Mathematician seeks biomarker to diagnose major depression

Vulnerability index could differentiate major depression disorders and predict suicide risk

By Kristen O’Reilly

UMass Medical School Communications

July 13, 2012
  Premananda Indic, PhD 

What if a psychiatrist could give a patient with depression a wrist monitor that analyzed the body’s physiological rhythms to determine whether the patient has a bipolar or a unipolar depression, or whether the patient is at risk for suicide?


A UMass Medical School bio-mathematician is working with researchers from Harvard Medical School, the University of Parma, Italy, and Swinburne University, Australia, to investigate such a biomarker, which has shown promise in early small trials. This Vulnerability Index (VI) could give psychiatrists a new objective diagnostic tool, rather than having to rely on patients who may be unwilling or unable to accurately describe their moods.

The index is derived from data gathered by an electronic actigraphic device—a monitor worn on the non-dominant wrist 24 hours a day—that records activity levels arising from body movements. According to Premananda Indic, PhD, research assistant professor in neurology, when compared with clinician assessment data as well as subjective data collected from surveys completed by outpatients at the University of Parma who were already diagnosed with major depression, the Vulnerability Index accurately differentiated between patients with bipolar and unipolar disorders, and showed a “strong correlation” with suicidal thinking in these patients.

“Treatments for bipolar and unipolar depression are very different, so having an objective indicator would be very helpful in starting the correct treatment quickly,” said Dr. Indic. “And if a suicide risk is uncovered, immediate family members and other care givers can be alerted to monitor a patient closely and be prepared for a potential intervention.”

Because this study involved only a small number of participants, the researchers are continuing to test the index in further clinical studies with larger populations at McLean Hospital in Belmont.

A bio-mathematician who studies the dynamics of physiological systems by employing methods in nonlinear dynamics and nonlinear signal processing, Indic had little background in mood disorders before investigating ways his mathematical expertise could be translated into clinical treatments. He teamed up with Paola Salvatore, MD, research associate in psychiatry at Harvard Medical School and McLean Hospital as well as assistant professor in psychiatry at the University of Parma, who is an expert in clinical mood disorders and shared an interest in the connection between circadian rhythms of psychomotor activity and depression.

“A nonlinear dynamics approach objectively analyzes the hidden-to-the-naked-eye dimension of biological rhythms in mood disorders while psychopathology explores the hidden realm of subjective experiences of individuals suffering from mood disorders that is often overlooked due to its ‘unreliable quality of being subjective,’” said Dr. Salvatore. “The potential correlation between objective measures and subjective disturbances can provide crucial insights regarding biological mechanisms of mood disorders, also making subjective experience of sufferers regain its central role in clinical practice.”

Previous studies have connected changes in circadian rhythms with clinical affective states, and actigraphy has specifically documented changes in motility in different phases of bipolar illness. A previously published study by Indic, Salvatore and other colleagues indicated higher VI scores were found in subjects with high vulnerability to bipolar disorder.

“This may indicate there is something in your physiology that is causing a mood change,” said Indic. “We don’t know the exact cause of this, but there may be something underlying it.”

Discovering a biomarker for suicide risk would be valuable for populations such as military veterans that have seen an increase in suicides due to post-traumatic stress syndrome.

The latest findings were published online in the June 12 edition of PLoS One. In addition to Indic and Salvatore, authors include Greg Murray, PhD, from the Swinburne University of Technology; Ross J Baldessarini, MD, from Harvard Medical School and McLean Hospital; and Carlo Maggini, MD, Mario Amore, MD, Tiziana Meschi, MD, and Loris Borghi, MD, from the University of Parma.