Disturbed frontal gyrification within families affected with schizophrenia

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Abstract

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.

Section snippets

Objectives of the study

Schizophrenia is a severe mental disorder leading to long-term disability in a substantial proportion of sufferers. About half of the pathophysiological variability can be explained by genetic factors. The intensive search for candidate genes has led to a number of informative chromosomal regions, but only recently to promising candidate genes such as dysbindin, neuregulin-1, G72/G30 and DAAO. A number of problems might have contributed to this long search, including the unsatisfactory

Patients and control subjects

The sample consisted of schizophrenic patients (n = 48), their relatives suffering from a psychiatric illness other than schizophrenia, psychotic illness or spectrum disorders (ICD10: F0–F1, F32–F59, F60.2–F9; mainly depression and/or alcohol dependence) (n = 29), their relatives without any diagnosed psychiatric illness (n = 53) and control subjects (n = 41) from the resident population beyond families with schizophrenia. Furthermore, the families were categorized as having one member (uniaffected) or

Influence of site of MRI, sex, age, family and other intervening variables

Mean age was significantly different between the four groups under study (Table 1). Comparing the distribution of males and females, there was no significant difference between diagnostic groups. The percentage of right-handers was lowest in family members (= FM) with schizophrenia, but there was no significant difference between the groups.

There were significant differences related to the site of MRI for right frontal GI and bilateral parieto-occipital GI. Looking at the influence of sex,

Discussion

The aim of this study was to further elucidate whether our recent finding of frontal hypergyria in schizophrenia (Vogeley et al., 2000, Vogeley et al., 2001) could be replicated in another larger, more representative sample comparing patients suffering from schizophrenia with a fairly large number of first-degree relatives with and without a psychiatric disorder as well as control subjects. This allows a detailed analysis based on the subgroups outlined above. We also extended our measurements

Acknowledgment

Supported by the Deutsche Forschungsgemeinschaft (Fa 241/2-3).

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