Cognitive function, treatment response to lithium, and social functioning in Japanese patients with bipolar disorder.

OBJECTIVES: Patients with bipolar disorder often suffer from cognitive impairment that significantly influences their functional outcome. However, it remains unknown whether lithium has a central role in cognition and functional outcome. We examined whether cognition and functional outcome were predicted by demographic and clinical variables, including the response to lithium, in lithium-treated patients with bipolar disorder. METHODS: We evaluated 96 lithium-treated euthymic patients with bipolar disorder and 196 age- and-gender-matched healthy controls, using the Brief Assessment of Cognition in Schizophrenia (BACS). The patients were also assessed using the Social Functioning Scale (SFS) and "The Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder" (Alda) scale, which was evaluated as either a continuous measure of the total scale or a dichotomous criterion. RESULTS: Multiple regression analysis revealed two key findings: first, that the premorbid intelligence quotient, age, and number of mood episodes were predictors of the BACS composite score; and, second, that the BACS composite score, negative symptoms, and continuous measure on the total Alda scale (but not its dichotomy) predicted the total SFS score. Structural equation modeling (SEM) was used to confirm these findings, and additionally revealed that the Alda scale was significantly associated with negative symptoms and also the number of mood episodes, regardless of how it was evaluated. CONCLUSIONS: SEM delineated how demographic and clinical variables, cognitive performance, and response to lithium treatment were causally associated with, and converged on, social function. The putative role of the Alda scale for social function warrants further study.

[Drainage for Subcutaneous Emphysema after Pulmonary Resection].

Severe subcutaneous emphysema sometimes develops after pulmonary resection. We report our management of ten patients who were treated with subcutaneous Penrose drainage. Water seal test at chest closure showed no air leakage in 5, and a small amount in 5. Chest X-ray at the progression of massive subcutaneous emphysema showed no obvious pneumothorax in 2, and slight apical pneumothorax in 8. Subcutaneous emphysema developed after removal of chest tubes in 6, and before removal in 4. Subcutaneous drains were inserted at the midclavicular line or the side chest in 8, and both in 2. Subcutaneous emphysema improved immediately after subcutaneous Penrose drainage with active compressive massage. Subcutaneous penrose drainage is easy and useful for relieving massive subcutaneous emphysema.

Association of the Hermansky-Pudlak syndrome type 4 (HPS4) gene variants with cognitive function in patients with schizophrenia and healthy subjects.

BACKGROUND: The Hermansky-Pudlak Syndrome Type 4 (HPS4) gene, which encodes a subunit protein of the biogenesis of lysosome-related organelles complex (BLOC)-3, which is involved in late endosomal trafficking, is associated with schizophrenia; however, its clinical relevance in schizophrenia remains unknown. The purpose of the present study was to investigate whether HPS4 is associated with cognitive functions in patients with schizophrenia and healthy controls and with the clinical profiles of patients with schizophrenia. METHODS: We investigated the association of variants of HPS4 with clinical symptoms and cognitive function in Japanese patients with schizophrenia (n = 240) and age-matched healthy control subjects (n = 240) with single nucleotide polymorphisms (SNP)- or haplotype-based linear regression. We analyzed five tagging SNPs (rs4822724, rs61276843, rs9608491, rs713998, and rs2014410) of HPS4 and 2-5 locus haplotypes of these five SNPs. The cognitive functions of patients and healthy subjects were evaluated with the Brief Assessment of Cognition in Schizophrenia, Japanese-language version, and the patients were assessed for their symptomatology with the Positive and Negative Symptom Scale (PANSS). RESULTS: In patients with schizophrenia, rs713998 was significantly associated with executive function under the dominant genetic model (P = 0.0073). In healthy subjects, there was a significant association between working memory and two individual SNPs under the recessive model (rs9608491: P = 0.001; rs713998: P = 0.0065) and two haplotypes (rs9608491-713998: P = 0.0025; rs61276843-9608491-713998: P = 0.0064). No significant association was found between HPS4 SNPs and PANSS scores or premorbid IQ, as measured by the Japanese version of the National Adult Reading Test. CONCLUSIONS: These findings suggested the involvement of HPS4 in the working memory of healthy subjects and in the executive function deficits in schizophrenia.

A two-factor structure for the Schedule for the Deficit Syndrome in schizophrenia.

The deficit subtype is hypothesized to constitute a homogeneous subgroup of schizophrenia patients. The Schedule for the Deficit Syndrome (SDS) was developed to categorize schizophrenia patients into deficit and non-deficit subtypes. Only one report, however, has suggested the use of a two-factor SDS. The present study used a two-factor SDS and examined the relationships between the factors and the demographic and clinical variables in deficit-type schizophrenia patients. Principal component analysis was performed on data obtained from 70 schizophrenia patients with the deficit syndrome. The two-factor SDS was replicated. Factor 1, avolition, was significantly correlated only with the relational disorder domain, which consisted of two negative items from the Positive and Negative Syndrome Scale. Factor 2, poor emotional expression, was significantly correlated with both the negative symptom domain, which consisted of three negative items, and the relational disorder domain. Since the SDS has two factors, there appear to be different underlying processes for these two factors.

Clinical Relapse of Anti-AMPAR Encephalitis Associated with Recurrence of Thymoma.

We report a rare case of anti-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) encephalitis presenting clinical relapse in association with recurrence of thymoma. Anti-AMPAR encephalitis is an autoimmune-mediated neurological disease, frequently accompanied by the presence of neoplasms, thus comprising the spectrum of paraneoplastic syndrome. A patient had been in remission for 34 months showed clinical relapse 3 months after the detection of recurrent thymoma. Clinical relapse of anti-AMPAR encephalitis after the recurrence of an initially detected neoplasm has not been previously reported. Our case therefore highlights the pathogenic relevance of specific tumor antigens as a trigger of anti-AMPAR antibody production and induction of the disease.

Attenuation of lung injury in allograft rejection using NF-kappaB decoy transfection-novel strategy for use in lung transplantation.

OBJECTIVE: Increased production of nitric oxide (NO) is known to be a marker of lung allograft rejection and lung injury. NO production is up-regulated directly or indirectly by nuclear factor-kappa B (NF-kappaB), a transcriptional factor of inflammatory cytokines and iNOS. We attempted to determine whether transfection of an NF-kappaB decoy into allografts could reduce NO production and ameliorate acute lung injury during allograft rejection. METHODS: Left lung transplantation was performed in pairs of Brown Norway (RT1n) and Lewis (RT1) rats. In Group NF (n=6), the allografts were flushed with 20 ml of PBS solution containing a hemagglutinating virus of Japan (HVJ) liposome-ODN complex as an NF-kappaB decoy and preserved for 60 min at 4 degrees C. A scramble decoy was used in the positive control (Group S, n=5) and simple PBS solution in the negative control (Group C, n=5). Five days after transplantation without use of immuno-suppressants, exhaled NO, gas exchange, and graft histological rejection score were determined. RESULTS: The exhaled NO level was significantly reduced in Group NF as compared with Group S (445+/-162 vs 1305+/-123 ppb, P<0.02), while improvements in PaO2 (197+/-28 vs. 60+/-18 mmHg, P<0.02) and rejection score (1.8+/-0.3 vs. 2.5+/-0.4) were also observed. There were no differences in these parameters between Groups S and C. CONCLUSIONS: Inhibition of NF-kappaB activation in the allograft by ODN decoy transfection into the donor lung ameliorated lung injury during acute allograft rejection. Our results imply a possible therapeutic target for the inflammation process in lung transplantation clinical settings.

Application of HVJ-liposome mediated gene transfer in lung transplantation-distribution and transfection efficiency in the lung.

OBJECTIVE: A novel hemagglutinating virus of Japan (HVJ)-liposome-mediated gene transfer system has been shown to have benefits of a high efficiency of transfection and low immunogenicity. The aims of this study were to determine the effect of re-transfection of the HVJ-liposome system via the airway, and to quantify the distribution of gene expression between transtracheal and transplantation approaches. METHODS: Beta-galactosidase (beta-gal) plasmid DNA was introduced into lung tissues using the HVJ-liposome method. Two groups of Sprague-Dawley (SD) rats received intratracheal instillation of 10 microg of the beta-gal gene, once on Day 0 in 1 group (Group Tb-1, n=4) and 3 times on Days 0-2 in another (Group Tb-3, n=4). In a third group of SD rats (Group Tx, n=5), an orthotopic left lung transplantation was performed after the donor lung was flushed with an HVJ-liposome complex solution and preserved for 1h. Gene expression and distribution in lung tissue was then quantified by counting the X-gal stained cells. RESULTS: Both the transtracheal and transplantation approaches resulted in low levels of transfection in the vascular endothelial cells (0.2+/-0.1 and 4.0+/-1.8%), respectively, but a moderate degree of transfection to the airway (11.0+/-7.1 and 28.0+/-20.7%) and alveolar cells (3.0+/-1.8 and 6.0+/-3.6%). Three repetitive injections via the airway increased gene expression in airway epithelial cells of 41.0+/-12.0% compared with the single administration of 11.0+/-4.3%. CONCLUSIONS: Our results suggest that the repeated transtracheal gene transfection using HVJ-liposome may have benefits for treatment of problems after lung transplantation. In addition, gene transfer using a flushing solution during harvest may provide an opportunity for gene manipulation in the setting of lung transplantation.

An association study of the Hermansky-Pudlak syndrome type 4 gene in schizophrenic patients.

OBJECTIVE: We encountered two Japanese siblings who had Hermansky-Pudlak syndrome (HPS) and major mental disorders (schizophrenia and major depression) as well. As it is known that HPS is caused by a local mutation in one of the human genes, named HPS1 to HPS8 and PLDN (HPS9), encoding subunit proteins involved in endosomal trafficking pathways, here, we report the mutation causing the siblings disease and a case-control association study of schizophrenia using polymorphisms of a gene to be screened in the mutation analysis. METHODS: We analyzed three HPS-causing genes, HPS1, HPS4, and HPS7, to identify a genetic mutation involved in the siblings. A case-control association study of nine tagging single-nucleotide polymorphisms of the entire genetic region of the HPS4 gene resulting from the screening in the siblings was carried out for schizophrenic patients (n=422) and controls (n=578). RESULTS: The two patients with HPS were homozygous for nonsense mutation (T/T) for the c.541C>T (rs119471022) in the HPS4 gene, which is mapped to human chromosome 22q12.1. The same nonsense mutation existed in the heterozygous state (C/T) in their mother and in two other siblings. The genotypic distribution of rs9608491 (C/T) in intron 4 showed a trend toward an association with schizophrenia as indicated by a corrected P-value of 0.053 controlling for multiple testing. Haplotype analyses showed that two of two-locus haplotypes, and all of three-locus, four-locus, and five-locus haplotypes, as they share rs9608491, yielded significant evidence for association with schizophrenia as shown by the following omnibus P-values. When rs4822724, rs61276843, rs9608491, rs713998, and rs2014410, five haplotype tagging single-nucleotide polymorphisms, are assigned serial numerals (1, 2, 3, 4, and 5), the omnibus P-values for the resulting haplotypes were P=0.0039 for 2-3, P=0.0142 for 3-4, P=0.0083 for 1-2-3, P=0.0187 for 2-3-4, P=0.0191 for 3-4-5, P=0.0270 for 1-2-3-4, P=0.0246 for 2-3-4-5, and 0.0261 for 1-2-3-4-5. CONCLUSION: These results suggest that the HPS4 gene confers a susceptibility to schizophrenia.

Subjective experiences of Japanese inpatients with chronic schizophrenia.

Knowledge of the subjective experience of patients has important implications for the understanding and treatment of schizophrenia. However, previous studies examining the clinical correlates of subjective experiences have yielded inconclusive results. The present study of Japanese inpatients with chronic schizophrenia aimed to reveal the factorial structure of patients' subjective experiences and to examine the relationships between identified factors and demographic and clinical variables. A systematic assessment was carried out of objective psychopathology and subjective experiences in 129 inpatients. A factor analysis of the data of patients' subjective experiences identified five factors. Delusions/hallucinations, as clinical variables, were significantly associated with three of these factors. Negative symptoms, extrapyramidal side effects, and female gender each had significant associations with only one of the factors. The first factor, which accounted for the highest percentage, did not correlate significantly with any of the clinical or demographic variables. Subjective experiences in chronic schizophrenia appear to have a heterogeneous structure and fall into two groups, one relatively independent of objective psychopathology and the other reflecting the clinical variable delusions/hallucinations.

Bizarre delusions and DSM-IV schizophrenia.

The present study investigated whether schizophrenia patients with and without DSM-IV bizarre delusions, categorized as bizarre delusions of Schneiderian first rank symptoms (SBD) and as non-Schneiderian bizarre delusions (non-SBD), differed on demographic or clinical features, in view of the weight given to bizarre delusions in the diagnosis of schizophrenia. One hundred and twenty-nine in-patients with schizophrenia were assessed systematically for both types of bizarre delusions on the five domains of psychopathology of the Positive and Negative Syndrome Scale (PANSS; delusions/hallucinations, thought disorder/disorganization, excitement, negative symptoms and depressive symptoms) and for extrapyramidal side-effects. Inter-rater reliabilities for SBD and non-SBD were assessed and were exceptionally high (kappa value 0.85 and 0.92, respectively). Neither SBD nor non-SBD were associated with any demographic or non-PANSS clinical characteristics tested. However, the presence of non-SBD was significantly associated with more severe psychopathology in all five domains of the PANSS, whereas the presence of SBD was significantly associated with more severe psychopathology in three domains only: delusions/hallucinations, thought disorder/disorganization and depressive symptoms. However, patients with only SBD did not differ from patients with only non-SBD on any demographic or clinical variables, including five psychopathological domains. These findings suggest that, despite showing more severe symptoms, patients with DSM-IV bizarre delusions do not constitute a clinically distinguishable subgroup.