The role of immuno-metabolic depression features in the effects of light therapy in patients with depression and type 2 diabetes mellitus: A randomized controlled trial

Immuno-metabolic depression (IMD) is proposed to be a form of depression encompassing atypical, energy-related symptoms (AES), low-grade inflammation and metabolic dysregulations. Light therapy may alleviate AES by modulating inflammatory and metabolic pathways. We investigated whether light therapy improves clinical and biological IMD features and whether effects of light therapy on AES or depressive symptom severity are moderated by baseline IMD features. Associations between changes in symptoms and biomarkers were explored. In secondary analyses, clinical trial data was used from 77 individuals with depression and type 2 diabetes mellitus (T2DM) randomized to four weeks of light therapy or placebo. AES severity and depressive symptom severity were based on the Inventory of Depressive Symptomatology. Biomarkers included 73 metabolites (Nightingale) summarized in three principal components and CRP, IL-6, TNF-α, INF-γ. Linear regression analyses were performed. Light therapy had no effect on AES severity, inflammatory markers and metabolite principle components versus placebo. None of these baseline features moderated the effects of light therapy on AES severity. Only a principle component reflecting metabolites implicated in glucose homeostasis moderated the effects of light therapy on depressive symptom severity (βinteraction = 0.65, P = 0.001, FDR = 0.003). Changes in AES were not associated with changes in biomarkers. Findings do not support the efficacy of light therapy in reducing IMD features in patients with depression and T2DM. We find limited evidence that light therapy is a more beneficial depression treatment among those with more IMD features. Changes in clinical and biological IMD features did not align over four-weeks' time. Trial registration: The Netherlands Trial Register (NTR) NTR4942. •Immunometabolic dysregulations link depression and cardiometabolic diseases.•Such dysregulations occur more in patients with atypical, energy-related symptoms.•Benefit of light therapy for an immuno-metabolic form of depression (IMD) is unclear.•Among diabetes patients, light therapy was not an effective treatment for IMD.•Whether this is also true in depression without diabetes remains unknown.