Molecular Psychiatry: Expression of immune-related genes in the brains of autistic patients

Data from postmortem brain tissue further prove that inflammation is linked
to autism.

         

According to a new study of thousands of postmortem brain samples, genes involved in immune system function have atypical expression patterns
in the brains of people with certain neurological and psychiatric disorders, including autism.

Of the 1275 immune genes studied, 765 (60 percent) were expressed elevated or decreased
in the brains of adults with one of six disorders: autism, schizophrenia, bipolar disorder, depression, Alzheimer's disease or Parkinson's disease.
Lead researcher Chunyu Liu, professor of psychiatry and behavioral sciences at Syracuse Northern Medical University in New York, said expression patterns vary from condition to condition, suggesting that each expression has different "characteristics.
"

Liu said the expression of immune genes has the potential to become a marker
of inflammation.
This immune activation—especially in the womb—has been linked to autism, although the mechanism is unclear
.

"My impression is that the immune system does not play a very small role in brain diseases," Liu said
.
"It's an important player
.
"

Christopher Coe, professor emeritus of biological psychology at the University of Wisconsin-Madison, said it was impossible to discern from the study whether immune activation played a role in a disease or whether the disease itself caused altered
immune activation.
He was not involved in the study
.

Coe said: "The study of the brain after death is informative
.
But not
absolutely.
”

Liu and his team analyzed the expression levels of 1275 immune genes in 2467 postmortem brain samples, of which 103 were from autistic people and 1178 from the control group
.
The data came from two transcriptomics databases — ArrayExpress and Gene Expression Omnibus — as well as other previously published studies
.

The brains of autistic people have an average of 275 genes expressed at different levels than controls; The brains of Alzheimer's patients had 638 differentially expressed genes, followed by schizophrenia (220), Parkinson's (97), bipolar disorder (58) and depression (27).

Expression levels in men with autism change more than in women with autism, while the brains of women with depression show more changes
than those of men with depression.
There were no gender differences
in the other four conditions.

Compared to other psychiatric disorders, autism-related expression patterns are closer to those of neurological disorders – Alzheimer's and Parkinson's
.
By definition, neurological disorders must have known physical features in the brain, such as the characteristic loss
of dopaminergic neurons in Parkinson's.
Researchers have not yet found this trait
of autism.

"This [similarity] gives us some additional direction to study
," Liu said.
Maybe one day we will better understand pathology
.
”

The findings were published in the November issue of the journal Molecular Psychiatry
.

Two genes, CRH and TAC1, were the most common alterations in these disorders: CRH was downregulated in all diseases except Parkinson's, and TAC1 was downregulated in all diseases except depression
.
Both genes affect the activation
of microglia, the brain's immune cells.

Atypical microglial activation may "disrupt normal neurogenesis and synaptogenesis," Coe said, similarly disrupting neuronal activity
under different conditions.

A 2018 study of postmortem brain tissue found similar expression of genes involved in astrocytes and synaptic function in people with autism, schizophrenia, or bipolar disorder
.
But the study found that microglial genes were overexpressed
only in autism.

Professor Michael Benros, head of biological and precision psychiatry research at the University of Copenhagen in Denmark, said people with higher upregulation of immune genes could have "neuroinflammation.
"
He was not involved in the study
.

"It could be interesting
to try to identify these potential subpopulations and of course provide them with more specific treatments," Benros said.

The study showed that most of the expression changes observed in brain tissue samples did not appear in
the gene expression pattern dataset of blood samples from people with the same disease.
Cynthia Schumann, a professor of psychiatry and behavioral sciences at the University of California's Davis Institute of Psychology, said the "somewhat surprising" finding shows the importance of
studying brain tissue.
She was not involved in the study
.

Schumann said, "If you want to understand the brain, you have to look at the brain itself
.
"

Liu and his team are creating cellular models to better understand whether inflammation is one of the factors contributing to the development of
brain diseases.