While observational studies show an association between 25(OH)vitamin D concentrations and depressive symptoms, intervention studies, which examine the preventive effects of vitamin D supplementation on the development of depression, are lacking. To estimate the role of lowered 25(OH)vitamin D concentrations in the etiology of depressive disorders, we conducted a two-sample Mendelian randomization (MR) study on depression, i.e., “depressive symptoms” (DS, n = 161,460) and “broad depression” (BD, n = 113,769 cases and 208,811 controls). Six single nucleotide polymorphisms (SNPs), which were genome-wide significantly associated with 25(OH)vitamin D concentrations in 79,366 subjects from the SUNLIGHT genome-wide association study (GWAS), were used as an instrumental variable. None of the six SNPs was associated with DS or BD (all p > 0.05). MR analysis revealed no causal effects of 25(OH)vitamin D concentration, either on DS (inverse variance weighted (IVW); b = 0.025, SE = 0.038, p = 0.52) or on BD (IVW; b = 0.020, SE = 0.012, p = 0.10). Sensitivity analyses confirmed that 25(OH)vitamin D concentrations were not significantly associated with DS or BD. The findings from this MR study indicate no causal relationship between vitamin D concentrations and depressive symptoms, or broad depression. Conflicting findings from observational studies might have resulted from residual confounding or reverse causation.

High dietary acid load may have detrimental effects on mental health during childhood and adolescence. We examined cross-sectional and prospective associations of dietary acid load and mental health problems in a population-based sample, using data from the German birth cohort studies GINIplus (German Infant Nutritional Intervention plus environmental and genetic influences on allergy development) and LISA (Influences of lifestyle-related factors on the immune system and the development of allergies in childhood). These studies included detailed assessments of dietary intake through a food frequency questionnaire (FFQ), mental health outcomes measured through the Strengths and Difficulties Questionnaire (SDQ), and covariates. Using logistic regression, cross-sectional associations between dietary acid load measured as potential renal acid load (PRAL) and SDQ subscales were assessed at age 10 years (N = 2350) and 15 years (N = 2061). Prospective associations were assessed, considering PRAL at 10 years as exposure and SDQ subscales at 15 years as outcome (N = 1685). Results indicate that children with a diet higher in PRAL have more emotional problems (OR = 1.33 (95% CI = 1.15; 1.54); p < 0.001), and show hyperactivity more often (1.22 (1.04; 1.43); p = 0.014) at 10 years. No significant associations were present either cross-sectionally at age 15 years, nor prospectively. Results were confirmed in sensitivity analyses. These findings reveal first evidence for potential relationships between PRAL and mental health in childhood, although we cannot exclude reverse causality, i.e., that dietary behavior and PRAL are influenced by mental status. Future studies should address confirmation and identify biological mechanisms.

Acute anorexia nervosa (AN) constitutes an extreme physiological state. We aimed to detect state related metabolic alterations during inpatient admission and upon short- and long-term weight regain. In addition, we tested the hypothesis that metabolite concentrations adapt to those of healthy controls (HC) after long-term weight regain. Thirty-five female adolescents with AN and 25 female HC were recruited. Based on a targeted approach 187 metabolite concentrations were detected at inpatient admission (T₀), after short-term weight recovery (T₁; half of target-weight) and close to target weight (T₂). Pattern hunter and time course analysis were performed. The highest number of significant differences in metabolite concentrations (N = 32) were observed between HC and T₁. According to the detected main pattern, metabolite concentrations at T₂ became more similar to those of HC. The course of single metabolite concentrations (e.g., glutamic acid) revealed different metabolic subtypes within the study sample. Patients with AN after short-term weight regain are in a greater “metabolic imbalance” than at starvation. After long-term weight regain, patients reach a metabolite profile similar to HC. Our results might be confounded by different metabolic subtypes of patients with AN.

(1) Background: Evidence has accumulated that patients with anorexia nervosa (AN) are at higher risk for vitamin D deficiency than healthy controls. In epidemiologic studies, low 25(OH) vitamin D (25(OH)D) levels were associated with depression. This study analyzed the relationship between 25(OH)D serum levels in adolescent patients and AN and depressive symptoms over the course of treatment. (2) Methods: 25(OH)D levels and depressive symptoms were analyzed in 93 adolescent (in-)patients with AN from the Anorexia Nervosa Day patient versus Inpatient (ANDI) multicenter trial at clinic admission, discharge, and 1 year follow up. Mixed regression models were used to analyze the relationship between 25(OH)D levels and depressive symptoms assessed by the Beck Depression Inventory (BDI-II). (3) Results: Although mean 25(OH)D levels constantly remained in recommended ranges (≥50 nmol/L) during AN treatment, levels decreased from (in)patient admission to 1 year follow up. Levels of 25(OH)D were neither cross-sectionally, prospectively, nor longitudinally associated with the BDI-II score. (4) Conclusions: This study did not confirm that 25(OH)D levels are associated with depressive symptoms in patients with AN. However, increasing risks of vitamin D deficiency over the course of AN treatment indicate that clinicians should monitor 25(OH)D levels.