title: Methylphenidate effects on blood serotonin and melatonin levels may help to synchronise biological rhythms in children with ADHD.
abstract: The neuroendocrine mediators that may contribute to ADHD (Attention deficit and hyperactivity disorder), serotonin and melatonin, are both thought to regulate circadian rhythms, neurological function and stress response. The objective of this study was to determine the effect of the chronic administration of prolonged release methylphenidate (PRMPH) on daily variations in blood serotonin and melatonin and on the excretion of 6-sulphatoxy-melatonin. A total of 179 children (136 males, 42 females) between the ages of 5 and 14 (9.70 ± 2.55) years were enrolled in a controlled quasi-experimental open clinical study. Of the sample, there were 136 Children with ADHD (based on DSM-IV-TR criteria), who were further grouped into subtypes, and the 42 siblings of the participants who did not ADHD patients. Blood samples were taken at 20:00 and 09:00; urine was collected between 21:00 and 09:00. In the ADHD group, the study protocol was repeated after 4.61 ± 2.3 months of treatment. Measurements included melatonin and serotonin by RIA and urine 6-S-aMT by ELISA. Factorial analyses were conducted by STATA 12.0.
  
  
  RESULTS
  ADHD patients showed reduced morning serotonin with a daily profile that was different than the control group due to the predominance of nocturnal concentrations. PRMPH did not result in any significant changes. Melatonin and its daily profile did not differ between controls and the ADHD group with a diurnal rhythm showing higher morning levels that disappear after PRMPH administration. Melatonin was higher in children with predominantly hyperactive-impulsive/conduct disorder subtype. PRMPH resulted in a decrease in 6-S-aMT excretion for both ADHD subtypes.
  
  
  CONCLUSIONS
  Chronic treatment with prolonged release methylphenidate induces subtle changes in the daily fluctuations and concentrations of both serotonin and melatonin. Improvement in Children's Depression Inventory (CDI) scores was not related to a morning increase in serotonin.
authors.affiliation: Servicio de Neuropediatría, Neuropsicología y Atención Temprana, Unidad de Gestión Clínica de Pediatría, Hospital Clínico Universitario San Cecilio, Granada, Spain. Electronic address: amolinac@ugr.es.
authors.forename: Antonio
authors.initials: A
authors.lastname: Molina-Carballo
authors.forename: Ana
authors.initials: A
authors.lastname: Naranjo-Gómez
authors.forename: José
authors.initials: J
authors.lastname: Uberos
authors.forename: Fuensanta
authors.initials: F
authors.lastname: Justicia-Martínez
authors.forename: María-José
authors.initials: MJ
authors.lastname: Ruiz-Ramos
authors.forename: Isabel
authors.initials: I
authors.lastname: Cubero-Millán
authors.forename: Francisco
authors.initials: F
authors.lastname: Contreras-Chova
authors.forename: María-Del-Carmen
authors.initials: MD
authors.lastname: Augustin-Morales
authors.forename: Hoda
authors.initials: H
authors.lastname: Khaldy-Belkadi
authors.forename: Antonio
authors.initials: A
authors.lastname: Muñoz-Hoyos
mesh_terms: D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000097:blood / Q000188:drug therapy*; D001827:Body Height / Q000187:drug effects; D015992:Body Mass Index; D001835:Body Weight / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000494:pharmacology / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D002940:Circadian Rhythm / Q000187:drug effects*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008550:Melatonin / Q000097:blood*; D008774:Methylphenidate / Q000494:pharmacology / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales; D011863:Radioimmunoassay; D012189:Retrospective Studies; D012701:Serotonin / Q000097:blood*
chemical_list: D000697:Central Nervous System Stimulants; D008774:Methylphenidate; D012701:Serotonin; D008550:Melatonin