Testing the Validity of Taxonic Schizotypy Using Genetic and Environmental Risk Variables.

Background: Meehl regarded schizotypy as a categorial liability for schizophrenia that is the product of genes, environment, and gene-environment interactions. We sought to test whether schizophrenia-related genotypes and environmental risk factors predict membership in classes defined by taxometric analyses of positive (cognitive-perceptual), negative (interpersonal), and disorganized schizotypy. Methods: Participants (n = 500) completed the Schizotypal Personality Questionnaire (SPQ) and provided information on the following risk factors: cannabis use, pregnancy and obstetric complications, social adjustment, and family history of psychosis. Saliva samples were obtained so that the frequency of single-nucleotide polymorphism (SNP) alleles associated with risk for developing schizophrenia could be determined. Genotyped SNPs were rs1625579 (MIR137), rs7004633 (MMP16), rs7914558 (CNNM2), and rs12966547 (CCDC68). Sets of SPQ items were subject to multiple coherent cut kinetic (CCK) analyses, including mean-above-minus-below-a-cut, maximum covariance, maximum eigenvalue, and latent modes analyses. Results: CCK analyses indicated latent taxonicity of schizotypy across the 3 item sets. The cognitive-perceptual class had a base rate of 25%, and membership was predicted by the rs7004633 SNP (odds ratio = 2.33, 95% confidence interval = 1.15-4.72 in adjusted analyses). Poor social adjustment predicted memberships in the interpersonal (16%) and disorganized (21%) classes. Classes were found not to be mutually exclusive. Conclusions: Schizotypy is taxonic and schizotypy class membership is predicted by genetic and environmental factors that predict schizophrenia. The findings hold the promise that a more complete understanding of schizotypy as a schizophrenia liability state will come from investigation of other genes and environmental factors associated with schizophrenia.

Paternal and maternal ages have contrasting associations with self-reported schizophrenia liability.

BACKGROUND: Older paternal age predicts schizophrenia diagnosis in offspring. If this relationship reflects a pathogenic process, paternal age should predict the expression of subclinical schizophrenia liability (schizotypy). We hypothesized that paternal and maternal ages predict positive, negative, and disorganized features of schizotypy, that family history of psychosis moderates the relationship of paternal age with schizotypy, and that stress sensitivity mediates the relationship of maternal age with schizotypy. METHOD: Two studies are reported, each of undergraduates (n=500 and n=211) who completed the Schizotypal Personality Questionnaire. The second was designed to replicate and extend the first and included assessment of stress sensitivity. RESULTS: In Study 1, older paternal age and younger maternal age predicted greater positive schizotypy (ß=.13 and ß=-.19, respectively). Parental ages did not predict negative or disorganized features and family history did not moderate the paternal age association. In Study 2, the same pattern of associations between parental ages and schizotypy components was observed. Additionally, stress sensitivity partially mediated the association of maternal age with positive schizotypy whereas it did not contribute to the paternal age association. CONCLUSION: The association between older paternal age and schizophrenia extends to self-reported positive features of schizophrenia liability, consistent with the notion that this relationship arises from a pathogenic process, such as de novo mutations. Importantly, younger maternal age was an equally potent predictor of positive schizotypy, with its association partially mediated by stress sensitivity.