The Role of Synaptic Dysfunction as a Key Driver in Autism Pathogenesis

Autism in childhood is a heterogeneous disease with around 110 phenotypes. Around 800 genes are affiliated with autism including members of neuro-ligand, neurexin, cadherin, GABA receptors, SHANK gene families, mutated UBE3 A on chromosome 15 and SNORD 116 precursor interaction. A predominant 4:1 male to female ratio is found in autistic spectrum disorder. 50 per cent of all autistic children show chromosome deletions and duplications, these are often found on the 15th and 16th chromosome. Copy number repeat variants in DNA are also well described in pathogenesis of autism patients. There is an overlap with other neurodevelopmental syndromes like tuberous sclerosis, Williams-syndrome, Phelan McDermid syndrome and Sphrintzen syndrome. The hypothesis of the term “atypical connectivity” in different brain regions with partial under- and overconnectivity with reduced brain networking at the psychosocial level was described. Different hypothesis about the origin of autism in children were described. The hypothesis of early lack of basic trust, mercury intoxication and different aspects concerning the origin of this extraordinary disease of 2 percent of children were stated but not confirmed to date. Especially low immature production of IgF-1 by oligodendrocytes in the corpus callosum leads to slowing of the PI3K/AKT chain activation of myelination that Ig-F1 could play an important role in the origin of the disease. Synaptic dysfunction with hypomyelination and impaired impulse transmission seem to play an extraordinary role with under- and overconnectivity with reduced brain networking at the psychosocial level in autistic children. Functional underconnectivity is found in 5 different brain areas, prefrontal, parieto-occipital, motor, somatosensory and the temporal region. Functional overconnectivity is often present in temporo-thalamic regions. Recent research shed light on synaptic dysfunctions with disrupted normal impulse signaling. In this review the different neurochemical findings and the correlation of synaptic dysfunction in autistic children will be closely evaluated.