Biomarkers as predictors of CBT responsiveness in major depressive disorder: The role of heart rate variability and inflammation

Objective: Biological risk factors for cardiovascular disease may relate to poor treatment responsiveness in major depressive disorder (MDD). These factors encompass low-grade inflammation and autonomic dysregulation, as indexed by decreased heart rate variability (HRV) and increased heart rate (HR). This secondary analysis examined whether higher levels of inflammatory markers or autonomic alterations relate to lower responsiveness to cognitive behavioral therapy (CBT) among individuals with MDD. Methods: Eighty antidepressant-free patients with MDD were randomly assigned to 14 weeks of CBT or waitlist (WL). Potential biological moderators at study entry included HR and HRV (24-h, daytime, nighttime) and inflammatory markers such as C-reactive protein (CRP), interleukin (IL)-6, and tumor necrosis factor (TNF)-alpha. Forty non-clinical controls were involved to verify biological alterations in MDD at study entry. Depressive symptoms were assessed at baseline and at the end of treatment. Results: Individuals with MDD exhibited reduced total 24-h HRV (i.e., triangular index) and daytime HRV (i.e., triangular index, HF-HRV, LF-HRV, RMSSD), as well as increased levels of inflammatory markers. Patients who received CBT exhibited stronger reductions in self- and clinician-rated depressive symptoms, compared to WL. False discovery rate-adjusted moderation analyses did not show overall moderating effects of biological measures on treatment responsiveness. However, higher CRP levels were specifically associated with poorer improvement in somatic depressive symptoms. Conclusions: There was no overall evidence for a moderating role of inflammation or autonomic features in CBT responsiveness in MDD. Higher levels of CRP might, however, specifically be associated with less improvement in somatic depressive symptoms during CBT.