In this study, we investigated the levels of EGF and HGF, two growth factors involved in neurodevelopment. Previous studies have found decreased levels of EGF in high functioning adults with autism [18
], but no studies have looked at children with ASD who are close to the onset of the disorder. We found that levels of plasma EGF were significantly reduced in young children with ASD as compared with similarly age-matched typically developing control children. This finding is consistent with that seen in adults with high functioning autism and may suggest that a deficiency in EGF is persistent throughout the time course of ASD.
Current research has demonstrated that EGF is involved in growth, differentiation, and maintenance of several tissues including the CNS and the gastrointestinal tract (GI) [14
]. Notably, abnormalities of both the CNS and the GI have been reported in ASD [26
]. In the CNS, EGF serves as a potent neurotrophic factor, and in vivo
studies have demonstrated the effect of EGF in promoting proliferation, differentiation, survival, and migration of multipotent neural progenitor cells and the differentiation of these cells into astrocytes and neurons [27
]. In this paper, we were limited to investigating EGF in plasma and not in cerebral spinal fluid. However, EGF rapidly transports across the blood-brain barrier [28
], suggesting peripheral EGF levels could be representative of levels in the CNS that may impact neurodevelopment.
In the GI tract, EGF is necessary for normal development of the intestinal mucosa, and mice deficient in EGF receptor suffer from symptoms similar to those of necrotizing enterocolitis, with gradual destruction of villi, become severely malnourished, and typically die before postnatal day 8 [16
]. EGF promotes wound healing in animal models of ulcerative colitis [29
]. Although GI symptoms affect a large proportion of children with ASD, the exact nature and extent of GI inflammation in ASD are still controversial [31
]. Interestingly, preliminary investigations in this study show that EGF levels are associated with increased bloating in children with ASD, as well as with raw, standard, and percentile rank scores on the Peabody picture vocabulary test-III and with the composite and nonverbal development quotient of the Mullen's test (P
< 0.05, data not shown). However, the meaning of this data is not clear and we will validate these findings in a larger replication cohort.
It has been previously reported that HGF was decreased in the plasma of adults with autism [20
]; however, we did not find a significant difference between children with ASD and typically developing children for plasma HGF levels. This may be due to age differences between the participants of our study and those in the previous reports. To our knowledge, the relationship between age and serum HGF levels has not been thoroughly established, but there is evidence that levels may decrease with age [35
Collectively, our data suggest that reduced levels of EGF are present in ASD. The roles of EGF and ASD require further research to better elucidate the relationship between this potent growth factor and ASD pathophysiology.