Does inflammation moderate the effect of vitamin D supplementation on depressive symptoms? Results of an interventional study in children and adolescents

PURPOSE: Studies in adults suggest antidepressant effects of vitamin D, possibly via anti-inflammatory pathways, but evidence in youth is lacking. In the first randomized controlled trial (RCT) in depressed, vitamin D-deficient adolescents (DRKS00009758), symptom reduction emerged in only one of three outcomes. This secondary analysis investigates whether baseline inflammatory status modifies the effect of vitamin D. METHODS: Data from 92 participants (78.3% ♀) of the RCT conducted at the Department of Child and Adolescent Psychiatry were analyzed. All participants were deficient in vitamin D [25(OH)D ≤ 30 nmol/l] and at least mild depressive symptoms [Beck Depression Inventory-II (BDI-II) ≥ 14]. Participants received 2640 IU/day of vitamin D or placebo for 28 days plus treatment as usual. Depressive symptoms were assessed via BDI-II and the Diagnostic System for Mental Disorders in Childhood and Adolescence (DISYPS), self- and proxy-rated. C-reactive protein (CRP) was measured at baseline as an inflammatory marker. Its impact on treatment effects was examined via interaction analyses and stratification by CRP status. RESULTS: In 81.5% of the participants, CRP levels were below the threshold for low-grade inflammation (3 mg/L). No consistent interaction between treatment and baseline CRP was observed across outcomes. A nominal interaction for self-rated DISYPS at the 3 mg/L threshold lost significance after correction for multiple testing. Stratified analyses using different CRP thresholds revealed no significant subgroup effects. CONCLUSIONS: Overall, our findings do not support the hypothesis that the antidepressant effects of vitamin D supplementation in children and adolescents depend on baseline CRP status—at least within a sample characterized by minimal baseline inflammation.