Preprints with The Lancet is part of SSRN´s First Look, a place where journals identify content of interest prior to publication. Authors have opted in at submission to The Lancet family of journals to post their preprints on Preprints with The Lancet. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. Preprints available here are not Lancet publications or necessarily under review with a Lancet journal. These preprints are early stage research papers that have not been peer-reviewed. The findings should not be used for clinical or public health decision making and should not be presented to a lay audience without highlighting that they are preliminary and have not been peer-reviewed. For more information on this collaboration, see the comments published in The Lancet about the trial period, and our decision to make this a permanent offering, or visit The Lancet´s FAQ page, and for any feedback please contact firstname.lastname@example.org.
Mediating Effects of Neural Targets on Depression, Weight and Anxiety Outcomes of an Integrated Collaborative Care Intervention: The ENGAGE-2 Mechanistic Pilot RCT
26 Pages Posted: 15 Jul 2021More...
Background: Integrated treatments for depression (and associated anxiety) and obesity are lacking; mechanisms are poorly investigated. This mechanistic pilot trial tested the degree to which engaging pre-specified neural targets at 2 months produces desired outcomes at 6 months.
Methods: Adults with a body mass index (BMI) of ≥30 (≥27, if Asian) and Patient Health Questionnaire-9 (PHQ-9) score of ≥10 were recruited from academic internal medicine clinics between March 1, 2019 and March 19, 2020, and followed for 6 months until August 31, 2020. Participants were randomized to receive usual care (n=35) or an integrated collaborative care intervention (n=71), providing 6 problem-solving therapy (PST) sessions for depression by 2 months, 3 additional PST sessions and 11 home videos on lifestyle changes for weight loss by 6 months. Outcomes were changes in BMI, Depression Symptom Checklist 20-item (SCL-20) scores, and Generalized Anxiety Disorder Scale (GAD-7) scores at 6 months. Neural targets were changes in affective, cognitive control, and default mode circuits by functional neuroimaging at 2 months.
Outcomes: Among 106 participants (mean [SD] age 47.0 [11.9] years, 76% women, 55% Blacks, 20% Latino, BMI 37.1 [6.0], SCL-20 1.2 [0.7], GAD-7 6.9 [4.8]), 86.8% completed the trial. The intervention led to significant reductions in SCL-20 (-0.3 [95% CI: -0.6, -0.1]) and GAD-7 (-2.9 [-4.7, -1.1]), but not BMI, at 6 months compared with usual care. Changes in the activation or functional connectivity of neural targets in the negative affect (anterior insula, subgenual and pregenual ACC, amygdala) and cognitive control circuits (dlPFC, dACC) at 2 months significantly correlated with changes in GAD-7, but not SCL-20 or BMI, at 6 months, and the correlations differed by the intervention vs. usual care. Effect sizes were medium to large (0.41ꟷ1.18 SDs). Changes in the neural targets of the cognitive control circuit, but not the negative affect circuit, at 2 months differed by treatment group. Effect sizes were medium (0.58ꟷ0.79 SDs).
Interpretation: Short-term changes in the cognitive control circuit mediated changes in anxiety symptoms, suggesting possible neural mechanisms to target for enhanced treatment effect.
Clinical Trial Registration Details: ClinicalTrials.gov Identifier: NCT03841682.
Funding Information: National Heart, Lung, and Blood Institute grant number UH2HL132368 and UH3HL132368.
Declaration of Interests: Dr. Jun Ma is a paid scientific consultant for Health Mentor, Inc. (San Jose, CA). Dr. Leanne M. Williams is on the Scientific Advisory Board for One Mind Psyberguide and the External Advisory Board for the Laureate Institute for Brain Research. Dr. Olusola A. Ajilore is the co-founder of Keywise AI and serves on the advisory boards of Blueprint Health and Embodied Labs. The other authors report no conflicts of interest. Dr. Thomas Kannampallil is a paid consultant for Pfizer, Inc, outside of this work
Ethics Approval Statement: The Institutional Review Boards for the University of Illinois at Chicago and Stanford University approved the study. All participants provided written consent.
Keywords: negative affect; cognitive control; functional neuroimaging; obesity; depression; anxiety
Suggested Citation: Suggested Citation