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

Nga Yan Tse,Jashelle Caga,John B Kwok,Sicong Tu,Rebekah M Ahmed,Carol Dobson-Stone,Yu Chen,Glenda M Halliday,Olivier Piguet,Emma M Devenney,John R Hodges,Matthew C Kiernan

doi:10.1007/s00415-022-11049-3

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.

Highlights

Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) can be considered as a continuum, with significant overlap across clinical, genetic and neuropathological features [1, 2]
The present study aims to present a detailed exploration of (i) a broad spectrum of schizotypal personality traits across the amyotrophic lateral sclerosis–frontotemporal dementia (ALS–FTD) spectrum using a comprehensive measure of positive schizotypy, negative schizotypy, and thought disorganisation as a measure of psychosis risk; and (ii) the association between grey matter volume reduction and the severity of schizotypal traits within each domain using voxel-based morphometry (VBM) analysis to establish the neural correlates of schizotypy subtypes
Comparisons between patient groups revealed significantly longer disease duration in behavioural variant FTD (bvFTD) compared to both ALS (p < 0.001) and ALS–FTD (p = 0.002) groups, while ALS and ALS–FTD groups were not found to differ in disease duration, ALSFRS-R score or site of onset (p > 0.05; Table 1)

Summary

Introduction

Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) can be considered as a continuum, with significant overlap across clinical, genetic and neuropathological features [1, 2]. One study has examined the prevalence of all three subtypes of psychosis in bvFTD and found negative psychotic symptoms in 95.5% of bvFTD patients, followed by disorganised thought disorders (81.8%) and positive symptoms (22.7%)[12]. Results Relative 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. Conclusions The 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

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