The contribution of platelets to peripheral BDNF elevation in children with autism spectrum disorder

Cristan A Farmer,Audrey E Thurm,Paul Kim,Bianca Honnekeri,Joan C Han,Susan E Swedo

doi:10.1038/s41598-021-97367-4

Abstract

Brain-derived neurotrophic factor (BDNF), a key peptide in neurocognitive development, has been reported to be elevated in the serum of children with autism spectrum disorder (ASD). In a few studies, however, no differences or the converse have been documented. As a secondary analysis of a natural history study, we examined differences in ELISA serum BDNF between a group of children aged 1 to 9 years (69% white) with ASD (n = 94) and those with typical development (n = 52) or non-ASD developmental delay (n = 21), while accounting for the potential confounding effects of platelet quantity. Platelet counts were measured within 4 h of blood draw using an automated cell counter. Taqman single nucleotide polymorphism (SNP) assays were used to genotype 11 SNPs within the BDNF locus. Unadjusted mean BDNF concentration was higher in children with ASD than in children with typical development (standardized mean difference = 0.23; 95% CI 0.07, 0.38), but not children with non-ASD developmental delay. The magnitude of this difference was reduced after adjusting for platelet count (standardized mean difference = 0.18; 95% CI 0.02, 0.33). Although some BDNF SNPs were related to BDNF concentration, the distributions of these genotypes did not differ across diagnostic groups. This study replicates previous work suggesting that average serum BDNF concentration is higher in ASD compared to typical development, and extends that work by highlighting the potentially confounding role of platelet counts. The etiology of platelet count differences warrants further elucidation. Nonetheless, our results suggest that elevation in BDNF may be partially explained by higher platelet counts in children with ASD, an association that should be considered in future analysis and interpretation.Registration: NCT00298246

Highlights

Brain-derived neurotrophic factor (BDNF), a key peptide in neurocognitive development, has been reported to be elevated in the serum of children with autism spectrum disorder (ASD)
The largest available meta-analysis found that across 27 studies encompassing 6,571 unique participants, BDNF was elevated in the blood of children with ASD compared to typically developing c hildren[7]; four other smaller meta-analyses have drawn the same c onclusion[8,9,10,11], as has at least one very recently published study not included in the previous meta-analyses[12]
Children diagnosed with DSM-IV-TR autistic disorder were enrolled in the autism spectrum disorder (ASD) group, those with significantly impaired cognitive ability but without ASD were enrolled in the non-ASD developmental delay (DD) group, and children with no behavioral or psychological concerns were enrolled in the typical development (TYP) group

Summary

Introduction

Brain-derived neurotrophic factor (BDNF), a key peptide in neurocognitive development, has been reported to be elevated in the serum of children with autism spectrum disorder (ASD). This study replicates previous work suggesting that average serum BDNF concentration is higher in ASD compared to typical development, and extends that work by highlighting the potentially confounding role of platelet counts. In situations where neither platelet counts nor platelet-poor samples are available, the interpretation of differences in BDNF depends on the assumption that platelet counts are similar across the comparison groups being investigated This is an especially relevant consideration for studies of BDNF in ASD, as some studies have found evidence for elevated platelet count in groups of children with ASD14,15 (others report no difference[16,17], and no meta-analysis is available)

Methods

Results

Discussion

Conclusion