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Exploring Links Between Psychosis and Frontotemporal Dementia Using Multimodal Machine Learning: Dementia Praecox
Nikolaos Koutsouleris1,2,3, Christos Pantelis4, Dennis Velakoulis4
1Department of Psychiatry and Psychotherapy, Ludwig Maximilian University, Munich, Germany.
JAMA Psychiatry
|August 3, 2022
Summary
Neuroimaging reveals shared brain patterns between frontotemporal dementia and psychosis, offering insights into early-stage psychosis risk and progression. These findings highlight potential neurobiological links and guide future diagnostic strategies.
Area of Science:
- Neuroimaging and Machine Learning
- Psychiatry and Neurology
- Genetics and Bioinformatics
Background:
- Behavioral and cognitive symptoms in severe psychotic disorders and dementia often overlap.
- Shared brain alterations between these conditions are debated and underexplored in at-risk individuals.
- Understanding these overlaps is crucial for early diagnosis and intervention in at-risk populations.
Purpose of the Study:
- To compare structural MRI patterns in behavioral-variant frontotemporal dementia (bvFTD), Alzheimer disease (AD), and schizophrenia using machine learning.
- To assess the predictive, prognostic, and progression relevance of these patterns in individuals at clinical high-risk (CHR) for psychosis or recent-onset depression (ROD).
- To investigate the genetic underpinnings of these patterns.
Main Methods:
- Utilized structural MRI data from 1870 individuals across five cohorts (bvFTD, AD, schizophrenia, major depression, mild cognitive impairment).
- Applied machine learning to derive and compare diagnostic patterns, testing prognostic value in CHR and ROD cohorts.
- Analyzed sociodemographic, clinical, genetic data, and 2-year functional outcomes, including pattern progression on follow-up MRI.
Main Results:
- The bvFTD pattern (prefrontal, insular, limbic volume reduction) was more prevalent in schizophrenia and major depression patients than AD patterns.
- bvFTD pattern expression was predicted by BMI, psychomotor slowing, and paranoid ideation; schizophrenia pattern linked to C9orf72 variant, CSF oligoclonal bands, and younger age.
- Both bvFTD and schizophrenia pattern expressions predicted 2-year psychosocial impairments in CHR patients and showed progression distinguishing recovery outcomes.
Conclusions:
- Neurobiological links, particularly involving prefrontal and salience systems, may connect bvFTD and psychosis.
- These findings suggest shared pathophysiological processes at the neuroanatomical interface between dementia and psychosis spectra.
- Further transdiagnostic research is essential to elucidate these shared mechanisms.
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