Psychosis implicates key brain systems

The brain mechanisms underlying psychosis are better understood thanks to new research. In people with psychosis, the study found abnormalities in the “filter” and the “predictor,” two crucial brain systems.

These attention-directing and reward-anticipating systems malfunction, resulting in symptoms like delusions and hallucinations. Through examining young people with 22q11.2 deletion syndrome, a disorder associated with an increased risk of psychosis, the researchers provide a more comprehensive understanding of the mechanisms underlying these dysfunctions, which may inform future therapeutic approaches and preventative measures.

Important Information:.

The study links common psychosis symptoms to brain patterns in people with 22q11.2 deletion syndrome.

It shows that the core causes of psychosis are abnormalities in the brain’s reward-prediction and filtering systems, which have an impact on how reality is perceived.

In order to detect and validate these dysfunctions, the research employed cutting-edge imaging and machine learning, which may provide new targets for treatment approaches.

Source: University of Stanford.

The “filter,” which focuses attention on significant external events and internal thoughts, and the “predictor,” which is made up of pathways that foretell rewards, are the two main brain systems that are broken in psychotic individuals.

When these systems malfunction, it becomes difficult to distinguish between reality and illusion, which can lead to hallucinations and delusions.

The results are based on brain scan data from children, teenagers, and young adults with psychosis. The study was led by Stanford Medicine and was published on April 11 in Molecular Psychiatry. The findings support an established theory about how deviations from reality happen.

Lead author Kaustubh Supekar, Ph.D., said of the study, “This work provides a good model for understanding the development and progression of schizophrenia, which is a challenging problem.”. B. clinical associate professor of behavioral sciences and psychiatry.

Scientists’ understanding of the underlying brain mechanisms and theoretical frameworks related to psychosis is advanced by the findings, which have been observed in individuals with psychosis of unknown origin and those with psychosis caused by a rare genetic disease called 22q11.2 deletion syndrome.

Psychosis is characterized by delusional beliefs, such as the belief that people who are not real exist, and hallucinations, such as hearing voices. In addition to being a defining feature of some severe mental diseases, such as schizophrenia and bipolar disorder, psychosis can happen on its own.

Disorganized speech and thinking, a decrease in energy and motivation, and social disengagement are other traits of schizophrenia.

The pathophysiology of schizophrenia remains poorly understood. Typically, the illness first manifests in teenagers or young adults, and most of them start taking antipsychotic drugs right away to treat their symptoms.

Researchers are unable to discern between the effects of the disease and the medications when examining brain scans from individuals who have been diagnosed with schizophrenia. Furthermore, they do not understand how the progression of schizophrenia alters the brain.

The Stanford Medicine team examined young individuals with 22q11.2 deletion syndrome, a genetic condition that carries a 30% risk of psychosis, schizophrenia, or both, between the ages of 6 and 39, in order to gain an early understanding of the disease process.

According to their findings, the brain function of patients with psychosis caused by mutation 22q11.2 is comparable to that of individuals with psychosis of unknown genesis. Furthermore, these brain patterns agreed with what the researchers had previously hypothesized to be causing symptoms of psychosis.

Senior study author Vinod Menon, Ph.D., stated, “The brain patterns we identified support our theoretical models of how cognitive control systems malfunction in psychosis.”. D. in the Rachael L. along with Walter F. Psychiatry and behavioral sciences professor Nichols, MD, is also the director of the Stanford Cognitive and Systems Neuroscience Laboratory.

He said that the brain’s cognitive control networks can be captured by thoughts unrelated to reality. This process interferes with cognitive control’s normal operation, giving intrusive thoughts the upper hand and leading to symptoms that are eventually identified as psychosis. “.

brain classification.

Normally, our attention is selectively drawn to significant internal ideas and external events by the salience network, the brain’s cognitive filtering system. With its assistance, we can put aside unreasonable ideas and insignificant occurrences and concentrate on what matters to us and is real, like paying attention to traffic to avoid getting into an accident.

Predicting what will be rewarding or significant involves the ventral striatum, a small brain region, and related dopaminergic brain pathways.

The study involved the collection of as much functional MRI brain-scan data from young individuals diagnosed with 22q11.2 deletion syndrome as possible. A total of 101 individuals were scanned at three different universities for the study.

The study also included brain scans from a number of comparison groups that did not have 22q11.2 deletion syndrome: 411 healthy controls, 101 individuals with autism, 123 individuals with attention deficit/hyperactivity disorder, and 120 individuals with early idiopathic psychosis.

Approximately 1 in 2,000 to 4,000 people have the genetic condition, which is characterized by partial deletion of the 22nd chromosome. People with the syndrome can also have autism or attention deficit hyperactivity disorder, which is why these conditions were included in the comparison groups. In addition, there is a thirty percent chance that they will experience schizophrenia or psychosis.

Utilizing a spatiotemporal deep neural network, a kind of machine learning algorithm, the researchers were able to compare the brain function patterns of all patients with 22q11.2 deletion syndrome to those of healthy individuals.

They created an algorithmic model that differentiated brain scans from individuals with 22q11.2 deletion syndrome from those without it using a cohort of patients whose brains were scanned at the University of California, Los Angeles.

With over 94% accuracy, the model predicted the syndrome. They verified the model on other cohorts of individuals with or without the genetic syndrome who underwent brain scans at Pontificia Universidad Católica de Chile and UC Davis. They found that the model categorized brain scans with 84–90% accuracy in these independent groups.

After that, the researchers looked into which aspects of the brain are most important in psychosis using the model. Previous research on psychosis had produced inconsistent findings, probably due to small sample sizes.

The anterior insula, a crucial component of the salience network or “filter,” and the ventral striatum, the “reward predictor,” were found to be the brain regions most responsible for psychosis in patients with 22q11.2 deletion syndrome, according to a comparison of brain scans from patients with and without psychosis. This finding held true for various patient cohorts.

The model discovered a significant overlap in the brain features of individuals with psychosis and 22q11.2 deletion syndrome compared to those with psychosis of unknown origin, suggesting that these brain features are typical of psychosis in general.

Again supporting the notion that the brain’s filtering and prediction centers are crucial to psychosis, a second mathematical model that was trained to separate all subjects with 22q11.2 deletion syndrome and psychosis from those who have the genetic syndrome but do not have psychosis was able to select brain scans from people with idiopathic psychosis with 77.5 percent accuracy.

Moreover, this model could not categorize persons with idiopathic autism or ADHD because it was exclusive to psychosis.

Menon stated that it was “quite exciting” to follow the path that led to the original query, “What are the dysfunctional brain systems in schizophrenia?” and to find parallels in this situation.

“The brain circuits that distinguish people with psychosis in 22q11.2 deletion syndrome are similar to those that we have identified in schizophrenia. This analogy strengthens our knowledge of psychosis as a disorder with recognizably consistent brain signatures. “.

These brain signatures, he continued, were not observed in individuals with the genetic syndrome who did not exhibit psychosis, suggesting potential future research avenues.

applications in the fields of prevention and treatment.

The results have implications for comprehending—and perhaps even preventing—psychosis in addition to confirming the scientists’ theory about how the illness develops.

Supekar stated, “I want to stop or postpone the onset of schizophrenia.”. According to him, there might be a way to prevent schizophrenia because the new findings align with the team’s earlier research on the brain centers that most contribute to adult-onset schizophrenia.

When schizophrenia is diagnosed, a great deal of brain damage has already happened, and it can be exceedingly challenging to reverse the disease’s progression. “.

He continued, “What we observed is that early on, functional interactions among brain regions within the same brain systems are abnormal.”. The anomalies become noticeable as early as age 7 or 8, not only when you get older and into your 20s. “.

In young individuals at risk of psychosis, such as those with 22q11.2 deletion syndrome or who have two parents who have schizophrenia, the researchers plan to use current treatments, such as transcranial magnetic stimulation or focused ultrasound, targeted at these brain centers to see if they prevent or delay the onset of the condition or lessen symptoms once they appear.

The findings also imply that tracking brain activity at the critical regions with functional magnetic resonance imaging may aid in the investigation of the mechanisms underlying the action of currently available antipsychotic drugs.

The “how” is now clear, according to Supekar, even though it’s still unclear why someone becomes detached from reality considering how dangerous it appears to be for one’s health. He stated, “It makes sense from a mechanistic point of view.”.

Menon stated, “Our findings highlight the significance of treating individuals with psychosis with compassion.” He and his colleagues hope that their research will increase scientific understanding while also igniting a social movement that promotes empathy and support for those who are going through psychosis.

He said, “I recently had the honor of interacting with members of our department’s early psychosis treatment group.”.

They conveyed a strong and unambiguous message: “We have more things in common than not. We all have our own highs and lows, just like everyone else. Their statements constituted a sincere plea for increased compassion and understanding for people who are afflicted with this illness. It was an appeal to adopt an empathetic and supportive perspective on psychosis. “.

The study included research from the University of Oxford, UC Davis, UCLA, Clinica Alemana Universidad del Desarrollo, and Pontificia Universidad Católica de Chile.

About this news about psychosis research.

Kaustubh Supekar wrote this.

Source: University of Stanford.

Stanford’s Kaustubh Supekar can be reached.

Image: Neuroscience News is credited with this image.

Original Study: Access restricted.

In a deep neural network-based multi-cohort study, Kaustubh Supekar et al. found “robust and replicable functional brain signatures of 22q11.2 deletion syndrome and associated psychosis.”. Psychiatry by Molecular Means.

Inabst.

Deep neural network-based multi-cohort study reveals robust and replicable functional brain signatures of 22q11.2 deletion syndrome and related psychosis.

deletion of 22q11.2 (22q11.2DS) is a significant genetic risk factor for psychosis. Small sample sizes and a focus on small single-site cohorts have made it difficult to identify reliable and repeatable functional brain signatures of 22q11.2DS and 22q11.2DS-associated psychosis.

Here, we use one of the largest multi-cohort data sets to date to identify functional brain signatures of 22q11.2DS and 22q11.2DS-associated psychosis, as well as their associations with idiopathic early psychosis.

We obtained multi-cohort clinical phenotypic and task-free fMRI data from 856 participants (101 22q11.2DS, 120 idiopathic early psychosis, 101 idiopathic autism, 123 idiopathic ADHD, and 411 healthy controls) in a case-control design.

The multi-cohort data were subjected to a novel spatiotemporal deep neural network (stDNN)-based analysis to detect functional brain signatures of 22q11.2DS and 22q11.2DS-associated psychosis.

Next, the hypothesis was tested using stDNN: the functional brain signatures of psychosis associated with 22q11.2DS overlap with early idiopathic psychosis, but not with autism or ADHD. With very high accuracies (86–94 percent) in the primary cohort and two fully independent cohorts without additional training, stDNN-derived brain signatures were able to distinguish 22q11.2DS from controls and 22q11.2DS-associated psychosis.

In the dopaminergic reward pathway’s striatum node and the salience network’s anterior insula node, there were strong indicators of 22q11.2DS-associated psychosis.

These characteristics did not separate those with idiopathic autism or ADHD from controls, but they did separate those with idiopathic early psychosis from controls. According to our findings, people with 22q11.2DS have a very different functional brain organization from people without the condition.

Significant empirical support for the theoretical aberrant salience-based model of psychosis is also provided by the overlap between the brain signatures of 22q11.2DS-associated psychosis and those of idiopathic early psychosis in the salience network and dopaminergic reward pathway.

By examining the neurobiological foundations of psychosis and its development, 22q11.2DS is a valuable genetic model for understanding 22q11.2DS and associated psychosis. These findings are corroborated across multiple independent cohorts.