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Risk for recurrent depression in MDD may be measured by functional MRI

Risk for recurrent depressive episodes among individuals with major depressive disorder may be predicted by functional MRI connectivity between the right superior anterior temporal lobe and the subgenual cingulate cortex and adjacent septal region during the experience of self-blaming relative to other-blaming emotions, according to findings in JAMA Psychiatry.

“Patients with remitted major depressive disorder (MDD) were previously found to display abnormal functional [MRI] connectivity between the right superior anterior temporal lobe and the subgenual cingulate cortex and adjacent septal region when experiencing self-blaming emotions relative to emotions related to blaming others (eg, ‘indignation or anger toward others’). This finding provided the first neural signature of biases toward overgeneralized self-blaming emotions (eg, ‘feeling guilty for everything’), known to have a key role in cognitive vulnerability to MDD,” Karen E. Lythe, PhD, of the University of Manchester and Manchester Academic Health Sciences Centre, England, and colleagues wrote. “It is unknown whether this neural signature predicts risk of recurrence, a crucial step in establishing its potential as a prognostic biomarker, which is urgently needed for stratification into pathophysiologically more homogeneous subgroups and for novel treatments.”

To determine if recurrent depressive episodes among individuals with MDD could be predicted by abnormal connectivity that occurs between the right superior anterior temporal lobe and subgenual cingulate cortex and adjacent septal region when experiencing self-blaming emotions, researchers assessed 75 psychotropic medication-free patients with remitted MDD.

Overall, 31 study participants remained stable in remission and 25 developed a recurring depressive episode within the 14 months of follow-up. The control cohort included 39 individuals with no history of MDD.

Researchers found that during the experience of self-blaming relative to other-blaming emotions, connectivity of the right superior anterior temporal lobe with the subgenual cingulate cortex and adjacent septal region predicted risk for subsequent recurring depressive episodes.

Patients with recurring MDD exhibited higher connectivity compared with the stable group and the control group.

Researchers found similar effects with the right ventral putamen, claustrum and the temporoparietal junction as distinctive of recurring MDD compared with stable MDD.

Together, these regions predicted MDD recurrence with 75% accuracy, according to researchers.

Most of the variance in connectivity of the right superior anterior temporal lobe with the subgenual cingulate cortex and adjacent septal region was independent of residual symptoms.

“We demonstrated that recurrence risk in MDD is predicted by a self-blame–selective increase in [right superior anterior temporal lobe] connectivity with the [subgenual cingulate cortex and adjacent septal region], right ventral putamen, claustrum, and right temporoparietal junction,” Lythe and colleagues wrote. “Our finding supports the hypothesis that self-blame–selective changes in connectivity with the [right superior anterior temporal lobe] have a causal role in the pathophysiology of MDD. A definitive proof of causality, however, will require showing that modulation of this neural signature by specific interventions has effects on clinical outcomes.” – by Amanda Oldt

Disclosure: Lythe reports no relevant financial disclosures. Please see the full study for a list of all authors’ relevant financial disclosures.