Koutsouleris, Nikolaos, Pantelis, Christos, Velakoulis, Dennis, McGuire, Philip, Dwyer, Dominic B., Urquijo-Castro, Maria-Fernanda, Paul, Riya, Popovic, David, Oeztuerk, Oemer, Kambeitz, Joseph, Salokangas, Raimo K. R., Hietala, Jarmo ORCID: 0000-0002-3179-6780, Bertolino, Alessandro, Brambilla, Paolo, Upthegrove, Rachel ORCID: 0000-0001-8204-5103, Wood, Stephen J., Lencer, Rebekka, Borgwardt, Stefan, Maj, Carlo, Nothen, Markus, Degenhardt, Franziska, Polyakova, Maryna, Mueller, Karsten, Villringer, Arno, Danek, Adrian ORCID: 0000-0001-8857-5383, Fassbender, Klaus ORCID: 0000-0003-3596-868X, Fliessbach, Klaus, Jahn, Holger ORCID: 0000-0003-3607-7651, Kornhuber, Johannes, Landwehrmeyer, Bernhard, Anderl-Straub, Sarah, Prudlo, Johannes, Synofzik, Matthis, Wiltfang, Jens, Riedl, Lina, Diehl-Schmid, Janine, Otto, Markus ORCID: 0000-0003-4273-4267, Meisenzahl, Eva, Falkai, Peter and Schroeter, Matthias L. (2022). Exploring Links Between Psychosis and Frontotemporal Dementia Using Multimodal Machine Learning Dementia Praecox Revisited. JAMA Psychiatry, 79 (9). S. 907 - 920. CHICAGO: AMER MEDICAL ASSOC. ISSN 2168-6238

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Abstract

IMPORTANCE The behavioral and cognitive symptoms of severe psychotic disorders overlap with those seen in dementia. However, shared brain alterations remain disputed, and their relevance for patients in at-risk disease stages has not been explored so far. OBJECTIVE To use machine learning to compare the expression of structural magnetic resonance imaging (MRI) patterns of behavioral-variant frontotemporal dementia (bvFTD), Alzheimer disease (AD). and schizophrenia; estimate predictability in patients with bvFTD and schizophrenia based on sociodemographic, clinical, and biological data; and examine prognostic value, genetic underpinnings, and progression in patients with clinical high-risk (CHR) states for psychosis or recent-onset depression (ROD). DESIGN, SETTING, AND PARTICIPANTS This study included 1870 individuals from S cohorts, including (1) patients with bvFTD (n =108), established AD (n = 44), mild cognitive impairment or early-stage AD (n = 96), schizophrenia (n = 157), or major depression (n = 102) to derive and compare diagnostic patterns and (2) patients with CHR (n = 160) or ROD (n = 161) to test patterns' prognostic relevance and progression. Healthy individuals (n = 1042) were used for age-related and cohort-related data calibration. Data were collected from January 1996 to July 2019 and analyzed between April 2020 and April 2022. MAIN OUTCOMES AND MEASURES Case assignments based on diagnostic patterns; sociodemographic, clinical, and biological data; 2-year functional outcomes and genetic separability of patients with CHR and ROD with high vs low pattern expression; and pattern progression from baseline to follow-up MRI scans in patients with nonrecovery vs preserved recovery. RESULTS Of 1870 included patients, 902 (48.2%) were female, and the mean (SD) age was 38.0 (19.3) years. The bvFTD pattern comprising prefrontal, insular, and limbic volume reductions was more expressed in patients with schizophrenia (65 of 157 [41.2%]) and major depression (22 of 102 [21.6%]) than the temporo-limbic AD patterns (28 of 157 [17.8%) and 3 of 102 [2.9%], respectively). bvFTD expression was predicted by high body mass index, psychomotor slowing, affective disinhibition, and paranoid ideation (R-2 = 0.11). The schizophrenia pattern was expressed in 92 of 108 patients (85.5%) with bvFTD and was linked to the C9orf72 variant, oligoclonal banding in the cerebrospinal fluid, cognitive impairment, and younger age (R 2 = 0.29). bvFTD and schizophrenia pattern expressions forecasted 2-year psychosocial impairments in patients with CHR and were predicted by polygenic risk scores for frontotemporal dementia, AD. and schizophrenia. Findings were not associated with AD or accelerated brain aging. Finally, 1-year bvFTD/schizophrenia pattern progression distinguished patients with nonrecovery from those with preserved recovery. CONCLUSIONS AND RELEVANCE Neurobiological links may exist between bvFTD and psychosis focusing on prefrontal and salience system alterations. Further transdiagnostic investigations are needed to identify shared pathophysiological processes underlying the neuroanatomical interface between the 2 disease spectra.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Koutsouleris, NikolaosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pantelis, ChristosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Velakoulis, DennisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
McGuire, PhilipUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dwyer, Dominic B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Urquijo-Castro, Maria-FernandaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Paul, RiyaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Popovic, DavidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Oeztuerk, OemerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kambeitz, JosephUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Salokangas, Raimo K. R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hietala, JarmoUNSPECIFIEDorcid.org/0000-0002-3179-6780UNSPECIFIED
Bertolino, AlessandroUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brambilla, PaoloUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Upthegrove, RachelUNSPECIFIEDorcid.org/0000-0001-8204-5103UNSPECIFIED
Wood, Stephen J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lencer, RebekkaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Borgwardt, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Maj, CarloUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nothen, MarkusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Degenhardt, FranziskaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Polyakova, MarynaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mueller, KarstenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Villringer, ArnoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Danek, AdrianUNSPECIFIEDorcid.org/0000-0001-8857-5383UNSPECIFIED
Fassbender, KlausUNSPECIFIEDorcid.org/0000-0003-3596-868XUNSPECIFIED
Fliessbach, KlausUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jahn, HolgerUNSPECIFIEDorcid.org/0000-0003-3607-7651UNSPECIFIED
Kornhuber, JohannesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Landwehrmeyer, BernhardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Anderl-Straub, SarahUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Prudlo, JohannesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Synofzik, MatthisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wiltfang, JensUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Riedl, LinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Diehl-Schmid, JanineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Otto, MarkusUNSPECIFIEDorcid.org/0000-0003-4273-4267UNSPECIFIED
Meisenzahl, EvaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Falkai, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schroeter, Matthias L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-698125
DOI: 10.1001/jamapsychiatry.2022.2075
Journal or Publication Title: JAMA Psychiatry
Volume: 79
Number: 9
Page Range: S. 907 - 920
Date: 2022
Publisher: AMER MEDICAL ASSOC
Place of Publication: CHICAGO
ISSN: 2168-6238
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
ANTERIOR CINGULATE CORTEX; VON ECONOMO NEURONS; BEHAVIORAL VARIANT; HIGH-RISK; SCHIZOPHRENIA; BRAIN; C9ORF72; INDIVIDUALS; DEPRESSION; DISORDERMultiple languages
PsychiatryMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/69812

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