Clinical evidence that a dysregulated master neural network modulator may aid in diagnosing schizophrenia.

There are no validated biomarkers for schizophrenia (SCZ), a disorder linked to neural network dysfunction. We demonstrate that collapsin response mediator protein-2 (CRMP2), a master regulator of cytoskeleton and, hence, neural circuitry, may form the basis for a biomarker because its activity is uniquely imbalanced in SCZ patients. CRMP2's activity depends upon its phosphorylation state. While an equilibrium between inactive (phosphorylated) and active (nonphosphorylated) CRMP2 is present in unaffected individuals, we show that SCZ patients are characterized by excess active CRMP2. We examined CRMP2 levels first in postmortem brains (correlated with neuronal morphometrics) and then, because CRMP2 is expressed in lymphocytes as well, in the peripheral blood of SCZ patients versus age-matched unaffected controls. In the brains and, more starkly, in the lymphocytes of SCZ patients <40 y old, we observed that nonphosphorylated CRMP2 was higher than in controls, while phosphorylated CRMP2 remained unchanged from control. In the brain, these changes were associated with dendritic structural abnormalities. The abundance of active CRMP2 with insufficient opposing inactive p-CRMP2 yielded a unique lowering of the p-CRMP2:CRMP2 ratio in SCZ patients, implying a disruption in the normal equilibrium between active and inactive CRMP2. These clinical data suggest that measuring CRMP2 and p-CRMP2 in peripheral blood might reflect intracerebral processes and suggest a rapid, minimally invasive, sensitive, and specific adjunctive diagnostic aid for early SCZ: increased CRMP2 or a decreased p-CRMP2:CRMP2 ratio may help cinch the diagnosis in a newly presenting young patient suspected of SCZ (versus such mimics as mania in bipolar disorder, where the ratio is high).

Effect of assertive case management intervention on suicide attempters with comorbid Axis I and II psychiatric diagnoses: secondary analysis of a randomised controlled trial.

BACKGROUND: Most suicide attempters suffer from psychiatric disorders, which are often comorbid with personality disorders. The effects of intervention on patients who have attempted suicide with comorbid Axis I and II diagnoses have not been fully elucidated. We evaluated whether assertive case management can reduce the repetition of suicidal behaviours in patients who had attempted suicide with comorbid Axis I and II diagnoses. METHODS: This study was a secondary analysis of a randomised controlled trial investigating whether assertive case management could reduce the repetition of suicide attempts, compared with enhanced usual care. Subjects were divided into those who had comorbid Axis I and II diagnoses (Axis I + II group), and those who had an Axis I diagnosis without Axis II comorbidity (Axis I group). Outcome measures were compared between patients receiving a case management intervention and patients receiving enhanced usual care, as allocated. The primary outcome measure was the incidence proportion of the first episode of recurrent suicidal behaviour at 6 months after randomisation. We calculated risk ratios (RR) with 95% confidence intervals (CI) at 6 months and 12 months after randomisation of patients in the Axis I and Axis I + II groups. RESULTS: Of 914 enrolled patients, 120 (13.1%) were in the Axis I + II group, and 794 (86.9%) were in the Axis I group. Assertive case management was significantly effective for the Axis I group on the primary outcome at 6 months (risk ratio [RR] 0.51, 95% confidence intervals [CI] 0.31 to 0.84). The RR of the Axis I + II group was 0.44 (95% CI 0.14 to 1.40). CONCLUSIONS: Assertive case management not only had an effect on patients who had attempted suicide with only Axis I disorders but may also have a similar effect on patients with comorbid Axis I and II disorders.

Clinical and brain structural effects of the Illness Management and Recovery program in middle-aged and older patients with schizophrenia.

AIMS: In this study, we implemented the Illness Management and Recovery (IMR) program for middle-aged and older patients with schizophrenia hospitalized for long periods and assessed the effect of the IMR program on psychiatric symptoms and psychosocial function. The effects of the IMR program on brain structure were also evaluated. METHODS: The IMR program was implemented for 19 patients with schizophrenia; 17 patients with schizophrenia receiving treatment as usual (TAU) were also recruited as controls. In all patients, mean age was 61.4 years (range, 50-77 years) and mean hospitalization duration was 13.1 years (range, 1-31 years) at enrollment. Structural magnetic resonance images and Positive and Negative Syndrome Scale (PANSS) and Global Assessment of Functioning (GAF) scores as clinical variables were obtained at the beginning and end of the IMR program. Longitudinal analyses were performed to compare the effects of the IMR program on clinical symptoms and cortical thickness in the superior temporal gyrus (STG) between the IMR and TAU groups. RESULTS: Significant improvements in GAF scores and the total, Insight and Judgment, and Positive components of the PANSS were found in the IMR group compared with the TAU group. Cortical thickness in the left STG was preserved in the IMR group compared with the TAU group. CONCLUSIONS: This is the first report demonstrating the effectiveness of the IMR program for improving psychotic symptoms and psychosocial function and protecting brain structure in middle-aged and older inpatients with schizophrenia hospitalized for long periods.

Effects of ABCB1 gene polymorphisms on autonomic nervous system activity during atypical antipsychotic treatment in schizophrenia.

BACKGROUND: There are interindividual differences in the adverse effects of atypical antipsychotics, which include autonomic nervous system (ANS) dysfunction. Accordingly, to clarify the interindividual differences in the adverse effects of specific atypical antipsychotics in schizophrenia, we investigated the association between ANS dysfunction and ATP-binding cassette transport sub-family B member 1 (ABCB1) gene polymorphisms in patients with schizophrenia. METHODS: In total, 233 Japanese patients with schizophrenia participated in this study. All of the participants received an atypical antipsychotic as monotherapy: 89 participants received risperidone, 69 olanzapine, 48 aripiprazole, and 27 quetiapine. ANS activity was assessed by means of a power spectral analysis of heart rate variability. Four single nucleotide polymorphisms (SNPs) in ABCB1 (rs1045642, rs1128503, rs2032582, and rs2235048) were genotyped using the TaqMan method. RESULTS: For aripiprazole, sympathetic and total autonomic nervous activities were significantly lower in the rs1045642 T allele carrier-rs2235048 C allele carrier group than in the rs1045642 non-T allele carrier-rs2235048 non-C allele carrier group. In addition, in the aripiprazole group, the T-C-T-A haplotype (rs1045642-rs2235048-rs1128503-rs2032582) was associated with decreased ANS activity. However, there were no significant associations between ANS activity and ABCB1 gene polymorphisms in the risperidone, olanzapine, and quetiapine groups. Multiple regression analysis revealed that sympathetic and total nervous activities were significantly associated with the ABCB1 rs1045642-rs2235048 genotype and the T-C-T-A haplotype (rs1045642-rs2235048-rs1128503-rs2032582). CONCLUSION: We suggest that ABCB1 genetic polymorphisms affect aripiprazole-related ANS dysfunction but do not affect risperidone-, olanzapine-, or quetiapine-related ANS dysfunction.

Association between dysfunction of autonomic nervous system activity and mortality in schizophrenia.

BACKGROUND: Patients with schizophrenia have a higher mortality risk than the general population. Additionally, the autonomic nervous system (ANS) activity of patients with schizophrenia is lower and more dysfunctional than that of the general population. Nonetheless, the association between ANS dysfunction and mortality in schizophrenia is unclear. The aim of this study was to investigate the association between ANS activity and mortality in schizophrenia and to evaluate the predictive values of heart rate variability for long-term survival. METHODS: This study involves the 10-year follow-up of a sample population consisting of 59 Japanese inpatients with schizophrenia between 60 and 70 years of age from 2007 to 2016. The ANS activity of all patients was evaluated using heart rate variability in 2007. RESULTS: Fifty-three participants could be followed up because they stayed in the hospital during the follow-up period. Of these patients, 11 died during follow-up. Their mean age at death was 70.55 ±â€¯3.45 years. The parasympathetic activity of nonsurvivors was significantly lower than that of survivors, and multiple logistic regression analysis showed a significant association between death and parasympathetic activity. CONCLUSION: We suggest that decreased parasympathetic activity could be associated with 10-year all-cause mortality in older schizophrenic patients.

Voxel-wise correlations between cognition and cerebral blood flow using arterial spin-labeled perfusion MRI in patients with Alzheimer's disease: a cross-sectional study.

BACKGROUND: To analyze voxel-wise correlation between cerebral blood flow (CBF) measured using ASL-MRI and cognition in patients with Alzheimer's disease (AD). METHODS: Forty-one patients diagnosed with AD or mild cognitive impairment due to AD were recruited for this study. CBF images were obtained using ASL-MRI (n = 41) with a post-labeling delay (PLD) of 1.5 and 2.5 s (PLD1.5 and PLD2.5, respectively) using a 3 T scanner, in addition to brain perfusion SPECT with N-isopropyl-4-[I-123]iodoamphetamine (n = 28). Voxel-based analyses were performed for ASL-MRI and SPECT using Mini-Mental State Examination (MMSE) scores as covariates. Differences in CBF between PLD1.5 and PLD2.5 were assessed using a paired t-test with SPM12. RESULTS: Significant positive correlations were observed between MMSE scores and CBF at PLD1.5 in the right posterior cingulate cortex (PCC), and both temporo-parietal association cortexes. At PLD2.5, significant positive correlations were determined for MMSE scores and CBF in the superior parietal lobule and the right temporo-parietal association cortex. SPECT showed significant positive correlations in the PCC and both temporo-parietal association cortexes (right-side dominant). PLD1.5 showed significantly higher CBF than PLD2.5 in the proximal areas of vascular territories of the anterior, middle, and posterior cerebral arteries. CONCLUSIONS: Significant positive correlations in CBF, measured with both ASL-MRI and SPECT, with cognition were found in the PCC and temporo-parietal association cortexes. PLD1.5 and PLD2.5 showed similar correlations with cognition, although the CBF images had significant differences.

Feasibility and efficacy of shared decision making for first-admission schizophrenia: a randomized clinical trial.

BACKGROUND: The feasibility of shared decision making (SDM) for patients with schizophrenia remains controversial due to the assumed inability of patients to cooperate in treatment decision making. This study evaluated the feasibility and efficacy of SDM in patients upon first admission for schizophrenia. METHODS: This was a randomized, parallel-group, two-arm, open-label, single-center study conducted in an acute psychiatric ward of Numazu Chuo Hospital, Japan. Patients with the diagnosis of schizophrenia upon their first admission were randomized into a SDM intervention group or a usual treatment group in a 1:1 ratio. The primary outcome was patient satisfaction at discharge. The secondary outcomes were attitudes toward medication at discharge and treatment continuation at 6 months after discharge. RESULTS: Twenty-four patients were randomly assigned. The trial was prematurely terminated due to slow enrollment. At discharge, the mean score on satisfaction was 23.7 in the SDM group and 22.1 in the usual care group (unadjusted mean difference: 1.6; 95% CI: -5.2 to 2.0). Group differences were not observed in attitude toward medication and treatment continuation. There was no statistically significant difference between the groups for the mean Global Assessment of Functioning score at discharge or length of stay as safety endpoint. CONCLUSIONS: No statistical differences were found between the SDM group and usual care group in the efficacy outcomes and safety endpoints. Large trials are needed to confirm the efficacy of the SDM program upon first admission for schizophrenia. TRIAL REGISTRATION: The study has been registered with ClinicalTrials.gov as NCT01869660 (registered 27 May, 2013).

Long term effects of smoking cessation in hospitalized schizophrenia patients.

BACKGROUND: The prevalence of smoking in patients with schizophrenia is higher than that in the general population and is an important medical issue. Short-term smoking cessation tends to worsen psychiatric symptoms in patients with schizophrenia but decreases sympathetic nervous system activity and improves plasma cholesterol levels in healthy people. Few studies have assessed the long-term effects of smoking cessation in patients with schizophrenia. METHODS: Subjects were 70 Japanese patients with schizophrenia (38 smokers, 32 non-smokers). We compared the following clinical parameters between the two groups at baseline (before smoking cessation) and in each group separately between baseline and at three years after smoking cessation: autonomic nervous system activity, plasma cholesterol levels, body weight, drug therapy, and Global Assessment of Functioning scores. We also compared the mean changes in clinical parameters throughout this study between the groups at both time points. Autonomic nervous system activity was assessed by power spectral analysis of heart rate variability. RESULTS: Parasympathetic nervous system activity and the doses of antiparkinsonian drugs in smokers were significantly higher than those in non-smokers at baseline. Smoking cessation was associated with significantly decreased sympathetic nervous system activity and decreased doses of antipsychotics and antiparkinsonian drugs at three years after smoking cessation. However, there was no significant difference in the mean change in clinical factors scores, except for Global Assessment of Functioning scores, between smokers and non-smokers at three years after smoking cessation. CONCLUSIONS: Our results suggest that smoking reduces both autonomic nervous system activity and the effectiveness of drug therapy with antipsychotics and antiparkinsonian drugs in patients with schizophrenia, but that both factors could be ameliorated over the long term by smoking cessation. Taken together with the findings of previous studies, smoking cessation in patients with schizophrenia has many long-term positive physiological effects.

Lateralized hippocampal volume increase following high-frequency left prefrontal repetitive transcranial magnetic stimulation in patients with major depression.

AIM: Repetitive transcranial magnetic stimulation (rTMS) has been applied as a treatment for patients with treatment-resistant depression in recent years, and a large body of evidence has demonstrated its therapeutic efficacy through stimulating neuronal plasticity. The aim of this study was to investigate structural alterations in the hippocampus (HIPP) and amygdala (AM) following conventional rTMS in patients with depression. METHODS: Twenty-eight patients with depression underwent 10 daily 20-Hz left prefrontal rTMS over 2 weeks. The left dorsolateral prefrontal cortex (DLPFC) was identified using magnetic resonance imaging-guided neuronavigation prior to stimulation. Magnetic resonance imaging scans were obtained at baseline and after the completion of rTMS sessions. The therapeutic effects of rTMS were evaluated with the 17-item Hamilton Depression Rating Scale (HAM-D17 ), and the volumes of the HIPP and AM were measured by a manual tracing method. RESULTS: Statistical analyses revealed a significant volume increase in the left HIPP (+3.4%) after rTMS but no significant volume change in the AM. No correlation was found between the left HIPP volume increase and clinical improvement, as measured by the HAM-D17 . CONCLUSION: The present study demonstrated that conventional left prefrontal rTMS increases the HIPP volume in the stimulated side, indicating a remote neuroplastic effect through the cingulum bundle.

Association of the Cholinergic Muscarinic M2 Receptor with Autonomic Nervous System Activity in Patients with Schizophrenia on High-Dose Antipsychotics.

BACKGROUND: Patients with schizophrenia have abnormal autonomic nervous system (ANS) activity compared with the general population. One reason for this difference is the muscarinic affinity for antipsychotic drugs; therefore, single nucleotide polymorphisms (SNPs) of the muscarinic receptor gene influence this ANS dysfunction. This study sought to determine the effect of SNPs of the cholinergic muscarinic receptor (CHRM) gene on ANS activity in patients with schizophrenia receiving antipsychotic drugs. METHODS: A total of 173 Japanese patients with schizophrenia were included in this study. Heart rate variability (HRV) was measured as an index of ANS activity. SNPs in CHRM1 (rs542269 and rs2075748), CHRM2 (rs324640, rs8191992, rs1824024, and rs7810473), and CHRM3 (rs3738435, rs4620530, and rs6429157) were genotyped using the TaqMan® method. Patients were grouped according to standard equivalent conversions of chlorpromazine (CP) into a high-CP group (HG; ≥1,000 mg) and a low-CP group (LG; <1,000 mg). ANS activity was compared between the groups. In addition, we compared the total, low-frequency (LF), high-frequency (HF), and LF/HF components of the patients' HRV, and the genotype of the SNPs in both the HG and LG groups. Bonferroni correction was applied for multiple comparisons, and the Bonferroni-corrected critical p value was <0.005. RESULTS: The A allele of the CHRM2 rs8191992 polymorphism in HG was associated with decreased ANS activity. CONCLUSION: Our results show reduced ANS activity in association with the CHRM2 rs8191992 polymorphism in patients with schizophrenia on high-dose antipsychotics. CHRM2 polymorphisms may play an important role in ANS activity in patients with schizophrenia.

A double-blind randomized study assessing safety and efficacy following one-year adjunctive treatment with bitopertin, a glycine reuptake inhibitor, in Japanese patients with schizophrenia.

BACKGROUND: Bitopertin, a glycine reuptake inhibitor, was investigated as a novel treatment for schizophrenia. We report all the results of a double-blind randomized study assessing safety and efficacy following 52-week adjunctive treatment with bitopertin in Japanese patients with schizophrenia. METHODS: This study enrolled Japanese outpatients with schizophrenia who met criteria for either "negative symptoms", i.e., patients with persistent, predominant negative symptoms of schizophrenia even after long-term treatment with antipsychotics or "sub-optimally controlled symptoms", i.e., patients with insufficiently improved symptoms of schizophrenia even after long-term treatment with antipsychotics, respectively. One hundred sixty-one patients were randomly assigned to receive 52-week treatments with bitopertin doses of 5, 10, or 20 mg/day at ratio of 1:5:5, where existing antipsychotics were concomitantly administered. Efficacy endpoints included Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression (CGI), and Personal and Social Performance (PSP). The purpose of the present study is primarily to evaluate the safety, and secondarily to investigate the clinical efficacy of bitopertin. RESULTS: One hundred fourteen patients (71 %) completed 52-week treatment with bitopertin. Most of the adverse events were mild or moderate in their severity. The patients in the 20-mg group experienced more adverse events than the patients in the other two groups. Common dose-dependent adverse events were somnolence and insomnia associated with worsening schizophrenia. The blood hemoglobin levels gradually decreased from baseline in a dose-dependent manner, but there were no patients with the decrease below 10 g/dL that would have led to their discontinuation. All the efficacy endpoints gradually improved in all the treatment groups for both of the two symptoms, while there were no clear differences among the three dose groups. CONCLUSIONS: Altogether, bitopertin was found to be generally safe and well-tolerated for the treatment of patients with schizophrenia. All three bitopertin treated groups showed improvements in all the efficacy endpoints for both of the two symptoms, i.e., "negative symptoms" and "sub-optimally controlled symptoms", throughout the duration of the study. TRIAL REGISTRATION: Japan Pharmaceutical Information Center, number JapicCTI-111627 (registered on September 20, 2011).

Social participation and quality-of-life of patients with traumatic brain injury living in the community: A mixed methods study.

OBJECTIVE: To investigate the quality-of-life (QoL) and social participation of patients with traumatic brain injury (TBI) living in the community in Japan. METHODS: A mixed-methods study of 29 post-TBI patients and 12 family members was conducted. Objective scales were used to evaluate QoL (Short Form Health Survey SF-36), depression (Zung Self-rating Depression Scale) and psychosocial function (Sydney Psychosocial Reintegration Scale, 2nd edition). Subjective views of changes in social functioning, participation and suitability of family support were obtained by a semi-structured interview. Participants were classified into 'change' and 'no-change' groups for social participation and between-group comparisons of QoL and determinant factors of QoL were evaluated. RESULTS: The SF-36 social role component was significantly associated with the suitability of family support, followed by their understanding. However, QoL was not significantly associated with changes in social participation. Social participation was particularly influenced by the absence of rehabilitation support for low-skill labourers and housewives, whether they lost their employment or not. CONCLUSIONS: Advances in rehabilitation services are required, particularly to meet the specific needs of housewives and low-skill labourers. Families should receive sufficient education and short- and long-term strategies for providing suitable support to patients and their families should be implemented.

Effects of NRG1 genotypes on orbitofrontal sulcogyral patterns in Japanese patients diagnosed with schizophrenia.

AIM: Numerous reports have described differences in the distribution of orbitofrontal cortex (OFC) sulcogyral patterns between patients with schizophrenia (SZ patients) and healthy controls (HC). Alterations in OFC morphology are also observed in those at high risk for developing SZ and in first-episode SZ, suggesting that genetic associations may be extant in determining OFC sulcogyral patterns. We investigated the association between single nucleotide polymorphisms (SNP) in NRG1 and OFC sulcogyral patterns. METHODS: A total of 59 Japanese patients diagnosed with SZ and 60 HC were scanned on a 1.5-T magnet. Patients were also assessed clinically. OFC sulcogyral patterns were evaluated for each participant, and genotyping was performed for four SNP in NRG1 (SNP8NRG243177, SNP8NRG221533, SNP8NRG241930, and rs1081062). RESULTS: There were significant differences in the distribution of OFC sulcogyral patterns between SZ patients and HC (χ(2) = 6.52, P = 0.038). SZ patients showed an increase in the frequency of Type III expression, which was associated with an earlier age of disease onset (ß = -0.302, F = 4.948, P = 0.030). Although no difference was found in genotype frequencies between SZ patients and HC, an NRG1 SNP, SNP8NRG243177, was associated with Type II expression in SZ patients (ß = 0.237, F = 4.120, P = 0.047). CONCLUSION: Our results suggest that OFC sulcogyral pattern formation in schizophrenia may be associated with NRG1 allele frequency, which is closely related to neurodevelopment.

Non-alcoholic fatty liver disease comorbid with major depressive disorder: The pathological features and poor therapeutic efficacy.

BACKGROUND AND AIM: Major depressive disorder (MDD) is an important public health problem, and it is often comorbid with many chronic diseases. The purpose of this study was to identify the clinical features of non-alcoholic fatty liver disease (NAFLD) patients comorbid with MDD and to investigate the influence of MDD on the effect of treatment in patients with NAFLD. METHODS: A total of 258 patients with biopsy-proven NAFLD were included. MDD was diagnosed according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision. The patients were followed up for 48 weeks under standard care for NAFLD, which consisted mainly of lifestyle modification. RESULTS: There were 32 patients comorbid with MDD. They were characterized by more severe histological steatosis and higher NAFLD activity score, and also significantly higher levels of serum aminotransferase, γ-glutamyl transpeptidase and ferritin, than age-and-sex-matched NAFLD patients without MDD. Moreover, NAFLD patients with MDD showed poor response to the standard care for NAFLD, in body weight loss and in other parameters. Particularly, NAFLD patients with unstable MDD (not in full/partial remission) showed severe resistance to the treatment. CONCLUSION: This is the first study to demonstrate the clinical features and response to therapy of NAFLD patients comorbid with MDD. The comorbid state of MDD was associated with more severe histological liver steatosis and worse treatment outcomes in patients with NAFLD. Further investigations are required to develop new lifestyle modification programs that enable NAFLD patients with MDD to achieve the treatment goal.

Clinical profiles of dementia with Lewy bodies with and without Alzheimer's disease-like hypometabolism.

OBJECTIVES: It is well known that Alzheimer's disease (AD)-type pathology is commonly present in dementia with Lewy bodies (DLB) brains and that the degree of AD-type pathology has an influence on the clinical characteristics of DLB. Although significant hypometabolism in the temporoparietal/precuneus on [(18)F]fluoro-d-glucose ((18)F-FDG) positron emission tomography (PET) scans is considered to support a diagnosis of AD, some DLB patients also exhibit this metabolic pattern. The clinical significance of the metabolic pattern on DLB remains unknown. METHODS: Twenty-three DLB patients, 10 AD patients, and 11 controls underwent (18)F-FDG PET scans. According to the degree of hypometabolism in the parietal/precuneus regions, representing the AD-like metabolic pattern, 12 patients were placed in the DLB-AD(+) group and 11 patients were placed in the DLB-AD(-) group. The demographics and clinical variables were compared among the four groups. RESULTS: In addition to the parietal/precuneus regions, the DLB-AD(+) group exhibited significantly greater posterior cingulate hypometabolism than the DLB-AD(-) group, although occipital metabolism did not differ. The prevalence of visual hallucinations and extracampine hallucinations, and the Bender-Gestalt test score were significantly higher in the DLB-AD(+) group than the DLB-AD(-) group, although there were no differences in the demographics and other examined clinical variables between the two DLB groups. These clinical differences were absent in the DLB-AD(-) group, AD group, and controls. CONCLUSIONS: Parietal/precuneus hypometabolism may be associated with clinical characteristics in DLB patients. Further multiple imaging modalities that are sensitive to AD-type pathology are needed to reveal the neurobiological basis of the AD-like metabolic pattern.

An autopsied case of corticobasal degeneration showing severe cerebral atrophy over a protracted disease course of 16 years.

The patient was a 72-year-old Japanese woman. At the age of 57, she started having difficulty performing daily work and developed agraphia. She also exhibited restlessness and loss of interest, and began to speak less. Thereafter, stereotypical behavior, gait disturbance and dysphagia were noted. CT scan demonstrated left-dominant frontal and temporal lobe atrophy. She died at the age of 72, about 16 years after the onset of symptoms. Neuropathologically, the brain weighed 867 g, and showed remarkable cerebral atrophy with degeneration of the white matter, predominantly in the left dorsal frontal lobe and anterior temporal lobe. Microscopically, severe neuronal loss and gliosis with rarefaction were found in the cerebral cortex, and severe destruction of myelin and axons was observed in the cerebral white matter. Moderate neuronal loss with gliosis was also found in the pallidum and substantia nigra. Gallyas-Braak staining and tau immunostaining revealed pretangle neurons, NFTs, ballooned neurons and astrocytic plaques in the cerebral cortex, subcortical nuclei and brainstem, and argyrophilic threads and coiled bodies in the subcortical white matter. Tau isoform-specific immunostaining revealed that most tau-immunoreactive structures were positive for 4-repeat (4R) tau, but some of the NFTs were positive for 3-repeat (3R) tau in the cerebral neocortex. Immunoblotting demonstrated an accumulation of 4R tau in the cerebral cortex and subcortical white matter. The patient was pathologically diagnosed as having corticobasal degeneration. Her long survival course likely accounts for the severe white matter degeneration and accumulation of 3R tau in NFTs.

Efficacy of shared decision making on treatment satisfaction for patients with first-admission schizophrenia: study protocol for a randomised controlled trial.

BACKGROUND: Shared decision making is a promising model for patient-centred medicine, resulting in better clinical outcomes overall. In the mental health field, interventions that consider the patient-centred perspective--such as patient quality of life, involvement in the treatment, treatment satisfaction, and working alliance--have increased and better clinical outcomes discovered for patients with schizophrenia. However, few studies have examined the efficacy of shared decision making for schizophrenia treatment. The objective of this study is to evaluate the effect of a shared decision making intervention compared to treatment as usual on patient satisfaction at discharge for first-admission patients with schizophrenia. METHODS/DESIGN: This is a randomised, parallel-group, two-arm, open-label, single-centre study currently being conducted in an acute psychiatric ward of Numazu Chuo Hospital, Japan. We are recruiting patients between 16 and 65 years old who are admitted to the ward with a diagnosis of schizophrenia without prior experience of psychiatric admission. Fifty-eight participants are being randomised into a shared decision making intervention group or a treatment as usual control group in a 1:1 ratio. The intervention program was developed based on a shared decision making model and is presented as a weekly course lasting the duration of the patients' acute psychiatric ward stay. The primary outcome measure is patient satisfaction at discharge as assessed by the Client Satisfaction Questionnaire. Due to the study's nature, neither the patient nor staff can be blinded. DISCUSSION: This is the first randomised controlled trial to evaluate the efficacy of shared decision making for patients with early-treatment-stage schizophrenia. The intervention program in this study is innovative in that it includes both of the patient and staff who are involved in the treatment. TRIAL REGISTRATION: The study has been registered with ClinicalTrials.gov as NCT01869660.

Association of the five-factor personality model with prefrontal activation during frontal lobe task performance using two-channel near-infrared spectroscopy.

AIM: The aim of this study was to investigate the biological background of the five-factor model using near-infrared spectroscopy and cognitive tasks. METHODS: Twenty right-handed healthy volunteers participated in this study. Their personality traits were assessed using the NEO Five-Factor Inventory, and changes in oxyhemoglobin concentration ([oxy-Hb]) were measured during cognitive tasks using a wireless near-infrared spectroscopy. RESULTS: The average [oxy-Hb] in the right prefrontal area had a significant positive correlation with the agreeableness score during the Stroop test at incongruent stimulus block. For the verbal fluency task, there were no significant correlations of bilateral [oxy-Hb] changes with any items. CONCLUSION: Higher agreeableness scores may involve less suppression to the default mode network related to resting state brain function. Keeping selective attention during the Stroop test may require more power of concentration than retrieving words during the verbal fluency task.

Primary visual cortical metabolism and rapid eye movement sleep behavior disorder in dementia with Lewy bodies.

AIM: Significant glucose hypometabolism in the primary visual cortex (PVC) is considered to support a diagnosis of dementia with Lewy bodies (DLB), but its relationship to the clinical features remains unknown. The purpose of this study was to assess the association between the metabolic pattern and clinical variables in DLB. METHODS: A total of 27 DLB patients who underwent [18F]fluoro-d-glucose (18F-FDG) positron emission tomography scans were examined. Demographics and clinical variables were compared between patients with and without glucose hypometabolism in the PVC. The correlations between the cerebral metabolic rate of glucose in the PVC and clinical variables were also investigated. RESULTS: Only the onset age of probable rapid eye movement sleep behavior disorder (RBD) was significantly different between patients with and withoutglucose hypometabolism in the PVC, being younger in patients with the metabolic pattern; there were no other differences in clinical variables. The onset age of probable RBD was significantly correlated with the cerebral metabolic rate of glucose in the PVC. CONCLUSIONS: Glucose hypometabolism in the PVC provides a potential mechanism for the link between antecedent RBD and the subsequent development of dementia in DLB patients. Glucose hypometabolism in the PVC may represent the effect of the pathophysiological process of DLB on RBD rather than a distinct condition in the disease progression. The physiological aspects of the link between this metabolic pattern and the onset of RBD remain unclear.