| 1 | Mol. Psychiatry 2001 Jul 6: 445-9 |
|---|---|
| PMID | 11443531 |
| Title | Increased S100B blood levels in unmedicated and treated schizophrenic patients are correlated with negative symptomatology. |
| Abstract | S100B, a calcium-binding protein produced by astroglial cells, is a marker of astroglial cellular integrity. It has been shown to be increased in acute brain damage and neurodegeneration. A recent study showed increased S100B levels in medicated acutely psychotic patients with schizophrenia. The study presented here included 26 drug-free patients with acute schizophrenia and 26 matched healthy controls. S100B blood concentrations were determined using a quantitative immunoassay upon admission and after 6 weeks of neuroleptic treatment. The PANSS was used to investigate psychopathology. Unmedicated schizophrenic patients showed significantly increased S100B levels compared to matched healthy controls. After 6 weeks of treatment, 11 patients showed normal S100B levels while in 15 patients the levels remained increased. These patients showed significantly higher PANSS negative scores upon admission and after 6 weeks of treatment. schizophrenic patients display a loss of astroglial integrity which is not caused by neuroleptic medication. Continuously increased S100B levels are associated with negative symptomatology. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 2 | Mol. Psychiatry 2001 Jul 6: 445-9 |
| PMID | 11443531 |
| Title | Increased S100B blood levels in unmedicated and treated schizophrenic patients are correlated with negative symptomatology. |
| Abstract | S100B, a calcium-binding protein produced by astroglial cells, is a marker of astroglial cellular integrity. It has been shown to be increased in acute brain damage and neurodegeneration. A recent study showed increased S100B levels in medicated acutely psychotic patients with schizophrenia. The study presented here included 26 drug-free patients with acute schizophrenia and 26 matched healthy controls. S100B blood concentrations were determined using a quantitative immunoassay upon admission and after 6 weeks of neuroleptic treatment. The PANSS was used to investigate psychopathology. Unmedicated schizophrenic patients showed significantly increased S100B levels compared to matched healthy controls. After 6 weeks of treatment, 11 patients showed normal S100B levels while in 15 patients the levels remained increased. These patients showed significantly higher PANSS negative scores upon admission and after 6 weeks of treatment. schizophrenic patients display a loss of astroglial integrity which is not caused by neuroleptic medication. Continuously increased S100B levels are associated with negative symptomatology. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 3 | Schizophr. Res. 2003 Aug 62: 231-6 |
| PMID | 12837519 |
| Title | Serum S100B is increased during early treatment with antipsychotics and in deficit schizophrenia. |
| Abstract | Previous studies reported controversial results concerning alterations of astrocytes in schizophrenia. Because S100B may be regarded as a marker for astrocytes, the objective of this study was to examine S100B serum concentrations in 30 patients with schizophrenia with a monoclonal two-site immunoluminometric assay that specifically detects S100B. An ANOVA revealed medication (p<0.005) and deficit vs. nondeficit syndrome (p<0.05) as factors that influenced S100B significantly. S100B was higher in schizophrenic patients treated with antipsychotic drugs for approximately 3 weeks (241.1+/-152.5 ng/l) in comparison with unmedicated patients (111.4+/-31.8 ng/l, p<0.005), and healthy age-matched controls (112.8+/-53.4 ng/l, p<0.001; Bonferroni corrected two-tailed Student's t-test). There was no difference of S100B between unmedicated patients and controls (p>0.05). Patients with deficit (250.6+/-154.9 ng/l) had higher S100B levels than patients with nondeficit schizophrenia (146.7+/-107.2 ng/l, p<0.05) or controls (p<0.005). S100B was positively correlated with the subscore 'thought disturbance' of the Brief Psychiatric Rating Scale (p<0.05). In summary, increased serum levels of S100B may indicate alterations of astrocytes during early treatment with antipsychotics and in deficit schizophrenia. Whether S100B is elevated due to injured astrocytes and a disrupted blood-brain barrier, or by active secretion of S100B by astrocytes, has to be clarified by further studies. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 4 | Schizophr. Res. 2003 Aug 62: 231-6 |
| PMID | 12837519 |
| Title | Serum S100B is increased during early treatment with antipsychotics and in deficit schizophrenia. |
| Abstract | Previous studies reported controversial results concerning alterations of astrocytes in schizophrenia. Because S100B may be regarded as a marker for astrocytes, the objective of this study was to examine S100B serum concentrations in 30 patients with schizophrenia with a monoclonal two-site immunoluminometric assay that specifically detects S100B. An ANOVA revealed medication (p<0.005) and deficit vs. nondeficit syndrome (p<0.05) as factors that influenced S100B significantly. S100B was higher in schizophrenic patients treated with antipsychotic drugs for approximately 3 weeks (241.1+/-152.5 ng/l) in comparison with unmedicated patients (111.4+/-31.8 ng/l, p<0.005), and healthy age-matched controls (112.8+/-53.4 ng/l, p<0.001; Bonferroni corrected two-tailed Student's t-test). There was no difference of S100B between unmedicated patients and controls (p>0.05). Patients with deficit (250.6+/-154.9 ng/l) had higher S100B levels than patients with nondeficit schizophrenia (146.7+/-107.2 ng/l, p<0.05) or controls (p<0.005). S100B was positively correlated with the subscore 'thought disturbance' of the Brief Psychiatric Rating Scale (p<0.05). In summary, increased serum levels of S100B may indicate alterations of astrocytes during early treatment with antipsychotics and in deficit schizophrenia. Whether S100B is elevated due to injured astrocytes and a disrupted blood-brain barrier, or by active secretion of S100B by astrocytes, has to be clarified by further studies. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 5 | Int. Rev. Neurobiol. 2004 -1 59: 445-70 |
| PMID | 15006498 |
| Title | S100B in schizophrenic psychosis. |
| Abstract | Recent findings have strengthened the hypothesis that a dysfunction of neuronal synapses and dendrites is relevant for the pathogenesis of schizophrenia. It might be present during neurodevelopment as well as in degenerative and regenerative processes of the mature brain. S1OOB, a small, Ca2+-binding, astrocytic protein, plays an important role in modulating the proliferation and differentiation of neurons and glia cells. It is involved in the regulation of cellular energy metabolism and interacts with many immunological functions of the brain. This review addresses findings from cell cultural and animal experiments potentially pertinent for the pathogenesis of schizophrenic psychoses. Morphological and functional data are analyzed and clinical studies reporting alterations of S1OOB concentrations in schizophrenic patients are reviewed. Evidence and limitations of the available studies are pointed out and promising future research strategies are outlined. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 6 | Mol. Psychiatry 2004 Oct 9: 897-9 |
| PMID | 15241436 |
| Title | Glial cell dysfunction in schizophrenia indicated by increased S100B in the CSF. |
| Abstract | -1 |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 7 | Int. Rev. Neurobiol. 2004 -1 59: 445-70 |
| PMID | 15006498 |
| Title | S100B in schizophrenic psychosis. |
| Abstract | Recent findings have strengthened the hypothesis that a dysfunction of neuronal synapses and dendrites is relevant for the pathogenesis of schizophrenia. It might be present during neurodevelopment as well as in degenerative and regenerative processes of the mature brain. S1OOB, a small, Ca2+-binding, astrocytic protein, plays an important role in modulating the proliferation and differentiation of neurons and glia cells. It is involved in the regulation of cellular energy metabolism and interacts with many immunological functions of the brain. This review addresses findings from cell cultural and animal experiments potentially pertinent for the pathogenesis of schizophrenic psychoses. Morphological and functional data are analyzed and clinical studies reporting alterations of S1OOB concentrations in schizophrenic patients are reviewed. Evidence and limitations of the available studies are pointed out and promising future research strategies are outlined. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 8 | Brain Dev. 2004 Apr 26: 190-6 |
| PMID | 15030908 |
| Title | Over-expression of S100B protein in children with cerebral palsy or delayed development. |
| Abstract | S100B protein plays a role in promoting the maturation of a variety of neurons in many different CNS regions. Behavioral dysfunction in S100B over-expressed transgenic mice and the chronic elevation of S100B in Down's syndrome and in schizophrenia suggest that S100B over-expression is related to abnormal brain function. Therefore, we believed that the over-expression of S100B protein might be implicated in developmental brain dysfunction. The purpose of this study was to evaluate the serum S100B protein levels in patients with developmental brain dysfunction, such as cerebral palsy and delayed development, and to determine the clinical relevance of serum S100B protein in these patients. The mean values of serum S100B protein were significantly increased in both conditions. Patients with cerebral palsy had a S100B protein level of 3455.8 +/- 5004.6 ng/L and those with delayed development of 2557.0 +/- 2321.0 ng/L, compared with a normal control level of 583.8 +/- 483.0 ng/L (P < 0.05). The over-expression of S100B (defined as the normal mean plus three standard deviations) was found in 47.1% of the total patient group (delayed development (47.5%) and cerebral palsy (47.0%)). The frequency of over-expression was not significantly related to clinical diagnosis, disease severity or to brain MRI findings. However, patients who had periventricular leukomalacia by brain MRI showed a wide range and very high levels of S100B exceeding 10,000 ng/L in some cases. These findings suggest that the pathogenesis implied by the over-expression of S100B protein during brain development may play a role in developmental brain dysfunction. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 9 | Neuropsychopharmacology 2004 May 29: 1004-11 |
| PMID | 14997170 |
| Title | S100B serum levels and long-term improvement of negative symptoms in patients with schizophrenia. |
| Abstract | S100B, a calcium-binding protein produced by astroglial cells, mediates paracrine and autocrine effects on neurons and glial cells. It regulates the balance between proliferation and differentiation in neurons and glial cells by affecting protective and apoptotic mechanisms. Post-mortem studies have demonstrated a deficit in synapses and dendrites in brains of schizophrenics. Recent studies have shown increased S100B levels in medicated acutely psychotic schizophrenic patients as well as unmedicated or drug naive schizophrenics. One study reported a positive correlation between negative symptoms and S100B. S100B serum levels (quantitative immunoassay) and psychopathology (Positive and Negative Syndrome Scale, PANSS) were examined upon study admission and after 12 and 24 weeks of standardized treatment in 98 chronic schizophrenic patients with primarily negative symptoms. Compared to age- and sex-matched healthy controls, the schizophrenic patients showed significantly increased S100B concentrations upon admission and after 12 and 24 weeks of treatment. High PANSS negative scores were correlated with high S100B levels. Regression analysis comparing psychopathology subscales and S100B identified negative symptomatology as the predicting factor for S100B. S100B is not just elevated during acute stages of disease since it remains elevated for at least 6 months following an acute exacerbation. With regard to psychopathology, negative symptomatology appears to be the predicting factor for the absolute S100B concentration. This might indicate that S100B in schizophrenic patients either promotes apoptotic mechanisms by itself or is released from astrocytes as part of an attempt to repair a degenerative or destructive process. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 10 | Neuropsychopharmacology 2004 May 29: 1004-11 |
| PMID | 14997170 |
| Title | S100B serum levels and long-term improvement of negative symptoms in patients with schizophrenia. |
| Abstract | S100B, a calcium-binding protein produced by astroglial cells, mediates paracrine and autocrine effects on neurons and glial cells. It regulates the balance between proliferation and differentiation in neurons and glial cells by affecting protective and apoptotic mechanisms. Post-mortem studies have demonstrated a deficit in synapses and dendrites in brains of schizophrenics. Recent studies have shown increased S100B levels in medicated acutely psychotic schizophrenic patients as well as unmedicated or drug naive schizophrenics. One study reported a positive correlation between negative symptoms and S100B. S100B serum levels (quantitative immunoassay) and psychopathology (Positive and Negative Syndrome Scale, PANSS) were examined upon study admission and after 12 and 24 weeks of standardized treatment in 98 chronic schizophrenic patients with primarily negative symptoms. Compared to age- and sex-matched healthy controls, the schizophrenic patients showed significantly increased S100B concentrations upon admission and after 12 and 24 weeks of treatment. High PANSS negative scores were correlated with high S100B levels. Regression analysis comparing psychopathology subscales and S100B identified negative symptomatology as the predicting factor for S100B. S100B is not just elevated during acute stages of disease since it remains elevated for at least 6 months following an acute exacerbation. With regard to psychopathology, negative symptomatology appears to be the predicting factor for the absolute S100B concentration. This might indicate that S100B in schizophrenic patients either promotes apoptotic mechanisms by itself or is released from astrocytes as part of an attempt to repair a degenerative or destructive process. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 11 | Neuropsychopharmacology 2004 May 29: 1004-11 |
| PMID | 14997170 |
| Title | S100B serum levels and long-term improvement of negative symptoms in patients with schizophrenia. |
| Abstract | S100B, a calcium-binding protein produced by astroglial cells, mediates paracrine and autocrine effects on neurons and glial cells. It regulates the balance between proliferation and differentiation in neurons and glial cells by affecting protective and apoptotic mechanisms. Post-mortem studies have demonstrated a deficit in synapses and dendrites in brains of schizophrenics. Recent studies have shown increased S100B levels in medicated acutely psychotic schizophrenic patients as well as unmedicated or drug naive schizophrenics. One study reported a positive correlation between negative symptoms and S100B. S100B serum levels (quantitative immunoassay) and psychopathology (Positive and Negative Syndrome Scale, PANSS) were examined upon study admission and after 12 and 24 weeks of standardized treatment in 98 chronic schizophrenic patients with primarily negative symptoms. Compared to age- and sex-matched healthy controls, the schizophrenic patients showed significantly increased S100B concentrations upon admission and after 12 and 24 weeks of treatment. High PANSS negative scores were correlated with high S100B levels. Regression analysis comparing psychopathology subscales and S100B identified negative symptomatology as the predicting factor for S100B. S100B is not just elevated during acute stages of disease since it remains elevated for at least 6 months following an acute exacerbation. With regard to psychopathology, negative symptomatology appears to be the predicting factor for the absolute S100B concentration. This might indicate that S100B in schizophrenic patients either promotes apoptotic mechanisms by itself or is released from astrocytes as part of an attempt to repair a degenerative or destructive process. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 12 | Rinsho Byori 2005 May 53: 395-9 |
| PMID | 15966402 |
| Title | [Analysis of reference values of serum S100B concentrations of Japanese adults]. |
| Abstract | S100B is a calcium-binding protein which exists in abundance in glial cells of the central nervous system (CNS). It is reported that the serum S100B level increase with various CNS diseases, such as stroke, head injury, schizophrenia, major depression and Alzheimer's disease. However, there are no reports on its reference values for the Japanese. The purpose of this study is to know the serum S100B concentrations of Japanese adults, free of any CNS diseases, according to sex, age and circadian rhythm. Moreover, the stability and reproducibility of its measurements of S100B in frozen serum over 7 months. Volunteers were 26 male and 25 female of Japanese adults. Venous blood samples were collected at given times of a day and serum was obtained by centrifugation at 4 degrees C. An automated chemiluminescence analyzer "LIAISON" and exclusive reagent Sangtec 100 (DiaSorin, Italy), was used for measurement of serum S100B concentrations. The serum S100B concentrations in Japanese adults corresponded well, with the reported values in Asians. Differences by age and sex were not found. S100B did not how circadian variation. The serum S100B concentrations measured in two months and in nine months after venipuncture were almost the same. The measurement of S100B by "LIAISON" showed excellent reproducibility and reliability. Furthermore, stability of serum S100B stored at -80 degrees C was good. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 13 | Biochem. Biophys. Res. Commun. 2005 Mar 328: 335-41 |
| PMID | 15670788 |
| Title | SNPs and haplotypes in the S100B gene reveal association with schizophrenia. |
| Abstract | The S100B gene locates in 21q22.3 and produces neurotrophin mainly in astrocytes of CNS which can act as an extensive marker of glial cell integrity. The synaptic destabilization hypothesis (GGF/SD) suggests that the functional deficiency of growth factors like S100B is involved in the etiology of schizophrenia and the S100B serum concentration is reported to be significantly increased in patients with acute schizophrenia and decreased in chronic schizophrenia patients. To validate the association between S100B and schizophrenia, 384 cases and 401 controls, all Chinese Han subjects, were recruited. Four SNPs V1 (-960C>G), V2 (-111C>T), V3 (2757C>G, rs1051169), and V4 (5748C>T, rs9722) were studied. And haplotype V3-V4 (G-C) showed a significant association with schizophrenia. Our study showed an association between schizophrenia and a possible susceptible haplotype V3-V4 (G-C) which possesses a genetic tendency for increased S100B expression. Our results suggest that S100B could be a susceptible gene for schizophrenia and provide indirect evidence for the GGF/SD hypothesis. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 14 | Schizophr. Res. 2005 Dec 80: 305-13 |
| PMID | 15964742 |
| Title | Increased serum S100B in elderly, chronic schizophrenic patients: negative correlation with deficit symptoms. |
| Abstract | In schizophrenia, elevations of serum and CSF S100B levels have been reported and related to state of the disease and negative symptoms. In elderly chronic schizophrenic inpatients with stable medication, S100B may be increased and correlated to psychopathology and neuropsychological deficits. We have measured serum levels of S100B in 41 elderly, chronic schizophrenic patients and 23 age- and gender-matched controls using an immunoluminometric assay. In patients, we assessed detailed psychopathology and neuropsychological performance and determined serum levels of haloperidol, clozapine and its two main metabolites desmethylclozapine and clozapine metabolite N-oxid by HPLC. S100B levels were increased in elderly chronic schizophrenic patients compared to healthy controls. In patients, levels were negatively correlated with deficit symptoms and positively with age. There were no significant differences of S100B between medication groups and no correlation with serum levels of antipsychotics or neuropsychological scores. Elevations of S100B in elderly chronic schizophrenic patients may be related to an active disease process lasting until old-age. Correlations point to the impact of S100B in neuroplasticity and ageing. Post-mortem studies should clarify the presence of altered S100B function in the brain and its relationship to neuroplastic or neurodegenerative processes. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 15 | Schizophr. Res. 2005 Dec 80: 305-13 |
| PMID | 15964742 |
| Title | Increased serum S100B in elderly, chronic schizophrenic patients: negative correlation with deficit symptoms. |
| Abstract | In schizophrenia, elevations of serum and CSF S100B levels have been reported and related to state of the disease and negative symptoms. In elderly chronic schizophrenic inpatients with stable medication, S100B may be increased and correlated to psychopathology and neuropsychological deficits. We have measured serum levels of S100B in 41 elderly, chronic schizophrenic patients and 23 age- and gender-matched controls using an immunoluminometric assay. In patients, we assessed detailed psychopathology and neuropsychological performance and determined serum levels of haloperidol, clozapine and its two main metabolites desmethylclozapine and clozapine metabolite N-oxid by HPLC. S100B levels were increased in elderly chronic schizophrenic patients compared to healthy controls. In patients, levels were negatively correlated with deficit symptoms and positively with age. There were no significant differences of S100B between medication groups and no correlation with serum levels of antipsychotics or neuropsychological scores. Elevations of S100B in elderly chronic schizophrenic patients may be related to an active disease process lasting until old-age. Correlations point to the impact of S100B in neuroplasticity and ageing. Post-mortem studies should clarify the presence of altered S100B function in the brain and its relationship to neuroplastic or neurodegenerative processes. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 16 | Nihon Shinkei Seishin Yakurigaku Zasshi 2006 Feb 26: 11-6 |
| PMID | 16637591 |
| Title | [S100B: astrocyte specific protein]. |
| Abstract | The S100B is a Ca2+ binding proteins of EF-hand type and is produced primarily by astrocytes in the central nervous system. This protein has been implicated in the Ca2+-dependent regulation of a variety of intracellular functions such as protein phosphorylation, enzyme activities, cell proliferation and differentiation, dynamics of cytoskeleton constituents, structural organization of membranes, intracellular Ca2+ homeostasis, inflammation, and protection from oxidative cell damage. Recent studies suggest that released S100B exerts paracrine and autocrine effects on neurons and glia. On the other hand, elevations of S100B levels in blood or cerebrospinal fluid have been observed in patients with Alzheimer's disease, Down's syndrome, amyotrophic lateral sclerosis, multiple sclerosis, schizophrenia, depression, cerebral stroke and traumatic brain injury, and the levels have reached micromol/L-order at focal regions. It has been documented that the excessive S100B promotes the expression of inducible nitric oxide synthase or pro-inflammatory cytokines and exhibits detrimental effects on neurons. On studies using some animal models of the cerebral stroke or Alzheimer's disease, it is suggested that the excessive S100B produced by activated astrocytes precedes neurodegenerations. Authors discussed the relationship between neurological disorders and the S100B. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 17 | J. Neurol. Neurosurg. Psychiatr. 2006 Nov 77: 1284-7 |
| PMID | 17043297 |
| Title | Increased cerebrospinal fluid and serum levels of S100B in first-onset schizophrenia are not related to a degenerative release of glial fibrillar acidic protein, myelin basic protein and neurone-specific enolase from glia or neurones. |
| Abstract | To assess levels of glial fibrillar acidic protein (GFAP), myelin basic protein (MBP), neurone-specific enolase (NSE) and S100B in patients with first-onset schizophrenia. We investigated CSF and serum samples from 12 patients with first-onset schizophrenia and from 17 control subjects by ELISA (GFAP, MBP) or immunoluminometric sandwich assays (NSE, S100B). Patients with schizophrenia had significantly higher levels of S100B in CSF (p = 0.004; 2.73 (SD 0.80) v 1.92 (0.58) microg/l) and serum (p = 0.032; 0.09 (0.03) v 0.08 (0.02) microg/l) in comparison with those in the matched control group. No diagnosis-dependent differences of protein concentration were seen for GFAP, MBP and NSE. Our finding of increased levels of S100B in patients with schizophrenia without an indication for significant glial (GFAP, MBP) or neuronal (NSE) damage may be interpreted as indirect evidence for increased active secretion of S100B during acute psychosis. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 18 | Eur Neuropsychopharmacol 2006 Oct 16: 469-80 |
| PMID | 16545550 |
| Title | Schizophrenia-associated neural growth factors in peripheral blood. A review. |
| Abstract | In this paper we review the findings on neural growth factors in the peripheral blood of schizophrenia patients. The studies we review provide evidence for the fact that in schizophrenia the levels of growth factors in peripheral blood are disturbed. The most robust results (7 studies) are reported for S100B protein, which seems to be elevated in acute psychosis and in patients with predominant negative symptoms. We conclude that there are aberrant levels of growth factors in peripheral blood in schizophrenia patients, probably most notably in patients with negative symptoms. Large-scale longitudinal multivariate studies, investigating the levels of several growth factors at the same time might give insight in etiological processes and identify clinically useful subsets of patients within the heterogeneous schizophrenia sample. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 19 | Neurotox Res 2006 Oct 10: 131-48 |
| PMID | 17062375 |
| Title | Schizophrenia as an inflammation-mediated dysbalance of glutamatergic neurotransmission. |
| Abstract | This overview tries to bridge the gap between psychoneuroimmunological findings and recent results from pharmacological, neurochemical and genetic studies in schizophrenia. schizophrenia is a disorder of dopaminergic neurotransmission, but modulation of the dopaminergic system by glutamatergic neurotransmission seems to play a key role. This view is supported by genetic findings of the neuregulin- and dysbindin genes, which have functional impact on the glutamatergic system. Glutamatergic hypofunction, however, is mediated by the N-methyl-D-aspartate (NMDA)-receptor antagonism. The only endogenous NMDA receptor antagonist identified up to now is kynurenic acid (KYNA). Despite the NMDA receptor antagonism, KYNA also blocks, in lower doses, the nicotinergic acetycholine receptor, i.e., increased KYNA levels can explain psychotic symptoms and cognitive deterioration. KYNA levels are described to be higher in the cerebrospinal fluid (CSF) and in critical central nervous system (CNS) regions of schizophrenics as compared to controls. Another line of evidence suggests that a (prenatal) infection is involved in the pathogenesis of schizophrenia. Due to an early sensitization process of the immune system or to a (chronic) infection, which is not cleared through the immune response, an immune imbalance between the type-1 and the type-2 immune responses takes place in schizophrenia. The type-1 response is partially inhibited, while the type-2 response is over-activated. This immune constellation is associated with inhibition of the enzyme indoleamine dioxygenase (IDO), because IDO - located in astrocytes and microglial cells - is inhibited by type-2 cytokines. IDO catalyzes the first step in tryptophan metabolism, the degradation from tryptophan to kynurenine, as does tryptophan 2,3-dioxygenase (TDO). Due to the inhibition of IDO, tryptophan-kynurenine is predominantly metabolized by TDO, which is located in astrocytes, not in microglial or other CNS cells. In schizophrenia, astrocytes in particular are activated, as increased levels of S100B appear. Additionally, they do not have the enzymatic equipment for the normal metabolism-route of tryptophan. Due to the lack of kynurenine hydroxylase (KYN-OHase) in astrocytes, KYNA accumulates in the CNS, while the metabolic pathway in microglial cells is blocked. Accordingly, an increase of TDO activity has been observed in critical CNS regions of schizophrenics. These mechanisms result in an accumulation of KYNA in critical CNS regions. Thus, the immune-mediated glutamatergic-dopaminergic dysregulation may lead to the clinical symptoms of schizophrenia. Therapeutic consequences, e.g., the use of anti-inflammatory cyclo-oxygenase-2 inhibitors, which can also decrease KYNA directly, are discussed. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 20 | Neurotox Res 2006 Oct 10: 131-48 |
| PMID | 17062375 |
| Title | Schizophrenia as an inflammation-mediated dysbalance of glutamatergic neurotransmission. |
| Abstract | This overview tries to bridge the gap between psychoneuroimmunological findings and recent results from pharmacological, neurochemical and genetic studies in schizophrenia. schizophrenia is a disorder of dopaminergic neurotransmission, but modulation of the dopaminergic system by glutamatergic neurotransmission seems to play a key role. This view is supported by genetic findings of the neuregulin- and dysbindin genes, which have functional impact on the glutamatergic system. Glutamatergic hypofunction, however, is mediated by the N-methyl-D-aspartate (NMDA)-receptor antagonism. The only endogenous NMDA receptor antagonist identified up to now is kynurenic acid (KYNA). Despite the NMDA receptor antagonism, KYNA also blocks, in lower doses, the nicotinergic acetycholine receptor, i.e., increased KYNA levels can explain psychotic symptoms and cognitive deterioration. KYNA levels are described to be higher in the cerebrospinal fluid (CSF) and in critical central nervous system (CNS) regions of schizophrenics as compared to controls. Another line of evidence suggests that a (prenatal) infection is involved in the pathogenesis of schizophrenia. Due to an early sensitization process of the immune system or to a (chronic) infection, which is not cleared through the immune response, an immune imbalance between the type-1 and the type-2 immune responses takes place in schizophrenia. The type-1 response is partially inhibited, while the type-2 response is over-activated. This immune constellation is associated with inhibition of the enzyme indoleamine dioxygenase (IDO), because IDO - located in astrocytes and microglial cells - is inhibited by type-2 cytokines. IDO catalyzes the first step in tryptophan metabolism, the degradation from tryptophan to kynurenine, as does tryptophan 2,3-dioxygenase (TDO). Due to the inhibition of IDO, tryptophan-kynurenine is predominantly metabolized by TDO, which is located in astrocytes, not in microglial or other CNS cells. In schizophrenia, astrocytes in particular are activated, as increased levels of S100B appear. Additionally, they do not have the enzymatic equipment for the normal metabolism-route of tryptophan. Due to the lack of kynurenine hydroxylase (KYN-OHase) in astrocytes, KYNA accumulates in the CNS, while the metabolic pathway in microglial cells is blocked. Accordingly, an increase of TDO activity has been observed in critical CNS regions of schizophrenics. These mechanisms result in an accumulation of KYNA in critical CNS regions. Thus, the immune-mediated glutamatergic-dopaminergic dysregulation may lead to the clinical symptoms of schizophrenia. Therapeutic consequences, e.g., the use of anti-inflammatory cyclo-oxygenase-2 inhibitors, which can also decrease KYNA directly, are discussed. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 21 | Clin. Chem. Lab. Med. 2007 -1 45: 1561-3 |
| PMID | 17970711 |
| Title | Increased serum S100B protein in chronic schizophrenic patients in Korea. |
| Abstract | -1 |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 22 | J. Neurosci. Res. 2007 May 85: 1373-80 |
| PMID | 17348038 |
| Title | S100B in neuropathologic states: the CRP of the brain? |
| Abstract | In 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 Keywords | schizophrenia, schizophrenic, schizophrenics |
| 23 | Am. J. Med. Genet. B Neuropsychiatr. Genet. 2007 Dec 144B: 1094-6 |
| PMID | 17525977 |
| Title | Candidate gene analysis of 21q22: support for S100B as a susceptibility gene for bipolar affective disorder with psychosis. |
| Abstract | A genome-wide scan in 60 bipolar affective disorder (BPAD) affected sib-pairs (ASPs) identified linkage on chromosome 21 at 21q22 (D21S1446, NPL = 1.42, P = 0.08), a BPAD susceptibility locus supported by multiple studies. Although this linkage only approaches significance, the peak marker is located 12 Kb upstream of S100B, a neurotrophic factor implicated in the pathology of psychiatric disorders, including BPAD and schizophrenia. We hypothesized that the linkage signal at 21q22 may result from pathogenic disease variants within S100B and performed an association analysis of this gene in a collection of 125 BPAD type I trios. S100B single nucleotide polymorphisms (SNPs) rs2839350 (P = 0.022) and rs3788266 (P = 0.031) were significantly associated with BPAD. Since variants within S100B have also been associated with schizophrenia susceptibility, we reanalyzed the data in trios with a history of psychosis, a phenotype in common between the two disorders. SNPs rs2339350 (P = 0.016) and rs3788266 (P = 0.009) were more significantly associated in the psychotic subset. Increased significance was also obtained at the haplotype level. Interestingly, SNP rs3788266 is located within a consensus-binding site for Six-family transcription factors suggesting that this variant may directly affect S100B gene expression. Fine-mapping analyses of 21q22 have previously identified transient receptor potential gene melastatin 2 (TRPM2), which is 2 Mb upstream of S100B, as a possible BPAD susceptibility gene at 21q22. We also performed a family-based association analysis of TRPM2 which did not reveal any evidence for association of this gene with BPAD. Overall, our findings suggest that variants within the S100B gene predispose to a psychotic subtype of BPAD, possibly via alteration of gene expression. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 24 | Prog. Neuropsychopharmacol. Biol. Psychiatry 2007 Mar 31: 361-4 |
| PMID | 17081670 |
| Title | Glial cell activation in a subgroup of patients with schizophrenia indicated by increased S100B serum concentrations and elevated myo-inositol. |
| Abstract | Post-mortem and in-vivo studies support the hypothesis that astrocytes might be involved in the pathogenesis of schizophrenia. To further substantiate this hypothesis two markers of astroglial activation (myo-inositol, S100B) acquired with independent methods ((1)H-MRS, quantitative immunoassay) were concomitantly measured in schizophrenic patients. Patients with increased S100B levels showed elevated myo-inositol concentrations. This pilot study demonstrates a concomitant elevation of two markers indicating astrocyte activation in a subgroup of schizophrenic patients. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 25 | Prog. Neuropsychopharmacol. Biol. Psychiatry 2007 Mar 31: 361-4 |
| PMID | 17081670 |
| Title | Glial cell activation in a subgroup of patients with schizophrenia indicated by increased S100B serum concentrations and elevated myo-inositol. |
| Abstract | Post-mortem and in-vivo studies support the hypothesis that astrocytes might be involved in the pathogenesis of schizophrenia. To further substantiate this hypothesis two markers of astroglial activation (myo-inositol, S100B) acquired with independent methods ((1)H-MRS, quantitative immunoassay) were concomitantly measured in schizophrenic patients. Patients with increased S100B levels showed elevated myo-inositol concentrations. This pilot study demonstrates a concomitant elevation of two markers indicating astrocyte activation in a subgroup of schizophrenic patients. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 26 | J. Neural Transm. Suppl. 2007 -1 -1: 269-80 |
| PMID | 17982903 |
| Title | The immunological basis of glutamatergic disturbance in schizophrenia: towards an integrated view. |
| Abstract | This overview presents a hypothesis to bridge the gap between psychoneuroimmunological findings and recent results from pharmacological, neurochemical and genetic studies in schizophrenia. In schizophrenia, a glutamatergic hypofunction is discussed to be crucially involved in dopaminergic dysfunction. This view is supported by findings of the neuregulin- and dysbindin genes, which have functional impact on the glutamatergic system. Glutamatergic hypofunction is mediated by NMDA (N-methyl-D-aspartate) receptor antagonism. The only endogenous NMDA receptor antagonist identified up to now is kynurenic acid (KYN-A). KYN-A also blocks the nicotinergic acetycholine receptor, i.e. increased KYN-A levels can explain psychotic symptoms and cognitive deterioration. KYN-A levels are described to be higher in the CSF and in critical CNS regions of schizophrenics. Another line of evidence suggests that of the immune system in schizophrenic patients is characterized by an imbalance between the type-1 and the type-2 immune responses with a partial inhibition of the type-1 response, while the type-2 response is relatively over-activated. This immune constellation is associated with the inhibition of the enzyme indoleamine 2,3-dioxygenase (IDO), because type-2 cytokines are potent inhibitors of IDO. Due to the inhibition of IDO, tryptophan is predominantly metabolized by tryptophan 2,3-dioxygenase (TDO), which is located in astrocytes, but not in microglia cells. As indicated by increased levels of S100B, astrocytes are activated in schizophrenia. On the other hand, the kynurenine metabolism in astrocytes is restricted to the dead-end arm of KYN-A production. Accordingly, an increased TDO activity and an accumulation of KYN-A in the CNS of schizophrenics have been described. Thus, the immune-mediated glutamatergic-dopaminergic dysregulation may lead to the clinical symptoms of schizophrenia. Therapeutic consequences, e.g. the use of antiinflammatory cyclooxygenase-2 inhibitors, which also are able to directly decrease KYN-A, are discussed. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 27 | J. Neural Transm. Suppl. 2007 -1 -1: 269-80 |
| PMID | 17982903 |
| Title | The immunological basis of glutamatergic disturbance in schizophrenia: towards an integrated view. |
| Abstract | This overview presents a hypothesis to bridge the gap between psychoneuroimmunological findings and recent results from pharmacological, neurochemical and genetic studies in schizophrenia. In schizophrenia, a glutamatergic hypofunction is discussed to be crucially involved in dopaminergic dysfunction. This view is supported by findings of the neuregulin- and dysbindin genes, which have functional impact on the glutamatergic system. Glutamatergic hypofunction is mediated by NMDA (N-methyl-D-aspartate) receptor antagonism. The only endogenous NMDA receptor antagonist identified up to now is kynurenic acid (KYN-A). KYN-A also blocks the nicotinergic acetycholine receptor, i.e. increased KYN-A levels can explain psychotic symptoms and cognitive deterioration. KYN-A levels are described to be higher in the CSF and in critical CNS regions of schizophrenics. Another line of evidence suggests that of the immune system in schizophrenic patients is characterized by an imbalance between the type-1 and the type-2 immune responses with a partial inhibition of the type-1 response, while the type-2 response is relatively over-activated. This immune constellation is associated with the inhibition of the enzyme indoleamine 2,3-dioxygenase (IDO), because type-2 cytokines are potent inhibitors of IDO. Due to the inhibition of IDO, tryptophan is predominantly metabolized by tryptophan 2,3-dioxygenase (TDO), which is located in astrocytes, but not in microglia cells. As indicated by increased levels of S100B, astrocytes are activated in schizophrenia. On the other hand, the kynurenine metabolism in astrocytes is restricted to the dead-end arm of KYN-A production. Accordingly, an increased TDO activity and an accumulation of KYN-A in the CNS of schizophrenics have been described. Thus, the immune-mediated glutamatergic-dopaminergic dysregulation may lead to the clinical symptoms of schizophrenia. Therapeutic consequences, e.g. the use of antiinflammatory cyclooxygenase-2 inhibitors, which also are able to directly decrease KYN-A, are discussed. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 28 | J. Neural Transm. Suppl. 2007 -1 -1: 269-80 |
| PMID | 17982903 |
| Title | The immunological basis of glutamatergic disturbance in schizophrenia: towards an integrated view. |
| Abstract | This overview presents a hypothesis to bridge the gap between psychoneuroimmunological findings and recent results from pharmacological, neurochemical and genetic studies in schizophrenia. In schizophrenia, a glutamatergic hypofunction is discussed to be crucially involved in dopaminergic dysfunction. This view is supported by findings of the neuregulin- and dysbindin genes, which have functional impact on the glutamatergic system. Glutamatergic hypofunction is mediated by NMDA (N-methyl-D-aspartate) receptor antagonism. The only endogenous NMDA receptor antagonist identified up to now is kynurenic acid (KYN-A). KYN-A also blocks the nicotinergic acetycholine receptor, i.e. increased KYN-A levels can explain psychotic symptoms and cognitive deterioration. KYN-A levels are described to be higher in the CSF and in critical CNS regions of schizophrenics. Another line of evidence suggests that of the immune system in schizophrenic patients is characterized by an imbalance between the type-1 and the type-2 immune responses with a partial inhibition of the type-1 response, while the type-2 response is relatively over-activated. This immune constellation is associated with the inhibition of the enzyme indoleamine 2,3-dioxygenase (IDO), because type-2 cytokines are potent inhibitors of IDO. Due to the inhibition of IDO, tryptophan is predominantly metabolized by tryptophan 2,3-dioxygenase (TDO), which is located in astrocytes, but not in microglia cells. As indicated by increased levels of S100B, astrocytes are activated in schizophrenia. On the other hand, the kynurenine metabolism in astrocytes is restricted to the dead-end arm of KYN-A production. Accordingly, an increased TDO activity and an accumulation of KYN-A in the CNS of schizophrenics have been described. Thus, the immune-mediated glutamatergic-dopaminergic dysregulation may lead to the clinical symptoms of schizophrenia. Therapeutic consequences, e.g. the use of antiinflammatory cyclooxygenase-2 inhibitors, which also are able to directly decrease KYN-A, are discussed. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 29 | Mol. Psychiatry 2007 Feb 12: 206-20 |
| PMID | 17033631 |
| Title | Improvement of cognitive functions in chronic schizophrenic patients by recombinant human erythropoietin. |
| Abstract | schizophrenia is increasingly recognized as a neurodevelopmental disease with an additional degenerative component, comprising cognitive decline and loss of cortical gray matter. We hypothesized that a neuroprotective/neurotrophic add-on strategy, recombinant human erythropoietin (rhEPO) in addition to stable antipsychotic medication, may be able to improve cognitive function even in chronic schizophrenic patients. Therefore, we designed a double-blind, placebo-controlled, randomized, multicenter, proof-of-principle (phase II) study. This study had a total duration of 2 years and an individual duration of 12 weeks with an additional safety visit at 16 weeks. Chronic schizophrenic men (N=39) with defined cognitive deficit (>or=1 s.d. below normal in the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)), stable medication and disease state, were treated for 3 months with a weekly short (15 min) intravenous infusion of 40,000 IU rhEPO (N=20) or placebo (N=19). Main outcome measure was schizophrenia-relevant cognitive function at week 12. The neuropsychological test set (RBANS subtests delayed memory, language-semantic fluency, attention and Wisconsin Card Sorting Test (WCST-64) - perseverative errors) was applied over 2 days at baseline, 2 weeks, 4 weeks and 12 weeks of study participation. Both placebo and rhEPO patients improved in all evaluated categories. Patients receiving rhEPO showed a significant improvement over placebo patients in schizophrenia-related cognitive performance (RBANS subtests, WCST-64), but no effects on psychopathology or social functioning. Also, a significant decline in serum levels of S100B, a glial damage marker, occurred upon rhEPO. The fact that rhEPO is the first compound to exert a selective and lasting beneficial effect on cognition should encourage new treatment strategies for schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 30 | Mol. Psychiatry 2007 Feb 12: 206-20 |
| PMID | 17033631 |
| Title | Improvement of cognitive functions in chronic schizophrenic patients by recombinant human erythropoietin. |
| Abstract | schizophrenia is increasingly recognized as a neurodevelopmental disease with an additional degenerative component, comprising cognitive decline and loss of cortical gray matter. We hypothesized that a neuroprotective/neurotrophic add-on strategy, recombinant human erythropoietin (rhEPO) in addition to stable antipsychotic medication, may be able to improve cognitive function even in chronic schizophrenic patients. Therefore, we designed a double-blind, placebo-controlled, randomized, multicenter, proof-of-principle (phase II) study. This study had a total duration of 2 years and an individual duration of 12 weeks with an additional safety visit at 16 weeks. Chronic schizophrenic men (N=39) with defined cognitive deficit (>or=1 s.d. below normal in the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)), stable medication and disease state, were treated for 3 months with a weekly short (15 min) intravenous infusion of 40,000 IU rhEPO (N=20) or placebo (N=19). Main outcome measure was schizophrenia-relevant cognitive function at week 12. The neuropsychological test set (RBANS subtests delayed memory, language-semantic fluency, attention and Wisconsin Card Sorting Test (WCST-64) - perseverative errors) was applied over 2 days at baseline, 2 weeks, 4 weeks and 12 weeks of study participation. Both placebo and rhEPO patients improved in all evaluated categories. Patients receiving rhEPO showed a significant improvement over placebo patients in schizophrenia-related cognitive performance (RBANS subtests, WCST-64), but no effects on psychopathology or social functioning. Also, a significant decline in serum levels of S100B, a glial damage marker, occurred upon rhEPO. The fact that rhEPO is the first compound to exert a selective and lasting beneficial effect on cognition should encourage new treatment strategies for schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 31 | Neurosci. Lett. 2008 Sep 442: 100-3 |
| PMID | 18638525 |
| Title | Distinct regulation of brain-derived neurotrophic factor and noradrenaline in S100B knockout mice. |
| Abstract | The mainly glia-derived protein S100B has been shown to be involved in the pathophysiology of diseases such as neurodegenerative diseases, schizophrenia or depression. These diseases go along with distinct changes of cerebral neurotransmitters and neurotrophic factors. Few and partly inconsistent data exist on the influence of cerebral S100B protein levels on different neurotransmitters. Therefore we investigated levels of serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA), noradrenaline (NA), dopamine (DA), brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the hippocampus, frontal cortex and residual neocortex in S100B knock out (S100B KO) mice compared to wildtype controls. There was a significant increase of hippocampal BDNF (+53%) and a decrease of hippocampal (-12%) and residual neocortical (-15%) NA in 10-month-old S100B KO mice compared to wildtype mice whereas the other mediators investigated did not show genotype-dependent changes. The increased hippocampal BDNF may represent an endogenous attempt to compensate trophic effects of S100B protein especially on serotonergic neurons, which have been shown to be unaffected in S100B KO mice previously. As referred to changes in NA levels functional studies are warranted to elucidate the link between S100B protein and the noradrenergic metabolism. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 32 | Prog. Neuropsychopharmacol. Biol. Psychiatry 2008 Dec 32: 1789-92 |
| PMID | 18718498 |
| Title | Memory impairment correlates with increased S100B serum concentrations in patients with chronic schizophrenia. |
| Abstract | Astrocyte activation indicated by increased S100B is considered a potential pathogenic factor for schizophrenia. To investigate the relationship between astrocyte activation and cognitive performance, S100B serum concentration, memory performance, and psychopathology were assessed in 40 first-episode and 35 chronic schizophrenia patients upon admission and after four weeks of treatment. Chronic schizophrenia patients with high S100B were impaired concerning verbal memory performance (AVLT, Auditory Verbal Learning Test) compared to chronic and first-episode patients with low S100B levels. The findings support the hypothesis that astrocyte activation might contribute to the development of cognitive dysfunction in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 33 | J Psychiatr Res 2008 Aug 42: 868-76 |
| PMID | 18001771 |
| Title | S100B-immunopositive glia is elevated in paranoid as compared to residual schizophrenia: a morphometric study. |
| Abstract | Several studies have revealed increased S100B levels in peripheral blood and cerebrospinal fluid (CSF) of patients with schizophrenia. In this context, it was postulated that elevated levels of S100B may indicate changes of pathophysiological significance to brain tissue in general and astrocytes in particular. However, no histological study has been published on the cellular distribution of S100B in the brain of individuals with schizophrenia to clarify this hypothesis. The cell-density of S100B-immunopositive glia was analyzed in the anterior cingulate, dorsolateral prefrontal (DLPF), orbitofrontal, and superior temporal cortices/adjacent white matter, pyramidal layer/alveus of the hippocampus, and the mediodorsal thalamic nucleus of 18 patients with schizophrenia and 16 matched control subjects. Cortical brain regions contained more S100B-immunopositive glia in the schizophrenia group relative to controls (P=0.046). This effect was caused by the paranoid schizophrenia subgroup (P=0.018). Separate analysis of white matter revealed no diagnostic main group effect (P=0.846). However, the white matter of patients with paranoid schizophrenia contained more (mainly oligodendrocytic) S100B-positive glia as compared to residual schizophrenia (P=0.021). These effects were particularly pronounced in the DLPF brain area. Our study reveals distinct histological patterns of S100B immunoeactive glia in two schizophrenia subtypes. This may be indicative of a heterogenic pathophysiology or distinct compensatory abilities: Astro-/oligodendroglial activation may result in increased cellular S100B in paranoid schizophrenia. On the contrary, residual schizophrenia may be caused by white matter oligodendroglial damage or dysfunction, associated with a release of S100B into body fluids. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 34 | Mol. Psychiatry 2009 Mar 14: 235-7 |
| PMID | 19229202 |
| Title | Elevated serum levels of the glial marker protein S100B are not specific for schizophrenia or mood disorders. |
| Abstract | -1 |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 35 | Gen. Physiol. Biophys. 2009 -1 28 Spec No Focus: F76-81 |
| PMID | 20093730 |
| Title | S100B in schizophrenia: an update. |
| Abstract | Recent research has supported a potential role of immune pathology in the etiopathogenesis of schizophrenic. In the CNS various viruses were identified in the brains of schizophrenic patients. Pro-inflammatory cytokines were found to be associated with the stage of disease. Microglial cells were reported to be activated in a subgroup of schizophrenic patients in post mortem as well as imaging studies. New research has demonstrated that astrocytes together with microglial cells are the major immunocompetent cells of the brain and play an important role in the regulation of neuronal proliferation and differentiation. S100B, a calcium binding astrocyte-specific cytokine, presents a marker of astrocytic activation. Scientific evidence for increased S100B in acute schizophrenia is very consistent. The picture is not as clear regarding schizophrenia subtypes in acute states but patients with persistent negative symptoms or deficit syndrome show constant high S100B concentrations. There is an association between high S100B and poor therapeutic response. The increased S100B concentrations appear to be functionally relevant since they are reflected by poor cognitive performance and cross validation with other methods make it unlikely that the findings are merely an epiphenomenon. These findings suggest that the activation of astrocytes might be an important pathogenic factor for the development of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 36 | Gen. Physiol. Biophys. 2009 -1 28 Spec No Focus: F76-81 |
| PMID | 20093730 |
| Title | S100B in schizophrenia: an update. |
| Abstract | Recent research has supported a potential role of immune pathology in the etiopathogenesis of schizophrenic. In the CNS various viruses were identified in the brains of schizophrenic patients. Pro-inflammatory cytokines were found to be associated with the stage of disease. Microglial cells were reported to be activated in a subgroup of schizophrenic patients in post mortem as well as imaging studies. New research has demonstrated that astrocytes together with microglial cells are the major immunocompetent cells of the brain and play an important role in the regulation of neuronal proliferation and differentiation. S100B, a calcium binding astrocyte-specific cytokine, presents a marker of astrocytic activation. Scientific evidence for increased S100B in acute schizophrenia is very consistent. The picture is not as clear regarding schizophrenia subtypes in acute states but patients with persistent negative symptoms or deficit syndrome show constant high S100B concentrations. There is an association between high S100B and poor therapeutic response. The increased S100B concentrations appear to be functionally relevant since they are reflected by poor cognitive performance and cross validation with other methods make it unlikely that the findings are merely an epiphenomenon. These findings suggest that the activation of astrocytes might be an important pathogenic factor for the development of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 37 | Psychiatry Res 2009 May 167: 66-72 |
| PMID | 19375171 |
| Title | Neuron-specific enolase is unaltered whereas S100B is elevated in serum of patients with schizophrenia--original research and meta-analysis. |
| Abstract | Previous studies reported altered levels of the astrocytic marker S100B in schizophrenia. To clarify mechanisms, we measured weekly serum levels of S100B together with the neuronal marker neuron-specific enolase in 20 patients with schizophrenia and 19 age- and gender-matched control subjects. S100B was elevated at admission and discharge in schizophrenic patients compared with control subjects, whereas there were no significant differences for neuron-specific enolase. Treatment had no impact on either S100B or neuron-specific enolase. A systematic, quantitative meta-analysis of all published studies involving 380 patients and 358 control subjects revealed elevated serum S100B in schizophrenia without any effect of antipsychotic treatment. Results suggest that increases of serum S100B are related to active secretion of S100B by astrocytes in combination with blood-brain barrier dysfunction in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 38 | Psychiatry Res 2009 May 167: 66-72 |
| PMID | 19375171 |
| Title | Neuron-specific enolase is unaltered whereas S100B is elevated in serum of patients with schizophrenia--original research and meta-analysis. |
| Abstract | Previous studies reported altered levels of the astrocytic marker S100B in schizophrenia. To clarify mechanisms, we measured weekly serum levels of S100B together with the neuronal marker neuron-specific enolase in 20 patients with schizophrenia and 19 age- and gender-matched control subjects. S100B was elevated at admission and discharge in schizophrenic patients compared with control subjects, whereas there were no significant differences for neuron-specific enolase. Treatment had no impact on either S100B or neuron-specific enolase. A systematic, quantitative meta-analysis of all published studies involving 380 patients and 358 control subjects revealed elevated serum S100B in schizophrenia without any effect of antipsychotic treatment. Results suggest that increases of serum S100B are related to active secretion of S100B by astrocytes in combination with blood-brain barrier dysfunction in schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 39 | Biol. Psychiatry 2009 Jun 65: 1107-10 |
| PMID | 19103440 |
| Title | A new pathophysiological aspect of S100B in schizophrenia: potential regulation of S100B by its scavenger soluble RAGE. |
| Abstract | Several studies have reported elevated S100B serum levels in schizophrenia. Our study focused on its scavenger, soluble receptor for advanced glycation end products (sRAGE). Given the benefits of sRAGE in metabolic and inflammatory diseases, we hypothesized a similar effect in schizophrenia. S100B and sRAGE concentrations were explored during acute paranoid schizophrenia and during reconvalescence. Serum samples from 26 inpatients were investigated on hospital admission (T0) and 6 weeks posttreatment (T6) by S100B-immunoluminometry and sRAGE-ELISA. Thirty-two matched healthy individuals served as controls. Psychopathology was monitored using the Positive and Negative Syndrome Scale (PANSS). S100B (p = .021) and sRAGE (p = .020) were elevated in schizophrenic patients at T0. S100B levels normalized under antipsychotic treatment (p = .003), whereas sRAGE increased further by T6 (p = .005). Changes of S100B during treatment correlated inversely with DeltasRAGE (r = -.422, p = .032). PANSS was negatively associated with sRAGE at T0 (positive score: r = -.415, p = .035; total score: r = -.395, p = .046). Our results provide support for a reduction of S100B levels during reconvalescence from acute paranoid schizophrenia that is regulated by its scavenger sRAGE. This mechanism could provide novel treatment strategies. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 40 | Biol. Psychiatry 2009 Jun 65: 1107-10 |
| PMID | 19103440 |
| Title | A new pathophysiological aspect of S100B in schizophrenia: potential regulation of S100B by its scavenger soluble RAGE. |
| Abstract | Several studies have reported elevated S100B serum levels in schizophrenia. Our study focused on its scavenger, soluble receptor for advanced glycation end products (sRAGE). Given the benefits of sRAGE in metabolic and inflammatory diseases, we hypothesized a similar effect in schizophrenia. S100B and sRAGE concentrations were explored during acute paranoid schizophrenia and during reconvalescence. Serum samples from 26 inpatients were investigated on hospital admission (T0) and 6 weeks posttreatment (T6) by S100B-immunoluminometry and sRAGE-ELISA. Thirty-two matched healthy individuals served as controls. Psychopathology was monitored using the Positive and Negative Syndrome Scale (PANSS). S100B (p = .021) and sRAGE (p = .020) were elevated in schizophrenic patients at T0. S100B levels normalized under antipsychotic treatment (p = .003), whereas sRAGE increased further by T6 (p = .005). Changes of S100B during treatment correlated inversely with DeltasRAGE (r = -.422, p = .032). PANSS was negatively associated with sRAGE at T0 (positive score: r = -.415, p = .035; total score: r = -.395, p = .046). Our results provide support for a reduction of S100B levels during reconvalescence from acute paranoid schizophrenia that is regulated by its scavenger sRAGE. This mechanism could provide novel treatment strategies. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 41 | Neurosci. Lett. 2009 Sep 462: 113-7 |
| PMID | 19539717 |
| Title | Increased serum S100B levels in chronic schizophrenic patients on long-term clozapine or typical antipsychotics. |
| Abstract | S100B is a calcium-binding protein, mainly produced and secreted by astrocytes, and it mediates the interaction among glial cells and between glial cells and neurons. Recently, several studies have shown increased serum 100B levels in patients with schizophrenia, suggesting that S100B might be relevant to the pathophysiology of schizophrenia. To examine the potentially differential effect of clozapine compared to typical antipsychotics on serum S100B and the relationship between S100B levels and psychopathology in patients with schizophrenia, 63 physically healthy patients with schizophrenia were compared with 50 age-, sex-matched normal controls. The psychopathology of patients was assessed by the Positive and Negative Syndrome Scale (PANSS). Serum S100B levels were measured by sandwich ELISA. The results showed that S100B levels were significantly elevated in chronic patients with schizophrenia than in healthy controls (p<0.0001). As compared with healthy controls, there was a significant increase in S100B levels in patients treated with both clozapine and typical antipsychotics (both p<0.0001). However, no significant difference in S100B was found between patients treated with clozapine and typical antipsychotic subgroups (p>0.05). Furthermore, there was no significant correlation between S100B and standardized drug doses or the duration of taking neuroleptic medications (both p>0.05). In addition, no significant correlation was observed between S100B and PANSS total score and its subscale scores (all >0.05). These findings suggest that serum S100B levels in chronic schizophrenia under antipsychotic medication may be increased, suggesting that a dysfunction of astrocytes and/or oligodendrocytes may play a role in the pathogenesis of schizophrenia. Long term treatment with both typical and atypical antipsychotics may produce similar effects on the S100B serum levels, which however remains to be characterized in a large sample of first-episode, medication-naïve patients with schizophrenia using a longitudinal design. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 42 | Neurosci. Lett. 2009 Sep 462: 113-7 |
| PMID | 19539717 |
| Title | Increased serum S100B levels in chronic schizophrenic patients on long-term clozapine or typical antipsychotics. |
| Abstract | S100B is a calcium-binding protein, mainly produced and secreted by astrocytes, and it mediates the interaction among glial cells and between glial cells and neurons. Recently, several studies have shown increased serum 100B levels in patients with schizophrenia, suggesting that S100B might be relevant to the pathophysiology of schizophrenia. To examine the potentially differential effect of clozapine compared to typical antipsychotics on serum S100B and the relationship between S100B levels and psychopathology in patients with schizophrenia, 63 physically healthy patients with schizophrenia were compared with 50 age-, sex-matched normal controls. The psychopathology of patients was assessed by the Positive and Negative Syndrome Scale (PANSS). Serum S100B levels were measured by sandwich ELISA. The results showed that S100B levels were significantly elevated in chronic patients with schizophrenia than in healthy controls (p<0.0001). As compared with healthy controls, there was a significant increase in S100B levels in patients treated with both clozapine and typical antipsychotics (both p<0.0001). However, no significant difference in S100B was found between patients treated with clozapine and typical antipsychotic subgroups (p>0.05). Furthermore, there was no significant correlation between S100B and standardized drug doses or the duration of taking neuroleptic medications (both p>0.05). In addition, no significant correlation was observed between S100B and PANSS total score and its subscale scores (all >0.05). These findings suggest that serum S100B levels in chronic schizophrenia under antipsychotic medication may be increased, suggesting that a dysfunction of astrocytes and/or oligodendrocytes may play a role in the pathogenesis of schizophrenia. Long term treatment with both typical and atypical antipsychotics may produce similar effects on the S100B serum levels, which however remains to be characterized in a large sample of first-episode, medication-naïve patients with schizophrenia using a longitudinal design. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 43 | Schizophr. Res. 2010 Jun 119: 40 |
| PMID | 20163935 |
| Title | REMOVAL: Elevated serum S100B protein in first-episode drug-naïve Chinese patients with schizophrenia. Retraction. |
| Abstract | -1 |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 44 | Mol. Psychiatry 2010 Jan 15: 3-4 |
| PMID | 20029405 |
| Title | Elevated S100B levels in schizophrenia are associated with insulin resistance. |
| Abstract | -1 |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 45 | Neuroscience 2010 Jun 167: 1025-31 |
| PMID | 20226844 |
| Title | Haloperidol and clozapine decrease S100B release from glial cells. |
| Abstract | Recent meta-analyses showed consistently elevated levels of S100B in serum and cerebrospinal fluid of schizophrenic patients. This finding has been attributed to glial pathology because S100B is produced by astrocytes and oligodendrocytes. However, S100B may be likewise associated with schizophrenia-related disturbances in glial cell as well as adipocyte energy supply and glucose metabolism. The influence of antipsychotic drugs on S100B levels remains unclear, and some studies have suggested that treatment with these drugs may actually contribute to the elevated S100B levels observed in schizophrenic patients. In this study, we explored the effects of the typical antipsychotic haloperidol and the atypical prototype drug clozapine on the release of S100B by astrocytic C6 cells and oligodendrocytic OLN-93 cells. Because of the association between schizophrenia and disturbances in energy metabolism, we assessed the effects of these drugs under basal condition (BC) compared to serum and glucose deprivation (SGD). We found that treatment of C6 and OLN-93 cells with haloperidol and clozapine reduced the release of S100B from C6 and OLN-93 cells under BC and SGD in vitro at a tissue concentration corresponding to the assumed therapeutic dose range of these drugs. These data suggest that elevated levels of S100B in bodily fluids of schizophrenic patients are normalized rather than increased by the effects of antipsychotic drugs on glial cells. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 46 | Neuroscience 2010 Jun 167: 1025-31 |
| PMID | 20226844 |
| Title | Haloperidol and clozapine decrease S100B release from glial cells. |
| Abstract | Recent meta-analyses showed consistently elevated levels of S100B in serum and cerebrospinal fluid of schizophrenic patients. This finding has been attributed to glial pathology because S100B is produced by astrocytes and oligodendrocytes. However, S100B may be likewise associated with schizophrenia-related disturbances in glial cell as well as adipocyte energy supply and glucose metabolism. The influence of antipsychotic drugs on S100B levels remains unclear, and some studies have suggested that treatment with these drugs may actually contribute to the elevated S100B levels observed in schizophrenic patients. In this study, we explored the effects of the typical antipsychotic haloperidol and the atypical prototype drug clozapine on the release of S100B by astrocytic C6 cells and oligodendrocytic OLN-93 cells. Because of the association between schizophrenia and disturbances in energy metabolism, we assessed the effects of these drugs under basal condition (BC) compared to serum and glucose deprivation (SGD). We found that treatment of C6 and OLN-93 cells with haloperidol and clozapine reduced the release of S100B from C6 and OLN-93 cells under BC and SGD in vitro at a tissue concentration corresponding to the assumed therapeutic dose range of these drugs. These data suggest that elevated levels of S100B in bodily fluids of schizophrenic patients are normalized rather than increased by the effects of antipsychotic drugs on glial cells. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 47 | J Psychiatr Res 2010 Oct 44: 971-8 |
| PMID | 20398908 |
| Title | Comprehensive copy number variant (CNV) analysis of neuronal pathways genes in psychiatric disorders identifies rare variants within patients. |
| Abstract | Copy number variations (CNV) have become an important source of human genome variability noteworthy to consider when studying genetic susceptibility to complex diseases. As recent studies have found evidences for the potential involvement of CNVs in psychiatric disorders, we have studied the dosage effect of structural genome variants as a possible susceptibility factor for different psychiatric disorders in a candidate gene approach. After selection of 68 psychiatric disorders' candidate genes overlapping with CNVs, MLPA assays were designed to determine changes in copy number of these genes. The studied sample consisted of 724 patients with psychiatric disorders (accounting for anxiety disorders, mood disorders, eating disorders and schizophrenia) and 341 control individuals. CNVs were detected in 30 out of the 68 genes screened, indicating that a considerable proportion of neuronal pathways genes contain CNVs. When testing the overall burden of rare structural genomic variants in the different psychiatric disorders compared to control individuals, there was no statistically significant difference in the total amount of gains and losses. However, 14 out of the 30 changes were only found in psychiatric disorder patients but not in control individuals. These genes include GRM7, previously associated to major depression disorder and bipolar disorder, SLC6A13, in anxiety disorders, and S100B, SSTR5 and COMT in schizophrenia. Although we have not been able to found a clear association between the studied CNVs and psychiatric disorders, the rare variants found only within the patients could account for a step further towards understanding the pathophysiology of psychiatric disorders. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 48 | Am. J. Med. Genet. B Neuropsychiatr. Genet. 2010 Jan 153B: 291-7 |
| PMID | 19330775 |
| Title | Risk variants in the S100B gene predict elevated S100B serum concentrations in healthy individuals. |
| Abstract | Several lines of evidence suggest an important role of the S100B protein and its coding gene in different neuropathological and psychiatric disorders like dementia, bipolar affective disorders and schizophrenia. To clarify whether a direct link exists between gene and gene product, that is, whether S100B variants directly modulate S100B serum concentration, 196 healthy individuals were assessed for S100B serum concentrations and genotyped for five potentially functional S100B SNPs. Functional variants of the serotonergic genes 5-HT1A and 5-HTT possibly modulating S100B serum levels were also studied. Further, publicly available human postmortem gene expression data were re-analyzed to elucidate the impact of S100B, 5-HT1A and 5-HTT SNPs on frontal cortex S100B mRNA expression. Several S100B SNPs, particularly rs9722, and the S100B haplotype T-G-G-A (including rs2186358-rs11542311-rs2300403-rs9722) were associated with elevated S100B serum concentrations (Bonferroni corrected P < 0.05). Of these, rs11542311 was also associated with S100B mRNA expression directly (Bonferroni corrected P = 0.05) and within haplotype G-A-T-C (rs11542311-rs2839356-rs9984765-rs881827; P = 0.004), again with the G-allele increasing S100B expression. Our results suggest an important role of S100B SNPs on S100B serum concentrations and S100B mRNA expression. It hereby links recent evidence for both, the impact of S100B gene variation on various neurological or psychiatric disorders like dementia, bipolar affective disorders and schizophrenia and the strong relation between S100B serum levels and these disorders. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 49 | Psychiatry (Edgmont) 2010 Dec 7: 20-3 |
| PMID | 21274392 |
| Title | The blood brain barrier and the role of ratiometric molecular analysis in schizophrenia. |
| Abstract | The etiology of schizophrenia and other chronic psychotic disorders is complicated considering the multifactorial contribution of developmental, biological, and environmental factors. The role of the blood brain barrier has not yet been established as part of schizophrenia etiology; however, in previous blood brain barrier articles, we discussed potential consequences of various biological abnormalities due to dysregulation of molecular components, such as cofactors,(1) signaling molecules,(2) enzymes,(3) cytokines,(4) and antibodies.(5) In this review, we will discuss the potential use of peripheral ratiometric molecular analysis relevant to the central nervous system for the evaluation of the development of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 50 | Cardiovasc Psychiatry Neurol 2010 -1 2010: 480707 |
| PMID | 20631894 |
| Title | S100B Serum Levels in Schizophrenia Are Presumably Related to Visceral Obesity and Insulin Resistance. |
| Abstract | Elevated blood levels of S100B in schizophrenia have so far been mainly attributed to glial pathology, as S100B is produced by astro- and oligodendroglial cells and is thought to act as a neurotrophic factor with effects on synaptogenesis, dopaminergic and glutamatergic neutrotransmission. However, adipocytes are another important source of S100B since the concentration of S100B in adipose tissue is as high as in nervous tissue. Insulin is downregulating S100B in adipocytes, astrocyte cultures and rat brain. As reviewed in this paper, our recent studies suggest that overweight, visceral obesity, and peripheral/cerebral insulin resistance may be pivotal for at least part of the elevated S100B serum levels in schizophrenia. In the context of this recently identified framework of metabolic disturbances accompanying S100B elevation in schizophrenia, it rather has to be attributed to systemic alterations in glucose metabolism than to be considered a surrogate marker for astrocyte-specific pathologies. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 51 | PLoS ONE 2010 -1 5: e11089 |
| PMID | 20559426 |
| Title | Serum S100B: a potential biomarker for suicidality in adolescents? |
| Abstract | Studies have shown that patients suffering from depression or schizophrenia often have immunological alterations that can be detected in the blood. Others reported a possible link between inflammation, a microgliosis and the blood-brain barrier (BBB) in suicidal patients. Serum S100B is a marker of BBB function commonly used to study cerebrovascular wall function. We measured levels of S100B in serum of 40 adolescents with acute psychosis, 24 adolescents with mood disorders and 20 healthy controls. Patients were diagnosed according to DSM-IV TR criteria. We evaluated suicidal ideation using the suicidality subscale of the Brief Psychiatric Rating Scale for Children (BPRS-C). Serum S100B levels were significantly higher (p<0.05) and correlated to severity of suicidal ideation in patients with psychosis or mood disorders, independent of psychiatric diagnosis. Patients with a BPRS-C suicidality subscores of 1-4 (low suicidality) had mean serum S100B values +/- SEM of 0.152+/-0.020 ng/mL (n = 34) compared to those with BPRS-C suicidality subscores of 5-7 (high suicidality) with a mean of 0.354+/-0.044 ng/mL (n = 30). This difference was statistically significant (p<0.05). Our data support the use of S100B as an adjunctive biomarker to assess suicidal risk in patients with mood disorders or schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 52 | J Psychiatr Res 2010 Dec 44: 1236-40 |
| PMID | 20510426 |
| Title | Increased serum S100B in never-medicated and medicated schizophrenic patients. |
| Abstract | S100B is a calcium-binding protein, which is produced primarily by glial cells. It modulates the proliferation and differentiation of neurons and glia by affecting protective and apoptotic mechanisms. Recently, several studies have shown increased serum S100B levels in patients with schizophrenia, suggesting that S100B might be relevant to the pathophysiology of schizophrenia. S100B levels were assessed using ELISA in the serum of 80 never-medicated early-stage and 82 medicated chronic schizophrenia patients and 97 healthy controls subjects. The psychopathology of schizophrenia was assessed by the Positive and Negative Syndrome Scale (PANSS). Our results showed significantly increased serum S100B levels in both never-medicated and medicated patients compared to normal controls (both p<0.0001). S100B in never-medicated patients was also markedly increased, compared with medicated patients (p<0.0001). S100B changes observed were irrespective of neuroleptic medication, gender, age, and smoking. Increased S100B levels in the early stage of schizophrenia suggest that glial cell activation or structural damage may be part of a neurodegenerative process in schizophrenia. The lower S100B levels in chronic than early-stage patients further suggest that antipsychotic treatment may reduce this neurodegeneration. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 53 | J Psychiatr Res 2010 Dec 44: 1236-40 |
| PMID | 20510426 |
| Title | Increased serum S100B in never-medicated and medicated schizophrenic patients. |
| Abstract | S100B is a calcium-binding protein, which is produced primarily by glial cells. It modulates the proliferation and differentiation of neurons and glia by affecting protective and apoptotic mechanisms. Recently, several studies have shown increased serum S100B levels in patients with schizophrenia, suggesting that S100B might be relevant to the pathophysiology of schizophrenia. S100B levels were assessed using ELISA in the serum of 80 never-medicated early-stage and 82 medicated chronic schizophrenia patients and 97 healthy controls subjects. The psychopathology of schizophrenia was assessed by the Positive and Negative Syndrome Scale (PANSS). Our results showed significantly increased serum S100B levels in both never-medicated and medicated patients compared to normal controls (both p<0.0001). S100B in never-medicated patients was also markedly increased, compared with medicated patients (p<0.0001). S100B changes observed were irrespective of neuroleptic medication, gender, age, and smoking. Increased S100B levels in the early stage of schizophrenia suggest that glial cell activation or structural damage may be part of a neurodegenerative process in schizophrenia. The lower S100B levels in chronic than early-stage patients further suggest that antipsychotic treatment may reduce this neurodegeneration. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 54 | J Psychiatr Res 2010 May 44: 429-33 |
| PMID | 19932492 |
| Title | Increased S100B serum levels in schizophrenic patients with tardive dyskinesia: association with dyskinetic movements. |
| Abstract | Several studies show that calcium-binding protein S100B is increased in schizophrenia and may be involved in the pathogenesis of tardive dyskinesia (TD). We therefore compared serum S100B levels in normal controls (n=60), schizophrenic patients with (n=32) and without TD (n=50). Assessments included the abnormal involuntary movement scale (AIMS) and the positive and negative syndrome scale (PANSS). Serum S100B levels were measured by enzyme-linked immunosorbent assay (ELISA). The results indicated that patients with TD had higher serum S100B levels than normals and those without TD. Serum S100B levels were positively correlated with AIMS scores in patients with TD. These data suggest that increased S100B levels may be related to neuro-degeneration, associated with TD pathophysiology. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 55 | J Psychiatr Res 2010 May 44: 429-33 |
| PMID | 19932492 |
| Title | Increased S100B serum levels in schizophrenic patients with tardive dyskinesia: association with dyskinetic movements. |
| Abstract | Several studies show that calcium-binding protein S100B is increased in schizophrenia and may be involved in the pathogenesis of tardive dyskinesia (TD). We therefore compared serum S100B levels in normal controls (n=60), schizophrenic patients with (n=32) and without TD (n=50). Assessments included the abnormal involuntary movement scale (AIMS) and the positive and negative syndrome scale (PANSS). Serum S100B levels were measured by enzyme-linked immunosorbent assay (ELISA). The results indicated that patients with TD had higher serum S100B levels than normals and those without TD. Serum S100B levels were positively correlated with AIMS scores in patients with TD. These data suggest that increased S100B levels may be related to neuro-degeneration, associated with TD pathophysiology. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 56 | Prog. Neuropsychopharmacol. Biol. Psychiatry 2011 Jul 35: 1291-6 |
| PMID | 21513766 |
| Title | In vitro S100B secretion is reduced by apomorphine: effects of antipsychotics and antioxidants. |
| Abstract | Astrocytes express dopamine receptors and respond to dopamine stimulation. However, the role of astrocytes in psychiatric disorders and the effects of antipsychotics on astroglial cells have only been investigated recently. S100B is a glial-derived protein, commonly used as a marker of astroglial activation in psychiatric disorders, particularly schizophrenia. We investigated S100B secretion in three different rat brain preparations (fresh hippocampal slices, C6 glioma cells and primary astrocyte cultures) exposed to apomorphine and antipsychotics (haloperidol and risperidone), aiming to evaluate, ex vivo and in vitro, whether dopamine activation and dopaminergic antagonists modulate astroglial activation, as measured by changes in the extracellular levels of S100B. The serum S100B elevation observed in schizophrenic patients is not reflected by the in vitro decrease of S100B secretion that we observed in hippocampal slices, cortical astrocytes and C6 glioma cells treated with apomorphine, which mimics dopaminergic hyperactivation. This decrease in S100B secretion can be explained by a stimulation of D2 receptors negatively coupled to adenyl cyclase. Antipsychotic medications and antioxidant supplementation were able to prevent the decline in S100B secretion. Findings reinforce the benefits of antioxidant therapy in psychiatric disorders. Based on our results, in hippocampal slices exposed to apomorphine, it may be suggested that antipsychotics could help to normalize S100B secretion by astrocytes. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 57 | Prog. Neuropsychopharmacol. Biol. Psychiatry 2011 Jul 35: 1291-6 |
| PMID | 21513766 |
| Title | In vitro S100B secretion is reduced by apomorphine: effects of antipsychotics and antioxidants. |
| Abstract | Astrocytes express dopamine receptors and respond to dopamine stimulation. However, the role of astrocytes in psychiatric disorders and the effects of antipsychotics on astroglial cells have only been investigated recently. S100B is a glial-derived protein, commonly used as a marker of astroglial activation in psychiatric disorders, particularly schizophrenia. We investigated S100B secretion in three different rat brain preparations (fresh hippocampal slices, C6 glioma cells and primary astrocyte cultures) exposed to apomorphine and antipsychotics (haloperidol and risperidone), aiming to evaluate, ex vivo and in vitro, whether dopamine activation and dopaminergic antagonists modulate astroglial activation, as measured by changes in the extracellular levels of S100B. The serum S100B elevation observed in schizophrenic patients is not reflected by the in vitro decrease of S100B secretion that we observed in hippocampal slices, cortical astrocytes and C6 glioma cells treated with apomorphine, which mimics dopaminergic hyperactivation. This decrease in S100B secretion can be explained by a stimulation of D2 receptors negatively coupled to adenyl cyclase. Antipsychotic medications and antioxidant supplementation were able to prevent the decline in S100B secretion. Findings reinforce the benefits of antioxidant therapy in psychiatric disorders. Based on our results, in hippocampal slices exposed to apomorphine, it may be suggested that antipsychotics could help to normalize S100B secretion by astrocytes. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 58 | Behav. Brain Res. 2011 Mar 217: 363-8 |
| PMID | 21070816 |
| Title | Risk variants in the S100B gene, associated with elevated S100B levels, are also associated with visuospatial disability of schizophrenia. |
| Abstract | Rs9722 and rs1051169 have been reported as affecting the levels of S100B in the serum or the brain, and haplotypes containing these two SNPs have been associated with schizophrenia. The current study investigated the role of the S100B gene in an endophenotype of schizophrenia-spatial disability. 304 schizophrenia patients and 196 healthy controls were given a block design task and a mental rotation task. Results showed that the two aforementioned SNPs and related haplotypes were associated with the spatial disability of schizophrenia patients. Specifically, risk factors for the elevated S100B levels, including the A allele of rs9722, the G allele of rs1051169, and the AG haplotype, were associated with a poorer performance on both tests of spatial ability, especially the mental rotation task. These results implicate a role for S100B gene polymorphisms in the cognitive functions of schizophrenia patients and encourage further investigation into spatial disability as an endophenotype of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 59 | Am. J. Med. Genet. B Neuropsychiatr. Genet. 2011 Sep 156B: 691-9 |
| PMID | 21714070 |
| Title | Functional assessment of a promoter polymorphism in S100B, a putative risk variant for bipolar disorder. |
| Abstract | Calcium-binding protein S100B has been implicated in the pathology of bipolar affective disorder (BPAD) and schizophrenia (SZ). S100B protein levels are elevated in serum of patients with both disorders compared to controls. We previously reported genetic association of a SNP in the promoter of S100B, rs3788266, with a psychotic form of BPAD. To test for genotypic effects of rs3788266 in vivo, S100B serum protein levels were measured in 350 Irish and German subjects of known S100B genotype. The functional effect of rs3788266 on S100B promoter activity was studied using the luciferase reporter system in U373MG glioblastoma and SH-SY5Y neuroblastoma cell lines. Allelic effects of rs3788266 on protein complex formation at the S100B promoter were investigated by an electrophoretic mobility shift assay. Higher mean serum S100B levels were associated with the risk G allele of rs3788266 in BPAD cases (P = 0.0001), unaffected relatives of BPAD cases (P < 0.0001) and unrelated controls (P < 0.0001). Consistent with the in vivo findings, luciferase gene expression was significantly increased in the presence of the G allele compared to the A allele in SH-SY5Y (P = <0.0001), and in U373MG (P = <0.0008) cell lines. The binding affinity of both SH-SY5Y and U373MG protein complexes for the S100B promoter was significantly stronger in the presence of G allele compared to the A allele promoter fragments. These data support rs3788266 as a functional promoter variant in the S100B gene where the presence of the G allele promotes increased gene expression and is associated with increased serum levels of the protein. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 60 | Clin. Chem. Lab. Med. 2011 Mar 49: 409-24 |
| PMID | 21303299 |
| Title | S100B protein in neurodegenerative disorders. |
| Abstract | "Classic" neurodegenerative disorders, such as Alzheimer's disease and amyotrophic lateral sclerosis share common pathophysiological features and involve progressive loss of specific neuronal populations, axonal or synaptic loss and dysfunction, reactive astrogliosis, and reduction in myelin. Furthermore, despite the absence of astrogliosis, impaired expression of astrocyte- and oligodendrocyte-related genes has been observed in patients with major psychiatric disorders, including schizophrenia and mood disorders. Because S100B is expressed in astrocytes and oligodendrocytes, its concentration in cerebrospinal fluid (CSF) or serum has been considered a suitable surrogate marker for the diagnostic or prognostic assessment of neurodegeneration. This review summarizes previous postmortem, CSF and serum studies regarding the role of S100B in this context. A general drawback is that only small single-center studies have been performed. Many potential confounding factors exist because of the wide extra-astrocytic and extracerebral expression of S100B. Due to lack of disease specificity, reliance on S100B concentrations for differential diagnostic purposes in cases of suspected neurodegenerative disorders is not recommended. Moreover, there is no consistent evidence for a correlation between disease severity and concentrations of S100B in CSF or serum. Therefore, S100B has limited usefulness for monitoring disease progression. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 61 | Psychoneuroendocrinology 2011 Jul 36: 919-23 |
| PMID | 21112154 |
| Title | Genetic variability within the S100B gene influences the personality trait self-directedness. |
| Abstract | Elevated serum levels of S100B have proven useful as an indicator of brain-injury but have also been shown in patients diagnosed with psychiatric disorders. Recently, associations were found between variations in the S100B gene and schizophrenia as well as bipolar affective disorder. The aim of the present study was to investigate whether some of these genetic variations influence general aspects of human behaviour as portrayed by normal dimensions of personality. Two single nucleotide polymorphisms within the S100B gene, 2757C>G and 5748C>T, were genotyped in two population based cohorts consisting of 42-year-old women (n=270) and 51-year-old men (n=247), respectively. The two polymorphisms were analysed with respect to personality traits assessed using the Temperament and Character Inventory (TCI). In men, the 2757C>G polymorphism was found to significantly influence the TCI dimension self-directedness with higher scores in 2757G homozygotes. A similar tendency towards association was seen in the female cohort; however, this correlation did not remain significant after correction for multiple comparisons. Furthermore, the 5748C>T polymorphism was highly associated with self-directedness in men. Self-directedness is an overall estimate of adaptive strategies to adjust behaviour to conceptual goals as well as coping strategies and is strongly correlated to general mental health and absence of personality disorder. These preliminary findings suggest that the S100B gene may be implicated not only in certain pathological brain conditions but also in processes involved in normal behaviour. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 62 | Schizophr. Res. 2012 Jan 134: 89-94 |
| PMID | 22019077 |
| Title | S100B gene polymorphisms predict prefrontal spatial function in both schizophrenia patients and healthy individuals. |
| Abstract | Animal studies have strongly implicated a role of S100B in spatial ability and our recent study of humans found that S100B gene polymorphisms (rs9722, rs1051169, and rs2839357) were associated with schizophrenia patients' spatial ability (as assessed by a block design task and a mental rotation task). In this study, we explored the associations between these and three additional SNPs in S100B and prefrontal functions (working memory and executive control) among 434 schizophrenia patients and 412 healthy controls. Results showed that, for both schizophrenia patients and healthy controls, two SNPs were significantly associated with prefrontal functions in the spatial domain (P value threshold was set at 0.014 after correcting for multiple comparisons), with the AA genotype of rs9722 and the GG genotype of rs2839357 linked to poorer performance. No SNP was associated with prefontal functions in the verbal domain (all Ps >0.05). These results extend our previous study and further confirm the important roles of the S100B gene in spatial abilities. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 63 | Neurochem. Int. 2012 Dec 61: 1144-50 |
| PMID | 22940693 |
| Title | Effects of the putative antipsychotic alstonine on glutamate uptake in acute hippocampal slices. |
| Abstract | A dysfunctional glutamatergic system is thought to be central to the negative symptoms and cognitive deficits recognized as determinant to the poor quality of life of people with schizophrenia. Modulating glutamate uptake has, thus, been suggested as a novel target for antipsychotics. Alstonine is an indole alkaloid sharing with atypical antipsychotics the profile in animal models relevant to schizophrenia, though divergent in its mechanism of action. The aim of this study was to evaluate the effects of alstonine on glutamate uptake. Additionally, the effects on glutathione content and extracellular S100B levels were assessed. Acute hippocampal slices were incubated with haloperidol (10?M), clozapine (10 and 100?M) or alstonine (1-100?M), alone or in combination with apomorphine (100?M), and 5-HT(2) receptor antagonists (0.01?M altanserin and 0.1?M SB 242084). A reduction in glutamate uptake was observed with alstonine and clozapine, but not haloperidol. Apomorphine abolished the effect of clozapine, whereas 5-HT(2A) and 5-HT(2C) antagonists abolished the effects of alstonine. Increased levels of glutathione were observed only with alstonine, also the only compound that failed to decrease the release of S100B. This study shows that alstonine decreases glutamate uptake, which may be beneficial to the glutamatergic deficit observed in schizophrenia. Noteworthily, the decrease in glutamate uptake is compatible with the reversal of MK-801-induced social interaction and working memory deficits. An additional potential benefit of alstonine as an antipsychotic is its ability to increase glutathione, a key cellular antioxidant reported to be decreased in the brain of patients with schizophrenia. Adding to the characterization of the novel mechanism of action of alstonine, the lack of effect of apomorphine in alstonine-induced changes in glutamate uptake reinforces that D(2) receptors are not primarily implicated. Though clearly mediated by 5-HT(2A) and 5-HT(2C) serotonin receptors, the precise mechanisms that result in the effects of alstonine on glutamate uptake warrant elucidation. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 64 | PLoS ONE 2012 -1 7: e43284 |
| PMID | 22916238 |
| Title | Validating serum S100B and neuron-specific enolase as biomarkers for the human brain - a combined serum, gene expression and MRI study. |
| Abstract | Former studies have investigated the potential of serum biomarkers for diseases affecting the human brain. In particular the glial protein S100B, a neuro- and gliotrophin inducing plasticity, seems to be involved in the pathogenesis and treatment of psychiatric diseases such as major depression and schizophrenia. Neuron-specific enolase (NSE) is a specific serum marker for neuronal damage. However, the specificity of these biomarkers for cell type and brain region has not been investigated in vivo until now. We acquired two magnetic resonance imaging parameters sensitive to changes in gray and white matter (T(1)-weighted/diffusion tensor imaging) and obtained serum S100B and NSE levels of 41 healthy subjects. Additionally, we analyzed whole brain gene expressions of S100B in another male cohort of three subjects using the Allen Brain Atlas. Furthermore, a female post mortal brain was investigated using double immunofluorescence labelling with oligodendrocyte markers. We show that S100B is specifically related to white matter structures, namely the corpus callosum, anterior forceps and superior longitudinal fasciculus in female subjects. This effect was observed in fractional anisotropy and radial diffusivity - the latest an indicator of myelin changes. Histological data confirmed a co-localization of S100B with oligodendrocyte markers in the human corpus callosum. S100B was most abundantly expressed in the corpus callosum according to the whole genome Allen Human Brain Atlas. In addition, NSE was related to gray matter structures, namely the amygdala. This effect was detected across sexes. Our data demonstrates a very high S100B expression in white matter tracts, in particular in human corpus callosum. Our study is the first in vivo study validating the specificity of the glial marker S100B for the human brain, and supporting the assumption that radial diffusivity represents a myelin marker. Our results open a new perspective for future studies investigating major neuropsychiatric disorders. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 65 | Brain Behav. Immun. 2012 May 26: 564-7 |
| PMID | 22326439 |
| Title | Increased S100B+ NK cell counts in acutely ill schizophrenia patients are correlated with the free cortisol index, but not with S100B serum levels. |
| Abstract | Several studies have provided evidence for increased S100B serum concentrations in schizophrenia. The pathophysiological significance of this finding is still uncertain because S100B is involved in many cellular mechanisms and is not astrocyte-specific as was previously assumed. S100B is also expressed by subsets of CD3+ CD8+ T cells and natural killer (NK) cells and may therefore be linked to the immune hypothesis of schizophrenia. We have quantified S100B+ CD3+ CD8+ T cells and NK cells by flow cytometry in the peripheral blood of 26 acutely ill schizophrenia cases and 32 matched controls. In parallel, S100B concentrations and the free cortisol index (FCI), a surrogate marker for stress axis activity, were determined in serum samples from the same blood draw. Psychopathology was monitored using the Positive and Negative Syndrome Scale (PANSS). The patient group had increased S100B+ NK cell counts (P=0.045), which correlated with the FCI (r=0.299, P=0.026) but not with the PANSS or the elevated (P=0.021) S100B serum concentrations. S100B+ CD3+ CD8+ T cell counts were not significantly changed in the patient group and did neither correlate with the FCI and PANSS, nor with S100B serum concentrations. In conclusion, despite the observation of an increase in S100B+ NK cells in schizophrenia patients, the lack of a correlation with serum S100B concentrations suggests that these cells are probably not a major source of S100B in the blood of schizophrenia patients. Notably, elevated S100B+ NK cell counts may be linked with stress axis activation. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 66 | J Psychiatry Neurosci 2012 Feb 37: 122-8 |
| PMID | 22146151 |
| Title | Is the Gly82Ser polymorphism in the RAGE gene relevant to schizophrenia and the personality trait psychoticism? |
| Abstract | The receptor for advanced glycation end products (RAGE) is the main receptor for S100B, an astrogial proinflammatory mediator that has been suggested to be involved in the pathophysiology of schizophrenia. To further elucidate the possible relevance of inflammation for mental functions, we investigated a functional polymorphism in the gene coding for RAGE in relation to personality traits and susceptibility to schizophrenia. We studied the Gly82Ser polymorphism (rs2070600, 244G>A) in 2 population-based cohorts of middle-aged participants assessed using the Karolinska Scales of Personality. In addition, we compared genotype frequencies between patients with schizophrenia and controls. The population-based cohorts included 270 women and 247 men, and the case-control study involved 138 patients with schizophrenia and 258 controls. In the population-based cohorts, 82Ser carriers were found to have significantly higher scores for the psychoticism personality trait comprising the detachment and suspicion subscales. The case-control study revealed that the 82Ser allele was significantly more frequent among patients than controls. This study was limited by the modest sample size and the use of a self-report measure to assess personality traits. Our findings suggest that the proven relation between certain personality traits and schizophrenia can at least to some extent be explained on a genetic level. Also, the activated S100B-RAGE axis may be an underlying cause, not only a consequence, of the disease. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 67 | Prog. Neuropsychopharmacol. Biol. Psychiatry 2013 Jun 43: 14-22 |
| PMID | 23246638 |
| Title | Interleukin-6-induced S100B secretion is inhibited by haloperidol and risperidone. |
| Abstract | Although inflammation may be a physiological defense process, imbalanced neuroinflammation has been associated with the pathophysiology of brain disorders, including major depression and schizophrenia. Activated glia releases a variety of pro-inflammatory cytokines that contribute to neuronal dysfunction. Elevated levels of S100B, a glia derived protein, have been observed in the serum and CSF of schizophrenic patients suggesting a glial role in the disease. We evaluated whether S100B secretion (in C6 glioma cells and hippocampal slices in Wistar rats) could be directly modulated by the main inflammatory cytokines (IL-1?, TNF-?, IL-6 and IL-8) altered in schizophrenia, as well as the possible involvement of mitogen-activated protein kinase (MAPK) pathways in these responses. We also investigated the effects of typical and atypical antipsychotic drugs on glial cytokine-induced S100B release. Our results suggest that S100B secretion is increased by pro-inflammatory cytokines via MAPK and that oxidative stress may be a component of this modulation. These results reinforce the idea that the S100B protein is involved in the inflammatory response observed in many brain diseases, including schizophrenia. Moreover the antipsychotics, haloperidol and risperidone, were able to inhibit the secretion of S100B following IL-6 stimulation in C6 glioma cells. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 68 | Prog. Neuropsychopharmacol. Biol. Psychiatry 2013 Jun 43: 14-22 |
| PMID | 23246638 |
| Title | Interleukin-6-induced S100B secretion is inhibited by haloperidol and risperidone. |
| Abstract | Although inflammation may be a physiological defense process, imbalanced neuroinflammation has been associated with the pathophysiology of brain disorders, including major depression and schizophrenia. Activated glia releases a variety of pro-inflammatory cytokines that contribute to neuronal dysfunction. Elevated levels of S100B, a glia derived protein, have been observed in the serum and CSF of schizophrenic patients suggesting a glial role in the disease. We evaluated whether S100B secretion (in C6 glioma cells and hippocampal slices in Wistar rats) could be directly modulated by the main inflammatory cytokines (IL-1?, TNF-?, IL-6 and IL-8) altered in schizophrenia, as well as the possible involvement of mitogen-activated protein kinase (MAPK) pathways in these responses. We also investigated the effects of typical and atypical antipsychotic drugs on glial cytokine-induced S100B release. Our results suggest that S100B secretion is increased by pro-inflammatory cytokines via MAPK and that oxidative stress may be a component of this modulation. These results reinforce the idea that the S100B protein is involved in the inflammatory response observed in many brain diseases, including schizophrenia. Moreover the antipsychotics, haloperidol and risperidone, were able to inhibit the secretion of S100B following IL-6 stimulation in C6 glioma cells. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 69 | BMC Psychiatry 2013 -1 13: 146 |
| PMID | 23705829 |
| Title | Levels of S100B are raised in female patients with schizophrenia. |
| Abstract | The neurotrophic factor, S100B, is released primarily from astrocytes, with serum and CSF levels of S100B reported as altered in schizophrenia. However, many of these reports are contradictory. Here, serum levels of S100B in schizophrenia and influence of age, gender, medication and illness severity were examined. Serum S100B levels were measured in patients with schizophrenia treated with clozapine. Lifestyle, metabolic and illness severity parameters were correlated with S100B concentrations. Data showed raised serum levels of S100B in schizophrenia female patients, but not male patients, compared to controls. Correlation analysis demonstrated a positive association between S100B serum concentrations and BMI. This study supports previous findings that adipocytes may contribute to S100B serum concentrations in females, in addition to astrocytes. This study also supports the hypothesis that metabolic effects of medication, lifestyle choices and the illness itself, may be contributing factors to altered levels of S100B. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 70 | Psychiatry Clin. Neurosci. 2013 Feb 67: 67-75 |
| PMID | 23438158 |
| Title | S100B and schizophrenia. |
| Abstract | The research for peripheral biological markers of schizophrenia, although abundant, has been unfruitful. In the last 2 decades, the S100B protein has made its own room in this area of research. S100B is a calcium-binding protein that has been proposed as a marker of astrocyte activation and brain dysfunction. Research results on S100B concentrations and schizophrenia clinical diagnosis are very consistent; patients with schizophrenia have higher S100B concentrations than healthy controls. The results regarding schizophrenia subtypes and clinical characteristics are not as conclusive. Age of patients, body mass index, illness duration and age at onset have been found to show no correlation, a positive correlation or a negative correlation with S100B levels. With respect to psychopathology, S100B data are inconclusive. Positive, negative and absence of correlation between S100B concentrations and positive and negative psychopathology have been reported. Methodological biases, such as day/night and seasonal variations, the use of anticoagulants to treat biological samples, the type of analytical technique to measure S100B and the different psychopathological scales to measure schizophrenia symptoms, are some of the factors that should be taken into account when researching into this area in order to reduce the variability of the reported results. The clinical implications of S100B changes in schizophrenia remain to be elucidated. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 71 | PLoS ONE 2013 -1 8: e82535 |
| PMID | 24358202 |
| Title | Replicated evidence of absence of association between serum S100B and (risk of) psychotic disorder. |
| Abstract | S100B is a potential marker of neurological and psychiatric illness. In schizophrenia, increased S100B levels, as well as associations with acute positive and persisting negative symptoms, have been reported. It remains unclear whether S100B elevation, which possibly reflects glial dysfunction, is the consequence of disease or compensatory processes, or whether it is an indicator of familial risk. Serum samples were acquired from two large independent family samples (n = 348 and n = 254) in the Netherlands comprising patients with psychotic disorder (n = 140 and n = 82), non-psychotic siblings of patients with psychotic disorder (n = 125 and n = 94) and controls (n = 83 and n = 78). S100B was analyzed with a Liaison automated chemiluminescence system. Associations between familial risk of psychotic disorder and S100B were examined. Results showed that S100B levels in patients (P) and siblings (S) were not significantly different from controls (C) (dataset 1: P vs. C: B = 0.004, 95% CI -0.005 to 0.013, p = 0.351; S vs. C: B = 0.000, 95% CI -0.009 to 0.008, p = 0.926; and dataset 2: P vs. C: B = 0.008, 95% CI -0.011 to 0.028, p = 0.410; S vs. C: B = 0.002, 95% CI -0.016 to 0.021, p = 0.797). In patients, negative symptoms were positively associated with S100B (B = 0.001, 95% CI 0.000 to 0.002, p = 0.005) in one of the datasets, however with failure of replication in the other. There was no significant association between S100B and positive symptoms or present use or type of antipsychotic medication. S100B is neither an intermediate phenotype, nor a trait marker for psychotic illness. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 72 | J Psychiatr Res 2013 Aug 47: 1054-60 |
| PMID | 23664672 |
| Title | Increased plasma agmatine levels in patients with schizophrenia. |
| Abstract | Agmatine is an endogenous substance, synthesized from l-arginine, and it is proposed to be a new neurotransmitter. Preclinical studies indicated that agmatine may have an important role in the pathophysiology of schizophrenia. This study was organized to investigate plasma agmatine in patients with schizophrenia and in healthy controls. Eighteen patients with schizophrenia and 19 healthy individuals constituted the subjects. Agmatine levels in the plasma were measured using the HPLC method. The S100B protein level, which is a peripheral biomarker for brain damage, was also measured using the ELISA method. While plasma levels of agmatine in patients with schizophrenia were significantly increased (p < 0.0001) compared to those of healthy individuals (control), there were no significant changes in the levels of S100B protein (p = 0.660). An ROC (receiver operating characteristic) curve analysis revealed that measuring plasma agmatine levels as a clinical diagnostic test would significantly differentiate between patients with schizophrenia and those in the control group (predictive value: 0.969; p < 0.0001). The predictive value of S100B measurements was not statistically significant (p > 0.05). A multiple regression analysis revealed that the age of the patient and the severity of the illness, as indicated by the PANSS score, significantly contributed the plasma agmatine levels in patients with schizophrenia. These results support the hypothesis that an excess agmatine release is important in the development of schizophrenia. The findings also imply that the plasma agmatine level may be a potential biomarker of schizophrenia. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 73 | Prog. Neuropsychopharmacol. Biol. Psychiatry 2014 Jan 48: 287-94 |
| PMID | 23085507 |
| Title | Immune system and glucose metabolism interaction in schizophrenia: a chicken-egg dilemma. |
| Abstract | Impaired 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 Keywords | schizophrenia, schizophrenic, schizophrenics |
| 74 | Schizophr. Res. 2014 Jun 156: 1-8 |
| PMID | 24742875 |
| Title | Pro-inflammatory cytokine levels are raised in female schizophrenia patients treated with clozapine. |
| Abstract | We have previously shown that the neurotrophic factor, S100B, is raised in serum samples of female patients with schizophrenia, but not male patients, compared to controls, and this may be associated with raised BMI. Here we analysed the levels of additional proinflammatory cytokines in patients with schizophrenia to further investigate these gender differences. The levels of six cytokines (IL1?, IL6, IL8, IL17, IL23, TNF?) were measured in serum samples obtained from patients with schizophrenia, treated with clozapine (n=91) and compared with healthy controls (n=50). Individual cytokine levels were measured using dot-immunoblotting methods and a 'cytokine signature' was also generated by summing all 6 cytokines. Treatment time, patient age, gender, illness severity and metabolic parameters were also measured. The levels of proinflammatory cytokines and BMI were significantly raised in female, but not male, patients treated with clozapine compared to healthy controls. Compared to individual cytokines, the 'cytokine signature' analysis showed less scatter of data although this 'cytokine signature' method did not improve separation of individual patients and controls. This study supports previous findings that raised BMI, which is likely associated with increased number of adipocytes, may contribute to increased cytokine serum concentrations in females. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 75 | Psychiatr. Clin. North Am. 2014 Dec 37: 679-705 |
| PMID | 25455071 |
| Title | The importance of glia in dealing with stress. |
| Abstract | Glia are starting to be accepted as the equal of neurons. Their impact on intelligence, environmental enrichment, and cerebral dominance forms the basis for understanding the role of glia in stress. Along with neurons, astrocytes, microglia, NG2 cells, and oligodendrocytes all contribute. Glia can even be protective against drug abuse. Glial effects on depression, mood disorders and schizophrenia are reviewed. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 76 | Eur Arch Psychiatry Clin Neurosci 2014 Jun 264: 311-6 |
| PMID | 24504531 |
| Title | S100B is downregulated in the nuclear proteome of schizophrenia corpus callosum. |
| Abstract | Here we report the downregulation of S100B in the nuclear proteome of the corpus callosum from nine schizophrenia patients compared to seven mentally healthy controls. Our data have been obtained primarily by mass spectrometry and later confirmed by Western blot. This is an intriguing finding coming from a brain region which is essentially composed by white matter, considering the potential role of S100B in the control of oligodendrocyte maturation. This data reinforce the importance of oligodendrocytes in schizophrenia, shedding more light to its pathobiology. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 77 | PLoS ONE 2014 -1 9: e106342 |
| PMID | 25202915 |
| Title | Systematic review and meta-analysis of circulating S100B blood levels in schizophrenia. |
| Abstract | S100B is a calcium-binding protein secreted in central nervous system from astrocytes and other glia cells. High blood S100B levels have been linked to brain damage and psychiatric disorders. S100B levels have been reported to be higher in schizophrenics than healthy controls. To quantify the relationship between S100B blood levels and schizophrenia a systematic literature review of case-control studies published on this topic within July 3rd 2014 was carried out using three bibliographic databases: Medline, Scopus and Web of Science. Studies reporting mean and standard deviation of S100B blood levels both in cases and controls were included in the meta-analysis. The meta-Mean Ratio (mMR) of S100B blood levels in cases compared to controls was used as a measure of effect along with its 95% Confidence Intervals (CI). 20 studies were included totaling for 994 cases and 785 controls. schizophrenia patients showed 76% higher S100B blood levels than controls with mMR?= 1.76 95% CI: 1.44-2.15. No difference could be found between drug-free patients with mMR?= 1.84 95%CI: 1.24-2.74 and patients on antipsychotic medication with mMR?= 1.75 95% CI: 1.41-2.16). Similarly, ethnicity and stage of disease didn't affect results. Although S100B could be regarded as a possible biomarker of schizophrenia, limitations should be accounted when interpreting results, especially because of the high heterogeneity that remained >70%, even after carrying out subgroups analyses. These results point out that approaches based on traditional categorical diagnoses may be too restrictive and new approaches based on the characterization of new complex phenotypes should be considered. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 78 | PLoS ONE 2014 -1 9: e106342 |
| PMID | 25202915 |
| Title | Systematic review and meta-analysis of circulating S100B blood levels in schizophrenia. |
| Abstract | S100B is a calcium-binding protein secreted in central nervous system from astrocytes and other glia cells. High blood S100B levels have been linked to brain damage and psychiatric disorders. S100B levels have been reported to be higher in schizophrenics than healthy controls. To quantify the relationship between S100B blood levels and schizophrenia a systematic literature review of case-control studies published on this topic within July 3rd 2014 was carried out using three bibliographic databases: Medline, Scopus and Web of Science. Studies reporting mean and standard deviation of S100B blood levels both in cases and controls were included in the meta-analysis. The meta-Mean Ratio (mMR) of S100B blood levels in cases compared to controls was used as a measure of effect along with its 95% Confidence Intervals (CI). 20 studies were included totaling for 994 cases and 785 controls. schizophrenia patients showed 76% higher S100B blood levels than controls with mMR?= 1.76 95% CI: 1.44-2.15. No difference could be found between drug-free patients with mMR?= 1.84 95%CI: 1.24-2.74 and patients on antipsychotic medication with mMR?= 1.75 95% CI: 1.41-2.16). Similarly, ethnicity and stage of disease didn't affect results. Although S100B could be regarded as a possible biomarker of schizophrenia, limitations should be accounted when interpreting results, especially because of the high heterogeneity that remained >70%, even after carrying out subgroups analyses. These results point out that approaches based on traditional categorical diagnoses may be too restrictive and new approaches based on the characterization of new complex phenotypes should be considered. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 79 | Front Cell Neurosci 2015 -1 9: 489 |
| PMID | 26733814 |
| Title | Changes in Astroglial Markers in a Maternal Immune Activation Model of Schizophrenia in Wistar Rats are Dependent on Sex. |
| Abstract | Data from epidemiological studies suggest that prenatal exposure to bacterial and viral infection is an important environmental risk factor for schizophrenia. The maternal immune activation (MIA) animal model is used to study how an insult directed at the maternal host can have adverse effects on the fetus, leading to behavioral and neurochemical changes later in life. We evaluated whether the administration of LPS to rat dams during late pregnancy affects astroglial markers (S100B and GFAP) of the offspring in later life. The frontal cortex and hippocampus were compared in male and female offspring on postnatal days (PND) 30 and 60. The S100B protein exhibited an age-dependent pattern of expression, being increased in the frontal cortex and hippocampus of the MIA group at PND 60, while at PND 30, male rats presented increased S100B levels only in the frontal cortex. Considering that S100B secretion is reduced by elevation of glutamate levels, we may hypothesize that this early increment in frontal cortex tissue of males is associated with elevated extracellular levels of glutamate and glutamatergic hypofunction, an alteration commonly associated with SCZ pathology. Moreover, we also found augmented GFAP in the frontal cortex of the LPS group at PND 30, but not in the hippocampus. Taken together data indicate that astroglial changes induced by MIA are dependent on sex and brain region and that these changes could reflect astroglial dysfunction. Such alterations may contribute to our understanding of the abnormal neuronal connectivity and developmental aspects of SCZ and other psychiatric disorders. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 80 | Clin Schizophr Relat Psychoses 2015 -1 9: 65-78B |
| PMID | 23491967 |
| Title | Does Systemic Inflammation Play a Role in Pediatric Psychosis? |
| Abstract | Human and animal studies have suggested an underlying inflammatory mechanism for a variety of neuropsychiatric disorders, including schizophrenia. To date, most available reports focused on adult patients. We wished to test the hypothesis that the first psychotic episode in youth is associated with inflammation. We studied patients admitted to a pediatric inpatient psychiatric unit. Patients (n=80) had new-onset psychosis diagnosed using DSM-IV TR criteria for Psychosis NOS, Schizophreniform Disorder or Schizoaffective Disorder. Patients were matched for age, race and gender with inpatient controls without psychosis within the same unit (n=66). We also compared these values to normal pediatric hematologic values. To study the role of inflammation in youth with psychosis, we collected serum samples of 28 children presenting with first-episode psychosis and compared their serum cytokine and S100B levels to eight healthy controls. In this study, we measured serum markers of systemic inflammation. Leukocyte counts revealed a statistically significant increase in absolute monocytes compared to patients without psychosis (0.61 ± 0.282 k/ml vs. 0.496 ± 0.14 k/ml; p<0.01) and lymphocytes (2.51 ± 0.84 k/ml vs. 2.24 ± 0.72 k/ml; p<0.05) in patients with psychosis. All other hematologic values were similar between the groups. In addition, psychosis was characterized by increased serum levels of S100B, a peripheral marker of blood-brain barrier (BBB) damage. Several inflammatory mediators (e.g., TNF-?, IL-1?, IL-6, IL-5, IL-10, and IFN-?) were elevated in children with psychosis. These results strongly support a link between systemic inflammation, blood-brain barrier disruption and first-episode psychosis in pediatric patients. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 81 | Curr. Med. Chem. 2016 -1 23: 1571-96 |
| PMID | 27048377 |
| Title | Identifying S100B as a Biomarker and a Therapeutic Target For Brain Injury and Multiple Diseases. |
| Abstract | The calcium binding protein S100B has attracted great attention as a biomarker for a variety of diseases. S100B is mainly expressed in glial cells and functions through intracellular and extracellular signaling pathways. The biological roles of S100B have been closely associated with its concentrations and its physiological states. The released S100B can bind to the receptor of advanced glycation end products and induce the initiation of multiple cell signaling transductions. The regulation of S100B bioactivities has been suggested through phosphoinositide 3 kinase/Akt, p53, mitogen-activated protein kinases, transcriptional factors including nuclear factor-kappaB, and cyclic adenosine monophosphate. The levels of S100B in the blood may function to predict the progress or the prognosis of many kinds of diseases, such as cerebrovascular diseases, neurodegenerative diseases, motor neuron diseases, traumatic brain injury, schizophrenia, depression, diabetes mellitus, myocardial infarction, cancer, and infectious diseases. Given that the activity of S100B has been implicated in the pathological process of these diseases, S100B should not be simply regarded as a biomarker, it may also function as therapeutic target for these diseases. Further elucidation of the roles of S100B may formulate innovative therapeutic strategies for multiple diseases. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 82 | Front Cell Neurosci 2016 -1 10: 46 |
| PMID | 26941608 |
| Title | Serum S100B Is Related to Illness Duration and Clinical Symptoms in Schizophrenia-A Meta-Regression Analysis. |
| Abstract | S100B has been linked to glial pathology in several psychiatric disorders. Previous studies found higher S100B serum levels in patients with schizophrenia compared to healthy controls, and a number of covariates influencing the size of this effect have been proposed in the literature. Here, we conducted a meta-analysis and meta-regression analysis on alterations of serum S100B in schizophrenia in comparison with healthy control subjects. The meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement to guarantee a high quality and reproducibility. With strict inclusion criteria 19 original studies could be included in the quantitative meta-analysis, comprising a total of 766 patients and 607 healthy control subjects. The meta-analysis confirmed higher values of the glial serum marker S100B in schizophrenia if compared with control subjects. Meta-regression analyses revealed significant effects of illness duration and clinical symptomatology, in particular the total score of the Positive and Negative Syndrome Scale (PANSS), on serum S100B levels in schizophrenia. In sum, results confirm glial pathology in schizophrenia that is modulated by illness duration and related to clinical symptomatology. Further studies are needed to investigate mechanisms and mediating factors related to these findings. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 83 | Neuroscience 2016 Jun 326: 105-16 |
| PMID | 27063100 |
| Title | Effects of enriched environment on alterations in the prefrontal cortex GFAP- and S100B-immunopositive astrocytes and behavioral deficits in MK-801-treated rats. |
| Abstract | A plethora of studies have indicated that enriched environment (EE) paradigm provokes plastic and morphological changes in astrocytes with accompanying increments of their density and positively affects the behavior of rodents. We also previously documented that EE could be employed to preclude several behavioral abnormalities, mainly cognitive deficits, attributed to postnatal N-methyl-d-aspartate (NMDA) receptor antagonist (MK-801) treatment, as a rodent model of schizophrenia (SCH) aspects. Given this, the current study quantitatively investigated the number of cells, presumed to be astrocytes, expressing two astroglia-associated proteins (S100B and glial fibrillary acidic protein (GFAP)) by immunohistochemistry in the prefrontal cortex (PFC), along with anxiety and passive avoidance (PA) learning behaviors by utilizing elevated plus maze (EPM) and shuttle-box tests, in MK-801-treated male wistar rats submitted to EE and non-EE rats. Following a treatment regime of sub-chronic MK-801 (1.0mg/kg i.p. daily for five consecutive days from postnatal day (P) 6), S-100B-positive cells and anxiety level were markedly increased, while the GFAP-positive cells and PA learning were notably attenuated. The trend of diminished GFAP-immunopositive cells and elevated S100B-immunostained cells in the PFC was reversed in the SCH-like rats by exposure of animals to EE, commencing from birth up to the time of experiments on P28-85. Additionally, EE exhibited an ameliorating effect on the behavioral abnormalities evoked by MK-801. Overall, present findings support that improper astrocyte functioning and behavioral changes, reminiscent of the many facets of SCH, occur consequential to repetitive administration of MK-801 and that raising rat pups in an EE mitigates these alterations. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 84 | Front Cell Neurosci 2016 -1 10: 33 |
| PMID | 27013967 |
| Title | Serum S100B Protein is Specifically Related to White Matter Changes in Schizophrenia. |
| Abstract | schizophrenia can be conceptualized as a form of dysconnectivity between brain regions.To investigate the neurobiological foundation of dysconnectivity, one approach is to analyze white matter structures, such as the pathology of fiber tracks. S100B is considered a marker protein for glial cells, in particular oligodendrocytes and astroglia, that passes the blood brain barrier and is detectable in peripheral blood. Earlier Studies have consistently reported increased S100B levels in schizophrenia. In this study, we aim to investigate associations between S100B and structural white matter abnormalities. We analyzed data of 17 unmedicated schizophrenic patients (first and recurrent episode) and 22 controls. We used voxel based morphometry (VBM) to detect group differences of white matter structures as obtained from T1-weighted MR-images and considered S100B serum levels as a regressor in an age-corrected interaction analysis. S100B was increased in both patient subgroups. Using VBM, we found clusters indicating significant differences of the association between S100B concentration and white matter. Involved anatomical structures are the posterior cingulate bundle and temporal white matter structures assigned to the superior longitudinal fasciculus. S100B-associated alterations of white matter are shown to be existent already at time of first manifestation of psychosis and are distinct from findings in recurrent episode patients. This suggests involvement of S100B in an ongoing and dynamic process associated with structural brain changes in schizophrenia. However, it remains elusive whether increased S100B serum concentrations in psychotic patients represent a protective response to a continuous pathogenic process or if elevated S100B levels are actively involved in promoting structural brain damage. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |
| 85 | Front Cell Neurosci 2016 -1 10: 33 |
| PMID | 27013967 |
| Title | Serum S100B Protein is Specifically Related to White Matter Changes in Schizophrenia. |
| Abstract | schizophrenia can be conceptualized as a form of dysconnectivity between brain regions.To investigate the neurobiological foundation of dysconnectivity, one approach is to analyze white matter structures, such as the pathology of fiber tracks. S100B is considered a marker protein for glial cells, in particular oligodendrocytes and astroglia, that passes the blood brain barrier and is detectable in peripheral blood. Earlier Studies have consistently reported increased S100B levels in schizophrenia. In this study, we aim to investigate associations between S100B and structural white matter abnormalities. We analyzed data of 17 unmedicated schizophrenic patients (first and recurrent episode) and 22 controls. We used voxel based morphometry (VBM) to detect group differences of white matter structures as obtained from T1-weighted MR-images and considered S100B serum levels as a regressor in an age-corrected interaction analysis. S100B was increased in both patient subgroups. Using VBM, we found clusters indicating significant differences of the association between S100B concentration and white matter. Involved anatomical structures are the posterior cingulate bundle and temporal white matter structures assigned to the superior longitudinal fasciculus. S100B-associated alterations of white matter are shown to be existent already at time of first manifestation of psychosis and are distinct from findings in recurrent episode patients. This suggests involvement of S100B in an ongoing and dynamic process associated with structural brain changes in schizophrenia. However, it remains elusive whether increased S100B serum concentrations in psychotic patients represent a protective response to a continuous pathogenic process or if elevated S100B levels are actively involved in promoting structural brain damage. |
| SCZ Keywords | schizophrenia, schizophrenic, schizophrenics |