Peripheral brain-derived neurotrophic factor in autism spectrum disorder: a systematic review and meta-analysis

Abstract

Brain-derived neurotrophic factor (BDNF) regulates neuronal survival and growth and promotes synaptic plasticity. Recently, researchers have begun to explore the relationship between peripheral BDNF levels and autism spectrum disorder (ASD), but the findings are inconsistent. We undertook the first systematic review and meta-analysis of studies examining peripheral BDNF levels in ASD compared with healthy controls. The PubMed, Embase, and Cochrane Library databases were searched for studies published before February 2016. Fourteen studies involving 2,707 participants and 1,131 incident cases were included. The meta-analysis provided evidence of higher peripheral BDNF levels in ASD compared with controls [standardized mean difference (SMD) = 0.63, 95% confidence interval (95% CI) = 0.18–1.08; P = 0.006]. Subgroup analyses revealed higher BDNF levels in ASD compared with controls for both serum [SMD = 0.58, 95% CI = 0.11–1.04; P = 0.02] and plasma [SMD = 1.27, 95% CI = 0.92–1.61; P < 0.001]. Studies of childhood yielded similar cumulative effect size [SMD = 0.78, 95% CI = 0.31–1.26; P = 0.001], while this was not true for the studies of adulthood [SMD = 0.04, 95% CI = −1.72–1.80; P = 0.97]. This meta-analysis suggests that peripheral BDNF levels are a potential biomarker of ASD.

Brain‐derived neurotrophic factor (BDNF) in children with ASD and their parents: a 3‐year follow‐up

“…In our well‐defined, non‐ID and narrow‐aged ASD sample, BDNF serum levels were found to be lower than in their age‐matched healthy controls. Our finding contradicts the findings of the recent published meta‐analyses that all used roughly the same high heterogeneous studies . But as mentioned above, the relevant research data are strikingly inconsistent and several possible confounding factors, both technical and in sample characteristics, could explain the reported differences.…”

“…The inconsistent findings on BDNF serum levels in ASD, the lack of correlations with clinical characteristics and the course of the disorder could be attributed to the possibility of a real and direct physiological correlation between BDNF serum levels and ASD that is obscured from numerous confounding factors (the presence of ID, allergy, age trajectories, etc). However, unless a specific pattern of these confounding factors is revealed and accounted for, serum BDNF levels cannot serve as a possible biomarker as overstated in the recent meta‐analysis by Zheng et al .…”

“…Unfortunately, these studies have been yielding inconsistent results (Table ) . However, four recent published meta‐analyses (roughly using the same studies) all reported higher levels of BDNF in children with ASD, but also significant statistical heterogeneity across studies . These differences could be attributed to methodological differences such as the analytic platforms used, assay methods, time of sample collection or preparation of serum or to differences in samples characteristics such as age, the presence of allergies or intellectual disability (ID), type of autism (regression vs non‐regression), autism severity or to the control subjects used.…”

Intronic miRNA miR-3666 Modulates its Host Gene FOXP2 Functions in Neurodevelopment and May Contribute to Pathogenesis of Neurological Disorders Schizophrenia and Autism

“…Autism candidate genes ERBB4 [95] and BDNF [96,97] have been associated with ASD. As shown in model 3 (Figure 5c).…”

The Genetic and Epigenetic Basis Involved in the Pathophysiology of ASD: Therapeutic Implications

“…Three recent meta-analysis show as children with ASD have increased peripheral blood levels of BDNF, strengthening the clinical evidence of an abnormal neurotrophic factor profile in this population. Peripheral BDNF levels are a potential biomarker of ASD [176][177][178].…”