Emerging Patterns of Neuronal Growth Desynchronization in Autism

Background: Pathological acceleration of brain growth in the first year of life and deceleration in the second and third year appear to play a pivotal role in the onset of clinical signs of autism (Courchesne et al., 2001, 2003; Courchesne and Pierce, 2005). Distortions of brain development are reflected in abnormal neuronal development and cortical minicolumn organization (Casanova et al 2002, 2006), and local dysgenesis (Bauman and Kemper, 1995, 1996; Kemper and Bauman 1993, 1998).

Objectives: We hypothesize that the (a) acceleration and deceleration of brain growth is a reflection of developmental cellular pathology, (b) acceleration of brain growth results in production of immature and smaller than normal neurons, (c) deceleration of brain growth results in acceleration of growth of neurons, (d) desynchronization of the growth of neurons in the brain in early childhood may play a critical role in shaping the clinical manifestations of autism.

Methods: To characterize sequential age and brain-subdivision-specific patterns of neuronal growth, 11 major subdivisions of the brain in one brain hemisphere of 14 autistic and 14 control subjects 4 to 56 years of age were examined. Unbiased morphometric methods of estimation of brain structure were applied, including the Cavalieri method, fractionator, and nucleator (Microbrightfield).

Results: Early childhood (4 - 8 years) was the period of significant delay of neuronal growth in the majority of examined brain structures including four nuclei of the amygdala, three striatal subdivisions (caudate, putamen and nucleus accumbens), thalamus, entorhinal cortex, dentate nucleus and Purkinje cells. None or insignificant delay was observed in the cornu Ammonis sectors 1-4, lateral geniculate body, inferior olive and nucleus of facial nerve. Late childhood was the period of significant acceleration of neuronal growth compensating for an early childhood delay.

Conclusions: The presence of a similar developmental delay of neuronal growth in the majority of examined structures in early childhood may indicate that (a) the developmental delay of the growth of neurons is regulated in a similar way in many brain regions, and that (b) each component of these complex neuronal networks may have its own contribution to the clinical phenotype of autism. The absence of a significant delay of neuronal growth in other brain regions suggests desynchronization of mechanisms controlling the growth of neurons. We hypothesize that interactions of incorrectly developing neurons/networks with non-affected brain networks may still result in dysfunction of both, affected and non-affected networks.