Association of Changes in Neural Targets and Dietary Outcomes among Patients with Comorbid Obesity and Depression: Post hoc Analysis of ENGAGE-2 Mechanistic Clinical Trial

Background: Disruptions in brain circuits that regulate cognition and emotion can hinder dietary change and weight loss among individuals with obesity and depression. Objective: The study aimed to investigate whether changes in brain targets in the cognitive control, negative affect, and positive affect circuits after 2-mo problem-solving therapy (PST) predict changes in dietary outcomes at 2 and 6 mo. Methods: Adults with obesity and depression from an academic health system were randomly assigned to receive PST (7-step problem -solving and behavioral activation strategies) over 2 mo or usual care. Seventy participants (mean age = 45.9 +/- 11.6 y; 75.7% women, 55.7% Black, 17.1% Hispanic, 20.0% White; mean BMI = 36.5 +/- 5.3 kg/m2; mean Patient Health Questionnaire-9 depression score = 12.7 +/- 2.8) completed functional MRI and 24-h food recalls. Ordinary least square regression analyses were performed. Results: Among intervention participants, increased left dorsal lateral prefrontal cortex (dLPFC) activity of the cognitive control circuit at 2 mo was associated with increased diet quality (8: 0.20; 95% CI: -0.02, 0.42) and decreased calories (8: -0.19; 95% CI: -0.33, -0.04), fat levels (8: -0.22; 95% CI: -0.39, -0.06), and high-sugar food intake (8: -0.18; 95% CI: -0.37, 0.01) at 6 mo. For the negative affect circuit, increased right dLPFC-amygdala connectivity at 2 mo was associated with increased diet quality (8: 0.32; 95% CI: -0.93, 1.57) and fruit and vegetable intake (8: 0.38; 95% CI: -0.75, 1.50) and decreased calories (8: -0.37; 95% CI: -1.29, 0.54), fat levels (8: -0.37; 95% CI: -1.50, 0.76), sodium concentrations (8: -0.36; 95% CI: -1.32, 0.60), and alcohol intake (8: -0.71; 95% CI: -2.10, 0.68) at 2 but not at 6 mo. The usual care group showed opposing associations. The 95% CIs of all between-group differences did not overlap the null, suggesting a sig-nificant treatment effect. Conclusions: Among adults with obesity and depression who underwent PST compared with those under usual care, improved dLPFC-amygdala regulation of negative affective brain states predicted dietary improvements at 2 mo, whereas improvements in dLPFC-based cognitive control predicted dietary improvements at 6 mo. These findings warrant confirmatory studies. This trial was at clinicaltrials.gov as NCT03841682.