Maria Giralt-López ¹ Salvador Miret ² Sílvia Campanera ² Monica Moreira ¹ Alejandro Sotero-Moreno ³ Marie-Odile Krebs ⁴ Lourdes Fañanás ⁵ Mar Fatjó-Vilas ^3*

• ¹ Department of Psychiatry, University Hospital Germans Trias i Pujol, Badalona, Spain
• ² Adult Mental Health Center of Lleida, University Hospital of Santa Maria, Lleida, Catalonia, Spain
• ³ FIDMAG Hermanas Hospitalarias Research Foundation, Barcelona, Catalonia, Spain
• ⁴ INSERM U1266 Institut de Psychiatrie et Neurosciences de Paris, Paris, Île-de-France, France
• ⁵ Department of Evolutionary Biology, Ecology and Environmental Sciences, Faculty of Biology, University of Barcelona, Barcelona, Catalonia, Spain

Background. Consistent findings indicate that Theory of Mind (ToM) is impaired in schizophrenia (SZ). To investigate whether such deficits are trait-or state-dependent, we investigated if ToM is modified by clinical liability markers (such as basic symptoms and psychotic-like experiences), focusing on the analysis of unaffected siblings of individuals diagnosed with SZ. Methods. The study included a total of 65 participants: 38 patients diagnosed with a schizophrenia-spectrum disorder and 27 healthy siblings. ToM was assessed using the Hinting Task (HT), Basic symptoms with The Frankfurt Complaint Questionnaire (FCQ), Psychoticlike-experiences with the Community Assessment of Psychic Experiences (CAPE) and Family history with the Family Interview for Genetic Studies. Results. First, a comparison of HT performance between patients and siblings (linear mixed model adjusted for age, sex and IQ) showed that patients presented lower scores than siblings (p=0.022). These differences did not remain significant after adjusting for clinical vulnerability markers. Second, within siblings, linear regression analyses (adjusted for age, sex, Intelligence Quotient (IQ) and family history) showed that higher FCQ Depressiveness and CAPE negative scores were related to poorer ToM performance (p=0.007 and p=0.032, respectively). Conclusions. Our findings suggest that clinical liability markers are valuable for delineating variations in ToM capabilities within healthy individuals. Moreover, our results indicate that ToM deficits are not solely linked to SZ but also extend to its clinical vulnerability, suggesting that ToM could serve as an endophenotypic marker. This implies that ToM could help distinguish particularly susceptible individuals from a population at risk, such as those with a genetic predisposition (siblings).