Additive Genetic Effects for Schizotypy Support a Fully-Dimensional Model of Psychosis-Proneness

Abstract

Schizotypy is an organization of traits mirroring psychosis-like symptoms and conveying individual psychosis-proneness. Schizotypy and schizophrenia share a genetic basis, wherefore initial schizotypy definitions considered a schizophrenic genotype as a condicio sine qua non. Since the search for a monogenetic schizotypy marker has proven in vain, it is believed that schizotypy is (genetically) based on multiple alleles, each of small effect-size. Schizophrenia may be viewed as a qualitative entity at the extreme of the schizotypy dimension. To date, however, it has not been shown that effects of individual schizotypy-related alleles or genotypes are additive, which would be necessary for the proposition of latent genetic schizotypy factors. Based on previous findings of significant associations of candidate polymorphisms with schizotypy, we chose to examine if these genetic effects were, indeed, additive regarding positive schizotypy. Using a sample of 288 healthy participants we calculated allele-wise and genotype-wise risk indices and examined, whether levels of positive schizotypy would significantly increase with genetic risk. Our findings show significant additive genetic effects of select polymorphisms on positive schizotypy and, thus, support the notion of a fully-dimensional and partially genetically based model of schizotypy.

The association of striatal volume and positive schizotypy in healthy subjects: intelligence as a moderating factor

“…Dopaminergic neurotransmission is central to striatal functioning, and findings from several (although not all; Ettinger et al ., 2012) experimental and pharmacological studies implicate an association of altered dopamine neurotransmission with schizotypy and psychosis-proneness (Ettinger et al ., 2013, 2014; Mohr and Ettinger, 2014). Schizotypy has, additionally, been associated with expression levels of dopaminergic genes (Grant et al ., 2014b) and dopamine receptor gene polymorphisms (Ettinger et al ., 2006; Grant et al ., 2013; Gurvich et al ., 2016), including additive effects thereof (Grant et al ., 2015). Taken together, those findings suggest that the dopamine hypothesis of schizophrenia (Howes et al ., 2017) also extends into the healthy domain (Grant et al ., 2015).…”

The Role of Schizotypy in the Study of the Etiology of Schizophrenia Spectrum Disorders

“…There is indication that rs4680 interacts with other relevant polymorphisms (eg, MAOA-uVNTR) 36 and with age. 42 Thus, rs4680 is indeed relevant for schizotypy, but further research in significantly larger samples is necessary to identify exactly which features are age-specifically related to which allele; this question is currently being examined by us in an international sample comprised of most samples from the aforementioned individual articles.…”

Is Schizotypy per se a Suitable Endophenotype of Schizophrenia? – Do Not Forget to Distinguish Positive from Negative Facets

“…The Meehlian model proposes the group of schizotypes to be discrete, making up 10% of the population and defined qua the presence of (few) specific genetic risk factors. The more common view in schizotypy research, however, is that schizotypy is continuously distributed throughout the population and is genetically based on a multitude of genetic loci, whereof each have only small effect sizes, but these effects interact ( 9 ) and are additive ( 25 ); similar to recent conceptions of schizophrenia genetics ( 26 , 27 ). This would give rise to an Eysenckian view ( 28 ) that schizophrenia be equal to extremely high schizotypy (or rather psychoticism in the Eysenckian model of personality) [q.v.…”