Altered peripheral BDNF mRNA expression and BDNF protein concentrations in blood of children and adolescents with autism spectrum disorder.
Findings from molecular genetic studies and analyses of postmortem and peripheral tissue led to the hypothesis that neurotrophins-as crucial moderators of neuroplasticity-impact on the pathophysiology of autism spectrum disorder (ASD). The study projects aimed to complement former results on the role of brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family with fundamental impact on brain development and function. The purpose of this work was to investigate peripheral BDNF mRNA expression and BDNF protein concentrations in ASD as potential surrogates for the effects observed in the central nervous system. In a BDNF protein quantification study, serum concentrations were analyzed using Enzyme-Linked Immunosorbent Assays in 24 male patients with ASD, all with an IQ > 70 (age 13.9 ± 3.0 years) and 20 age- and gender-matched healthy control subjects (age 14.4 ± 2.1 years; p = 0.522). In a further independent project, a BDNF mRNA expression analysis, mRNA levels from total blood were assessed by quantitative real-time polymerase chain reaction in a sample of 16 male ASD patients (age 10.8 ± 2.2), 15 age- and gender-matched healthy controls (age 12.1 ± 2.2) and 15 patients with attention deficit hyperactivity disorder as a clinical control group (age 11.8 ± 2.2; p = 0.207). In the protein quantification project, significantly decreased BDNF serum concentrations were found in ASD cases compared to healthy control children (t = -2.123, df = 42, p < 0.05). Analysis of covariance (ANCOVA) revealed this result in accordance with significant reductions in BDNF mRNA expression in ASD, observed in the mRNA expression study (F = 3.65; df = 2.43; p < 0.05); neither age nor IQ confounded the result, as indicated by ANCOVA (F = 3.961; df = 2.41; p < 0.05, η (2) = 0.162). Our study projects supported the notion that neurotrophins are involved in the pathophysiology of ASD. Further studies may eventually contribute to the identification of distinct peripheral mRNA expression and protein concentration patterns possibly supporting diagnostic and therapeutic processes.
Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Fuechsleinstraße 15, 97080, Wuerzburg, Germany, taurines@kjp.uni-wuerzburg.de.
Regina
R
Taurines
Monica
M
Segura
Martin
M
Schecklmann
Laura
L
Albantakis
Edna
E
Grünblatt
Susanne
S
Walitza
Thomas
T
Jans
Benjamin
B
Lyttwin
Michael
M
Haberhausen
Frank M
FM
Theisen
Berthold
B
Martin
Wolfgang
W
Briegel
Johannes
J
Thome
Christina
C
Schwenck
Marcel
M
Romanos
Manfred
M
Gerlach
D000293:Adolescent; D000367:Age Factors; D000704:Analysis of Variance; D001289:Attention Deficit Disorder with Hyperactivity / Q000097:blood; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood*; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007360:Intelligence; D007361:Intelligence Tests; D008297:Male; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000097:blood
D019208:Brain-Derived Neurotrophic Factor; D012333:RNA, Messenger; C579455:BDNF protein, human