Olfactory threshold selectively predicts positive psychometric schizotypy.

Olfactory impairment might be useful as a non-invasive pre-morbid biological marker of psychosis. People with schizophrenia show consistent impairments, but an association between olfaction and schizotypy in non-clinical populations is inconclusive and has been somewhat controversial. This is important as impairment in patients may be artefacts of antipsychotic medication. Meta-analyses indicate small effect sizes in non-clinical populations, suggesting prior negative studies may have been underpowered to demonstrate them. We measured olfaction and psychometrically-defined schizotypy in a sample of 739 non-clinical volunteers [mean age 23.1]. Subsets reported whether they had a history of mental illness in the family or smoked. We used (sniffin' sticks) to measure threshold detection, discrimination and identification of odours. O-LIFE was used to measure schizotypy. Lower olfactory-threshold selectively predicted higher scores on the positive dimension, unusual experiences. This association was most evident in sub-groups reporting history of mental illness in the family and/or smoking. There was a weak trend for an association between identification and introvertive anhedonia and discrimination and cognitive disorganisation in those with a history of mental illness in the family. These data support the idea that olfaction merits further investigation as a biomarker for psychosis and that olfactory-threshold detection in particular has potential to selectively predict unusual experiences. Variability in previous studies may have been exacerbated by including different proportions of participants with history of mental illness in the family and/or smoking. We propose that non-clinical participants be stratified by these factors in future studies of olfaction and potentially any study that measures psychometric schizotypy.

Specialized Information Processing Deficits and Distinct Metabolomic Profiles Following TM-Domain Disruption of Nrg1.

Although there is considerable genetic and pathologic evidence for an association between neuregulin 1 (NRG1) dysregulation and schizophrenia, the underlying molecular and cellular mechanisms remain unclear. Mutant mice containing disruption of the transmembrane (TM) domain of the NRG1 gene constitute a heuristic model for dysregulation of NRG1-ErbB4 signaling in schizophrenia. The present study focused on hitherto uncharacterized information processing phenotypes in this mutant line. Using a mass spectrometry-based metabolomics approach, we also quantified levels of unique metabolites in brain. Across 2 different sites and protocols, Nrg1 mutants demonstrated deficits in prepulse inhibition, a measure of sensorimotor gating, that is, disrupted in schizophrenia; these deficits were partially reversed by acute treatment with second, but not first-, generation antipsychotic drugs. However, Nrg1 mutants did not show a specific deficit in latent inhibition, a measure of selective attention that is also disrupted in schizophrenia. In contrast, in a "what-where-when" object recognition memory task, Nrg1 mutants displayed sex-specific (males only) disruption of "what-when" performance, indicative of impaired temporal aspects of episodic memory. Differential metabolomic profiling revealed that these behavioral phenotypes were accompanied, most prominently, by alterations in lipid metabolism pathways. This study is the first to associate these novel physiological mechanisms, previously independently identified as being abnormal in schizophrenia, with disruption of NRG1 function. These data suggest novel mechanisms by which compromised neuregulin function from birth might lead to schizophrenia-relevant behavioral changes in adulthood.