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Subgenual cingulate cortex hyperactivity key to MDD pathophysiology

Using repetitive transcranial magnetic stimulation combined with electroencephalography, researchers found that subgenual cingulate cortex activity in patients with major depressive disorder was significantly higher than in healthy controls.

These findings suggest that subgenual cingulate cortex hyperactivity may be a significant biological target in the treatment of MDD, according to the published in JAMA Network Open.

Prior research has shown that hyperactivity in the subgenual cingulate cortex (SGC) is correlated with MDD and anticorrelated with activity in the dorsolateral prefrontal cortex (DLPFC); this association has also been shown to predict responsiveness to repetitive transcranial magnetic stimulation (rTMS) treatment, Itay Hadas, PhD, from the Centre for Addiction and Mental Health, University of Toronto, and colleagues wrote

To better understand DLPFC-SGC connectivity in MDD, researchers compared baseline SGC hyperactivity in patients with MDD and healthy controls and compared SGC activity in patients with MDD before and after active or sham high-frequency transcranial magnetic stimulation (rTMS) treatment in a diagnostic study.

They quantified subgenual cingulate cortex hyperactivity activity using significant current density (SCD) and effective connectivity between the left DLPFC and SGC using significant current scattering (SCS). Also, they evaluated MDD using the 17-item Hamilton Rating Scale for Depression.

Overall, 30 patients with MDD were compared with 30 healthy controls at rTMS treatment baseline. After rTMS treatment, 26 patients with MDD who received active rTMS treatment were compared with 17 patients with MDD who received sham treatment.

Hadas and colleagues found that SGC activity after TMS was significantly higher in patients with MDD than in healthy controls (SCD: P = .004; SCS: P = .02). SCD indexing had a high accuracy (77%) in distinguishing patients with MDD from healthy controls. In addition, depression scores were linked to current density at the SGC (P = .03).

After active rTMS treatment, SGC hyperactivity in patients with MDD was attenuated after active rTMS compared with sham rTMS (SCD: P = .004; SCS: P = .006), according to the . Furthermore, the researchers found a link between SGC-localized source measures and symptom improvement on the 17-item Hamilton Rating Scale for Depression in patients receiving active rTMS (P = .047), but not in those receiving sham.

“These findings support the hypothesis of SGC involvement in the pathophysiology and clinical improvement of MDD and also provide an objective biological target to differentiate mood states in MDD and to differentiate patients with MDD from healthy controls,” Hadas and colleagues wrote. – by Savannah Demko

Disclosure: Hadas reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.