A Whole Methylome CpG-SNP Association Study of Psychosis in Blood and Brain Tissue

Oord, Edwin J. C. G. van den; Clark, Shaunna L.; Xie, Lin; Shabalin, Andrey A.; Dozmorov, Mikhail G.; Kumar, Gaurav; Vladimirov, Vladimir I.; Magnusson, Patrik K. E.; Åberg, Karolina A.

doi:10.1093/schbul/sbv182

Cited by 41 publications

(26 citation statements)

References 71 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On the basis of this rationale, several large expression and epigenetic studies have been conducted in peripheral blood lymphocytes. 36 , 37 , 38 A comparison of the co-expression of genes in human brain and human blood revealed co-expression modules that are preserved across tissues, supporting the notion that polymorphisms will result in similar deficits in different cell types. 39 Furthermore, the expression levels of key genes in the preserved modules tended to be more heritable than genes in modules that were not preserved.…”

Section: Introductionmentioning

confidence: 77%

Consistently altered expression of gene sets in postmortem brains of individuals with major psychiatric disorders

Darby¹,

Yolken²,

Sabunciyan³

2016

Transl Psychiatry

View full text Add to dashboard Cite

The measurement of gene expression in postmortem brain is an important tool for understanding the pathogenesis of serious psychiatric disorders. We hypothesized that major molecular deficits associated with psychiatric disease would affect the entire brain, and such deficits may be shared across disorders. We performed RNA sequencing and quantified gene expression in the hippocampus of 100 brains in the Stanley Array Collection followed by replication in the orbitofrontal cortex of 57 brains in the Stanley Neuropathology Consortium. We then identified genes and canonical pathway gene sets with significantly altered expression in schizophrenia and bipolar disorder in the hippocampus and in schizophrenia, bipolar disorder and major depression in the orbitofrontal cortex. Although expression of individual genes varied, gene sets were significantly enriched in both of the brain regions, and many of these were consistent across diagnostic groups. Further examination of core gene sets with consistently increased or decreased expression in both of the brain regions and across target disorders revealed that ribosomal genes are overexpressed while genes involved in neuronal processes, GABAergic signaling, endocytosis and antigen processing have predominantly decreased expression in affected individuals compared to controls without a psychiatric disorder. Our results highlight pathways of central importance to psychiatric health and emphasize messenger RNA processing and protein synthesis as potential therapeutic targets for all three of the disorders.

show abstract

Section: Introductionmentioning

confidence: 77%

Consistently altered expression of gene sets in postmortem brains of individuals with major psychiatric disorders

Darby¹,

Yolken²,

Sabunciyan³

2016

Transl Psychiatry

View full text Add to dashboard Cite

show abstract

“…As psychotic episodes are related with increased neuroinflammation and activated microglia [ 120 , 121 ], it can be hypothesized that pro-inflammatory cytokines may be modulating BDNF mRNA expression via interaction of NF-κB or CREB transcription factors. It is known that schizophrenia patients have upregulated genes for inflammatory cytokines [ 122 , 123 ], and downregulated Bdnf gene transcription [ 124 , 125 ]. Neuroinflammation could be the key factor for the decrease of Bdnf gene expression in schizophrenic patients, as pro-inflammatory cytokines increase methylation of Bdnf gene, leading to a decrease of CREB binding to the specific Bdnf site.…”

Section: Bdnf In Psychiatric Disordersmentioning

confidence: 99%

Brain-Derived Neurotrophic Factor in Brain Disorders: Focus on Neuroinflammation

et al. 2018

View full text Add to dashboard Cite

Brain-derived neurotrophic factor (BDNF) is one of the most studied neurotrophins in the healthy and diseased brain. As a result, there is a large body of evidence that associates BDNF with neuronal maintenance, neuronal survival, plasticity, and neurotransmitter regulation. Patients with psychiatric and neurodegenerative disorders often have reduced BDNF concentrations in their blood and brain. A current hypothesis suggests that these abnormal BDNF levels might be due to the chronic inflammatory state of the brain in certain disorders, as neuroinflammation is known to affect several BDNF-related signaling pathways. Activation of glia cells can induce an increase in the levels of pro- and antiinflammatory cytokines and reactive oxygen species, which can lead to the modulation of neuronal function and neurotoxicity observed in several brain pathologies. Understanding how neuroinflammation is involved in disorders of the brain, especially in the disease onset and progression, can be crucial for the development of new strategies of treatment. Despite the increasing evidence for the involvement of BDNF and neuroinflammation in brain disorders, there is scarce evidence that addresses the interaction between the neurotrophin and neuroinflammation in psychiatric and neurodegenerative diseases. This review focuses on the effect of acute and chronic inflammation on BDNF levels in the most common psychiatric and neurodegenerative disorders and aims to shed some light on the possible biological mechanisms that may influence this effect. In addition, this review will address the effect of behavior and pharmacological interventions on BDNF levels in these disorders.

show abstract

“…Investigating the AL concept in patients with psychotic disorders might also improve our understanding of the mechanisms underlying epigenetic alterations. Indeed, psychotic disorders are also characterized by a number of epigenetic alterations, especially differential DNA methylation, with some concordant patterns in the brain and peripheral tissues (61,62). Our group also revealed that a history of childhood trauma might be associated with lower methylation of LINE-1 sequences, representing surrogate measures of global DNA methylation (14).…”

Section: Summary Of Evidence and Future Directionsmentioning

confidence: 53%

Stress, Allostatic Load, and Psychosis: One Step Forward in Research But Where to Go Next?

Misiak

2020

Front. Psychiatry

View full text Add to dashboard Cite

Stress exposure leads to the activation of several biological mechanisms that have been termed allostasis. These processes enable adaptation to novel situations; however; their prolonged activation exerts systemic and detrimental effects called the allostatic load (AL). The AL concept represents one of useful paradigms to describe biological consequences of chronic stress that might lead to a number of disease outcomes. The AL index, which is a collective measure of cardiovascular, metabolic, neuroendocrine, and immune dysregulations associated with stress exposure, has been found to predict morbidity and mortality in non-clinical populations. Consequently, it has been proposed that the AL concept might be a useful framework to describe biological consequences of chronic stress exposure in patients with psychotic disorders. This perspective article is an overview of studies investigating the AL index and its clinical correlates in patients with psychotic disorders. These studies have consistently reported elevated AL index in patients at the early and chronic course of psychosis. In addition, the AL index has been associated with a higher severity of positive and depressive symptoms, working memory impairments, and lower general functioning. The article provides some critical appraisal of studies in this field and indicates several future directions for investigating the AL concept in psychosis.

show abstract

A Whole Methylome CpG-SNP Association Study of Psychosis in Blood and Brain Tissue

Cited by 41 publications

References 71 publications

Consistently altered expression of gene sets in postmortem brains of individuals with major psychiatric disorders

Consistently altered expression of gene sets in postmortem brains of individuals with major psychiatric disorders

Brain-Derived Neurotrophic Factor in Brain Disorders: Focus on Neuroinflammation

Stress, Allostatic Load, and Psychosis: One Step Forward in Research But Where to Go Next?

Contact Info

Product

Resources

About