A breakthrough study has provided new insights into the biological basis of mood disorders, such as depression and bipolar, that offers a promising blood test aimed at a personalised approach to treatment.
The study by Indiana University School of Medicine researchers led by Dr Alexander Niculescu, professor of psychiatry, builds on previous research conducted by Niculescu and his colleagues into blood biomarkers that track suicidality as well as pain, post-traumatic stress disorder (PTSD), and Alzheimer’s disease.
The team has developed a blood test composed of RNA biomarkers that can distinguish how severe a patient’s depression is, their risk of severe depression in the future, and their risk of future bipolar disorder, or manic-depressive illness. The test also informs tailored medication choices for patients.
A breakthrough in mental disorder diagnosis
The study, funded by the National Institutes of Health and which took place over four years with over 300 participants recruited primarily from the patient population at the Richard L. Roudebush VA Medical Center in Indianapolis, used a careful four-step approach of discovery, prioritisation, validation, and testing.
“We have pioneered the area of precision medicine in psychiatry over the last two decades, particularly over the last 10 years. This study represents a current state-of-the-art outcome 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 such as oncology. Ultimately, the mission is to save and improve lives.”
The researchers recorded what changed in terms of the biomarkers in the study participant’s blood over the period between the highs and lows. They then used large databases developed from all previous studies in the field to cross-validate and prioritise their findings, validating the top 26 candidate biomarkers in independent cohorts of people with clinically severe depression or mania. The biomarkers were tested in additional independent cohorts to determine how strong they were at predicting who is ill, and who will become ill in the future.
This allowed the researchers to demonstrate how to match patients with medications, including finding a new potential medication to treat depression.
Niculescu said: “Through this work, we wanted to develop blood tests for depression and for bipolar disorder, to distinguish between the two and to match people to the right treatments.
“Blood biomarkers are emerging as important tools in disorders where subjective self-report by an individual, or a clinical impression of a health care professional, are not always reliable. These blood tests can open the door to precise, personalised matching with medications, and objective monitoring of response to treatment.”
Niculescu’s team also found that mood disorders are underlined by circadian clock genes – the genes that regulate seasonal, day-night, and sleep-wake cycles.
“That explains why some patients get worse with seasonal changes, and the sleep alterations that occur in mood disorders,” Niculescu said.
The research has opened the door for their findings to be translated into clinical practice, as well as help with new drug development.
“Blood biomarkers offer real-world clinical practice advantages. The brain cannot be easily biopsied in live individuals, so we’ve worked hard over the years to identify blood biomarkers for neuropsychiatric disorders,” Niculescu said. “Given the fact that 1 in 4 people will have a clinical mood disorder episode in their lifetime, the need for and importance of efforts such as ours cannot be overstated.”