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

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. 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. 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. 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.