Epigenetic Mechanisms in Schizophrenia

Background

Psychiatric disorders are potentially destabilizing conditions that affect a large number of people. These disorders are typified by symptoms that negatively impact the capacity of an individual to engage in daily life activities. The primary treatment intervention for these disorders is the administration of antipsychotics. Antipsychotic interventions, however, achieve incomplete responses to treatment among many patients. The development of a rational drug has been a major challenge due to the lack of comprehensive unifying information concerning the molecular etiology of this disease. The complex genetic architecture of schizophrenia is also an impediment to the development of an effective pharmacological intervention.

A comprehensive review of literature can help to advance knowledge on the pathophysiology of schizophrenia together with the underlying genetic risk architecture, thus paving way for the development of novel treatment interventions (Akbarian, 2014).

Epidemiological studies propose that the pathophysiology of schizophrenia is triggered by an interaction between individual genes and environmental factors (Roth, Lubin, Sodhi & Kleinman, 2009) Research further suggests that the molecular mechanisms that mediate the interactions between these factors play are integral to the onset of schizophrenia. Recent studies also report that epigenetic mechanisms remain labile throughout the lifespan of a cell. These mechanisms are however subject to a range of environmental factors. This indicates that epigenetic mechanisms provide an attractive molecular hypothesis for the role played by environmental factors in the development of schizophrenia.

Disease Description

Schizophrenia is a common psychiatric condition associated with the abnormal interpretation of reality. Approximately 1% of the population suffers from Schizophrenia (Fletcher-Flinn, 2016).

The debilitating mental impact of this disorder makes it hard for an individual to participate in social, economic, and self-care activities. This disorder is typified by a range of symptoms including delusions, disorganized thoughts and hallucinations. These symptoms are categorized as positive symptoms. The negative symptoms of schizophrenia, on the other hand, are apathy, social withdrawal and decreased ability to experience pleasure (Akbarian 2014).

The etiology of schizophrenia is not only complex but also poorly understood. The pathogenesis of this disorder is attributed to a wide range of factors including environmental factors, genetic complications, and neurodevelopmental disturbance (Shorter & Miller, 2015)

This shows that pathogenesis is the interplay of complex genetic and environmental factors. However, no factor has been recognized as the sole cause of this disorder (Smigielski, Jagannath, Rössler, Walitza & Grünblatt, 2020).

Individuals suffering from schizophrenia experience a wide range of health challenges. These challenges are contributed by the fact that the ability to make rational decisions decreases significantly once a person develops schizophrenia (Shen, 2016). For instance, it is estimated that schizophrenia reduces the lifespan of a person by 15 years. The high risk of death is attributed to cardiovascular disorders and suicidal thoughts that are synonymous with schizophrenia.

Schizophrenia is also linked with decreased performance across various measurable parameters including neurochemical balance, synaptic connectivity, neuron number, and volume as well as sensory gating (Föcking et al., 2019).

Irrefutably, numerous neuropathological interpretations of schizophrenia have been postulated over the years. These interpretations together with the complicated genetic risk architecture make it challenging to develop a drug that can address all psychotic mechanisms associated with schizophrenia (Smigielski, Jagannath, Rössler, Walitza & Grünblatt, 2020). The treatment of schizophrenia is based on pharmacological interventions. Individuals are given medications targeting the dopaminergic, monoaminergic, and serotoninergic receptors in the brain (Migdalska-Richards & Mill, 2019). Unfortunately, these medications do not achieve the anticipated response in most patients. Although treatment may improve the mental health of a person, the cognitive impairment associated with this disorder is more disabling in addition to being a permanent feature (Fletcher-Flinn, 2016). Numerous studies are being undertaken to explain the factors that contribute to the incomplete response to treatment.

Genetics

The human genome constitutes 3 billion base pairs of DNA. The DNA is contained in the 23 pairs of chromosomes in the human cells (Jackson, Marks, May, & Wilson, 2018). The DNA functions as the long-term data storage center of the body cells. It also encodes the amino acid sequence in proteins subsequently leading to the formation of normally functioning cells and organs. The presence of DNA variations may, thus, lead to the development of nonfunctional proteins.

Since genetic material can be passed down to the offspring from a parent, children may suffer from genetic disorders that were present in parents. Consequently, genetic factors have irrefutably been shown to play a greater or lesser role in the development of diseases (Jackson, Marks, May, & Wilson, 2018). These genetic factors are mainly attributed to variations in DNA as well as the differences in functions of the DNA. Whereas some of these variations further increase an individual’s risk of certain disorders such as heart diseases, others may reduce the susceptibility to certain conditions. Notably, despite diseases related to genetic abnormalities are individually rare, they contribute to over 80% of the rare diseases (Jackson, Marks, May, & Wilson, 2018).

Schizophrenia is one of the severe mental disorders associated with genetic abnormalities. The inheritance pattern of this disease is, however, largely unknown. The risk of schizophrenia is believed to be greater among family members than unrelated individuals. This, however, does not imply that close relatives of a person with schizophrenia will eventually develop this disorder (McCutcheon, Marques & Howes, 2020). Evidence from twin studies has revealed the possibility of genetic components playing a role in schizophrenia. Nevertheless, only a few genetic loci have been linked to this disorder (McCutcheon, Marques & Howes, 2020). This indicates that further research is still needed to enhance the understanding of genetic impacts on the disorder.

Significance of Epigenetic Mechanisms

Epigenetics is a term used in describing the covalent modifications of chromatin.

Chromatin is the DNA–histone protein complex found in the nucleus of the body cells including the brain cells. Epigenetic mechanisms describe the process through which alterations occur in the chromatin subsequently perpetuating long-term changes in genetic activity in the central nervous system. These changes also contribute to transient variation in gene transcription that plays a role in activity-dependent modulation essential for cognition (Roth, Lubin, Sodhi & Kleinman, 2009).

The exploration of the epigenetic factors of diseases is an important exercise that improves understanding of the potential causes, effects, and treatment interventions of certain disorders. Scientists have long attempted to describe disorders by genetic and environmental factors. Moosavi and Ardekani (2016), however, made it clear that the role of epigenetics in the development of diseases has only gained momentum in the last five decades. The subject of epigenetics has attracted the interest of many parties exploring disorders such as complicated mental disorders, cancers, addiction, and memory disorders among many others.

The definition of epigenetic mechanisms illustrates that the entire content of the DNA is the same in all somatic cells of a particular species (Moosavi & Ardekani, 2016). However, gene expression patterns may differ in certain types of cells. This variation can be clonally inherited. This presumption expresses the significance of studying the epigenetic mechanisms of psychiatric disorders. A comprehensive evaluation of these mechanisms helps to gather more information concerning the role they play in influencing gene activity in various stages. For instance, it is only through epigenetic mechanisms that gene modifications at the translation and post-translation as well as transcriptional and post-transcriptional levels can be better understood (Moosavi & Ardekani, 2016).

Irrefutably, certain epigenetic mechanisms have the potential to contribute to a wide spectrum of consequences leading to more varieties in morphogenesis, adaptability, variability, and cell differentiation (Moosavi & Ardekani, 2016). Therefore, epigenetics helps to broaden the understanding of DNA, histones, and DNA-Binding proteins that play an integral role in changing the chromatin structure without altering the nucleotide sequence of the DNA.

Epigenetics also helps to reveal how alterations can be passed on from one generation to another.

Research Question

The research question that will guide this exercise is based on the epigenetic mechanisms of schizophrenia. Undeniably, epigenetic mechanisms like methylation of the DNA and modification of histone molecules allow for dynamic changes in gene expression throughout the life of the body cells including neurons. This expresses the possibility that these modifications play a role in the emergence of schizophrenia and other psychotic conditions.

The relevance of this essay to Epigenetics

Despite schizophrenia being one of the extensively studied major psychiatric disorders, scientists have not been able to come up with unifying neuropathology. Further, treatment is only 100% beneficial to some patients. Therefore, a review of the epigenetic mechanisms of schizophrenia is important in understanding the pathogenesis of this disorder. This review provides a platform on which to explore crucial aspects of epigenetics. The exercise will generate information essential for the advancement of existing knowledge not only on neurobiology but also on the treatment of schizophrenia. Although reproducible data on molecular alterations associated with schizophrenia exist, the underlying transcriptional and post-transcriptional mechanisms of schizophrenia are largely unclear. This essay explores the epigenetic mechanisms of gene expression related to schizophrenia including DNA methylation and histone modifications. The essay also contains information that can potentially increase the understanding of epigenetic mechanisms and their impact on cognition and complex behaviors subsequently pointing to the therapeutic capability of epigenetic drugs and their targets in the nervous system. Since researchers have suggested the possibility of a connection between epigenetic mechanisms and the risk of schizophrenia, this exercise helps to further dig into evidence on whether pharmacological agents acting on epigenetic pathways can be utilized to address psychotic disorders