Schizophrenie als Gyrifikationsstörung?

Abstract

An increased gyrification index (GI) has been demonstrated in the frontal lobe of patients with schizophrenia. This hypergyria may serve as a neurodevelopmental or endophenotypic marker in this disease. Schizophrenia patients show subtle motor symptoms and cognitive deficits possibly related to the dysfunction of a fronto-thalamo-cerebellar network including the cerebellum. Additionally, the cerebellar vermis showed volume reductions in schizophrenia. Alterations in gyrification of the cerebellum may indicate neurodevelopmental disturbances of migration and brain folding. Hence, in a post-mortem study we investigated the GI in cerebellar subregions of schizophrenia patients and GI in the cerebellum of a probable animal model of schizophrenia, the reeler mouse. Using a stereologic workstation, consisting of a light microscope (Olympus), motorized specimen, PC and stereology software (Stereoinvestigator, MBF Bioscience) we determined the GI (inner contour of the gyri/outer contour of the cerebellum) according to the methods of Vogeley et al. (2000) and Zilles et al. (1998). We investigated 4 coronal sections (20µm) of the medial cerebellum in 9 schizophrenia patients and 10 healthy controls as well as 6 sagittal sections of the cerebellum of 11 homozygous, 23 heterozygous reeler mice and 17 wildtype mice. In the vermis of schizophrenia patients, the GI was reduced compared to controls (method of Vogeley et al.: p=0.015, method of Zilles et al.: p=0.020). In contrast, in both hemispheres of the cerebellum, no differences have been detected. In the cerebellum of homozygous reeler mice compared to heterozygous reeler mice and wildtype mice, GI was decreased (p<0.001). The decreased GI in the vermis of schizophrenia patients points to neurodevelopmental disturbances since the GI is mainly determined during the perinatal period. However, the underlying neurobiological processes remain to be determined. Reelin is a protein involved in migration of neurons during development and the heterozygous reeler mouse may represent an animal model of behavioral disturbances in schizophrenia, while the homozygous mutation is lethal during the postnatal period. Decreased expression of reelin may lead to gyrification disturbances, which has been shown in our study in homozygous reeler mice. The further role of reelin in gyrification disturbances of the vermis in schizophrenia patients should be investigated.