Insulin-Like Growth Factors

Abstract

In autism, disruption of normal neurobiological mechanisms is found, but it is not known which specific developmentally important molecules might be involved in this disorder. Increased cerebral volume or brain weight is found across studies in autism. Pathological brain growth and premature developmental arrest are suggested to be restricted to the first years of life. We found a correlation between insulin-like growth factor-1 (IGF-1) concentrations and head growth in children with autism but not in the controls. At an early stage of infantile autism, the cerebrospinal fluid (CSF) concentration of IGF-1 was lower than in the comparison group, but not in older children. This suggests a disruption of normal neurobiological mechanisms at an early age. Furthermore, we also found normal CSF nerve growth factor (NGF) in autism, but low NGF and normal IGF-1 in Rett syndrome (RS). There is evidence that IGF-1 is important for cerebellar development, and low CSF IGF-1 concentrations may lead to cerebellar abnormalities. In autism, almost all neuropathological studies have reported decreased numbers of Purkinje cells in the cerebellum. NGF is important for cholinergic neurons of the forebrain, and the cholinergic system is affected in RS. Therefore, autism and RS could be distinguished by their different levels of the two growth factors. This is in agreement with the different morphological and neurochemical findings in the two syndromes. In autism, there seems to be a disruption of normal neurobiological mechanisms due to “premature growth without guidance.” The data suggest that the IGF system may play an important role in the pathophysiology of autism. Autism is a behaviorally defined condition in which social interaction and reciprocal communication are disturbed. Aberrant behavioral expression in children with autism is usually noticed by the parents, typically between 12 and 24 months of age. The diagnosis is based on clinical criteria. The etiopathogenesis is unknown. Disruption of normal neurobiological mechanisms has been found, but it is not known what specific developmentally important molecules might be involved in this disorder. Nelson et al. 2001 [1] have suggested that in autism there is a relationship between abnormal concentrations of growth factors and abnormal patterns of brain growth. Knowledge of the important roles of neurotrophic factors in relation to the development of the brain is growing.