Epigenetics of Schizophrenia

Gavin, David P.; Floreani, Christina

doi:10.1016/b978-0-12-801311-3.00005-6

Cited by 20 publications

(10 citation statements)

References 242 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition to the aforementioned approaches, epigenetic abnormalities may be a potential target for the treatment of patients with schizophrenia [ 108 ]. Recent data have indicated that epigenetic abnormalities in the disorder are more complex and include a combination of restrictive chromatin, open chromatin, and dysfunctional communication between various epigenetic mediators, leading to faulty regulation [ 109 , 110 ]. Epigenetic factors can account for both genetic and environmental risks and their interactions in the pathogenesis of schizophrenia.…”

Section: Novel Treatment Targetsmentioning

confidence: 99%

New Targets for Schizophrenia Treatment beyond the Dopamine Hypothesis

Yang

Tsai

2017

IJMS

222

129

View full text Add to dashboard Cite

Schizophrenia has been primarily associated with dopamine dysfunction, and treatments have been developed that target the dopamine pathway in the central nervous system. However, accumulating evidence has shown that the core pathophysiology of schizophrenia might involve dysfunction in dopaminergic, glutamatergic, serotonergic, and gamma-aminobutyric acid (GABA) signaling, which may lead to aberrant functioning of interneurons that manifest as cognitive, behavioral, and social dysfunction through altered functioning of a broad range of macro- and microcircuits. The interactions between neurotransmitters can be modeled as nodes and edges by using graph theory, and oxidative balance, immune, and glutamatergic systems may represent multiple nodes interlocking at a central hub; imbalance within any of these nodes might affect the entire system. Therefore, this review attempts to address novel treatment targets beyond the dopamine hypothesis, including glutamate, serotonin, acetylcholine, GABA, and inflammatory cytokines. Furthermore, we outline that these treatment targets can be possibly integrated with novel treatment strategies aimed at different symptoms or phases of the illness. We anticipate that reversing anomalous activity in these novel treatment targets or combinations between these strategies might be beneficial in the treatment of schizophrenia.

show abstract

Section: Novel Treatment Targetsmentioning

confidence: 99%

New Targets for Schizophrenia Treatment beyond the Dopamine Hypothesis

Yang

Tsai

2017

IJMS

222

129

View full text Add to dashboard Cite

show abstract

“…This strategy holds the promise to elucidate the function of non-coding, disease-associated loci, and moves towards the development of testable hypotheses regarding biological processes involved in the pathogenesis of SCZ and other disorders. For further information see the following reviews and the references therein: (Keverne, 2014) (Svrakic et al, 2013) (Gavin and Floreani, 2014) (Akbarian, 2014) (Jakovcevski and Akbarian, 2012). …”

Section: The Role Of the Neuroepigenome In Schizophreniamentioning

confidence: 99%

Understanding the genetic liability to schizophrenia through the neuroepigenome

Fullard

Halene

Giambartolomei

et al. 2016

Schizophrenia Research

View full text Add to dashboard Cite

The Psychiatric Genomics Consortium-Schizophrenia Workgroup (PGC-SCZ) recently identified 108 loci associated with increased risk for schizophrenia (SCZ). The vast majority of these variants reside within non-coding sequences of the genome and are predicted to exert their effects by affecting the mechanism of action of cis regulatory elements (CREs), such as promoters and enhancers. Although a number of large-scale collaborative efforts (e.g. ENCODE) have achieved a comprehensive mapping of CREs in human cell lines or tissue homogenates, it is becoming increasingly evident that many risk-associated variants are enriched for expression Quantitative Trait Loci (eQTLs) and CREs in specific tissues or cells. As such, data derived from previous research endeavors may not capture fully cell-type and/or region specific changes associated with brain diseases. Coupling recent technological advances in genomics with cell-type specific methodologies, we are presented with an unprecedented opportunity to better understand the genetics of normal brain development and function and, in turn, the molecular basis of neuropsychiatric disorders. In this review, we will outline ongoing efforts towards this goal and will discuss approaches with the potential to shed light on the mechanism(s) of action of cell-type specific cis regulatory elements and their putative roles in disease, with particular emphasis on understanding the manner in which the epigenome and CREs influence the etiology of SCZ.

show abstract

“…Epigenetic changes in brain are widely hypothesized to partly mediate risk for schizophrenia. 34 Multiple epigenetic changes have been assessed in schizophrenia (reviewed in 35 ), and methylation differences in peripheral blood 36–38 and brain 39 have been associated with schizophrenia. Of the many epigenetic changes, chromatin accessibility is particularly important and is a conserved eukaryotic feature characteristic of active regulatory elements, including promoters, enhancers, silencers, insulators, transcription factor binding sites and active histone modifications.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Chromatin Accessibility in Prefrontal Cortex of Schizophrenia Cases and Controls

Bryois

Garrett

Song

et al. 2017

Preprint

View full text Add to dashboard Cite

Schizophrenia genome-wide association (GWA) studies have identified over 150 regions of the genome that are associated with disease risk, yet there is little evidence that coding mutations contribute to this disorder. To explore the mechanism of non-coding regulatory elements in schizophrenia, we performed ATAC-seq on adult prefrontal cortex brain samples from 135 individuals with schizophrenia and 137 controls, and identified 118,152 ATAC-seq peaks. These accessible chromatin regions in brain are highly enriched for SNP-heritability for schizophrenia (10.6 fold enrichment, P=2.4×10−4, second only to genomic regions conserved in Eutherian mammals) and replicated in an independent dataset (9.0 fold enrichment, P=2.7×10−4). This degree of enrichment of schizophrenia heritability was higher than in open chromatin found in 138 different cell and tissue types. Brain open chromatin regions that overlapped highly conserved regions exhibited an even higher degree of heritability enrichment, indicating that conservation can identify functional subsets within regulatory elements active in brain. However, we did not identify chromatin accessibility differences between schizophrenia cases and controls, nor did we find an interaction of chromatin QTLs with case-control status. This indicates that although causal variants map within regulatory elements, mechanisms other than differential chromatin may govern the contribution of regulatory element variation to schizophrenia risk. Our results strongly implicate gene regulatory processes involving open chromatin in the pathogenesis of schizophrenia, and suggest a strategy to understand the hundreds of common variants emerging from large genomic studies of complex brain diseases.

show abstract

Epigenetics of Schizophrenia

Cited by 20 publications

References 242 publications

New Targets for Schizophrenia Treatment beyond the Dopamine Hypothesis

New Targets for Schizophrenia Treatment beyond the Dopamine Hypothesis

Understanding the genetic liability to schizophrenia through the neuroepigenome

Evaluation of Chromatin Accessibility in Prefrontal Cortex of Schizophrenia Cases and Controls

Contact Info

Product

Resources

About