Integrated Cognitive and Balance Intervention Improves Most Symptoms of Depression

The ENGAGE-2 Mechanistic Pilot trial was a randomized clinical trial conducted at the University of Illinois at Chicago and Stanford University between 2019 and 2020.

An integrated intervention for comorbid depression and obesity significantly improved symptoms of depression but had no effect on weight loss. These findings were published in Biological Psychiatry Global Open Science.

The ENGAGE-2 Mechanistic Pilot trial was a randomized clinical trial conducted at the University of Illinois at Chicago and Stanford University between 2019 and 2020. Participants (N=106) with comorbid depression (Patient Health Questionnaire-9 [PHQ-9] ≥10) and obesity (BMI ≥27-30 kg/m2, depending on ethnicity) were randomized in a 2:1 ratio to receive Integrated Coaching for Better Mood and Weight version 2 (I-CARE2) or usual care. I-CARE2 comprised 9 1-on-1 sessions of a 7-step problem-solving and behavioral activation intervention, with antidepressants as needed, and 11 home-based group lifestyle balance video sessions for weight loss over a total of 6 months. Depression, BMI, and functional magnetic resonance imaging were evaluated at baseline and 2 and 6 months.

The intervention (n=71) and control (n=35) cohorts were aged mean 46.7 (SD, 11.7) and 47.4 (SD, 12.5) years, 77% and 74% were women, 58% and 49% were Black, BMI was 37.0 (SD, 6.0) and 37.2 (SD, 6.3) kg/m2, and PHQ-9 scores were 12.9 (SD, 2.9) and 12.8 (SD, 2.4) points, respectively.

At least 1 intervention session was completed by 91.5% of participants. Six individuals did not complete any intervention. The mean number of completed sessions was 6.9 (SD, 2.6).

At 6 months, the I-CARE2 intervention was associated with significant improvements to the Depression Symptom Checklist 20-item (SCL-20; between-group difference, -0.3; 95% CI, -0.6 to -0.1; P =.002) and the Generalized Anxiety Disorder Scale (GAD-7; between group difference, -2.9; 95% CI, -4.7 to -1.1; P =.002) scores. More I-CARE2 recipients achieved clinical remission for depression (43% vs 22%; P =.04) and anxiety (63% vs 39%; P =.04) symptoms.

No effect on BMI was observed (between group difference, -0.3; 95% CI, -1.0 to 0.4; P =.45).

Changes in neural targets were not significantly associated with changes in SCL-20 or BMI.

Changes in GAD-7 scores at 6 months were associated with changes in neural targets in the negative affect and cognitive control circuits among both cohorts and effect sizes suggested medium to large effects.

The change in GAD-7 scores were associated with the opposing activation patterns between groups for nonconscious threat stimuli in the amygdala, cognitive control circuit of the left dorsolateral prefrontal cortex, and cognitive control circuit (all P ≤.03).

There were 50 nonserious adverse events and 7 serious events. No events were related with the study.

This study was limited by its small sample size and short study duration.

“In conclusion, compared with usual care, the study intervention led to significantly improved depression but not weight loss, and the results on neural targets were null for both of these primary outcomes,” stated the study authors.

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


Lv N, Ajilore OA, Xiao L, et al. Mediating effects of neural targets on depression, weight and anxiety outcomes of an integrated collaborative care intervention: The ENGAGE-2 Mechanistic Pilot RCT. Bio Psych Global Open Sci. Published online April 5, 2022. doi: 10.1016/j.bpsgos.2022.03.012