Progress in cytogenetics: implications for child psychopathology.

OBJECTIVE

This review considers the impact of chromosomal studies on the understanding of childhood neuropsychiatric syndromes, highlighting key discoveries, advances in technology, and new challenges faced by clinicians trying to interpret recent findings.

METHOD

We review the literature on the genetics of child psychiatric disorders, including autism, childhood-onset schizophrenia, attention-deficit/hyperactivity disorder, and Tourette syndrome, with a focus on studies of chromosomal structure.

RESULTS

Over several decades, cytogenetic investigations have led to key findings relevant to child psychiatry. During this time, technology has transitioned from light microscopy to molecular cytogenetics to microarray-based detection of structural variation, resulting in a dramatic increase in the resolution of such approaches. Each of these methods has contributed to the understanding of the genetic bases of developmental neuropsychiatric disorders. Moreover, the implementation of microarray technology has prompted a reconceptualization of the nature of human genetic variation, demonstrating that both the sequence of DNA as well as the fine structure of chromosomes vary in affected and unaffected individuals.

CONCLUSIONS

The study of chromosomal variation at high resolution continues to be a promising area of research that is yielding critical data regarding the genetic underpinnings of childhood psychiatric disorders. Preliminary data indicate that apparently identical submicroscopic variations in chromosomal structure may predispose to a very broad range of phenotypes. These findings suggest that disruption of the same basic neurodevelopmental mechanisms, such as synapse function, may result in outcomes that span a broad sweep of DSM-IV psychiatric diagnoses.