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Astrocytic abnormalities and global DNA methylation patterns in depression and suicide.

ABSTRACT: Astrocytes are glial cells specific to the central nervous system and involved in numerous brain functions, including regulation of synaptic transmission and of immune reactions. There is mounting evidence suggesting astrocytic dysfunction in psychopathologies such as major depression, however, little is known about the underlying etiological mechanisms. Here we report a two-stage study investigating genome-wide DNA methylation associated with astrocytic markers in depressive psychopathology. We first characterized prefrontal cortex samples from 121 individuals (76 who died during a depressive episode and 45 healthy controls) for the astrocytic markers GFAP, ALDH1L1, SOX9, GLUL, SCL1A3, GJA1 and GJB6. A subset of 22 cases with consistently downregulated astrocytic markers was then compared with 17 matched controls using methylation binding domain-2 (MBD2) sequencing followed by validation with high-resolution melting and bisulfite Sanger sequencing. With these data, we generated a genome-wide methylation map unique to altered astrocyte-associated depressive psychopathology. The map revealed differentially methylated regions (DMRs) between cases and controls, the majority of which displayed reduced methylation levels in cases. Among intragenic DMRs, those found in GRIK2 (glutamate receptor, ionotropic kainate 2) and BEGAIN (brain-enriched guanylate kinase-associated protein) were most significant and also showed significant correlations with gene expression. Cell-sorted fractions were investigated and demonstrated an important non-neuronal contribution of methylation status in BEGAIN. Functional cell assays revealed promoter and enhancer-like properties in this region that were markedly decreased by methylation. Furthermore, a large number of our DMRs overlapped known Encyclopedia of DNA elements (ENCODE)-identified regulatory elements. Taken together, our data indicate significant differences in the methylation patterns specific to astrocytic dysfunction associated with depressive psychopathology, providing a potential framework for better understanding this disease phenotype.

SUBMITTER: Nagy C

PROVIDER: S-EPMC5293540 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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Astrocytic abnormalities and global DNA methylation patterns in depression and suicide.

Nagy C C Suderman M M Yang J J Szyf M M Mechawar N N Ernst C C Turecki G G

Molecular psychiatry 20140325 3

Astrocytes are glial cells specific to the central nervous system and involved in numerous brain functions, including regulation of synaptic transmission and of immune reactions. There is mounting evidence suggesting astrocytic dysfunction in psychopathologies such as major depression, however, little is known about the underlying etiological mechanisms. Here we report a two-stage study investigating genome-wide DNA methylation associated with astrocytic markers in depressive psychopathology. We ...[more]

PMID: 24662927

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Project description:BackgroundDiabetic patients, during the course of the disease, are most likely to experience depressive symptoms that might ultimately lead to suicidal ideation or suicide. The size of literature in diabetes depression/suicide is a good indicator of national and international efforts to address psychological co-morbidities associated with diabetes mellitus (DM). Therefore, the objective of this study was to give a comprehensive analysis, both quantitative and qualitative, of scientific literature in diabetes depression/suicide.MethodsSciVerse Scopus was used to retrieve relevant literature up to 2016.ResultsIn total, 1664 journal documents were retrieved with an average of 26.9 citations per article and an h-index of 98. Publications started in 1949 but showed a steep and noticeable increase after 2001. Retrieved articles were published in 641 different journals with Diabetes Care journal being the top productive one with a total of 130 (7.8%) articles. Researchers from 83 different countries participated in retrieved publications. Researchers from the United States of America participated in publishing 685 articles. There was a strong and positive correlation between research output and Gross Domestic Product (r?=?0.083; p?<?0.001) but not with prevalence or mortality caused by DM. Researchers from 4870 different institutions/organizations participated in publishing retrieved articles. Publications from the University of Washington, Seattle, USA had the highest h-index (38), while "VA medical centers" had the highest number of publications (75; 4.5%). In total, 5715 authors appeared in retrieved articles giving an average of 3.4 authors per article. Top cited articles focused on prevalence, impact of depression on glycemic control, and potential risk of diabetic complications. The total number of publications in depression/suicide in diabetic patients was lesser than that in cardiac (1938) or in cancer (1828) patients. However, publications in diabetes depression/suicide exceeded those in cardiac and cancer in the last 2 years of the study period.ConclusionThe current study showed a noticeable growth of publications indicative of the importance of this topic. Research focusing on the psychiatric component of diabetes mellitus needs to be strengthened and encouraged. At the practical level, screening for depression/suicide among patients attending primary healthcare clinics is needed to optimize health and quality of life of diabetic patients.

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Astrocytic abnormalities and global DNA methylation patterns in depression and suicide.

Publications

Astrocytic abnormalities and global DNA methylation patterns in depression and suicide.

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