Trial results for a study investigating psychotherapies for Major Depressive Disorder were posted on ClinicalTrials.gov on 2025-06-03, involving 64 participants.
Background
Abnormalities in the Positive Valence System (PVS) are associated with depressive symptoms and reduced behavioral activation, particularly in mid- and late-life depression. Psychotherapy remains a cornerstone of depression treatment, with ongoing research seeking to refine and personalize approaches. This study aimed to investigate the engagement of the PVS during exposure to social rewards within a novel streamlined psychotherapy, with the goal of identifying neuroimaging and behavioral profiles linked to treatment response and guiding future personalization.
Trial design
This completed study, designated as Phase NA, enrolled 64 participants with Major Depressive Disorder. The trial compared two psychotherapy approaches: "Engage & Connect" Psychotherapy and Symptom Review and Psychoeducation (SRP). The study aimed to investigate the engagement of the Positive Valence System during exposure to social rewards as part of the "Engage & Connect" psychotherapy, and to identify neuroimaging and behavioral profiles associated with treatment response.
Key results
The trial reported several key measurements and analyses:
- Change in Resting State fMRI Connectivity of the Positive Valence System (rsFC correlation coefficient):
- For "Engage & Connect" Psychotherapy, mean change was 0.18 (Standard Error 0.03).
- For Symptom Review and Psychoeducation (SRP), mean change was 0.18 (Standard Error 0.02).
- Further measurements for "Engage & Connect" Psychotherapy showed a mean change of 0.24 (Standard Error 0.02).
- For Symptom Review and Psychoeducation (SRP), a mean change of 0.29 (Standard Error 0.02) was observed.
- Another measurement for "Engage & Connect" Psychotherapy showed a mean change of 0.25 (Standard Error 0.03).
- For Symptom Review and Psychoeducation (SRP), a mean change of 0.24 (Standard Error 0.03) was observed.
- Change in Montgomery Asberg Depression Rating Scale (MADRS) (score on a scale):
- For "Engage & Connect" Psychotherapy, mean change was 23.66 (Standard Deviation 4.62).
- For Symptom Review and Psychoeducation (SRP), mean change was 24.81 (Standard Deviation 3.39).
- Further measurements for "Engage & Connect" Psychotherapy showed a mean change of 13.82 (Standard Deviation 7.56).
- For Symptom Review and Psychoeducation (SRP), a mean change of 18.62 (Standard Deviation 7.03) was observed.
- Another measurement for "Engage & Connect" Psychotherapy showed a mean change of 11.86 (Standard Deviation 8.97).
- For Symptom Review and Psychoeducation (SRP), a mean change of 14.66 (Standard Deviation 8.89) was observed.
- Key Analyses:
- A Mixed Models Analysis for functional connectivity within the orbital prefrontal cortex (OFC) showed a mean difference (final values) of 0.4727, with a p-value of 0.6249.
- Another Mixed Models Analysis, using a fixed effect for treatment and time, and a random effect for subject level, showed a mean difference (final values) of 3.8176, with a p-value of 0.525 for the time by treatment interaction.
- A third Mixed Models Analysis, also using a fixed effect for treatment and time, and a random effect for subject level, showed a mean difference (final values) of 0.6503, with a p-value of 0.844 for the time by treatment interaction.
What this means
The posted results indicate that for the analyzed outcomes, including changes in resting state fMRI connectivity and Montgomery Asberg Depression Rating Scale (MADRS) scores, there was no statistically significant difference between the "Engage & Connect" Psychotherapy and the Symptom Review and Psychoeducation (SRP) groups. The p-values from the mixed models analyses (0.6249, 0.525, and 0.844) suggest that any observed differences in mean values between the two psychotherapy approaches were not statistically significant. This suggests that both approaches had similar effects on the measured neuroimaging and clinical outcomes in this study population.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for the study NCT04487730, titled "Social Reward and Its Effect on Brain Functions in Psychotherapies for Mid- and Late-Life Depression", were posted on 2025-06-03 on clinicaltrials.gov.