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MZ Twins Discordant for Schizophrenia

Within-Pair EEG Concordance

In an EEG study of 91 healthy subjects with repeated assessments, 40 pairs of healthy MZ twins, 27 pairs of MZ twins discordant for schizophrenia, and 13 pairs of MZ twins concordant for schizophrenia, we investigated (1) the trait quality of brain-wave patterns with respect to inter-individual differences, intra-individual stability over time, and within-pair MZ concordance, (2) the characteristics of brain-wave patterns that allow one to discriminate reliably between affected and unaffected individuals, and (3) the characteristics of brain-wave patterns that reflect the severity of illness. Most parameters chosen to quantify brain-wave characteristics were found to possess distinct trait-like qualities, as indicated by large inter-individual differences, great stability over time, and high within-pair concordances in healthy MZ twins.

Non-Genetic Pathologic Brain Developments

In comparison to healthy controls, MZ twins discordant and concordant for schizophrenia exhibited a much lower within-pair EEG concordance, although the majority of correlation coefficients differed significantly from zero. Accordingly, abnormalities of brain-wave patterns associated with schizophrenia and differently manifested in MZ co-twins concordant for schizophrenia seem to reflect non-genetic, idiosynchratic pathologic developments of genetically identical brains. These abnormalities allowed us to discriminate reproducibly between affected and unaffected individuals by means of a multivariate discriminant function with an overall accuracy of 80%.

Severity of Illness

The severity of illness, as derived from the brain-wave discriminant function, was closely related to the severity of illness provided by psychopathology scores and overall AXIS V social functioning. In consequence, the non-genetic, highly individual pathologic development of brain-wave patterns in schizophrenia clearly limit the usefulness of these quantities as biological markers for investigations into the genetic predisposition to this illness.

References

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Stassen HH, Coppola R. Torrey EF, Gottesman II, Kuny S, Rickler KC, Hell D: EEG differences in monozygotic twins discordant and concordant for schizophrenia. Psychophysiology 1999; 36,1: 109-117
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Weisbrod M, Hill H, Sauer H, Niethammer R, Guggenbühl S, Stassen HH: Nongenetic pathologic developments of brain-wave patterns in monozygotic twins discordant and concordant for schizophrenia. Am J Med Genetics B 2004; 125: 1-9
concordance
Fig. 3: Within-pair concordances of psychopathology syndrome scores in mz and dz twins where at least one co-twin suffers from a schizophrenic disorder. No more than 55% of mz and 15% of dz co-twins are concordant for schizophrenia, thus displaying highly significant deviations from the expected mz:dz ratio of 2:1 for genetically additive traits. This deviation indicates the existence of strong non-linearities. The boundary between unaffected and affected ("0.5") is somewhat arbitrary but does not change the principal finding.
Detailed analyses of our family data showed that: (1) patients with a clinical diagnosis of schizoaffective disorders have the highest genetic vulnerability; (2) the gentic vulnerability is not constant but depends on the age of onset and the severity of psychopathology scores; (3) genetic vulnerability appears to be ethnicity-independent. All this is valid on a group level but must not necessarily be true for a particular patient.
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