Genetic analysis reveals biological mechanisms shared in depression, bipolar disorder and schizophrenia

Researchers from the Max Planck Institute of Psychiatry (MPI), Helmholtz Munich and the University of Sydney identified biological mechanisms shared between psychiatric disorders.

To do this, the team analyzed the samples of post-mortem cerebral tissue of the dorsolateral prefrontal cortex (DLPFC). The DLPFC is the center of reasoning and emotions in the brain, and is often involved in psychiatric disorders. Samples of affected individuals, most of whom were patients with schizophrenia and healthy witnesses were included in the study, now published in Translational psychiatry.

The research team has combined several different layers of genetic data. “Contrary to studies that examine the expression of genes as a whole, we have analyzed the level of exon to better understand the structure of genes. This detailed approach allowed us to better understand how genetic variation influences the risk of illness,” explains the first author Karolina World.

The exons are the essential segments containing information from a gene. In addition to providing the protein construction plan, they also determine what versions of a protein ultimately arise from a gene. This occurs thanks to alternative splicing, a process that occurs in more than 95% of human genes.

The inclusion of the level of exon in the analysis was an important step: although the samples of psychiatric patients and healthy witnesses were not significantly different at the level of the gene, they were significantly different at the level of the exon. “The risk of developing a psychiatric disorder therefore seems not only depending on what you have, but how your genes are expressed,” explains Janine Knauer-Arly, head of the Genomic Medical Project Group at MPI.

The team has integrated different genetic data, including variations in individual DNA base pairs (unique nucleotide polymorphisms, or SNP), rare genetic variants and polygenic risk scores, which summarize the risk of a person’s disease by aggregating all relevant genetic variants. In this way, the researchers discovered disturbances in the ways linked to the circadian rhythm, the release of the stress hormone cortisol and the dopamine of neurotransmitters – the three disorders included the three disorders.

These results show that psychiatric disorders share a common biological basis. In the long term, this knowledge can help researchers classify psychiatric disorders not only on the basis of symptoms, but also on the basis of biological mechanisms. This paradigm shift is an important step towards diagnostics and more precise treatment.