Abstract
OBJECTIVES: Histamine, a critical regulator of attention and inflammatory processes, may play a role in symptoms of attention-deficit/hyperactivity disorder (ADHD). METHODS: Data were from the baseline visit of a multi-site randomized controlled trial in children aged 6-12 with symptoms of ADHD and emotional dysregulation, the Micronutrients for ADHD in Youth (MADDY) study. Parent-reported intake of high-histamine foods was assessed with the VioScreen questionnaire; symptoms of ADHD with the Child & Adolescent Symptom Inventory, version-5 (CASI-5) Inattention and Hyperactivity/Impulsivity subscales, and emotional dysregulation with the Strengths & Difficulties Questionnaire-Dysregulation Profile. Urinary histamine was analyzed with liquid chromatography-mass spectrometry, with reference ranges for children < 10 and 10-12 years old. RESULTS: Thirty percent of children < 10 years old and 81% of children 10-12 (57% overall) had urinary histamine levels above the upper limit of the reference range. Urinary histamine was not associated with inattention, hyperactivity/impulsivity, or emotional dysregulation, nor intake of high-histamine foods, in the entire sample (N = 83). In a sensitivity analysis, participants with urinary histamine levels above the reference range had inattention scores 0.26 points higher on the CASI-5 than participants within the reference range (β = 0.26; 95% CI, 0.01, 0.52; p = 0.043). CONCLUSIONS: In this secondary data analysis, urinary histamine levels were not associated with severity of hyperactivity/impulsivity or emotional dysregulation, or intake of high-histamine foods. Children with high urinary histamine had increased inattention compared to those with normal histamine levels. Limitations include the homogeneity of the sample and the lack of a comparison group without ADHD.