The whole-body perspective and the role of miRNA-143 in Schizophrenia

Medical News: Schizophrenia, a complex mental disorder, has long been viewed as a condition primarily affecting the brain. However, new research is shifting this view towards a "whole-body" concept of schizophrenia, suggesting that the disease might involve multiple bodily systems. This Medical News report delves into the implications of this fresh perspective, highlighting the role of miRNA-143, a small molecule implicated in various functions across the body. The study was conducted by researchers from the Royal College of Surgeons in Ireland (RCSI) and Soochow University, China, and sheds new light on the biological mechanisms that could influence the course and symptoms of schizophrenia.


The whole-body perspective and the role of miRNA-143 in Schizophrenia

Schizophrenia: A Whole-Body Disease?
Traditionally, schizophrenia has been considered a brain disorder, characterized by psychotic symptoms such as hallucinations, delusions, and cognitive impairments. However, growing evidence points to the involvement of other bodily systems, including the cardiovascular system, metabolic processes, immunity, and even the gut-brain axis. This article highlights how the new research provides insights into how schizophrenia might be more than a brain condition but one that affects the whole body.
 
In the first phase of their study, the research team sought to explore how schizophrenia is linked to cardiovascular disease, diabetes, and immune dysfunctions. They examined how the gut-brain connection, a vital link between mental health and digestive health, plays a part in the symptoms experienced by patients with schizophrenia.
 
Cardiovascular Abnormalities in Schizophrenia
The study found compelling evidence that schizophrenia patients exhibit abnormalities in cardiovascular structure and function. These abnormalities are not merely a consequence of lifestyle or medication but are intrinsic to the disease itself. Through advanced imaging techniques, researchers observed smaller left and right ventricular volumes in the hearts of patients, along with thicker heart walls. These changes increase the risk of cardiovascular disease, a significant factor in the reduced life expectancy observed in schizophrenia patients.
 
The link between these cardiac anomalies and schizophrenia is further supported by genetic data. Researchers discovered that patients with a higher genetic risk for schizophrenia also have an elevated risk of developing heart disease. This highlights the potential for genetic risk factors to exert effects beyond the brain, influencing other crucial systems within the body.
 
Metabolic Syndrome and Diabetes: A Hidden Risk
Metabolic syndrome, a cluster of conditions that increase the risk of heart disease, stroke, and type 2 diabetes, is another key area of concern for schizophrenia patients. The study revealed that those with schizophrenia have a much higher likelihood of developing metabolic syndrome, with significant elevations in fasting blood glucose levels, insulin resistance, and abnormal cholest erol levels. Interestingly, patients with schizophrenia are also more likely to have a family history of diabetes, suggesting that genetic factors contributing to schizophrenia might also predispose individuals to metabolic issues.
 
In addition, the team found that metabolic abnormalities in schizophrenia were present even before the introduction of antipsychotic medications, which are known to affect metabolism. This suggests that metabolic dysfunction is a core component of the disease rather than a side effect of treatment.
 
The Role of the Immune System
Schizophrenia has also been linked to immune system dysfunctions. The study identified increased levels of inflammatory markers, such as cytokines, in the blood of schizophrenia patients. These markers, including interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), indicate a chronic state of inflammation.
 
Moreover, researchers noted higher levels of immune cells like monocytes and neutrophils in patients with schizophrenia, pointing to an overactive immune response. These findings suggest that immune dysregulation may play a significant role in the disease's progression and symptoms. Chronic inflammation may also explain some of the physical health issues that schizophrenia patients face, such as cardiovascular disease and diabetes.
 
Cancer and Schizophrenia: An Unexpected Link
Another surprising finding from the study was the relationship between schizophrenia and certain types of cancer. Schizophrenia patients were found to be at a higher risk of developing breast, lung, and colorectal cancers. While this association might partly be due to lifestyle factors, such as smoking, there is also evidence to suggest that schizophrenia and cancer share common genetic risk factors.
 
Genetic analysis revealed that several genes implicated in schizophrenia are also involved in the development of various cancers. For instance, miRNA-143, the molecule at the center of this study, has been shown to influence both cancer development and schizophrenia risk, making it a crucial point of intersection between the two conditions.
 
Gut-Brain Axis: The Missing Link?
The gut-brain axis, which refers to the communication between the gastrointestinal system and the brain, is increasingly being recognized as a critical factor in mental health. In schizophrenia, disruptions to the gut microbiome - the community of microorganisms in the digestive tract - have been linked to symptom severity. This study highlights how genetic factors affecting the gut could also influence brain function, leading to the psychiatric symptoms seen in schizophrenia.
 
Notably, changes in gut health and microbiome composition are common in schizophrenia patients, and these changes could exacerbate inflammation and other immune responses, further complicating the disease.
 
miRNA-143: The Key to Understanding Schizophrenia?
At the core of this groundbreaking research is the molecule miRNA-143, a small RNA molecule that regulates gene expression. miRNA-143 was found to be significantly involved in several key areas related to schizophrenia, including brain function, immune response, metabolism, and cardiovascular health.
 
In schizophrenia, miRNA-143 appears to influence brain processes by regulating dopamine levels, a neurotransmitter closely linked to the disease's symptoms. Additionally, miRNA-143 is involved in controlling the expression of neuregulin-1 (NRG1), a protein that plays a vital role in brain development and has long been associated with schizophrenia.
 
Beyond the brain, miRNA-143 is also implicated in the regulation of insulin sensitivity and cardiovascular function. This multi-system involvement makes miRNA-143 an exemplary molecule that could explain why schizophrenia affects various parts of the body beyond the brain.
 
A Step Towards New Treatments
One of the most promising aspects of the study is its potential for developing new treatments. By targeting miRNA-143, researchers hope to create therapies that not only address the psychiatric symptoms of schizophrenia but also the physical health issues associated with the disease. For instance, manipulating miRNA-143 could help reduce inflammation, improve cardiovascular health, and prevent metabolic syndrome, offering a more holistic approach to treatment.
 
Conclusion: A Whole-Body Approach to Schizophrenia
This study marks a significant shift in how we understand schizophrenia. Rather than being a purely brain-based disorder, schizophrenia is increasingly seen as a whole-body condition, affecting multiple systems. The involvement of miRNA-143 across these systems suggests that schizophrenia may result from coordinated molecular processes rather than random genetic events.
 
As research continues to unravel the complex web of interactions between the brain, body, and genes, new avenues for treatment and prevention are likely to emerge. By focusing on molecules like miRNA-143, we may soon be able to develop therapies that not only improve mental health outcomes but also address the physical comorbidities that shorten the lifespan of people with schizophrenia.
 
The study findings were published in the peer-reviewed journal: Biomolecules.
https://www.mdpi.com/2218-273X/14/9/1185
 
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