Differences in gene expression may explain mental disorder symptoms

Differences in gene expression may explain why mental illnesses with similar genetic roots can have such different symptoms, according to a new study.

Genome-wide association studies (GWAS) have shown that the risk of being affected by many psychiatric disorders is affected by many of the same genetic variants. However, patient experiences are diverse, with 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' said Dr Francis McMahon, a senior author of the study and chief of the Human Genetics Branch at the US National Institute of Mental Health (NIMH) in Bethseda, Maryland.

When RNA copies are made of genes in the cell nucleus, the resulting transcripts are called  messenger RNAs (mRNAs), and these function as the template to make proteins. 

Messenger RNA can be altered by a process called splicing, meaning a single gene can contain the code for multiple different mRNAs and therefore encode for several proteins. Errors in splicing are seen in many diseases, resulting in changes at the protein level, causing disruptions to biological pathways.

Researchers from the NIMH examined the genes and mRNA transcripts in post-mortem tissue from a brain region associated with mood disorders and emotion regulation. They compared samples from 200 individuals including those with schizophrenia, bipolar disorder, and major depressive disorder and also control individuals with no reported mental health disorders. 

The results, published in Neuropsychopharmacology, showed small differences in the genomes of individuals with different mental disorders, but much more pronounced changes were seen in the sequences of mRNA transcripts.

'Most transcripts that were expressed differently – produced in higher versus lower levels – turned out to be expressed in opposite directions in people with different disorders. Some transcripts were expressed in the same direction in individuals with mood disorders and the opposite direction in individuals with schizophrenia,' said Dr McMahon.

This variation was partly attributed to changes in mRNA splicing, which may explain why individuals with the same genetic mutations experience mental disorders differently.

More research is needed to better understand the functions of different transcripts, the timing of splicing, and the differences between brain regions and cell types.