Elevated BDNF Linked to Depressive Symptoms in Patients with Asthma, With Hiroshi Iwamoto, MD, PhD

Depressive symptoms are common in patients with asthma and are consistently linked to poorer disease control and greater severity. However, emerging evidence suggests that asthma-related depression may be biologically distinct from major depressive disorder (MDD), with elevated levels of brain-derived neurotrophic factor (BDNF) in patients with asthma.

In this multicenter observational study, investigators analyzed data from 140 adults with asthma enrolled in the Physical Activity in Bronchial Asthma (PACTAS) study. Serum BDNF levels were measured using an enzyme-linked immunosorbent assay, while depressive and anxiety symptoms were assessed using the Hospital Anxiety and Depression Scale (HADS). Daily physical activity was objectively quantified using a triaxial accelerometer.

Contrary to patterns seen in MDD, where reduced BDNF is a hallmark, serum BDNF levels were positively associated with depressive symptom severity in patients with asthma (P <.001). Patients with clinically relevant depressive symptoms (HADS-D ≥8) had significantly greater BDNF levels than those without.

Elevated BDNF was also independently associated with greater asthma severity, as reflected by higher treatment step, and poorer asthma control. Exploratory mediation analyses suggested that BDNF may partially mediate the relationship between asthma severity and depressive symptoms. These findings suggest that depressive symptoms in asthma may reflect disease-related inflammatory or stress pathways rather than the neurotrophic deficits characteristic of primary depression.

HCPLive conducted a Q&A with investigator Hiroshi Iwamoto, MD, PhD, from Hiroshima University in Japan, on clinical implications of these findings and how they may inform a more integrated approach to managing asthma and mental health.

HCPLive: How should clinicians rethink depressive symptoms in asthma, given that higher—not lower—BDNF levels were associated with worse mood?Iwamoto: Clinicians should consider that depressive symptoms in asthma may not share the same biological background as primary major depressive disorder. In asthma, elevated BDNF may reflect physiological stress or disease burden.

HCPLive: What does the association between elevated BDNF and asthma severity reveal about the brain–lung axis in chronic airway disease?Iwamoto: Our study does not provide direct evidence of a brain–lung axis. Rather, it shows an association between asthma severity, circulating BDNF levels, and depressive symptoms, which may warrant further mechanistic investigation.

HCPLive: Do your findings suggest that depressive symptoms in asthma are more closely linked to disease burden than to primary major depressive disorder?Iwamoto: Yes. Our results indicate that depressive symptoms in asthma appear to be more closely associated with asthma severity and disease burden than with the biological profile typically seen in primary major depressive disorder.

HCPLive: How should clinicians address poor asthma control and physical inactivity when managing depressive symptoms in patients with asthma?Iwamoto: Management may benefit from optimizing asthma control and addressing physical inactivity, alongside screening and support for depressive symptoms, rather than focusing solely on psychiatric treatment.

HCPLive: Given that antidepressants increase BDNF in major depressive disorder, how should clinicians interpret elevated BDNF levels in patients with asthma who have depressive symptoms?Iwamoto: In asthma, elevated BDNF should not automatically be interpreted as a marker of antidepressant response. It may instead reflect asthma-related inflammation or stress, although patients with comorbid major depressive disorder may still benefit from antidepressant therapy.

HCPLive: What are the limitations of applying traditional depression biomarkers or frameworks to patients with asthma based on your data?Iwamoto: Traditional biomarkers and frameworks derived from major depressive disorder may not fully capture the mechanisms of asthma-related depressive symptoms.

HCPLive: Is there a realistic future role for serum BDNF as a clinical biomarker in asthma, or is its value primarily mechanistic at this stage?Iwamoto: At present, the value of serum BDNF is primarily mechanistic. Its potential role as a clinical biomarker will require validation in longitudinal and interventional studies.

HCPLive: Based on your findings, what should an integrated, day-to-day clinical approach to asthma-related depressive symptoms look like today?Iwamoto: An integrated approach should address asthma control, physical activity, and mental health simultaneously, with collaboration between respiratory and mental health care when needed.

HCPLive: What further research is needed on this topic?Iwamoto: Further longitudinal and interventional studies are needed to clarify the temporal and causal relationships between asthma severity, BDNF levels, and depressive symptoms, and to determine whether BDNF can help stratify depressive symptoms or guide personalized management in asthma.

References

Kawamoto K, Iwamoto H, Hirano T, et al. Brain-Derived Neurotrophic Factor Levels Are Associated With Depressive Symptoms in Patients With Asthma. J Allergy Clin Immunol Pract. Published online November 11, 2025. doi:10.1016/j.jaip.2025.11.001