Neurodevelopmental sequelae associated with gray and white matter changes and their cellular basis: A comparison between Autism Spectrum Disorder, ADHD and dyslexia

• Gray matter changes that accompany ASD may reflect changes in synapses and white matter changes reflect changes in myelination due to pathologies of oligodendrocytes.
• De novo copy-number variations confer substantial risk for ASD.
• Genetic studies have consistently indicated that ADHD is a highly heritable disorder.
• There is significant overlap of shared biological processes disrupted by large rare CNVs for ADHD and autism.

Many psychiatric diseases, such as major depression and schizophrenia, are accompanied by patterns of gray matter and white matter changes in the cortex that may be due to structural pathologies of synapses and their dendrites in the gray matter on the one hand and to pathologies in myelinating oligodendrocytes on the other. Here the possibility has been briefly examined that such a generalization might also hold for Autistic Spectrum Disorders (ASD). Evidence is presented that gray matter changes that accompany ASD may in fact reflect changes in synapses and subsequently of their dendrites, whereas those in the white matter reflect changes in myelination due to pathologies of oligodendrocytes. It is proposed that such structural pathologies during development provide a coherent biological model not only for the onset and course of ASD but also provide the basis for development and systematic evaluation of new treatment strategies.