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The present study aimed to investigate the test-retest reliability of the Wechsler Intelligence Scale for Children-Fourth edition (WISC-IV) in a sample of 138 children with autism spectrum disorder (ASD) from a child psychiatric clinic in Tokyo, Japan. The stability coefficient of the Full Scale Intelligence Quotient (FSIQ), which is composed of four indices, was very high at .83, while those of the Verbal Comprehension Index (VCI), Perceptual Reasoning Index (PRI), Working Memory Index (WMI), and Processing Speed Index (PSI) individually were moderate to high, ranging from .62 to .79. Comparisons among three age groups revealed that the coefficients for children aged 5 to 7 years tended to be lower than those for children aged 11 years and older. With respect to relative strengths and weaknesses between index scores, approximately half of children did not exhibit the same trend in the second test. These results revealed that the FSIQ and index scores are stable in the long term in children with ASD aged 11 years and older, and that the PSI and discrepancies in index scores are less stable. Thus, practitioners should take into account ecological information and the test-taking behaviors of children when interpreting WISC-IV results for children with ASD.

BackgroundSchizophrenia is a chronic relapsing psychiatric disorder that is characterized by many symptoms and has a high heritability. A previous study showed that specific lipid molecules belong to phosphatidylinositol (PI) and phosphatidylserine (PS) was reduced in the postmortem prefrontal cortex of patients with schizophrenia1. However, signaling pathways contributing to the lipid changes remain unknown. Here we performed two types of transcriptome analyses in patients with schizophrenia: an un-biased transcriptome analysis solely based on RNA-seq data and a correlation analysis between levels of gene expression and lipids.Methodology/Principal FindingsRNA-Seq analysis was performed in the postmortem prefrontal cortex from 10 subjects with schizophrenia and 5 controls. Correlation analysis between the transcriptome and lipidome from 9 subjects which are the same samples in the previous lipidomics study1 (Table 1). Extraction of differentially expressed genes (DEGs) and further sequence and functional group analysis revealed changes of gene expression levels in phosphoinositide 3-kinase (PI3K)-Akt signaling and the complement system. In addition, a correlation analysis clarified alterations in several signaling/metabolic pathways including lipid-correlated genes, most of which are not found as DEGs in transcriptome analysis alone.Table 1.Characteristics of patients from whom postmortem brain samples were obtained.Abbreviations: PMI, postmortem interval, the time that has elapsed since a person has died; DOI, duration of illness, The samples used in correlation analysis are shown by black circles.ConclusionsThis study provided results of the first integrated analysis of the schizophrenia-associated transcriptome and lipidome within the PFC and revealed that lipid-correlated alterations in the transcriptome are enriched in specific pathways including PI3K-Akt signaling.

Clozapine is currently the only effective drug for treatment-resistant schizophrenia; nonetheless, its pharmacological mechanism remains unclear, and its administration is limited because of severe adverse effects. By comparing the binding proteins of clozapine and its derivative olanzapine, which is safer but less effective than clozapine, we attempted to clarify the mechanism of action specific to clozapine.First, using the polyproline rod conjugates attached with clozapine or olanzapine, clozapine-binding proteins in extracts from the cerebra of 7-week-old ICR mice were isolated and separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify proteins. Second, the effect of clozapine on tubulin polymerization was determined turbidimetrically. Finally, the cellular effects of clozapine were observed in HeLa cells by immunofluorescence microscopy.Alpha and β tubulins were the most abundant clozapine-binding proteins. We also found that clozapine directly binds with α and β tubulin heterodimers to inhibit their polymerization to form microtubules and disturbs the microtubule network, causing mitotic arrest in HeLa cells.These results suggest that α and β tubulin heterodimers are targeted by the clozapine and the microtubules are involved in the etiology of schizophrenia.

Associations between attention-deficit/hyperactivity disorder (ADHD) and chronic pain disorders, such as fibromyalgia, have been reported. However, associations between persistent chronic nonspecific low back pain (CNLBP) and ADHD have not yet been investigated.This study aimed to investigate the positive rates of possible ADHD, as assessed by self-reported ADHD scales, in patients with persistent CNLBP, using data from self-reported questionnaires completed by patients and their families. This study also aimed to compare the self-reported scores obtained from existing standardized data for healthy individuals, and to examine whether the ADHD scale scores of patients with persistent CNLBP are associated with pain variables.Cross-sectional study.The specialized pain clinic at our university hospital.This cross-sectional study included 60 consecutive patients with persistent CNLBP who were diagnosed with a possible somatic symptom disorder and were referred to a psychiatrist in our pain clinic. The Conners' Adult ADHD Rating Scales (CAARS) self-report (CAARS-S) and observer-rated (CAARS-O) questionnaires were utilized. We investigated the CAARS scores, and the association between the CAARS subscale scores and pain variables (pain duration and pain Numeric Rating Scale) in patients with persistent CNLBP.Of the 60 patients, 19 (31.7%) were positive on both CAARS-S and CAARS-O questionnaires (T-score65). The ADHD indices, which comprised subscales of the CAARS estimating the necessity of treatment for ADHD, were significantly higher in both male and female patients with persistent CNLBP than in the Japanese standardized sample (P0.005). CAARS-S hyperactivity/restlessness, CAARS-O hyperactivity/restlessness, and the Diagnostic and Statistical Manual of Mental Disorders, fourth edition hyperactive-impulsive symptom subscale scores also correlated with the pain intensity (P0.05).In this study, ADHD tendency was evaluated using only a self-reported questionnaire. Hence in the future, accurate and precise assessments of ADHD symptoms using structured clinical interviews conducted by ADHD experts are warranted. Additionally, the study only included patients with persistent CNLBP. Therefore in the future, it will be valuable to investigate ADHD scale scores (e.g., CAARS) among patients with CNLBP and nonspecific low back pain with larger sample sizes.Our findings revealed that the subscale scores on an ADHD scale were considerably high in patients with persistent CNLBP. As a previous study of our clinical experience indicates that persistent CNLBP can be substantially relieved by administering ADHD medications, ADHD screening is warranted in the treatment of persistent CNLBP.

This study was a systematic review of research using the Wechsler Intelligence Scale for Children (WISC) with Autism Spectrum Disorder (ASD) to examine cognitive characteristics of children with ASD beyond the impact of revisions based on WISC and diagnostic criteria changes. The classic “islets of ability” was found in individuals with full-scale IQs

Benign adult familial myoclonic epilepsy (BAFME) is an autosomal dominant disease characterized by adult-onset tremulous hand movement, myoclonus, and infrequent epileptic seizures. Recently, intronic expansion of unstable TTTCA/TTTTA pentanucleotide repeats in SAMD12, TNRC6A, or RAPGEF2 was identified as pathological mutations in Japanese BAFME pedigrees. To confirm these mutations, we performed a genetic analysis on 12 Japanese BAFME pedigrees. A total of 143 participants, including 43 familial patients, 5 suspected patients, 3 sporadic nonfamilial patients, 22 unaffected familial members, and 70 unrelated controls, were screened for expanded abnormal pentanucleotide repeats in SAMD12, TNRC6A, RAPGEF2, YEAT2, MARCH6, and STARD7. DNA samples were analyzed using Southern blotting, long-range polymerase chain reaction (PCR), repeat-primed PCR, and long-range PCR followed by Southern blotting. Of the 51 individuals with clinically diagnosed or suspected BAFME, 49 carried a SAMD12 allele with an expanded TTTCA/TTTTA pentanucleotide repeat. Genetic and clinical anticipation was observed. As in previous reports, the one patient with homozygous mutant alleles showed more severe symptoms than the heterozygous carriers. In addition, screening for expanded pentanucleotide repeats in TNRC6A revealed that the frequency of expanded TTTTA repeat alleles in the BAFME group was significantly higher than in the control group. All patients who were clinically diagnosed with BAFME, including those in the original family reported by Yasuda, carried abnormally expanded TTTCA/TTTTA repeat alleles of SAMD12. Patients with BAFME also frequently carried a TTTTA repeat expansion in TNRC6A, suggesting that there may be unknown factors in the ancestry of patients with BAFME that make pentanucleotide repeats unstable.

Aim: Cognitive dysfunction and negative symptoms interfere social participation in patients with schizophrenia. Cognitive remediation has proven effective for cognitive deficits. While there are few effective treatments for the negative symptoms of schizophrenia, music therapy is expected to ameliorate negative symptoms. With the goal of improving both cognitive dysfunction and negative symptoms, we originally developed a program of Music Therapy incorporated into Cognitive Remediation (MTCR). We introduce the MTCR program and our preliminary results of conducting MTCR in patients with schizophrenia. Methods: The program was based on the NEAR (neuropsychological educational approach to cognitive remediation) program. The MTCR program uses instrumental performances and ensemble vocal performances to train cognitive functions, which consists of 30 sessions in total, with each session being 60 minutes long (45 minutes of music, 15 minutes of verbal session). The participants attended sessions semiweekly in groups of fewer than 12 members. We measured the participants’ symptoms twice, before the intervention and after the final session. For both measurements, we used the BACS and BPRS. Thirty-six individuals (26 men, 10 women; average age of 42.4 years) with schizophrenia participated in this study. They participated in an average of 28.2 sessions. Results: BACS total scores (p < 0.05), “verbal fluency” (p < 0.01) and “attention” (p < 0.02) subtests improved significantly. Overall BPRS scores were essentially unchanged, but significant improvement was observed in the “emotional withdrawal” (p < 0.05) and “blunted affect” (p < 0.07). “Hostility” (p < 0.05), “bizarre behavior” (p < 0.01), “mannerisms and posturing” (p < 0.01), and “disorientation” (p < 0.03) also improved significantly. Conclusions: The present study demonstrated that MTCR program can improve both cognitive dysfunction and negative symptoms of patients with schizophrenia, which implies that it can also potentially facilitate the social participation of such patients.

Erratum in: Fukushima J Med Sci. 2019;65(2):68-69., The present adjunct study of the Japan Environment and Children's Study (JECS) aimed to determine the occurrence of developmental disorders in Fukushima Prefecture, which was exposed to low-dose radiation. At two medical institutions in Fukushima City, we enrolled 339 pregnant women from September 2013 through May 31, 2014, who delivered 335 neonates (174 male, including one set of twins) between November 4, 2013 and November 11, 2014. The parents of four neonates declined to participate in the present study and one neonate died. Therefore, 334 families agreed to participate in additional surveys until March 2017. Child Behavior Checklists (CBCL) were mailed to all 334 families during the month of their infant's second birthday and we received 236 responses (response rate, 70%). All responses were below the 69th percentile in the CBCL, and no responses indicated significant problem behaviors. Boys tended to have higher values for items associated with developmental problems, but symptoms of autism were not evident. The mental health of the mothers indicated in the previous study might not have influenced the children. Autism spectrum disorder (ASD) is not obvious by the age of three years and thus it might become apparent as the children grow older.

Abstract. Background: Suicide is a major concern after the 2011 earthquake and nuclear accident in Fukushima. Aims: This study delineates characteristics of the disaster-related suicides in Fukushima. Method: Data provided by the Fukushima Prefectural Police and data published by the Fukushima or Japanese Government were analyzed. Numbers of disaster-related suicides and evacuees were compared among the three prefectures affected. Age, sex, occupation, and means for disaster-related suicides in Fukushima were compared with overall suicides in Fukushima or Japan. History of medical treatment, changes in job and family structure after the disaster, and signs of contemplation were examined within the disaster-related suicides of Fukushima. Results: While other prefectures have experienced a drop in disaster-related suicides, Fukushima has not. Age-standardized disaster-related suicide rates were remarkably higher in men than in women. Moreover, disaster-related suicide rates in Fukushima were higher in women in their 50s and 80s as compared with overall suicide rates in Fukushima or Japan. Limitations: No detailed comparisons were made between disaster-related and non-disaster-related suicides. Conclusion: Disaster-related suicide rates were higher in men than in women. Also, it was found that the disaster-related suicide rates of elderly women were higher compared with overall suicide rates in Japan and Fukushima. In addition, many who died by suicide showed signs of contemplation before the attempt and had started psychiatric treatment. Improvement of suicide risk assessment skills for mental health professionals and gatekeeper training among residents will be essential to prevent disaster-related suicides.

Perineuronal nets comprise chondroitin sulfate moieties and their core proteins, and their neuropathological alterations have been implicated in schizophrenia. To explore the molecular mechanism of the perineuronal net impairments in schizophrenia, we measured the immunoreactivity of chondroitin sulfate moieties, major components of perineuronal nets, in three brain regions (postmortem dorsolateral prefrontal cortex, caudate nucleus, and hippocampus) of schizophrenia patients and control subjects. Immunoblotting for chondroitin 4-sulfate and chondroitin 6-sulfate moieties revealed a significant increase in intensity of a 180 kD band of chondroitin 4-sulfate immunoreactivity in the hippocampus of patients, although we detected no significant alteration in their immunoreactivities with any other molecular sizes or in other brain regions. The levels of immunoreactivity were not correlated with postmortem interval, age, or storage time. We failed to find such an increase in a similar molecular range of the chondroitin 4-sulfate immunoreactivity in the hippocampus of the rats chronically treated with haloperidol. These results suggest that the level alteration of the chondroitin 4-sulfate moiety might contribute to the perineuronal net abnormality found in patients with schizophrenia.

Background Men score higher on mental rotation tasks compared to women and suffer from depression and anxiety at half the rate of women. The objective of this study was to confirm the gender-specific effects of depression and anxiety on mental rotation performance. Methods We collected data in non-experimental conditions from 325 university students at three universities. Participants completed rating scales of depressive and anxiety symptoms, and then simultaneously performed a mental rotation task using tablet devices. Results We observed no significant difference between men and women in the depressive and anxiety symptoms and task response time. Men had a significantly higher correct answer rate compared with women. The scores of depression and anxiety of all participants were positively correlated. Task response time correlated positively with intensity of depressive symptoms and anxiety in women, but not in men. Women with high depressive symptoms had significantly longer response times than did women with low depressive symptoms, while men had no differences due to depressive symptoms. Limitations We did not directly examine brain functions; therefore, the underlying neurobiological results are only based on previous knowledge and action data. Conclusions The pathology of depression and anxiety was reflected in the correct answer rate and response time in relation to the gender difference of brain function used in mental rotation.

Using near-infrared spectroscopy, we examined changes in the concentration of oxygenated hemoglobin ([oxy-Hb]) in the frontal lobe during a verbal fluency task in 20 patients with schizophrenia (10 patients each receiving olanzapine [OLZ] and risperidone [RIS]) and 10 healthy controls. We found that [oxy-Hb] levels in the prefrontal region were higher in the patients receiving OLZ than in those receiving RIS. These results suggest that antipsychotic drugs have different effects on cerebral hemodynamic patterns, which may reflect frontal lobe function. Further studies with a larger sample size are needed to verify our preliminary findings.

Objective: We introduce Utena’s Brief Objective Measures of 4 Axes for Psychic Function and Energy (UBOM-4), a new brief test battery for evaluating psychic function concerning intellect, emotion, volition, and imagination. To date, insufficient general population data on the UBOM have been collected. This study aimed to establish the normative values for the general population in UBOM-4 and examine the effects of age, sex, and mental health status on the values. Methods: The General Health Questionnaire, 12-item version (GHQ-12) and UBOM-4 were administered to 149 individuals working in or attending professional schools or universities (73 males, 76 females; age: 19 - 65 years). Participants were classified as healthy based on their GHQ-12 responses and psychiatrist interviews. Results: UBOM-4 measures (mean ± SD) were: pulse rate difference (PRD or UBOM-pulse), −0.72 ± 4.31 beats/min; ruler catching time (RCT or UBOM-ruler), 18.42 ± 3.73 cm; degree of randomness (DOR or UBOM-random), 0.94 ± 0.18; mean randomizing time (MRT or UBOM-time), 0.60 ± 0.31 sec. The Baum Test drawings were classified as usual (86%) and unusual patterns (14%). Sex effects were observed for RCT (UBOM-ruler) and DOR (UBOM-random), but not for PRD (UBOM-pulse) and MRT (UBOM-time). Therefore, the normative values for RCT (UBOM-ruler) (males: 17.37 ± 3.25 cm; females: 19.42 ± 3.90 cm) and DOR (UBOM-random) (males: 0.92 ± 0.18; females: 0.95 ± 0.18) should be differentiated by sex. The patterns of the Baum Test drawings were affected by age, with individuals over 51 years showing the unusual pattern more frequently (42%). Discussion: Compared to previous results for healthy individuals, the present results were similar for RCT (UBOM-ruler), DOR (UBOM-random), MRT (UBOM-time), and the drawing pattern, but different for PRD (UBOM-pulse). This difference is probably because PRD is sensitive to test situation habituation, sex of examiner, order of subtests, etc. Thus, PRD (UBOM-pulse) should be measured after the subject-examiner relationship stabilizes. Conclusion: Our results suggest that UBOM-4 can be widely used in clinical settings, utilizing the present results as a reference.

Individuals with schizophrenia exhibit cognitive impairments, which are related to impairments in social functions. This study investigated the effects of cognitive remediation on cognitive, social, and daily living impairment. Participants were individuals with schizophrenia between 20 and 60 years old (N = 44). Participants were randomly assigned to two groups: a cognitive remediation intervention group and a non-intervention control group. The control group was provided with conventional drug therapy and either day care or occupational therapy. The intervention group was provided with the "neuropsychological educational approach to cognitive remediation" developed by Medalia and co-workers. We assessed cognitive functions using the brief assessment of cognition in schizophrenia (BACS), and evaluated social and daily living functions using the global assessment of functioning (GAF) scale. Significant group by time interaction effects indicated that verbal memory, working memory, attention, and executive function showed significantly greater improvement at post-intervention for the intervention group than the control group. Social and daily living function also improved in the intervention group and improvements were maintained one year after intervention. These preliminary findings indicate that the combination of cognitive remediation and psychiatric rehabilitation is effective for facilitating improvements in cognitive function and social and daily living functions in individuals with schizophrenia.

Benign adult familial myoclonic epilepsy (BAFME) is an autosomal dominant disease characterized by adult-onset tremulous hand movement, myoclonus, and infrequent epileptic seizures. Recently, intronic expansion of unstable TTTCA/TTTTA pentanucleotide repeats in SAMD12, TNRC6A, or RAPGEF2 was identified as pathological mutations in Japanese BAFME pedigrees. To confirm these mutations, we performed a genetic analysis on 12 Japanese BAFME pedigrees. A total of 143 participants, including 43 familial patients, 5 suspected patients, 3 sporadic nonfamilial patients, 22 unaffected familial members, and 70 unrelated controls, were screened for expanded abnormal pentanucleotide repeats in SAMD12, TNRC6A, RAPGEF2, YEAT2, MARCH6, and STARD7. DNA samples were analyzed using Southern blotting, long-range polymerase chain reaction (PCR), repeat-primed PCR, and long-range PCR followed by Southern blotting. Of the 51 individuals with clinically diagnosed or suspected BAFME, 49 carried a SAMD12 allele with an expanded TTTCA/TTTTA pentanucleotide repeat. Genetic and clinical anticipation was observed. As in previous reports, the one patient with homozygous mutant alleles showed more severe symptoms than the heterozygous carriers. In addition, screening for expanded pentanucleotide repeats in TNRC6A revealed that the frequency of expanded TTTTA repeat alleles in the BAFME group was significantly higher than in the control group. All patients who were clinically diagnosed with BAFME, including those in the original family reported by Yasuda, carried abnormally expanded TTTCA/TTTTA repeat alleles of SAMD12. Patients with BAFME also frequently carried a TTTTA repeat expansion in TNRC6A, suggesting that there may be unknown factors in the ancestry of patients with BAFME that make pentanucleotide repeats unstable.

The relationships between −141C insertion/deletion (Ins/Del) polymorphisms in the dopamine D2 receptor gene and the two dopamine system integrators, i.e., dopamine- and cAMP-regulated phosphoprotein of molecular weight 32 kDa (DARPP-32) and calcineurin (CaN), are still unclear. In this study, we assessed the effect of this polymorphism on DARPP-32 and CaN protein expression in the postmortem striatum of patients with schizophrenia and control individuals. The expression levels of truncated DARPP and CaN were lower in Del allele carriers. These findings provide important insights into the mechanism by which this genotype could result in a poor response to antipsychotic drugs.

Many neuroimaging studies have demonstrated structural changes in the superior temporal gyrus (STG) in patients with schizophrenia. Several postmortem studies have reported on the pathogenesis of schizophrenia, but few reports have investigated alterations in molecules in the STG. In addition, several studies have suggested that calcineurin (CaN) inadequacy may be a risk factor for schizophrenia, but no reports about CaN expression in the STG in schizophrenia have been published. We compared the density of CaN-immunoreactive (CaN-IR) neurons in the STG from 11 patients with schizophrenia with that of 11 sex- and age-matched controls. We used immunohistochemical analysis with rabbit polyclonal antibodies against human CaN. In the STG, the density of CaN-IR neurons in layers II - VI in the group with schizophrenia was significantly higher than that in the control group. Our results confirmed pathological changes in the STG in patients with schizophrenia, suggesting that alterations in the CaN pathway play a role in the pathogenesis of schizophrenia.

Aims: To investigate rates of attention-deficit hyperactivity disorder (ADHD) in patients with chronic pain attending a pain clinic, the effects of a screening measure for ADHD in patients with chronic pain, and the effects of ADHD drugs on both pain and ADHD symptoms. Methods: We retrospectively surveyed 110 patients with chronic pain visiting the Anesthesiology and Pain Relief Center at the University of Tokyo in Japan, who had also consulted a psychiatrist, between April 2012 and July 2015. Results: Of the total of 110 patients with chronic pain, 35 (31.8%) were also diagnosed with ADHD, and the average Wender Utah Rating Scale (WURS) score among the ADHD patients was 39.0 ± 22.1 (n = 25). Only 36.0% of these patients exceeded the cutoff value, suggesting that 64.0% of the patients with ADHD were not identified by screening with the WURS. Twenty-six patients initiated treatment with ADHD medication, with dosage adjustment completed in 21. Of these 21 patients 20 (95.0%) had improved ADHD symptoms. Improved pain symptoms were observed in 14 patients (66.6%), with a reduction in the pain numerical rating scale of 64.7% ± 30.1%. Conclusions: This is the first study investigating the comorbidity of ADHD and chronic pain at pain clinics showing a high level of comorbidity and amelioration of pain and ADHD symptoms with treatment. Careful interpretation is required when the WURS is used to screen patients with chronic pain.

Regional cerebral blood flow (rCBF) studies of major depression have yielded variable results. The present study employed a longitudinal observation method to measure rCBF every 3 months during treatment. Thirteen patients with major depressive disorder underwent single-photon emission computed tomography (SPECT) with 99mTc-HMPAO three times over a 6-month period. rCBF was analyzed with the Statistical Parametric Mapping. The findings were compared to scans from 14 normal control subjects. Depression symptoms were rated using the Hamilton Rating Scale for Depression. At baseline, the main regions with lower rCBF compared to controls were the middle and inferior frontal gyri, superior temporal gyrus, and cingulate cortex. Three months later, despite significant improvement of depressive symptoms, decreased rCBF was observed in the same regions, but to lesser extent. At 6 months, depressive symptoms showed continued improvement, and rCBF in the superior temporal gyrus increased up to control levels, but rCBF in the temporal pole, cingulate, and inferior frontal gyrus remained low. The results of the present study suggest that there might be time- and state-dependent differences in rCBF recovery in patients with major depression.

The Akt signaling pathway involves various cellular processes and depends on extracellular stimuli. Since Akt signaling participates in cytoprotection, synapse plasticity, axon extension, and neurotransmission in the nervous system, alteration in Akt signaling might be a potential cause of schizophrenia. In this study, we performed multiplex fluorescent bead based immunoassays for members of the Akt signaling pathway in postmortem brains of controls and patients with schizophrenia. Vascular endothelial growth factor receptor 2 (VEGFR2/KDR) was significantly decreased in the prefrontal cortex (PFC) of patients with schizophrenia, and the expression level of VEGFR2 was inversely correlated with the positive symptom subscale of the Diagnostic Instrument for Brain Studies (DIBS) in patients with schizophrenia. There was also an increase in phosphorylated Akt1 in the PFC in the patients, though the ratio of phospho/total Akt1 is not significantly different. In the nucleus accumbens (NAcc) there was no significant difference in expression and phosphorylation levels of Akt signaling proteins. Genetic analysis revealed a significant correlation of a SNP of KDR (rs7692791) with ERK1/2 and Akt1 phospho/total rates. Since VEGFR2 participates in angiogenesis and neurotrophic activation, either or both functions might be responsible for onset of schizophrenia.

BackgroundAfter the 3.11 complex disaster, fear of radioactive contamination and forced evacuation influenced a number of residents to seek psychiatric care.ObjectivesThis study assessed the sequential changes in the number of new outpatients and patients with acute stress disorder (ASD), post-traumatic stress disorder (PTSD), adjustment disorder, and depression after the Fukushima disaster.MethodsWe distributed questionnaires to 77 psychiatric institutions to determine the number of new outpatients between March and June in 2010, 2011, and 2012.FindingsThere were 771, 1000, and 733 new patients in 2010, 2011, and 2012, respectively. We observed a statistically significant increase in new patients with ASD or PTSD and a significant decrease in patients with depression in 2011, which returned to predisaster levels in 2012.ConclusionsThere were time- and disease-dependent changes in the numbers of psychiatric care-seeking individuals after the 3.11 complex disaster in Fukushima.

BACKGROUND The calcineurin (CaN) inhibitor, tacrolimus, is widely used in patients undergoing allogeneic organ transplantation and in those with certain allergic diseases. Recently, several reports have suggested that CaN is also associated with schizophrenia. However, little data are currently available on the direct effect of tacrolimus on the human brain. CASE A 23-year-old Japanese female experienced severe delusion of persecution, delusional mood, suspiciousness, aggression, and excitement. She visited our hospital and was diagnosed with schizophrenia. When she was 27 years old, she had severe general fatigue, persistent fever, systemic joint pain, gingival bleeding, and breathlessness and was diagnosed with acute myelomonocytic leukemia. Later she underwent bone marrow transplantation (BMT), she was administered methotrexate and cyclosporin A to prevent graft versus host disease (GVHD). Three weeks after BMT, she showed initial symptoms of GVHD and was prescribed tacrolimus instead of cyclosporin A. Seven months after BMT at the age of 31 years, she died of progression of GVHD. Pathological anatomy was examined after her death, including immunohistochemical analysis of her brain using anti-CaN antibodies. For comparison, we used our previous data from both a schizophrenia group and a healthy control group. No significant differences were observed in the percentage of CaN-immunoreactive neurons among the schizophrenia group, healthy control group, and the tacrolimus case (all P>0.5, analysis of covariance). Compared with the healthy control group and schizophrenia group, the percentages of CaN-immunoreactive neurons in layers III-VI of the BA46 and the putamen tended to be lower in the tacrolimus case. CONCLUSION Tacrolimus may decrease CaN immunoreactivity in some regions of the human brain. Thus, tacrolimus may introduce side effects such as cognitive dysfunction and extrapyramidal symptoms. In addition, we also found that the effect of tacrolimus on CaN immunore-activity in human brain was stronger than the effect of schizophrenia.

Psychiatric side-effects are the main reason for discontinuation of interferon (IFN)-based therapy. Recent developments in near-infrared spectroscopy (NIRS) have enabled non-invasive clarification of brain functions in psychiatric disorders. We prospectively evaluated brain activation in 20 chronic hepatitis C patients with or without IFN-based therapy by using NIRS during a verbal fluency task (VFT).The relative concentrations of oxygenated hemoglobin were measured while patients completed a questionnaire survey at the start of treatment and at 4 and 12 weeks during treatment, using NIRS.The VFT performance did not change among the two groups. Patients with IFN-based therapy showed significantly lower activation during VFT in frontal channels at 12 weeks than those at the start of treatment and control (P

The five-factor model of the Positive and Negative Syndrome Scale (PANSS) for schizophrenia symptoms is the most common multiple-factor model used in analyses; its use may improve evaluation of symptoms in schizophrenia patients. Plasma monoamine metabolite levels are possible indicators of clinical symptoms or response to antipsychotics in schizophrenia. We investigated the association between five-factor model components and plasma monoamine metabolites levels to explore the model's biological basis. Plasma levels of homovanillic acid (HVA), 3-methoxy-4-hydroxyphenylglycol (MHPG), and 5-hydroxyindoleacetic acid (5-HIAA) were measured using high-performance liquid chromatography in 65 Japanese patients with schizophrenia. Significant negative correlation between plasma 5-HIAA levels and the depression/anxiety component was found. Furthermore, significant positive correlation was found between plasma MHPG levels and the excitement component. Plasma HVA levels were not correlated with any five-factor model component. These results suggest that the five-factor model of the PANSS may have a biological basis, and may be useful for elucidating the psychopathology of schizophrenia. Assessment using the five-factor model may enable understanding of monoaminergic dysfunction, possibly allowing more appropriate medication selection. Further studies of a larger number of first-episode schizophrenia patients are needed to confirm and extend these results.

Aims Facial emotion perception is considered to provide a measure of social cognition. Numerous studies have examined the perception of emotion in patients with schizophrenia, and the majority has reported impaired ability to recognize facial emotion perception. We aimed to investigate the correlation between facial expression recognition and other domains of social cognition and neurocognition in Japanese patients with schizophrenia. Methods Participants were 52 patients with schizophrenia and 53 normal controls with no history of psychiatric diseases. All participants completed the Hinting Task and the Social Cognition Screening Questionnaire. The Brief Assessment of Cognition in Schizophrenia was administered only to the patients. Facial emotion perception measured by the Facial Emotion Selection Test (FEST) was compared between the patients and normal controls. Results Patients performed significantly worse on the FEST compared to normal control subjects. The FEST total score was significantly positively correlated with scores of the Brief Assessment of Cognition in Schizophrenia attention subscale, Hinting Task, Social Cognition Screening Questionnaire Verbal Working Memory and Metacognition subscales. Stepwise multiple regression analysis revealed that verbal working memory function was positively related to the facial emotion perception ability in patients with schizophrenia. Conclusions These results point to the concept that facial emotion perception and some types of working memory use common cognitive resources. Our findings may provide implications for cognitive rehabilitation and related interventions in schizophrenia.

Cognitive impairment is a symptom of schizophrenia and strongly associated with impaired social function. In recent years, cognitive interventions (cognitive remediation therapies) have been implemented and their results have also been reported. Intervention studies have been conducted using a variety of methods that differ in terms of terminology, approach, and targeted cognitive domains. In this study, we examined trends in recent cognitive remediation research conducted subsequent to the meta-analyses of McGurk et al. (2007) and Wykes et al. (2011). We identified studies conducted between 2009 and 2013 to examine computer-assisted cognitive remediation and collated and analyzed the literature describing their major results and trends. Our results indicated improved cognitive performance subsequent to cognitive remediation therapy using computer programs. We found promising outcomes, particularly in reasoning and problem solving, verbal learning and memory, verbal working memory, and attention and vigilance, which replicated the findings of Wykes et al. (2011).