Abstract
Aberrant activity of the subcallosal cingulate (SCC) is a common theme across pharmacologic treatment efficacy prediction studies. The functioning of the SCC in psychotherapeutic interventions is relatively understudied, as are functional differences among SCC subdivisions. We conducted functional connectivity analyses (rsFC) on resting-state functional magnetic resonance imaging (fMRI) data, collected before and after a course of cognitive behavioral therapy (CBT) in patients with major depressive disorder (MDD), using seeds from three SCC subdivisions. Resting-state data were collected from unmedicated patients with current MDD (Hamilton Depression Rating Scale-17>16) before and after 14-sessions of CBT monotherapy. Treatment outcome was assessed using the Beck Depression Inventory (BDI). Rostral anterior cingulate (rACC), anterior subcallosal cingulate (aSCC), and Brodmann's area 25 (BA25) masks were used as seeds in connectivity analyses that assessed baseline rsFC and symptom severity, changes in connectivity related to symptom improvement after CBT, and prediction of treatment outcomes using whole-brain baseline connectivity. Pretreatment BDI negatively correlated with pretreatment rACC~dorsolateral prefrontal cortex and aSCC~lateral prefrontal cortex rsFC. In a region-of-interest longitudinal analysis, rsFC between these regions increased post-treatment (p<0.05FDR). In whole-brain analyses, BA25~paracentral lobule and rACC~paracentral lobule connectivities decreased post-treatment. Whole-brain baseline rsFC with SCC did not predict clinical improvement. rsFC features of rACC and aSCC, but not BA25, correlated inversely with baseline depression severity, and increased following CBT. Subdivisions of SCC involved in top-down emotion regulation may be more involved in cognitive interventions, while BA25 may be more informative for interventions targeting bottom-up processing. Results emphasize the importance of subdividing the SCC in connectivity analyses.
Highlights
Cognitive behavioral therapy (CBT) is an evidence-based treatment for major depressive disorder (MDD), yielding remission rates of 43–52% [1], which means about half of patients are ineffectively treated or left with significant residual symptoms
The anterior subcallosal cingulate (aSCC)-left lateral prefrontal cortex (lPFC) increased from negative restingstate functional connectivity (rsFC) pretreatment to near zero following treatment, and this change in rsFC was positively correlated with change in Beck Depression Inventory (BDI) at a trend level (t(18) = 2.04, p = 0.056FDR)
Results suggested that the strength of rsFC between the aSCC and rostral anterior cingulate cortex (rACC) seeds and cortical areas involved in top-down cognitive control of emotions tracked symptom severity
Summary
Cognitive behavioral therapy (CBT) is an evidence-based treatment for major depressive disorder (MDD), yielding remission rates of 43–52% [1], which means about half of patients are ineffectively treated or left with significant residual symptoms. Differences in the functional connectivity of the SCC that are predictive of treatment response have been identified [2]. Aberrant activity of the subcallosal cingulate (SCC) is a common theme across pharmacologic treatment efficacy prediction studies. We conducted functional connectivity analyses (rsFC) on resting-state functional magnetic resonance imaging (fMRI) data, collected before and after a course of cognitive behavioral therapy (CBT) in patients with major depressive disorder (MDD), using seeds from three SCC subdivisions. Rostral anterior cingulate (rACC), anterior subcallosal cingulate (aSCC), and Brodmann’s area 25 (BA25) masks were used as seeds in connectivity analyses that assessed baseline rsFC and symptom severity, changes in connectivity related to symptom improvement after CBT, and prediction of treatment outcomes using whole-brain baseline connectivity. Results emphasize the importance of subdividing the SCC in connectivity analyses
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