Demographic, Premorbid, and Clinical Characteristics of Schizophrenia Spectrum Patients with High and Low Polygenic Liability to the Disorder.

Background/objectives: Schizophrenia is a clinically heterogeneous complex disorder with a substantial polygenic basis. The discovery of phenotypes indexing genetic differences advances research into the schizophrenia etiology but has proven to be challenging. The study aimed to further clarify the relationships of schizophrenia polygenic risk scores (SZ-PRSs) with a comprehensive array of schizophrenia antecedents and presentations using a culturally and ethnically homogeneous sample of schizophrenia spectrum patients.

Methods: The top and bottom deciles (n = 172) of the SZ-PRS distribution in a group of 861 patients were compared on information derived from medical records using logistic regression.

Results: High SZ-PRSs were associated with female sex, family history of a wide range of neuropsychiatric conditions, moderately poor premorbid social and cognitive adjustment in childhood, the schizophrenia diagnosis, and positive and "abnormal" psychomotor symptoms. The low-SZ-PRS group demonstrated an accumulation of both individuals with milder forms of SZ spectrum disorders and those with severe premorbid abnormalities in the social, cognitive, and neurological domains.

Conclusions: The results highlight moderately poor premorbid social and cognitive adjustment as characteristic manifestations of the polygenic component of the schizophrenia etiology and provide the first piece of PRS-based evidence for the long-standing idea of a higher liability threshold in women. The presence of milder and severe cases in the bottom SZ-PRS decile, suggesting its etiological heterogeneity, might be an important source of the inconsistency in the previous research on SZ-PRSs' relationship with schizophrenia phenotypes and should be considered in future studies.