Response to Treatment in Treatment-Naïve MDD Associates With Changes to rsFC

Changes to brain resting-state functional connectivity (rsFC) were observed in remission from major depression after antidepression medication or cognitive behavioral therapy (CBT). These findings were published in the American Journal of Psychiatry in Advance.

Patients (n=131) who had treatment-naïve major depressive disorder (MDD) were recruited at Emory University and Grady Hospital in the United States between 2007 and 2013 for the Predictors of Remission in Depression to Individual and Combined Treatments (PReDICT) study. Patients were randomly assigned in a 1:1:1 ratio to receive 12 weeks of CBT (n=40), 30-60 mg/day duloxetine, or 10-20 mg/day escitalopram (pooled antidepressant group n=91). The CBT intervention comprised 16 1-hour sessions. The primary outcome for this analysis was the change in whole-brain rsFC based on functional magnetic resonance imaging (fMRI). Outcomes were compared with a group of healthy controls (n=35). Remission was defined as having Hamilton Depression Rating Scale (HAM-D) scores of less than or equal to 7 at weeks 10 and 12.

Patients had a mean age of 39.8 (SD, 11.4) years, 56.5% were women, 60.3% were White, 54.2% had a single lifetime depressive episode, 43.5% had a current anxiety disorder, and they had a HAM-D score of 18.8 (SD, 3.2) points. The control group was aged 36.7 (SD, 8.7) years and 60.0% were women.

Using fMRI data, the changes in rsFC were associated with remission among both the CBT (t, 4.66; P <.001) and antidepressant (t, 4.42; P <.001) recipients. The rsFC changes were not associated with response without remission (t, 1.64; P =.113) or nonresponse (t, 1.15; P =.257).

Among the patients who remitted, significant interactions were observed in the left and right superior parietal lobules, left inferior parietal lobule, right posterior insula, left precuneus, and left V1.

The subset of patients who had no change in the subcallosal cingulate cortex (SCC) connectivity with the left medial motor cortex had no change in HAM-D scores by week 12 (R², 0.02; P =.11).

Stratified by treatment, the CBT remitters had an increase in the posterior cingulate cortex (PCC) connectivity to the superior frontal cortex and the rsFC in the executive control and salience networks whereas the medication remitters had reduced PCC-middle frontal cortex and executive control and salience networks rsFC patterns. The CBT remitters also showed a change in the affective network rsFC.

Compared with controls, at baseline the patients who would ultimately remit to treatment tended to have greater attention network connectivity to the left medial motor cortex compared with controls. After remission, the strength of the connection was decreased among patients compared with controls.

A significant time-by-treatment interaction was observed for the sum of rsFC of the SCC to the midbrain and ventrolateral/ventromedial prefrontal cortex or anterior insula (P <.003). This significant pattern was driven by the CBT remitters.

The major limitation of this study was the small sample size.

Study authors concluded, “It is likely that failure to engage the executive control network during CBT will predict failure of that treatment modality; how soon such engagement could be evaluated to justify a change of treatment is a future research question.”

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.