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

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Abstract

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.

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Acknowledgments

Funding for this study was provided by the Health Research Fund (FIS; Spanish Ministry of Science and Innovation), FIS-PI07-0603; the FIS played no further role in the study design; in the collection, analysis and interpretation of data; in the writing of the report or in the decision to submit the paper for publication.

We wish to thank Mrs. Puri Ubago-Corpas for her supervision and support.

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Authors and Affiliations

  1. Departamento de Pediatría, Facultad de Medicina, Universidad de Granada, Avda de Madrid 12, 18012, Granada, Spain

    Isabel Cubero-Millán, María-José Ruiz-Ramos, Antonio Molina-Carballo, Sylvia Martínez-Serrano, Luisa Fernández-López, Irene Machado-Casas, Pilar Tortosa-Pinto, Aida Ruiz-López, José Uberos & Antonio Muñoz-Hoyos

  2. Servicio de Neuropediatría, Neuropsicología y Atención Temprana, Unidad de Gestión Clínica de Pediatría, Complejo Hospitalario Granada, Hospital Clínico San Cecilio, Avda Dr. Olóriz 16, Granada, Spain

    Antonio Molina-Carballo, Irene Machado-Casas, José Uberos & Antonio Muñoz-Hoyos

  3. Departamento de BioEstadística, Facultad de Medicina, Universidad de Granada, Granada, Spain

    Juan-de-Dios Luna-del-Castillo

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  1. Isabel Cubero-Millán
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  2. María-José Ruiz-Ramos
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Corresponding authors

Correspondence to Antonio Molina-Carballo or Antonio Muñoz-Hoyos.

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The study design and outcome variables were approved by the Hospital Ethics Committee and the Health Research Fund of the Spanish Ministry of Science and Innovation.

Contributors

AMC, JU and AMH designed the study and wrote the protocol. ICM, MJRR, SMS, LFL, PTP, ARL and IMC performed the sample collection and managed the literature searches and analyses. AMC, AMH and JDLC undertook the statistical analysis; and ICM, MJRR and AMC wrote the first draft of the manuscript. All of the researchers contributed to and have approved the final manuscript.

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The authors declare that they have no conflict of interest.

Additional information

This work is part of María-José Ruiz-Ramos doctoral thesis.

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Cubero-Millán, I., Ruiz-Ramos, MJ., Molina-Carballo, A. et al. BDNF concentrations and daily fluctuations differ among ADHD children and respond differently to methylphenidate with no relationship with depressive symptomatology. Psychopharmacology 234, 267–279 (2017). https://doi.org/10.1007/s00213-016-4460-1

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