Journal of Pain Management and Therapy

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Commentary - Journal of Pain Management and Therapy (2023) Volume 7, Issue 5

A short note on Neuroepigenetics of schizophrenia.

Stols Daniela*

Department of Vascular Medicine, Amsterdam UMC, Location AMC, Meibergdreef, Amsterdam, Netherlands

*Corresponding Author:
Stols Daniela
Department of Vascular Medicine
Amsterdam UMC, Location AMC, Meibergdreef
Amsterdam, Netherlands

Received:25-Aug-2023,Manuscript No. AAPMT-23-113341; Editor assigned: 28-Aug-2023, PreQC No. AAPMT-23-113341(PQ); Reviewed:11-Sept-2023, QC No. AAPMT-23-113341; Revised:16-Sept-2023, Manuscript No. AAPMT-23-113341(R); Published:23-Sept-2023, DOI: 10.35841/aapmt- 7.5.164

Citation: Daniela S. A short note on Neuroepigenetics of schizophrenia. J Pain Manage Ther. 2023;7(5):164

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Schizophrenia, a complex and debilitating mental disorder, has intrigued researchers for centuries. Despite significant advancements in our understanding of its genetic and environmental factors, the precise mechanisms underlying schizophrenia remain elusive. In recent years, the emerging field of neuroepigenetics has provided a new lens through which to explore the intricate interplay between genes and the environment in the context of this perplexing disorder. This article delves into the neuroepigenetics of schizophrenia, shedding light on the epigenetic modifications that may contribute to its development and progression. Schizophrenia is a severe mental disorder characterized by a range of symptoms, including hallucinations, delusions, disorganized thinking, and social withdrawal. It typically manifests in early adulthood and can have a profound impact on an individual's life, affecting their ability to work, maintain relationships, and lead a fulfilling existence. While genetics undoubtedly play a role in the development of schizophrenia, it is far from being solely a genetic disorder.

Neuroepigenetic revolution

Epigenetics is the study of heritable changes in gene function that do not involve alterations to the underlying DNA sequence. Instead, epigenetic modifications can influence gene expression by modifying the structure of DNA or the proteins with which it interacts. The most well-known epigenetic mechanisms include DNA methylation and histone modifications, both of which can influence how genes are turned on or off. Neuroepigenetics, a specialized branch of epigenetics, focuses on the epigenetic processes that occur within the nervous system, including the brain. This burgeoning field has garnered significant attention in recent years as researchers seek to unravel the complex web of epigenetic changes that underlie neurological and psychiatric disorders, including schizophrenia[1].

Epigenetic mechanisms in schizophrenia

DNA methylation: One of the most extensively studied epigenetic mechanisms in schizophrenia is DNA methylation. DNA methylation involves the addition of a methyl group (CH3) to a cytosine base in the DNA molecule. This modification often leads to gene silencing, preventing the associated gene from being expressed. Studies have identified differential DNA methylation patterns in individuals with schizophrenia compared to healthy controls. Notably, these differences often involve genes associated with brain development, synaptic function, and neurotransmitter regulation. For example, the Reelin gene, which plays a crucial role in neuronal migration and synaptic plasticity, has been found to have altered methylation patterns in individuals with schizophrenia. Furthermore, environmental factors such as prenatal exposure to stress, malnutrition, or toxins can influence DNA methylation patterns and increase the risk of developing schizophrenia later in life. These findings highlight the complex interplay between genetic predisposition and environmental influences in the epigenetic regulation of schizophrenia.

Histone modifications: Histones are proteins that package DNA into a compact structure called chromatin, and modifications to these proteins can also impact gene expression. Various histone modifications, including acetylation, methylation, and phosphorylation, play critical roles in regulating gene activity within the brain. In schizophrenia, dysregulation of histone modifications has been implicated in the altered expression of genes related to neurotransmitter systems, neurodevelopmental processes, and synaptic plasticity. For instance, changes in histone acetylation have been linked to disruptions in dopamine signaling, a key factor in the pathophysiology of schizophrenia. Interestingly, histone-modifying enzymes can be targeted by pharmacological interventions, raising the possibility of epigenetic-based therapies for schizophrenia. However, further research is needed to elucidate the specific mechanisms involved and develop effective treatments[2].

Non-Coding RNAs: Non-coding RNAs (ncRNAs) are a diverse group of RNA molecules that do not code for proteins but instead play crucial roles in regulating gene expression. MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are two classes of ncRNAs that have been implicated in the pathogenesis of schizophrenia. MiRNAs are short RNA molecules that can bind to messenger RNAs (mRNAs) and prevent their translation into proteins, thereby regulating gene expression. Aberrant miRNAs expression has been observed in the brains of individuals with schizophrenia, affecting genes involved in synaptic function, neurodevelopment, and neuronal plasticity. LncRNAs are longer RNA molecules that can interact with DNA, RNA, and proteins to modulate gene expression. Some lncRNAs have been shown to influence the expression of genes associated with schizophrenia susceptibility, providing potential therapeutic targets.

Epigenetic clocks: Epigenetic clocks are emerging tools that use DNA methylation patterns to estimate a person's biological age, which may not necessarily correspond to their chronological age. Recent studies have suggested that individuals with schizophrenia often exhibit accelerated epigenetic aging, which could contribute to the cognitive decline and physical health issues often seen in this population. The underlying mechanisms driving this accelerated epigenetic aging in schizophrenia are not fully understood, but it may involve chronic stress, inflammation, and disrupted cellular processes. Investigating these processes may provide valuable insights into the complex relationship between schizophrenia and epigenetic changes.

Interplay of genetics and environment

Schizophrenia is a prime example of the intricate interplay between genetic and environmental factors in the development of a complex disorder. While genetics undoubtedly contribute to susceptibility, the epigenetic modifications discussed here provide a mechanism through which environmental factors can shape gene expression and increase the risk of schizophrenia. Prenatal factors such as maternal stress, malnutrition, and exposure to toxins can alter the epigenetic landscape of a developing fetus, potentially priming the individual for later onset of schizophrenia. Additionally, postnatal experiences, including childhood trauma and chronic stress, can further modify epigenetic marks, influencing the course and severity of the disorder[3].

Therapeutic implications

The neuroepigenetics of schizophrenia holds promise for the development of novel therapeutic interventions. While pharmacological treatments for schizophrenia primarily target neurotransmitter systems, epigenetic-based therapies could provide a more precise and personalized approach.

Targeting DNA methylation: One potential avenue for treatment is the manipulation of DNA methylation patterns using demethylating agents or gene-specific targeting approaches. However, caution is warranted, as global changes in DNA methylation can have unintended consequences. Developing therapies that selectively target specific genes or pathways implicated in schizophrenia is a challenging but promising endeavour[4].

Modulating histone modifications: Histone-modifying enzymes represent attractive targets for drug development. Small molecules that can selectively modulate histone acetylation or methylation patterns could restore normal gene expression in individuals with schizophrenia. Nevertheless, more research is needed to identify the precise targets and mechanisms involved.

RNA-based therapies: Harnessing the power of non-coding RNAs presents another avenue for intervention. Developing miRNA mimics or inhibitors that can restore normal gene expression patterns is a burgeoning field with potential applications in schizophrenia treatment. Additionally, lncRNAs may serve as novel targets for drug development.

Epigenetic clock reversal: Slowing down or reversing accelerated epigenetic aging in individuals with schizophrenia could have significant clinical implications. Identifying interventions, such as lifestyle modifications or pharmacological agents, which can reset the epigenetic clock, may improve outcomes for affected individuals[5].


Schizophrenia remains a complex and enigmatic disorder that challenges our understanding of the brain's inner workings. The emerging field of neuroepigenetics has provided valuable insights into the epigenetic modifications that underlie the development and progression of schizophrenia. DNA methylation, histone modifications, non-coding RNAs, and accelerated epigenetic aging all contribute to the intricate web of epigenetic changes observed in this disorder. Neuroepigenetics continues to grow, so does the promise of novel therapeutic interventions for schizophrenia. Targeting specific epigenetic marks and processes could provide a more precise and personalized approach to treatment, potentially improving the lives of millions affected by this devastating disorder. However, the road ahead is challenging, and further research is needed to unravel the complexities of the neuroepigenetics of schizophrenia fully.


  1. Reddy JK, Hashimoto T.Peroxisomal β-oxidation and peroxisome proliferator-activated receptor α: an adaptive metabolic system.Annu Rev Nutr. 2001;21(1):193-230.
  2. Indexed at, Google Scholar, Cross Ref

  3. Lopez D, Irby RB, McLean MP.Peroxisome proliferator-activated receptor α induces rat sterol carrier protein x promoter activity through two peroxisome proliferator-response elements.Mol. Cell. Endocrinol. 2003;205(1-2):169-84.
  4. Indexed at, Google Scholar, Cross Ref

  5. Pineda Torra I, Jamshidi Y, Flavell DM, et al.Characterization of the human PPARα promoter: Identification of a functional nuclear receptor response element.Mol Endocrinol. 2002;16(5):1013-28.
  6. Indexed at, Google Scholar, Cross Ref

  7. Kersten S, Seydoux J, Peters JM, et al.Peroxisome proliferator-activated receptor α mediates the adaptive response to fasting.J Clin Invest. 1999;103(11):1489-98.
  8. Indexed at, Google Scholar, Cross Ref

  9. French SJ, Cecil JE.Oral, gastric and intestinal influences on human feeding.Physiol Behav. 2001;74(4-5):729-34.
  10. Indexed at, Google Scholar, Cross Ref

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