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Epigenetic modifications in schizophrenia and related disorders: molecular scars of environmental exposures and source of phenotypic variability


Richetto, Juliet; Meyer, Urs (2021). Epigenetic modifications in schizophrenia and related disorders: molecular scars of environmental exposures and source of phenotypic variability. Biological Psychiatry, 89(3):215-226.

Abstract

Epigenetic modifications are increasingly recognized to play a role in the etiology and pathophysiology of schizophrenia and other psychiatric disorders with developmental origins. Here, we summarize clinical and preclinical findings of epigenetic alterations in schizophrenia and relevant disease models and discuss their putative origin. Recent findings suggest that certain schizophrenia risk loci can influence stochastic variation in gene expression through epigenetic processes, highlighting the intricate interaction between genetic and epigenetic control of neurodevelopmental trajectories. In addition, a substantial portion of epigenetic alterations in schizophrenia and related disorders may be acquired through environmental factors and may be manifested as molecular "scars." Some of these scars can influence brain functions throughout the entire lifespan and may even be transmitted across generations via epigenetic germline inheritance. Epigenetic modifications, whether caused by genetic or environmental factors, are plausible molecular sources of phenotypic heterogeneity and offer a target for therapeutic interventions. The further elucidation of epigenetic modifications thus may increase our knowledge regarding schizophrenia's heterogeneous etiology and pathophysiology and, in the long term, may advance personalized treatments through the use of biomarker-guided epigenetic interventions.

Abstract

Epigenetic modifications are increasingly recognized to play a role in the etiology and pathophysiology of schizophrenia and other psychiatric disorders with developmental origins. Here, we summarize clinical and preclinical findings of epigenetic alterations in schizophrenia and relevant disease models and discuss their putative origin. Recent findings suggest that certain schizophrenia risk loci can influence stochastic variation in gene expression through epigenetic processes, highlighting the intricate interaction between genetic and epigenetic control of neurodevelopmental trajectories. In addition, a substantial portion of epigenetic alterations in schizophrenia and related disorders may be acquired through environmental factors and may be manifested as molecular "scars." Some of these scars can influence brain functions throughout the entire lifespan and may even be transmitted across generations via epigenetic germline inheritance. Epigenetic modifications, whether caused by genetic or environmental factors, are plausible molecular sources of phenotypic heterogeneity and offer a target for therapeutic interventions. The further elucidation of epigenetic modifications thus may increase our knowledge regarding schizophrenia's heterogeneous etiology and pathophysiology and, in the long term, may advance personalized treatments through the use of biomarker-guided epigenetic interventions.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:05 Vetsuisse Faculty > Institute of Veterinary Pharmacology and Toxicology
Dewey Decimal Classification:570 Life sciences; biology
Scopus Subject Areas:Life Sciences > Biological Psychiatry
Uncontrolled Keywords:Biological Psychiatry
Language:English
Date:1 February 2021
Deposited On:19 Feb 2021 15:40
Last Modified:21 Feb 2021 21:59
Publisher:Elsevier
ISSN:0006-3223
OA Status:Hybrid
Publisher DOI:https://doi.org/10.1016/j.biopsych.2020.03.008
Project Information:
  • : FunderSNSF
  • : Grant ID310030_188524
  • : Project TitleResilience and Susceptibility in A Mouse Model of Infection-Mediated Neurodevelopmental Disorders
  • : FunderSNSF
  • : Grant IDPZ00P3_180099
  • : Project TitleMicrobiota-dependent epigenetic programming of specific CNS cell populations
  • : FunderFP7
  • : Grant ID228662
  • : Project TitleIREMO - intelligent REactive polymer composites MOulding

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