Motor dexterity in schizophrenia spectrum disorders: Familiality and association with polygenic risk scores

Abstract

[EN]Objective: Motor dexterity (MD), a potential endophenotype for schizophrenia spectrum disorders, might exhibit familiality, showing greater similarity among biological relatives. Moreover, MD deficits in first-episode psychosis (FEP) patients may be related to their increased genetic liability for schizophrenia (SCZ). We examined MD familiality and its association with genetic risk for SCZ. We controlled disorder severity by analysing FEP patients with SCZ and other psychosis (OP) separately. Methods: Cross-sectional family study including 133 FEP patients and 244 of their first-degree relatives and 202 healthy controls. We used the grooved pegboard test to assess MD and estimated polygenic scores for SCZ (PGS-SCZ) in the participants. Statistical analysis included linear mixed models and intraclass correlation coefficient (ICC) Results: MD has low familiality (ICC = 0.10) in the whole sample of FEP patients and their relatives. In SCZ families, there was a trend toward MD familiality (p = 0.063). In OP families, MD was familial only in unaffected relatives (ICC = 0.33). FEP patients showed the highest PGS-SCZ, followed by parents, siblings, and healthy controls. No significant association was found between PGS-SCZ and MD. Conclusions: MD shows low familiality in FEP patients. Further research is needed to assess differences by severity of the disorder. Genetic risk for SCZ is not directly linked to MD but may influence it indirectly through neurodevelopment. PGS-SCZ was not associated with MD deficits in FEP patients, possibly reflecting the limited capacity of this tool to capture shared genetic liability between these traits. Environmental factors, in conjunction with genetic predisposition, may significantly contribute to MD development.