Does CBT change the brain? A systematic review of neuroimaging RCTs on anxiety disorders, depression and obsessive-compulsive disorder

Cognitive behavioral therapy (CBT) is effective for anxiety disorders, depression and obsessive-compulsive disorder (OCD), but the neurobiological mechanisms of change remain unclear. This systematic review synthesized neuroimaging evidence from randomized controlled trials (RCTs) to examine whether CBT can be considered a neurobiological intervention. Following PRISMA guidelines (PROSPERO: CRD420251239465), PubMed, Scopus and PsycInfo were searched for RCTs of CBT in adults with anxiety disorders, depression or OCD-spectrum disorders reporting pre- and post-treatment neuroimaging. Risk of bias was assessed with RoB 2, and findings were synthesized narratively. Seventeen RCTs were included (OCD = 5, anxiety disorders = 6, depression = 6), using task-based fMRI (n = 8), resting-state fMRI (n = 6), structural MRI (n = 2) or PET (n = 1). Changes after CBT involved emotional reactivity regions, prefrontal and frontoparietal control systems and their connectivity, with disorder-specific patterns: reduced threat reactivity in anxiety disorders, altered cognitive control networks in OCD, and altered mood-related, self-referential and reward connectivity in depression. Neural and clinical change did not always coincide, and comparisons with pharmacotherapy were mixed. Five studies were at high risk of bias. These findings provide preliminary support for CBT as a neurobiological intervention, although small samples and heterogeneous protocols limit conclusions.