Surface morphology of the orbitofrontal cortex in individuals at risk of psychosis: a multicenter study.

Changes in the surface morphology of the orbitofrontal cortex (OFC), such as a fewer orbital sulci and altered sulcogyral pattern of the 'H-shaped' orbital sulcus, have been reported in schizophrenia, possibly reflecting abnormal neurodevelopment during gestation. However, whether high-risk subjects for developing psychosis also exhibit these gross morphologic anomalies is not well documented. This multicenter MRI study from four scanning sites in Japan investigated the distribution of the number of intermediate and posterior orbital sulci, as well as the OFC sulcogyral pattern, in 125 individuals with an at-risk mental state (ARMS) [of whom 22 later developed psychosis (ARMS-P) and 89 did not (ARMS-NP)] and 110 healthy controls. The ARMS group as a whole had a significantly lower number of intermediate and posterior orbital sulci compared with the controls, which was associated with prodromal symptomatology. However, there was no group difference in OFC pattern distribution. The ARMS-P and -NP groups did not differ in OFC surface morphology. These results suggest that gross morphology of the OFC in high-risk subjects may at least partly reflect neurodevelopmental pathology related to vulnerability to psychosis.

Subcortical Brain Volume Abnormalities in Individuals With an At-risk Mental State.

Previous structural magnetic resonance imaging studies of psychotic disorders have demonstrated volumetric alterations in subcortical (ie, the basal ganglia, thalamus) and temporolimbic structures, which are involved in high-order cognition and emotional regulation. However, it remains unclear whether individuals at high risk for psychotic disorders with minimal confounding effects of medication exhibit volumetric changes in these regions. This multicenter magnetic resonance imaging study assessed regional volumes of the thalamus, caudate, putamen, nucleus accumbens, globus pallidus, hippocampus, and amygdala, as well as lateral ventricular volume using FreeSurfer software in 107 individuals with an at-risk mental state (ARMS) (of whom 21 [19.6%] later developed psychosis during clinical follow-up [mean = 4.9 years, SD = 2.6 years]) and 104 age- and gender-matched healthy controls recruited at 4 different sites. ARMS individuals as a whole demonstrated significantly larger volumes for the left caudate and bilateral lateral ventricles as well as a smaller volume for the right accumbens compared with controls. In male subjects only, the left globus pallidus was significantly larger in ARMS individuals. The ARMS group was also characterized by left-greater-than-right asymmetries of the lateral ventricle and caudate nucleus. There was no significant difference in the regional volumes between ARMS groups with and without later psychosis onset. The present study suggested that significant volume expansion of the lateral ventricle, caudate, and globus pallidus, as well as volume reduction of the accumbens, in ARMS subjects, which could not be explained only by medication effects, might be related to general vulnerability to psychopathology.

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 one's 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 Spearman's 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.

No regional gray matter volume reduction observed in young Japanese people at ultra-high risk for psychosis: A voxel-based morphometry study.

OBJECTIVES: Structural brain magnetic resonance imaging studies of individuals at ultra-high risk (UHR) for psychosis have shown subtle but widespread reductions in baseline gray matter volume (GMV) in the frontal, temporal, and limbic regions compared with healthy controls (HC). These regions coincide with regions of reduced GMV in patients with established psychosis and have led to the consideration of structural changes in UHR as a potential biomarker for future transition to psychosis. However, most studies have been from Europe, North America, and Australia, with few reports from other regions, and two recent studies from Asian countries have failed to detect regional GMV reduction in UHR, suggesting the need for further analysis of an Asian sample. In this study, we investigated GMV reduction in Japanese UHR subjects. RESULTS: The study used voxel-based morphometry to compare magnetic resonance imaging brain scans between 45 UHR individuals recruited by a specialist and 33 HCs. This showed no significant GMV reduction in the UHR group compared with the healthy control group. This negative result may be attributable to characteristics of Asian samples, such as a low prevalence of illicit drug use, or to the heterogeneous nature of UHR subjects.

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 Organization's 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.

Increased Occipital Gyrification and Development of Psychotic Disorders in Individuals With an At-Risk Mental State: A Multicenter Study.

BACKGROUND: Anomalies of brain gyrification have been reported in schizophrenia, possibly reflecting its neurodevelopmental pathology. However, it remains elusive whether individuals at risk for psychotic disorders exhibit deviated gyrification patterns, and whether such findings, if present, are predictive of transition to psychotic disorders. METHODS: This multicenter magnetic resonance imaging study investigated brain gyrification and its relationship to later transition to psychotic disorders in a large sample of at-risk mental state (ARMS) individuals. T1-weighted magnetic resonance imaging scans were obtained from 104 ARMS individuals, of whom 21 (20.2%) exhibited the transition to psychotic disorders during clinical follow-up (mean = 4.9 years, SD = 2.6 years), and 104 healthy control subjects at 4 different sites. The local gyrification index (LGI) of the entire cortex was compared across the groups using FreeSurfer software. RESULTS: Compared with the control subjects, ARMS individuals showed a significantly higher LGI in widespread cortical areas, including the bilateral frontal, temporal, parietal, and occipital regions, which was partly associated with prodromal symptomatology. ARMS individuals who exhibited the transition to psychotic disorders showed a significantly higher LGI in the left occipital region compared with individuals without transition. CONCLUSIONS: These findings suggested that increased LGI in diverse cortical regions might represent vulnerability to psychopathology, while increased LGI in the left occipital cortex might be related to subsequent manifestation of florid psychotic disorders as a possible surrogate marker.

Reduced Thickness of the Anterior Cingulate Cortex in Individuals With an At-Risk Mental State Who Later Develop Psychosis.

BACKGROUND: Despite the fact that only a part of the individuals with at-risk mental state (ARMS) for psychosis do develop psychosis, biological markers of future transition to psychosis have not been well documented. Structural abnormality of the anterior cingulate gyrus (ACG), which probably exists prior to the onset of psychosis, could be such a risk marker. METHODS: We conducted a multicenter magnetic resonance imaging (MRI) study of 3 scanning sites in Japan. 1.5-T 3D MRI scans were obtained from 73 ARMS subjects and 74 age- and gender-matched healthy controls. We measured thickness, volume, and surface area of the ACG using labeled cortical distance mapping and compared these measures among healthy controls, ARMS subjects who later converted to overt psychosis (ARMS-C), and those who did not (ARMS-NC). RESULTS: Seventeen of 73 (23%) ARMS subjects developed overt psychosis within the follow-up period. The thickness of the left ACG was significantly reduced in ARMS-C relative to healthy subjects (P = .026) while both ARMS-C (P = .001) and ARMS-NC (P = .01) had larger surface areas of the left ACG compared with healthy controls. CONCLUSION: Further studies will be needed to identify potential markers of future transition to psychosis though cortical thinning of the ACG might be one of the candidates.

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). Pearson's 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.

Correction: Criticism and Depression among the Caregivers of At-Risk Mental State and First-Episode Psychosis Patients.

[This corrects the article DOI: 10.1371/journal.pone.0149875.].

Criticism and Depression among the Caregivers of At-Risk Mental State and First-Episode Psychosis Patients.

Expressed emotion (EE), especially criticism, is an important predictor of outcomes for the patient for a wide range of mental health problems. To understand complex links between EE and various relevant variables in early phase psychosis, this study examined criticism, distress of caregivers, other patients', and caregivers' variables, and links between criticism and these variables in those with at-risk mental state (ARMS) for psychosis and first-episode psychosis (FEP). The participants were 56 patients (mean age 18.8 ± 4.2 years) with ARMS and their caregivers (49.4 ± 5.8 years) and 43 patients (21.7 ± 5.2 years) with FEP and their caregivers (49.3 ± 7.4 years). We investigated criticisms made by caregivers using the Japanese version of the Family Attitude Scale and caregiver depressive symptoms via the self-report Beck Depression Inventory. We also assessed psychiatric symptoms and functioning of the patients. Approximately one-third of caregivers of patients with ARMS or FEP had depressive symptoms, predominately with mild-to-moderate symptom levels, whereas only a small portion exhibited high criticism. The level of criticism and depression were comparable between ARMS and FEP caregivers. The link between criticism, caregivers' depression, and patients' symptoms were observed in FEP but not in ARMS caregivers. These findings imply that the interaction between criticism and caregivers' and patients' mental states may develop during or after the onset of established psychosis and interventions for the caregivers should be tailored to the patient's specific stage of illness. Interventions for FEP caregivers should target their emotional distress and include education about patient's general symptoms.

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.

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.