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Using Blood Tests to Diagnose Depression and Bipolar Disorder

By: Sai Srihaas Potu

Major depressive disorder and generalized anxiety disorder are among the most commonly diagnosed mental illnesses in the USA; both are associated with a high societal and economic burden. Treatment for major depressive disorder and generalized anxiety disorder consists of pharmacological and psychological interventions. Three commonly used psychological interventions are cognitive behavioral therapy (CBT), interpersonal therapy, and supportive therapy.

Depression is the most prevalent psychiatric disorder worldwide and is the most common mental illness appearing in primary care. According to the World Health Organization (WHO), approximately 350 million people suffer from depression worldwide. As for global morbidity, measured in disability-adjusted life years, depressive episodes increased by 37% between 1990 and 2010, and it has been projected that by 2030, it will be the leading cause of disability in developed countries.

Approximately 20% of all depressed patients develop a chronic course. Untreated depression is associated with a decreased quality of life, increased suicide risk (four times more than the general population), and progressively worse health.

Furthermore, diagnosis is complicated, since it is often based on criteria as opposed to very specific symptoms, which may be difficult to recognize by poorly trained professionals. Furthermore, oftentimes, patients do not seek out health assistance due to social stigma. It is commonly believed that the probability of experiencing a depressive episode increases with certain genetic, cognitive, medical, environmental, and social factors.

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.

This new blood test can distinguish the severity of a person’s depression and their risk for developing severe depression at a later point. The test can also determine if a person is at risk for developing bipolar disorder. Researchers say the blood test can also assist in tailoring individual options for therapeutic interventions.

Led by Alexander B. Niculescu, MD, Ph.D., Professor of Psychiatry at IU School of Medicine, the study 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.

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.

The researchers believe that 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, is 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.

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.

A depressive episode in the context of a major depressive disorder is a period characterized by low mood and other depression symptoms that lasts for 2 weeks or more. When experiencing a depressive episode, a person can try to make changes to their thoughts and behaviors to help improve their mood. Symptoms of a depressive episode can persist for several weeks or months at a time. Less commonly, depressive episodes last for over a year.

Blood biomarkers offer real-world clinical practice advantages. The brain cannot be easily biopsied in live individuals, so researchers worked hard over the years to identify blood biomarkers for neuropsychiatric disorders. 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 cannot be overstated. It is important that researchers continue to analyze and understand the biomarkers behind depressive episodes as they could be very prevalent during the COVID-19 pandemic.


1. H. Le-Niculescu, K. Roseberry, S.S. Gill, et al. Precision medicine for mood disorders: objective assessment, risk prediction, pharmacogenomics, and repurposed drugs. Molecular Psychiatry. 2021.

2. Hegerl U, Bottner A-C, Holtschmidt-Täschner B, et al. Onset of depressive episodes is faster in patients with bipolar versus unipolar depressive disorder: evidence from a retrospective comparative study. Journal of Clinical Psychiatry. 2008.

3. Nuggerud-Galeas S., Oliván Blázquez B., Perez Yus M. C., Valle-Salazar B., Aguilar-Latorre A., Magallón Botaya R. Factors associated with depressive episode recurrences in primary care: a retrospective, descriptive study. Frontiers in Psychology. 2020.