Disturbed frontal gyrification within families affected with schizophrenia

Objective: Recently, in a post-mortem and a subsequent structural MR study, a significantly increased gyrification index (GI) was demonstrated in the frontal lobe in individuals with schizophrenia. To examine whether frontal lobe hypergyria is region-specific and whether this might be a suitable endophenotype in the search for the genetic basis of schizophrenia, the frontal as well as parieto-occipital GI were determined in MRI scans of families affected with schizophrenia. Method: In the MRI scans of 48 subjects suffering from schizophrenia, in 82 of their first-degree relatives and in 41 control subjects, the GI was determined in three sections anterior to the genu of the corpus callosum and three sections posterior to the splenium, thus allowing for a selective determination of this measure in the frontal as well as the parietal lobe. Outer and inner contours constituting the GI was determined in each section by manual tracing. Statistical analysis was performed using MANOVA with factors diagnostic group and intervening factors from preliminary analyses. Results: The frontal, but not parieto-occipital GI was significantly higher in schizophrenic patients as well as unaffected relatives compared with control subjects (right: 7%, F = 13.24, df = 3, 155, p < 0.0005, left: 6%, F = 8.92, df = 3, 155, p < 0.0005). There was no overall difference between affected and unaffected family members. On the left side however, there was a significant interaction between diagnostic group and genetic loading (F = 4.68, df = 2, 101, p = 0.01): significantly higher GI was found in affected compared with unaffected family members only in uniaffected and not multiaffected families. Conclusions: These results support our primary finding of hypergyria in the frontal lobe in schizophrenic patients. Compared to the parietal lobe, hypergyria seems to affect the frontal lobe selectively and serves as a suitable neurodevelopmental, possibly even an endophenotypic marker. (c) 2006 Elsevier Ltd. All rights reserved.