BDNF concentrations and daily fluctuations differ among ADHD children and respond differently to methylphenidate with no relationship with depressive symptomatology

• Published in: Psychopharmacology Vol. 234; no. 2; pp. 267 - 279
• Main Authors: Cubero-Millán, Isabel, Ruiz-Ramos, María-José, Molina-Carballo, Antonio, Martínez-Serrano, Sylvia, Fernández-López, Luisa, Machado-Casas, Irene, Tortosa-Pinto, Pilar, Ruiz-López, Aida, Luna-del-Castillo, Juan-de-Dios, Uberos, José, Muñoz-Hoyos, Antonio
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 2017; Springer Nature B.V
• Subjects: Adolescent; Attention Deficit Disorder with Hyperactivity - blood; Attention Deficit Disorder with Hyperactivity - drug therapy; Attention Deficit Disorder with Hyperactivity - psychology; Attention deficit hyperactivity disorder; Biomarkers - blood; Biomedical and Life Sciences; Biomedicine; Brain-Derived Neurotrophic Factor - blood; Central Nervous System Stimulants - pharmacology; Central Nervous System Stimulants - therapeutic use; Child; Child, Preschool; Children & youth; Comorbidity; Depression - blood; Depression - drug therapy; Depression - psychology; Female; Humans; Impulsive Behavior - drug effects; Impulsive Behavior - physiology; Male; Mental depression; Methylphenidate - pharmacology; Methylphenidate - therapeutic use; Neurosciences; Original Investigation; Pharmacology/Toxicology; Prospective Studies; Psychiatry; Treatment Outcome; Human; ADHD; Daily rhythms; Comorbidities; BDNF; Serum; Depressive symptoms; ADHD subgroups; Children; Methylphenidate
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-016-4460-1

Rationale Brain-derived neurotrophic factor (BDNF) enhances the growth and maintenance of several monoamine neuronal systems, serves as a neurotransmitter modulator and participates in the mechanisms of neuronal plasticity. Therefore, BDNF is a good candidate for interventions in the pathogenesis and/or treatment response of attention deficit hyperactivity disorder (ADHD). Objective We quantified the basal concentration and daily fluctuation of serum BDNF, as well as changes after methylphenidate treatment. Method A total of 148 children, 4–5 years old, were classified into groups as follows: ADHD group ( n  = 107, DSM-IV-TR criteria) and a control group (CG, n  = 41). Blood samples were drawn at 2000 and 0900 hours from both groups, and after 4.63 ± 2.3 months of treatment, blood was drawn only from the ADHD group for BDNF measurements. Factorial analysis was performed (Stata software, version 12.0). Results Morning BDNF (36.36 ± 11.62 ng/ml) in the CG was very similar to that in the predominantly inattentive children (PAD), although the evening concentration in the CG was higher (CG 31.78 ± 11.92 vs PAD 26.41 ± 11.55 ng/ml). The hyperactive–impulsive group, including patients with comorbid conduct disorder (PHI/CD), had lower concentrations. Methylphenidate (MPH) did not modify the concentration or the absence of daily BDNF fluctuations in the PHI/CD children; however, MPH induced a significant decrease in BDNF in PAD and basal day/night fluctuations disappeared in this ADHD subtype. This profile was not altered by the presence of depressive symptoms. Conclusions Our data support a reduction in BDNF in untreated ADHD due to the lower concentrations in PHI/CD children, which is similar to other psychopathologic and cognitive disorders. MPH decreased BDNF only in the PAD group, which might indicate that BDNF is not directly implicated in the methylphenidate-induced amelioration of the neuropsychological and organic immaturity of ADHD patients.