Genetic Variation of Chromosome 1q42: Etiologic Mechanism of Congenital Disorders of Neuronal Migration and Synaptogenesis

The cytoarchitectural defects of schizophrenia are predominantly “mild” alterations of dendrites and cell positioning, which are subtle in comparison to those in the lissencephalies and many presentations of mental retardation. Moreover, they are studied in adult brains and, thus, subject to the many potentially confounding effects of such things as medication history, substance abuse, lifestyle variables and stress. Thus, the ability to identify subtle fetal brain abnormalities in utero, such as operationally-defined mild lateral ventricular enlargement as an isolated finding, and longitudinally follow this genotyped cohort, some of whom may be at increased risk for neurodevelopmental disorders including schizophrenia, will be informative. The demonstration of co-segregation of genetic variation (e.g., within the DISC1 gene) and mild lateral ventricular enlargement, and the opportunity to seek linkages in parents and sibs would be extremely persuasive that genetic variations (e.g., in DISC1) cause or contribute to mild lateral cerebroventricular enlargement, which may be a risk factor and anatomic intermediate phenotype of schizophrenia.