Summary: Researchers have discovered shared biological mechanisms in the main psychiatric disorders when analyzing postmortem brain samples of the dorsolateral prefrontal cortex. Instead of watching the gene expression widely, they approached the level of exon, the construction blocks that influence how proteins are made.
They discovered that gene activity differences were only apparent at this finer scale, not at the total gene level. The study revealed that interruptions in the regulation of stress hormones, signaling dopamine and circadian rhythms are common to multiple disorders, including schizophrenia.
Key facts:
Exon level insights: psychiatric patients showed differences of healthy individuals only at the exon level, not at the total gene level. Shared legs: interruptions in the circadian rhythm, the release of cortisol and dopamine roads were common among the disorders.
Source: Max Planck Society
Researchers from the Max Planck Psychiatry, Helmholtz Munich and Sydney University identified biological mechanisms that are shared between psychiatric disorders.
To do so, the equipment analyzed postmortem brain tissue samples of the dorsolateral prefrontal cortex.
This area of the brain is the center of reasoning and emotions in the brain, it is often involved in psychiatric disorders. The study included samples of affected individuals, most of which were patients with schizophrenia, and healthy controls.
What makes this study special: the research team combined several different layers of genetic data.
“In contrast to the studies that analyze the gene expression as a whole, we analyze the level of exon to better understand the structure of the genes. This detailed approach gave us a better understanding of how genetic variation influences the risk of disease,” explains the first author Karolina Worf.
Exons are the essential segments that contain information from a gene. In addition to providing the plan to build proteins, they also determine which versions of a protein ultimately arise from a gene. This happens through the alternative joint, a process that occurs in more than 95 percent of human genes.
Exon Differences
Including the exon level in the analysis was an important step: while the samples of 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 not only to depend only on the genes you have, but how their genes are expressed,” explains Janine Knauer-Arloth, leader of the medical genomics of the group of projects at the Max Planck Psychiatry Institute.
The team integrated different genetic data, including variations in pairs of individual DNA bases (single nucleotide polymorphisms), rare genetic variants and polygenic risk scores, which summarizes a person’s risk of disease by adding all relevant genetic variants.
In this way, the researchers discovered interruptions on the roads related to the circadian rhythm, the release of cortisol stress hormone and the dopamine neurotransmitter, in the three disorders included.
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 based on symptoms, but also based on biological mechanisms. This paradigm change is a significant step towards more precise diagnoses and treatment.
On this news of genetic research and mental health
Author: Anke Schlee
Source: Max Planck Society
Contact: Anke Schlee – Max Planck Society
Image: The image is accredited to Neuroscience News
Original research: open access.
“Exon’s variant interaction and multimodal evidence identify endocrine deregulation in severe psychiatric disorders that affect exciting neurons” by Janine Knauer-Arloth et al. Translational psychiatry
Abstract
The variant interaction of exon and multimodal evidence identify endocrine deregulation in severe psychiatric disorders that affect exciting neurons
Bipolar (BD) disorder, major depressive disorder (MDD) and schizophrenia share genetic architecture, however, their molecular mechanisms are still difficult to achieve.
Common and rare genetic variants contribute to neuronal dysfunction, impacting cognition and behavior.
This study investigates the molecular effects of genetic variants in human individual cortical cell types using a single exon analysis approach.
INTEGRATING EXON-LEVEL EQTLS (COMMON VARIANTS INFLUENCING EXON EXONSION) AND JOINT EXON EQT-SCORES (COMBINING POLYGENIC RISK SCORES WITH EXON-LEVEL Gene Expression) FROM A POSTMORTEM PSYCHIATRIC COHORT (BD = 15, MDD = 24, SCHIZOPHRENIA = 68 Schizophrenia-Focused Rare Variant data from the Schema Consortium, We identified 110 core the genes enriched in the tracks, including the circadian drag (Fdr = 0.02), the synthesis of cortisol and the secretion (Fdr = 0.026) and the dopaminergic synapse (FDR = 0.038).
The additional enriched pathways included hormone signaling (FDRS <0.0298, including insulin, GNRH, aldosterone and growth hormone paths) and, in particular, adrenergical signaling in cardiomyocytes (FDR = 0.0028). These routes highlight shared molecular mechanisms in the three disorders.
The single -cortical region nucleus
Our results demonstrate the power to integrate multimodal genetic and transcriptomic data at the exon level.
This approach goes beyond diagnoses based on symptoms towards molecular classifications, identifying possible therapeutic objectives for psychiatric disorders.
