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Background Patients with schizophrenia (SCZ) display impaired executive functions compared with healthy controls (HCs). Furthermore, unaffected first-degree relatives (FRs) of patients with SCZ independently perform worse executive functions than do HCs. However, few studies have investigated the differences in executive functions assessed among patients with SCZ, FRs, and HCs, and the findings are inconsistent. Methods We investigated diagnostic differences in executive functions, namely (1) numbers of categories achieved (CA), (2) total errors (TE), and (3) percentage of perseverative errors of Nelson types (%PEN), using the Wisconsin card sorting test among patients with SCZ (n = 116), unaffected FRs (n = 62), and HCs (n = 146) at a single institute. Correlations between these executive functions and clinical variables were investigated. Results Significant differences existed in all executive functions among diagnostic groups (CA, F2,319 = 15.5, P = 3.71 × 10–7; TE, F2,319 = 16.2, P = 2.06 × 10–7; and %PEN, F2,319 = 21.3, P = 2.15 × 10–9). Patients with SCZ had fewer CA and more TE and %PEN than those of HCs (CA, Cohen’s d = −0.70, P = 5.49 × 10–8; TE, d = 0.70, P = 5.62 × 10–8; and %PEN, d = 0.82, P = 2.85 × 10−10) and FRs (TE, d = 0.46, P = 3.73 × 10–3 and %PEN, d = 0.38, P = .017). Of the 3 executive functions, CA and %PEN of FRs were intermediately impaired between patients with SCZ and HCs (CA, d = −0.41, P = .011 and %PEN, d = 0.41, P = .012). In contrast, no significant difference in TE existed between FRs and HCs (d = 0.22, P = .18). Although CA and TE were affected by the duration of illness (P .017). Conclusions Executive function, particularly %PEN, could be a useful intermediate phenotype for understanding the genetic mechanisms implicated in SCZ pathophysiology.

Schizophrenia patients (SCZ) display widespread cognitive deficits that are strongly associated with functional outcomes. Cognitive impairments occur along a genetic continuum among SCZ, their unaffected first-degree relatives (FRs) and healthy controls (HCs). Although SCZ impairs the premorbid intelligence quotient (IQ) and causes a subsequent intelligence decline (ID), a decrease in present IQ from the premorbid level, it remains unclear when during the illness course these impairments develop. Differences in premorbid and present IQ and ID were investigated among 125 SCZ, 61 FRs and 107 HCs, using analysis of covariance and a paired t-test. Furthermore, these subjects were classified into preserved and deteriorated IQ groups based on the degree of ID, and we investigated which factors contribute to this classification. We found significant differences in premorbid and present IQ among the diagnostic groups. Compared with HCs, SCZ and FRs displayed lower premorbid and present IQ. There was no significant difference in premorbid IQ between SCZ and FRs, but SCZ had a significantly lower present IQ than FRs. Only SCZ showed a significant ID. As most FRs and HCs did not display an ID, there were fewer subjects with deteriorated IQ among FRs and HCs than among SCZ. Subjects with preserved IQ showed higher educational attainment than those with deteriorated IQ among SCZ and FRs. These findings suggest that the impairment of premorbid IQ and the ID in SCZ become evident before and around the time of onset, respectively, and different pathophysiological mechanisms might be related to these impairments.

Background Cigarette smoking is consistently more common among schizophrenia patients than the general population worldwide; however, the findings of studies in Japan are inconsistent. Recently, the smoking rate has gradually decreased among the general population. Methods We performed a meta-analysis of smoking status in a large Japanese cohort of (1) 1845 schizophrenia patients and 196845 general population and (2) 842 schizophrenia patients and 766 psychiatrically healthy controls from 12 studies over a 25-year period, including 301 patients and 131 controls from our study. Results In our case-control sample, schizophrenia patients had a significantly higher smoking rate than healthy controls (P=.031). The proportion of heavy smokers (P=.027) and the number of cigarettes smoked per day (P=8.20×10–3) were significantly higher among schizophrenia patients than healthy controls. For the smokers in the schizophrenia group, atypical antipsychotics dosage was positively correlated with cigarettes per day (P=1.00×10–3). A meta-analysis found that schizophrenia patients had a higher smoking rate than the general population for both men (OR=1.53, P=.035; schizophrenia patients, 52.9%; general population, 40.1%) and women (OR=2.40, P=1.08×10–5; schizophrenia patients, 24.4%; general population, 11.8%). In addition, male schizophrenia patients had a higher smoking rate than male healthy controls (OR=2.84, P=9.48×10–3; schizophrenia patients, 53.6%; healthy controls, 32.9%), but the difference was not significant for women (OR=1.36, P=.53; schizophrenia patients, 17.0%; healthy controls,14.1%). Among both males and females, schizophrenia patients had a higher smoking rate than both the general population (OR=1.88, P=2.60×10–5) and healthy controls (OR=2.05, P=.018). These rates were not affected by the patients’ recruitment year (P>.05). The cigarettes per day values of schizophrenia patients and the general population were 22.0 and 18.8, respectively. Conclusions Schizophrenia patients are approximately 2 times more likely to smoke than the general population and healthy controls based on data collected over a decade in Japan.

Personality is one of important factors in the pathogenesis of schizophrenia because it affects patients' symptoms, cognition and social functioning. Several studies have reported specific personality traits in patients with schizophrenia compared with healthy subjects. However, the results were inconsistent among studies. The NEO Five-Factor Inventory (NEO-FFI) measures five personality traits: Neuroticism (N), Extraversion (E), Openness (O), Agreeableness (A) and Conscientiousness (C). Here, we performed a meta-analysis of these personality traits assessed by the NEO-FFI in 460 patients with schizophrenia and 486 healthy subjects from the published literature and investigated possible associations between schizophrenia and these traits. There was no publication bias for any traits. Because we found evidence of significant heterogeneity in all traits among the studies, we applied a random-effect model to perform the meta-analysis. Patients with schizophrenia showed a higher score for N and lower scores for E, O, A and C compared with healthy subjects. The effect sizes of these personality traits ranged from moderate to large. These differences were not affected by possible moderator factors, such as gender distribution and mean age in each study, expect for gender effect for A. These findings suggest that patients with schizophrenia have a different personality profile compared with healthy subjects.

BackgroundReduced gray matter volumes in the superior temporal gyrus (STG) have been reported in patients with schizophrenia. Such volumetric abnormalities might denote alterations in cortical thickness, surface area, local gyrification or all of these factors. The STG can be anatomically divided into five subregions using automatic parcellation in FreeSurfer: lateral aspect of the STG, anterior transverse temporal gyrus of Heschl gyrus (HG), planum polare (PP) of the STG, planum temporale (PT) of the STG and transverse temporal sulcus.MethodsWe acquired magnetic resonance imaging (MRI) 3T scans from 40 age- and sex-matched patients with schizophrenia and 40 healthy subjects, and the scans were automatically processed using FreeSurfer. General linear models were used to assess group differences in regional volumes and detailed thickness, surface area and local gyrification.ResultsAs expected, patients with schizophrenia had significantly smaller bilateral STG volumes than healthy subjects. Of the five subregions in the STG, patients with schizophrenia showed significantly and marginally reduced volumes in the lateral aspect of the STG and PT of the STG bilaterally compared with healthy subjects. The volumetric alteration in bilateral lateral STG was derived from both the cortical thickness and surface area but not local gyrification. There was no significant laterality of the alteration in the lateral STG between patients and controls and no correlation among the structures and clinical characteristics.ConclusionsThese findings suggest that of five anatomical subregions in the STG, the lateral STG is one of the most meaningful regions for brain pathophysiology in schizophrenia.

Schizophrenia patients have increased mortality and morbidity, mainly due to premature cardiovascular disease resulting from decreased physical activity (PA). However, which PA intensity is impaired in the patients and how factors such as social function and quality of life (QoL) are related to decreased PA is unknown. To assess PA, social function and QoL, the International Physical Activity Questionnaire (IPAQ), Social Functioning Scale (SFS) and Schizophrenia Quality of Life Scale (SQLS), respectively, were used in 109 schizophrenia patients and 69 healthy subjects. A meta-analysis comparing PA intensities (vigorous, moderate and light) assessed by the single PA measurement between schizophrenia patients and healthy subjects after including our case–control sample was performed. Furthermore, the effects of social function and QoL on each level of PA intensity were investigated in patients and controls. The meta-analysis in 212 schizophrenia patients and 132 healthy subjects revealed that patients showed lower total PA, particularly vigorous PA, than controls (I2 = 0, Hedges’ g = − 0.41, P = 2.80 × 10−4). The decreased total PA was correlated with impaired total SFS scores (β = 0.24, P = 2.86 × 10−3), withdrawal (β = 0.23, P = 3.74 × 10−3) and recreation (β = 0.23, P = 3.49 × 10−3) without significant heterogeneity between patients and controls. In contrast, the decreased total PA was affected by low independence–performance (β = 0.22, P = 0.034), employment/occupation (β = 0.27, P = 8.74 × 10−3), psychosocial (β = − 0.24, P = 0.021) and motivation/energy (β = − 0.26, P = 0.013), but only in patients. Similar findings were obtained for vigorous PA but not moderate or light PA. Our findings suggest that the impaired vigorous PA in schizophrenia patients may be mediated by schizophrenia-specific factors of social functioning and QoL. Understanding these factors has important implications for increasing PA participation in schizophrenia patients.

Cognitive impairments are a core feature in schizophrenia patients (SCZ) and are also observed in first-degree relatives (FR) of SCZ. However, substantial variability in the impairments exists within and among SCZ, FR and healthy controls (HC). A cluster-analytic approach can group individuals based on profiles of traits and create more homogeneous groupings than predefined categories. Here, we investigated differences in the Brief Assessment of Cognition in Schizophrenia (BACS) neuropsychological battery (six subscales) among SCZ, unaffected FR and HC. To identify three homogeneous and meaningful cognitive groups regardless of categorical diagnoses (SCZ, FR and HC), cognitive clustering was performed, and differences in the BACS subscales among the cognitive cluster groups were investigated. Finally, the effects of diagnosis and cognition on brain volumes were examined. As expected, there were significant differences in the five BACS subscales among the diagnostic groups. The cluster-analytic approach generated three meaningful subgroups: (i) neuropsychologically normal, (ii) intermediate impaired and (iii) widespread impaired. The cognitive subgroups were mainly affected by the clinical diagnosis, and significant differences in all BACS subscales among clusters were found. The effects of the diagnosis and cognitive clusters on brain volumes overlapped in the frontal, temporal and limbic regions. Frontal and temporal volumes were mainly affected by the diagnosis, whereas the anterior cingulate cortex (ACC) volumes were affected by the additive effects of diagnosis and cognition. Our findings demonstrate a cognitive continuum among SCZ, FR and HC and support the concept of cognitive impairment and the related ACC volumes as intermediate phenotypes in SCZ., Highlights • Cognitive impairments in the BACS subscales were a continuum among SCZ, FR and HC. • Cognitive clustering based on the BACS regardless of clinical diagnosis was performed. • Neuropsychologically normal, intermediately impaired and widespread impaired cognitive clusters were identified. • The cognitive clusters were mainly affected by the clinical diagnosis (SCZ, FR and HC). • Frontal and temporal volumes were mainly affected by the diagnosis. • The ACC volumes were affected by the additive effects of diagnosis and cognition.

Family history (FH) is predictive of the development of major psychiatric disorders (PSY). Familial psychiatric disorders are largely a consequence of genetic factors and typically exhibit more severe impairments. Decreased prefrontal activity during verbal fluency testing (VFT) may constitute an intermediate phenotype for PSY. We investigated whether familial PSY were associated with a greater severity of prefrontal dysfunction in accordance with genetic loading. We measured prefrontal activity during VFT using near-infrared spectroscopy (NIRS) in patients with schizophrenia (SCZ, n = 45), major depressive disorder (MDD, n = 26) or bipolar disorder (BIP, n = 22) and healthy controls (HC, n = 51). We compared prefrontal activity among patients with or without FH and HC. Patients in the SCZ, MDD and BIP patient groups had lower prefrontal activity than HC subjects. Patients with and without FH in all diagnostic groups had lower prefrontal activity than HC subjects. Moreover, SCZ patients with FH had lower prefrontal activity than SCZ patients without FH. When we included patients with SCZ, MDD or BIP in the group of patients with PSY, the effects of psychiatric FH on prefrontal activity were enhanced. These findings demonstrate the association of substantially more severe prefrontal dysfunction with higher genetic loading in major psychiatric disorders.

A new efficient dihydroperoxidation protocol of a wide variety of carbonyl compounds with molecular oxygen, anthracene, and 2-propanol under light irradiation afforded their corresponding gem-dihydroperoxides in high yields.

Background Cognitive impairments are a core feature in schizophrenia patients and are also observed in first-degree relatives of the schizophrenia patients. However, substantial variability in the impairments exists within and among schizophrenia patients, first-degree relatives and healthy controls. A cluster-analytic approach can group individuals based on profiles of traits and create more homogeneous groupings than predefined categories. Methods Here, we investigated differences in the Brief Assessment of Cognition in Schizophrenia (BACS) neuropsychological battery (six subscales) among 81 schizophrenia patients, 20 unaffected first-degree relatives and 25 healthy controls. To identify three homogeneous and meaningful cognitive groups regardless of categorical diagnoses (schizophrenia patients, first-degree relatives and healthy controls), cognitive clustering was performed using a k-means clustering analysis approach, and differences in the BACS subscales (verbal memory, digit sequencing, token motor, verbal fluency, symbol coding and Tower of London) among the cognitive cluster groups were investigated. Finally, the effects of diagnosis and cognition on brain volumes were examined. Results As expected, there were significant differences in the five BACS subscales among the diagnostic groups (verbal memory, F2,123=20.6, P=1.90 × 10–8; digit sequencing, F2,123=8.0, P=5.65 × 10–4; token motor, F2,123=16.0, P=6.92 × 10–7; verbal fluency, F2,123=14.8, P=1.79 × 10–6 and symbol coding, F2,123=28.8, P=5.64 × 10–11). The cluster-analytic approach generated three meaningful subgroups: (i) neuropsychologically normal (Cluster 1, N=36), (ii) intermediate impaired (Cluster 2, N=60) and (iii) widespread impaired (Cluster 3, N=30). The cognitive subgroups were mainly affected by the clinical diagnosis (χ2=46.7, P=5.33 × 10-10), and significant differences in all BACS subscales among clusters were found (verbal memory, F2,123=64.1, P=8.49 × 10–20; digit sequencing, F2,123=35.7, P=5.89 × 10–13; token motor, F2,123=71.7, P=2.29 × 10–21; verbal fluency, F2,123=84.2, P=9.05 × 10–24; symbol coding, F2,123=115.6, P=5.70 × 10–29 and Tower of London, F2,123=6.9, P=1.43 × 10–3). The effects of the diagnosis (SCZ

As part of a new thermal response test (TRT) and to determine ground thermal conductivities, vertical temperature profiles were obtained using retrievable optical fiber sensors inserted into the U-tubes of two ground heat exchangers (GHEs) installed at Maebaru City (Fukuoka, Kyushu) and Kushiro City (Hokkaido), Japan. Measured profiles and outlet temperatures from TRTs were history-matched with the cylindrical source function. Nonlinear regression was used to estimate the vertical distribution of ground thermal conductivities. The computed distribution is consistent with measured data indicating both the reliability of the optical fiber thermometer and TRT interpretation. It is expected that TRTs and optical fiber thermometers will prove to be increasingly useful for optimizing the depth of the GHEs installed in heterogeneous formations, and consequently will minimize installation costs of geothermal heat pump systems.

The latest genome-wide association study of schizophrenia identified 108 distinct genomic loci that contribute to schizophrenia. Brain development and function depend on the precise regulation of gene expression. The expression of many genes is differentially regulated across brain regions and developmental time points. We investigated the specific gene expression patterns arising from the 108 schizophrenia-associated loci using multiple publicly available databases and multiple regional brain datasets from developing and adult post-mortem human brains. The temporal-spatial expression analysis revealed that the genes in these loci were intensively enriched in the cortex during several developmental stages. These cortex-specific genes were particularly expressed in the fetal brain and adult neocortex.

A new convenient metal-free oxidation protocol of a wide variety of alkenes with molecular oxygen and benzaldehyde under visible light irradiation of fluorescent lamp afforded their corresponding epoxides in 49―99% yields.

We developed an efficient dihydroperoxidation protocol of various carbonyl compounds with molecular oxygen and anthraquinone in 2-propanol under visible light irradiation with a fluorescent lamp, which produced corresponding gem-dihydroperoxides in high yields.

A new efficient dihydroperoxidation protocol of a wide variety of carbonyl compounds with molecular oxygen, anthracene, and 2-propanol under light irradiation afforded their corresponding gem-dihydroperoxides in high yields.

gem-Dihydroperoxides were easily obtained from the corresponding carbonyl compounds in high yields through a catalyst-free method with aqueous H2O2 (35%) in 1,2-dimethoxyethane at room temperature.

gem-Dihydroperoxides were easily obtained from the corresponding carbonyl compounds in high yields through a catalyst-free method with aqueous H(2)O(2) (35%) in 1,2-dimethoxyethane at room temperature.

We developed an efficient dihydroperoxidation protocol of various carbonyl compounds with molecular oxygen and anthraquinone in 2-propanol under visible light irradiation with a fluorescent lamp, which produced corresponding gem-dihydroperoxides in high yields.