Brain Connectivity in Autism: The Significance of Null Findings

Autism spectrum disorder (ASD) has become a case study for illustrating the difficulty in tracing a psychiatric disorder to its underlying causes—psychological, genetic, or neurological. Aside from theories derived from the very criteria used to diagnose ASD, one would be hard-pressed to find a psychological theory that is not hotly disputed. Genetic investigations revealed that very large sample sizes are required to tease out the very small effects of very many genes, or large effects of genes present in only very few cases. Meanwhile, investigators doing work at the neurological level have held out hope that their theories might, finally, serve to provide a compact and reliable explanation of ASD that could best mediate between the genes and the phenotype. A new study by Lefebvre et al. ( 1) in this issue of Biological Psychiatry is beginning to cast some doubt that a simple anatomical story will emerge.