Ch. Scharfetter

Schizophrenia and smoking: Evidence for a common neurobiological basis?

Several previous investigations have suggested that the gene for the alpha 7-nicotinic receptor may play a role in the pathogenesis of schizophrenia and may be responsible for the heavy smoking among schizophrenic patients. In a study of 129 healthy controls and 127 schizophrenic, schizoaffective, and bipolar patients we have aimed 1) to confirm the potential association between schizophrenia and the alpha 7-nicotinic receptor, 2) to test the diagnostic specificity of alpha 7-receptor subunits with respect to psychiatric diagnoses, and 3) to investigate potential receptor differences between smokers and nonsmokers in the general population. Our analysis included the two dinucleotide polymorphisms D15S1360 and L76630 that are localized in a genomic fragment containing the alpha 7-nicotinic receptor gene CHRNA7. Highly significant differences (P < 0.0001) between the allele distributions of patients and controls were detected for these two markers with all three diagnostic subgroups contributing to the discrimination. An independently ascertained replication sample of 24 patients confirmed this finding. Our results suggested an unspecific vulnerability that depended on the severity of overall psychopathology in terms of the co-occurrence of psychopathology with no clear-cut boundary between the diagnostic entities. In comparison with healthy controls, this vulnerability was lowest among schizophrenics, intermediate among bipolars, and highest among schizoaffectives. As to the question of alpha 7-receptor differences between smokers and nonsmokers among the healthy control subjects, our analysis revealed no significant differences, thus indicating that the differences between patients and controls are more than just a smoker/nonsmoker distinction. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:173-177, 2000.

Towards an Understanding of Sensory Soft Signs of Schizophrenia

Neurological soft signs are considered to be non-localizing findings and clinical neurodysfunctional correlates of schizophrenia. Sensory signs in 21 chronic schizophrenic patients were compared with those of healthy subjects. The schizophrenic patients differed significantly from the controls in graphesthesia testing; there was no clear-cut impairment of other somatic sensory modalities. The graphesthesia learning effect was weaker in the patient group. No unequivocal correlation could be found between psychopathology or course variables and dysgraphesthesia. The authors hypothesize that an impairment in graphesthesia testing may reflect a working memory deficit in schizophrenics.

Integration of genetic maps by polynomial transformations

Currently available genetic maps differ in a variety of basic features; in particular, with respect to the total length of the genome. Consequently, the question arises as to the extent to which genetic maps are compatible to each other, as well as to the methods with which genetic maps can be transformed into one another. We propose a set of nonlinear, polynomial transformations that enable the integration of genetic maps at a sufficiently high overall precision. Our analysis of six major, publicly available maps, and iteratively optimized polynomials of up to degree 5, yielded differences of </= +/-0.8 cM between empirical and reconstructed marker locations for >90% of points. Similarly, we determined, at a slightly worse overall fit, those polynomials that enabled the reconstruction of sex-specific recombination estimates from sex-averaged data. Our results suggest that polynominal transformations may become a valuable extension of standard map construction methods due to a rapid integration of newly developed markers into existing maps. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:108-113, 2000.

Morbid risks of subgroups of affective disorders: Some methodological and empirical results

Based on two independently ascertained family studies, the problem of analysing disorders with variable age of onset has been investigated by means of survival analysis. This method of approach results in empirical risk functions which can be used directly as weights for age correction in the analysis of pedigrees. The main interest of the present investigation has been focused on the reproducibility of such risk functions and on their specificity with respect to clinical diagnosis. For this purpose, one family study was referred to as a calibration sample for estimating empirical risk functions, whereas, the second family study served as a test sample in order to test the hypotheses under discussion. As it turned out, the empirically derived functions from both the calibration and test samples are indeed comparable, thus suggesting that, for sufficiently representative calibration samples, the differences between the two populations of (1) affected and (2) susceptible individuals may be less important than expected. As to the specificity of these risk functions, the underlying diagnostic structure of the calibration samples (as represented by four diagnostic subgroups) could be characterized by distinct types of risk functions, each of which, in addition, reflects the severity of the respective affective disorder.