What happens in the brain of a person with psychosis?

Psychosis can occur when the brain has difficulty filtering incoming information and predicting what will happen, according to a new study.

Psychosis is a disorder in which patients experience hallucinations, such as hearing voices, and harbor delusional beliefs, such as the impression that people exist who are not real. Psychosis can occur on its own and is a hallmark of certain serious mental illnesses such as bipolar disorder and schizophrenia. Schizophrenia is also characterized by social withdrawal, disorganized thinking and speech, and reduced energy and motivation.

It is difficult to study how schizophrenia develops in the brain. The disease mostly occurs in adolescents or young adults, who usually start taking antipsychotics early to relieve symptoms. When researchers analyze brain scans of people with existing schizophrenia, they cannot distinguish the effects of the disease from the effects of medication. They also don’t know how schizophrenia changes the brain as the disease progresses.

When researchers analyze brain scans of people with existing schizophrenia, they cannot distinguish the effects of the disease from the effects of medication

To get an early insight into the disease progression, the Stanford Medicine team studied young people ages 6 to 39 with 22q11.2 deletion syndrome, a genetic disorder in which patients lack the 22q11.2 gene Psychosis, schizophrenia or both is more common in 30% of patients.

They found that the brain function of patients with 22q11.2 suffering from psychosis was similar to that of people with psychosis of unknown cause. And these brain patterns were consistent with what researchers had previously suspected triggered the symptoms of psychosis.

What goes wrong in a brain with psychosis?

In the brains of people with psychosis, there are two key systems that fail: a “filter” that directs attention to important external events and internal thoughts, and a “predictor” made up of pathways that anticipate rewards.

Malfunctions of these systems make it difficult to recognize what is real, which manifests itself in the form of hallucinations and delusions. “This work provides a good model for understanding the development and progression of schizophrenia, which is a difficult problem,” said senior author Kaustubh Supekar, PhD, clinical associate professor of psychiatry and behavioral sciences.

The results, observed in people with a rare genetic disorder called 22q11.2 deletion syndrome who suffer from psychosis, as well as in people with psychosis of unknown cause, improve scientists’ understanding of the underlying brain mechanisms and theoretical frameworks associated with psychosis .

“The brain patterns we identified support our theoretical models of dysfunction of cognitive control systems in psychosis,” said study lead author Dr. Vinod Menon, Rachael L. and Walter F. Nichols Professor of Psychiatry and Behavioral Sciences and Director of the Stanford Cognitive and Systems Neuroscience Laboratory.

Thoughts that are not linked to reality can capture the brain’s cognitive control networks, he explained. “This process impairs the normal function of cognitive control and allows intrusive thoughts to dominate, culminating in symptoms that we recognize as psychosis.”

Brain organization

Normally also the brain’s cognitive filter system known as the salience network– works behind the scenes to focus our attention on important internal thoughts and external events. With your help, We can discard irrational thoughts and unimportant events and focus on what is real and are meaningful to us, such as paying attention to traffic to avoid a collision.

The ventral striatum, a small region of the brain, and its associated dopamine-controlled brain pathways play an important role in predicting what will be worthwhile or important.

For the study, researchers collected all possible data from fMRI brain scans of young people with 22q11.2 deletion syndrome, a total of 101 people scanned at three different universities.

The genetic disorder, characterized by the deletion of part of chromosome 22, affects 1 in 2,000 to 4,000 people. In addition to the 30 percent risk of schizophrenia or psychosis, people with this syndrome may also have autism or attention deficit hyperactivity disorder, which is why these conditions were included in the comparison groups.

Artificial intelligence to interpret the results

The researchers used artificial intelligence, specifically a type of machine learning algorithm called a spatiotemporal deep neural network, to characterize patterns of brain function in all patients with 22q11.2 deletion syndrome compared to healthy subjects.

Using a cohort of patients whose brains were scanned at the University of California, Los Angeles, they developed an algorithmic model that distinguished the brain scans of people with 22q11.2 deletion syndrome from those without 22q11.2 deletion syndrome. The model predicted the syndrome with over 94% accuracy. They validated the model in additional groups of people with and without the genetic syndrome who had received brain scans at UC Davis and the Pontificia Universidad Católica de Chile, and showed that in these independent groups the model classified the brain scans with an accuracy of 84% . . at 90%.

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The researchers then used the model to investigate which brain features play the most important role in psychosis. Previous studies on psychosis had not produced consistent results, probably because their sample sizes were too small.

By comparing brain scans of patients with 22q11.2 deletion syndrome who did and did not have psychosis, researchers showed that the brain areas that contribute most to psychosis are the anterior insula (an important part of the salience network or “filter”) are. ) and the ventral striatum (the “reward predictor”); This was true for different patient cohorts.

When comparing the brain characteristics of people with 22q11.2 deletion syndrome and psychosis with those of people with psychosis of unknown cause, the model found a significant overlap, suggesting that these brain characteristics are typical of psychosis in general.

A second mathematical model, trained to distinguish all subjects with 22q11.2 deletion syndrome and psychosis from those with genetic syndrome but without psychosis, selected brain scans of people with idiopathic psychosis with an accuracy of 77.5%, which again supports the idea of ​​filtering and prediction centers of the brain are crucial in psychosis.

Furthermore, this model was specific to psychosis: it could not classify people with idiopathic autism or ADHD.

“It was quite exciting to retrace our steps to our original question – ‘What are the dysfunctional brain systems in schizophrenia?’ – and to discover similar patterns in this context,” said Menon. “At the neural level, the features that distinguish individuals with psychosis in 22q11.2 deletion syndrome reflect the signaling pathways we have identified in schizophrenia.” “This parallel strengthens our understanding of psychosis as a disorder with identifiable and consistent brain signatures.” However, these brain signatures were not observed in people with the genetic syndrome but without psychosis, providing clues for future research directions, he added.

Applications for treatment or prevention

The findings not only support scientists’ theories about the origins of psychosis, but also have implications for understanding the disease and potentially preventing it.

“One of my goals is to prevent or delay the development of schizophrenia,” says Supekar. The fact that the new findings are consistent with the team’s previous research on the brain centers that contribute most to schizophrenia in adults suggests there may be a way to prevent it. “In schizophrenia, a lot of damage has already occurred in the brain at the time of diagnosis and it can be very difficult to change the course of the disease.”

“What we saw is that functional interactions between brain regions within the same brain system are initially abnormal,” he added. “The anomalies don’t start at 20 years old; They are obvious even at 7 or 8.”

Researchers plan to use existing treatments such as transcranial magnetic stimulation or focused ultrasound to target these brain centers in young people at risk for psychosis, such as those who suffer from 22q11.2 deletion syndrome or have two schizophrenic parents Whether they prevent them, either delay the onset of the disease or relieve the symptoms once they appear.

The results also suggest that using fMRI to monitor brain activity in key centers could help scientists study the effects of existing antipsychotic medications.

While it remains a mystery why a person distances themselves from reality – given how risky it appears to their well-being – the “how” is now understandable, says Supekar. “From a mechanistic perspective, it makes sense,” he says.

“Our findings underscore the importance of approaching people with psychosis with compassion,” Menon said, adding that his team hopes their work advances not only scientific understanding but also a cultural shift toward empathy and support for patients with psychoses.

“I recently had the privilege of meeting members of the early psychosis treatment group in our department. “His message was clear and powerful: ‘We have more similarities than differences.’ “Like everyone else, we experience our own ups and downs.” His words were a heartfelt call for greater empathy and understanding towards those living with this disease. “It was a call to view psychosis through a lens of empathy and solidarity.”


Robust and reproducible functional brain signatures of 22q11.2 deletion syndrome and associated psychosis: a deep neural network-based multi-cohort study

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