For the first time, researchers from Beth Israel Deaconess Medical Center (BIDMC) have identified two clusters of depressive symptoms that respond to two distinct treatment targets in patients undergoing transcranial magnetic brain stimulation (TMS).
TMS is a non-invasive procedure that affects brain activity with powerful magnetic fields.
The findings, published in the American Journal of Psychiatry, shed new light on the brain circuitry behind specific symptoms of depression and may pave the way for personalized TMS therapy for depression and other psychiatric or neurological disorders.
Specifically, the analysis identified two distinct clusters of depressive symptoms, with each responding better to a different TMS target.
One cluster included symptoms such as sadness, decreased interest, and suicidality, while a smaller cluster included symptoms such as irritability, sexual disinterest and insomnia. The researchers referred to these symptom clusters as “dysphoric” and “anxiosomatic,” respectively.
Depression is the leading cause of disability worldwide, affecting as many as one in four women and one in eight men in their lifetime. According to the most recent government statistics, more than 17 million adults in the United States struggled with depression in 2017.
Clinicians have long recognized that depression manifests in different ways across individuals; official diagnostic criteria include weight loss or weight gain, excessive sleeping or insomnia, inability to concentrate or obsessive rumination.
However, the field of psychiatry has yet to reach a consensus classification of depression subtypes based on distinct symptoms, and any previously proposed classification schemes have failed to improve treatment outcomes.
“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 was approved in 2008 for the treatment of depression in adults who were non-responsive to antidepressant drugs. Currently, TMS practitioners use head measurements to position the machine’s magnetic coil outside the patient’s scalp. This can result in the stimulation of other brain circuits. Despite the imprecision, the well-tolerated therapy has a 50% to 60% success rate, higher than most antidepressant drugs.
Taking advantage of that variation, the research team, 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, analyzed outcomes for two independent groups of patients who were undergoing TMS for treatment-resistant depression.
Patients’ symptoms were self-reported with a validated questionnaire as well as assessed by clinicians.
The team mapped each patient’s TMS site to underlying brain circuits — a technique pioneered by Fox at BIDMC — and compared these maps to the total change in depression symptoms across participants.
The analysis identified two distinct clusters of depressive symptoms, with each responding better to a different TMS target. One cluster, called “dysphoric,” included symptoms such as sadness, decreased interest, and suicidality, while a smaller cluster, called “anxiosomatic,” included symptoms such as irritability, sexual disinterest and insomnia.
Next, to validate the findings, the scientists used these cluster maps to accurately predict clinical improvement in a separate set of patients. The results are consistent with recent studies identifying different symptom clusters — or biotypes — in people with depression. However, Siddiqi and Fox’s study takes the reverse approach.
“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 neuro-anatomy and behavior. We started with depression and anxiety, but this approach could also be used to find a treatment target for any cluster of psychiatric symptoms.”
Source: PsychCentral Clusters of Depressive Symptoms Respond to Different TMS Targets