Authors Accepted Manuscript

Deficits of cognitive theory of mind and its

relationship with functioning in individuals with an
at-risk mental state and first-episode psychosis
Noriyuki Ohmuro, Masahiro Katsura, Chika Obara,
Tatsuo Kikuchi, Atsushi Sakuma, Kunio Iizuka,
Yumiko Hamaie, Fumiaki Ito, Hiroo Matsuoka,
Kazunori Matsumoto

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DOI:
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S0165-1781(16)30080-4
http://dx.doi.org/10.1016/j.psychres.2016.06.051
PSY9802

To appear in: Psychiatry Research

Received date: 15 January 2016
Revised date: 11 April 2016
Accepted date: 26 June 2016
Cite this article as: Noriyuki Ohmuro, Masahiro Katsura, Chika Obara, Tatsuo
Kikuchi, Atsushi Sakuma, Kunio Iizuka, Yumiko Hamaie, Fumiaki Ito, Hiroo
Matsuoka and Kazunori Matsumoto, Deficits of cognitive theory of mind and its
relationship with functioning in individuals with an at-risk mental state and firstepisode
psychosis, Psychiatry
Research,
http://dx.doi.org/10.1016/j.psychres.2016.06.051
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Full title:
Deficits of cognitive theory of mind and its relationship with functioning in individuals with an at-risk
mental state and first-episode psychosis
Authors:
Noriyuki Ohmuro a, Masahiro Katsura a, Chika Obara b, Tatsuo Kikuchi b, Atsushi Sakuma a, Kunio Iizuka a,
Yumiko Hamaie a,b, Fumiaki Ito a, Hiroo Matsuoka a,b,c, Kazunori Matsumoto a,b,c
Affiliations:
a
Department of Psychiatry, Tohoku University Hospital, 1-1, Seiryo-machi, Aoba-ku, Sendai, Miyagi, Japan
b
Department of Psychiatry, Tohoku University Graduate School of Medicine, 2-1, Seiryo-machi, Aoba-ku,
Sendai, Miyagi, Japan
c
Department of Preventive Psychiatry, Tohoku University Graduate School of Medicine, 2-1, Seiryo-machi,
Aoba-ku, Sendai, Miyagi, Japan
Contact information for the corresponding author:
Name of the corresponding author: Noriyuki Ohmuro
Address: Department of Psychiatry, Tohoku University Hospital, 1-1, Seiryo-machi, Aoba-ku, Sendai,
Miyagi 980-8574, Japan
Tel.: +81 22 717 7262; Fax: +81 22 717 7266
E-mail address: ohmuro24@yahoo.co.jp

Abstract
Disturbance of theory of mind (ToM) and its relationship with functioning in schizophrenia is well
documented; however, this is unclear in spectrum disorders like at-risk mental state (ARMS) and
first-episode psychosis (FEP). To assess mental state reasoning ability, the total score of the Theory of
Mind Picture Stories Task questionnaire was compared among 36 Japanese individuals with ARMS, 40
with FEP, and 25 healthy controls (HC). Pearsons correlations between ToM performance and global and
social functioning indices were examined. ToM performance for FEP and ARMS subjects was significantly
lower than that for HC, though the significance of the difference between the ARMS and HC disappeared
when controlling for premorbid IQ. ToM deficits in ARMS subjects were confirmed only in the
comprehension of higher-order false belief. Only among FEP subjects were ToM performance and global
functioning significantly correlated, though the significance disappeared when controlling for
neurocognitive performance or dose of antipsychotics. No significant correlation between ToM
performance and social functioning was observed in the FEP and ARMS groups. The current findings
suggest that ToM deficits emerge in ARMS subjects confined within a higher-order domain, and that the
1

relationship between ToM impairment and functional deterioration might be established after psychosis
onset.
Keywords: mentalizing; cognitive theory of mind; mental state reasoning; social cognition; global
functioning; social functioning; ultra-high risk

1. Introduction
Cognitive deficits are a core feature of schizophrenia and associated with related functional
impairment (Green, 1996; Green et al., 2000). Recent findings from a meta-analysis have revealed that
social cognition deficits can predict related social dysfunction more directly than can those in
neurocognition (Fett et al., 2011).
Theory of mind (ToM), defined as an ability to infer others mental state, is one of the main social
cognition domains affected in schizophrenia (Brne, 2005a; Chung et al., 2014; Green et al., 2008). ToM
disturbance has clinically important implications such as an association with paranoid ideation (Bentall et
al., 2009; Craig et al., 2004; Frith, 1992) and poor functioning (Bora et al., 2006; Brne et al., 2005a;
Dodell-Feder et al., 2013; Pinkham and Penn, 2006). Because ToM disturbance was observed in chronic
patients with schizophrenia and those with first-episode psychosis (FEP) (Achim et al., 2012; Bliksted et al.,
2014; Bora and Pantelis, 2013; Green et al., 2012; Ho et al., 2015; Horan et al., 2011; Kettle et al., 2008;
Koelkebeck et al., 2010; Langdon et al., 2013; Mazza et al., 2012; Ntouros et al., 2014; Thompson et al.,
2012), it is assumed to emerge in early-phase psychosis. However, it remains unclear whether ToM deficits
occur before the onset of psychosis. Two previous meta-analyses showed ToM impairment with
medium-effect sizes in subjects with an at-risk mental state (ARMS), denoting a clinical high-risk state for
psychosis and presumably a putative prodromal phase thereof (Bora and Pantelis, 2013; Lee et al., 2015).
However, there were apparent inconsistencies in the study results. Some demonstrated ToM deficits in
subjects with ARMS (Chung et al., 2008; Green et al, 2012; Hur et al., 2013; Kim et al., 2011; Szily and
Kri, 2009; Thompson et al., 2012; Zhang et al., 2015); others did not (Brne et al., 2011; Couture et al.,
2008; Gill et al., 2014; Healey et al., 2013; Stanford et al., 2011). This could be partly due to the
heterogeneity of the ARMS (Fusar-Poli et al., 2013; McGorry et al., 2006). Because most, if at all, ARMS
individuals will not develop psychosis (Fusar-Poli et al., 2012a), ToM disturbance among these subjects
was attenuated, compared to among subjects with psychosis, or was limited within the higher-order
domain, which would make it possible to know that someone else thinks that a third person believes
something (Brne, 2005a). Another reason could be differences in the tasks in these studies (Bora and
Pantelis, 2013). Three of the five negative studies used the Eyes Test (Baron-Cohen et al., 2001),
considered a mental-state decoding task or affective ToM task; most positive studies used mental-state
reasoning tasks (Bora and Pantelis, 2013) or cognitive ToM tasks (Shamay-Tsoory and Aharon-Peretz,
2007). A lesion study suggested that affective and cognitive ToM have a different neural basis
(Shamay-Tsoory and Aharon-Peretz, 2007); earlier studies suggested that mental state reasoning, but not
decoding, seems impaired in the ARMS (Bora and Pantelis, 2013).
ToM disturbances association with poor functioning in schizophrenia has been repeatedly replicated
(Bora et al., 2006; Brne et al., 2005a; Dodell-Feder et al., 2013; Pinkham and Penn, 2006; Stewart et al.,
2009). However, results were inconsistent in terms of whether ToM disturbances in the ARMS are related
to their functional impairments; one study exhibited a significant correlation between ToM performance
and social functioning (Barbato et al., 2013); another did not (Stanford et al., 2011). Because individuals
with ARMS are likely to exhibit prolonged low functioning, irrespective of transition to psychosis
3

(Addington et al., 2011; Lin et al. 2015), it is important to elucidate the pathological mechanism of
functional impairment among these people, to develop effective interventions.
In this study, to detect deficits in cognitive ToM, we employed the Theory of Mind Picture Stories
Task (Brne et al., 2005b) as a mental state reasoning task and compared the ToM performance of healthy
controls (HC) and FEP and ARMS subjects. Through the task, we analyzed participants cognitive ToM
performance, in relation to several hierarchical components such as understanding first- to third-order false
beliefs. We also investigated ToM performances correlation with social and global functioning in FEP and
ARMS subjects. We hypothesized that ToM performance among FEP and ARMS subjects was impaired,
that ARMS subjects ToM performance would be disturbed only within the higher-order domain and fall
between that of patients with FEP and HC (Bora and Pantelis, 2013), and that ToM performance would
correlate with global and social functioning among FEP and ARMS subjects.
2. Methods
2.1. Participants
Participants included 1435-year-old, Japanese-speaking individuals with ARMS (n=36), with FEP
(n=40), and HC (n=25). The exclusion criteria were (i) serious suicide or violence risk, due to a personality
disorder; (ii) current substance dependence; (iii) intellectual disability (IQ<70); (iv) comorbid diagnosis of
autistic spectrum disorders, or (v) neurological disorder, head injury, or any other significant medical
condition associated with psychiatric symptoms.
ARMS and FEP participants were recruited from the Sendai At-Risk Mental State and First Episode
(SAFE) clinic at Tohoku University Hospital, a specialized clinic for early psychosis (Katsura et al., 2014;
Mizuno et al., 2009). They were referred to this clinic by health providers or through self-referral. Trained
psychiatrists and psychologists assessed them with the clinical and cognitive measures described below.
Participants meeting the ARMS or FEP criteria were followed up at the SAFE clinic. The data
reported herein are baseline data from the ARMS or FEP participants who consented to participation.
The ARMS group was assessed using the Japanese version of the Comprehensive Assessment of
At-Risk Mental States (CAARMS-J, Miyakoshi et al., 2009); diagnosis was confirmed by the clinical team.
Participants had no history of DSM-IV psychotic disorders and met one or more of the following ARMS
criteria (Yung et al., 2004): (i) attenuated psychotic symptoms (APS), (ii) brief limited intermittent
psychotic symptoms (BLIPS; a psychotic episode that resolves within 1 week), and (iii) state and trait risk
factors (i.e., a recent decline in functioning, plus either a first-degree relative with psychosis or a
schizotypal personality disorder). The ARMS groups composition according to categories was 81% (n=29)
for APS; state and trait risk factors, 3% (n=1); APS plus state and trait risk factors, 17% (n=6). Four (11%)
of the ARMS participants made a transition at follow-up and were included in the current analyses. Mean
follow-up duration was 25.6 months (SD=17.6, median 24.5).
Participants included in the FEP group met the CAARMS-J criteria for psychosis and had Positive
and Negative Syndrome Scale (PANSS, Kay et al., 1987) scores of 4 on items for delusion, hallucinatory
4

behavior, grandiosity, suspiciousness, or unusual thought content for >1 week. Participants were
experiencing their first episode or in subsequent remission during cognitive assessment and were all stable
enough to undergo cognitive examination. Baseline diagnoses in the FEP group included schizophrenia
(60%, n=24,), schizophreniform disorder (10%, n=4), brief psychotic disorder (3%, n=1), delusional
disorder (3%, n=1), bipolar disorder with psychotic features (5%, n=2), and psychotic disorder not
otherwise specified (20%, n=8).
HC were all students and volunteers recruited through intramural advertisement from Tohoku
University. All participants reported never having been diagnosed with a psychiatric disorder.
The study was authorized by the Ethics Committee of Tohoku University Graduate School of
Medicine and Tohoku University Hospital. Written informed consent was obtained from 18-year-old
participants and from parents of <18-year-olds, with their written assent.
2.2. Measures
2.2.1. ToM assessment
The Theory of Mind Picture Stories Task (Brne et al., 2005b) was employed in the current study.
This task comprises six cartoon picture stories depicting cooperation of two characters, one character
deceiving another, or two characters cooperating to deceive a third one. In each story, the participants were
asked to sequence four cards in a logically correct order and answer questions regarding ToM ability, such
as inferring a characters intention. In each sequencing task, two points were given for the first and last
correctly sequenced cards, and one point each for correct sequencing of the two middle cards; thus, there
were six maximum points per picture story, with a maximum sum score of 36 points. In each questionnaire,
one point was given for each correct answer. Then, a maximum overall score of 59 points was given (36
points for sequencing and 23 for questionnaires).
The advantage of this task is that analysis of the questionnaire results enables assessment of each
component of ToM performance, namely, first-order (i.e., inferring someones mental state) belief,
first-order false belief, second-order (i.e., inferring someones thinking about another ones mental state)
belief, second-order false belief, third-order (i.e., inferring someones thinking about anothers idea about
someones mental state) false belief, reciprocity, deception, and cheating detection, with reality questions
included to rule out major attention problems among participants. We set the total questionnaire score as a
primary variable because our preliminary results showed this to more sensitively measure participants
ToM performance than could the total score of the whole task.
In this study, the administered Japanese version of the task was developed by the current authors, with
the permission of the original tasks author.
2.2.2. Clinical assessments
The Global Assessment of Functioning (GAF, American Psychiatric Association, 1994) assessed
5

global functioning. Social functioning was assessed with the Japanese version of the Social Functioning
Scale (SFS, Birchwood et al., 1990; the Japanese version of the SFS, Nemoto et al., 2008), a self-report
questionnaire developed for patients with schizophrenia, which includes subscales for the following
domains: social engagement/withdrawal, interpersonal communication, independence-performance,
recreation, prosocial, independence-competence, and employment/occupation. Higher GAF and SFS scores
reflect higher functioning. Psychopathology (positive symptoms, negative symptoms, depression, and
anxiety) was assessed with the PANSS; higher scoring reflected more severe symptoms. Estimated
premorbid IQ was assessed using the Japanese version of the National Adult Reading Test (NART, Nelson,
1982; JART, Matsuoka et al., 2006). Neurocognition was assessed through the Brief Assessment of
Cognition in Schizophrenia (BACS) (Keefe et al., 2004) Japanese version (Kaneda et al., 2007) in which
a composite z-score was calculated through means described elsewhere (Ohmuro et al., 2015). Higher
scoring in JART and BACS reflected higher performance.
2.3. Statistical analysis
One-way ANOVAs were used to compare the ARMS, FEP, and HCs demographic variables (i.e., age
at testing and estimated premorbid IQ), ToM task scores, and composite BACS z-scores. Tukeys post-hoc
tests determined specific group differences. The Kruskal-Wallis test was used to compare education
duration among the three groups. Further, ANCOVAs were conducted to compare the three groups total
ToM questionnaire scores, to control for the effect of variables possibly associated with ToM (i.e., age at
examination, years of education, JART score, BACS composite z-score, and dose of medicated
antipsychotics). T-tests were performed to compare the ARMS and FEP groups on GAF, total SFS, and
PANSS scores, and dose of medicated antipsychotics. Fishers exact tests compared the gender ratio across
the three groups and antipsychotic medication in the ARMS and FEP groups. Pearsons correlations were
calculated to examine the relationships between the total ToM task questionnaire score and the global and
social functioning indices (i.e., GAF and total SFS score) in the ARMS and FEP groups. Moreover, partial
correlation analyses were performed to confirm whether ToM in these subjects can exclusively correlate
with functioning indices when the variables described above covary, which could have an association with
ToM.
Statistical analyses were conducted using SPSS for Windows (version 17.0). Testing was two-tailed at
a 5% significance level.
3. Results
3.1. Demographic data
Table 1 summarizes the demographic data. More females than males were in each group, due to the
high proportion of female clients at the SAFE clinic. Age at assessment did not significantly differ across
the groups, but the groups significantly differed in years of education, premorbid IQ, and neurocognition.
6

HC had a higher education level, estimated premorbid IQ, and neurocognitive performance, compared to
the FEP and ARMS groups.
3.2. Clinical variables and medication status
Clinical characteristics and medication status in the FEP and ARMS groups are summarized in Table
2. The ARMS groups global functioning, indicated by the GAF score, was significantly higher than that of
the FEP group; no significant difference in social functioning, indicated by the SFS total score, was found
between the two groups. As for psychopathology, the ARMS group had significantly less positive, negative,
and general symptoms.
Eight participants (22%) in the ARMS group were medicated with antipsychotics at testing; the
proportion was significantly lower than that in the FEP group (38 participants, 95%). The mean daily dose
in the ARMS group was significantly lower than that in the FEP group.
3.3. ToM performance
The ToM task results are summarized in Table 3. The mean questionnaire score significantly differed
across the three groups and follow-up Tukeys tests indicated that the FEP and ARMS groups significantly
differed from the HC group (p<0.001; p=0.007) and a trend-level difference was found between the FEP
and ARMS groups (p=0.07). Following a regression analysis, only premorbid IQ (JART score) was entered
as a covariate for ANCOVA. Consequently, the ARMS and HC groups scores no longer differed
significantly when the JART score was controlled.
Significant differences were observed in three out of eight questionnaire sub-items (i.e., first to third
orders of false belief); post-hoc tests revealed that mean scores in the FEP group were significantly lower
than those in the HC on all the three items and that the ARMS groups score was significantly lower than
that of the HC on the second-order false-belief item and at a trend-level (p=0.07) on the third-order
false-belief item. As a result of the test of homogeneity of regression slopes and the regression analysis, no
variable met the assumption for ANCOVA.
The mean sequencing score significantly differed among the three groups and a follow-up test
indicated that the sequencing score in the FEP group was significantly lower than that in the ARMS
(p=0.008). The mean total score significantly differed among the three groups and a post-hoc test indicated
that the total score in the FEP group was significantly lower than that in the ARMS and HC (p=0.002;
p<0.001).
The mean and SD of the total questionnaire score for ARMS subjects who later transitioned to
psychosis were 21.0 and 1.8, respectively (Data not shown in the tables. Due to the low number of these
subjects, a statistical comparison with those who did not transition was not performed.)
3.4. The correlations between ToM performance and global and social functioning
7

The correlations between the total questionnaire score and the global and social functioning indices
are shown in Figure 1. In the FEP group, ToM performance, indicated by the total questionnaire score,
significantly correlated with global functioning, indicated by the GAF score; no significant correlation was
found in the ARMS group. The correlation in the FEP group remained significant when partial correlation
analysis was conducted, controlling for age at examination, years of education, or estimated premorbid IQ;
the significant correlation was no longer found when the dose of antipsychotics or neurocognitive
performance was entered as a partial correlation coefficient.
No correlation was found between ToM performance and social functioning, indicated by the total
SFS score, in either the FEP or the ARMS group.
3.5. Additional analysis
All groups had more female than male participants. Therefore, we examined sex differences in ToM
performance as a post-hoc analysis. No significant sex difference was found.
4. Discussion
In this study, we used the cognitive ToM task assessing a reasoning-ability mental state and found
ToM disturbance among ARMS and FEP participants. As we expected, the mean ARMS ToM task
questionnaire score fell between that of FEP patients and HC, though the difference in the ARMS and FEP
groups scores reached marginal significance. Importantly, ToM deficits in FEP were presented in first- to
third-order false-belief domains, whereas those in the ARMS were significant only in second-order and
marginally significant in third-order false-belief domains. These findings suggest that a common social
cognitive pathology might inhere in FEP and ARMS patients within higher-order domains, even though
most ARMS individuals will not develop psychosis (Fusar-Poli et al., 2012a). We also found an association
between ToM performance and global function in FEP, but not ARMS patients. Nevertheless, some of these
findings disappeared when controlling for several variables, suggesting a partial relationship between these
and ToM.
4.1. ToM disturbance in ARMS
The present ToM disturbance finding in ARMS subjects was consistent with previous studies that
showed ToM disturbance using the False Belief task (Chung et al., 2008; Hur et al., 2013; Kim et al., 2011),
Strange Story task (Chung et al., 2008; Hur et al., 2013; Kim et al., 2011), Cartoon task (Chung et al., 2008;
Hur et al., 2013; Kim et al., 2011), Faux Pas Test (Zhang et al., 2015), and the Eyes Test (Szily and Keri,
2009), when compared to HC. Additionally, in accordance with the present study, two previous studies have
demonstrated ToM disturbance in FEP and ARMS participants using the Awareness of Social Inference Test
(Green et al., 2012) and the Hinting task and the Visual Jokes task (Thompson et al., 2012). Conversely,
several studies found no ToM disturbance in ARMS participants (Brne et al., 2011; Couture et al., 2008;
8

Healey et al., 2013; Gill et al., 2014; Stanford et al., 2011). Because three of five previous negative
studies employed the Eyes Test (Couture et al., 2008; Healey et al., 2013; Stanford et al., 2011), which is
assumed to assess an ability to decode an affective mental state, ARMS individuals may have less
impairment in this social cognitive process. Previous studies using the Eyes Test in patients with FEP
(Kettle et al., 2008) or chronic schizophrenia (Kelemen et al., 2005; Kington et al., 2000; Russell et al.,
2000) showed significant impairments, compared to HC.
Nonetheless, the disappearance of the significant difference in ToM performance when controlling for
estimated premorbid IQ should be noted. In this study, premorbid IQ was not matched and significantly
differed across the three groups. Findings regarding the effect of IQ on ToM performance differed across
studies. Chung et al. (2008) showed a significant difference between ARMS individuals and IQ-matched
HC in ToM performance. In Hur et al. (2013), ARMS participants and HC did not show a significant
difference both in ToM performance and IQ. However, when all the participants were split into higher- and
lower-IQ groups, there was a significant difference in ToM performance between individuals with ARMS
and HC in the lower-IQ group, and none in the higher-IQ group. Further, Stanford et al. (2011) showed IQ
to be a significant predictor of ToM performance, and that diagnosis no longer predicted ToM performance
when IQ was considered in their general linear model. Additionally, ToM performances relationship with
neurocognition should be considered. These correlated in previous studies (Addington et al., 2010; Barbato
et al., 2013; Koelkebeck et al., 2010). When the correlations between ToM performance and neurocognition
(BACS composite z-score) were examined among current subjects, they were not significant, but did not
seem ignorable (FEP: r=0.15, p=0.35; ARMS: r=0.30, p=0.08; HC: r=-0.25, p=0.22), which may have an
effect on the current results. Current and previous findings suggest the possibility of partial effects of
general intelligence and neurocognition on ToM impairment in ARMS subjects, and note the importance of
evaluating these performances when assessing ToM among these subjects. Nevertheless, as these
performances in general ARMS individuals have been known to be lower than those in healthy people
(Fusar-Poli et al., 2012b), comparisons of ToM abilities between ARMS and healthy subjects with full
matching or covariance of these factors may cause the underestimation of ToM deficits in the general
population of ARMS individuals in real settings.
4.2. Theory of Mind Picture Stories Task and different components of ToM
The Theory of Mind Picture Stories Task has the benefit of detecting reasoning capacity of others
mental state in detail, by analyzing several hierarchical subcomponents of cognitive ToM abilities.
Previously, one study involving ARMS subjects employed the Theory of Mind Picture Stories Task for a
functional Magnetic Resonance Imaging (MRI) study (Brne et al., 2011). In that study, there was no
significant difference between ARMS subjects and HC in ToM performance; however, the small sample
size (n=10, in ARMS) therein makes a direct comparison of previous and current study findings difficult.
The analysis in each component revealed that comprehension ability of the first-, second-, and third-order
false belief had significantly deteriorated in FEP participants, whereas only the significant disturbance in
the comprehension of the second-order false belief and the trend-level disturbance in the comprehension of
9

the third-order false belief were shown among ARMS participants. Since the comprehension of the secondor third-order false belief may demand higher levels of reasoning ability of others mental states, as we
initially hypothesized, the current task may have enabled sensitive detection of even a subtle social
cognitive impairment among ARMS subjects. Disturbance of the comprehension of others false beliefs, as
ascertained in previous studies involving FEP (Achim et al., 2012; Inoue et al., 2006; Langdon et al., 2013;
Mazza et al., 2012) and ARMS subjects (Chung et al., 2008; Hur et al., 2013; Kim et al., 2011), may
emerge in the early stage of a psychosis onset.
Furthermore, we must consider the possibility that less disturbance of observed ToM performance in
the ARMS group could be caused by the dilution of ToM deficits in ARMS subjects who would later
transition to psychosis with those in subjects who would never transition. This is because false positives
for true schizophrenia spectrum disorders are always obtained for the ARMS groups subgroups, with their
inclusion potentially attenuating deficits driven by true prodrome cases.
4.3. Association between ToM ability and functioning
Findings of the relationship between ToM abilities and functioning seem more inconsistent among
FEP and ARMS individuals than in those with established schizophrenia. In accordance with the present
study, some studies did not find any association between FEP individuals ToM performance and social
functioning (Horan et al., 2011; Sullivan et al., 2014), whereas other studies did (Achim et al., 2012; Mazza
et al., 2012; Stouten et al., 2015; Sullivan et al., 2013). In the present study, we found a correlation between
ToM performance and, not social, but global functioning in FEP subjects, though the significance of the
correlation disappeared when the dose of antipsychotics or neurocognitive performance covaried. ToM
disturbance in ARMS subjects was not associated with either social or global functioning in the present
study, similar to a previous study (Stanford et al., 2011). Further, Barbato et al.s (2013) analysis with
Structural Equation Modeling (SEM) demonstrated that, although both the path from neurocognition to
social functioning and that from social cognition to social functioning were both significant in the basic
model, these relationships did not remain significant when social cognition was entered as a mediator in the
mediation model. One reason for the inconclusive findings in the earlier phase of psychosis may be the
heterogeneity of clinical characteristics and course thereof in these populations (Fusar-Poli et al., 2013;
McGorry et al., 2006). Thus, many factors, other than ToM abilities, might have an impact on social and
global functioning of individuals with FEP or ARMS. In particular, the relationship between neurocognition
and social cognition should be noted, as the finding by Barbato et al. (2013) and the current result, with the
significance in the correlation between ToM performance and global function in the FEP group
disappearing when controlling for neurocognitive performance, would support this. Similarly, Stouten et al.
(2015) showed that not only deficits in social cognition, including ToM, but also neurocognitive
impairment and severity of negative symptoms, were associated with lower psychosocial functioning
among FEP subjects. Thus, the present and previous findings suggest that ToM measures are limited and
possibly not sufficiently sensitive to show relationships with functional impairment among FEP or ARMS
individuals. We must integrate several relevant factors with ToM measures, to determine such relationships.
10

Furthermore, several previous studies investigated the longitudinal relationship between ToM
performance and social functioning, which would help us estimate when such a relationship becomes
established in the course of schizophrenia. In Horan et al.s (2011) study, although ToM performance in
FEP participants at baseline did not correlate with baseline social functioning, it predicted social
functioning at 12-month follow-up. In contrast, in Sullivan et al.s (2014) study, baseline ToM performance
did not predict social functioning outcomes at either 6- or 12-month follow-up. Further, a randomized
controlled trial of Individual Placement and Support (IPS) versus treatment as usual, showed that baseline
social cognitive performance, including ToM, did not predict vocational outcome, whereas neurocognitive
performance did (Allott et al., 2013). Current and previous findings regarding subjects with FEP and
chronic schizophrenia (Bora et al., 2006; Brne et al., 2005a; Dodell-Feder et al., 2013; Pinkham and Penn,
2006) show that the relationship between ToM performance and functioning could be established after the
onset of psychosis and may develop afterwards.
In addition, partial correlation results imply that the dose of antipsychotics may have influenced the
correlation between ToM performance and global functioning in the FEP group. The effect of
antipsychotics on ToM performance was investigated in previous studies (Kucharska-Pietura and Mortimer,
2013; Mizrahi et al., 2007; Savina and Beninger, 2007; Sergi et al., 2007), though results are not yet
conclusive.
4.4. Limitation
There were some limitations in the current study. First, since the ToM task employed in the present
study was based on behavioral assessment, merely using cartoon stories, it could only assess off-line
deliberate reasoning (Couchman et al., 2012). However, in real life, mentalizing is likely to arise
automatically and implicitly. To assess this on-line ToM, using implicit and non-verbal tasks would be
more applicable (Das et al., 2012; Kovcs et al., 2014).
Second, the distribution of the ToM questionnaire scores across the HC and ARMS groups suggests
that this task has a ceiling effect; some specific sub-scores were considerably low. Although the ceiling
effect is common in studies on psychotic disorders (Greeen et al., 2008), to detect subtle differences
between healthy and ARMS subjects, a more sophisticated task with greater variance in the performance of
healthy subjects might be appropriate.
Third, the sample was relatively small, which made it difficult to generalize the current findings and
introduce a more sophisticated approach like path analysis. Moreover, a small sample size might reduce
statistical power, particularly in correlation analyses, contrasting with the findings reported by Barbato et al.
(2013), which included 137 ARMS participants, with a ToM performance that significantly correlated with
their social functioning, with a modest effect size (r=0.18). Furthermore, the small sample size and the
relatively low transition rate precluded comparing the ToM performance of those who transitioned to
psychosis and those who did not, and examining correlations between ToM deficits and functional
impairment among those who transitioned.
Fourth, the neurocognitive performance assessed with the BACS on the current ARMS group was
11

relatively lower than that shown in previous studies (Fusar-Poli et al., 2012b). As discussed in our
previously published article (Ohmuro et al., 2015), most of the current participants were recruited for
assessment using the BACS; so, this may partly be due to the characteristics of the ARMS and HC samples
recruited in our setting, which could limit the generalizability of the current findings.
Fifth, in this study, participants sex was disproportionate. Previous studies demonstrated that sex
differences in brain activity were associated with ToM (Krach et al., 2009) and female superiority in ToM
performance among patients with schizophrenia (Abu-Akel et al., 2013). Thus, a higher ratio of female
participants in the current study could affect each of the three groups ToM performance. Although sex
differences in ToM performance were not observed in the current study, this disproportion may have had a
certain effect on the generalizability of the current findings.
Future research examining ARMS and FEP subjects, using larger samples, conducting multivariate
analyses, and comparing converters to psychosis and non-converters, is needed.
4.5. Conclusions
In this study, cognitive ToM performance was examined in ARMS and FEP subjects, using a mental
state reasoning ToM task. The study ascertained deficits in ToM in both FEP and ARMS subjects, though
changes in ToM in the ARMS did not remain significant when controlling for their premorbid IQ. These
ToM deficits were mainly explained by difficulty in the comprehension of false belief and the disturbance
was limited within higher-order cognitive ToM among ARMS individuals. The relationship between
deficits in cognitive ToM and global functioning was ascertained only in the FEP group, though this
relationship was not significant when controlling for neurocognitive performance or dose of medicated
antipsychotics. Current and previous findings showing an established relationship between ToM deficits
and low functioning in individuals with established schizophrenia suggest that ToM deficits might emerge
only within the higher-order reasoning domain in the prodromal or high-risk state and progress involving
diverse domains, including lower-order or affective ones, as psychosis develops and progress. The
relationship between ToM impairment and functional deterioration might be established in the more
chronic stage of the course of schizophrenia.

12

Acknowledgements
We thank Emi Sunakawa, Tomohiro Uchida, and Rie Koshimichi for their help with the cognitive
assessments.
Conflicts of Interest
This work was supported by JSPS KAKENHI Grant Numbers 22390219, 23791307, and 25860984. The funding
source had no role to play in the study design; in the collection, analysis and interpretation of data; in the writing of
the report; and in the decision to submit the article for publication.

13

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21

Table 1
ARMS
(n=36)

FEP
(n=40)

HC
(n=25)

Statistic
value

Number of males (%)

14 (38.9)

11 (27.5)

11 (44.0)

Exact test

0.35

M (SD) Age in years at

testing

20.9 (4.7)

22.9 (6.3)

21.3 (1.0)

F=1.79

0.17

M (SD) Years of education 12.5 (2.4)

12.5 (2.0)

14.4 (0.9)

H=17.8

<0.001

M (SD) Premorbid IQ

101.1 (11.7)

99.1 (8.3)

112.0 (6.5)

F=16.0

<0.001

M (SD) Neurocognition
(BACS composite z-score)

-2.60 (1.58)

-2.47 (1.59)

0 (1)

F=28.1

<0.001

Demographic data
ARMS: At-Risk Mental State; FEP: First-Episode Psychosis; HC: Healthy Control; premorbid IQ was
measured through the Japanese version of the National Adult Reading Test (JART); BACS: Brief
Assessment of Cognition in Schizophrenia

22

Table 2
Clinical variables and medication status
ARMS
(n=36)

FEP
(n=40)

Statistic
value

GAF, M (SD)

49.9 (7.7)

42.3 (14.70)

t=2.79

0.007

SFS total, M (SD)

103.5 (21.9)

111.4 (24.6)

t=-1.47

0.15

PANSS positive, M (SD)

12.9 (3.1)

17.5 (6.8)

t=-3.84

<0.001

PANSS negative, M (SD)

12.4 (4.0)

16.6 (7.8)

t=-3.04

0.004

PANSS general, M (SD)

32.0 (5.8)

37.5 (14.3)

t=-2.22

0.03

8 (22%)

38 (95%)

Exact test

<0.001

371.9 (343.1)
01709

t=-5.76

<0.001

Clinical variables

Medications
Antipsychotics, n (%)

Mean dose (CP eq.) (mg) (SD) 45.9 (97.3)

range (mg)
0300

ARMS: At-Risk Mental State; FEP: First-Episode Psychosis; GAF: Global Assessment of
Functioning; SFS: Social Functioning Scale; PANSS: Positive and Negative Syndrome Scale; CP:
chlorpromazine; SD: standard deviation

23

Table 3
Results of ToM picture stories task
(Max FEP ARMS
score)
Questionnaire
score

HC

Multiple
comparison
HC > FEP,
ARMS

23

18.8 19.9
(2.4) (2.7)

21.7
(1.3)

12.77

<0.001

First-order belief

0.9 0.9
(0.3) (0.2)

0.9
(0.3)

0.57

0.57

First-order false
belief

2.4 2.6
(0.7) (0.7)

2.8
(0.6)

3.23

0.04

Second-order
belief

2.0 2.0
(0.0) (0.0)

2.0
(0.0)

Second-order
false belief

2.2 2.3
(0.9) (0.9)

2.8
(0.4)

6.27

0.003

HC > FEP,
ARMS

Third-order false

2.3

8.85

<0.001

HC > FEP

Questionnaire
subcategories

belief

1.1

1.6

(1.1) (1.2)

(1.1)

HC > FEP

1.00

Reciprocity

2.8 2.7
(0.4) (0.6)

2.9
(0.3)

2.23

0.11

Deception

3.8 3.8
(0.5) (0.4)

4.0
(0.2)

1.41

0.25

Cheating
detection

1.9 1.8
(0.4) (0.4)

2.0
(0.0)

2.30

0.11

(Reality)

1.9 2.0
(0.4) (0.0)

2.0
(0.0)

2.90

0.06

Sequencing
score

36

32.0 34.2
(3.9) (2.5)

33.9
(2.4)

5.34

0.006

ARMS >
FEP

Total score

59

50.1 54.0
(4.9) (4.0)

55.6
(2.6)

12.12

<0.001

HC, ARMS
> FEP

24

ToM: Theory of Mind; ARMS: At-Risk Mental State; FEP: First-Episode Psychosis;
HC: Healthy Control; Data indicate the mean with the standard deviation; Post-hoc
multiple comparisons were performed using Tukeys test.
Figure 1.
Correlations between the total questionnaire score in the ToM task and the indices of
functioning

ToM: Theory of Mind; ARMS: At-Risk Mental State; FEP: First-Episode Psychosis;
GAF: Global Assessment of Functioning; SFS: Social Functioning Scale; asterisk
indicates significant p-value (*p<0.05)

Highlights

FEP and ARMS subjects scored higher than HC on the cognitive ToM task

ARMS subjects had ToM deficits in the comprehension of higher-order false

belief

ARMS subjects ToM disturbance was not related to social or global functioning

25

FEP subjects ToM performance correlated with global functioning

26