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J Mol Neurosci. 2019 Aug;68(4):688-695. doi: 10.1007/s12031-019-01332-w. Epub 2019 May 9.

Impact of Auditory Integration Therapy (AIT) on the Plasma Levels of Human Glial Cell Line-Derived Neurotrophic Factor (GDNF) in Autism Spectrum Disorder.

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Department of Physiology, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
Autism Research and Treatment Center, Riyadh, Saudi Arabia.
Shaik AL-Amodi Autism Research Chair, King Saud University, Riyadh, Saudi Arabia.
Central Laboratory, Center for Female Scientific and Medical Colleges, King Saud University, Riyadh, Saudi Arabia.
Medicinal Chemistry Department, National Research Centre, Dokki, Cairo, Egypt.
CONEM Saudi Autism Research Group, King Saud University, Riyadh, Saudi Arabia.
Council for Nutritional and Environmental Medicine (CONEM), Toften 24, 8610, Mo i Rana, Norway.
Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.
CONEM Scientific Secretary, Verona, Italy.
Department of Pediatrics, Faculty of Medicine, Ain Shams University, 17 Asem Abd El-Hamid Street off Makram Ebaid, Nasr City, Cairo, 11511, Egypt.


Neurotrophic factors, including the glial cell line-derived neurotrophic factor (GDNF), are of importance for synaptic plasticity regulation, intended as the synapses' ability to strengthen or weaken their responses to differences in neuronal activity. Such plasticity is essential for sensory processing, which has been shown to be impaired in autism spectrum disorder (ASD). This study is the first to investigate the impact of auditory integration therapy (AIT) of sensory processing abnormalities in autism on plasma GDNF levels. Fifteen ASD children, aged between 5 and 12 years, were enrolled and underwent the present research study. AIT was performed throughout 10 days with a 30-min session twice a day. Before and after AIT, Childhood Autism Rating Scale (CARS), Social Responsiveness Scale (SRS), and Short Sensory Profile (SSP) scores were calculated, and plasma GDNF levels were assayed by an EIA test. A substantial decline in autistic behavior was observed after AIT in the scaling parameters used. Median plasma GDNF level was 52.142 pg/ml before AIT. This level greatly increased immediately after AIT to 242.05 pg/ml (P < 0.001). The levels were depressed to 154.00 pg/ml and 125.594 pg/ml 1 month and 3 months later, respectively, but they were still significantly higher compared with the levels before the treatment (P = 0.001, P = 0.01, respectively). There was an improvement in the measures of autism severity as an effect of AIT which induced the up-regulation of GDNF in plasma. Further research, on a large scale, is needed to evaluate if the cognitive improvement of ASD children after AIT is related or not connected to the up-regulation of GDNF.


Auditory integration training; Autism; Childhood Autism Rating Scale; Glial cell line–derived neurotrophic factor; Short Sensory Profile; Social Responsiveness Scale


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