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Patients With Specific Treatment-Resistant Depression Biotype Improve With TMS

Patients with a particular cognitive biotype of treatment-resistant depression are more likely to experience improvement with transcranial magnetic stimulation (TMS) compared with other patients, according to a study published in Nature Mental Health that was carried out in collaboration with the National Veterans Administration (VA).

“We previously identified a cognitive biotype of depression characterized by treatment resistance, impaired cognitive control behavioral performance, and dysfunction in the cognitive control circuit, comprising the dorsolateral prefrontal cortex (dLPFC) and dorsal anterior cingulate cortex (dACC),” wrote lead author Leonardo Tozzi, MD, PhD, of the Department of Psychiatry and Behavioral Sciences at Stanford University School of Medicine, Stanford, California, and study coauthors.

"Major depressive disorder (MDD) is highly prevalent and the leading cause of disability. Despite the availability of multiple treatment options, we lack tests for identifying which treatment is most likely to benefit each individual. Most patients cycle through multiple trial-and-error treatment trials, often over years, and some patients become resistant to treatment," authors wrote. "The need for precision treatments is especially urgent for veterans given the high prevalence of depression with comorbid conditions and a higher rate of suicide compared with the civilian population."

The study included 43 veterans with treatment-resistant depression who received therapeutic TMS to the left dLPFC. Before TMS, after early TMS, and after all TMS sessions, participants were assessed via functional magnetic resonance imaging during a computerized Go–NoGo task, as well as with behavioral cognitive control tests and symptom questionnaires.

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Researchers grouped patients based on dLPFC–dACC connectivity during the Go–NoGo task. Those with reduced dLPFC–dACC connectivity were deemed cognitive biotype +, and those without intact dLPFC–dACC connectivity were considered cognitive biotype −.

Patients with cognitive biotype + experienced significant improvements in cognitive control circuit connectivity and behavioral performance as early as 5 sessions into TMS therapy, the study found. 

Moreover, gains after the final TMS session were substantial enough to diminish the difference between patients with and without the biotype, Dr Williams told the website Medical Xpress.

However, patients with cognitive biotype − did not show significant changes with TMS.

“In conclusion, this study shows that dLPFC–dACC connectivity measured during a cognitive control task is a promising biomarker for the stratification of a cognitive biotype of depression, which might be particularly suited to TMS treatment,” researchers wrote. “This connectivity measure also offers a potential response biomarker for quantifying the trajectory of improvement in the cognitive biotype.”

References

Tozzi L, Bertrand C, Hack LM, et al. A cognitive neural circuit biotype of depression showing functional and behavioral improvement after transcranial magnetic stimulation in the B-SMART-fMRI trial. Nature Mental Health. 2024;2:987-998. doi:10.1038/s44220-024-00271-9

Fadelli I. Transcranial magnetic stimulation shows promise for treatment-resistant depression biotype. Medical Xpress. July 24, 2024. Accessed September 1, 2024.