Background. Theory of Mind (ToM) is impaired in individuals with schizophrenia (SZ). Given the neurodevelopmental nature of both social cognition and SZ, variations in ToM abilities likely originate early in life. Thus, indirect markers of altered neurodevelopment, such as neurological soft signs (NSS) and premorbid adjustment (PA), may help explain these differences. Methods. The study included 38 patients with schizophrenia-spectrum disorder (SSD), 26 healthy siblings and 47 controls. ToM was assessed using the Hinting Task (HT). NSS were evaluated with the Neurological Evaluation Scale (NES) and PA with the Premorbid Adjustment Scale (PAS), yielding Social and Academic scores. Intelligence Quotient (IQ) was estimated two subtests of the WAIS-III and Family History (FH) through the Family Interview for Genetic Studies (FIGS). Results. First, patients presented more deficits in two subscales of the NES (motor coordination and sequencing of complex motor acts) than siblings and controls, with siblings performing intermediate in the sequencing subscale (linear mixed models, adjusted for age, sex and IQ). Patients showed worse social PA than siblings during childhood and late adolescence. Second, patients showed poorer HT performance than siblings and controls, but the neurodevelopmental markers did not modulate such differences. Third, within each group, neurodevelopmental vulnerability markers were not associated with ToM performance (linear regression analyses adjusted for age, sex, IQ and FH). Conclusion. In our sample, while patients showed more evidence of neurodevelopmental deviances than siblings and controls, such differences did not contribute to ToM variability, suggesting that they may stem from different neurodevelopment-related pathways. Keywords: Schizophrenia, Theory of Mind, Neurological Soft Signs, Premorbid Adjustment, unaffected siblings, endophenotype.

The authors have declared no competing interest.

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was funded by: (i) Fundació La Marató de TV3, (ii) Fundación Alicia Koplowitz, (iii) ERA-NET NEURON (PIM2010ERN-00642 and ANR-2010-NEUR-002-01b), (iv) the Instituto de Salud Carlos III through the project PI20/01002, the PFIS contract (FI21/00093) to N Hostalet, and the Miguel Servet contract (CP20/00072) to M Fatjó-Vilas (cofunded by the European Regional Development Fund/European Social Fund "Investing in your future"), (v) a PIF-Salut contract to AS-M (SLT017/20/000233), (vi) the Comissionat per a Universitats i Recerca del DIUE, of the Generalitat de Catalunya regional authorities (2021SGR01475 and 2021SGR00706).

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The study involving humans was approved by the Ethics Committee of the University of Barcelona (IRB0003099). The study was conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in the study.

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The dataset generated for this study is available on request to the corresponding authors.