Examining Relationships Among Depression Treatment, Brain-Derived Neurotrophic Factor (BDNF), and Depressive Symptom Clusters in Primary Care Patients with Depression

Abstract

Depression is a heterogeneous mental health condition, varying in presentation across individuals. A candidate etiology that may help account for this heterogeneity is the neurotrophin hypothesis of depression, which proposes that stress downregulates brain-derived neurotrophic factor (BDNF) expression, leading to aberrant neurogenesis and depression. This etiology may manifest in a distinct symptom profile that may be reflected in depressive symptoms or symptom clusters. The effect of psychological interventions on BDNF is not known. Additionally, it is not known if BDNF levels mediate intervention effects on depressive symptom clusters. Using data from the eIMPACT trial (NCT02458690, supported by R01 HL122245), I examined baseline associations of BDNF with depressive symptoms and depressive symptom clusters. Also, I examined if the modernized collaborative care intervention for depression (internet CBT, telephonic CBT, and select antidepressant medications) affected BDNF and if changes in BDNF mediated intervention effects on cognitive/affective and somatic depressive symptom clusters. 216 participants (primary care patients with depression and elevated cardiovascular disease risk ≥50 years from a safety net healthcare system) were randomized to 12 months of the eIMPACT intervention (n=107) or usual primary care for depression (primary care providers supported by embedded behavioral health clinicians and affiliated psychiatrists; n=109). Plasma BDNF was measured with commercial ELISA kits. Depressive symptoms were assessed by the PHQ-9 (M=15.1, SD=5.0) from which cognitive/affective and somatic subscale scores were computed. No significant baseline associations were observed between BDNF and individual depressive symptoms or depressive symptom clusters. The intervention did not improve BDNF over 12 months. Similarly, 12-month changes in BDNF were not associated with 12-month changes in PHQ-9 cognitive/affective or somatic subscale scores. However, the intervention significantly improved PHQ-9 cognitive/affective and somatic subscale scores over 12 months. 12-month changes in BDNF did not mediate the effect of the intervention on 12-month changes in the PHQ-9 subscale scores. These findings suggest that modernized collaborative care for depression does not improve BDNF. Modernized collaborative care does yield improvements in both cognitive/affective and somatic depressive symptom clusters, albeit not via changes in BDNF.