Alexander B. Niculescu, MD, PhD. Credit: IU School of Medicine
Worldwide, 1 in 4 people will suffer from a depressive episode during their lifetime.
While current diagnostic and treatment approaches are largely trial and error, a breakthrough study by Indiana University School of Medicine sheds new light on the biological basis of mood disorders and offers a promising blood test aimed at a precise medicine approach to treatment.
Led by Alexander B. Niculescu, MD, PhD, Professor of Psychiatry at the IU School of Medicine, the study was published today (April 8, 2021) in the journal with great impact. Molecular psychiatry. The work builds on previous research conducted by Niculescu and his colleagues into blood biomarkers covering suicide as well as pain, post-traumatic stress disorder and Alzheimer’s disease.
‘We have been a pioneer in the field of precision medicine in psychiatry for the past two decades, especially in the last ten years. This study is a current result of our efforts, ‘Niculescu said. ‘This is part of our effort to bring psychiatry from the 19th century into the 21st century. To help it become like other contemporary fields like oncology. Ultimately, the mission is to save and improve lives. ”
The team’s work describes the development of a blood test, composed of RNA biomarkers, which can distinguish how severe a patient’s depression is, the risk that they may develop severe depression in the future, and the risk of future bipolar disorder (manic-depressive illness). The test also provides information on custom medicine choices.
This comprehensive study took place over four years, with more than 300 participants recruited primarily from the patient population at Richard L. Roudebush VA Medical Center in Indianapolis. The team used a rigorous four-step approach of discovery, prioritization, validation, and testing.
First, the participants were followed over time, with researchers observing them in high and low mood conditions – each time recording what changed in terms of the biological markers (biomarkers) in their blood between the two states.
Next, Niculescu’s team used large databases developed from all previous studies in the field, to cross-validate and prioritize their findings. From here, researchers validated the top 26 candidate biomarkers in independent groups of clinically severe people with depression or mania. Finally, the biomarkers were tested in additional groups to determine how strongly they predicted who was ill and who would become ill in the future.
From this approach, researchers were then able to demonstrate how to fit patients with medication – even to find a new potential medication to treat depression.
“Through this work, we wanted to develop blood tests for depression and bipolar disorder, to distinguish between the two and match people to the right treatments,” Niculescu said. ‘Blood biomarkers appear as important tools in disorders where subjective self-report by an individual, or a clinical impression of a health professional, is not always reliable. These blood tests can open the door for precise, personal adjustments with medication, and objective monitoring of response to treatment. ”
In addition to the diagnostic and therapeutic advances discovered in their latest study, Niculescu’s team found that mood disorders are underlined by circadian clock genes – the genes that regulate seasonal, day-and-sleep-wake cycles.
“This explains why some patients get worse with seasonal changes and the sleep changes that occur with mood disorders,” Niculescu said.
According to Niculescu, the work done by his team opened the door for their findings to be translated into clinical practice, as well as assistance with the development of new drugs. Niculescu has focused on collaborating with pharmaceutical companies and other physicians to begin applying some of their tools and discoveries in real-world situations, and he believes the work his team is doing is essential to improving the quality of life for many patients.
‘Blood biomarkers offer clinical practice benefits in the real world. The brain cannot be easily biopsied in living individuals, which is why we have worked hard over the years to identify blood biomarkers for neuropsychiatric disorders, ”said Niculescu. “Given the fact that 1 in 4 people will have a clinical mood disorder during their lifetime, the need for and importance of efforts like ours cannot be overstated.”
Reference: “Precision Medicine for Mood Disorders: Objective Assessment, Risk Prediction, Pharmacogenomics and Reused Drugs” by H. Le-Niculescu, K. Roseberry, SS Gill, DF Levey, PL Phalen, J. Mullen, A. Williams, S Bhairo, T. Voegtline, H. Davis, A. Shekhar, SM Kurian en AB Niculescu, 8 April 2021, Molecular psychiatry.
DOI: 10.1038 / s41380-021-01061-w
This research was supported by the National Institutes of Health under grant number 1DP20D007363 and R01mh117431 and a VA merit award 2I01CX000139. The content is the sole responsibility of the Indiana University School of Medicine and does not necessarily represent the official views of the National Institutes of Health or the VA.