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Schizophrenia and Aging May Share a Biological Basis

06 MAR, 2024

Brain tissue samples from people with schizophrenia and from older adults have strikingly similar sets of changes in gene activity in two types of brain cells, suggesting a common biological basis for the cognitive impairment often seen in people with schizophrenia and in older people, according to new research.

The work also implicates a cell type not previously known to affect genetic vulnerability for schizophrenia.
The discoveries arose from training an artificial intelligence model to analyze gene activity across many kinds of cells in brain tissue samples from nearly 200 people.

An unexpected cell relationship:

The researchers analyzed patterns of gene activity, known as gene expression, in more than 1 million cells from postmortem brain tissue from 191 people.
They found that in individuals with schizophrenia and in older adults without schizophrenia, two brain cell types — astrocytes and neurons — had lower activity of genes that support the junctions between neurons, called synapses, compared to healthy or younger people.

The team also discovered tightly synchronized changes in gene expression in the two cell types. When neurons lowered the expression of certain genes related to synapses, astrocytes did too.

The team called this coordinated set of changes the Synaptic Neuron and Astrocyte Program, or SNAP.
They found that even in healthy young people, the expression of SNAP genes always increased or decreased in a coordinated way in neurons and astrocytes.

Shared roots:

Schizophrenia is well known for causing hallucinations and delusions, which can be at least partly treated with medications. But it also causes debilitating cognitive decline, which has no effective treatments. Cognitive decline is common in aging as well.

The new findings suggest that the cognitive changes in both conditions might involve similar cellular and molecular alterations in the brain.
Looking deeper into SNAP

To their surprise, the researchers also found that SNAP varied greatly even among people without schizophrenia, suggesting that SNAP could be involved in cognitive differences in healthy humans.
Much of this variation was explained by age. SNAP declined substantially in many — but not all — older individuals, including both people with and without schizophrenia.



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