Depression Can Now Be Classified And Treated Differently

So far depression could be clubbed into different types, however, it has not led to better treatment outcomes. Depression can now be classified into two specific brain clusters and can be treated differently by transcranial magnetic brain stimulation (TMS), say researchers.

In patients who received transcranial magnetic brain stimulation (TMS) for the treatment of depression, physician-scientists have for the first time discovered two clusters of depressed symptoms that responded to two different neuroanatomical therapeutic targets.

The research team’s discoveries provide new insight into the brain circuitry that underlies depressive symptoms and may enable customised TMS treatment for depression and other psychiatric or neurological disorders.

Depression and the way it manifests

One in four women and one in eight men may experience depression at some point in their lives, making it the most common cause of disability worldwide. According to the most recent government statistics, more than 17 million adults in the United States struggled with the disease in 2017, but clinicians have long understood that depression manifests differently in each person; official diagnostic criteria include weight loss or weight gain, excessive sleeping or insomnia, an inability to focus, or obsessive rumination. Although prior proposed classification methods did not lead to better treatment outcomes, the discipline of psychiatry has yet to arrive to a consensual classification of depression subgroups based on distinctive clinical traits.

Two clusters of depressive symptoms

In patients who underwent transcranial magnetic brain stimulation (TMS) for the treatment of depression, physician-scientists at Beth Israel Deaconess Medical Centre (BIDMC) have now, for the first time, identified two clusters of depressive symptoms that responded to two different neuroanatomical treatment targets.

The team’s research, which was published in the American Journal of Psychiatry, sheds new light on the brain circuitry that underlies depressive symptoms and may help with customised TMS treatment for depression and other psychiatric or neurological problems.

Personalized medicine in psychiatry

“We’ve known for over a century that different brain regions have different functions, and now we can finally translate this into symptom-specific treatment targets,” said Shan H. Siddiqi, MD, a neuropsychiatrist in the Division of Cognitive Neurology at BIDMC and an Instructor in Psychiatry at Harvard Medical School. “We hope this discovery will help to usher in a new era of personalized medicine in psychiatry.”

TMS, a non-invasive therapy that uses strong magnetic fields to alter brain activity, was authorised in 2008 for the treatment of depression in individuals who did not respond well to antidepressant medication. The magnetic coil of the machine is now placed outside the patient’s scalp by TMS practitioners using head measurements, which causes some unintentional variance in the brain circuitry activated. Despite the uncertainty, the well-tolerated therapy has a success rate of roughly 50% to 60%, which is greater than other antidepressant medications.

Identifying two distinct clusters of depressive symptoms

Siddiqi and associates examined outcomes for two distinct cohorts of patients who underwent TMS for treatment-resistant depression by taking advantage of that variation, including senior author Michael D. Fox, MD, PhD, Director of the Laboratory for Brain Network Imaging and Modulation at BIDMC and an Associate Professor of Neurology at Harvard Medical School. Patients self-reported their symptoms using a standardised questionnaire, and a doctor also evaluated them.

Fox developed the method at BIDMC, and Siddiqi and colleagues used it to map each patient’s TMS site to underlying brain circuits. They then compared these maps to the overall change in depression symptoms across individuals. Two unique groups of depressed symptoms were discovered by the investigation, and each grouping responded better to a different TMS target. A larger cluster of symptoms included irritation, sexual boredom, and insomnia, whereas a smaller cluster comprised symptoms including sorrow, diminished interest, and suicidality. These symptom clusters were described by the researchers as “dysphoric” and “anxiosomatic,” respectively.

Improvement based on separate symptom clusters

The scientists then applied these cluster maps to successfully forecast clinical improvement in a different group of patients to corroborate the analyses’ conclusions. The team’s findings are in line with current research that categorises persons with depression into various symptom groupings, or “biotypes.” The study by Siddiqi and Fox, however, adopts the opposite strategy.

“Rather than identify biotypes and then searching for ways to treat them, we started with therapeutic response to an anatomically targeted treatment,” said Siddiqi. “Our novel approach harnesses TMS to causally link neuroanatomy and behaviour. We started with depression and anxiety, but this approach could also be used to find a treatment target for any cluster of psychiatric symptoms.”

Story Source:

Materials provided by Beth Israel Deaconess Medical Center. Note: Content may be edited for style and length.

Journal Reference:

Shan H. Siddiqi, Stephan F. Taylor, Danielle Cooke, Alvaro Pascual-Leone, Mark S. George, Michael D. Fox. Distinct Symptom-Specific Treatment Targets for Circuit-Based Neuromodulation. American Journal of Psychiatry, 2020; 177 (5): 435 DOI: 10.1176/appi.ajp.2019.19090915

Cite This Page:

Beth Israel Deaconess Medical Center. “Targeting depression: Researchers ID symptom-specific targets for treatment of depression.” ScienceDaily. ScienceDaily, 4 May 2020. <>.

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