Abstract
Schizophrenia is a severe psychiatric disorder with a complex array of signs and symptoms that causes very significant disability in young people. While schizophrenia has a strong genetic component, with heritability around 80%, there is also a very significant range of environmental exposures and stressors that have been implicated in disease development and neuropathology, such as maternal immune infection, obstetric complications, childhood trauma and cannabis exposure. It is postulated that epigenetic factors, as well as regulatory non-coding RNAs, mediate the effects of these environmental stressors. In this review, we explore the most well-known epigenetic marks, including DNA methylation and histone modification, along with emerging RNA mediators of epigenomic state, including miRNAs and lncRNAs, and discuss their collective potential for involvement in the pathophysiology of schizophrenia implicated through the postmortem analysis of brain tissue. Given that peripheral tissues, such as blood, saliva, and olfactory epithelium have the same genetic composition and are exposed to many of the same environmental exposures, we also examine some studies supporting the application of peripheral tissues for epigenomic biomarker discovery in schizophrenia. Finally, we provide some perspective on how these biomarkers may be utilized to capture a signature of past events that informs future treatment.
Highlights
Schizophrenia (SZ) is a debilitating psychiatric disorder that affects 0.7% of people at some point in their life [1]
We examine some of the current literature exploring changes in DNA methylation, histone modifications, and RNA mediators of epigenomic state, including microRNAs and long non-coding RNAs, in the brain and peripheral tissue in schizophrenia patients and discuss their involvement in disease etiology and potential application as state and trait biomarkers of environmental exposures
Detectable in body fluids are expressed in many tissues, and a large proportion are thought to originate from blood cells, such that disturbances in blood cell counts and hemolysis can change plasma levels of miRNA biomarkers by up to 50-fold [150]; so, the observation of alterations in their concentrations in one pathology does not mean that the same miRNA cannot contribute to other diseases
Summary
Schizophrenia (SZ) is a debilitating psychiatric disorder that affects 0.7% of people at some point in their life [1]. As an alternative to studies focusing on the central nervous system, epigenetic dysregulation in peripheral tissues, such as blood, serum, saliva, and olfactory epithelium, which are more accessible in living patients, have been widely investigated While these studies are useful for detecting biomarkers, they can provide additional insight into disease etiology with some concordance reported between gene expression and epigenomic modification in blood and brain tissue. We know from a wealth of imaging [14], neurophysiology [15], and neuropathological examination [16] that this disorder is associated with a loss of structural and functional connectivity [17], which could be derived to some extent by epigenomic mechanisms that fail to integrate environmental input received through neural activity or other signaling mechanisms This is supported through several lines of evidence from the genetics, through cell biology, to molecular neuropathology. Evidence for the involvement of these dynamic nucleic acids in schizophrenia and other psychiatric syndromes has been emerging, which collectively weaves a rich tapestry for molecular dysfunction in epigenomic regulation, expressed through the disruption of neural connectivity and homeostasis
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