Objective Schizotypy may be a forerunner of schizophrenia-spectrum disorders (SSD). In this study we examined for the first time the association between schizotypy and prefrontal function, quality of life (QoL) and general psychopathology (GenPsych) in 27 healthy subjects with no family history of SSD and 50 unaffected first-degree relatives of SSD patients, taking into consideration the clinical profile of their affected relative.

Method Participants completed the Schizotypal Personality Questionnaire, Quality of Life Enjoyment/Satisfaction Questionnaire, Symptom-Checklist-90-Revised (SCL-90R) and a Spatial Working Memory/Strategy (SWM) task. Clinical loading for the relatives was estimated as a continuous variable (0 score for controls) based on the average of Z-scores of age at illness-onset, illness-severity, Global Assessment of Functioning and number of hospitalisations of their affected relative. Associations between clinical loading, paranoid, negative, cognitive/perceptual schizotypy and metrics from QoL, SCL-90R and SWM outcome variables were examined with separate univariate regressions controlling for age and smoking habit.

Results Low QoL and high SCL-90R scores (all metrics) were predicted by high Negative (R2 range: 0.469–0.677) and Paranoid (R2 range: 0.434–0.695) Schizotypy (Ps<0.001). High Cognitive Perceptual Schizotypy predicted only higher SCL-90R metrics (P values <0.05; R2 range: 0.508–0.309). Poor strategy was predicted by high negative schizotypy and clinical loading together (Ps<0.05; R2:0.269).

Conclusions These findings suggest a dissociable role of different schizotypy types in psychopathology development, impoverishment of social context and prefrontal function in the schizophrenia-spectrum; also that different early-intervention approaches for psychosis should be considered, depending on the prevalent schizotypal traits of the individual at-risk.