Naltrexone modulates contextual processing in depression.
J ChenA MizunoT LyewH T KarimJ F KarpAlexandre Y DombrovskiM PeciñaPublished in: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology (2020)
Context, the information surrounding an experience, can significantly alter the meaning and the affective responses to events. Yet the biological mechanisms through which context modulate experiences are not entirely understood. Here, we hypothesized that the µ-opioid system-extensively implicated in placebo effects, a clinical phenomenon thought to rely on contextual processing-modulates the effects of contextual information on emotional attributions in patients with depression. To test this hypothesis, 20 unmedicated patients with depression completed a randomized, double-blind, placebo-controlled, crossover study of one dose of 50 mg of naltrexone, or placebo immediately before completing two sessions of the Contextual Framing fMRI task. This task captures effects of valenced contextual cues (pleasant vs. unpleasant) on emotional attribution (the rating of subtle emotional faces: fearful, neutral, or happy). Behaviorally, we found that emotional attribution was significantly moderated by the interaction between contextual cues and subtle emotional faces, such that participants' ratings of valenced faces (fearful and happy), compared to neutral, were more negative during unpleasant, compared to pleasant context cues. At a neural level, context-induced blood-oxygen-level-dependent responses in the ventromedial prefrontal cortex, the dorsal anterior cingulate, the dorsolateral prefrontal cortex, and the lateral orbitofrontal cortex, significantly moderated the effects of context on emotional attribution, and were blunted by naltrexone. Furthermore, the effects of naltrexone on emotional attribution were partially abolished in more severely depressed patients. Our results provide insights into the molecular alterations underlying context representation in patients with depression, providing pivotal early data for future treatment studies.
Keyphrases
- prefrontal cortex
- double blind
- placebo controlled
- depressive symptoms
- functional connectivity
- sleep quality
- clinical trial
- end stage renal disease
- spinal cord
- minimally invasive
- mental health
- chronic kidney disease
- machine learning
- prognostic factors
- resting state
- chronic pain
- study protocol
- pain management
- health information
- current status
- social media
- neuropathic pain
- spinal cord injury
- deep learning
- artificial intelligence
- phase ii
- advanced cancer
- patient reported outcomes
- working memory