Brain-derived neurotrophic factor involved in autism: meta-analysis

By Reuters Staff

NEW YORK (Reuters Health) - Peripheral blood levels of brain-derived neurotrophic factor (BDNF) are significantly increased in children with autism spectrum disorder (ASD) relative to healthy control children, a large meta-analysis indicates.

The findings support "accumulating evidence" BDNF may be implicated ASD, write Dr. Yong Cheng of the National Institute of Child Health and Human Development in Bethesda, Maryland and co-authors in JAMA Pediatrics online September 19.

BDNF plays a key role in neuronal survival and growth, cell differentiation, synapse formation, synaptic plasticity, and cognitive functions, they point out, and altered BDNF expression has been linked to several neuropsychiatric diseases, including depression and schizophrenia. But studies of the association between blood BDNF levels and ASD have yielded mixed results.

To investigate further, Dr Cheng and colleagues did a systematic review and meta-analysis of 19 studies measuring peripheral blood levels of BDNF in children with ASD (n=1411) compared with healthy control children (n=1485).

They found significantly elevated BDNF levels in the children with ASD relative to that seen in the healthy controls (Hedges g = 0.49; 95% CI, 0.185 to 0.794; P=0.002). However, there was significant heterogeneity among studies (P

Subgroup analyses of four studies that used dried blood spot samples from neonates diagnosed with ASD later in life found no association with blood levels of BDNF (Hedges g = 0.38; 95% CI, -0.244 to 1.011; P=0.23). In contrast, the 15 studies that analyzed blood samples from children with ASD after diagnosis did find increased BDNF levels in the ASD group compared with the healthy group (Hedges g = 0.52; 95% CI, 0.206 to 0.842; P=0.001).

"Through sensitivity analysis, we conclude that our results were not unduly influenced by a particular study. In addition, we found no indication that the outcome of the present meta-analysis was caused by publication bias," the authors say.

"To the best of our knowledge," they add, "this meta-analysis is the first to be performed on this subject. Because the role of circulating BDNF levels in children with ASD has been controversial for more than a decade, and therefore their significance with respect to the etiology of ASD remains elusive, this study provides clinical evidence that children with ASD have increased peripheral blood levels of BDNF. This finding offers a novel perspective into a potential molecular pathway that contributes to the developmental outcomes of ASD."

What remains unclear, they say, is whether an increase in BDNF levels is a cause for ASD development or an epiphenomenon, "such as a counterbalance consequence of ASD development. However, the hypothesis that the hyperactivity of BDNF contributes to the development of ASD is plausible in view of the early postnatal neocortical overgrowth that has been proposed as a core mechanism of ASD, and BDNF is a well-known potent stimulator of neuronal growth."

Dr. Cheng and colleagues think studies looking into BDNF levels as a potential key to early diagnosis and a therapeutic target of ASD are warranted.

Dr. Cheng was unavailable for comment by press time.

The study had no commercial funding and the authors have disclosed no conflicts of interest.

SOURCE: https://bit.ly/2cTEOKy

JAMA Pediatr 2016.