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



We quantified the basal concentration and daily fluctuation of serum BDNF, as well as changes after methylphenidate treatment.



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).



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.



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.
Departamento de Pediatría, Facultad de Medicina, Universidad de Granada, Avda de Madrid 12, 18012, Granada, Spain.
Isabel
I
Cubero-Millán
Departamento de Pediatría, Facultad de Medicina, Universidad de Granada, Avda de Madrid 12, 18012, Granada, Spain.
María-José
MJ
Ruiz-Ramos
Departamento de Pediatría, Facultad de Medicina, Universidad de Granada, Avda de Madrid 12, 18012, Granada, Spain. amolinac@ugr.es.|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. amolinac@ugr.es.
Antonio
A
Molina-Carballo
Departamento de Pediatría, Facultad de Medicina, Universidad de Granada, Avda de Madrid 12, 18012, Granada, Spain.
Sylvia
S
Martínez-Serrano
Departamento de Pediatría, Facultad de Medicina, Universidad de Granada, Avda de Madrid 12, 18012, Granada, Spain.
Luisa
L
Fernández-López
Departamento de Pediatría, Facultad de Medicina, Universidad de Granada, Avda de Madrid 12, 18012, Granada, Spain.|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.
Irene
I
Machado-Casas
Departamento de Pediatría, Facultad de Medicina, Universidad de Granada, Avda de Madrid 12, 18012, Granada, Spain.
Pilar
P
Tortosa-Pinto
Departamento de Pediatría, Facultad de Medicina, Universidad de Granada, Avda de Madrid 12, 18012, Granada, Spain.
Aida
A
Ruiz-López
Departamento de BioEstadística, Facultad de Medicina, Universidad de Granada, Granada, Spain.
Juan-de-Dios
JD
Luna-Del-Castillo
Departamento de Pediatría, Facultad de Medicina, Universidad de Granada, Avda de Madrid 12, 18012, Granada, Spain.|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.
José
J
Uberos
Departamento de Pediatría, Facultad de Medicina, Universidad de Granada, Avda de Madrid 12, 18012, Granada, Spain. amunozh@ugr.es.|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. amunozh@ugr.es.
Antonio
A
Muñoz-Hoyos
D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000097:blood* / Q000188:drug therapy* / Q000523:psychology; D015415:Biomarkers / Q000097:blood; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood*; D000697:Central Nervous System Stimulants / Q000494:pharmacology / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D003863:Depression / Q000097:blood* / Q000188:drug therapy* / Q000523:psychology; D005260:Female; D006801:Humans; D007175:Impulsive Behavior / Q000187:drug effects / Q000502:physiology; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology / Q000627:therapeutic use*; D011446:Prospective Studies; D016896:Treatment Outcome
D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor; D000697:Central Nervous System Stimulants; D008774:Methylphenidate; C579455:BDNF protein, human
ADHD; ADHD subgroups; BDNF; Children; Comorbidities; Daily rhythms; Depressive symptoms; Human; Methylphenidate; Serum