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Josef Parnas

Publications and source records attributed to Josef Parnas.

24 records · Page 2Linked to original sources
PubMed2002

A global perspective on genetic variation at the ADH genes reveals unusual patterns of linkage disequilibrium and diversity.

Variants of different Class I alcohol dehydrogenase (ADH) genes have been shown to be associated with an effect that is protective against alcoholism. Previous work from our laboratory has shown that the two sites showing the association are in linkage disequilibrium and has identified the ADH1B Arg47His site as causative, with the ADH1C Ile349Val site showing association only because of the disequilibrium. Here, we describe an initial study of the nature of linkage disequilibrium and genetic variation, in population samples from different regions of the world, in a larger segment of the ADH cluster (including the three Class I ADH genes and ADH7). Linkage disequilibrium across approximately 40 kb of the Class I ADH cluster is moderate to strong in all population samples that we studied. We observed nominally significant pairwise linkage disequilibrium, in some populations, between the ADH7 site and some Class I ADH sites, at moderate values and at a molecular distance as great as 100 kb. Our data indicate (1) that most ADH-alcoholism association studies have failed to consider many sites in the ADH cluster that may harbor etiologically significant alleles and (2) that the relevance of the various ADH sites will be population dependent. Some individual sites in the Class I ADH cluster show Fst values that are among the highest seen among several dozen unlinked sites that were studied in the same subset of populations. The high Fst values can be attributed to the discrepant frequencies of specific alleles in eastern Asia relative to those in other regions of the world. These alleles are part of a single haplotype that exists at high (>65%) frequency only in the eastern-Asian samples. It seems unlikely that this haplotype, which is rare or unobserved in other populations, reached such high frequency because of random genetic drift alone.

Alcohol Dehydrogenase↗
PubMed2002

A multivariate prediction model of schizophrenia.

Univariate prediction models of schizophrenia may be adequate for hypothesis testing but are narrowly focused and limited in predictive efficacy. Therefore, we used a multivariate design to maximize the prediction of schizophrenia from premorbid measures and to evaluate the relative importance of various predictors. Two hundred twelve Danish subjects with at least one parent diagnosed in the schizophrenia spectrum (high risk) and 99 matched subjects with no such parent (low risk) were assessed on 25 premorbid variables in seven domains (genetic risk, birth factors, autonomic responsiveness, cognitive functioning, rearing environment, personality, and school behavior) when the subjects averaged 15 years of age. Twenty-five years later, 33 subjects had received lifetime diagnoses of schizophrenia. Discriminant function analyses were used to discriminate schizophrenia outcomes from no mental illness and nonschizophrenia outcomes on the basis of premorbid measures. Regardless of the comparison group used, schizophrenia was predicted by the interaction of genetic risk with rearing environment, and disruptive school behavior. Within the high-risk group, two-thirds of schizophrenia outcomes were correctly predicted by these premorbid measures; three-quarters of those with no mental illness were also correctly predicted. Prediction was enhanced among those with two schizophrenia spectrum parents, lending support to a multiplicative gene x environment model. Implications for early identification/primary prevention efforts are discussed.

Adolescent↗
PubMed2002

Reduced P300 amplitude in a visual recognition task in patients with schizophrenia.

We studied top-down visual processes in schizophrenia by analyzing visual event-related potentials (ERPs) during a gestalt recognition task, after subjects (patients with schizophrenia, n = 10; controls, n = 14) were trained to perceive three different geometrical shapes. Recognition performance of patients was poorer under both the figure and the nonfigure conditions then that of normal controls. ERPs analysis indicated that P300 amplitudes of the patients were significantly smaller than those of controls during correct figure detection trials. Moreover, topographical analysis of the differences in ERPs during the figure vs the nonfigure condition showed an earlier, more positive and more widely distributed P300 in controls than in patients with schizophrenia. Our study supports the misconnection hypothesis of schizophrenia and highlights the difficulty of the patients to refer to previous experience in order to filter incoming information. In a visual recognition task, this misconnection syndrome might induce a failure to integrate information stored in the frontal and prefrontal sites with incoming stimuli.

Adult↗
PubMedDate not supplied

Phenomenology of anomalous self-experience in early schizophrenia.

Disorders of self-experience were emphasized in classic literature and in phenomenological psychiatry as essential clinical features of the schizophrenia spectrum disorders, but are neglected in the contemporary psychopathology due to epistemologically motivated distrust of studying anomalies of subjectivity. Based on our own and other empirical studies, we present here detailed clinical phenomenological descriptions of nonpsychotic anomalies of self-experience that may be observable in the prodromal phases of schizophrenia and in the schizotypal disorders. Anomalies of self-experience are grouped according the experiential domain that appears to be affected and are illustrated by short vignettes or verbatim quotes from the patients. It is suggested that disorders of the self deserve further systematic empirical investigations, also from an etiological perspective. Self-disorders may turn out to be potentially useful as a psychopathological organizer of the schizophrenia spectrum disorders. Psychopathological emphasis on these disorders may also help to integrate the search for the neurodevelopmental mechanisms in schizophrenia with developmental-psychological research on the ontogenesis of the self.

Adult↗