Brain Copy Number Variants and Neuropsychiatric Traits

In this issue of Biological Psychiatry, genomic analysis of patients with neuropsychiatric disease reveals the presence of rare copy number variants (CNVs) in about 2% of the approximately 400 brains examined ( ). CNVs represent deviations from the normal diploid state (n = 2) at a given position or locus in the human genome because of a deletion or duplication at that locus. The CNVs identified have been associated previously with psychiatric illness in large-scale, case-control studies that utilized genomic DNA isolated from blood lymphocytes; however, such CNV have not been directly observed in brains of individuals with neuropsychiatric illness. Such findings are not unanticipated because the genetics and genomics of psychiatric disease have progressed tremendously during the last 3–4 years. Viewed from one perspective, 2% may perhaps be considered by some to signify that the role of genetics in such illnesses may be minor. Alternatively, given that an estimated 1% of the world's population may have schizophrenia, the use of genomic analysis as part of the differential diagnosis and evaluation of these patients may allow the etiology of millions of individual's psychiatric condition to more clearly be diagnosed as part of a workup investigating one of many potential causes in a differential diagnostic list. Moreover, studying larger cohorts of brains from patients or genomic DNA isolated from blood lymphocytes using even more powerful human genome analyses tools may reveal genetic networks involved in disease and may enable additional novel psychiatric disease susceptibility CNV mutations to be identified. The findings of Ye et al. ( ) are of interest because they clearly establish the presence of rare, neuropsychiatric disease–associated CNV in the genomic DNA of brains from patients diagnosed with psychiatric illness.