CBT+ for Depression

This study investigates the effects of a novel intervention approach, intentionally sequencing aerobic exercise immediately prior to therapy sessions (i.e., cognitive behavioral therapy \[CBT\]) to determine its effects on both specific and common factors underlying the antidepressant effect of CBT (i.e., mechanisms of CBT). To assess the utility of this treatment augmentation, investigators plan to conduct a randomized controlled trial involving 40 adults with Major Depressive Disorder who will watch a nature documentary while either resting quietly (termed 'CalmCBT') or exercising at a moderate intensity ('ActiveCBT') immediately prior to 8 weekly sessions of CBT. It is hypothesized that target CBT mechanisms of antidepressant action (i.e., self-reported working alliance and behavioral activation) will be more effectively engaged by ActiveCBT vs. CalmCBT.

Frontline treatments for major depressive disorder (MDD), including cognitive behavioral therapy (CBT), have limited effectiveness, with half of patients not responding to CBT and half relapsing within 2 years. Strategies that increase the potency of MDD treatments are needed. We are testing a novel treatment strategy using aerobic exercise to prime a subsequent CBT session ('ActiveCBT'). Exercise priming is hypothesized to lead to greater engagement of CBT mechanisms of action through both common and specific factors linked to depression outcomes; this CBT augmentation approach has yet to be empirically tested. The study will consist of an 8-week randomized controlled trial in 40 adults with MDD performing 30-minutes of moderate exercise or quiet rest (CalmCBT vs. ActiveCBT) prior to weekly CBT sessions. Using a time- and attention-matched control, all participants will view a standardized documentary series for these 30 pre-therapy minutes with the only difference between groups being exercise or calmly resting. This project will also employ machine learning and natural language processing via the Lyssn platform to objectively evaluate the language and words used during therapy. The overall goals are to: 1) demonstrate exercise priming effects on target CBT mechanisms, 2) link psychological and neuroplastic exercise priming to CBT mechanisms, and 3) explore the sensitivity of objective machine learning-based markers from Lyssn to ActiveCBT-induced therapy differences. This trial will establish the potential for a subsequent confirmatory efficacy trial to rigorously test the potential of exercise priming to enhance treatment. If this innovative, biologically-informed approach successfully 'primes' subsequent therapy, this could be used to augment other treatments and in other disorders, significantly improving mental health treatment.

Eligibility Criteria:
Inclusion Criteria:

* Diagnosed with DSM-5 MDD, confirmed via SCID.
* Having current depressive symptoms of at least mild severity defined by HAM-D rating ≥8.
* Being between age 18 and 65.
* Either not engaging in any mental health treatment (e.g., medication, psychological, or behavioral) OR on a stable mental health treatment regimen and willing to maintain it for the length of the intervention.
* Willing and safe to exercise based on the Physical Activity Readiness Questionnaire.
* Being CBT-naïve (as defined by never undergoing structured CBT).

Exclusion Criteria:

* currently pregnant, nursing, or planning to become pregnant,
* severe obesity (BMI=40)
* diagnosed with lifetime or current Psychosis, Mania, or Bipolar Disorder, via the SCID
* diagnosed with current Substance Use Disorder, via the SCID
* pose an imminent risk of self-harm or harm to others, assessed via the C-SSRS
* exhibit behavioral disturbance (e.g., aggression, mild-moderate cognitive impairment) that would significantly interfere with study participation, assessed by clinical research personnel