Prospective observational study (n=120) assessing belief-updating in TRD patients before and 24 hours after a single antidepressant dose; a 60-patient subset will undergo fMRI (ketamine or monoaminergic treatments in routine care).
This prospective case-control observational study examines neural mechanisms of belief updating about the future in patients with treatment-resistant depression (TRD) before and 24 hours after a single antidepressant dose given in routine clinical care.
Participants complete a 40-trial belief-updating task and rating scales; 60 of 120 participants will have fMRI scans pre- or 24 h post-treatment to assess BOLD responses to positive versus negative disconfirming information.
Primary outcome is the interaction of testing time (before vs after a single dose) and information valence (positive vs negative) on BOLD response; secondary aims include behavioural bias changes and correlation with global clinical improvement (MADRS).
Behavioural testing and fMRI prior to first antidepressant dose
Functional MRI with 40-trial belief updating task; behavioural ratings (valence, familiarity, vividness, relevance, controllability, arousal).
Behavioural testing and fMRI 24 hours after a single antidepressant dose (ketamine or monoaminergic)
Single subanaesthetic ketamine infusion administered in routine clinical care; fMRI performed 24 h after infusion.
Single monoaminergic antidepressant dose administered in routine care with behavioural testing only (behavioural-only subgroup of 60 patients).