Methylphenidate does not restore the reduced serum BDNF levels in ADHD children

Abstract

Statement of the problem: Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family of trophic factors, which is the most abundant neurotrophin in the brain. BDNF exerts its effects by binding to the tropomyosin-related kinase B (TrkB) receptor. It enhances the growth and maintenance of several neuronal systems, serves as a neurotransmitter modulator, and participates in mechanisms of neuronal plasticity, such as long-term potentiation and learning. We aim to quantify the basal concentration and daily fluctuation of serum BDNF, as well as its possible change in response to prolonged release methylphenidate in an open, quasi-experimental and controlled study. Methods: A total of 148 (115 males, 33 females) patients, of 9.77 (256) years old, were subdivided in two group. (1) Control group (n=37; 27 males, 10 females); healthy siblings of the Attention deficit hyperactivity disorder (ADHD) patients. (2) ADHD group (n=111; 88 males, 23 females), without epilepsy and with a normal value in an abbreviated intelligence test Kaufman Brief Intelligence Test (KBIT). In all subjects, after written informed consent, we performed identical clinical, psychometric and biochemical study, before and after (only ADHD group) treatment. ADHD group were diagnosed according Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria and sub-classified in the primary ADHD subtypes by EDAH scale. Measurement: BDNF by ELISA (IBL International, ref. RB59041), in serum samples obtained at 09:00 and 20:00 h, before and after 4,63 (2,3) months of the daily morning ingestion of PRMPH. Statistic: factorial analyses using statistical package STATA 12.0. Funding: Grant of Spanish government, FIS-PI07-0603. Results: Serum BDNF (ng/ml) in ADHD children Control group Pre-PRMPH Post-PRMPH Day Night Day Night Day Night 36.36±11.62 31.78±11.92 31.96±12.57 28.40±12.50 29.43±12.00 26.73±12.32 Basal measurements: Day/night comparisons: z = –2.76, p=0.006. Group comparison: z=–2.19; p=0.028. ADHD pre vs. post: χ2=2.64, p = 0.1042; day vs. night: χ2=9.8, p=0.0017. Conclusion: The ADHD patients show reduced BDNF serum concentrations in relation with siblings controls, concordant with the known pathophysiological mechanisms. Our results do not support the only previous contribution that indicates an increase of BDNF in untreated ADHD children, with positive correlation with the severity of the symptoms of inattention. In addition, we report for the first time “basal” response to treatment with PRMPH, with somewhat surprising results, because as neuronal trophic factor, one might expect an increase in serum in response to methylphenidate, that ameliorates neuropsychological and organic immaturity, proven the last in studies of volumetric magnetic resonance imaging (MRI).

Keywords

• methylphenidate
• reduced serum
• BDNF levels
• ADHD
• children