Cytokine serum levels, autologous mixed lymphocyte reaction and surface marker analysis in never medicated and chronically medicated schizophrenic patients

Theodoropoulou, St.; Spanakos, Gregory; Baxevanis, Constantin N.; Economou, Michael; Gritzapis, Angelos D.; Papamichail, Michail; Stefanis, Costas N.

doi:10.1016/s0920-9964(00)00007-4

Cited by 168 publications

(84 citation statements)

References 39 publications

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“…A combination of genetic and environmental factors resulting in some immune dysregulation in general and the lack of the CMV IgG antibodies in particular could be the most plausible speculations. While there are no specific research results supporting this finding in existing literature, the activation of the immune system and prolonged neuroinflammation are well established phenomena implicated in the etiopathogenesis and symptomatology of schizophrenia (Lin et al, 1998;Nikkila et al, 1999;Kim et al, 2000;Theodoropoulou et al, 2001;Ebrinc et al, 2002;Patterson, 2002;Zhang et al, 2002;Garver et al, 2003;Zhang et al, 2004;Coelho et al, 2008;Potvin et al, 2008;Doorduin et al, 2009;Kim et al, 2009;Song et al, 2009;Drexhage et al, 2010;Romero et al, 2010;Drexhage et al, 2011;Weigelt et al, 2011;Beumer et al, 2012;Brito-Melo et al, 2012). Other mechanisms could also be considered.…”

Section: Discussionmentioning

confidence: 84%

Association between antibodies to multiple infectious and food antigens and new onset schizophrenia among US military personnel

Li¹,

Weber²,

Fisher³

et al. 2013

Schizophrenia Research

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a b s t r a c t a r t i c l e i n f oIntroduction: Multiple studies have documented immune activation in many individuals with schizophrenia suggesting that antigens capable of generating a prolonged immune response may be important environmental factors in many cases of this disorder. While existing studies have found single-agent associations of antibodies to food and neurotropic infectious agents with schizophrenia, a simultaneous examination of multiple agents may shed light on agent interactions or possible etiopathogenic pathways. Methods: We used traditional regression and novel statistical techniques to examine associations of single and combined infectious and food antigens with schizophrenia. We tested 6106 serum samples from 855 cases and 1165 matched controls. Results: Higher antibody levels to casein were borderline significant in the prediction of schizophrenia (HR = 1.08, p = 0.06). Study participants with higher cytomegalovirus (CMV) IgG antibody levels had a reduced risk of developing schizophrenia (HR = 0.90; p = 0.02). While IgG antibodies to gliadin, Toxoplasma gondii, vaccinia, measles, and human herpesvirus-6 (HHV-6) showed no significant independent associations with schizophrenia, the increase in antibody levels to several combinations of agents, to include casein, measles, CMV, T. gondii and vaccinia, was predictive of an 18-34% increase in the risk of developing schizophrenia. Conclusion: Certain patterns of antibodies, involving some agents, were predictive of developing schizophrenia, with the magnitude of association rising when the level of antibodies increased to two or more agents. A heightened antibody response to a combination of several infectious/food antigens might be an indicator of an altered immune response to antigenic stimuli.Published by Elsevier B.V.

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Section: Discussionmentioning

confidence: 84%

Association between antibodies to multiple infectious and food antigens and new onset schizophrenia among US military personnel

Li¹,

Weber²,

Fisher³

et al. 2013

Schizophrenia Research

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“…There is increasing evidence, both from the literature and from studies carried out within our own group, to suggest that disease-related changes can be detected outside the brain (11,13,14). Various immune alterations have been reported previously in schizophrenia (15)(16)(17)(18), and disease-related changes are detectable in T cells (19). In the present study we extended our search for biomarkers to proteomics profiling of peripheral blood CD3 ϩ T cells.…”

Section: Molecular and Cellular Proteomics 7: 1204 -1213 2008mentioning

confidence: 78%

Increased α-Defensins as a Blood Marker for Schizophrenia Susceptibility

Craddock

Huang

Jackson

et al. 2008

Molecular & Cellular Proteomics

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Schizophrenia is a severe psychotic illness affecting 1% of the general population. There are no consistent pathological features, and the disorder is defined by a complex symptomatology, which overlaps with other psychiatric illnesses. Diagnosis is based on a clinical interview, relying on the patient meeting criteria according to diagnosis manuals, including Diagnostic and Statistical Manual of Mental Disorders, 4th Ed. and International Statistical Classification of Diseases, 10th Revision. Because of the ambiguous symptoms, the diagnostic process can take many months and often years. Rapid and effective treatment has been shown to impact positively on disease progression and outcome, and it is therefore important to identify disease-associated biomarkers allowing early diagnosis. Reliable biomarkers can be used for the development of diagnostic tests and may also help us understand the underlying pathology of this disorder. In the present study, proteins from anti-CD3 stimulated and unstimulated peripheral blood T cell lysates from 15 minimally medicated and unmedicated patients and 15 age-, sex-, race-, and smoking-matched controls were profiled on cation exchange (CM10) chips using SELDI-TOF. Partial least squares discriminate analysis was used to separate patient and control groups according to the expression of 108 detected peaks, and two peaks of 3,374 and 3,450 Da, corresponding to ␣-defensins based on masses and cationic properties, were found to contribute significantly to the separation of patient and control groups. Reduction of T cell lysates with DTT resulted in a 6-Da shift in the mass of these peaks consistent with the presence of three cysteine bonds in the structure, confirming them as ␣-defensins. Quantification of ␣-defensins in T cell lysates from six patients and 18 healthy controls was carried out by ELISA, which also showed that ␣-defensin levels were significantly increased in patient lysates when com- Schizophrenia is worldwide one of the most severe psychiatric disorders with a prevalence of 1% in the general population. The causes of this devastating disorder are still undetermined, although schizophrenia is widely believed to have a multifactorial etiology with contribution from both heritable and environmental factors. Despite decades of research, we have failed to find consistent pathological features across cases, making laboratory-based diagnosis impossible at the present time. Among the most widely reported findings in schizophrenia are decreased cerebral volume with ventricular enlargement (for a review, see Ref. 1) and a greater prevalence of neurological soft signs (2) as well as hypofrontality (3). There is robust evidence to support a heritable risk to the development of schizophrenia, and individuals with an affected relative have an increased chance of developing schizophrenia. The risk increases with the closeness of the relative but only reaches ϳ50% concordance in monozygotic twins (4), suggesting that environmental risk factors play an important role. Patterns of in...

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“…Various studies have analyzed serum and plasma levels of cytokines, including interleukin-2 (IL-2) (Cazzullo et al, 2002(Cazzullo et al, , 2001Kim et al, 2001;Szulc et al, 2001;Theodoropoulou et al, 2001), IL-4 (Cazzullo et al, 2002(Cazzullo et al, , 2001), IL-6, (Kim et al, 2001;Kudoh et al, 2001;Haack et al, 1999;Akiyama, 1999;Monteleone et al, 1997), IL-10 (Cazzullo et al, 2002Maes et al, 2002), and TNF-a (Theodoropoulou et al, 2001;Kudoh et al, 2001;Haack et al, 1999;Monteleone et al, 1997;Naudin et al, 1996), in order to better understand the role of immune activation in schizophrenic disorders (Muller et al, 2001). The findings from such studies in the periphery have been contradictory.…”

Section: Studies Of Immune Activation In Schizophreniamentioning

confidence: 99%

Elevated Interleukin-6 in the Cerebrospinal Fluid of a Previously Delineated Schizophrenia Subtype

Garver

Tamas

Holcomb

2003

Neuropsychopharmacol

133

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Evidence of immune activation has occasionally, but not consistently, been reported in schizophrenia. Investigations of cytokine abnormalities in serum, and occasionally in CSF, have yielded inconsistent results, which have been difficult to resolve. In such studies, schizophrenia has been assumed to consist of a single process rather than a group of disorders. This study assesses differences in the proinflammatory cytokine, interleukin-6 (IL-6) in the cerebrospinal fluid (CSF) in two previously delineated subtypes of schizophrenics ('delayed-responders' (DR) (n ¼ 23) and 'poor-responders' (PR) (n ¼ 8)) during periods of neuroleptic-free psychotic exacerbation, and in a comparison group of normal controls (n ¼ 14). The two response subtypes were separated by subsequent treatment response (greater/less than 60% reduction of SAPS scores from baseline during 6 months of systematic treatment). The IL-6 assay, a sandwich enzyme-linked immunosorbent assay, was sensitive and reliable to detect IL-6 levels in the CSF of all subjects. CSF IL-6 was found to be significantly higher in the DR than the PR (P ¼ 0.017) and the controls (P ¼ 0.013). In addition to supporting the concept of heterogeneity in schizophrenia, this study also provides evidence that a central immune process may be occurring centrally in one subtype of schizophrenia.

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Cytokine serum levels, autologous mixed lymphocyte reaction and surface marker analysis in never medicated and chronically medicated schizophrenic patients

Cited by 168 publications

References 39 publications

Association between antibodies to multiple infectious and food antigens and new onset schizophrenia among US military personnel

Association between antibodies to multiple infectious and food antigens and new onset schizophrenia among US military personnel

Increased α-Defensins as a Blood Marker for Schizophrenia Susceptibility

Elevated Interleukin-6 in the Cerebrospinal Fluid of a Previously Delineated Schizophrenia Subtype

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