Is Serum Brain Derived Neurotrophic Factor (BDNF) a Reliable Biological Marker for Autism?

Background: Brain-derived neurotrophic factor (BDNF) plays an important role during neuronal differentiation and survival, and in the formation and plasticity of synaptic connections. Since disruptions in synaptic plasticity has been linked to autism, several studies have examined serum BDNF levels in children with autism but the results are conflicting. This may be due in part to a lack of diagnostic stringency, age of subjects, and/or different inclusion/exclusion criteria used in those studies. 

Objectives: The objective of this study was to compare levels of BDNF in serum from well-characterized male and female children with and without autism to determine whether BDNF is a robust biological marker for ASD.

Methods:  Twenty-one children with autism met the inclusion criteria for this study. An autism diagnosis was assessed by a licensed psychologist using the ADOS and ADI-R. Subjects in the ASD groups were not taking any medications for at least 2 weeks prior to participation in this study. Twenty-one age- and gender-matched healthy children, without siblings on the autism spectrum, were included as controls. All controls completed a health history questionnaire and underwent a developmental screening using the ABAS-II. The mean age, standard deviation and age range for each study group are reported in Table 1. A fasting morning blood sample was obtained from all subjects, processed according to standard protocols and the sera frozen immediately at -80^oC until use. Serum BDNF was measured by ELISA (R&D Systems) at the University of Maryland Cytokine Core Laboratory. Samples were diluted 1:20 and run in duplicate. BDNF data were reported as pg/ml serum. Linear regression was used for all analyses. Binary independent variables (i.e. ASD and gender) were dummy-coded and continuous variables (i.e. age) were mean centered prior to analyses. 

Table 1: The mean age, SD and age range for subjects in each study group.

Group	N	Mean Age (St Dev)	Range
Males w/ ASD	10	4.50 (1.57)	2.3-6.6
Females w/ASD	11	5.21 (1.37)	3.0-7.3
Control males	10	4.87 (1.20)	3.1-6.3
Control females	11	5.14 (1.36)	2.3-6.7

Results: Mean serum BDNF levels within each group is shown in Table 2. Overall, serum BDNF levels were lower in ASD subjects compared with controls (t=-2.7, p=0.011), however, there was no interaction between age or gender (t=1.4, p=0.168 and t=-0.3 and p=0.770, respectively). 

Table 2: The mean +/- SEM levels of serum BDNF per group.

Group	Mean BDNF (pg/ml)	SEM
Males w/ ASD	676.42	88.44
Females w/ASD	788.31	114.53
Control males	1103.68	129.81
Control females	950.20	105.00

Conclusions:  These results suggest that serum BDNF is lower in children with autism compared to controls but there was no effect of age and gender. Serum BDNF may be a useful sub-diagnostic biological marker in ASD but further research is needed in a larger cohort to confirm this finding.