Shimako Nishiyama

Gray matter changes in subjects at high risk for developing psychosis and first-episode schizophrenia: a voxel-based structural MRI study

Objectives: The aim of the present study was to use a voxel-based magnetic resonance imaging method to investigate the neuroanatomical characteristics in subjects at high risk of developing psychosis compared with those of healthy controls and first-episode schizophrenia patients. Methods: This study included 14 subjects with at-risk mental state (ARMS), 34 patients with first-episode schizophrenia, and 51 healthy controls. We used voxel-based morphometry with the Diffeomorphic Anatomical Registration through Exponentiated Lie Algebra tools to investigate the whole-brain difference in gray matter volume among the three groups. Results: Compared with the healthy controls, the schizophrenia patients showed significant gray matter reduction in the left anterior cingulate gyrus. There was no significant difference in the gray matter volume between the ARMS and other groups. Conclusion: The present study suggests that alteration of the anterior cingulate gyrus may be associated with development of frank psychosis. Further studies with a larger ARMS subjects would be required to examine the potential role of neuroimaging methods in the prediction of future transition into psychosis.

Schizotypal disorder and schizophrenia: A profile analysis of neuropsychological functioning in Japanese patients

This study compares neuropsychological functioning in a Japanese schizophrenia spectrum disorder group and a group of healthy Japanese volunteers. Participants were 37 patients diagnosed with schizophrenia, 28 schizotypal patients, and 99 psychiatrically-normal volunteers. A wide range of cognitive measures were examined. All participants completed a Japanese version of a neuropsychological battery assessing executive function, working memory, processing speed, language, verbal memory, and spatial organization. Comparisons of neuropsychological function demonstrated similarities and differences between patients diagnosed with schizotypal disorder and those diagnosed with schizophrenia. Impairments in verbal memory, language, and processing speed were common to both patient groups and may represent a vulnerability to schizophrenia. Impairments in aspects of working memory, spatial organization and executive function were preferentially observed in schizophrenia and may be features of the overt manifestation of psychosis. Possible differences in the contributions of prefrontal and temporo-limbic structures provide direction for further studies.

Increased pituitary volume in subjects at risk for psychosis and patients with first-episode schizophrenia.

Enlarged pituitary gland has been reported in schizophrenia, possibly reflecting hypothalamic–pituitary–adrenal hyperactivity. The aim of the present study was to examine whether individuals at risk of psychosis also have similar changes.

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.

Increased Frontal Gyrification Negatively Correlates with Executive Function in Patients with First-Episode Schizophrenia

Abstract Previous neuroimaging studies of gyrification, a possible marker of early neurodevelopment, in schizophrenia patients have reported inconsistent results. In addition, it remains unclear whether aberrant gyrification in schizophrenia patients, if present, is associated with cognitive impairment, which is one of the core features of schizophrenia. Magnetic resonance images were obtained from 62 patients with first‐episode schizophrenia and 57 healthy control subjects. Using FreeSurfer software, local gyrification index (LGI) of the entire cortex was compared between the groups. The relationship between LGI and performance in the Wisconsin Card Sorting Test (WCST) was also examined in a subgroup of patients (n= 28). Compared with the controls, the patients showed a significantly higher LGI in a wide range of bilateral frontal regions as well as in the right inferior parietal and bilateral occipital regions. The number of WCST categories archived in patients was negatively correlated with the LGI mainly in the rostral middle frontal and anterior cingulate regions in the right hemisphere. Our findings suggested a widespread hypergyrification pattern in schizophrenia patients, which supported early neurodevelopmental abnormalities. Our results also suggested that executive dysfunction in schizophrenia patients may be at least partly related to aberrant neurodevelopment, especially in the right frontal regions.

Possible relation between olfaction and anxiety in healthy subjects

While olfaction is a sense closely associated with the limbic system and emotions, the relation between emotional status and olfactory functioning has not been well documented. This study aimed to examine the possible effect of anxiety on olfaction in healthy subjects.

Associations between daily living skills, cognition, and real-world functioning across stages of schizophrenia; a study with the Schizophrenia Cognition Rating Scale Japanese version

Cognitive function is impaired in patients with schizophrenia-spectrum disorders, even in their prodromal stages. Specifically, the assessment of cognitive abilities related to daily-living functioning, or functional capacity, is important to predict long-term outcome. In this study, we sought to determine the validity of the Schizophrenia Cognition Rating Scale (SCoRS) Japanese version, an interview-based measure of cognition relevant to functional capacity (i.e. co-primary measure). For this purpose, we examined the relationship of SCoRS scores with performance on the Brief Assessment of Cognition in Schizophrenia (BACS) Japanese version, a standard neuropsychological test battery, and the Social and Occupational Functioning Assessment Scale (SOFAS), an interview-based social function scale. Subjects for this study (n = 294) included 38 patients with first episode schizophrenia (FES), 135 with chronic schizophrenia (CS), 102 with at-risk mental state (ARMS) and 19 with other psychiatric disorders with psychosis. SCoRS scores showed a significant relationship with SOFAS scores for the entire subjects. Also, performance on the BACS was significantly correlated with SCoRS scores. These associations were also noted within each diagnosis (FES, CS, ARMS). These results indicate the utility of SCoRS as a measure of functional capacity that is associated both with cognitive function and real-world functional outcome in subjects with schizophrenia-spectrum disorders.

Altered depth of the olfactory sulcus in subjects at risk of psychosis

STAI trait at intake 65.3 ± 10.9 – – STAI state at intake 58.4 ± 11.3 – – BDI at intake 24.1 ± 10.0 – – SAPS total at scanning 20.4 ± 10.9 – – SANS total at scanning 48.5 ± 19.4 – – Intracranial volume (cm) 1460 ± 132 1500 ± 146 F (1, 37) = 2.45, p = 0.126 Olfactory sulcus length (mm) F (1, 36) = 0.71, p = 0.404 Left 43.0 ± 2.7 43.9 ± 2.6 Right 43.1 ± 3.4 43.9 ± 3.1 Olfactory sulcus depth (mm) F (1, 36) = 19.62, p b 0.001 Left 11.6 ± 1.4 13.7 ± 1.0 Right 12.3 ± 1.0 14.3 ± 1.5

Quality of life in individuals with attenuated psychotic symptoms: Possible role of anxiety, depressive symptoms, and socio-cognitive impairments

Individuals with Clinical High-Risk state for Psychosis (CHR-P) are reported to exhibit impaired quality of life (QOL) similar to that observed in schizophrenia, but its determinants remain unclear. We investigated the QOL of 33 subjects with CHR-P, 45 patients with schizophrenia, and 63 healthy subjects using the Quality of Life Scale (QLS). The CHR-P and schizophrenia groups were administered the Brief Assessment of Cognition in Schizophrenia (BACS), the Schizophrenia Cognition Rating Scale (SCoRS), and the Social and Occupational Functioning Assessment Scale (SOFAS) for socio-cognitive functions; and the Positive and Negative Syndrome Scale (PANSS) and the State-Trait Anxiety Inventory for clinical symptoms. The CHR-P group was also assessed using the Beck Depression Inventory. The CHR-P and schizophrenia groups had a significantly lower QLS score to the same degree compared with controls, which was predominantly associated with the SOFAS, SCoRS, and PANSS negative/general scores. For the CHR-P, the severity of anxiety and depressive symptoms was also correlated with a lower QLS score. Regression analyses demonstrated that the QLS score was predicted by SOFAS (for both groups) and SCoRS (for CHR-P) scores. Our findings suggest the importance of addressing socio-cognitive dysfunctions as well as anxiety and depressive symptoms for better QOL in CHR-P.

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.