Offspring of monozygotic twins discordant for schizophrenia

We studied the incidence of psychopathologic disorder in offspring of monozygotic twins discordant for schizophrenia. The original material was based on a complete national sample of twins who were hospitalized for functional psychosis in Norway. A comparison of adult offspring of schizophrenic monozygotic twins with offspring of their nonpsychotic cotwins showed that although there are more schizophrenic and schizophreniclike cases in the first group, an observation that may be ascribed to environmental factors, the difference is not statistically significant.     

Neuropsychological assessment of monozygotic twins discordant for schizophrenia

A comparison of monozygotic twins discordant for schizophrenia controls for genetic variance and reduces variance due to environmental circumstances, thus serving to highlight differences due to phenotypic-related variables. In this study, we assessed 16 such twin pairs on a wide range of neuropsychological tests. The affected twins tended to perform worse than their unaffected counterparts on most of the tests. Deficits were especially severe on tests of vigilance, memory, and concept formation, suggesting that dysfunction is greatest in the frontotemporal cortex. While manifest symptoms were not highly associated with neuropsychological scores, global level of functioning was. To address the issue of genetic liability, we also compared the sample of discordant unaffected twins with a sample of seven pairs of normal monozygotic twins. No significant differences between the groups were found for any neuropsychological test. In fact, the results suggest that neuropsychological dysfunction is a consistent feature of schizophrenia and that it is related primarily to the clinical disease process and not to genetic or nonspecific environmental factors.     

Synaesthesia: discordant male monozygotic twins

Grapheme-color synaesthesia, a condition in which achromatic graphemes elicit vivid experiences of color is believed to be a genetically determined trait. We describe a study of 10-year-old twin brothers who are physically identical in appearance but who have considerably different conscious experiences. A phenotypic analysis that measured the consistency of grapheme-color pairings over test-retest confirmed that one twin has grapheme-color synaesthesia and the other twin does not. A genotypic analysis using sixteen microsatellite loci confirmed that the twins are monozygotic. These findings are problematic for previous suggestions that synaesthesia is an X-linked dominant trait. At the very least, the findings show that the penetrance of the genotype for synaesthesia is incomplete and that any view suggesting that synaesthesia is simply an X-linked dominant trait is therefore also incomplete and possibly even incorrect. The findings also negate a previous suggestion, based on a study of female monozygotic twins, that discordance of synaesthesia in identical twins is due to X-inactivation. In general, the findings raise serious questions regarding whether it is possible at this time to establish the genetic contribution to synaesthesia.     

Olfactory impairment in monozygotic twins discordant for schizophrenia

Objective Several studies demonstrated olfactory dysfunction in patients with schizophrenia, some reported deficient olfaction in unaffected relatives of schizophrenics as well. This study differentially assessed olfactory acuity as well as smell identification and smell discrimination in monozygotic twins discordant for schizophrenia and healthy, monozygotic control twins, to determine the genetic basis of different olfactory modalities and their association to schizophrenia. Method The SniffinSticks test,a comprehensive and standardized olfactory test, was employed to assess the olfactory function of 10 monozygotic twin pairs discordant for schizophrenia versus 10 age- and sexmatched healthy,monozygotic twin pairs. Results Olfaction of affected monozygotic twins was globally impaired. Partial olfactory impairment of their unaffected co–twins may point to a genetic cause of olfactory impairment in schizophrenia. The influence of genetic factors was most evident for olfactory acuity and least evident for smell identification. All olfactory functions declined with duration of illness. Side of stimulus presentation did not influence olfactory performance. Conclusions Genetic factors associated with olfactory dysfunction may contribute to schizophrenia. The degree of the genetic influence on olfaction depends on the olfactory domain under examination.     

Neuropsychological performance of monozygotic twins discordant for bipolar disorder.

BACKGROUND: A paradigm that involves cognitive assessment of monozygotic (MZ) twins discordant for a neuropsychiatric disorder (here bipolar illness) allows for the examination of both disease-specific impairments (in the comparison of affected to unaffected twins) and risk factors (in the comparison of unaffected twins to normal twins). METHODS: Neuropsychological functions were evaluated in seven MZ twin pairs discordant for bipolar illness and seven pairs of normal MZ twins in an attempt to highlight cognitive abilities associated with manifestations of disease and genetic risk factors. At the time of testing, 3 of the affected twins were euthymic, 2 had depressive symptoms, and 2 had manic symptoms; all were receiving medication. All twins receive neuropsychological tests to evaluate intelligence, attention, visuospatial skills, language, learning and memory, and problem solving. RESULTS: Statistical analyses revealed that the affected twins were significantly impaired as compared to the unaffected (and normal) twins on some measures of visuospatial functioning and some verbal memory measures. In contrast to a sample of MZ twins discordant for schizophrenia studied previously, the cognitive impairments we observed in bipolar twins were mild in nature and fairly circumscribed. The unaffected twins performed significantly worse than normal controls on a Brown-Petersen memory task, verbal list learning, and overall Wechsler Memory Quotient. CONCLUSIONS: These data suggest that while some visuospatial deficits and verbal memory deficits may be features of bipolar disorder related to disease parameters, mild attenuations in overall memory or retrieval function may be related to genetic factors associated with the illness.     

Synaesthesia: a case study of discordant monozygotic twins

We describe a study of 11-year-old twin sisters who are physically identical in appearance but who have considerably different conscious experiences. One twin appears to be a synaesthete in that she states that she has specific colour experiences (i.e. photisms) whenever she views, hears or thinks of digits. The other twin does not report such conscious experiences when viewing, hearing or thinking about digits. A genotypic analysis using eight microsatellite loci plus the gender of the twins and their parents confirmed that the twins are monozygotic. A phenotypic analysis using a modification of the Stroop task confirmed that only one twin is a synaesthete. We suggest that the discordance in synaesthesia may be due to either an epigenetic event, X chromosome inactivation, or a mutation of a synaesthesia gene.     

Regional cerebral glucose metabolism in monozygotic twins discordant for Alzheimer's disease

We investigated regional cerebral glucose metabolic rates (rCMRgluc) with positron emission tomography using 2-[18F]fluoro-2-deoxy-D-glucose (FDG) in 7 monozygotic twin pairs discordant for Alzheimer's disease (AD). Ten healthy volunteers with comparable mean age and educational level served as controls. In the hippocampus, the mean +/- SD rCMRgluc were 0.20 +/- 0.03 micromol/ml/min for the demented twins, 0.21 +/- 0.03 micromol/ml/min for their non-demented co-twins, and 0.23 +/- 0.02 micromol/ml/min for the controls. The mean hippocampal rCMRgluc was reduced in the demented twins (p = 0.006), compared with the controls. In the lateral temporal cortex, the mean +/- SD rCMRgluc were 0.27 +/- 0.05, 0.28 +/- 0.04, and 0.32 +/- 0.02 micromol/ml/min, respectively. These mean rates were reduced both in the demented (p = 0.02) and the non-demented (p = 0.01) twins, compared with the controls. In conclusion, in the demented twins, the reduction of rCMRgluc was detected in the hippocampus and lateral temporal cortex, i.e. the 2 brain areas which show early changes in pathological and imaging studies in AD. Their non-demented co-twins showed milder reductions, which may be an indication of genetic susceptibility for dementia, and an early sign of a dementing illness in them.     

Dichotic listening in monozygotic twins discordant and concordant for schizophrenia.

Emotional and neutral word versions of the fused rhymed words dichotic listening test were administered to members of 18 pairs of monozygotic twins discordant for schizophrenia, 7 pairs concordant for schizophrenia, and 7 pairs of normal twins. In the discordant group, affected twins had smaller right ear advantages than did their unaffected cotwins for neutral words. The difference was completely attenuated with the presentation of emotional words or in less powerful between-group comparisons that included twins concordant for schizophrenia and normal twins. It is unlikely that this finding reflects an abnormality in the lateralized representation of language, both because we did not find a correlation between handedness scores and dichotic listening scores and because emotional stimuli normalized results. The finding may reflect abnormalities in the allocation of attention for priming language centers in the left hemisphere. 'At risk' subjects, i.e., the unaffected members of the discordant pairs, did not differ significantly from normal monozygotic twins on measures of dichotic listening.     

Plasma CPK levels in monozygotic and dizygotic twins discordant for schizophrenia

Plasma creatine phosphokinase (CPK) activity was determined in single samples of 9 monozygotic and 14 dizygotic twin pairs chosen from an earlier study on the basis of their having been discordant for clinical schizophrenia. The correlations within the MZ pairs was 0.89, and within the DZ pairs was 0.40. The results support a conclusion of genetic control of plasma CPK activity. The mean levels of activity were not abnormal, however.     

Copper perturbation in 2 monozygotic twins discordant for degree of cognitive impairment

BACKGROUND: Recent evidence indicates that peripheral tissue markers can provide information regarding changes affecting cellular metabolism in Alzheimer disease (AD). We previously reported that serum copper levels can discriminate subjects with AD from normal control subjects (with 60% sensitivity and 95% specificity) and from patients with vascular dementia (with 63% sensitivity and 85% specificity). OBJECTIVE: To study the correlation between AD and serum levels of transition metals and markers of peripheral oxidative stress. DESIGN: Case study. SETTING: General hospital inpatient wards and outpatient clinics.Patients A pair of elderly monozygotic female twins discordant for AD. MAIN OUTCOME MEASURES: Biochemical analyses of peripheral-blood transition metals and indicators of oxidative stress and neurologic and neuropsychological assessments of clinical status for presence of cognitive impairment and AD. RESULTS: Serum copper and total peroxide levels were both 44% higher in the twin with greater cognitive impairment and a diagnosis of AD. CONCLUSIONS: The cases reported support the hypothesis of a major involvement of copper and oxidative abnormalities in AD.