Shiro Suda

A Postpartum Model in Rat : Behavioral and Gene Expression Changes Induced by Ovarian Steroid Deprivation

BACKGROUNDnPostpartum depression (PPD) affects approximately 10% to 20% of women during the first 4 weeks of the postpartum period and is characterized by labile mood with prominent anxiety and irritability, insomnia, and depressive mood. During the postpartum period, elevated ovarian hormones abruptly decrease to the early follicular phase levels that are postulated to play a major role in triggering PPD. However, the underlying neurobiological mechanisms that contribute to PPD have not been determined.nnnMETHODSnIn the present study, we examined the effect of ovarian steroids, administered at levels that occur during human pregnancy followed by rapid withdrawal to simulate postpartum conditions, on behavior and gene expression in the rat.nnnRESULTSnThe results of behavioral testing reveal that the hormone-simulated postpartum treatment results in the development of a phenotype relevant to PPD, including vulnerability for helplessness, increased anxiety, and aggression. Real-time quantitative polymerase chain reaction (PCR) demonstrated transient regulation of several genes, including Ca(2+)/calmodulin-dependent protein kinase II (CAMKII), serotonin transporter (SERT), myocyte enhancer factor 2A (MEF2A), brain-derived neurotrophic factor (BDNF), gamma-aminobutyric acid type A receptor alpha 4 (GABAARA4), mothers against decapentaplegic homolog 4 (SMAD4), and aquaporin 4 (AQP4) that could underlie these behavioral effects.nnnCONCLUSIONSnThese studies provide an improved understanding of the effects of withdrawal from high doses of ovarian hormones on behavior and gene expression changes in the brain that could contribute to the pathophysiology of PPD.

Disruption of reelin signaling attenuates methamphetamine-induced hyperlocomotion

To clarify whether reelin signaling is involved in dopaminergic neurotransmission in the adult mouse brain, we investigated dopamine function in mice lacking reelin (reeler). We found that methamphetamine‐induced locomotor activity is significantly attenuated in reeler mice. To elucidate the mechanism of this phenomenon, we first investigated presynaptic dopamine release; however, there were no significant differences in wildtype, heterozygous reeler and homozygous reeler mice. Next, we examined the locomotor response to intra‐accumbens injection of dopamine D1 and D2 receptor agonists, and found that lack of reelin signaling results in decreases in both D1 and D2 receptor‐mediated dopaminergic functions. In addition, we measured dopamine receptor binding in the striatum, and found that both D1 and D2 classes of dopamine receptors are reduced in reeler mice. Furthermore, we found that the phosphorylation levels of DARPP‐32 are also changed by lack of reelin signaling. Finally, to distinguish between a developmental role of reelin or an acute role of reelin in adult mouse, we intraventricularly infused CR‐50, a monoclonal antibody against reelin. Interestingly, infusion of CR‐50 also significantly reduced methamphetamine‐induced hyperlocomotion in wildtype mice, showing that reelin has an acute role in the dopaminergic system. These results indicate that reelin signaling plays a pivotal role in the dopaminergic system in adult mice, especially in postsynaptic levels.

Electroconvulsive therapy for burning mouth syndrome

Objective:u2002 Burning mouth syndrome (BMS) is an orofacial pain disorder characterized by a chronic, idiopathic burning sensation of the oral mucosa that mostly affects middle‐aged women. Although both psychological and neuropathological factors have been postulated to underlie BMS, the pathogenic mechanism of the condition remains controversial, as do the treatment strategies.

Need for close watch on children's health after Fukushima disaster.

www.thelancet.com Vol 378 August 6, 2011 485 I support Tetsuya Tanimoto and colleagues’ call to mobilise the scientifi c community and develop ideas to protect the health of the workers involved in the battle to stabilise the damaged nuclear reactors at the Fukushima Daiichi nuclear power plant, together with that of residents of the surrounding areas. Strontium-90 (90Sr) is a fi ssion product of uranium and plutonium and is frequently released in high quantities during nuclear accidents such as the one at Fukushima. Chemically similar to calcium, 90Sr is a bone-seeker radioactive isotope and gets preferentially incorporated into bone, especially in areas of active bone remodelling. Once introduced into the body, 90Sr can accumulate and persist in skeletal tissues for decades. It is a β-emitter with a half-life of about 29 years. Internal exposure to 90Sr results in high radiation doses to both bone tissue and bone marrow, where skeletal progenitors and haemopoietic stem cells reside. Exposure to 90Sr is associated with development of bone cancer in several animal models. In the past three decades, research into osteoporosis has led to the development of several antiresorptive drugs capable of inhibiting bone remodelling—the coupled process of bone resorption and bone formation. Importantly, clinical evidence suggests that preventive administration of diff erent types of bisphosphonates is able to reduce incorporation of strontium into bone. Among the latest additions to the antiresorptive drug class, the anti-RANKL monoclonal antibody denosumab can achieve a 6-month reversible inhibition of bone-remodelling after a single dose given by subcutaneous injection. All these drugs are associated with fairly safe toxicological profi les. I would like to encourage investigators worldwide to explore the possibility of antiresorptive drugs as a means to reduce the permanent incorporation of 90Sr into bone tissues, and thus to reduce the risk of bone cancer, and possibly leukaemia, in people exposed to radionuclides during nuclear accidents.

Differences in vulnerability to traumatic stress among patients with psychiatric disorders: One-year follow-up study after the Great East Japan Earthquake

The aim of this study was to evaluate differences in vulnerability to traumatic stress and the 1‐year course of post‐traumatic stress symptoms among patients with pre‐existing psychiatric disorders after the Great East Japan Earthquake.

Sleep complaints are associated with reduced left prefrontal activation during a verbal fluency task in patients with major depression: A multi-channel near-infrared spectroscopy study

BACKGROUNDnRecent studies have indicated the potential clinical use of near-infrared spectroscopy (NIRS) as a tool for assisting in the diagnosis of major depressive disorder (MDD). Although sleep complaints are often manifested in MDD, no study has elucidated the possible association between the objective evaluation of sleep and NIRS signals in MDD.nnnMETHODSnFourteen patients with MDD and 15 healthy controls wore waist actigraphy equipment before the NIRS scan to investigate sleep parameters. We performed a 52-channel NIRS scan and measured changes in oxygenated hemoglobin ([oxy-Hb]) during a verbal fluency task.nnnRESULTSnIn patients with MDD, a significant negative correlation was observed between the 17-item Hamilton Depressive Rating Scale score and cerebral reactivity of the right temporal region (ps:=-0.804 to -0.762; FDR-corrected; p=0.008-0.012). The Pittsburgh Sleep Questionnaire Index, which enables assessment of continuous sleep quality and disturbances, was negatively correlated with [oxy-Hb] changes in the left prefrontal cortex (ps=-0.630 to -0.551; FDR-corrected; p=0.043-0.048). Actigraphic sleep variables prior to the NIRS measurement showed no significant correlation with [oxy-Hb] changes.nnnLIMITATIONSnThe limitations were small sample size with the low severity of depression and the use of actigraphy for only one night.nnnCONCLUSIONnSelf-rated sleep disturbance were associated with decreased left prefrontal reactivity during a verbal fluency task in patients with MDD. Our result indicates that the reactivity of the prefrontal region is susceptible to sleep complaints, providing further evidence to support potential clinical application of NIRS.

Unilateral hippocampal infarction associated with an attempted suicide: a case report

IntroductionIn our case report we describe the case of a patient who experienced a stroke in her left hippocampus that was found following an attempted suicide via glyphosate overdose. To the best of our knowledge this is the first case report to describe a hippocampal infarction associated with a drug overdose.Case presentationA 64-year-old Japanese woman was brought to our emergency department after ingestion of an unknown dose of glyphosate surfactant herbicide in order to attempt suicide. On admission, she was assumed to be presenting with depression or psychiatric illness, however, sudden-onset memory deficit became apparent. The patient manifested delirium, confusion, and severe anxiety. In addition, short-term memory loss was prominent, with the patient forgetting her attempted suicide. Following an array of standard tests and a brain computed tomography scan (which only showed an old infraction), we performed a magnetic resonance imaging scan and neuropsychological evaluations. The brain magnetic resonance image revealed a small high-intensity lesion in the dorsal part of the left hippocampal body, and memory tests demonstrated severe short-term recall deficits. We diagnosed her with a left hippocampal infarction and administered a course of 75mg of clopidogrel. She gradually became less confused over the course of a week, and a follow-up memory test revealed partial improvement in some domains. No abnormalities were found on a follow-up brain scan. However, despite rehabilitation, memory impairments remain.ConclusionsIt is important to note that had the symptom of short-term memory been absent or less severe, she might have been misdiagnosed with depression or another psychiatric illness. Although a computed tomography scan failed to detect hippocampal lesions, a diffusion-weighted magnetic resonance imaging scan clearly revealed a lesion within the left hippocampus. Therefore, in addition to assessments focusing on psychiatric illnesses that might be the root cause of an attempted suicide, organic factors should be considered along with radiological examination and precise memory assessments for diagnosing similar cases.

Association of Transcription Factor Gene LMX1B with Autism

Multiple lines of evidence suggest a serotoninergic dysfunction in autism. The role of LMX1B in the development and maintenance of serotoninergic neurons is well known. In order to examine the role, if any, of LMX1B with autism pathophysiology, a trio-based SNP association study using 252 family samples from the AGRE was performed. Using pair-wise tagging method, 24 SNPs were selected from the HapMap data, based on their location and minor allele frequency. Two SNPs (rs10732392 and rs12336217) showed moderate association with autism with p values 0.018 and 0.022 respectively in transmission disequilibrium test. The haplotype AGCGTG also showed significant association (pu200a=u200a0.008). Further, LMX1B mRNA expressions were studied in the postmortem brain tissues of autism subjects and healthy controls samples. LMX1B transcripts was found to be significantly lower in the anterior cingulate gyrus region of autism patients compared with controls (pu200a=u200a0.049). Our study suggests a possible role of LMX1B in the pathophysiology of autism. Based on previous reports, it is likely to be mediated through a seretoninergic mechanism. This is the first report on the association of LMX1B with autism, though it should be viewed with some caution considering the modest associations we report.

Electroconvulsive Therapy for Catatonia With Deep Venous Thrombosis: A Case Series

ObjectivenCatatonia is a motor dysregulation syndrome often accompanied by deep vein thrombosis (DVT) and pulmonary embolism (PE). Although electroconvulsive therapy (ECT) is effective for catatonia, it is unknown whether ECT contributes to the onset of a PE from a residual DVT. The objective of this case series is to examine and propose safety methods for ECT in catatonia patients with a DVT.nnnMethodsnData were obtained retrospectively via chart review for 5 psychiatric inpatients diagnosed with catatonia based on DSM-IV-TR or DSM-5 criteria from April 2010 to March 2017 who underwent ECT after developing a DVT.nnnResultsnAll 5 patients received anticoagulation therapy after the onset of DVT and underwent subsequent ECT. Three patients had distal DVT (thromboses located below the knee in the calf veins) before ECT, which did not result in an onset of PE in the course of ECT. One had a proximal DVT (thromboses in the popliteal vein and above), and the ECT session was completed without the occurrence of PE. In the fifth patient, a proximal DVT developed into a PE after an ECT session.nnnConclusionsnThese results suggest that it is important to determine the location of a DVT and to continue anticoagulation therapy until a proximal DVT disappears before ECT is performed.

Night duty and decreased brain activity of medical residents: A wearable optical topography study

ABSTRACT Background: Overwork, fatigue, and sleep deprivation due to night duty are likely to be detrimental to the performance of medical residents and can consequently affect patient safety. Objective: The aim of this study was to determine the possibility of deterioration of cerebral function of sleep-deprived, fatigued residents using neuroimaging techniques. Design: Six medical residents were instructed to draw blood from artificial vessels installed on the arm of a normal cooperator. Blood was drawn at a similar time of the day, before and after night duty. To assess sleep conditions during night duty, the participants wore actigraphy units throughout the period of night duty. Changes in cerebral hemodynamics, during the course of drawing blood, were measured using a wearable optical topography system. Results: The visual analogue scale scores after night duty correlated negatively with sleep efficiency during the night duty (ρ = −0.812, p = 0.050). The right prefrontal cortex activity was significantly decreased in the second trial after night duty compared with the first (p = 0.028). The extent of [oxy-Hb] decrease, indicating decreased activity, in the right dorsolateral prefrontal cortex correlated negatively with the Epworth sleepiness score after night duty (ρ = −0.841, p = 0.036). Conclusions: Sleep deprivation and fatigue after night duty, caused a decrease in the activity of the right dorsolateral prefrontal cortex of the residents, even with a relatively easy routine. This result implies that the brain activity of medical residents exposed to stress on night duty, although not substantially sleep-deprived, was impaired after the night duty, even though they apparently performed a simple medical technique appropriately. Reconsideration of the shift assignments of medical residents is strongly advised. Abbreviations: DLPFC: Dorsolateral prefrontal cortex; ESS: Epworth sleepiness scale; PSQI: Pittsburgh sleep quality index; ROI: Regions of interest; VAS: Visual analogue scale; WOT: Wearable optical topography