Distinctness of mental disorders is due to different gene re
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A new study suggests that differences in the expression of gene transcripts-readouts copied from DNA that help maintain and build our cells-hold the key to understand how mental disorders with shared genetic risk factors result in different patterns of onset, symptoms, course of illness, and treatment responses.

Major mental disorders, such as schizophrenia, bipolar disorder, and major depressive disorder, share common genetic roots, but each disorder presents differently in each individual. Researchers investigated why disorders present differently, despite this seeming genetic similarity.

They evaluated expressed genes and gene transcripts in postmortem subgenual anterior cingulate cortex (sgACC), a key component of limbic circuits linked to mental illness. RNA obtained postmortem from 200 donors diagnosed with bipolar disorder, schizophrenia, major depression, or no psychiatric disorder was deeply sequenced to quantify expression of over 85,000 gene transcripts, many of which were rare.

--The researchers found only modest differences in gene expression between individuals with a mental disorder and individuals without a mental disorder.

--However, when they focused on the transcripts, they found two to three times as many differences between individuals in the two groups.

--The most noticeable differences emerged when the researchers compared transcripts between two groups of individuals with a mental disorder—e.g., bipolar disorder versus schizophrenia, depression versus schizophrenia, or depression versus bipolar disorder.

--Parts of a gene's instructions may be kept in or left out during the transcription process. A common genetic variant that regulates this inclusion and exclusion, called splicing quantitative trait loci (sQTLs), may play a notable role in the inherited risk for each disorder.

"We found that subtle differences in gene expression across different disorders reflect more pronounced and diagnosis-specific changes at the level of transcripts," said the author.

Neuropsychopharmacology
Source: https://doi.org/10.1038/s41386-020-00949-5
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