Dissecting Schizotypy and Its Association With Cognition and Polygenic Risk for Schizophrenia in a Nonclinical Sample

Jeggan Tiego; Kate Thompson; Aurina Arnatkeviciute; Ziarih Hawi; Amy Finlay; Kristina Sabaroedin; Beth Johnson; Mark A Bellgrove; Alex Fornito

doi:10.1093/schbul/sbac016

Dissecting Schizotypy and Its Association With Cognition and Polygenic Risk for Schizophrenia in a Nonclinical Sample

Schizophr Bull. 2023 Sep 7;49(5):1217-1228. doi: 10.1093/schbul/sbac016.

Authors

Jeggan Tiego^{1

2

3}, Kate Thompson^{1

2

3}, Aurina Arnatkeviciute^{1

2}, Ziarih Hawi^{1

2}, Amy Finlay^{1

2}, Kristina Sabaroedin^{1

2

3}, Beth Johnson^{1

2}, Mark A Bellgrove^{1

2}, Alex Fornito^{1

2

3}

Affiliations

¹ Turner Institute for Brain and Mental Health, Monash University, Clayton, VIC 3800, Australia.
² School of Psychological Sciences, Monash University, Clayton, VIC 3800, Australia.
³ Monash Biomedical Imaging, Monash University, 770 Blackburn Rd, Clayton, VIC 3800, Australia.

Abstract

Schizotypy is a multidimensional construct that captures a continuum of risk for developing schizophrenia-spectrum psychopathology. Existing 3-factor models of schizotypy, consisting of positive, negative, and disorganized dimensions have yielded mixed evidence of genetic continuity with schizophrenia using polygenic risk scores. Here, we propose an approach that involves splitting positive and negative schizotypy into more specific subdimensions that are phenotypically continuous with distinct positive symptoms and negative symptoms recognized in clinical schizophrenia. We used item response theory to derive high-precision estimates of psychometric schizotypy using 251 self-report items obtained from a non-clinical sample of 727 (424 females) adults. These subdimensions were organized hierarchically using structural equation modeling into 3 empirically independent higher-order dimensions enabling associations with polygenic risk for schizophrenia to be examined at different levels of phenotypic generality and specificity. Results revealed that polygenic risk for schizophrenia was associated with variance specific to delusional experiences (γ = 0.093, P = .001) and reduced social interest and engagement (γ = 0.076, P = .020), and these effects were not mediated via the higher-order general, positive, or negative schizotypy factors. We further fractionated general intellectual functioning into fluid and crystallized intelligence in 446 (246 females) participants that underwent onsite cognitive assessment. Polygenic risk scores explained 3.6% of the variance in crystallized intelligence. Our precision phenotyping approach could be used to enhance the etiologic signal in future genetic association studies and improve the detection and prevention of schizophrenia-spectrum psychopathology.

Keywords: general intellectual functioning; negative symptoms; polygenic risk; positive symptoms; schizophrenia; schizotypy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Cognition
Female
Humans
Psychopathology
Schizophrenia* / complications
Schizotypal Personality Disorder* / diagnosis
Self Report