Noriyuki Ohmuro

A naturalistic longitudinal study of at-risk mental state with a 2.4 year follow-up at a specialized clinic setting in Japan

OBJECTIVE The notion of at-risk mental state (ARMS) is valuable for identifying individuals in a putative prodromal state of psychosis and for reducing conversion risk by pharmacological and psychological interventions. However, further systematic study is required because 1) diagnostic reliability in various clinical settings is not yet established; 2) predictive ability is insufficient; 3) optimal interventions in diversified populations are elusive; and 4) little evidence from non-Western regions exists. METHODS A naturalistic longitudinal study was conducted at a specialized clinic for early psychosis at a university hospital in Sendai, Japan. Individuals with ARMS (n=106) were recruited and followed up with case-by-case treatment. RESULTS Two-thirds of the participants were psychiatrist referrals, and 83 were followed up for at-least 1 year (mean follow-up=2.4 years). Fourteen developed psychosis and the estimated (by Kaplan-Meier) cumulative transition rate was 11.1% at 12, 15.4% at 24, and 17.5% at 30 months. At the end-point, about 30% of the 83 followed-up participants including 11 converters received antipsychotic medication. Compared to non-converters, converters showed more severe attenuated psychotic symptoms, including ego-boundary disturbance, formal thought disorder, and emotional disturbance. CONCLUSIONS The present study replicated previous major Western longitudinal studies, in terms of clinical characteristics, psychosis transition rate, and antipsychotic prescription rate. Our results emphasize the importance of phenomenological assessment of ARMS and intensive care in a clinical setting.

Application of the Comprehensive Assessment of At‐Risk Mental States (CAARMS) to the Japanese population: reliability and validity of the Japanese version of the CAARMS

Aim: The putative prodromal state of schizophrenia has been conceptualized as an at‐risk mental state (ARMS), which is identified on the basis of ultra‐high‐risk (UHR) criteria, and the Comprehensive Assessment of At‐Risk Mental States (CAARMS) has been developed as a specific instrument. However, the generalizability of CAARMS and the concept of ARMS have not been established. In this study, we tested the reliability and validity of the Japanese version of CAARMS (CAARMS‐J).

Differential impacts of duration of untreated psychosis (DUP) on cognitive function in first-episode schizophrenia according to mode of onset

BACKGROUND The mode of onset and the course of schizophrenia illness exhibit substantial individual variations. Previous studies have pointed out that the mode of onset affects the duration of untreated psychosis (DUP) and clinical outcomes, such as cognitive and social functioning. This study attempted to clarify the association between the DUP and clinical features, taking the different modes of onset into consideration, in a prospective longitudinal study examining patients with first-episode schizophrenia. METHODS This study was conducted in six areas of Japan. Patients with first-episode schizophrenia were followed for over 18 months. Cognitive function, psychopathology, and social functioning were assessed at baseline and at 6, 12, and 18-month follow-up points. RESULTS We identified 168 patients and sufficient information was available to determine the DUP and the mode of onset for 156 patients (92.9%): 79 had an acute onset, and 77 had an insidious onset. The DUP was significantly associated with quality of life (QOL), social functioning, and cognitive function at most of the follow-up points in the insidious-onset group. The DUP and negative symptoms at baseline were significant predictors of cognitive function at the 18-month follow-up in the insidious-onset group. CONCLUSIONS The present results further support the hypothesis that the DUP affects QOL, social functioning, and cognitive function over the course of illness, especially in patients with an insidious onset. Effective strategies for detecting and caring for individuals with insidious onset early during the course of schizophrenia will be essential for achieving a full patient recovery.

Relationship between cognitive insight and attenuated delusional symptoms in individuals with at-risk mental state

Cognitive insight, defined as the ability to evaluate and correct one׳s own distorted beliefs and misinterpretations, is hypothesized to contribute to the development of psychotic symptoms. We investigated cognitive insight in individuals with at-risk mental state (ARMS), which is associated with a clinically high risk of psychosis. Sixty individuals with ARMS were compared with 200 healthy controls in terms of cognitive insight measured using the Beck Cognitive Insight Scale. We also investigated the relationship between cognitive insight and attenuated delusional symptoms. In addition, we examined differences in the cognitive insight of individuals with ARMS with or without near-threshold delusional symptoms and differences in the cognitive insight of individuals with ARMS with or without later transition to psychosis. The results showed that individuals with ARMS exhibited higher self-certainty than healthy controls, indicating impairments in cognitive insight in the former. More importantly, our results revealed that self-certainty was correlated with attenuated delusional symptoms and that individuals with ARMS who had near threshold delusional symptoms had higher self-certainty. These findings indicate that overconfidence in one׳s own beliefs or judgments might be related to the formation and maintenance of attenuated delusions in individuals with ARMS.

The association between cognitive deficits and depressive symptoms in at-risk mental state: A comparison with first-episode psychosis

Cognitive deficits and a high prevalence of depressive symptoms have been reported in at-risk mental state (ARMS) for psychosis, but the relationships between these variables remain unclear. The Brief Assessment of Cognition in Schizophrenia (BACS) was administered to 50 individuals with ARMS, 50 with first-episode psychosis (FEP), and 30 healthy controls (HC). Clinical symptoms were assessed by the Positive and Negative Syndrome Scale (PANSS) and the Beck Depression Inventory-2nd edition (BDI-II). Composite z-scores in BACS were compared between the three groups. Pearson correlations between composite z-scores on the BACS and indices of clinical symptoms were compared in the ARMS and FEP groups. The mean composite z-scores on the BACS for the ARMS (-2.82) and FEP (-2.85) groups were significantly lower than the HC group (P<0.001); no differences between the ARMS and FEP groups emerged (P=0.995). Cognitive deficits and depressive symptoms were significantly correlated in the ARMS group (PANSS depression: r=-0.36, P=0.010; BDI-II: r=-0.34, P=0.02), while the correlation between cognitive deficits and negative symptoms was significant in the FEP group (r=-0.46, P=0.001) and approached significance in the ARMS group (r=-0.25, P=0.08). The correlation between cognitive deficits and depressive symptoms significantly differed between the ARMS and FEP groups (PANSS depression: Z=2.50, P=0.012; BDI-II: Z=1.96, P=0.0499). Thus, a relationship between cognitive deficits and depression appears to be specific to ARMS compared to FEP.

Deficits of cognitive theory of mind and its relationship with functioning in individuals with an at-risk mental state and first-episode psychosis

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 relationship between ToM impairment and functional deterioration might be established after psychosis onset.

Emotional processing during speech communication and positive symptoms in schizophrenia.

The recognition of emotion is often impaired in patients with schizophrenia. The relationship of this deficit with symptoms of psychosis remains unclear. In the current study, we investigated the relationship between emotional processing and positive psychotic symptoms in schizophrenia.

The relationship between cognitive insight and cognitive performance among individuals with at-risk mental state for developing psychosis

Impairments in cognitive insight-the capacity to appraise and modify ones own distorted beliefs-are believed to be associated with the formation of psychosis. Nevertheless, the association between cognitive insight and cognitive function among people with at-risk mental state (ARMS) for developing psychotic illness has not been made clear. In this study, we used the Beck Cognitive Insight Scale (BCIS) to assess cognitive insight and the Brief Assessment of Cognition in Schizophrenia (BACS) and the Wisconsin Card Sorting Test (WCST) to assess cognitive functions. Fifty subjects with ARMS and 29 healthy volunteers were recruited as participants. The scores for the two groups on the BCIS, BACS, and WCST were compared and Spearmans rank correlations between the domains of the BCIS and cognitive performance were examined in each group. No significant differences were found in BCIS scores between these groups, whereas all of the cognitive function scores were poorer in the participants with ARMS. In the ARMS group, higher self-certainty on the BCIS was significantly correlated with lower performance in the mean number of categories achieved (ρ=-0.31, P=0.03) and perseverative errors of the Nelson type (ρ=0.29, P=0.04) on the WCST. This indicates that excessively high self-certainty might be linked with weaknesses in cognitive flexibility or set-shifting ability in people with ARMS.

The associations between quality of life and clinical symptoms in individuals with an at-risk mental state and first-episode psychosis

Quality of life (QOL) is strongly associated with severity of clinical symptoms and is often compromised in patients with chronic or first-episode psychosis (FEP). However, it remains unclear whether baseline QOL in individuals with an at-risk mental state (ARMS) for psychosis is higher or lower than that in patients with FEP, or what specific clinical symptoms relate to a decreased QOL in individuals with ARMS and FEP. The World Health Organizations WHOQOL-BREF, an instrument assessing QOL, was administered to 104 individuals with ARMS and 53 with FEP. Clinical symptoms were assessed by the Positive and Negative Syndrome Scale and the Beck Depression Inventory-II. We compared the four domain scores of the WHOQOL-BREF between the two groups, and calculated Pearson correlations between each WHOQOL-BREF domain score and the clinical symptoms and compared these correlations between the groups. We observed significant correlations between poor QOL and severity of depressive symptoms in both the FEP and ARMS group. No between-group differences were found in any correlation coefficients between WHOQOL-BREF domains and clinical symptoms. Thus, depressive symptoms should be investigated as a key factor relating to poor QOL in both individuals with ARMS and those with FEP.

Federated multi-site longitudinal study of at-risk mental state for psychosis in Japan

There has been recent accumulation of evidence and clinical guidance regarding the at-risk mental state (ARMS) for psychosis. However, most studies have been observational cohort and intervention studies of Western populations. To assess the validity of the ARMS concept and the transition rate to psychosis in a non-Western nation, we retrospectively combined and analyzed clinical data of individuals diagnosed with ARMS who were prospectively followed-up at three specialized clinical services for ARMS in Japan. In total, we included 309 individuals with ARMS, of whom 43 developed overt psychosis. We estimated cumulative transition rates to psychosis with the Kaplan-Meier method, obtaining rates of 12% at 12, 16% at 24, 19% at 36, and 20% at 48 months. Only two individuals reported past cannabis use. Despite several differences among the three sites, transition rates did not differ among them. Furthermore, the transition rate of children aged between 14 and 17 years did not differ from that of individuals aged 18 years or older. Regression analysis revealed that meeting the brief limited intermittent psychotic symptoms (BLIPS) criterion was associated with an increased risk of transition to psychosis, whereas genetic risk factors were not. Although antipsychotic prescription was relatively frequent in this cohort, there was no evidence supporting frequent use of antipsychotics for this population. In conclusion, our findings support the assertion that the current concept of ARMS is applicable in Japan. Development of local clinical guidelines and training for clinicians is necessary to disseminate this concept to more clinical settings.