transforming-growth-factor-beta and Child-Development-Disorders--Pervasive

To examine levels of 3 neurotrophic factors (NTFs): Brain derived neurotrophic factor (BDNF), Neurotrophin-4 (NT-4), and transforming growth factor-β (TGF-β) in dried blood spot samples of neonates diagnosed with autism spectrum disorders (ASD) later in life and frequency-matched controls.. Biologic samples were retrieved from the Danish Newborn Screening Biobank. NTFs for 414 ASD cases and 820 controls were measured using Luminex technology. Associations were analyzed with continuous measures (Tobit regression) as well as dichotomized at the lower and upper 10th percentiles cutoff points derived from the controls' distributions (logistic regression).. ASD cases were more likely to have BDNF levels falling in the lower 10th percentile (odds ratios [OR], 1.53 [95% confidence intervals (CI), 1.04-2.24], P-value = 0.03). Similar pattern was seen for TGF-β in females with ASD (OR, 2.36 [95% CI, 1.05-5.33], P-value = 0.04). For NT-4, however, ASD cases diagnosed with ICD-10 only were less likely to have levels in upper 10th percentile compared with controls (OR, 0.22 [95% CI, 0.05-0.98], P-value = 0.05).. Results cautiously indicate decreased NTFs levels during neonatal period in ASD. This may contribute to the pathophysiology of ASD through impairments of neuroplasticity. Further research is required to confirm our results and to examine the potential therapeutic effects of NTFs in ASD.

Topics: Brain-Derived Neurotrophic Factor; Case-Control Studies; Child Development Disorders, Pervasive; Confidence Intervals; Denmark; Female; Humans; Infant, Newborn; Male; Nerve Growth Factors; Odds Ratio; Retrospective Studies; Risk Factors; Transforming Growth Factor beta

Topics: Brain-Derived Neurotrophic Factor; Child Development Disorders, Pervasive; Female; Humans; Male; Nerve Growth Factors; Transforming Growth Factor beta

Topics: Brain-Derived Neurotrophic Factor; Child Development Disorders, Pervasive; Female; Humans; Male; Nerve Growth Factors; Transforming Growth Factor beta

Evidence suggests that some developmental disorders, such as autism spectrum disorders (ASDs), are caused by errors in brain plasticity. Given the important role of matrix metalloproteinases (MMPs) and neurotrophins (NTs) in neuroplasticity, amniotic fluid samples for 331 ASD cases and 698 frequency-matched controls were analyzed for levels of MMP-9, brain-derived neurotrophic factor, NT-4 and transforming growth factor-β utilizing a Danish historic birth cohort and Danish nationwide health registers. Laboratory measurements were performed using an in-house multiplex sandwich immunoassay Luminex xMAP method, and measurements were analyzed using tobit and logistic regression. Results showed elevated levels of MMP-9 in ASD cases compared with controls (crude and adjusted tobit regression P-values: 0.01 and 0.06). Our results highlight the importance of exploring the biologic impact of MMP-9 and potential therapeutic roles of its inhibitors in ASD and may indicate that neuroplastic impairments in ASD may present during pregnancy.

Topics: Adult; Amniotic Fluid; Brain-Derived Neurotrophic Factor; Case-Control Studies; Child Development Disorders, Pervasive; Cohort Studies; Denmark; Female; Humans; Infant, Newborn; Male; Matrix Metalloproteinase 9; Nerve Growth Factors; Neuronal Plasticity; Odds Ratio; Pregnancy; Transforming Growth Factor beta