Altered peripheral BDNF mRNA expression and BDNF protein concentrations in blood of children and adolescents with autism spectrum disorder

被引:50
作者
Taurines, Regina [1 ]
Segura, Monica [2 ]
Schecklmann, Martin [3 ]
Albantakis, Laura [1 ]
Gruenblatt, Edna [4 ]
Walitza, Susanne [4 ]
Jans, Thomas [1 ]
Lyttwin, Benjamin [1 ]
Haberhausen, Michael [5 ]
Theisen, Frank M. [6 ]
Martin, Berthold [1 ]
Briegel, Wolfgang [7 ]
Thome, Johannes [8 ,9 ]
Schwenck, Christina [10 ]
Romanos, Marcel [1 ]
Gerlach, Manfred [1 ]
机构
[1] Univ Wurzburg, Dept Child & Adolescent Psychiat, Fuechsleinstr 15, D-97080 Wurzburg, Germany
[2] Univ Int Catalunya, Fac Med & Hlth Sci, Barcelona, Spain
[3] Univ Regensburg, Dept Psychiat & Psychotherapy, D-93053 Regensburg, Germany
[4] Univ Zurich, Dept Child & Adolescent Psychiat, Zurich, Switzerland
[5] Univ Marburg, Dept Child & Adolescent Psychiat, Marburg, Germany
[6] Herz Jesu Krankenhaus, Dept Child & Adolescent Psychiat, Fulda, Germany
[7] Leopoldina Hosp, Dept Child & Adolescent Psychiat, Schweinfurt, Germany
[8] Univ Rostock, Dept Psychiat & Psychotherapy, D-18055 Rostock, Germany
[9] Swansea Univ, Coll Med, Swansea, W Glam, Wales
[10] Goethe Univ Frankfurt, Dept Child & Adolescent Psychiat, Frankfurt, Germany
基金
瑞士国家科学基金会;
关键词
Autism spectrum disorder (ASD); Brain-derived neurotrophic factor (BDNF); ADHD; Neurodevelopmental disorders; Peripheral expression; NEUROTROPHIC FACTOR BDNF; DEFICIT-HYPERACTIVITY DISORDER; MENTAL-RETARDATION; DEPRESSED-PATIENTS; HUMAN PLATELETS; WORKING-MEMORY; SERUM-LEVELS; RAT-BRAIN; GENE; ASSOCIATION;
D O I
10.1007/s00702-014-1162-x
中图分类号
R74 [神经病学与精神病学];
学科分类号
100204 [神经病学];
摘要
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 +/- A 3.0 years) and 20 age- and gender-matched healthy control subjects (age 14.4 +/- A 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 +/- A 2.2), 15 age- and gender-matched healthy controls (age 12.1 +/- A 2.2) and 15 patients with attention deficit hyperactivity disorder as a clinical control group (age 11.8 +/- A 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, eta (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.
引用
收藏
页码:1117 / 1128
页数:12
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