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Abstract Background: A ttention-deficit/hyperactivity disorder (ADHD) is the most common neurodevelopmental disorders in childhood and adolescence, affecting 2.2 to 17.8% of all school-aged children and adolescents. ADHD in children has been associated with a wide range of developmental deficits including limitations of learning or control of executive functions as well as global impairments of social skills. The Diagnostic Statistical Manual of fifth revision, DSM-5, defines ADHD as a neurodevelopmental disorder characterized by impairing levels of inattention, disorganization, and/or hyperactivity– impulsivity. Inattention and disorganization involve failure to stay on task, seeming not to listen, and losing materials, at levels that are not consistent with age or developmental level. Hyperactivity– impulsivity entails overactivity, fidgeting, inability to stay seated, intruding into other people’s activities, and inability to wait. In childhood, ADHD frequently overlaps with other mental disorders including oppositional defiant disorder and conduct disorder. The causes of ADHD are not fully understood; however, several environmental (e.g., exposure to certain foods or inhalants) and genetic risk factors have been proposed. It has been suggested that dietary interventions such as ω-3 FA and vitamin and mineral supplementation might affect ADHD symptoms. Recently a number of studies have proposed that vitamin D might play a role in ADHD pathogenesis. The mechanisms by which vitamin D might affect a number of neurological diseases, including ADHD, are not clear. Nevertheless, there is evidence demonstrating the widespread presence of vitamin D receptors and 1α-hydroxylase (the enzyme responsible for the formation of the active vitamin) in the human brain; therefore, it is suggested that vitamin D might have neurohormonal properties in the human brain. Furthermore, a recent study proposed that vitamin D directly upregulates expression of tyrosine hydroxylase (a ratelimiting enzyme in dopamine synthesis) by binding to the nuclear vitamin D receptor. It is also suggested that this vitamin is involved in the synthesis of serotonin in the brain. Subjects and Methods: • Study type: Cross sectional, observational, case – control study. • Sample size and Duration: A sample size of 108 cases divided equally between healthy children and ADHD cases achieves a power of 80% to detect a moderate effect size using Chi square test with level of significance of 0.05. The study included 54 children diagnosed with ADHD. Another 54 age and sex matched normal children were taken as a control group. from August 2022 to January 2023. • Site of the study: The sample was selected from the Child Psychiatry Outpatient Clinic, Benha Mental Health Hospital, Qalyubia, Egypt. All children who fulfilled the inclusion criteria were included in the study. Inclusion criteria: • Age ranges between 5 and 16 years. • Both sexes were included. • Informed consent from parents or caregivers of the child enrolling in the study. Exclusion criteria: • Intelligence quotient (IQ) <75. • Presence of other medical conditions as chronic medical disorders e.g. Diabetes mellitus….etc. Hearing and visual impairment, or medications side effects, which may results in hyperactivity and impaired sleep rhythm. • Presence of other neuropsychiatric disorders identified by The Mini International Neuropsychiatric Interview for children and adolescents (M.I.N.I.Kid). • Patients with Calcium supplements or vitamin D supplements during the last 6 month before the study. • Patients with history of epilepsy or anti-epileptic drugs. • Subjects excluded due to either refusal of the parent or difficulty in drawing blood from very uncooperative subjects. • Tools used: All selected children were subjected to the following: • A semi-structured interview to their parents or caregivers emphasizing the demographic data as age, sex, residency, school grades, the history of the illness, family history including consanguinity between parents, presence of similar condition in family, other psychiatric disorders in the family. The condition of pregnancy, labor, type of labor, feeding, vaccination, milestones, scholastic achievement, relations, social and communication skills. Past history of medical or surgical condition or trauma, neuropsychiatric symptoms and signs noted by the caregivers…etc. • The Mini International Neuropsychiatric Interview for children and adolescents (M.I.N.I.Kid) to identify psychiatric symptoms/disorders as aggression, conduct disorder, anxiety, mood symptoms and disorders, phobia, delayed speech and tics. • Conner’s Parent Rating Scale applied to detect subtypes and severity of ADHD. • Stanford Binet Intelligence Scale provides a comprehensive coverage of intelligence and cognitive abilities • Assessment of habitual vitamin D intake by using a validated food frequency questionnaire. • Estimation of the serum level of human 25 hydroxy vitamin D using Snibe Maglumi 800 Fully Automatic Immunoassay Analyzer. Results: The demographic and anthropometric data between the ADHD group and the control group were matched. The mean age for the ADHD group was 8. 11 ± 2. 55 years, they were 45 males (83. 3%) and 9 females (16. 7%). Possible allergic condition were found among 16. 7% of ADHD patients, while 11. 1% of the control group had medical comorbidities; 7.4% of ADHD patients had psychiatric comorbidities, while none of the individuals in the control group were positive for psychiatric comorbidities with no significant difference in psychiatric or medical comorbidities between the two groups. Regarding habitual vitamin D intake, There was a significant decrease in weekly vitamin D intake received by ADHD when compared to control group (p=0. 001). The median weekly vitamin D intake for the ADHD group was 615. 2 IU (range: 180. 8 – 841. 6 IU), which was lower than the median weekly vitamin D intake for the control group was 664. 0 IU (range: 437. 6 – 1212. 0 IU), p<0. 001. The new diagnosis group had a mean age of 7. 37 ± 2. 59 years, which was significantly younger than that of the old diagnosis group, who had a mean age of 8. 85 ± 2. 32 years. The new diagnosis group had 21 males (77. 8%) and 6 females (22. 2%), while the old diagnosis group had 24 males (88. 9%) and 3 females (11. 1%). No significant differences were found between old and new subgroups regarding gender, BMI, associated comorbidities, Weekly Vitamin D Intake via FFQ and 25-Hydroxy Vitamin D Level. Regarding serum level of human 25 hydroxy vitamin D, The ADHD group had a mean level of 18. 20 ± 6. 46, while the control group had a mean level of 31. 72 ± 18. 03. The median (range) for 25-Hydroxy Vitamin D level was 18. 9 (6. 8 – 35. 2) for the ADHD group and 25. 5 (9. 1 – 89. 9) for the control group; 17 participants (31. 5%) in the control group had sufficient levels, while only 1 participant (1. 9%) in the ADHD group had sufficient levels. 36 participants (66. 7%) in the control group had insufficient levels of 25-Hydroxy Vitamin D, while 46 participants (85. 2%) in the ADHD group had insufficient levels. One participant (1. 9%) in the control group had deficient levels of 25-Hydroxy Vitamin D, while 7 participants (13. 0%) in the ADHD group had deficient levels. Overall, the data suggests that ADHD is a disorder with a wide range of symptoms, and the Conners Parent Rating Scale is a useful tool for assessing the severity of these symptoms. The majority of patients in this sample exhibited symptoms that exceeded the average range than the controls. Regarding drugs received by old cases of ADHD, Among these participants, 14 (51. 9%) received Atomoxetine as a medication for ADHD, 8 (29. 6%) received a combination of Atomoxetine and behavioral therapy, and 5 (18. 5%) received only behavioral therapy as a treatment for ADHD. There is no statistically significant difference in hydroxy25 vitamin D level among the three treatment groups, with the highest level was attributed to Atomoxetine & Behavioral therapy, p > 0.05. There is no significant association between 25-Hydroxy Vitamin D Level and medical/psychiatric comorbidities among ADHD patients, but there is a significant association between 25-Hydroxy Vitamin D Level and mother intake of Vitamin D during pregnancy among ADHD patients. Conclusion: The present results suggest an association between 25-OH-vitamin D concentration and ADHD in childhood. Although the nature and direction of the causal relationship between serum vitamin D level and ADHD remains unclear, the present study found a noteworthy association. This realationship warrants further investigation to define the exact role of vitamin D in the pathogenesis of ADHD. CONCLUSION The present study revealed that there was a significant difference in sufficiency of 25-Hydroxy Vitamin D level between the ADHD group and the healthy group as ADHD patients were found to have significantly lower levels of 25-Hydroxy Vitamin D and had more insufficient levels of this vitamin compared to the control group. Furthermore, the present study revealed a significant decrease in weekly vitamin D intake received by ADHD when compared to control group. Ascending severity of cognitive problem / inattention was significantly associated with decreasing vitamin D level. • Clinical recommendations: 1- Routine checkup of vitamin D level is recommended in ADHD and more attention for nutritional history of children with ADHD. 2- Prevention and early recognition of vitamin D deficiency particularly in ADHD children is so important, since its treatment is an easy, available, cheap, and safe approach. 3- The results of current study highlight the importance of evaluation and supplementation of vitamin D in Egytian children with ADHD, although the small sample size focus the need for farther studies. • Research recommendations 1- More studies should be done to include large samples of patients and wide demographic distribution to ensure that vitamin D is deficient in Egyptian children with ADHD. 2- Further studies with wider scope on large number of patients entailing vitamin D administration as an adjuvant treatment are needed to clarify the therapeutic effects of vitamin D supplementation. 3- Relationship between serum vitamin D level and ADHD warrants farther investigation to define the exact role of vitamin D in the pathogenesis of ADHD. 4- Large scale prospective studies needed to approve that vitamin D deficiency is a cause of ADHD. 5- Further studies that includes investigations of other vitamins and minerals such as serum calcium, serum phosphorous and serum alkaline phosphatase. 6- Prospective longitudinal studies are needed to determine whether lower vitamin D levels predispose individuals with comorbid ADHD; or whether those with comorbid ADHD have lower levels of vitamin D due to differences in clinical or psychologic behavior. |