Schizotypal traits across the amyotrophic lateral sclerosis-frontotemporal dementia spectrum: pathomechanistic insights.

Content Provider	Europe PMC
Author	Tse, Nga Yan Tu, Sicong Chen, Yu Caga, Jashelle Dobson-Stone, Carol Kwok, John B. Halliday, Glenda M. Ahmed, Rebekah M. Hodges, John R. Piguet, Olivier Kiernan, Matthew C. Devenney, Emma M.
Abstract	BackgroundPsychiatric presentations similar to that observed in primary psychiatric disorders are well described across the amyotrophic lateral sclerosis–frontotemporal dementia (ALS–FTD) spectrum. Despite this, schizotypal personality traits associated with increased risks of clinical psychosis development and poor psychosocial outcomes have never been examined. The current study aimed to provide the first exploration of schizotypal traits and its neural underpinnings in the ALS–FTD spectrum to gain insights into a broader spectrum of psychiatric overlap with psychiatric disorders.MethodsSchizotypal traits were assessed using the targeted Schizotypal Personality Questionnaire in 99 participants (35 behavioural variant FTD, 10 ALS–FTD and 37 ALS patients, and 17 age-, sex- and education-matched healthy controls). Voxel-based morphometry analysis of whole-brain grey matter volume was conducted.ResultsRelative to controls, pervasive schizotypal personality traits across positive and negative schizotypy and disorganised thought disorders were identified in behavioural variant FTD, ALS (with the exception of negative schizotypy) and ALS–FTDALS–FTD patients (all p < .013), suggesting the presence of a wide spectrum of subclinical schizotypal symptoms beyond classic psychotic symptoms. Atrophy in frontal, anterior cingulate and insular cortices, and caudate and thalamus was involved in positive schizotypy, while integrity of the cerebellum was associated with disorganised thought disorder traits.ConclusionsThe frontal–striatal–limbic regions underpinning manifestation of schizotypy in the ALS–FTDALS–FTD spectrum are similar to that established in previous schizophrenia research. This finding expands the concept of a psychiatric overlap in ALS–FTD and schizophrenia, and suggests potentially common underlying mechanisms involving disruptions to frontal-striatal-limbic networks, warranting a transdiagnostic approach for future investigations.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00415-022-11049-3.
ISSN	03405354
Journal	Journal of Neurology
Volume Number	269
PubMed Central reference number	PMC9294025
Issue Number	8
PubMed reference number	35279757
e-ISSN	14321459
DOI	10.1007/s00415-022-11049-3
Language	English
Publisher	Springer Berlin Heidelberg
Publisher Date	2022-03-13
Publisher Place	Berlin/Heidelberg
Access Restriction	Open
Rights License	Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. © The Author(s) 2022
Subject Keyword	Frontotemporal dementia Amyotrophic lateral sclerosis Motor neuron disease Schizotypy Neuropsychiatry
Content Type	Text
Resource Type	Article
Subject	Neurology Neurology (clinical)