Whole-exome sequencing and gene-based rare variant association tests suggest that PLA2G4E might be a risk gene for panic disorder.

Panic disorder (PD) is characterized by recurrent and unexpected panic attacks, subsequent anticipatory anxiety, and phobic avoidance. Recent epidemiological and genetic studies have revealed that genetic factors contribute to the pathogenesis of PD. We performed whole-exome sequencing on one Japanese family, including multiple patients with panic disorder, which identified seven rare protein-altering variants. We then screened these genes in a Japanese PD case-control group (384 sporadic PD patients and 571 controls), resulting in the detection of three novel single nucleotide variants as potential candidates for PD (chr15: 42631993, T>C in GANC; chr15: 42342861, G>T in PLA2G4E; chr20: 3641457, G>C in GFRA4). Statistical analyses of these three genes showed that PLA2G4E yielded the lowest p value in gene-based rare variant association tests by Efficient and Parallelizable Association Container Toolbox algorithms; however, the p value did not reach the significance threshold in the Japanese. Likewise, in a German case-control study (96 sporadic PD patients and 96 controls), PLA2G4E showed the lowest p value but again did not reach the significance threshold. In conclusion, we failed to find any significant variants or genes responsible for the development of PD. Nonetheless, our results still leave open the possibility that rare protein-altering variants in PLA2G4E contribute to the risk of PD, considering the function of this gene.

Methylphenidate enhances neural stem cell differentiation.

BACKGROUND: The psychostimulant methylphenidate (MPH) is the first choice of drug treatment in Attention-Deficit/Hyperactivity Disorder (ADHD). Since therapy often begins at a time when the brain is still developing and the long-term consequences of MPH are still not fully clarified, we examined the influences of an acute treatment with MPH on the differentiation and proliferation of murine neural stem cells (mNSC). FINDINGS AND CONCLUSION: We found that MPH enhanced neuronal differentiation and inhibited neural proliferation.

[Case of schizophrenia in which depressive and negative symptoms relapsed on switching from oral risperidone to risperidone long-acting injection].

I report a case of schizophrenia in which depressive and negative symptoms relapsed on switching from oral risperidone to risperidone long-acting injection (RLAI). The patient, with a 31-year history of schizophrenia, did not fully understand his disease. Therefore, adherence to medication had been extremely poor. The discontinuation of medication led to the recurrence of the disease. After hospital treatment, he was discharged to a group home. From then, the disease had been kept in remission by risperidone at 4 mg/day, and RLAI was introduced for the purpose of further social reintegration and QOL improvement. After starting RLAI at 25 mg, however, a stiff expression and irritability appeared. Therefore, RLAI was increased up to 50 mg, but depressive and negative symptoms relapsed. Subsequently, RLAI was discontinued and oral risperidone was re-administered, and the above mental symptoms improved in a relatively rapid manner. The difference in the ratio of plasma and brain concentrations between each active moiety, risperidone and 9-OH risperidone (paliperidone), resulting from the difference in administration routes, was suggested to be involved as the main factor. In this case, it is likely that positive symptoms did not relapse because plasma concentrations of the active moiety itself were well maintained by introducing RLAI. However, depressive and negative symptoms relapsed possibly as a result of reduced affinity for the alpha2A receptor with relatively decreased plasma concentrations of 9-OH risperidone when compared to oral administration. Another possibility is that negative symptoms were secondary induced by excess administration of antipsychotics, but there has been no such report on RLAI so far. For the reason noted above, careful follow-up is considered necessary when switching from oral risperidone to RLAI because mental symptoms might get worse.

[Chitin/cisplatin--an adhesive anticancer drug].

The authors devised an adhesive anticancer drug delivery system using 70% deacetyalated chitin (DAC-70) and cisplatin (CDDP). We prepared two different types of the drug carriers; namely, DAC-70 viscous solution and DAC-70 lyophilized granules, which easily provided viscous solution when mixed with a liquid. We then formed a novel CDDP-loaded system by mixing each vehicle with CDDP solution. Each product showed a stronger tissue-adhesive force at 37 degrees C than that of 25 degrees C. More than 90% of total CDDP was released from the system within 24 hours. A large amount of the CDDP released from the system revealed it to be free CDDP when the DAC granule was used as the carrier, while the amount of free CDDP was less than 20% in the case of the DAC viscous solution. When the DAC-CDDP solution was given into the peritoneal cavity of rats, the CDDP remained there and only a little was transferred into the peripheral blood. We could also provide loco-regional pleurodesis by injecting the novel solution into the rat pleural cavity. These data suggest that our newly devised system has a great potential in cancer chemotherapy for the patients with malignant pleural effusion and ascites.

Pathway to psychiatric care in Japan: A multicenter observational study.

BACKGROUND: This study examines pathways to psychiatric care in Japan using the same method as the collaborative study carried out in 1991 under the auspices of the World Health Organization. METHODS: Thirteen psychiatric facilities in Japan were involved. Of the 228 patients who contacted psychiatric facilities with any psychiatric illness, eighty four visiting psychiatric facilities for the first time were enrolled. Pathways to psychiatric care, delays from the onset of illness to treatment prior to reaching psychiatrists were surveyed. RESULTS: Thirty three patients (39.4%) directly accessed mental health professionals, 32 patients (38.1%) reached them via general hospital, and 13 patients (15.5%) via private practitioners. The patients who consulted mental health professionals as their first carers took a longer time before consulting psychiatrists than the patients who consulted non-mental health professionals as their first carers. The patients who presented somatic symptoms as their main problem experienced longer delay from the onset of illness to psychiatric care than the patients who complained about depressive or anxiety symptoms. Prior to the visit to mental health professionals, patients were rarely informed about their diagnosis and did not receive appropriate treatments from their physicians. Private practitioners were more likely to prescribe psychotropics than physicians in general hospitals, but were less likely to inform their patients of their diagnosis. CONCLUSION: This first pathway to psychiatric care study in Japan demonstrated that referral pathway in Japan heavily relies on medical resources. The study indicates possible fields and gives indications, underlining the importance of improving skills and knowledge that will facilitate the recognition of psychiatric disorders presenting with somatic and depressive symptoms in the general health care system and by private practitioners.

[A novel anticancer drug delivery system -DAC-70/CDDP].

We devised a muco-adhesive anticancer drug delivery system using 70% deacetylated chitin (DAC-70) and cisplatin (CDDP) and 5-fluorouracil (5-FU). The adhesive force between the system and human colonic mucosa was measured ex vivo, and a release profile of each drug was examined in vitro. Each system demonstrated a stronger muco-adhesive force at 37 degrees C than that of 25 degrees C. The CDDP-loaded system showed a sustained release of the drug while the 5-FU-loaded system exhibited an initial bursting of the agent. We presume that the release profile of CDDP and 5-FU is closely related to both degradability of the chitin and interactions between the chitin and each drug. The DAC-70/CDDP system would be clinically promising in loco-regional cancer chemotherapy.