Association of schizophrenia onset age and white matter integrity with treatment effect of D-cycloserine: a randomized placebo-controlled double-blind crossover study.

BACKGROUND: It has been reported that drugs which promote the N-Methyl-D-aspartate-type glutamate receptor function by stimulating the glycine modulatory site in the receptor improve negative symptoms and cognitive dysfunction in schizophrenia patients being treated with antipsychotic drugs. METHODS: We performed a placebo-controlled double-blind crossover study involving 41 schizophrenia patients in which D-cycloserine 50 mg/day was added-on, and the influence of the onset age and association with white matter integrity on MR diffusion tensor imaging were investigated for the first time. The patients were evaluated using the Positive and Negative Syndrome Scale (PANSS), Scale for the Assessment of Negative Symptoms (SANS), Brief Assessment of Cognition in Schizophrenia (BACS), and other scales. RESULTS: D-cycloserine did not improve positive or negative symptoms or cognitive dysfunction in schizophrenia. The investigation in consideration of the onset age suggests that D-cycloserine may aggravate negative symptoms of early-onset schizophrenia. The better treatment effect of D-cycloserine on BACS was observed when the white matter integrity of the sagittal stratum/ cingulum/fornix stria terminalis/genu of corpus callosum/external capsule was higher, and the better treatment effect on PANSS general psychopathology (PANSS-G) was observed when the white matter integrity of the splenium of corpus callosum was higher. In contrast, the better treatment effect of D-cycloserine on PANSS-G and SANS-IV were observed when the white matter integrity of the posterior thalamic radiation (left) was lower. CONCLUSION: It was suggested that response to D-cycloserine is influenced by the onset age and white matter integrity. TRIAL REGISTRATION: UMIN Clinical Trials Registry (number UMIN000000468 ). Registered 18 August 2006.

[French psychiatric therapeutic system for adults, an overview of mental health legislations].

In this article, the authors present an overview of the current French psychiatric therapeutic system for adults and legislation focusing on hospitalization procedures and patients' rights advocacy. The aim of this article is to compare the psychiatric therapeutic system in France with that in Japan and to reflect on problems related to involuntary hospitalization in Japan, especially "hospitalization for medical care and protection." French psychiatry has been developing for about 150 years, and is based on the 1838 Statute (la loi 1838). Historically, J-E. Esquirol, defined two modalities of hospital admission: voluntary hospitalization and compulsory hospitalization. The 1838 statute also stipulated in-patients' rights. In the 1960's, the sector psychiatric therapeutic system, "sectorisation," was introduced in France. According to this system, the continuity of treatment is regarded as important and all people with psychiatric disorders are treated continuously by the same therapeutic team in a sector that comprised of 70,000 inhabitants. Following this, the psychiatric ordinance of 1986 defined additionally 12 types of new therapeutic structures. It elaborated French community psychiatry with various intra-/extra-hospital institutions, and also encouraged "hospitalization with consent" (Hospitalisation libre), thus placing more importance on the subjective judgements and autonomy of patients. In accord with "sectorisation", the law of 1990 concerning hospitalization and the advocacy of inpatients' rights defined new procedures of psychiatric hospitalization: "hospitalization at the request of a third party" (Hospitalisation sur demande d'un tiers) and "compulsory hospitalisation" (Hospitalisation d'office). The reform of the law in 2011 went so far as to change the name of each category of admission: i.e. substituting "psychiatric medical care" for "hospitalisation". It also introduces an evaluation system to review involuntary hospitalization after 24 hours, 72 hours and 15 days during the early stages of hospitalization. This demonstrates the importance of judicial inspection in advocating for clients in determining the continuation of the psychiatric hospitalization. In discussion, we propose three suggestions in terms of quality of treatment and patients' rights advocacy concerning the future reform of psychiatric legislation in Japan: 1) institute an evaluation system to examine the validity of involuntary hospitalization, especially in the early phase of hospitalization; 2) recognize the necessity of making third parties such as Psychiatric Review Board or the courts responsive to the needs of psychiatric patients 3) ameliorate the Japanese Protector System for patients to bring it in line with contemporary contractual treatment of patients and to show a greater respect for patients' autonomy.

Reliability and diagnostic validity for schizophrenia of the Japanese version of the Bonn Scale for Assessment of Basic Symptoms (BSABS).

Schizophrenia is defined by operative diagnostic criteria in DSM-IV with some typical symptoms as hallucinations and duration of the disease. Huber focused on the subjective experience of patients and coined the term "basic symptoms" and created BSABS. Our study investigated the reliability and the diagnostic validity of the 5 clusters of BSABS for DSM-IV-based diagnosis of schizophrenia with a cohort of 105 patients. Good inter-rater reliability was obtained except for one item D.10. As evaluated by Spearman's rank correlation coefficients, among the 5 clusters excluding Cluster 2, internal consistency was good. This suggests that, although each cluster is heterogeneous, cluster symptoms are the expression of physiological and biological disturbances of schizophrenia. Receiver Operating Characteristic Curve analysis was also used to show the ability of each cluster to discriminate schizophrenia. Results showed that the area representing the powers in discriminate schizophrenia of Cluster 4 "Adynamia", which is considered related to the dynamic aspect of thinking, was highest, at 0.739. Cluster 1 "Information processing disturbances" which has a predictive ability for schizophrenia showed 0.714 and Cluster 3 "Impaired tolerance to normal stress" showed 0.711. Our findings suggest that, although these clusters symptoms differ from DSM-IV criteria, they are related to fundamental process of schizophrenia. Use of some of these three clusters with other neurophysiological markers could allow clinical evaluation of schizophrenia from a new perspective.

[A case of thiamine deficiency with psychotic symptoms--blood concentration of thiamine and response to therapy].

We report the case of a 63-year-old woman with thiamine deficiency who showed auditory hallucinations, a delusion of persecution, catatonic stupor, and catalepsy but no neurological symptoms including oculomotor or gait disturbance. Brain MRI did not show high-intensity T2 signals in regions including the thalami, mamillary bodies, or periaqueductal area. Her thiamine concentration was 19 ng/mL, only slightly less than the reference range of 20-50 ng/mL. Her psychosis was unresponsive to antipsychotics or electroconvulsive therapy, but was ameliorated by repetitive intravenous thiamine administrations at 100-200 mg per day. However, one month after completing intravenous treatment, her psychosis recurred, even though she was given 150 mg of thiamine per day orally and her blood concentration of thiamine was maintained at far higher than the reference range. Again, intravenous thiamine administration was necessary to ameliorate her symptoms. The present patient indicates that the possibility of thiamine deficiency should be considered in cases of psychosis without neurological disturbance and high-intensity T2 MRI lesions. Also, this case suggests that a high blood thiamine concentration does not necessarily correspond to sufficient thiamine levels in the brain. Based on this, we must reconsider the importance of a high dose of thiamine administration as a therapy for thiamine deficiency. The validity of the reference range of the thiamine concentration, 20-50 ng/mL, is critically reviewed.