Methylome-Wide Association Study of Schizophrenia

Åberg, Karolina A.; McClay, Joseph L.; Nerella, Srilaxmi; Clark, Shaunna L.; Kumar, Gaurav; Chen, Wenan; Khachane, Amit N.; Xie, Linying; Hudson, Alexandra D; Gao, Guimin; Harada, Aki; Hultman, Christina M.; Sullivan, Patrick F.; Magnusson, Patrik K. E.; Oord, Edwin J. C. G. van den

doi:10.1001/jamapsychiatry.2013.3730

Cited by 228 publications

(115 citation statements)

References 74 publications

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“…Further studies have reported that in PBMC from people during their first onset of Sz there were 603 CpG sites (2% of CpG sites) that were differentially methylated [119] , the genes that were particularly affected were related to the nuclear lumen, transcription factor binding, and nucleotide binding. Using whole blood, a methylome wide association study showed that 139 CpG sites (0.003% of CpG sites involved in analyses) were differently methylated in people with Sz, highly implicating an exon and 3'UTR of FAM63B and an intron of RELN [117] . Overall, differentially methylated CpG sites can be detected in peripheral blood of people with Sz and many of the methylation was reported in the promoter regions of genes, therefore they may affect transcription of these genes.…”

Section: Epigenetics and Micrornamentioning

confidence: 99%

Biomarkers in schizophrenia: A focus on blood based diagnostics and theranostics

Lai

Scarr

Udawela

et al. 2016

WJP

137

108

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Identifying biomarkers that can be used as diagnostics or predictors of treatment response (theranostics) in people with schizophrenia (Sz) will be an important step towards being able to provide personalized treatment. Findings from the studies in brain tissue have not yet been translated into biomarkers that are practical in clinical use because brain biopsies are not acceptable and neuroimaging techniques are expensive and the results are inconclusive. Thus, in recent years, there has been search for blood-based biomarkers for Sz as a valid alternative. Although there are some encouraging preliminary data to support the notion of peripheral biomarkers for Sz, it must be acknowledged that Sz is a complex and heterogeneous disorder which needs to be further dissected into subtype using biological based and clinical markers. The scope of this review is to critically examine published blood-based biomarker of Sz, focusing on possible uses for diagnosis, treatment response, or their relationship with schizophreniaassociated phenotype. We sorted the studies into six categories which include: (1) brain-derived neurotrophic factor; (2) inflammation and immune function; (3) neurochemistry; (4) oxidative stress response and metabolism; (5) epigenetics and microRNA; and (6) transcriptome and proteome studies. This review also summarized the molecules which have been conclusively reported as potential blood-based biomarkers for Sz in different blood cell types. Finally, we further discusses the pitfall of current blood-based studies and suggest that a prediction model-based, Sz specific, blood World Journal of Psychiatry W J P oriented study design as well as standardize blood collection conditions would be useful for Sz biomarker development.

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Section: Epigenetics and Micrornamentioning

confidence: 99%

Biomarkers in schizophrenia: A focus on blood based diagnostics and theranostics

Lai

Scarr

Udawela

et al. 2016

WJP

137

108

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“…Such studies have suggested the possibility of identifying biomarkers for schizophrenia [47,48,49,50,51,52], major depressive disorder [53,54] and posttraumatic stress disorder [55], and have also been used to study medication-induced metabolic changes [56,57]. In bipolar disorder, metabolomic studies have been undertaken in urine samples to identify potential biomarkers [58,59,60,61]. We report our findings from unbiased metabolic profiling of fibroblasts from patients with bipolar disorder and healthy controls, under normal growth conditions as well as under physiologic perturbations.…”

Section: Discussionmentioning

confidence: 99%

Perturbational Profiling of Metabolites in Patient Fibroblasts Implicates α-Aminoadipate as a Potential Biomarker for Bipolar Disorder

et al. 2016

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Many studies suggest the presence of aberrations in cellular metabolism in bipolar disorder. We studied the metabolome in bipolar disorder to gain insight into cellular pathways that may be dysregulated in bipolar disorder and to discover evidence of novel biomarkers. We measured polar and nonpolar metabolites in fibroblasts from subjects with bipolar I disorder and matched healthy control subjects, under normal conditions and with two physiologic perturbations: low-glucose media and exposure to the stress-mediating hormone dexamethasone. Metabolites that were significantly different between bipolar and control subjects showed distinct separation by principal components analysis methods. The most statistically significant findings were observed in the perturbation experiments. The metabolite with the lowest p value in both the low-glucose and dexamethasone experiments was α-aminoadipate, whose intracellular level was consistently lower in bipolar subjects. Our study implicates α-aminoadipate as a possible biomarker in bipolar disorder that manifests under cellular stress. This is an intriguing finding given the known role of α-aminoadipate in the modulation of kynurenic acid in the brain, especially as abnormal kynurenic acid levels have been implicated in bipolar disorder.

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“…Bromberg et al found no difference in peripheral leukocyte methylation profile between patients with schizophrenia and healthy controls 44. Recently, one methylome-wide association study found some candidate sites of methylation in blood samples in patients with schizophrenia 45. Similar abnormal methylation profiles were also found by Kinoshita et al46 Indeed, our results partially agreed with the sex-dependent difference of methylation profile found in the study by Shimabukuro et al42; however, there were significantly higher 5-hmc levels in men than in women, but not in 5-mc levels.…”

Section: Discussionmentioning

confidence: 99%

Age-associated decrease in global DNA methylation in patients with major depression

Tseng¹,

Lin²,

Yu³

et al. 2014

NDT

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BackgroundEvidence has supported a role of DNA methylation in the pathophysiology of mood disorders. The purpose of the current study is to examine 5-methylcytosine (5-mc) and 5-hydroxymethylcytosine (5-hmc) levels in patients with major depressive disorder (MDD) at different disease states.MethodsForty-nine patients with MDD and 25 healthy control subjects were included. The severity in the disease was assessed by using the 17-item Hamilton Rating Scale of Depression (HAM-D) (HAM-D ≥19 for severe MDD and HAM-D ≤7 for remitted MDD). The 5-mc and 5-hmc levels in leukocyte DNA were measured using an enzyme-linked immunosorbent assay-based method.ResultsWe found a significant decrease in 5-hmc and trends of decreasing 5-mc levels in patients with severe MDD compared to healthy controls (P=0.059 for 5-mc and P=0.013 for 5-hmc). The decrease in the level exists only in the older age group (P=0.035 for 5-mc and P=0.002 for 5-hmc) but not in the younger age group (P=0.077 for 5-mc and P=0.620 for 5-hmc). In addition, the 5-mc level was found to be inversely correlated with disease severity (P=0.011).ConclusionOur results support a decrease in global DNA methylation associated with age in patients with severe depression. Further studies are needed to clarify the role of the methylation level as a disease marker of depression and whether antidepressant treatment changes the methylation profiles.

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Methylome-Wide Association Study of Schizophrenia

Cited by 228 publications

References 74 publications

Biomarkers in schizophrenia: A focus on blood based diagnostics and theranostics

Biomarkers in schizophrenia: A focus on blood based diagnostics and theranostics

Perturbational Profiling of Metabolites in Patient Fibroblasts Implicates α-Aminoadipate as a Potential Biomarker for Bipolar Disorder

Age-associated decrease in global DNA methylation in patients with major depression

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