Brief rapport: Perceptual aberration in patients at ultra‐high risk for psychosis

Ultra‐high risk (UHR) is considered a forerunner of psychosis, but most UHR individuals do not later convert, yet remain symptomatic, disabled and help‐seeking. Thus, there is an increased recognition of the UHR phenotype as a syndrome in itself, rather than merely a risk syndrome. It is therefore essential to investigate outcomes other than transition to psychosis. For this purpose, perceptual aberration appears to be a distinct, as well as a stable and less state‐specific vulnerability indicator. We aimed to investigate perceptual aberration and associations with functional, neuro and social cognitive risk factors in an UHR sample.


| INTRODUCTION
The ultra-high risk (UHR) state (Lin et al., 2013) for psychotic disorders captures the putative prodromal phase of psychosis, and is considered a forerunner of frank psychosis.Patients in this state present discrete yet identifiable psychotic symptoms (Glenthøj et al., 2015), and the conversion rate to overt psychosis within 3 years is 18%-30% (Fusar-Poli et al., 2013;Salazar de Pablo et al., 2021).Although most UHR individuals do not later fulfil criteria for psychotic disorders, many remain symptomatic, disabled and help-seeking (Lim et al., 2015).Hence, it is essential to investigate outcomes other than transition to psychosis, particularly psychosocial outcome (Lin et al., 2013).
UHR is most commonly assessed with extensive clinical interviews such as comprehensive assessment of at-risk mental states (CAARMS; Yung et al., 2005) and structured interview for prodromal syndromes (SIPS;Fusar-Poli et al., 2016), particularly assessing attenuated psychotic symptoms.Perceptual aberration taps into a more distinct domain comprising distortions of the perception of one's own body (Chapman et al., 1978), and is also considered an indicator of psychosis proneness (Arzy et al., 2011).Patients with psychotic illness and in UHR exhibit higher perceptual aberration than healthy controls (HC; Brosey & Woodward, 2014).However, UHR individuals who convert to psychotic disorders do not differ significantly from non-converters on perceptual aberration (Bang et al., 2019).Thus, although clinical state and perceptual aberrations co-vary to some extent, perceptual aberration appears to be a rather stable and less state-specific vulnerability indicator (Brosey & Woodward, 2014).Additionally, perceptual aberrations may be more specific for disorders within the psychosis spectrum, hereby contrasting, that is, neurocognitive risk factors which may be shared across diagnostic categories (Wang et al., 2022).
However, to our knowledge this is the first study to examine perceptional aberration scale while exploring clinical, functional and cognitive correlates in a Danish sample of identified UHR-individuals.Knowledge on relations between perceptual aberration as measured with a selfreport questionnaire feasible in a clinical setting, and identified risk factors such as cognitive functions, could provide clues for both the development of indicated prevention and early intervention strategies in UHR groups.
With the current study, we wish to extend the existing knowledge on what characterizes the UHR state.The aims are to compare the level of perceptual aberration of UHR individuals to healthy controls and to analyse associations between perceptual aberration and CAARMS, functionality and neuro and social cognitive deficits within UHR.When investigating associations between PAS and established risk factors within the UHR sample, it is necessary to establish the level of PAS in line with previous findings.Hence, we compare the level of perceptual aberration of UHR individuals to HC and examine associations between perceptual aberration and CAARMS, functional level and neuro and social cognitive deficits within the UHR group.
We propose the following hypotheses.
• Perceptual aberration is higher in UHR than in HC.
• Perceptual aberration is not associated with severity of subthreshold psychotic symptoms as measured by CAARMS in UHR.This is necessary to establish PAS as a measure that does not merely reflect the severity of CAARMS • Higher PAS scores are associated with reduced level of functioning and impaired neuro and social cognition in UHR.

| Participants
All analyses were performed on baseline data from a randomized clinical trial (Glenthøj et al., 2020) that evaluated a cognitive remediation intervention in the UHR population.Population 120 UHR individuals meeting standardized 'at-risk'-criteria based on CAARMS (Yung et al., 2005), and 64 HC were included (Table 1 for details).
For the original study, healthy controls were matched to UHR individuals on gender, age (±2 years), ethnicity and parental socioeconomic status.

| Ultra-high risk
To identify patients meeting the UHR criteria we applied CAARMS (Yung et al., 2005).CAARMS is a semi-structured interview covering seven domains (including positive symptoms and cognitive change), and the scores on these subdomains can be combined into a composite score, which is the measure we use.CAARMS comprise a global rating scale (ranging 0-6 where 0 is no symptoms present) and a frequency scale (ranging 0-6 where 0 is no occurrence).The composite score was computed by weighing intensity of symptoms by their frequency, and has a range from 0 to 144 (Lim et al., 2015).

| Neuro and social cognition
To assess a range of cognitive domains found to be impaired in UHR

| Statistical analyses
Normality tests showed PAS scores to be non-normally distributed so non-parametric tests were applied.PAS scores of UHR and HC were compared using Mann-Whitney U test.Correlations between PAS and CAARMS, functioning and cognitive scores were tested using Spearmans RHO (ρ).Following Maher et al. (2013), the cutoffs for effect size of the correlation were small with ρ between 0.10 and 0.30, medium effect size with ρ between 0.30 and 0.50 and a large effect size with ρ between 0.50 and 0.70 (Maher et al., 2013).No outliers were identified after a visual investigation using scatterplots.
Statistical significance was set at p < .05.The statistical analyses were performed using SPSS25 (IBM Corp., Armonk, New York).

| RESULTS
We identified a difference in PAS score between healthy controls

| DISCUSSION
As expected, the UHR group had a substantially higher mean PAS score than HC.The score of 8.2 was comparable to previous findings in both patients with psychotic disorders (Arzy et al., 2011;Brosey & Woodward, 2017;Lenzenweger, 1994), and patients in UHR (Bang et al., 2019).This indicates that, as opposed to fully formed psychotic symptoms, subtle perceptual anomalies are equally pronounced in early as well as manifest psychotic stages.Further, PAS was not associated with CAARMS composite score.Both findings support the view of PAS as a stable and less state-specific vulnerability indicator.
PAS was significantly associated with measures of functioning, neuro and social cognition.The correlations were not strong, and only one measure in each domain was statistically significant, but as PAS was associated with aspects of all investigated domains, it suggests a pattern of widespread deficits.Although the correlational nature of the data should be taken into consideration when interpreting the results, the findings also suggest that impairments in perceptual aberration increase the probability of other impairments being present.As these impairments are known risk factors for the development of psychosis, this strengthens the validity of perceptual aberration as a risk factor.Furthermore, this supports previous findings suggesting that perceptual aberration constitute a central component in the development of psychotic illness, as delusions in early schizophrenia result in one way or another from the reorganization of the perceptual field (Smeets et al., 2012).
The observed association between PAS and executive functions is in keeping with the literature finding executive functions to relate to psychosis development (Bolt et al., 2018).Executive functions, as measured with the SOC in this study, comprise problem-solving and planning (Keefe et al., 2006).Executive functions works by top-down processing (Duncan, 2010;Miller & Cohen, 2001), involving lowerlevel cognitive functions in the regulation and control of cognition, behaviour and emotions to support an adequate response to tasks (Gilbert & Burgess, 2008).Hence, the demonstrated association between deficits in higher-order planning and problem-solving abilities and distortions of the perceptional information which may be a prerequisite for adequate executive functioning are not surprising.
Although impaired executive functions have been identified across diagnostic categories (Wang et al., 2022), the executive functions linked to PAS may represent a particular cognitive endophenotype linked to psychosis proneness (Snitz et al., 2006;Szöke et al., 2005).
This notion is supported by a study demonstrating heightened levels of PAS scores in relatives to patients with schizophrenia intermediate to healthy controls (Clementz et al., 1991).
The study is limited by relatively low power which reduces the probability of detecting significant associations.Further, the analysis entails a risk of multiplicity.Including multiple outcome measures in our analyses may involve a potential risk for multiplicity involving the risk of significant associations being spurious.Hence, our findings should be evaluated within a hypothesis-generating, exploratory perspective with p-values close to .05 being appraised cautiously.However, as cognition and functioning are complex constructs, it is relevant to include multiple measures to capture different and multifaceted aspects of the two domains.The analyses are explorative.

| CONCLUSION
Perceptual aberration was found to be more impaired in the UHR group than among HC, and to a degree comparable to that of psychotic illness.This is consistent with a view of perceptual aberration as a stable vulnerability indicator that varies little with clinical state.
Perceptual aberration was found to be associated with measures of functioning and neuro and social cognition in UHR, suggesting a distinct pattern of impairments within the UHR.

FUNDING INFORMATION
The
T A B L E 2 Correlations between perceptual aberration and functional, neuro and social cognitive characteristics in an ultra-high-risk group.
FOCUS trial was funded by was funded by The Danish Council for Independent Research (DFF-4004-00314); TrygFoundation (ID 108119); the Mental Health Services in the Capital Region of Denmark; the research fund of the Capital Region of Denmark; Lundbeck Foundation Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, CINS (R155-2013-16 337).Tina D. Kristensen is supported in part by a 2021 NARSAD Young Investigator Grant from the Brain and Behaviour Research Foundation (ID 30112), as a designated Gregory & Tyler Starling Investigator.
Comprehensive Assessment of At-Risk Mental States; GF-S, Global Functioning Social; GF-R, Global Functioning Role; Ms, milliseconds; SCSQ, Social Cognition Screening Questionnaire; TASIT, The Awareness of Social Inference Test.