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1.
Transl Psychiatry ; 6(12): e981, 2016 12 13.
Article in English | MEDLINE | ID: mdl-27959328

ABSTRACT

Dysregulation of immune system functions has been implicated in schizophrenia, suggesting that immune cells may be involved in the development of the disorder. With the goal of a biomarker assay for psychosis risk, we performed small RNA sequencing on RNA isolated from circulating immune cells. We compared baseline microRNA (miRNA) expression for persons who were unaffected (n=27) or who, over a subsequent 2-year period, were at clinical high risk but did not progress to psychosis (n=37), or were at high risk and did progress to psychosis (n=30). A greedy algorithm process led to selection of five miRNAs that when summed with +1 weights distinguished progressed from nonprogressed subjects with an area under the receiver operating characteristic curve of 0.86. Of the five, miR-941 is human-specific with incompletely understood functions, but the other four are prominent in multiple immune system pathways. Three of those four are downregulated in progressed vs. nonprogressed subjects (with weight -1 in a classifier function that increases with risk); all three have also been independently reported as downregulated in monocytes from schizophrenia patients vs. unaffected subjects. Importantly, these findings passed stringent randomization tests that minimized the risk of conclusions arising by chance. Regarding miRNA-miRNA correlations over the three groups, progressed subjects were found to have much weaker miRNA orchestration than nonprogressed or unaffected subjects. If independently verified, the leukocytic miRNA biomarker assay might improve accuracy of psychosis high-risk assessments and eventually help rationalize preventative intervention decisions.


Subject(s)
Gene Expression/genetics , Genetic Predisposition to Disease/genetics , Leukocytes/immunology , MicroRNAs/genetics , Psychotic Disorders/genetics , Psychotic Disorders/immunology , Adolescent , Adult , Child , Disease Progression , Down-Regulation/genetics , Female , Genetic Testing , Humans , Immune System Phenomena/genetics , Longitudinal Studies , Male , Monocytes/immunology , Risk Assessment , Schizophrenia/genetics , Schizophrenia/immunology , Schizotypal Personality Disorder/genetics , Schizotypal Personality Disorder/immunology , Young Adult
2.
Bull Exp Biol Med ; 162(1): 86-88, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27878726

ABSTRACT

Associations between schizotypal traits and genes coding for inflammation markers (Creactive protein and TNF-α) were studied in 222 healthy men who completed the Schizotypal Personality Questionnaire (SPQ-74). CRP -717A>G and TNFα -308 G>A polymorphisms were genotyped. Carriers of low-active allele G of the CRP gene differed from subjects with genotype AA by a trend toward more manifest schizotypal traits in general and scores on the Interpersonal factor, which corresponds to negative syndrome in schizophrenia, and Constricted affect and Odd behavior scales. These results could be interpreted in favor of the hypothesis on a compensatory increase of CRP concentrations in subjects with abnormalities of CNS development that predispose to schizophrenia.


Subject(s)
Alleles , C-Reactive Protein/genetics , Polymorphism, Single Nucleotide , Schizotypal Personality Disorder/genetics , Tumor Necrosis Factor-alpha/genetics , Adolescent , Adult , Biomarkers/metabolism , C-Reactive Protein/immunology , Gene Expression , Gene Frequency , Genotype , Humans , Male , Middle Aged , Phenotype , Promoter Regions, Genetic , Schizotypal Personality Disorder/diagnosis , Schizotypal Personality Disorder/immunology , Schizotypal Personality Disorder/psychology , Surveys and Questionnaires , Tumor Necrosis Factor-alpha/immunology
3.
Psychiatry Res ; 66(2-3): 145-52, 1997 Feb 07.
Article in English | MEDLINE | ID: mdl-9075278

ABSTRACT

Dysfunction of T-cell mediated immunity, which is indicated by deficient production of interleukin-2 (IL-2) and elevated levels of the soluble interleukin-2 receptor (sIL-2R), has been consistently demonstrated in schizophrenia. Recent studies on interferon-gamma (IFN-gamma), a cytokine which is also produced by T-helper cells, have indicated a lowered production in acute schizophrenia. It is not known whether this deficit is restricted to cases of acute schizophrenia or whether it is also present in residual schizophrenia and in first degree relatives, and therefore might be associated with genetic liability to the disease. We investigated 27 individuals (schizophrenics and first degree relatives) of 6 families with multiple occurrence of schizophrenia and 27 age- and sex-matched healthy controls. The production of IFN-gamma was lowered only in the acutely ill schizophrenic individuals, when compared to both controls and first degree relatives. In the context of current knowledge, this result indicates that the production of IFN-gamma can be discussed as a marker of acute exacerbation of schizophrenia, but it is not likely to represent a phenotypic marker of a genetic trait associated with the disease.


Subject(s)
Interferon-gamma/blood , Schizophrenia/genetics , Schizophrenic Psychology , Acute Disease , Adult , Female , Genetic Markers/genetics , Humans , Interferon-gamma/genetics , Male , Middle Aged , Phenotype , Psychiatric Status Rating Scales , Risk Factors , Schizophrenia/diagnosis , Schizophrenia/immunology , Schizotypal Personality Disorder/diagnosis , Schizotypal Personality Disorder/genetics , Schizotypal Personality Disorder/immunology , Schizotypal Personality Disorder/psychology , T-Lymphocytes, Helper-Inducer/immunology
4.
Biol Psychiatry ; 28(6): 467-74, 1990 Sep 15.
Article in English | MEDLINE | ID: mdl-2223917

ABSTRACT

Health et al. (1989) reported that serum from 96% of unmedicated schizophrenic patients contained IgG autoantibodies specific for the septal region of rhesus monkey brain, compared with 0% of nonschizophrenic control subjects and 6% of schizophrenic patients who were on neuroleptic medication. Using the same technique of crossed immunoelectrophoresis, we have tried to replicate this finding. In contrast to the original report, we observed "positive" precipitin arcs with IgG concentrates from all 14 serum samples tested. The failure of immunoelectrophoretic methods to provide convincing evidence of pathogenic autoantibodies in schizophrenia in no way detracts from the hypothesis that autoimmune processes are involved in some forms of schizophrenia. Such methods have not proved useful in established autoimmune diseases such as Graves' disease and myasthenia gravis in which the pathogenic autoantibodies against cell-surface receptors can only be detected by assays which measure functional interactions with such receptors.


Subject(s)
Autoantibodies/analysis , Autoantigens/immunology , Schizophrenia/immunology , Schizophrenic Psychology , Septum Pellucidum/immunology , Adolescent , Adult , Animals , Antibody Specificity/immunology , Cross Reactions/immunology , Humans , Immunoelectrophoresis, Two-Dimensional , Immunoglobulin G/analysis , Macaca mulatta , Male , Schizophrenia, Catatonic/immunology , Schizophrenia, Paranoid/immunology , Schizotypal Personality Disorder/immunology
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