Prompt improvement of difficulty with sleep initiation and waking up in the morning and daytime somnolence by combination therapy of suvorexant and ramelteon in delayed sleep-wake phase disorder: a case series of three patients.

Patients with delayed sleep-wake phase disorder (DSWPD) suffer from difficulties in sleep initiation at night, difficulties in waking up at the socially required time, and daytime somnolence. About half of the patients resist conventional light therapy and melatonin therapy. Therapy using hypnotics is not recommended due to its adverse effects. Recently, suvorexant, an orexin receptor antagonist, has become available for clinical use. The drug is relatively safer than traditional hypnotics such as benzodiazepines. We report three DSWPD patients who were successfully treated by the combination therapy of suvorexant and ramelteon. The first case was a 19-year-old woman who was experiencing difficulties in sleep initiation, difficulty in waking up in the morning, and daytime somnolence. She showed a prompt response to the combination therapy of suvorexant and ramelteon. Her sleep phase advanced, and her daytime somnolence reduced. The second and third cases were 21-year-old and 17-year-old men, respectively, who also showed significant sleep phase advances. Although case 2 was resistant to ramelteon treatment, his sleep phase advanced after suvorexant started. His difficulty in falling asleep and his habit of daytime napping disappeared after the combination therapy of suvorexant and ramelteon was started. Case 3 also showed a prompt response. His difficulties in falling asleep and waking up in the morning were ameliorated immediately after suvorexant with ramelteon was started. No obvious side effects were observed. Therapy using the combination therapy of suvorexant and ramelteon might be a reasonable option for DSWPD patients.

Electroconvulsive shock restores the decreased coverage of brain blood vessels by astrocytic endfeet and ameliorates depressive-like behavior.

BACKGROUND: Although growing evidence indicates that ECT affects astrocytes, the exact mechanisms of the therapeutic effect of ECT are still unknown. Astrocytic endfeet express the water channel aquaporin (AQP) 4 abundantly and ensheath brain blood vessels to form gliovascular units. It has been shown that the coverage of blood vessels by AQP4-immunostained endfeet is decreased in the prefrontal cortex (PFC) of patients with major depression. This study was made to determine whether ECT restores the astrocytic coverage of blood vessels with amelioration of depressive symptoms. METHODS: After electroconvulsive shock (ECS) administration to rats, the forced swimming test (FST) and Y-maze test were performed. Subsequently, immunofluorescence analysis was conducted to measure the coverage of blood vessels by astrocytic endfeet in the PFC and hippocampus by using the endothelial cell marker lectin and anti-AQP4 antibody. We also performed Western blot to examine the effects of ECS on the hippocampal expression of AQP4 and the tight junction molecule claudin-5. RESULTS: Gunn rats showed learned helplessness and impaired spatial working memory, compared to normal control Wistar rats. ECS significantly improved the depressive-like behavior. Gunn rats showed a decrease in astrocytic coverage of blood vessels, that was significantly increased by ECS. ECS significantly increased expression of AQP4 and claudin-5 in Gunn rats. CONCLUSIONS: ECS increased the reduced coverage of blood vessels by astrocytic endfeet in the mPFC and hippocampus with amelioration of depressive-like behavior. Therefore, therapeutic mechanism of ECT may involve restoration of the impaired gliovascular units by increasing the astrocytic-endfoot coverage of blood vessels.

Gunn rats with glial activation in the hippocampus show prolonged immobility time in the forced swimming test and tail suspension test.

INTRODUCTION: Recent studies imply that glial activation plays a role in the pathogenesis of psychiatric disorders, such as schizophrenia and major depression. We previously demonstrated that Gunn rats with hyperbilirubinemia show congenital gliosis and schizophrenia-like behavior. METHODS: As it has been suggested that major depression involves glial activation associated with neuroinflammation, we examined whether Gunn rats show depression-like behavior using the forced swimming test (FST) and the tail suspension test (TST). In addition, we quantitatively evaluated both microgliosis and astrogliosis in the hippocampus of Gunn rats using immunohistochemistry analysis of the microglial marker ionized calcium-binding adaptor molecule (Iba) 1 and the astrocytic marker S100B. RESULTS: Both the FST and TST showed that immobility time of Gunn rats was significantly longer than that of normal control Wistar rats, indicating that Gunn rats are somewhat helpless, a sign of depression-like behavior. In the quantification of immunohistochemical analysis, Iba1immunoreactivity in the dentate gyrus (DG), cornu ammonis (CA) 1, and CA3 and the number of Iba1-positive cells in the CA1 and CA3 were significantly increased in Gunn rats compared to Wistar rats. S100B immunoreactivity in the DG, CA1, and CA3 and the number of S100B-positive cells in the DG and CA3 were significantly increased in Gunn rats compared to Wistar rats. CONCLUSION: Our findings suggest that both microglia and astrocyte are activated in Gunn rats and their learned helplessness could be related to glial activation.

May salivary alpha-amylase level be a useful tool for assessment of the severity of schizophrenia and evaluation of therapy? A case report.

Background. Previous studies suggested dysfunction of the autonomic nervous system (ANS) in schizophrenia patients, but the mechanism remains unclear. Recently, the measurement of salivary alpha-amylase (sAA) has been considered a useful tool for evaluating ANS, especially the sympathoadrenal medullary system. Furthermore, there was a report that patients with schizophrenia showed much higher sAA level than normal controls. Methods. We present the case of a 51-year-old female with catatonic schizophrenia. She needed the treatment of electroconvulsive therapy (ECT). We evaluated her sAA level and her psychiatric symptoms during the treatment. Results. Before ECT treatment, she showed high sAA level. Her sAA level decreased during the course of ECT, and this attenuation was accompanied by improvement of schizophrenic symptoms. Conclusion. We consider that measurement of the sAA level may be one of the useful biological markers for assessment of psychotic state and efficacy of treatment in patients with schizophrenia.

Yi-gan san for treatment of charles bonnet syndrome (visual hallucination due to vision loss): an open-label study.

BACKGROUND: Recent studies indicate that the traditional Japanese herbal medicine yi-gan san (YGS, yokukan-san in Japanese) may be safe and useful for treating behavioral and psychological symptoms in dementia, borderline personality disorder, neuroleptic-induced tardive dyskinesia, and treatment-resistant schizophrenia. Visual hallucinations are common and often distressing consequences of vision loss, particularly in age-related macular degeneration. Charles Bonnet syndrome (CBS) is defined by the triad of complex visual hallucinations, ocular pathology causing visual deterioration, and preserved cognitive status. We aimed at evaluating both the efficacy and safety of YGS in patients with CBS. METHODS: Twenty patients diagnosed with CBS were investigated, according to the diagnostic criteria established by Gold and Rabins and Teunisse. Participants were treated in a 4-week open-label study with YGS at an average daily dose of 5.8 ± 2.6 g (2.5-7.5 g). Psychometric instruments used to assess efficacy included the Neuropsychiatric Inventory, hallucination subscale of the Positive and Negative Syndrome Scale, and Clinical Global Impression. No cases of serious adverse events were attributed to the study's drug therapy. RESULTS: A significant decrease in visual hallucination was observed at 2 and 4 weeks in the Neuropsychiatric Inventory, hallucination subscale of the Positive and Negative Syndrome Scale, and Clinical Global Impression scores. CONCLUSIONS: Yi-gan san may be an effective and safe therapy to control visual hallucination in patients with CBS and should be further tested in double-blind, placebo-controlled trials. Given the design characteristics of this trial, the present findings should be taken cautiously.