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Language activation in monozygotic twins discordant for schizophrenia.
- Filip Spaniel, Jaroslav Tintera, Jiri Horacek, Monika Dezortova, Milan Hajek (6 April 2004)
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Filip Spaniel, M.D. Psychiatric Center Prague, Ústavní 91, 181 03 Prague 8,Czech Republic, Jaroslav Tintera, Jiri Horacek, Monika Dezortova, Milan Hajek
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spaniel{at}pcp.lf3.cuni.cz Filip Spaniel, et al.
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Sir: In the February issue of BJP Dr. Sommer and colleagues reported in their study decreased language lateralization measured with functional MRI (fMRI) in 12 MZ twin pairs discordant for schizophrenia compared to 12 healthy MZ twin pairs. The authors didn’t find significant differences in language lateralization between affected twins and their non-schizophrenic co-twins. In the December 2003 issue of the Czech peer-reviewed psychiatric journal, Psychiatrie, we published preliminary data from a study that examined hemispheric dominance for language processing by means of fMRI in four monozygotic twin pairs discordant for schizophrenia. Although the activation task differed from the one employed by Dr. Sommer, the lateralization index was calculated according to the same method within identical VOIs. In our study the subjects were cued to generate, by thinking, as many words as possible starting with a letter of the alphabet presented on a screen during a Verbal fluency task paradigm. All of the twins were right- handed as assessed with the Edinburgh Handedness Inventory. Genetic analysis (the concordance in 16 short tandem repeats markers) confirmed monozygosity of the twin pairs. All subjects were native Czech speakers. The results indicated that language processing was significantly less lateralized in affected twins compared with their non- schizophrenic co-twins (p<0,05, Wilcoxon Signed Ranks Test, robustness assessed by analysis of 10,000 Monte Carlo permutations, the mean laterality index 0,90, S.D. 0,12 for unaffected twins and 0,73, S.D. 0,17 for affected twins). There were no statistical differences in the laterality index during the Verbal fluency paradigm between unaffected twins from the discordant MZ pairs and the four control MZ twin pairs (unpublished data). The different findings in these two studies could theoretically arise from the different activation paradigms used. An alternative explanation of the discrepancies could lie in the subjects enrolled in our study. Since the aim of our work was to assess relative contribution of non-genetic factors in previously reported decreased language lateralization in schizophrenia, the exclusion criterion was (in contrast to Dr. Sommer´s study) any family history of schizophrenia or other major psychiatric disorder. This particular study strategy allowed selection of an extreme population presumably represented by sporadic forms of the disease. In addition, stringent diagnostic criteria were used in that only subjects with schizophrenia were enrolled in the study. In conclusion, because of discordance and an absence of family history of psychiatric illness, the differences in language lateralization within discordant pairs in our study could be attributable to disease-specific non-genetic factors in an extreme population of sporadic cases of the illness. The occurrence of psychiatric disorders in non-schizophrenic co-twins and the fact that the subjects were not controlled for family history of psychosis suggest a substantial degree of genetic predisposition for schizophrenia in unaffected co-twins expressed as overall decrease in language lateralization within the discordant twin group used in the study of Dr. Sommer and her colleagues. Supported by grant NF 6794-3/2001 from the Internal Grant Agency of Czech Republic. Španiel, F., Tintěra, J., Hájek, T. et al. (2003) Language lateralization in monozygotic twins discordant for schizophrenia. Evidence from functional MRI. Psychiatrie, 4, 301-303 |
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