Link to video on the SUCEDE YouTube Channel
In our most recent bibliographic session, our colleague Marta Hernández García presented a detailed review of the article recently published in Molecular Psychiatry (2026) titled: “Splitting schizophrenia: divergent cognitive and educational outcomes revealed by genomic structural equation modelling.”
This study addresses a fundamental question in modern psychiatry: the need to move beyond diagnoses based exclusively on clinical symptoms to understand the biological and genetic foundations underlying psychotic disorders.
The Approach: Decomposing Genetic Risk:
The research utilizes an advanced method called Genomic Structural Equation Modelling (Genomic SEM) and a “GWAS by subtraction” approach. The primary goal was to break down the genetic risk of schizophrenia into two distinct components:
- Schizophrenia-Specific Component (SZspecific): Genetic variants associated exclusively with this disorder.
- Shared Psychosis Component (PSYshared): Genetic risk common to both schizophrenia and bipolar disorder.
Key Findings and the “Educational Paradox”:
One of the most interesting points of the session was the resolution of a paradox previously observed in genetic studies:
- Traditionally, Genome-Wide Association Studies (GWAS) showed a positive genetic correlation between schizophrenia and educational attainment.
- However, clinically, schizophrenia is typically associated with lower cognitive performance and fewer years of schooling.
The study by Watson et al. reveals that this relationship diverges depending on the genetic component: while the risk shared with bipolar disorder is positively associated with education, the schizophrenia-specific risk shows a negative association with IQ and general cognition.
Implications: Toward Precision Psychiatry:
The results reinforce the hypothesis that schizophrenia is a heterogeneous construct including:
- Neurodevelopmental pathways: More closely linked to early cognitive deficits and specific brain structures such as the hippocampus and striatum.
- Shared pathways with other disorders: Featuring distinct genetic profiles and functional outcomes.
As discussed during the meeting, these findings are vital for our work within the SUCEDE project, as they emphasize the importance of identifying biotypes based on neurophysiological and genetic data, rather than relying on traditional diagnostic categories that may mask the underlying biological reality.
Genomics thus offers us a powerful tool to overcome the limitations of current classifications and move toward more personalized and precise treatments.