Haruo Fujino

Abnormal asymmetries in subcortical brain volume in schizophrenia

Subcortical structures, which include the basal ganglia and parts of the limbic system, have key roles in learning, motor control and emotion, but also contribute to higher-order executive functions. Prior studies have reported volumetric alterations in subcortical regions in schizophrenia. Reported results have sometimes been heterogeneous, and few large-scale investigations have been conducted. Moreover, few large-scale studies have assessed asymmetries of subcortical volumes in schizophrenia. Here, as a work completely independent of a study performed by the ENIGMA consortium, we conducted a large-scale multisite study of subcortical volumetric differences between patients with schizophrenia and controls. We also explored the laterality of subcortical regions to identify characteristic similarities and differences between them. T1-weighted images from 1680 healthy individuals and 884 patients with schizophrenia, obtained with 15 imaging protocols at 11 sites, were processed with FreeSurfer. Group differences were calculated for each protocol and meta-analyzed. Compared with controls, patients with schizophrenia demonstrated smaller bilateral hippocampus, amygdala, thalamus and accumbens volumes as well as intracranial volume, but larger bilateral caudate, putamen, pallidum and lateral ventricle volumes. We replicated the rank order of effect sizes for subcortical volumetric changes in schizophrenia reported by the ENIGMA consortium. Further, we revealed leftward asymmetry for thalamus, lateral ventricle, caudate and putamen volumes, and rightward asymmetry for amygdala and hippocampal volumes in both controls and patients with schizophrenia. Also, we demonstrated a schizophrenia-specific leftward asymmetry for pallidum volume. These findings suggest the possibility of aberrant laterality in neural pathways and connectivity patterns related to the pallidum in schizophrenia.

Glutamate Networks Implicate Cognitive Impairments in Schizophrenia: Genome-Wide Association Studies of 52 Cognitive Phenotypes

Cognitive impairments are a core feature in patients with schizophrenia. These deficits could serve as effective tools for understanding the genetic architecture of schizophrenia. This study investigated whether genetic variants associated with cognitive impairments aggregate in functional gene networks related to the pathogenesis of schizophrenia. Here, genome-wide association studies (GWAS) of a range of cognitive phenotypes relevant to schizophrenia were performed in 411 healthy subjects. We attempted to replicate the GWAS data using 257 patients with schizophrenia and performed a meta-analysis of the GWAS findings and the replicated results. Because gene networks, rather than a single gene or genetic variant, may be strongly associated with the susceptibility to schizophrenia and cognitive impairments, gene-network analysis for genes in close proximity to the replicated variants was performed. We observed nominal associations between 3054 variants and cognitive phenotypes at a threshold of P < 1.0 × 10− 4. Of the 3054 variants, the associations of 191 variants were replicated in the replication samples (P < .05). However, no variants achieved genome-wide significance in a meta-analysis (P > 5.0 × 10− 8). Additionally, 115 of 191 replicated single nucleotide polymorphisms (SNPs) have genes located within 10 kb of the SNPs (60.2%). These variants were moderately associated with cognitive phenotypes that ranged from P = 2.50 × 10− 5 to P = 9.40 × 10− 8. The genes located within 10 kb from the replicated SNPs were significantly grouped in terms of glutamate receptor activity (false discovery rate (FDR) q = 4.49 × 10− 17) and the immune system related to major histocompatibility complex class I (FDR q = 8.76 × 10− 11) networks. Our findings demonstrate that genetic variants related to cognitive trait impairment in schizophrenia are involved in the N-methyl-d-aspartate glutamate network.

A Meta-Analysis of Hypnosis for Chronic Pain Problems: A Comparison Between Hypnosis, Standard Care, and Other Psychological Interventions

Abstract Hypnosis is regarded as an effective treatment for psychological and physical ailments. However, its efficacy as a strategy for managing chronic pain has not been assessed through meta-analytical methods. The objective of the current study was to conduct a meta-analysis to assess the efficacy of hypnosis for managing chronic pain. When compared with standard care, hypnosis provided moderate treatment benefit. Hypnosis also showed a moderate superior effect as compared to other psychological interventions for a nonheadache group. The results suggest that hypnosis is efficacious for managing chronic pain. Given that large heterogeneity among the included studies was identified, the nature of hypnosis treatment is further discussed.

Performance on the Wechsler Adult Intelligence Scale-III in Japanese patients with schizophrenia.

Patients with schizophrenia have been reported to perform worse than non‐schizophrenic populations on neuropsychological tests, which may be affected by cultural factors. The aim of this study was to examine the performance of a sizable number of patients with schizophrenia on the Japanese version of the Wechsler Adult Intelligence Scale‐III (WAIS‐III) compared with healthy controls.

Whole-exome sequencing and neurite outgrowth analysis in autism spectrum disorder

Autism spectrum disorder (ASD) is a complex group of clinically heterogeneous neurodevelopmental disorders with unclear etiology and pathogenesis. Genetic studies have identified numerous candidate genetic variants, including de novo mutated ASD-associated genes; however, the function of these de novo mutated genes remains unclear despite extensive bioinformatics resources. Accordingly, it is not easy to assign priorities to numerous candidate ASD-associated genes for further biological analysis. Here we developed a convenient system for identifying an experimental evidence-based annotation of candidate ASD-associated genes. We performed trio-based whole-exome sequencing in 30 sporadic cases of ASD and identified 37 genes with de novo single-nucleotide variations (SNVs). Among them, 5 of those 37 genes, POGZ, PLEKHA4, PCNX, PRKD2 and HERC1, have been previously reported as genes with de novo SNVs in ASD; and consultation with in silico databases showed that only HERC1 might be involved in neural function. To examine whether the identified gene products are involved in neural functions, we performed small hairpin RNA-based assays using neuroblastoma cell lines to assess neurite development. Knockdown of 8 out of the 14 examined genes significantly decreased neurite development (P<0.05, one-way analysis of variance), which was significantly higher than the number expected from gene ontology databases (P=0.010, Fishers exact test). Our screening system may be valuable for identifying the neural functions of candidate ASD-associated genes for further analysis and a substantial portion of these genes with de novo SNVs might have roles in neuronal systems, although further detailed analysis might eliminate false positive genes from identified candidate ASD genes.

Estimated cognitive decline in patients with schizophrenia: A multicenter study

Studies have reported that cognitive decline occurs after the onset of schizophrenia despite heterogeneity in cognitive function among patients. The aim of this study was to investigate the degree of estimated cognitive decline in patients with schizophrenia by comparing estimated premorbid intellectual functioning and current intellectual functioning.

Predicting employment status and subjective quality of life in patients with schizophrenia

Although impaired social functioning, particularly poor employment status, is a cardinal feature of patients with schizophrenia and leads to decreased quality of life (QOL), few studies have addressed the relationship between these two clinical issues. The aim of this study was to determine whether employment status predicts subjective QOL and to evaluate a model in which functional capacity mediates the relationship between general cognitive performance and employment status. Ninety-three patients with schizophrenia were administered a comprehensive battery of cognitive tests, the UCSD Performance-based Skills Assessment-Brief version (UPSA-B), the Social Functioning Scale (SFS), and the Subjective Quality of Life Scale (SQLS). First, we evaluated a model for predicting the employment/occupation subscale score of the SFS using path analysis, and the model fitted well (χ2 (4) = 3.6, p = 0.46; CFI = 1.0; RMSEA < 0.001, with 90% CIs: 0–0.152). Employment status was predicted by negative symptoms and functional capacity, which was in turn predicted by general cognitive performance. Second, we added subjective QOL to this model. In a final path model, QOL was predicted by negative symptoms and employment status. This model also satisfied good fit criteria (χ2 (7) = 10.3, p = 0.17; CFI = 0.987; RMSEA = 0.072, with 90% CIs: 0–0.159). The UPSA-B and SFS scores were moderately correlated with most measures of cognitive performance. These results support the notion that better employment status enhances subjective QOL in patients with schizophrenia.

Standing postural instability in patients with schizophrenia: Relationships with psychiatric symptoms, anxiety, and the use of neuroleptic medications.

The purpose of this study was to assess postural instability in patients with schizophrenia using a pressure-sensitive platform and to examine the effects of anxiety, psychiatric symptoms, and the use of neuroleptic medications on postural sway. Participants were 23 patients with schizophrenia and 23 healthy controls. We found that the patients showed greater overall postural instability than the controls. Furthermore, they demonstrated greater instability when the test was performed with the eyes closed than with the eyes open. However, removal of visual input had less impact on the indices of postural instability in the patients than in the controls, suggesting that schizophrenia is associated with difficulties in integrating visual information and proprioceptive signals. Furthermore, in contrast to the controls, anxiety exacerbated postural instability in the patients. There were significant associations between postural stability and psychiatric symptoms in the patients without extrapyramidal symptoms, whereas medication dose did not significantly correlate with postural stability.

Polygenetic components for schizophrenia, bipolar disorder and rheumatoid arthritis predict risk of schizophrenia

Genome-wide association studies (GWASs) have revealed a polygenic component to the risk of Schizophrenia (SCZ) that comprises the additive effects of a large number of common independent singlenucleotide polymorphisms (SNPs) with weak effects (Purcell et al., 2009; Ripke et al., 2014). Polygenic risk profile scores (PRS) for SCZ in discovery GWAS samples explain approximately 20% of the variance in the liability for SCZ in independent target subjects (Ripke et al., 2014). An important factor in determining whether the polygenic component can predict a target trait in independent subjects is the sample size of the discovery sample (Dudbridge, 2013). The Cross-Disorder Group of the Psychiatric Genomics Consortium (PGC) examined shared polygenetic features among major psychiatric disorders [SCZ, Bipolar Disorder (BIP), Major Depression Disorder (MDD), Autism Spectrum Disorder (ASD) and Attention Deficit Hyperactivity Disorder (ADHD)] in individuals of European descent (Smoller et al., 2013) and found shared cross-disorder effects among the adultonset disorders SCZ, BIP and MDD. These findings could be due to common genetic factors for the risk of SCZ and other psychiatric disorders. To our knowledge, it is unknown whether the polygenic component can predict a target trait in an independent ethnic sample of individuals of non-European ancestry. In addition, SCZmay share a genetic component with autoimmune and/or metabolic non-psychiatric disorders. Here, we tested the hypothesis that genetic variants related to the risk of SCZ overlap with genetic variants related to psychiatric and non-psychiatric disorders by conducting a polygenic component analysis. As shown in Supplementary Table S1, we used publicly available GWASdatasets as discovery samples to calculate PRS for five psychiatric disorders [SCZ, BIP (Smoller et al., 2013), MDD (Smoller et al., 2013), ASD (Smoller et al., 2013) and ADHD (Smoller et al., 2013)] and five non-psychiatric diseases [Rheumatoid Arthritis (RA) (Stahl et al., 2010), Ulcerative Colitis (UC) (Liu et al., 2015), Crohns Disease (CD) (Liu et al., 2015), Coronary Artery Disease (CAD) (Schunkert et al., 2011) and Type 2 Diabetes (T2D) (Mahajan et al., 2014)]. Three types of GWASs for SCZ [the most recent available GWAS by the Schizophrenia Working Group of the PGC (PGC2 SCZ) (Ripke et al., 2014), PGC1 plus Swedish SCZ (PGC1 + Swe) (Ripke et al., 2013) and crossdisorder SCZ (Smoller et al., 2013)] were used as discovery samples. Furthermore, meta-analyzed data among cross-disorders or between SCZ and BIP in cross-disorder GWAS were also used. PRSs derived from these GWASswere calculated for Japanese target subjects (341 patients with SCZ and 588 controls). Details of the samples included in the discovery and target GWASs are summarized in Supplementary Methods, Results, Figs. S1–S2, and Tables S1–S4. Briefly, genotyping data from multiple sites were

Subjective experience of Dohsa-hou relaxation: a qualitative study

The body is an important aspect of the psychotherapy process, having substantial links with the development of psychological functions. This study aims to describe and categorize the subjective experiences of Dohsa-hou relaxation. Twenty university students participated in this study. Participants received three Dohsa-hou relaxation sessions and were interviewed after each session. Interview data were analyzed using content analysis, and the responses were segregated into categories. Reported experiences changed over the three sessions, with some participants reporting subjective changes in their daily lives. Through Dohsa-hou, participants eased their unintended tension and became more aware of their bodily feelings. These findings further contribute to understanding the changes in body awareness and subjective experiences.