APR 16, 2024 4:04 AM PDT

How Dysfunction in Two Brain Systems Can Lead to Psychosis

WRITTEN BY: Carmen Leitch

New research has suggested that the delusions and hallucinations that psychosis patients experience results from the malfunction of two important systems in the brain; one system acts as a filter that ensures we pay attention to internal thoughts and external events while another functions as a predictor pathway that anticipates rewards. When these systems do not work properly, it can become difficult to discern what is real and what is not. The findings have been reported in Molecular Psychiatry.

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In psychosis, people have delusions and hallucinations that can seem very real, and these can become a hallmark of mental illnesses such as bipolar disorder and schizophrenia. Social withdrawal, a lack of energy and motivation, and disorganized thinking or speech can also be symptoms of schizophrenia. Understanding these disorders arise and progress is extremely challenging, however.

Individuals with 22q11.2 deletion syndrome carry a 30 percent increase in the risk of psychosis or schizophrenia, and their brain function is similar to those with psychosis arising for unknown reasons.

In this research, the investigators assessed brains scans of young people and children with 22q11.2 deletion syndrome, those with psychosis of an unknown cause, and people who are not affected by psychosis. A machine learning tool known as a spatiotemporal deep neural network was used to characterize patterns of brain function in the scans. The results have confirmed previous suggestions of how psychosis patients break with reality.

The brain patterns in these patients was similar to what has been hypothesized to cause their symptoms, noted senior study author Professor Vinod Menon, PhD, the director of the Stanford Cognitive and Systems Neuroscience Laboratory, among other appointments.

The tool was able to predict who had 22q11.2 deletion syndrome with over 94 percent accuracy. It was then validated on another set of brain scans.

The brain has a system to filter cognition; it is known as the salience network. This process ensures we focus on important thoughts as well as external events. Irrational ideas and unimportant occurrences can thus be ignored in favor of what is meaningful. For example, our minds may wander, but we have to stay focused enough while driving to avoid an accident; this system helps us do that.

Another part of the brain called the ventral striatum is crucial to predicting when something will be important or rewarding.

The researchers used their tool and the scans to determine which parts of the brain were most likely to be involved in psychosis. This revealed that the anterior insula, a critical part of the salience network, and the ventral striatum were most closely related to the disorder. This was true even for different cohorts of patients.

Even when thoughts are not connected to reality, they can still capture the cognition control networks of the brain. “This process derails the normal functioning of cognitive control, allowing intrusive thoughts to dominate, culminating in symptoms we recognize as psychosis,” added Menon.

This work could open up new options for treating or preventing psychosis. When patients with schizophrenia are diagnosed, a lot of brain damage has already happened and it can be very challenging to improve outcomes for patients. But these scans could help show who is most at risk, and potentially help them before all that damage happens.

“One of my goals is to prevent or delay [the] development of schizophrenia,” said lead study author Kaustubh Supekar, PhD, clinical associate professor of psychiatry and behavioral sciences at Stanford University School of Medicine.

“What we saw is that, early on, functional interactions among brain regions within the same brain systems are abnormal. The abnormalities do not start when you are in your 20s; they are evident even when you are seven or eight.”

Existing methods such as focused ultrasound may potentially be a way to target the affected brain centers in young people who are at risk for psychosis, for example. Functional MRIs may be another method to monitor patients so that clinicians can see whether treatments are working.

“Our discoveries underscore the importance of approaching people with psychosis with compassion,” Menon said.

Sources: Stanford University, Molecular Psychiatry

About the Author
Bachelor's (BA/BS/Other)
Experienced research scientist and technical expert with authorships on over 30 peer-reviewed publications, traveler to over 70 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
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