Neuron-specific enolase is unaltered whereas S100B is elevated in serum of patients with schizophrenia - Original research and meta-analysis

Queen-Elisabeth-Hospital, Department of Psychiatry, 10362 Berlin, Germany.
Psychiatry Research (Impact Factor: 2.47). 05/2009; 167(1-2):66-72. DOI: 10.1016/j.psychres.2008.01.002
Source: PubMed


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.

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    • "When two markers of astroglial activation (myo-inositol and S100β) were assessed by 1 H-MRS or quantitative immunoassay, respectively, patients with increased S100β levels also had elevated concentrations of myo-inositol, suggesting a general dysfunction of glial cells not restricted to the specific astrocytic protein (i.e., S100β) (Rothermundt et al., 2007). A recent meta-analysis has revealed elevated serum S100β in schizophrenia without any effects of antipsychotics and has proposed that this increase is related to active secretion of the protein by astrocytes in combination with blood–brain barrier dysfunction in schizophrenia (Schroeter et al., 2009). However, there have been negative studies as well (Uzbay et al, 2013; van der Leeuw et al., 2013). "
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    ABSTRACT: Astrocytes regulate multiple processes in the brain ranging from trophic support of developing neurons to modulation of synaptic neurotransmission and neuroinflammation in adulthood. It is, therefore, understandable that pathogenesis and pathophysiology of major psychiatric disorders involve astrocyte dysfunctions. Until recently, there has been the paucity of experimental approaches to studying the roles of astrocytes in behavioral disease. A new generation of in vivo models allows us to advance our understanding of the roles of astrocytes in psychiatric disorders. This review will evaluate the recent studies that focus on the contribution of astrocyte dysfunction to behavioral alterations pertinent to schizophrenia and will propose the possible solutions of the limitations of the existing approaches.
    Schizophrenia Research 11/2014; DOI:10.1016/j.schres.2014.10.044 · 3.92 Impact Factor
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    • "During the last twenty years the S100B protein has gained attention in the research area for peripheral biomarkers of schizophrenia [ 66 ] . We carried out a meta - analysis including both the studies considered in those of Schroeter et al . , 2009 [ 23 , 24 ] and seven new studies [ 39 , 40 , 45 , 51 , 52 , 53 , 55 ] . Our results confirmed the in - creased S100B values in cases than controls found by Schroeter et al ; in addition , we could carry out sensitivity and stratified analyses in order to assess the presence of confounding factors and effect modifiers . Subgroups analys"
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    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.
    PLoS ONE 09/2014; 9(9):e106342. DOI:10.1371/journal.pone.0106342 · 3.23 Impact Factor
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    • "Patients have increased striatal presynaptic dopamine function (synthesis and release) (Fusar-Poli & Meyer-Lindenberg, 2013a), but no difference in presynaptic dopamine transporter density (Howes et al. 2012; Fusar-Poli & Meyer-Lindenberg, 2013a, b) Patients have poor information processing, language skills, verbal learning, prospective memory, working memory and theory of mind (Bokat & Goldberg, 2003; Dickinson et al. 2007; Bora et al. 2009a; Forbes et al. 2009; Wang et al. 2009; Bora & Pantelis, 2013) Medium effect sizes a Patients show increases in volume of the basal ganglia, lateral and third ventricles and increased frequency of large cavum septum pellucidum. They show reductions in whole brain volume, grey matter volume in the frontal lobe, superior temporal gyrus, medial temporal lobe, thalamus, insula, anterior cingulate, amygdala, inferior parietal gyrus and cerebellum, and reduced white matter in the mid-sagittal corpus callosum (Wright et al. 2000; Baiano et al. 2007; Arnone et al. 2008; Kempton et al. 2010; Adriano et al. 2010, 2012; Chan et al. 2011; Olabi et al. 2011; Trzesniak et al. 2011a, b; Shepherd et al. 2012; Fusar-Poli et al. 2013; Haijma et al. 2013) Patient show increased N400 peak latency and decreased N400 effect during semantic priming tasks, as well as more negative N400 amplitude during congruent stimuli, particularly tasks involving long stimulus onset asynchrony (>500 ms) (Wang et al. 2011) Patients have decreased levels of N-acetyl aspartate (Brugger et al. 2011; Kraguljac et al. 2012) First-degree relatives of patients show deficits in general intelligence, executive functioning, attention, language, visual and verbal memory, short-and long-term episodic memory, theory of mind, and smooth pursuit eye movement (Sitskoorn et al. 2004; Szoke et al. 2005; Whyte et al. 2005; Snitz et al. 2006; Trandafir et al. 2006; Calkins et al. 2008; Bora & Pantelis, 2013) People at high clinical risk for psychosis show deficits in theory of mind (Bora & Pantelis, 2013) Neurocognition and social cognition are related to functional outcomes (Fett et al. 2011; Schmidt et al. 2011; Irani et al. 2012) Patients report greater aversive emotion and arousal to neutral stimuli (Cohen & Minor, 2010; Llerena et al. 2012) Patients with a current substance use disorder have fewer negative symptoms than patients without a current substance use disorder (Potvin et al. 2006) Patients with former cannabis use perform better on cognitive tasks than patients without former cannabis use (Yucel et al. 2012) Small effect sizes a Cognitive deficits are greater in schizophrenia than bipolar disorder (Krabbendam et al. 2005; Bora et al. 2009b; Stefanopoulou et al. 2009) and are related to lower levels of insight (Aleman et al. 2006) Negative and disorganized symptoms are related to lower IQ, poor reasoning, attention, executive functioning, language skills, learning, speed of processing, visual and verbal memory and social cognition (Nieuwenstein et al. 2001; de Gracia Dominguez et al. 2009; Dibben et al. 2009; Ventura et al. 2010, 2013) Patients are more likely to be non-right handed (Sommer et al. 2001) There is increased severity of negative symptoms in patients with a family history of psychosis compared with patients without a family history (Esterberg et al. 2010), and significant concordance of disorganized and reality distortion symptoms between siblings with schizophrenia (Rietkerk et al. 2008) People at high clinical risk for psychosis show deficits in general intelligence, executive functioning, verbal and visual memory, verbal fluency, attention, working memory and social cognition (Fusar-Poli et al. 2012b) Moderate-quality evidence Large effect sizes a Patients have increased S100B protein levels in serum (Schroeter et al. 2009) Patients have increased markers for human endogenous retroviruses, Chlamydophilia pneumoniae, Chlamydophilia psittaci, Toxocara and Toxoplasma gondii (Arias et al. 2011; Torrey et al. 2012) Patients and their first-degree relatives show increased P50 ratio (not latency), indicating reduced sensory gating (Bramon et al. 2004; de Wilde et al. 2007), which may not be improved by antipsychotic medication (Su et al. 2012) Patients show reduced mismatch negativity, and the effect size increases with increasing duration of illness (Umbricht & Krljes, 2005) Patients have increased occurrence of minor physical anomalies of the head, eyes, mouth, ears, hands and feet (Weinberg et al. 2007; Xu et al. 2011) Patients show increased rigidity of thought, poor IQ, pre-morbid IQ, perceptual problem solving ability, attention, short-term and long-term memory, olfactory identification and acuity, executive functioning, social and emotion processing, slower motor and processing speed, smooth pursuit eye movement and self-recognition (Johnson-Selfridge & Zalewski, 2001; Schultz & Searleman, 2002; Pelletier et al. 2005; Dickinson et al. 2007; Sprong et al. 2007; O'Driscoll & Callahan, 2008; Bora et al. 2009a; Mesholam-Gately et al. 2009; Rajji et al. 2009; Chan et al. 2010a; Knowles et al. 2010; Kohler et al. 2010; Khandaker et al. 2011; Cohen et al. 2012; Savla et al. 2012; Waters et al. 2012) Antipsychotic-free patients have increased sleep latency and total sleep time, and decreased sleep efficiency and stage 2 sleep (Chouinard et al. 2004) Patients and their first-degree relatives show increased neurological soft signs, including dysfunction in motor coordination and sequencing, sensory integration and disinhibition compared with controls (Chan et al. 2010b, c) Patients with a cocaine use disorder show increased extrapyramidal symptoms (Potvin et al. 2009) Medium effect sizes a Patients have reduced blood BDNF concentrations, regardless of medication dosage or medication status (Green et al. 2011) Patients have increased markers for Borna disease virus (Arias et al. 2011) Patients show increases in immune system molecules IFN-γ, TGF-β, TNF-α and IL-6; acutely relapsed patients also show increases in IL-10, IL-IRA and IL-8; and first-episode (untreated) patients also show increases in sIL-2R, IL-1β and IL-12. 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    ABSTRACT: Background. True findings about schizophrenia remain elusive; many findings are not replicated and conflicting results are common. Well-conducted systematic reviews have the ability to make robust, generalizable conclusions, with good meta-analyses potentially providing the closest estimate of the true effect size. In this paper, we undertake a systematic approach to synthesising the available evidence from well-conducted systematic reviews on schizophrenia. Method. Reviews were identified by searching Medline, EMBASE, CINAHL, Current Contents and PsycINFO. The decision to include or exclude reviews, data extraction and quality assessments were conducted in duplicate. Evidence was graded as high quality if reviews contained large samples and robust results; and as moderate quality if reviews contained imprecision, inconsistency, smaller samples or study designs that may be prone to bias. Results. High- and moderate-quality evidence shows that numerous psychosocial and biomedical treatments are effective. Patients have relatively poor cognitive functioning, and subtle, but diverse, structural brain alterations, altered electrophysiological functioning and sleep patterns, minor physical anomalies, neurological soft signs, and sensory alterations. There are markers of infection, inflammation or altered immunological parameters; and there is increased mortality from a range of causes. Risk for schizophrenia is increased with cannabis use, pregnancy and birth complications, prenatal exposure to Toxoplasma gondii, childhood central nervous system viral infections, childhood adversities, urbanicity and immigration (first and second generation), particularly in certain ethnic groups. Developmental motor delays and lower intelligence quotient in childhood and adolescence are apparent. Conclusions. We conclude that while our knowledge of schizophrenia is very substantial, our understanding of it remains limited.
    Psychological Medicine 02/2014; 44(16). DOI:10.1017/S0033291714000166 · 5.94 Impact Factor
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