INDIANAPOLIS – Worldwide, 1 in 4 people will suffer from a depressive episode during their lifetime.
Although current approaches to diagnosis and treatment are mostly trial and error, a groundbreaking study by Indiana University School of Medicine researchers sheds new light on the biological basis of mood disorders and offers a promising blood test aimed at accessing precision medicine in treatment.
Under the leadership of Alexander B. Niculescu, Ph.D., Professor of Psychiatry at the IU School of Medicine, the study was published today in a highly influential journal Molecular psychiatry . The work is based on previous research conducted by Niculescu and colleagues on blood biomarkers that track suicide, as well as pain, posttraumatic stress disorder and Alzheimer’s disease.
“We have been pioneers in the field of precision medicine in psychiatry for the last two decades, especially in the last 10 years. This study represents the current top outcome of our efforts,” Niculescu said. “This is part of our efforts to move psychiatry from the 19th to the 21st century. To help it become like other modern areas like oncology. Ultimately, the mission is to save and improve lives.”
The team’s work describes the development of a blood test, composed of an RNA biomarker, that can distinguish how severe a patient’s depression is, the risk of developing severe depression in the future, and the risk of future bipolar disorder (manic-depressive illness). The test also informs patients about customized drug choices.
This comprehensive study took place over four years, and over 300 participants were recruited primarily from the patient population at Richard L. Roudebush VA Medical Center in Indianapolis. The team used a careful approach of detection, prioritization, validation and testing in four steps.
First, participants were monitored over time, and researchers observed them in both high and low moods – each time noting what had changed in terms of biological markers (biomarkers) in their blood between the two states.
Further, Niculescu’s team used large databases developed from all previous field studies, to cross-validate and prioritize their findings. From here, researchers confirmed 26 major candidate biomarkers in independent groups of clinically difficult people with depression or mania. Finally, biomarkers were tested in additional independent groups to determine how strong they are in predicting who is sick and who will get sick in the future.
From this approach, researchers were then able to show how to pair patients with medications – they even found a new potential cure for depression.
“Through this work, we wanted to develop blood tests for depression and bipolar disorder, to differentiate between the two and adapt people to the right treatments,” Niculescu said. “Blood biomarkers emerge as important tools in disorders in which an individual’s subjective self-report or clinical impression of a healthcare professional is not always reliable. These blood tests can open the door to accurate, personalized drug matching and objective monitoring of treatment responses.”
In addition to the diagnostic and therapeutic advances revealed in their latest study, Niculescu’s team found that mood disorders are underlined by circadian clock genes – genes that regulate seasonal, day-night and waking sleep.
“This explains why some patients are exacerbated by seasonal changes and sleep changes that occur with mood disorders,” Niculescu said.
According to Niculescu, the work done by his team opened the door to translate their findings into clinical practice, as well as help develop new drugs. Focusing on working with pharmaceutical companies and other physicians in an attempt to begin applying some of their tools and discoveries in real-world scenarios, Niculescu said he believes the work his team does is vital to improving the quality of life of countless patients.
“Blood biomarkers offer real benefits of clinical practice. The brain cannot be easily biopsied in living individuals, so we have worked hard for years to identify blood biomarkers for neuropsychiatric disorders,” Niculescu said. “Given the fact that 1 in 4 people will have an episode of clinical mood disorder during their lifetime, the need and importance of an effort like ours cannot be overestimated.”
This research was supported by the National Institutes of Health under award numbers 1DP20D007363 and R01mh117431 and the VA Merit Award 2I01CX000139. Content is the sole responsibility of Indiana University School of Medicine and does not necessarily represent the official views of the National Institutes of Health or the VA.
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