Serum brain-derived neurotrophic factor, glial-derived neurotrophic factor, nerve growth factor, and neurotrophin-3 levels in children with attention-deficit/hyperactivity disorder

Abstract

It has been suggested that neurotrophins are involved in the etiopathogenesis of attention-deficit/hyperactivity disorder (ADHD). This study aimed to investigate whether there are differences in serum brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF), nerve growth factor (NGF), and neurotrophin-3 (NTF3) levels between children with ADHD and healthy controls. A total of 110 treatment-naive children with the combined presentation of ADHD and 44 healthy controls aged 8-18 years were enrolled in this study. The severity of ADHD symptoms was determined by scores on the Conners' Parent Rating Scale-Revised Short and Conners' Teacher Rating Scale-Revised Short. The severity of depression and anxiety symptoms of the children were evaluated by the self-report inventories. Serum levels of neurotrophins were measured using commercial enzyme-linked immunosorbent assay kits. The multivariate analysis of covariance (MANCOVA) revealed a significant main effect of groups in the levels of serum neurotrophins, an effect that was independent of age, sex, and the severity of the depression and anxiety. The analysis of covariance (ANCOVA) indicated that the mean serum GDNF and NTF3 levels of ADHD patients were significantly higher than that of controls. However, serum BDNF and NGF levels did not show any significant differences between groups. No correlations between the levels of serum neurotrophins and the severity of ADHD were observed. These results suggest that elevated serum GDNF and NTF3 levels may be related to ADHD in children.

Alterations of Growth Factors in Autism and Attention-Deficit/Hyperactivity Disorder

“…GDNF is widely involved in the survival of serotonergic and dopaminergic neurons because it has neuroprotective effects against neuroinflammation and oxidative damage (21). Untreated children with ADHD show high plasma levels of GDNF (21).…”

“…GDNF is widely involved in the survival of serotonergic and dopaminergic neurons because it has neuroprotective effects against neuroinflammation and oxidative damage (21). Untreated children with ADHD show high plasma levels of GDNF (21). These high GDNF levels have a positive correlation with inattention, hyperactivity, and impulsivity behaviors (11), which are the main clinical manifestations of ADHD.…”

“…These alterations in the pro-NGF and/or NGF levels are related to attentional, learning, and memory impairments shown by ADHD patients (24, 25). Neurotrophins also play a role in the pathophysiology of ADHD (21). Alterations in neurotrophin-3 (NTF3) expression are considered a risk factor for ADHD in childhood (2).…”

“…Alterations in neurotrophin-3 (NTF3) expression are considered a risk factor for ADHD in childhood (2). Serum NTF3 levels are increased in untreated patients (21). …”

The Non-Survival Effects of Glial Cell Line-Derived Neurotrophic Factor on Neural Cells

“…In fact, new functions associated with changes in the expression of downstream effector genes were recently described, such as promotion of proliferation and specification, neurite growth, synaptic and electrophysiological maturation, soma expansion and expression of phenotype-specific proteins. Additionally, GDNF might participate in both homeostasis (pain modulation (Merighi, 2016 )) and pathophysiological states (depression (Sharma et al, 2016 ) and attention-deficit/hyperactivity disorder (Bilgiç et al, 2017 )). Because most of the GDNF-associated research has been centered on the promotion of neuronal survival, with a substantial body of knowledge about this function, this review does not cover neuroprotection, but we aim to review the non-survival effects of GDNF.…”