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Theoretical models of neural mechanisms underlying cognitive behavior therapy (CBT) for major depressive disorder propose that psychotherapy changes neural functioning of prefrontal cortical regions associated with cognitive-control processes, as well as brain regions involved in threat- or salience-related reactivity. However, individuals with major depressive disorder can be vulnerable to recurrence of depression symptoms after intervention, suggesting that underlying neural mechanisms of major depressive disorder can persist despite treatment.

To identify brain regions resistant to or responsive to change following CBT, investigators including Marlene Strege, PhD (postdoctoral research fellow), and Greg Siegle, PhD (Professor of Psychiatry and Clinical and Translational Science), from Pitt Psychiatry, collected functional magnetic resonance imaging (fMRI) data from a cohort of individuals with major depressive disorder before and after receiving CBT, as well as from a comparison group of individuals without depression. 

In a paper published in Psychological Medicine, the scientists reported nonresponse in a cerebellar region and response in prefrontal and parietal regions.

“When interviewing individuals who underwent CBT for depression a decade ago, I found that treated depression often involves chronic subclinical symptoms and episode recurrence,” said Dr. Strege, the study’s first author. “These findings and the larger supporting literature prompted the question: which brain processes remain unaddressed by our interventions? In the current study, we identified a vermis-centered cerebellar cluster exhibiting persistent aberrant functioning after CBT. The presence of post-treatment neural vulnerabilities with poor long-term clinical outcomes highlights depression’s chronic nature and supports continued assessments after treatment.” 

“These findings could help to provide new insights into why depression sometimes recurs following therapy, and what we could do about it. Identifying this cerebellar region, which reacts differently in depressed vs. never-depressed people before treatment but does not change in therapy, gives us a new target for interventions geared to treat the whole syndrome. Interventions such as exercise, which target cerebellar function, may thus be particularly fruitful as adjuncts for traditional therapies” said Dr. Siegle, the study’s senior author.

Trying to name what doesn't change: Neural nonresponse to Cognitive Therapy for depression
Strege MV, Richey JA, Siegle GJ.
Psychological Medicine, 1-12. doi:10.1017/S0033291723000727