Trial reportEBioMedicine2021
Early changes in neural circuit function engaged by negative emotion and modified by behavioural intervention are associated with depression and problem-solving outcomes: A report from the ENGAGE randomized controlled trial.
Trial report in EBioMedicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02246413 (RCT on Co-management of Obesity, Depression, and Elevated CVD Risk in Primary Care-- Engaging Self-regulation Targets to Understand the Mechanisms of Behavior Change and Improve Mood and Weight Outcomes), which is not on this map. Cited by 15 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
RCT on Co-management of Obesity, Depression, and Elevated CVD Risk in Primary Care-- Engaging Self-regulation Targets to Understand the Mechanisms of Behavior Change and Improve Mood and Weight Outcomes
Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- Integrated Behavioral Interventions for Adults with Comorbid Obesity and Depression: a Systematic Review.Current diabetes reports · 2022Pooled it
- Examining fronto-limbic brain and sleep mechanisms of antidepressant effects in cognitive-behavioral therapy for insomnia.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Trial
- Ketamine's acute effects on negative brain states are mediated through distinct altered states of consciousness in humans.Nature communications · 2023Trial
- Effects of a virtual voice-based coach delivering problem-solving treatment on emotional distress and brain function: a pilot RCT in depression and anxiety.Translational psychiatry · 2023Trial
- 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.The Journal of nutrition · 2023Trial
- Developing Clinically Interpretable Neuroimaging Biotypes in Psychiatry.Biological psychiatry · 2026Review
- Neuropsychological Mechanisms Associated with the Effectiveness of AI-Delivered Health Promotion Programs: A Comprehensive Meta-Analysis.Brain sciences · 2026Review
- Towards an expanded neurocognitive account of ketamine's rapid antidepressant effects.The international journal of neuropsychopharmacology · 2025Review
- Neuroimaging for precision medicine in psychiatry.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Review
- Brain Circuit-Derived Biotypes for Treatment Selection in Mood Disorders: A Critical Review and Illustration of a Functional Neuroimaging Tool for Clinical Translation.Biological psychiatry · 2024Review
- Adaptive cognitive control circuit changes associated with problem-solving ability and depression symptom outcomes over 24 months.Science translational medicine · 2024Article
- Study of a PST-trained voice-enabled artificial intelligence counselor for adults with emotional distress (SPEAC-2): Design and methods.Contemporary clinical trials · 2024Article
- Mediating Effects of Neural Targets on Depression, Weight, and Anxiety Outcomes of an Integrated Collaborative Care Intervention: The ENGAGE-2 Mechanistic Pilot Randomized Clinical Trial.Biological psychiatry global open science · 2023Article
- Affective neural circuits and inflammatory markers linked to depression and anxiety symptoms in patients with comorbid obesity.Journal of psychiatric research · 2023Article
- Astrocyte reactivation in medial prefrontal cortex contributes to obesity-promoted depressive-like behaviors.Journal of neuroinflammation · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 8 institutions in 1 country.
Funding
Abstract
backgroundDepression exerts a staggering toll that is worsened with co-occurring chronic conditions such as obesity. It is imperative to develop more effective interventions for depression and to identify objective and biological plausible neural mechanisms to understand intervention outcomes. The current study uses functional neuroimaging to determine whether a behavioural intervention changes the negative affect circuit and whether these changes relate to subsequent improvements in both symptom and problem-solving outcomes in depressed patients with co-occurring obesity.
methodsThis study ('ENGAGE') was a pre-planned element of the randomized controlled trial, 'RAINBOW' (ClinicalTrials.gov NCT02246413). 108 depressed patients with obesity were randomized to receive an integrated collaborative care intervention (I-CARE) or usual care. Participants underwent functional neuroimaging using an established facial emotion task at baseline and two months (coinciding with the first two months of intervention focused on problem-solving therapy ('PST')). Amygdala, insula and anterior cingulate cortex activation was extracted using pre-planned definitions and standardized methods. The primary health and behavioural outcomes were depression symptom severity and problem-solving ability respectively, assessed at baseline, the main 6-month outcome point and at 12-month follow up. Mediation analyses used an intent-to-treat approach.
findingsPST, relative to usual care, reduced amygdala activation engaged by threat stimuli at two months. This reduction mediated subsequent improvements in depression severity in an intervention-dependent manner. PST did not change insula activation at two months but did temper the strength of the relationship between insula activation and improvements in problem-solving ability.
interpretationThe negative affect circuit may be an important neural target and potential mediator of PST in patients with comorbid obesity.
fundingUS National Institutes of Health/National Heart Lung and Blood Institute R01 HL119453 and UH2/UH3 HL132368.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.