Is DNA methylation responsible for immune system dysfunction in schizophrenia?

Khojasteh-Fard, Maryam; Tabrizi, Mina; Amoli, Mahsa M.

doi:10.1016/j.mehy.2011.06.034

Cited by 4 publications

(3 citation statements)

References 115 publications

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“…Epigenetics is defined as the study of mitotically or meiotically heritable variations in gene function that cannot be explained by changes in DNA sequence (Petronis et al 2000). DNA methylation, which is the transference of a methyl group to the 5-carbon position of the cytosine in a CpG dinucleotide, is one of the major mechanisms of epigenetic modifications, and DNA methylation patterns are affected by environmental factors and genetic variants (Roth and Sweatt 2011;Numata et al 2012), both of which are involved in the pathophysiology of SCZ (Khojasteh-Fard et al 2011;Rutter et al 2006;Gejman et al 2011).…”

Section: Introductionmentioning

confidence: 99%

Aberrant DNA Methylation of Blood in Schizophrenia by Adjusting for Estimated Cellular Proportions

et al. 2014

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DNA methylation, which is the transference of a methyl group to the 5'-carbon position of the cytosine in a CpG dinucleotide, is one of the major mechanisms of epigenetic modifications. A number of studies have demonstrated altered DNA methylation of peripheral blood cells in schizophrenia (SCZ) in previous studies. However, most of these studies have been limited to the analysis of the CpG sites in CpG islands in gene promoter regions, and cell-type proportions of peripheral leukocytes, which may be one of the potential confounding factors for DNA methylation, have not been adjusted in these studies. In this study, we performed a genome-wide DNA methylation profiling of the peripheral leukocytes from patients with SCZ and from non-psychiatric controls (N = 105; 63 SCZ and 42 control subjects) using a quantitative high-resolution DNA methylation microarray which covered across the whole gene region (485,764 CpG dinucleotides). In the DNA methylation data analysis, we first estimated the cell-type proportions of each sample with a published algorithm. Next, we performed a surrogate variable analysis to identify potential confounding factors in our microarray data. Finally, we conducted a multiple linear regression analysis in consideration of these factors, including estimated cell-type proportions, and identified aberrant DNA methylation in SCZ at 2,552 CpG loci at a 5% false discovery rate correction. Our results suggest that altered DNA methylation may be involved in the pathophysiology of SCZ, and cell heterogeneity adjustments may be necessary for DNA methylation analysis.

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Section: Introductionmentioning

confidence: 99%

Aberrant DNA Methylation of Blood in Schizophrenia by Adjusting for Estimated Cellular Proportions

et al. 2014

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“…Due to the roles of IL‐4, IL‐10, and IFN‐γ in the initiation, development, and regulation of the Th1/Th2 system, the IFN‐γ/IL‐4 and IFN‐γ/IL‐10 ratios have been deemed indicators of Th1/Th2 immunity. Although Th1/Th2 imbalance has been implicated in SCH, the vast majority of relevant studies examined individual Th1/Th2 cytokines . Only two studies examined IFN‐γ/IL‐4 in SCH; one found unchanged in vitro ratios, while the other noted increased in vivo ratios …”

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confidence: 99%

Is T‐helper type 2 shift schizophrenia‐specific? Primary results from a comparison of related psychiatric disorders and healthy controls

Chiang

Riedel²,

Schwarz³

et al. 2013

Psychiatry Clin Neurosci

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Aim: An imbalance between T-helper type 1 (Th1) and type 2 (Th2) cytokines has been implicated in schizophrenia, although empirical evidence is rare. The aim of this study was to examine if a Th1/Th2 imbalance occurs in schizophrenia and schizophrenia-related disorder.Methods: Twenty-six subjects with schizophrenia, 26 subjects with schizophrenia-related disorders, and 26 healthy controls were recruited. The Human Th1/Th2 Cytokine Cytometric Bead Array Kit-II was utilized to assess serum Th1/Th2 cytokines and ratios simultaneously. MANOVA was used to detect differences among the three diagnostic groups in distinct Th1/ Th2 cytokines/ratios. Pearson/Spearman correlations were used to examine the relationships between distinct Th1/Th2 cytokines/ratios and clinical/ psychopathological data in schizophrenia.Results: Interferon (IFN)-g/interleukin (IL)-4, IFN-g/ IL-10, IL-2/IL-4, and tumor necrosis factor (TNF)-a/IL-4 ratios were significantly decreased in schizophrenia, but not in schizophrenia-related disorders compared to healthy controls. IFN-g/IL-4 and IFN-g/ IL-10 in schizophrenia subjects positively correlated with age, but not in schizophrenia-related disorder subjects or in healthy controls. Conclusion:A clear Th2 shift was observed in schizophrenia, but not in schizophrenia-related disorders. The Th2 shift in schizophrenia appeared to be an aberrant developmental phenomenon.

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“…In recent studies, studies of epigenetic regulation in the human brain have been applied to mental disorders, including schizophrenia and major depression [92][93][94][95][96]. In recent studies, studies of epigenetic regulation in the human brain have been applied to mental disorders, including schizophrenia and major depression [92][93][94][95][96].…”

Section: Bdnf Gene and Epigenetic Regulation In Schizophreniamentioning

confidence: 99%

Effects of Antipsychotics on the BDNF in Schizophrenia

Tl¹

2013

Current Medicinal Chemistry

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Brain-derived neurotropic factor (BDNF) is involved in the development of the brain, and likely influences the neuroplasticity in schizophrenia. BDNF is also believed to interact with other neurotransmitter systems implicated in schizophrenia, such as dopamine, glutamate, serotonin and GABA. Therefore, BDNF is a candidate gene for schizophrenia. In past decades, the blood (serum or plasma) BDNF protein levels and BDNF gene alleles and genotypes to the clinical features of schizophrenia, such as age of onset, clinical subtypes, symptom severity, and drug response, have been evaluated among different populations. However, the results are still inconsistent. Further, different drugs have been reported to have different effects on BDNF protein levels. A cross-sectional survey revealed that serum BDNF levels in chronic schizophrenic patients treated with clozapine exceeded those of patients treated with risperidone or with typical antipsychotics. In recent times, BDNF epigenetic studies have also been conducted in clinical studies of schizophrenia to address the question of why patients with the same gene genotype and alleles have different clinical presentations. In addition, the effects of different antipsychotic drugs on gene methylation and protein acetylation have also been reported. In conclusion, more data are needed regarding BDNF in the brain and in peripheral blood, including protein levels, single nucleotide polymorphisms, epigenetic regulation, and clinical data in order to understand the role of BDNF in schizophrenia.

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Is DNA methylation responsible for immune system dysfunction in schizophrenia?

Cited by 4 publications

References 115 publications

Aberrant DNA Methylation of Blood in Schizophrenia by Adjusting for Estimated Cellular Proportions

Aberrant DNA Methylation of Blood in Schizophrenia by Adjusting for Estimated Cellular Proportions

Is T‐helper type 2 shift schizophrenia‐specific? Primary results from a comparison of related psychiatric disorders and healthy controls

Effects of Antipsychotics on the BDNF in Schizophrenia

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