Breakthrough Identifies First Mechanism Behind Cognitive Disorders in Schizophrenia

Schizophrenia, a complex and debilitating mental disorder affecting approximately 1% of the global population, remains a significant challenge for medical treatment. While current medications can effectively manage positive symptoms such as hallucinations and delusions, there is a critical need for better therapies targeting negative symptoms like social withdrawal and lack of motivation, as well as cognitive impairments including attention deficits and memory issues.

Recent research has shed light on the biological underpinnings of these cognitive challenges. Historically, studies have linked impairments in oligodendrocytes—the cells responsible for producing myelin, which insulates neuronal axons and facilitates rapid neural communication—with schizophrenia. Now, a pioneering study demonstrates that the genetic risk factors for schizophrenia impact not only neurons but also oligodendrocytes, revealing a novel mechanism behind the disorder's cognitive symptoms.

Led by Peter Falkai of LMU University Hospital of Psychiatry and Florian Raabe of the Max Planck Institute of Psychiatry, the research team developed a rapid protocol for creating oligodendrocytes from induced pluripotent stem cells (iPSCs). They obtained blood samples from schizophrenia patients exhibiting white matter abnormalities—common in the disease—and transformed these samples into iPSCs, which then differentiated into oligodendrocytes in cell culture.

The scientists observed that the oligodendrocytes derived from schizophrenia patients showed distinct morphological features, appearing more 'mature' compared to those from healthy controls. This unexpected result suggested a possible 'prematuration' phenotype in these cells at early developmental stages. Since postmortem analyses typically show impaired oligodendrocytes and disrupted myelination in schizophrenia brains, this finding offers new insights into disease pathology.

Further investigations are planned to examine the functionality of these cells, including their ability to myelinate and interact with neurons. The ongoing work aims to expand the sample size for validation and explore the potential of these cells to serve as targets for novel treatments. Additionally, the team is exploring the creation of three-dimensional brain model systems, such as spheroids or organoids, to better mimic the human brain environment.

Reflecting on the findings, Falkai highlighted that although it remains unclear whether oligodendrocyte abnormalities are primary or secondary effects, these cells are evidently crucial in schizophrenia's development. The discovery paves the way for personalized approaches in treating the disorder, especially if specific oligodendrocyte phenotypes are associated with particular patient subgroups. Ultimately, this research provides a significant step toward understanding and addressing the cognitive deficits in schizophrenia.

Source: https://medicalxpress.com/news/2025-08-mechanism-cognitive-disorders-schizophrenia.html