R. Strobl

Genome scan for susceptibility loci for schizophrenia and bipolar disorder

BACKGROUND Despite the widely accepted view that schizophrenia and bipolar disorder represent independent illnesses and modes of inheritance, some data in the literature suggest that the diseases may share some genetic susceptibility. The objective of our analyses was to search for vulnerability loci for the two disorders. METHODS A genomewide map of 388 microsatellite DNA markers was genotyped in five schizophrenia and three bipolar disorder Austrian families. Linkage analyses was used to compute the usual parametric logarithm of the likelihood of linkage (LOD) scores and nonparametric linkage analysis (NPL scores Z(all)) was used to assess the pattern of allele sharing at each marker locus relative to the presence of the disease (GENEHUNTER). Affected status was defined as severe affective disorder or schizophrenia. RESULTS Across the genome, p values associated with NPL scores resulted in evidence (i.e., p <.0007) for linkage at marker D3S1265 on chromosome 3q (NPL score Z (all) = 3.74, p =.0003). Two other markers (on 3q and 6q) showed p values of <.01. CONCLUSIONS We detected a potential susceptibility locus for bipolar disorder and schizophrenia on chromosome 3q, which has not been reported previously. The possibility of a false positive result has to be taken into account. Our data suggest shared loci for schizophrenia and bipolar affective disorders and are consistent with the continuum model of psychosis.

Genome Scan for Susceptibility Loci for Schizophrenia

Objective: Schizophrenia is a relatively common, often chronic and debilitating mental illness. Evidence from various studies has clearly demonstrated that genetic factors contribute substantially to the etiology. The goal of this study was to identify chromosomal regions likely to contain schizophrenia susceptibility genes. Methods: A genome-wide map of 388 microsatellite DNA markers was genotyped in 5 schizophrenia families. Nonparametric linkage analysis (Genehunter) was used to assess the pattern of allele sharing at each marker locus relative to the presence of disease. Results: Nonparametric linkage scores did not reach a genome-wide level of statistical significance (p < 0.00002) or a p value suggestive of linkage (p < 0.007) for any marker; however, one p value suggested replicated linkage (p < 0.01) at chromosome 6p24 in region D6S309 (p = 0.0047). Furthermore, 11 markers resulted in p < 0.05 at chromosomes 6p, 6q, 10q, 12q and 14q. Conclusions: Despite the differences in diagnostic schemes, in markers used and methods of analyses between studies published so far, we think that our result supports the notion that there is possibly some consistent evidence for replicated linkage of a schizophrenia susceptibility locus around the region of D6S309 at chromosome 6p24.

Efficiency of Continuous Positive Airway Pressure versus Theophylline Therapy in Sleep Apnea: Comparative Sleep Laboratory Studies on Objective and Subjective Sleep and Awakening Quality

Sleep apnea is the most common sleep-related breathing disorder characterized by repetitive episodes of hypoxemia. Therapies include behavioral, surgical, orthodontic, pneumological, and pharmacological interventions. The aim of the present study was to compare the efficiency of pneumological therapy by nasal continuous positive airway pressure (CPAP) versus a pharmacological approach with theophylline (Respicur retard® 400 mg) on respiratory variables as well as objective and subjective sleep and awakening quality in patients with moderate sleep apnea measured by polysomnography and psychometry. Under CPAP therapy all respiratory variables improved and normalized, while under theophylline only the apnea-hypopnea index and the desaturation index improved but still did not return to normal values. Regarding sleep initiation and maintenance, CPAP therapy prolonged sleep latency and reduced movement time, while patients treated with theophylline showed reduced total sleep period, total sleep time and sleep efficiency. Sleep architecture demonstrated an increase in deep sleep and REM stages under CPAP therapy, and remained unchanged under theophylline. Concerning subjective sleep and awakening quality, both treatments improved well-being in the morning. Regarding objective awakening quality, reaction time performance was improved in both groups. In conclusion, CPAP treatment is more effective than theophylline regarding respiratory variables as well as the normalization of sleep maintenance and sleep architecture in sleep apnea patients.

The Unified Biosocial Model of Personality in Schizophrenia Families and Controls

This report describes the application of a unified biosocial model of personality developed by C.R. Cloninger to a sample of families identified through a proband with schizophrenia and a sample of controls. Families of schizophrenic patients were ascertained in USA and Austria. We could detect differences between females and males in their response to positive reinforcement (Reward Dependence) and differences between young and old people with respect to the response to new and/or exciting situations (Novelty Seeking). In general, results obtained for individuals from schizophrenia families and controls were similar. These results are not substantially influenced by psychiatric disorders in individuals. Psychiatric diagnosis may have an influence on the third dimension of Cloninger’s model, designated Harm Avoidance. Analysis showed that patients with a diagnosis of schizophrenia or from the schizophrenia spectrum try harder to avoid punishment or aversive stimuli than family members with another psychiatric disorder or without a psychiatric diagnosis as well as controls. The results are promising and further research is needed to evaluate the structure of the proposed personality model in families and the relationship of personality to psychiatric status.

No proof of linkage between schizophrenia-related disorders including schizophrenia and chromosome 2q21 region

SummaryWe examined linkage between schizophrenia and schizophrenia-related disorders and five genetic markers on chromosome 2 in fourteen families ascertained through affected probands in St. Louis and Vienna. The chromosomal region 2q21 was considered a candidate locus for schizophrenia because of a report of a balanced translocation 2;18 (q21;q23) in a schizophrenia family. Linkage analyses were conducted for three disease models: a narrow model including schizophrenia only; an intermediate model including a spectrum of schizophrenia-related disorders; and a broad model including major affective disorders. Multipoint linkage analyses excluded linkage across the region (about 50cM) for the intermediate disease model. The same was generally true for the broad affection status model. None of the two-point and multipoint analyses showed definite linkage of schizophrenia to any marker. The most prominent positive association was between D2S44 and a broad affection status model, giving a two-point lod score of 1.71 at 0.20 recombination fraction.

Non-concordance by gender for schizophrenia and related disorders in sibships.

We analysed gener-concordance rates among 29 prospectively sampled schizophrenic probands and their 39 affected and 71 unaffected siblings. We did not find any unusual concordance rates. We found no samegender concordance particularly in siblings affected by schizophrenia and related disorders. We considered unaffected siblings in an additional attempt to make valid and unbiased comparisons between genders, but this reduced the number of informative sibships to 20. We stratified the siblings of probands by sibship and by the probands gender in order to check gender distribution within families. The data do not support hypotheses that schizophrenia is pseudo-autosomal or male-female chromosomally transmitted.