Worldwide, 1 in 4 people will suffer from a depressive episode in their
lifetime.
While current diagnosis and treatment approaches are largely trial and
error, a breakthrough 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 a precision medicine approach to
treatment.
Led by Alexander B. Niculescu, MD, PhD, Professor of Psychiatry at IU School
of Medicine, the study was published today in the high impact journal
Molecular Psychiatry . The work builds on previous research conducted by
Niculescu and his colleagues into blood biomarkers that track suicidality as
well as pain, post-traumatic stress disorder and Alzheimer's disease.
"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," said Niculescu. "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 team's work describes the development of a blood test, composed of RNA
biomarkers, that can distinguish how severe a patient's depression is, the
risk of them developing severe depression in the future, and the risk of
future bipolar disorder (manic-depressive illness). The test also informs
tailored medication choices for patients.
This comprehensive study 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. The team used a careful
four-step approach of discovery, prioritization, validation and testing.
First, the participants were followed over time, with researchers observing
them in both high and low mood states--each time recording what changed in
terms of the biological markers (biomarkers) in their blood between the two
states.
Next, Niculescu's team utilized 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
cohorts of clinically severe people with depression or mania. Last, 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.
From this approach, researchers were then able to demonstrate how to match
patients with medications--even finding a new potential medication to treat
depression.
"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," said Niculescu. "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, personalized
matching with medications, 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-night and
sleep-wake cycles.
"That explains why some patients get worse with seasonal changes, and the
sleep alterations that occur in mood disorders," said Niculescu.
According to Niculescu, the work done by his team has opened the door for
their findings to be translated into clinical practice, as well as help with
new drug development. Focusing on collaboration with pharmaceutical
companies and other doctors in a push to start applying some of their tools
and discoveries in real-world scenarios, Niculescu said he believes the work
being done by his team is vital in improving the quality of life for
countless patients.
"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," said
Niculescu. "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."
Reference:
H. Le-Niculescu, K. Roseberry, S. S. Gill, D. F. Levey, P. L. Phalen, J.
Mullen, A. Williams, S. Bhairo, T. Voegtline, H. Davis, A. Shekhar, S. M.
Kurian, A. B. Niculescu. Precision medicine for mood disorders: objective
assessment, risk prediction, pharmacogenomics, and repurposed drugs.
Molecular Psychiatry, 2021; DOI:
10.1038/s41380-021-01061-w
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