We examined whether correlations previously found between symptoms of schizophrenia patients and the amplitude of an event-related potential (ERP), the N400, could be also found between schizotypal experiences of healthy subjects and the N400. We chose a semantic categorization task previously used with patients. Schizotypal experiences were measured with the schizotypal personality questionnaire (SPQ). The effects of the other factors were controlled for when assessing the correlations between each SPQ factor and N400s. These correlations were assessed at each electrode site to see whether their distribution on the scalp follows that of the N400 effect. Disorganization and interpersonal scores were found to correlate with ERPs in the N400 time window, as previously reported for the comparable symptoms of patients. However, the scalp distribution of these correlations differed from that of the N400 effect.

A previous study suggests that the amplitude of the N400 event-related potentials (ERPs) of healthy subjects does not vary with their delusional-like ideations. This contrasts with the smaller N400 amplitudes observed in more- than in less-deluded schizophrenia patients. Here, we hypothesize that these smaller N400 amplitudes were related to the paranoid feelings patients had during the ERP recording. We thus induced this type of feelings in healthy subjects. Delusional-like ideation was assessed with the schizotypal personality questionnaire. Thirty-four healthy subjects completed a semantic categorization task. Paranoid feelings were significantly enhanced by the induction. In these conditions, greater delusional-like ideation scores were associated with smaller N400 amplitudes and larger late positive components. Controlling for the two other schizotypal factors strengthened these results. These findings may help us understand why delusions persist.

Emotional distress and reasoning biases are two factors known to contribute to delusions. As a step towards elucidating mechanisms underlying delusions, the main aim of this study was to evaluate a possible "jumping to new conclusions" reasoning bias in healthy people with delusional ideation and its association with emotions. We surveyed 80 healthy participants, measuring levels of depression, anxiety, cognitive error and delusional ideation. Participants completed two versions of the beads task to evaluate their reasoning style. Results showed that people with delusional ideation reached a conclusion after less information, as expected. Interestingly, they also tended to change their conclusions more often than people without delusional ideation and did so with greater conviction. Depression and cognitive errors were strong predictors of delusional ideation but not of reasoning style. We conclude that delusional ideation in non-psychotic individuals is independently predicted by depressive symptoms and by a high conviction in new conclusions.

Hyperhomocysteinemia adversely affects fundamental aspects of fetal development, adulthood, and aging, but the role of elevated homocysteine levels in these birth defects and adult diseases remains unclear. Mouse models are valuable for investigating the causes and consequences of hyperhomocysteinemia. We used a phenotype-based approach to identify mouse mutants for studying the relation between single gene mutations, homocysteine levels as a measure of the status of homocysteine metabolism, and gene expression profiles as a way to assess the impact of protein deficiency in mutant mice on steady-state transcription levels of genes in the folate-homocysteine pathways. These mutants were selected based on their propensity to produce phenotypes that are reminiscent of those associated with anomalies in folate-homocysteine metabolism in humans. We report identification of new, single-gene mouse models of homocysteinemia and characterization of their molecular and physiological impact on folate-homocysteine metabolism. Mutations in several genes involved in the hedgehog and WNT signal transduction pathways, as well as a gene involved in lipid metabolism, resulted in elevated homocysteine levels and altered expression profiles of folate-homocysteine metabolism genes. These results begin to unravel the complex relations between elevation of a single amino acid in the blood and the diverse birth defects and adult diseases associated with hyperhomocysteinemia.