavior. Multivariate analysis revealed that higher PANSS-EC score was associated with elevated CRP after controlling for the covariates age, sex, BMI and smoking.
This study identified a potential biological correlate (inflammation) of a specific behavioral endophenotype (aggression) in schizophrenia inpatients.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
78Schizophr Bull 2016 Mar 42: 386-95
PMID26392628
TitleShared Immune and Repair Markers During Experimental Toxoplasma Chronic Brain Infection and Schizophrenia.
AbstractChronic neurologic infection with Toxoplasma gondii is relatively common in humans and is one of the strongest known risk factors for schizophrenia. Nevertheless, the exact neuropathological mechanisms linking T gondii infection and schizophrenia remain unclear. Here we utilize a mouse model of chronic T gondii infection to identify protein biomarkers that are altered in serum and brain samples at 2 time points during chronic infection. Furthermore, we compare the identified biomarkers to those differing between "postmortem" brain samples from 35 schizophrenia patients and 33 healthy controls. Our findings suggest that T gondii infection causes substantial and widespread immune activation indicative of neural damage and reactive tissue repair in the animal model that partly overlaps with changes observed in the brains of schizophrenia patients. The overlapping changes include increases in C-reactive protein (CRP), interleukin-1 beta (IL-1?), interferon gamma (IFN?), plasminogen activator inhibitor 1 (PAI-1), tissue inhibitor of metalloproteinases 1 (TIMP-1), and vascular cell adhesion molecule 1 (VCAM-1). Potential roles of these factors in the pathogenesis of schizophrenia and toxoplasmosis are discussed. Identifying a defined set of markers shared within the pathophysiological landscape of these diseases could be a key step towards understanding their specific contributions to pathogenesis.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
79Mol. Psychiatry 2016 Apr 21: 554-64
PMID26169974
TitleC-reactive protein is increased in schizophrenia but is not altered by antipsychotics: meta-analysis and implications.
AbstractThe inflammatory hypothesis of schizophrenia (SZ) posits that inflammatory processes and neural-immune interactions are involved in its pathogenesis, and may underpin some of its neurobiological correlates. SZ is the psychiatric disorder causing the most severe burden of illness, not just owing to its psychiatric impairment, but also owing to its significant medical comorbidity. C-reactive protein (CRP) is a commonly used biomarker of systemic inflammation worldwide. There are some conflicting results regarding the behaviour of CRP in SZ. The aims of this study were to verify whether peripheral CRP levels are indeed increased in SZ, whether different classes of antipsychotics divergently modulate CRP levels and whether its levels are correlated with positive and negative symptomatology. With that in mind, we performed a meta-analysis of all cross-sectional studies of serum and plasma CRP levels in SZ compared to healthy subjects. In addition, we evaluated longitudinal studies on CRP levels before and after antipsychotic use. Our meta-analyses of CRP in SZ included a total of 26 cross-sectional or longitudinal studies comprising 85?000 participants. CRP levels were moderately increased in persons with SZ regardless of the use of antipsychotics and did not change between the first episode of psychosis and with progression of SZ (g=0.66, 95% confidence interval (95% CI) 0.43 to 0.88, P<0.001, 24 between-group comparisons, n=82?962). The extent of the increase in peripheral CRP levels paralleled the increase in severity of positive symptoms, but was unrelated to the severity of negative symptoms. CRP levels were also aligned with an increased body mass index. Conversely, higher age correlated with a smaller difference in CRP levels between persons with SZ and controls. Furthermore, CRP levels did not increase after initiation of antipsychotic medication notwithstanding whether these were typical or atypical antipsychotics (g=0.01, 95% CI -0.20 to 0.22, P=0.803, 8 within-group comparisons, n=713). In summary, our study provides further evidence of the inflammatory hypothesis of SZ. Whether there is a causal relationship between higher CRP levels and the development of SZ and aggravation of psychotic symptoms, or whether they are solely a marker of systemic low-grade inflammation in SZ, remains to be clarified.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal
80Psychopharmacology (Berl.) 2016 May 233: 1559-73
PMID26037944
TitleIs there a role for immune-to-brain communication in schizophrenia?
Abstractschizophrenia is characterised by hallucinations, delusions, depression-like so-called negative symptoms, cognitive dysfunction, impaired neurodevelopment and neurodegeneration. Epidemiological and genetic studies strongly indicate a role of inflammation and immunity in the pathogenesis of symptoms of schizophrenia. Evidence accrued over the last two decades has demonstrated that there are a number of pathways through which systemic inflammation can exert profound influence on the brain leading to changes in mood, cognition and behaviour. The peripheral immune system-to-brain communication pathways have been studied extensively in the context of depression where inflammatory cytokines are thought to play a key role. In this review, we highlight novel evidence suggesting an important role of peripheral immune-to-brain communication pathways in schizophrenia. We discuss recent population-based longitudinal studies that report an association between elevated levels of circulating inflammatory cytokines and subsequent risk of psychosis. We discuss emerging evidence indicating potentially important role of blood-brain barrier endothelial cells in peripheral immune-to-brain communication, which may be also relevant for schizophrenia. Drawing on clinical and preclinical studies, we discuss whether immune-mediated mechanisms could help to explain some of the clinical and pathophysiological features of schizophrenia. We discuss implication of these findings for approaches to diagnosis, treatment and research in future. Finally, pointing towards links with early-life adversity, we consider whether persistent low-grade activation of the innate immune response, as a result of impaired foetal or childhood development, could be a common mechanism underlying the high comorbidity between certain neuropsychiatric and physical illnesses, such as schizophrenia, depression, heart disease and type-two diabetes.
SCZ Keywordsschizophrenia, schizophrenic, schizotypal