The results, published in the journal European Neuropsychopharmacology, provide new evidence on the biological complexity of schizophrenia and could, in the future, help to identify clinical profiles more accurately from the early stages of the illness and facilitate personalized treatment strategies.
Autistic traits and negative symptoms are common in schizophrenia spectrum disorders, and can manifest as early as the first-episode psychosis. These manifestations include compromising social-communication difficulties, restricted-repetitive behaviours, diminished emotional expression, apathy or loss of motivation. Their co-occurrence and clinical overlap complicate diagnosis, prognosis and treatment planning, with a significant impact on patients’ clinical course and day-to-day functioning.
The study, a longitudinal, multicentre investigation involving various CIBERSAM research groups, analysed 203 people experiencing first-episode psychosis. The research team assessed various clinical manifestations related to autistic traits and negative symptoms using standardized scales and linked these to measures that take into account numerous genetic variants associated with autism spectrum disorder, schizophrenia, cognitive performance and educational attainment. It also explored genetic indicators linked to key biological processes, such as neurodevelopment, synaptic function, immune response, apoptosis and endocrine regulation, and related these to the clinical manifestations.
The results show that autistic traits and negative symptoms do not constitute homogenous dimensions; rather, some of their components may have partially distinct genetic bases. In particular, the researchers observed that a higher genetic load associated with autism spectrum disorder was consistently linked to a greater presence of restricted and repetitive behaviours, both at the initial assessment and after one year of follow-up.
“Our results suggest the importance of analysing autistic and negative symptoms with greater precision. By separating them into different categories based on clinical manifestations, we observed genetic patterns that are not detected when only the broad clinical categories are considered,” explains Gisela Mezquida, the study’s first author.
The study, funded by the Carlos II Health Institute and CIBERSAM, also suggests, on an exploratory basis, that certain biological pathways related to neurodevelopment, synaptic function and immune regulation may be involved in specific autistic traits and negative symptoms. However, the authors stress that these findings must be validated in larger, independent samples before they can be translated into clinical practice.
According to Àlex G. Segura and Miquel Bioque, co-leaders of the study, “this work reinforces that idea that the psychiatry of the future should combine clinical, genetic and biological information to identify subgroups of patients with specific needs.” They add that “better stratification from the first psychotic episode could help to design more personalized and potentially more effective interventions.”
Although these findings do not yet have an immediate clinical application, they provide new evidence regarding the biological complexity of schizophrenia and represent a further step towards precision psychiatry.
Reference article
G. Mezquida, A. Perez-Ramos, N. Guasch-Capella, M.F. Forte, M. Parellada, S. Amoretti, M. Serra-Navarro, J. Galvañ, M.J. Cuesta, A. Mané, E. De la Serna, M. Mitjans, M. Bioque, C. García-Rizo, A.G. Segura, Acronym PEPs Group. The genetic architecture of autistic traits and negative symptoms in non-affective first-episode psychosis: an exploratory longitudinal study. European Neuropsychopharmacology. https://doi.org/10.1016/j.euroneuro.2026.112859.
