Schizophrenia candidate gene ERBB4: covert routes of vulnerability to psychosis detected at the population level.

Prior genetic and functional evidence established ERBB4 as a probable schizophrenia susceptibility gene that may confer risk via modulating brain information processing dependent on the integrity of frontotemporal brain circuitry. Utilizing retrospective data drawn from the cross-sectional population-based Athens Study of Psychosis Proneness and Incidence of Schizophrenia (ASPIS) (n = 1127), we attempted to independently replicate and further extend previous findings by examining the effects of ERBB4 gene variants on 3 broad population-based psychosis-related phenotypes: verbal working memory (VWM), trait schizotypy, and stress-induced subclinical psychotic experiences (PE). Three common ERBB4 single nucleotide polymorphisms that were previously associated with schizophrenia and impaired frontotemporal-related information processing (rs7598440, rs839523, and rs707284), their haplotypes, and corresponding diplotypes were tested. VWM performance was significantly associated with rs839523 and rs707284 markers even after correction for multiple testing, thus validating reported findings that have implicated ERBB4 gene variation on working memory. No associations were detected between these ERBB4 variants and trait schizotypy. However, we were able to detect a significant effect of rs7598440 marker on PE expressed under stressful environmental conditions. Combined haplotype analysis of the above 3 markers, identified a "yin-yang" pattern of association, confirmed at the diplotype level. While GGG haplotype homozygotes were associated with "protective" effects on VWM performance and PE, AAA "risk" haplotype carriers were associated with worse VWM performance and simultaneously exhibited significantly elevated PE. This dual, possibly pleiotropic, impact on frontotemporal circuitry and increased sensitivity to psychosocial stress may represent subtle manifestations of ERBB4-related vulnerability to psychosis, expressed at the population level.

Selective attention and the three-process memory model for the interpretation of verbal free recall in amyotrophic lateral sclerosis.

The present study investigates selective attention and verbal free recall in amyotrophic lateral sclerosis (ALS) and examines the contribution of selective attention, encoding, consolidation, and retrieval memory processes to patients' verbal free recall. We examined 22 non-demented patients with sporadic ALS and 22 demographically related controls using Stroop Neuropsychological Screening Test (SNST; selective attention) and Rey Auditory Verbal Learning Test (RAVLT; immediate & delayed verbal free recall). The item-specific deficit approach (ISDA) was applied to RAVLT to evaluate encoding, consolidation, and retrieval difficulties. ALS patients performed worse than controls on SNST (p < .001) and RAVLT immediate and delayed recall (p < .001) and showed deficient encoding (p = .001) and consolidation (p = .002) but not retrieval (p = .405). Hierarchical regression analysis revealed that SNST and ISDA indices accounted for: (a) 91.1% of the variance in RAVLT immediate recall, with encoding (p = .016), consolidation (p < .001), and retrieval (p = .032) significantly contributing to the overall model and the SNST alone accounting for 41.6%; and (b) 85.2% of the variance in RAVLT delayed recall, with consolidation (p < .001) and retrieval (p = .008) significantly contributing to the overall model and the SNST alone accounting for 39.8%. Thus, selective attention, encoding, and consolidation, and to a lesser extent of retrieval, influenced both immediate and delayed verbal free recall. Concluding, selective attention and the memory processes of encoding, consolidation, and retrieval should be considered while interpreting patients' impaired free recall. (JINS, 2012, 18, 1-10).