Abstract
Background: A seminal study found higher subgenual frontal cortex resting-state connectivity with two left ventral frontal regions and the dorsal midbrain to predict better response to psychotherapy versus medication in individuals with treatment-naïve major depressive disorder (MDD). Here, we examined whether these subgenual networks also play a role in the pathophysiology of clinical outcomes in MDD with early treatment-resistance in primary care.
Methods: Forty-five people with current MDD who had not responded to ≥2 serotonergic antidepressants (n=43, meeting pre-defined fMRI minimum quality thresholds) were enrolled and followed up over four months of standard care. Functional MRI resting-state connectivity between the pre-registered subgenual frontal cortex seed and three previously identified left ventromedial, ventrolateral prefrontal/insula, and dorsal midbrain regions was extracted. Clinical outcome was the percentage change on the self-reported Quick Inventory of Depressive Symptomatology (16-item).
Results: We observed a reversal of our pre-registered hypothesis in that higher resting-state connectivity between the subgenual cortex and the a priori ventrolateral prefrontal/insula region predicted favorable rather than unfavorable clinical outcomes (rs[39]=-.43, p=.006). This generalized to the sample including participants with suboptimal fMRI quality (rs[43]=-.35, p=.02). In contrast, no effects (rs[39]=.12, rs[39]=-.01) were found for connectivity with the other two pre-registered regions and in a “whole brain” analysis (voxel-based Family-Wise Error-corrected p<.05).
Conclusions: Subgenual connectivity with the ventrolateral prefrontal cortex/insula is relevant for subsequent clinical outcomes in current MDD with early treatment-resistance. Its positive association with favorable outcomes could be explained primarily by psychosocial rather than the expected pharmacological changes during the follow-up period.
Trial Registration: ClinicalTrials.gov: NCT04342299, https://clinicaltrials.gov/ct2/show/NCT04342299
Methods: Forty-five people with current MDD who had not responded to ≥2 serotonergic antidepressants (n=43, meeting pre-defined fMRI minimum quality thresholds) were enrolled and followed up over four months of standard care. Functional MRI resting-state connectivity between the pre-registered subgenual frontal cortex seed and three previously identified left ventromedial, ventrolateral prefrontal/insula, and dorsal midbrain regions was extracted. Clinical outcome was the percentage change on the self-reported Quick Inventory of Depressive Symptomatology (16-item).
Results: We observed a reversal of our pre-registered hypothesis in that higher resting-state connectivity between the subgenual cortex and the a priori ventrolateral prefrontal/insula region predicted favorable rather than unfavorable clinical outcomes (rs[39]=-.43, p=.006). This generalized to the sample including participants with suboptimal fMRI quality (rs[43]=-.35, p=.02). In contrast, no effects (rs[39]=.12, rs[39]=-.01) were found for connectivity with the other two pre-registered regions and in a “whole brain” analysis (voxel-based Family-Wise Error-corrected p<.05).
Conclusions: Subgenual connectivity with the ventrolateral prefrontal cortex/insula is relevant for subsequent clinical outcomes in current MDD with early treatment-resistance. Its positive association with favorable outcomes could be explained primarily by psychosocial rather than the expected pharmacological changes during the follow-up period.
Trial Registration: ClinicalTrials.gov: NCT04342299, https://clinicaltrials.gov/ct2/show/NCT04342299
| Original language | English |
|---|---|
| Article number | 100308 |
| Pages (from-to) | 100308 |
| Journal | Biological Psychiatry: Global Open Science |
| Volume | 4 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 13 Mar 2024 |
Keywords
- Biomarker
- Depression
- fMRI
- Prognosis
- Resting-state
- Subgenual cortex