The similarities between schizophrenia and dementia have been revealed for the first time

Summary: Research shows striking similarities in behavior and neuroanatomical changes in people with schizophrenia and behavioral variant frontotemporal dementia.

A source: Max Planck Institute

For the first time, researchers have compared schizophrenia and frontotemporal dementia — diseases located in the frontal and temporal parts of the brain.

This idea can be traced back to Emil Kraepelin, who coined the term “dementia praecox” in 1899 to describe progressive mental and emotional decline in young patients. His approach was quickly challenged because only 25% of sufferers showed this type of disease.

But now, with the help of imaging and machine learning, scientists have found the first valid signs of neuroanatomical patterns in the brains of patients with frontotemporal dementia.

It is rare for scientists in basic research to return to conclusions that are more than 120 years old. In the case of Nikolaos Koutsouleris and Matthias Schröter, researchers and physicians, this was the case.

It is about Emil Kraepelin, founder of the Max Planck Institute of Psychiatry (MPI) as well as the Ludwig Maximilian University of Munich Psychiatric Hospital (LMU) and his coined term “dementia praecox” in 1899.

It was his definition of a young person who was drifting further and further away from reality and falling into an irreversible, dementia-like state. Kraepelin lived to disprove his concept.

At the beginning of the 20th century, experts began to use the term “schizophrenia” for these patients, because the disease does not go so badly in all people.

Kraepelin came up with the idea of ​​frontotemporal disease, which he thought was the cause of the sometimes debilitating course of patients located in the frontal and temporal lobes of the brain. Personality, social behavior and empathy are controlled here.

“But that thought was lost because no pathological evidence of the neurodegenerative processes seen in Alzheimer’s disease was found in the brains of these patients,” says Kousouleris, who works at Kraepelin’s labs, MPI and LMU.

“I’ve wanted to work on this question since I became a psychiatrist,” he says. Fifteen years later, with a large enough dataset, imaging techniques and machine learning algorithms, the professor has the tools to find the answers.

He found the right partner in Matthias Schröter, who studies neurodegenerative diseases, particularly frontotemporal dementias, at the Max Planck Institute for Human Cognitive and Brain Sciences.

Similarities between schizophrenia and frontotemporal dementia

Frontotemporal dementia (FTD), especially the behavioral variant (bvFTD), is difficult to recognize in its early stages because it is often confused with schizophrenia. Thus, the similarities are clear: both groups of patients have personality and behavioral changes.

A dramatic development often ensues for the victims and their loved ones. Because the two disorders are located in the frontal, temporal, and insular regions of the brain, direct comparisons are obvious.

“They seem to be on a similar spectrum of symptoms, so we wanted to look for common signatures or patterns in the brain,” says Cousouleris, describing his plan.

With an international team, Koutsouleris and Schroeter used artificial intelligence to train neuroanatomical classifiers for both disorders, which were applied to brain data from different groups.

The results were published in the journal JAMA Psychiatry41% of schizophrenic patients met the classifier’s bvFTD criteria.

“When we saw this in schizophrenic patients as well, it raised alarm bells, suggesting that the two disorders are similar,” Koutsouleris and Schroeter recalled.

The research team found that the higher the patients’ bvFTD scores, measuring the similarity between the two diseases, the more likely they were to have a “bvFTD-like” phenotype and the less likely they were to improve their symptoms over two years.

The 23-year-old patient did not recover

“I wanted to know why my 23-year-old schizophrenia, with its symptoms of hallucinations, delusions, and cognitive deficits, had not improved after two years. He continued his studies and found a girlfriend. “I have seen these young people over and over again who have not recovered at all,” says Kousouleris.

When the researchers also examined the correlations in 23-year-old high-risk patients, they confirmed at the neuroanatomical level what Kraepelin was the first to describe so convincingly: some patients had no improvement at all. contradiction.

Neuroanatomical models of schizophrenia. Credit: Koutsouleris

Similar neural structures were affected, notably the default mode network and the fetal brain network responsible for attention control, empathy and social behavior showed reduced volume in the gray matter region where neurons are located. In bvFTD, some neurons (von Economo neurons) are lost; in schizophrenia, these neurons are also altered. This is reflected by the neuroanatomical index: after one year, it has doubled in severely affected people.

In comparison, the scientists also calculated the Alzheimer’s score using a specific classifier and did not find these effects there.

“This means that the concept of dementia praecox can no longer be completely eliminated; “We provide the first evidence that Kraepelin is not wrong, at least in some patients,” says Schroeter.

Today, or in the near future, this means that experts can predict which subgroups patients belong to.

“Intensive therapeutic support can then be started at an early stage to take advantage of the remaining recovery potential,” Koutsouleris says.

Additionally, new personalized therapies may be developed for this subgroup that promote proper maturation and connectivity of affected neurons and prevent their destruction as part of the disease process.

About it Schizophrenia and Dementia Research News

Author: Press service
A source: Max Planck Institute
The connection: Press service – Max Planck Institute
Photo: Image courtesy of Koutsouleris

See also

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Original research: Closed access.
“Exploring the Relationship between Psychosis and Frontotemporal Dementia Using Multimodal Machine Learning” Nikolaos Koutsouleris et al. JAMA Psychiatry


Abstract

Exploring the Association between Psychosis and Frontotemporal Dementia Using Multimodal Machine Learning

an important

Behavioral and cognitive symptoms of severe psychotic disorders overlap with those seen in dementia. However, general brain changes remain controversial, and their relevance for patients at risk disease stages has not yet been studied.

The goal

using machine learning to compare structural magnetic resonance imaging (MRI) patterns of behavioral variant frontotemporal dementia (bvFTD), Alzheimer’s disease (AD) and schizophrenia; Assessment of prognosis based on sociodemographic, clinical and biological data in patients with bvFTD and schizophrenia; and examining the prognostic significance, genetic basis and progression of patients with clinical high-risk (CHR) states for psychosis or recent-onset depression (ROD).

Design, installation and participants

This study included 1870 individuals from 5 cohorts, including (1) bvFTD (n = 108), established AD (n = 44), mild cognitive impairment or early-stage AD (n = 96), schizophrenia (n = 157) patients with , or major depression (n = 102) to obtain and compare diagnostic patterns and (2) to test the prognostic relevance and progression of patterns in patients with CHR (n = 160) or ROD (n = 161). Healthy individuals (n = 1042) were used to calibrate the age- and cohort-related data. Data were collected from January 1996 to July 2019 and analyzed from April 2020 to April 2022.

Main outcomes and measures

Tasks based on diagnostic schemes; sociodemographic, clinical and biological data; 2-year functional outcomes and genetic segregation of patients with CHR and ROD. and pattern progression from baseline to follow-up MRI scans in patients with nonrecovery and sustained recovery.

Results

Of the 1870 patients, 902 (48.2%) were female and the mean (SD) age was 38.0 (19.3) years. The bvFTD pattern, which includes prefrontal, insular, and limbic volume reduction, was more common in patients with schizophrenia (65 of 157). [41.2%]) and major depression (22 of 102 [21.6%]) than temporo-limbic AD samples (28 of 157 [17.8%] and 102 out of 3 [2.9%], respectively). Expression of bvFTD was predicted by higher body mass index, psychomotor slowing, affective disinhibition, and paranoid thinking (Rtwo= 0.11). A schizophrenic pattern was observed in 92 (85.5%) of 108 patients with bvFTD and C9orf72 variant, cerebrospinal fluid oligoclonal banding, cognitive impairment, and age (Rtwo= 0.29). bvFTD pattern expression predicted 2-year psychosocial impairment in patients with CHR and was predicted by polygenic risk scores for frontotemporal dementia, AD, and schizophrenia. The findings were not associated with AD or accelerated brain aging. Finally, 1-year bvFTD/schizophrenia pattern progression distinguished patients who did not recover from those who recovered.

Conclusions and relevance

Neurobiological links may exist between bvFTD and psychosis, focusing on changes in the prefrontal and salient systems. Additional transdiagnostic studies are needed to identify common pathophysiological processes underlying the neuroanatomical interface between the 2 disease spectrums.

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