Serum ferritin, vitamin B12, folic acid, and blood count-derived inflammatory biomarkers in children and adolescents with attention deficit/hyperactivity disorder: a case-control study

Abstract

Attention deficit/hyperactivity disorder (ADHD) ranks among the most diagnosed neurodevelopmental conditions of childhood, yet its pathophysiology remains only partially clarified. Iron, together with vitamin B12 and folate, serves as a necessary cofactor for dopaminergic signaling, and subclinical systemic inflammation has been suggested as a possible contributing mechanism. This study compared serum ferritin, vitamin B12, folic acid, complete blood count derived inflammatory ratios between ADHD children and healthy peers and explored how these biomarkers relate to the intensity of ADHD symptoms. This case control study was carried out within the Neuropsychiatry Department at Assiut University Hospital and enrolled 100 children meeting DSM-5 TR diagnostic criteria for ADHD, verified using the Kiddie Schedule for Affective Disorders and Schizophrenia for School Age Children Present and Lifetime Version (K-SADS-PL), with symptom severity graded via the Conners’ Parent Rating Scale Revised Long Form (CPRS-R-L). An additional 100 healthy children served as controls. Serum ferritin, vitamin B12, and folic acid concentrations were assayed, alongside a complete blood count used to derive the neutrophil to lymphocyte (NLR), monocyte to lymphocyte (MLR), and platelet to lymphocyte (PLR) ratios. Children with ADHD exhibited markedly reduced serum ferritin (34.95 ± 20.83 vs. 51.41 ± 19.80 ng/mL), vitamin B12 (213.49 ± 148.67 vs. 304.06 ± 177.57 pg/mL), and folic acid (2.58 ± 2.14 vs. 3.97 ± 2.74 ng/mL) concentrations relative to controls (all p < 0.001). NLR, MLR, PLR, and mean platelet volume were elevated in the ADHD cohort, whereas lymphocyte count and hemoglobin were reduced (all p < 0.05). Regression modeling showed that diminished ferritin levels independently forecast greater inattentive (B = -0.089), hyperactive-impulsive (B = -0.157), and combined (B = -0.146) symptom scores. ADHD in this cohort was associated with a distinct biochemical signature of ferritin, vitamin B12, and folate insufficiency together with evidence of a low-grade systemic inflammatory state, and lower ferritin independently predicted symptom severity. These inexpensive, widely available biomarkers may hold value as adjunctive screening and intervention targets in children who have ADHD.