“This is very exciting because right now, there isn’t a blood marker for disorders affecting the brain.”
BALTIMORE — A pioneering new blood test is being developed to detect mental health disorders. Johns Hopkins Children’s Center researchers are hoping this blood test can identify psychiatric and neurological issues, including postpartum depression, schizophrenia, and epilepsy. This research illuminates a novel method of detecting disease-associated changes in the brain by analyzing genetic material found in human blood.
The study, published in the journal Molecular Psychiatry, centers on the analysis of extracellular vesicles (EVs) in the blood. EVs are tiny, fatty sacs filled with genetic materials like messenger RNA (mRNA), which play a crucial role in cell communication. These vesicles are released by all tissues in the body, including the brain, carrying specific pieces of mRNA that reflect the gene activity within their tissue of origin.
This research builds upon a previous Johns Hopkins Medicine study from September 2022, which observed altered EV communication in pregnant women who later developed postpartum depression.
“We only detected placenta-specific EVs during the pregnancy, and not after birth. This was a proof of concept, that we can detect EVs that are coming from a specific tissue or organ,” says study senior author Dr. Sarven Sabunciyan, an assistant professor of pediatrics at the Johns Hopkins University School of Medicine, in a university release.
By examining EVs containing mRNA from lab-grown human brain tissue and comparing these findings to known brain functions and disorders, the team has identified specific mRNAs in the blood that are linked to various brain disorders. These mRNAs serve as potential biological markers for conditions that are currently diagnosed primarily through clinical interviews, thus representing a significant advancement in the field.
“This is very exciting, because right now, there isn’t a blood marker for disorders affecting the brain,” explains study co-author Dr. Lena Smirnova, an assistant professor in the Department of Environmental Health and Engineering at the Johns Hopkins Bloomberg School of Public Health. “Essentially, these conditions are diagnosed by clinical interviews between patients and providers.”
The development of a blood test to detect these disorders would be a monumental step forward, allowing for early intervention and potentially preventing severe outcomes such as suicidal behavior.
The study’s methodology involved identifying brain-specific mRNAs in blood EVs and verifying their association with brain functions and disorders through extensive genetic pathway analysis. This led to the discovery of 13 mRNAs linked to postpartum depression, showcasing the potential of EV mRNAs as indicators of brain activity and pathology.
The ultimate goal of this research is to create a straightforward blood test that can detect changes in blood EV mRNA levels indicative of mental disorders, thereby providing a non-invasive, accessible diagnostic tool. Future directions for the team include applying this technique to develop tests for other conditions, such as autism spectrum disorder.
However, researchers have noted that their findings, particularly those related to depression, might be specific to postpartum depression, as the study was conducted with samples from female participants only. This highlights the need for further research to validate these biomarkers across a broader spectrum of brain disorders.
Bipolar Disorder Blood Test Under Development
Scientists have long been working to use blood tests as an easier way to diagnose various conditions. Researchers at Cambridge University have developed a novel approach to diagnosing bipolar disorder by combining an online psychiatric assessment with a blood test. The study, published in JAMA Psychiatry in October, aims to address the frequent misdiagnosis of bipolar disorder as major depressive disorder, which can lead to inappropriate treatment and potential harm to patients.
Bipolar disorder affects approximately 80 million people worldwide and is characterized by extreme mood swings, including periods of low mood and mania. However, patients often seek medical attention during depressive episodes, leading to misdiagnosis in nearly 40 percent of cases. Distinguishing between bipolar disorder and major depressive disorder is crucial, as the two conditions require different pharmacological treatments.
The research team utilized samples and data from the UK’s Delta study, which involved over 3,000 participants diagnosed with major depressive disorder within the past five years and currently experiencing depressive symptoms. Participants completed an extensive online mental health assessment and provided dried blood samples for analysis of over 600 metabolites.
The study found that the blood test alone could accurately diagnose up to 30 percent of bipolar disorder patients, with its effectiveness significantly improving when combined with the digital mental health assessment. The biomarkers primarily correlated with lifetime manic symptoms and remained significant even after accounting for potential confounding factors, such as medication.
While comprehensive psychiatric assessments are highly effective for diagnosing bipolar disorder, they often involve long waiting times and extensive durations. The researchers believe that incorporating biomarker testing into the diagnostic process could ensure patients receive the appropriate treatment more quickly and alleviate some of the pressures on medical professionals.
The study emphasizes the biological basis of mental illness, helping patients understand that their condition is not just “in their mind.” Furthermore, the identification of biomarkers could lead to the discovery of potential drug targets for mood disorders, paving the way for better treatments in the future.
The researchers suggest that a combination of the online assessment and biomarker test would be ideal, as they complement each other and cater to different patient preferences. With the research being an exciting development in the field, a patent has been filed by Cambridge Enterprise, the University’s commercialization arm.
Anxiety Biomarkers?
Scientists at Indiana University developed a blood test that they say can objectively measure anxiety, determine an individual’s risk of developing anxiety, and identify the most effective treatment options. The test, which analyzes RNA biomarkers in the blood, has been validated and is being developed for wider use by physicians at MindX Sciences.
Anxiety is a challenging condition to diagnose and treat, as it often goes unrecognized until symptoms become severe. The current approach relies on subjective self-reporting and can lead to the prescription of potentially addictive medications. The new blood test, with study results published in March 2023, aims to provide a more objective and personalized approach to anxiety diagnosis and treatment.
Professor Alexander Niculescu, MD, PhD, and his team have previously developed blood tests for various mental health conditions, including pain, depression, bipolar disorder, and post-traumatic stress disorder. This latest study followed a similar approach, assessing three independent groups: discovery, validation, and testing. Participants underwent blood tests every three to six months or whenever they experienced a new psychiatric hospitalization.
By examining RNA biomarkers in the blood, researchers were able to identify a patient’s current state of anxiety and match them with specific medications and nutraceuticals that may be most effective based on their personal biology. The test can also help inform other treatment options, such as cognitive behavioral therapy or lifestyle changes, and evaluate an individual’s risk of developing higher levels of anxiety in the future.
The potential benefits of this new blood test are significant, as it could help identify individuals with undiagnosed anxiety, prevent unnecessary suffering, and reduce the reliance on potentially addictive medications. Additionally, the test could contribute to the development of new, personalized treatments for anxiety that focus on individual biomarkers.
Prof. Niculescu believes that this new test could be used in combination with other blood tests to provide a comprehensive view of a patient’s overall mental health and risk of future mental health problems. The goal is to offer a panel test as part of a patient’s regular wellness visits to evaluate their mental health over time and prevent future distress.
Gene Discovery Could Yield Depression Screening
A major study conducted by scientists at Yale University and published in Nature Neuroscience in 2021 revealed that 170 genes are linked to depression. The findings shed light on the genetic complexity of depression and could lead to the development of a blood test for easier diagnosis and personalized treatment options.
The study analyzed data from 2.5 million individuals worldwide, including 1.2 million people from Britain, Finland, and customers of genetics company 23andMe. Researchers compared this data to an additional 1.3 million DNA samples from 23andMe and found 178 statistically significant genetic variations associated with depression. The study also included more than 300,000 U.S. veterans, which may help identify those at risk of developing major depression, anxiety, or PTSD.
The genetic mutations discovered in this study provide insights into the underlying biology of depression. For example, the NEGR1 protein, found in the hypothalamus, has been linked to depression, confirming previous research by the late Yale neuroscientist Ronald Duman. Understanding the functions of these genetic variants could lead to the development of targeted drugs for depression treatment.
The study’s co-senior authors, Professor Murray Stein from UC-San Diego and Professor Joel Gelernter from Yale University, emphasize the importance of these findings in bringing forward new ways to treat people suffering from depression. The genetic complexity of depression and related mental illnesses means that there may be hundreds or even thousands of mutations yet to be discovered.
Depression affects around 16 million Americans at any given time, with rates rising over the last decade and doubling during the coronavirus pandemic. Symptoms include low mood, lethargy, loss of pleasure, decreased appetite, and reduced libido. The identification of genetic factors contributing to depression could lead to the development of a screening program and personalized treatment options, potentially improving the lives of millions of people affected by this debilitating condition.
Blood Test Could Even Detect Suicidal Thoughts
Researchers at the University of California San Diego School of Medicine have made a significant breakthrough by identifying potential blood markers that could detect suicidal thoughts in individuals with major depressive disorder. This discovery, published in Translational Psychiatry this past December, opens up new possibilities for early intervention and personalized treatment approaches, potentially saving lives.
While traditionally associated with psychological symptoms, the research highlights the physical dimensions of depression, particularly in cellular metabolism. By focusing on metabolic markers, researchers aim to refine diagnostic and treatment strategies for mental illnesses.
The implications of this research are far-reaching. A blood test capable of identifying individuals at higher risk of suicide could allow doctors to intervene early and prevent tragedies. Moreover, the unique metabolic changes revealed in the study offer potential targets for individualized treatment, such as supplementing specific nutrient deficiencies like folate or carnitine, rather than relying on a one-size-fits-all approach. Understanding the role of mitochondrial dysfunction in depression also opens doors for developing new drugs that target this critical cellular machinery, with potential benefits for other chronic diseases linked to depression.
The study analyzed blood samples from 99 individuals with treatment-refractory depression who also experienced suicidal thoughts. The researchers found unique patterns in five different chemicals circulating in the blood, indicating metabolic changes associated with depression and suicidal ideation. This remarkable ability to discern individuals at heightened risk for suicide based on blood metabolites could lead to a groundbreaking diagnostic tool.
Metabolomics, the study of chemical processes involving metabolites, has played a crucial role in this research. Dr. Robert Naviaux, a study co-author, emphasizes the importance of this technology in understanding how body chemistry influences mental states and behaviors. The identification of specific biomarkers related to suicidal ideation underscores the potential of metabolomics in transforming mental health diagnostics and treatment.
The possibility of a blood test for detecting suicidal thoughts opens new doors in personalizing mental health care, allowing for early intervention in high-risk individuals and exploring novel treatment approaches. This research paves the way for investigating the metabolic aspects of depression and its comorbidities, potentially improving outcomes for the many diseases that lead to depression and, ultimately, helping to save more lives.
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Modern psychiatrists still believe that mental disorders are from experiences in life, not biologically based. They think a person can talk his way out of a metabolic disorder. They are still promoting the religious/mythological theories of Jung and Freud.