Recent years have seen considerable progress in epidemiological and molecular genetic research into environmental and genetic factors in schizophrenia, but methodological uncertainties remain with regard to validating environmental exposures, and the population risk conferred by individual molecular genetic variants is small. There are now also a limited number of studies that have investigated molecular genetic candidate gene-environment interactions (G × E), however, so far, thorough replication of findings is rare and G × E research still faces several conceptual and methodological challenges. In this article, we aim to review these recent developments and illustrate how integrated, large-scale investigations may overcome contemporary challenges in G × E research, drawing on the example of a large, international, multi-center study into the identification and translational application of G × E in schizophrenia. While such investigations are now well underway, new challenges emerge for G × E research from late-breaking evidence that genetic variation and environmental exposures are, to a significant degree, shared across a range of psychiatric disorders, with potential overlap in phenotype.
ObjectiveTo test if specific correlations exist between cognitive measures and psychotic dimensions in schizophrenic subjects and if similar correlations, between cognition and schizotypal dimensions, are present in non-psychotic subjects.MethodsWe administered the same battery of cognitive tests (Source Monitoring, Verbal Fluency [VF] and Stroop tests) to schizophrenic subjects (N = 54), their first-degree relatives (N = 37) and controls (N = 41). Scores of negative, positive and disorganisation dimensions were derived from the Signs and Symptoms of Psychotic Illness scale in schizophrenic subjects, and from the Schizotypal Personality Questionnaire in relatives and controls.ResultsIn schizophrenic subjects, as hypothesised, the negative dimension correlated with performance on VF and disorganisation with performance in the Stroop test. The positive dimension did not correlate with any cognitive measure.With only one exception, the significant correlations observed in non-psychotic subjects did not match correlations seen in schizophrenic subjects. In non-psychotic subjects greater disorganisation was associated with more clustered words in VF suggesting that excessive automatic spreading of activation in semantic networks could underlie this dimension.ConclusionAs a whole, data lent partial support to our hypothesis of specific cognitive–clinical correlations in schizophrenic subjects but did not support the existence of similar correlations in non-psychotic subjects.
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