Brain-Derived Neurotrophic Factor in children with Autism Spectrum Disorder

Abstract

BackgroundAutism Spectrum Disorder (ASD) is a complex neurobehavioral syndrome with no known biomarker so far for early detection. It has been challenging, both to classify typical autism and associate a suitable biomarker with clinical phenotype spectrum. Brain-derived neurotrophic factor (BDNF) has emerged as a key neurotrophin regulating synaptic plasticity, neuronal differentiation and survival.PurposeRecently, BDNF depletion is reported in neurodegenerative as well as in psychiatric disorders, associated with severity of neurological dysfunction. Role of BDNF as a biomarker in ASD is gaining significance. Pre-clinical results have linked BDNF depletion in autism and mental retardation, however, with conflicting findings.MethodsIn view of this, a preliminary study was carried out to measure serum BDNF levels in 48 children with ASD and mental retardation, and 29 age-matched controls.ResultsSerum BDNF levels were found significantly higher (p<0.001) in atypical autistic subjects (clinically milder phenotype) as compared to controls, but not in typical ASD cases (clinically severe phenotype). BDNF levels were significantly lower in females with typical/Rett Syndrome (p<0.05), but not in males with typical autism (p>0.1), as compared to controls. Lower BDNF levels indicate impairment in neuroprotective mechanism, while higher levels may imply a manifested protective response.ConclusionOur study highlights the differential BDNF response based on the severity of neurobehavioral deficit, indicating a possible neuroprotective role of this molecule and supporting its exploration in targeted therapy in ASD.

Autistic traits and neuropsychological performance in 6- to-10-year-old children: a population-based study

“…BDNF is involved in activity-dependent synaptic plasticity and there have been a number of studies linking BDNF with ASD (Armeanu, Mokkonen, & Crespi, 2017;Bryn et al, 2015;Kasarpalkar, Kothari, & Dave, 2014;Saghazadeh & Rezaei, 2017;Wang et al, 2015). Within the context of a genetic predisposition for ASD, coupled with environmental factors that result in over excitation of neurons, BDNF levels increase dramatically, resulting in the presence of a fatty coating around the neurons and megalencephaly (Merzenich, Van Vleet, Nahum, 2014).…”

Severity of ASD symptoms and their correlation with the presence of copy number variations and exposure to first trimester ultrasound

“…BDNF is a neurotrophic factor related to neuronal maturation and synaptic synthesis. BDNF is elevated in children with ASD [Bryn et al, ; Kasarpalkar et al, ; Zhang et al, ] and genes associated with neurodevelopmental disorders impact BDNF expression [Briz et al, ; Koh, Lim, Byun,& Yoo, ; Louhivuori et al, ; Ouyang et al, ]. Prenatal exposure to other environmental toxins impact BDNF: Bisphenol A altered DNA methylation in mice [Kundakovic et al, 2014] and valproate increased BDNF mRNA and protein levels in mice and rats [Almeida, Roby, & Krueger, ].…”

From the genetic architecture to synaptic plasticity in autism spectrum disorder

“…Several studies [150][151][152] , which have not all been replicated 153 , have reported an increase in BDNF levels in the blood of patients with ASD. In addition, high plasma levels of serotonin and N-acetylserotonin, as well as low plasma levels of melatonin, are more frequently observed in individuals with ASD than in controls 154,155 .…”