ABSTRACT
Our goal was to establish whether altered hippocampal morphology represents a trait marker for genetic vulnerability in schizophrenia. We outlined the hippocampi on high-resolution MR images obtained from matched samples of control and discordant monozygotic and dizygotic co-twins (N = 40 pairs). Hippocampal measures were used in statistical tests specifically designed to identify disease-associated genetic and nongenetic influences on morphology. 3D surface average maps of the hippocampus were additionally compared in biological risk groups. Smaller hippocampal volumes were confirmed in schizophrenia. Dizygotic affected co-twins showed smaller left hippocampi compared to their healthy siblings. Disease-associated effects were not present between monozygotic discordant co-twins. Monozygotic, but not dizygotic, unaffected co-twins exhibited smaller left hippocampi compared to control twins, supporting genetic influences. Surface areas and posterior volumes similarly revealed schizophrenia and genetic liability effects. Results suggest that hippocampal volume reduction may be a trait marker for identifying individuals possessing a genetic predisposition for schizophrenia.
Subject(s)
Hippocampus/pathology , Schizophrenia/genetics , Schizophrenia/pathology , Adult , Female , Humans , Image Processing, Computer-Assisted , Male , Middle Aged , Twins, Dizygotic , Twins, MonozygoticABSTRACT
Patients with schizophrenia exhibit abnormalities in midsagittal corpus callosum area, shape, and/or displacement. Our goal was to confirm these findings and to establish the genetic and nongenetic contributions to altered callosal morphology in schizophrenia. Relationships between ventricular enlargements potentially contributing to callosal displacements were assessed as a secondary goal. High-resolution magnetic resonance images were obtained from co-twins of monozygotic and dizygotic pairs discordant for schizophrenia and healthy control twins (N = 40 pairs). Investigators blind to group status segmented the corpus callosum and ventricles in native brain volumes aligned using a rigid-body transformation with no scaling. Total and parcellated midsagittal callosal areas and measures indexing vertical displacements of the corpus callosum were used in statistical tests to identify schizophrenia and sex effects and to dissociate genetic and nongenetic influences on morphology. Anatomical mesh modeling methods provided group average and surface variability maps of the callosum. Callosal areas did not differ between groups defined by sex or biological risk. Vertical displacements of the callosum, pronounced in male patients, were confirmed in schizophrenia and observed between dizygotic, but not monozygotic co-twins discordant for schizophrenia. Like their affected twins, however, unaffected monozygotic co-twins of the schizophrenia probands exhibited significant callosal displacements. Lateral and third ventricle enlargements were related to callosal displacements. Results clearly support that genetic rather than disease-specific or shared environmental influences contribute to altered callosal morphology in schizophrenia. An upward bowing of the callosum may thus provide an easily identifiable neuroanatomic marker to screen individuals possessing a biological vulnerability for schizophrenia.
