DNA methylation of the BDNF gene and its relevance to psychiatric disorders

Ikegame, Tempei; Bundo, Miki; Murata, Y.; Kasai, Kiyoto; Kato, Takeshi; Iwamoto, Kazuya

doi:10.1038/jhg.2013.65

Cited by 146 publications

(121 citation statements)

References 65 publications

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“…Concordant DNA methylation profiles in brain and blood samples from the same individuals suggest that blood might hold promise as surrogate for brain tissue to detect DNA methylation. [28][29][30] Genome-wide methylation arrays revealed similar methylation patterns for the HOX genes in breast cancers and white blood cells, which suggests that methylation is more likely to be a normal developmental and tissue-specific process that does not directly relate to the malignant mechanism. 31 Interestingly, functional in silico analysis using the MENT database showed no correlation with gene expression in normal brain and blood tissues for the methylation of 2 HOXB7 promoter CpGs but there is evidence that lower HOXB7 methylation values in brain tightly regulate Figure 3.…”

Section: Discussionmentioning

confidence: 98%

DNA methylation analysis of Homeobox genes implicatesHOXB7hypomethylation as risk factor for neural tube defects

et al. 2015

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Section: Discussionmentioning

confidence: 98%

DNA methylation analysis of Homeobox genes implicatesHOXB7hypomethylation as risk factor for neural tube defects

et al. 2015

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“…25,[27][28][29][30][31][32][33]36 To reach this goal, we stressed pregnant dams with a combination of stressors: restraint stress with 24-h constant light disturbance throughout the gestational period. Light disturbance has been reported to induce anxiety-like and depressive-like responses in both rodents and humans.…”

Section: Discussionmentioning

confidence: 99%

Gestational stress induces depressive-like and anxiety-like phenotypes through epigenetic regulation of BDNF expression in offspring hippocampus

et al. 2016

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Exposure to stressful life events during pregnancy exerts profound effects on neurodevelopment and increases the risk for several neurodevelopmental disorders including major depression. The mechanisms underlying the consequences of gestational stress are complex and remain to be elucidated. This study investigated the effects of gestational stress on depressive-like behavior and epigenetic modifications in young adult offspring. Gestational stress was induced by a combination of restraint and 24-hour light disturbance to pregnant dams throughout gestation. Depressive-like and anxiety-like behaviors of young adult offspring were examined. The expression and promoter methylation of brain derived neurotrophic factor (BDNF) were measured using RT-qPCR, Western blot, methylated DNA immunoprecipitation (MeDIP) and chromatin immunoprecipitation (ChIP). In addition, the expressions of histone deacetylases (HDACs) and acetylated histone H3 lysine 14 (AcH3K14) were also analyzed. Our results show that offspring from gestational stress dams exhibited depressive-like and anxiety-like behaviors. Biochemically, stress-offspring showed decreased expression of BDNF, increased expression of DNMT1, HDAC1, and HDAC2, and decreased expression of AcH3K14 in the hippocampus as compared to non-stress offspring. Data from MeDIP and ChIP assays revealed an increased methylation as well as decreased binding of AcH3K14 on specific BDNF promoters. Pearson analyses indicated that epigenetic changes induced by gestational stress were correlated with depressive-like and anxiety-like behaviors. These data suggest that gestational stress may be a suitable model for understanding the behavioral and molecular epigenetic changes observed in patients with depression.

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“…Using DNA from whole blood, it has also been suggested that the promotor region of the BDNF gene has higher methylation levels in people with Sz [31] and this alteration may also be present in the brain [32] . Although the meta analysis showed that serum/plasma BDNF levels did not correlate with either the positive or negative symptom in Sz people [30] , the plasma BDNF levels were positively correlated (r 2 = 0.14) with certain cognitive functions (e.g., semantic generation tasks) [33] and auditory processing after computerized cognitive training [34] .…”

Section: General Description Of the Included Studiesmentioning

confidence: 99%

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

Lai

Scarr

Udawela

et al. 2016

WJP

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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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DNA methylation of the BDNF gene and its relevance to psychiatric disorders

Cited by 146 publications

References 65 publications

DNA methylation analysis of Homeobox genes implicatesHOXB7hypomethylation as risk factor for neural tube defects

DNA methylation analysis of Homeobox genes implicatesHOXB7hypomethylation as risk factor for neural tube defects

Gestational stress induces depressive-like and anxiety-like phenotypes through epigenetic regulation of BDNF expression in offspring hippocampus

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

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