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- Researchers identify shared biological mechanisms in depression, bipolar disorder and schizophrenia
- New insights due to genetic analyses at the exon level
- Identifying common biological mechanisms is a step towards biology-based classification and treatment of psychiatric disorders
Researchers at the Max Planck Institute of Psychiatry (MPI), Helmholtz Munich and the University of Sydney identified biological mechanisms that are shared across psychiatric disorders. To do so, the team analyzed postmortem brain tissue samples from the dorsolateral prefrontal cortex (DLPFC). The DLPFC is the center for reasoning and emotions in the brain, and is often implicated in psychiatric disorders. Samples from affected individuals, most of whom were schizophrenia patients, and healthy controls were included in the study.
What makes this study special: The research team combined several different layers of genetic data. “In contrast to studies that look at gene expression as a whole, we analyzed the exon level to better understand the structure of the genes. This detailed approach gave us a better understanding of how genetic variation influences disease risk”, first author Karolina Worf explains.
Exons are the essential, information-containing segments of a gene. In addition to providing the blueprint for building proteins, they also determine which versions of a protein ultimately arise from a gene. This happens through alternative splicing, a process that occurs in over 95 percent of human genes.
Including the exon level in the analysis was an important step: While samples from psychiatric patients and healthy controls were not significantly different at the gene level, they were significantly different at the exon level. “The risk of developing a psychiatric disorder seems to therefore not just depend on what genes you have, but how your genes are expressed”, Janine Knauer-Arloth, leader of the Project Group Medical Genomics at the MPI, explains.
The team integrated different genetic data, including variations in individual base pairs of DNA (single nucleotide polymorphisms, or SNPs), rare genetic variants and polygenic risk scores, which summarize a person’s disease risk by aggregating all relevant genetic variants. This way, the researchers discovered disruptions in pathways related to the circadian rhythm, the release of the stress hormone cortisol, and the neurotransmitter dopamine — across all three included disorders.
These results show that psychiatric disorders share a common biological basis. In the long-term, this knowledge can help researchers to classify psychiatric disorders not only based on symptoms, but also based on biological mechanisms. This paradigm shift is significant a step towards more precise diagnoses and treatment.
Janine Knauer-Arloth
arloth@psych.mpg.de
Translational Psychiatry, 2025
https://doi.org/10.1038/s41398-025-03366-8
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