Parasomnia induced by lemborexant: a case report.

Lemborexant, an orexin receptor antagonist, is effective not only for sleep disorders but also for preventing and treating delirium. To date, no complex sleep-related behaviors due to lemborexant have been reported. Herein, we present the case of a 69-year-old male patient who was hospitalized for oral floor and tongue cancer and developed delirium after surgery; however, upon lemborexant dosage increase, used to treat insomnia, he developed abnormal nocturnal behavior. This symptom rapidly improved when lemborexant was discontinued. Distinguishing parasomnia from delirium is important because the treatment of these two conditions differs. Although rapid eye movement sleep behavior or sleepwalking was the cause of this parasomnia, a definitive diagnosis could not be established. If qualitatively distinct abnormal behavior is observed compared to delirium after increasing lemborexant dosage, the possibility of parasomnia should be considered.

Reduced functional connectivity in the prefrontal cortex of elderly catatonia patients: A longitudinal study using functional near-infrared spectroscopy.

Catatonia is a syndrome that manifests in patients with mental disorders and general medical conditions. However, functional changes to the brain that cause catatonia remain unknown. In the present study, we used functional near-infrared spectroscopy (fNIRS) to assess spontaneous hemodynamic activities in the brain at the times of onset and resolution of catatonic symptoms in patients with catatonia. We used 22-channel and 49-channel fNIRS to examine hemodynamic activities in the prefrontal cortex (PFC), and both frontal and parietal cortices, respectively. A total of ten patients who were diagnosed with catatonia were included in the study. Resting state measurements were taken for five minutes at the time of the onset and resolution of catatonic symptoms. Analyses were performed for the prefrontal region and the motor cortex within the parietal-frontal region of the brain. Functional connectivity between the cerebral hemispheres was evaluated systematically based on spontaneous oscillation of Δ[HbO2]. In the PFC, the resting state functional connectivity (RSFC) was significantly lower in the catatonic state than in the eyes-closed non-catatonic state (p = 0.047). The study demonstrated that the RSFC in the PFC, measured using fNIRS, may be an objective indicator of the change in catatonic symptoms.

57R2A, a newly established monoclonal antibody against mouse GPR56, marks long-term repopulating hematopoietic stem cells.

GPR56 molecule, a G-protein-coupled receptor, was suggested to be expressed in mouse hematopoietic stem cells (HSCs) by gene expression analyses. However, little is known about the cell surface expression of GPR56 protein in mouse HSCs due to the absence of an appropriate monoclonal antibody against GPR56 for flow cytometry analyses. In the present study, we established a novel monoclonal antibody against mouse GPR56 (57R2A) to examine the expression and distribution of GPR56 protein in HSCs. A flow cytometry analysis using 57R2A showed that GPR56 was highly expressed in the CD34-, c-Kit+, Sca-1+, lineage-negative (Lin-) fraction, which are highly enriched with HSCs. The competitive long-term repopulation (LTR) assay showed that LTR cells were included only within the GPR56+ fraction (≤15%) of bone marrow mononuclear cells (BMMNCs), but not within the remaining GPR56- fraction (85%), suggesting that all HSCs express GPR56 protein on their surface. Furthermore, we showed that double staining of BMMNCs with only 57R2A and AMM2 (monoclonal antibody against the HSC marker MPL) enabled enrichment of all LTR cells in the double-positive fraction (0.8% of BMMNCs), within which the LTR potency was consistent with the expression of both GPR56 and MPL. In conclusion, these findings for 57R2A suggest that all HSCs in mouse BMMNCs express GPR56 protein on their surface and that GPR56 is a positive marker for HSCs.

Jitteriness/Anxiety Syndrome Developing Immediately following Initiation of Oral Administration of Sertraline.

Here, we report our experience with patients in whom jitteriness/anxiety syndrome developed immediately following the start of oral sertraline administration. Administration was discontinued in these patients on day 2, and the jitteriness/anxiety syndrome improved the following day. Jitteriness/anxiety syndrome may develop immediately following oral administration of even low doses of sertraline, and improvement can be expected if sertraline is promptly discontinued.

Patterns of hippocampal atrophy differ among Alzheimer's disease, amnestic mild cognitive impairment, and late-life depression.

AIM: This study investigated whether the characteristic changes in hippocampal atrophy seen in coronal scans are useful for differentiating Alzheimer's disease (AD), amnestic mild cognitive impairment (aMCI), and major depressive disorder (MDD). METHODS: Subjects included 58 patients with AD, 33 with aMCI, 20 with MDD, and 22 normal controls, all aged 60 years or older. For each subject, eight coronal short TI inversion recovery images perpendicular to the hippocampal longitudinal axis were obtained. Images were manually measured using the conventional region of interest method of quantitative analysis. RESULTS: The overall trend in the corrected volumes of the hippocampus was AD < aMCI < MDD < normal controls. We found atrophy in all slices in AD, atrophy centred on the hippocampal head in aMCI, and atrophy in the slice of the hippocampal body 12 mm from the amygdala in MDD. CONCLUSIONS: The present study suggested that our method of comparing hippocampal atrophy by region may be useful in distinguishing AD, aMCI, MDD, and normal controls.

Comparison of alterations in cerebral hemoglobin oxygenation in late life depression and Alzheimer's disease as assessed by near-infrared spectroscopy.

BACKGROUND: Patients with Alzheimer's disease (AD) often present with apathy symptoms resembling the decreased motivation observed in depressed patients. Therefore, differentiating the initial phase of AD from late life depression may be difficult in some cases. Near-infrared spectroscopy (NIRS) is a functional neuroimaging modality that uses near-infrared light to measure changes in hemoglobin concentration on the cortical surface during activation tasks. The objective of this study was to investigate differences in brain activation associated with late life depression and with AD by means of NIRS. METHODS: NIRS was performed in 30 patients with depression, 28 patients with AD, and 33 healthy controls, all aged 60 years or older. During two tasks, a verbal fluency task and a visuospatial task, changes in oxygenated hemoglobin concentration in the frontal and parietal cortices were investigated. RESULTS: In the visuospatial task, cortical activation was lower in the depressed group than in the AD group, and significant differences were observed in the parietal cortex. CONCLUSIONS: NIRS can detect differences in brain activation between patients with late life depression and those with AD. NIRS is a promising tool for the differential diagnosis of late life depression and AD.

[Psychiatric occupational therapy practice in Shinshu University Hospital--collaboration with psychiatrist].

This report describes psychiatric occupational therapy practice and collaboration between occupational therapists and psychiatrists at Shinshu University Hospital. Collaboration with psychiatrists enables us to provide the following occupational therapy programs. (1) Individual occupational therapy approaches for patients at the early recovery stage in the psychiatric ward. (2) Psychoeducational interventions by a multi-disciplinary team (MDs, nurses, OTRs, PSWs, CPs). (3) Occupational therapy approaches used in combination with m-ECT for severe psychiatric disorders. (4) Recovery support programs for psychiatric outpatients. It is suggested that occupational therapists should collaborate with psychiatrists in order to facilitate rehabilitation services for people with psychiatric disorders.

Comparison of diagnostic names of mental illnesses in medical documents before and after the adoption of a new Japanese translation of 'schizophrenia'.

AIM: The name of a disease entered in medical documents often differs from the true diagnosis in psychiatric practice. We examined the effects of different translations of 'schizophrenia' into Japanese on the usage of disease names in documents. METHODS: We conducted a retrospective survey of the names of diseases used in the medical documents of 250 outpatients with schizophrenia or depression. These patients had attended our department of psychiatry between 1998 and 2000. We also investigated the names of the diseases of 226 outpatients who had first visited our department between 2003 and 2007. We defined the diagnosis (based on ICD-10) as the 'ICD-10 disease name' and the name of the disease written in medical documents as the 'disease name in documents'. We classified the documents that were used to apply for national psychiatric care and welfare services as 'official documents' and those submitted to others as 'private documents'. RESULTS: Prior to 2000, the term 'seishin-bunretsu-byo' ('split-mind disease'; old translation of 'schizophrenia') was used in 72.3% of official documents and 3.6% of private documents. In 2003 and later, the term 'togo-shitcho-sho' ('integration disorder'; new translation of 'schizophrenia') was used in 98.0% of official documents and 21.7% of private documents. CONCLUSION: The use of 'togo-shitcho-sho' in official documents has become established. On the other hand, terms such as 'nervous breakdown' and 'depressive state' are still commonly used in private documents after the adoption of the new Japanese translation of schizophrenia.

In vivo efficacy of anti-MPL agonist antibody in promoting primary human hematopoietic cells.

In a previous study, we generated novel antithrombopoietin receptor agonist antibodies as therapeutic candidates. In this report, we investigated the in vivo effects of one of these antibodies, MA01G4344U, on primary human hematopoietic cells using xenotransplantation. NOD/Shi-scid, IL-2Rgamma(null) (NOG) mice were pretreated by total-body irradiation and received a transplant of human cord blood-derived CD34(+) cells. Weekly intraperitoneal injection of MA01G4344U (100 microg/mouse per week) or Peg-rhMGDF (5 microg/mouse per week) or phosphate-buffered saline (PBS) was performed. Human cells in peripheral blood were analyzed by flow cytometry and bone marrow cells were analyzed by flow cytometry and colony assay. MA01G4344U successfully increased the number of human CD41(+) platelets and human CD45(+) cells in peripheral blood. In the bone marrow, MA01G4344U increased the number of human CD45(+)/CD34(+) cells, which resulted in more multilineage progenitor cells. The efficacy of MA01G4344U in promoting primary human hematopoietic cells in vivo suggests its therapeutic potential for thrombocytopenic and pancytopenic disorders.

Expression profile analysis of aorta-gonad-mesonephros region-derived stromal cells reveals genes that regulate hematopoiesis.

The aorta-gonad-mesonephros (AGM) region is involved in the generation and maintenance of the first definitive hematopoietic stem cells (HSCs). A mouse AGM-derived cell line, AGM-S3, was shown to support the development of HSCs. To elucidate the molecular mechanisms regulating early hematopoiesis, we obtained subclones from AGM-S3, one of which was hematopoiesis supportive (S3-A9) and the other one of which was non-supportive (S3-A7), and we analyzed their gene expression profiles by gene chip analysis. In the present study, we found that Glypican-1 (GPC1) was highly expressed in the supportive subclone AGM-S3-A9. Over-expression of GPC1 in non-supportive cells led to the proliferation of progenitor cells in human cord blood when cocultured with the transfected-stromal cells. Thus, GPC1 may have an important role in the establishment of a microenvironment that supports early events in hematopoiesis.

Switching constant domains enhances agonist activities of antibodies to a thrombopoietin receptor.

We enhanced the activities of two agonist antibodies specific for the thrombopoietin receptor (c-MPL) by switching domains within their constant regions to those of different antibody isotypes. Our results suggest the importance of the hinge region in modulating agonist activity. The antibodies' thrombopoietin-like activity in vitro and in vivo, as well as the desirable pharmacokinetic profile conferred by retaining the whole-IgG structure, suggests that they provide a valuable option for treating thrombocytopenia.

Thrombopoietin/MPL signaling regulates hematopoietic stem cell quiescence and interaction with the osteoblastic niche.

Maintenance of hematopoietic stem cells (HSCs) depends on interaction with their niche. Here we show that the long-term (LT)-HSCs expressing the thrombopoietin (THPO) receptor, MPL, are a quiescent population in adult bone marrow (BM) and are closely associated with THPO-producing osteoblastic cells. THPO/MPL signaling upregulated beta1-integrin and cyclin-dependent kinase inhibitors in HSCs. Furthermore, inhibition and stimulation of THPO/MPL pathway by treatments with anti-MPL neutralizing antibody, AMM2, and with THPO showed reciprocal regulation of quiescence of LT-HSC. AMM2 treatment reduced the number of quiescent LT-HSCs and allowed exogenous HSC engraftment without irradiation. By contrast, exogenous THPO transiently increased quiescent HSC population and subsequently induced HSC proliferation in vivo. Altogether, these observations suggest that THPO/MPL signaling plays a critical role of LT-HSC regulation in the osteoblastic niche.

Negative regulation of platelet clearance and of the macrophage phagocytic response by the transmembrane glycoprotein SHPS-1.

SHPS-1 is a receptor-type glycoprotein that binds and activates the protein-tyrosine phosphatases SHP-1 and SHP-2, and thereby negatively modulates intracellular signaling initiated by various cell surface receptors coupled to tyrosine kinases. SHPS-1 also regulates intercellular communication in the neural and immune systems through its association with CD47 (integrin-associated protein) on adjacent cells. Furthermore, recent studies with fibroblasts derived from mice expressing an SHPS-1 mutant that lacks most of the cytoplasmic region suggested that the intact protein contributes to cytoskeletal function. Mice homozygous for this SHPS-1 mutation have now been shown to manifest thrombocytopenia. These animals did not exhibit a defect in megakaryocytopoiesis or in platelet production. However, platelets were cleared from the bloodstream more rapidly in the mutant mice than in wild-type animals. Furthermore, peritoneal macrophages from the mutant mice phagocytosed red blood cells more effectively than did those from wild-type mice; in addition, they exhibited an increase both in the rate of cell spreading and in the formation of filopodia-like structures at the cell periphery. These results indicate that SHPS-1 both contributes to the survival of circulating platelets and down-regulates the macrophage phagocytic response.