Docosahexaenoic Acid Promotes Axon Outgrowth by Translational Regulation of Tau and Collapsin Response Mediator Protein 2 Expression.

n-3 PUFAs are essential for neuronal development and brain function. However, the molecular mechanisms underlying their biological effects remain unclear. Here we examined the mechanistic action of docosahexaenoic acid (DHA), the most abundant n-3 polyunsaturated fatty acids in the brain. We found that DHA treatment of cortical neurons resulted in enhanced axon outgrowth that was due to increased axon elongation rates. DHA-mediated axon outgrowth was accompanied by the translational up-regulation of Tau and collapsin response mediator protein 2 (CRMP2), two important axon-related proteins, and the activation of Akt and p70 S6 kinase. Consistent with these findings, rapamycin, a potent inhibitor of mammalian target of rapamycin (mTOR), prevented DHA-mediated axon outgrowth and up-regulation of Tau and CRMP2. In addition, DHA-dependent activation of the Akt-mTOR-S6K pathway enhanced 5'-terminal oligopyrimidine tract-dependent translation of Tau and CRMP2. Therefore, our results revealed an important role for the Akt-mTOR-S6K pathway in DHA-mediated neuronal development.

Does social capital reduce child behavior problems? Results from the Great East Japan Earthquake follow-up for Children Study.

PURPOSE: We sought to investigate the association between social capital and child behavior problems in Iwate prefecture, Japan, in the aftermath of the 2011 Great East Japan Earthquake. METHODS: Children and their caregivers were recruited from four nursery schools in coastal areas affected by the tsunami, as well as one in an unaffected inland area (N = 94). We assessed the following via caregiver questionnaire: perceptions of social capital in the community, child behavior problems (Child Behavior Checklist, Strength and Difficulty Questionnaire), post-traumatic stress disorder (PTSD) symptoms, child's exposure to trauma (e.g. loss of family members), and caregiver's mental health (Impact of Event Scale-R for PTSD symptoms; K6 for general mental health). We collected details on trauma exposure by interviewing child participants. Structural equation modeling was used to assess whether the association between social capital and child behavior problems was mediated by caregiver's mental health status. RESULTS: Children of caregivers who perceived higher community social capital (trust and mutual aid) showed fewer PTSD symptoms. Furthermore, caregiver's mental health mediated the association between social trust and child PTSD symptoms. Social capital had no direct impact on child behavior problems. CONCLUSIONS: Community social capital was indirectly associated (via caregiver mental health status) with child behavior problems following exposure to disaster. Community development to boost social capital among caregivers may help to prevent child behavior problems.

The characteristics of the suicide attempter according to the onset time of the suicidal ideation.

OBJECTIVE: To determine the timing of development of suicidal ideation and factors associated therewith in suicide attempters who required psychiatric emergency treatment. METHODS: Of a total of 2818 suicide attempters in Japan who presented to the primary or secondary emergency department of Iwate Medical University Hospital (hereinafter, referred to as our hospital) or Iwate Prefecture Advanced Emergency and Critical Care Center (hereinafter, referred to as the emergency center), an affiliated institution to our hospital, during the 12-year period from April 1, 2002-March 31, 2014, 2274 patients for whom the timing of development of suicidal ideation was identified were included in the study. The study subjects were classified into three groups according to the timing of development of suicide ideation: the "same-day" group, those who developed suicidal ideation and attempted suicide on the same day; the "short-term" group, those who developed suicidal ideation 2-7 days before attempting suicide; and the "long-term" group, those who developed suicidal ideation more than 7 days before attempting suicide. Factors associated with the development of suicidal ideation in each group were analyzed by a multiple logistic regression analysis with background factors, the diagnosis according to the ICD and the situations before and after the suicide attempt as explanatory variables. RESULTS: The same-day group was characterized by a high female ratio, high global functioning, low stress level, non-depressed status and a lack of seeking consultation. In contrast, the long-term group was characterized by low global functioning and a high stress level, suggesting that these patients exhibit consultation behavior, but have not received psychiatric services. In the short-term group, only male gender was identified as a significant factor. DISCUSSION: For those patients who developed suicidal ideation and attempted suicide on the same day, treatment strategies focusing on the acquisition of coping skills and stress management are recommended. For those with suicidal ideation lasting for more than a week or recurrent ideation, early detection and subsequent early treatment of such ideation are essential. In intermediate cases, treatment strategies that make the full use of mental health management in the workplace and gate-keeping are likely to be effective.

Predictors for delayed encephalopathy following acute carbon monoxide poisoning.

BACKGROUND: In Japan, many carbon monoxide (CO) poisoning cases are transported to emergency settings, making treatment and prognostic assessment an urgent task. However, there is currently no reliable means to predict whether "delayed neuropsychiatric sequelae (DNS)" will develop after acute CO poisoning. This study is intended to find out risk factors for the development of DNS and to characterize the clinical course following the development of DNS in acute CO poisoning cases. METHODS: This is a retrospective cohort study of 79 consecutive patients treated at a single institution for CO poisoning. This study included 79 cases of acute CO poisoning admitted to our emergency department after attempted suicide, who were divided into two groups consisting of 13 cases who developed DNS and 66 cases who did not. The two groups were compared and analyzed in terms of clinical symptoms, laboratory findings, etc. RESULTS: Predictors for the development of DNS following acute CO poisoning included: serious consciousness disturbance at emergency admission; head CT findings indicating hypoxic encephalopathy; hematology findings including high creatine kinase, creatine kinase-MB and lactate dehydrogenase levels; and low Global Assessment Scale scores. The clinical course of the DNS-developing cases was characterized by prolonged hospital stay and a larger number of hyperbaric oxygen (HBO) therapy sessions. CONCLUSION: In patients with the characteristics identified in this study, administration of HBO therapy should be proactively considered after informing their family, at initial stage, of the risk of developing DNS, and at least 5 weeks' follow-up to watch for the development of DNS is considered necessary.

[After the Great East Japan Earthquake : suicide prevention and a gatekeeper program].

When considering approaches to mental health in areas affected by the 2011 Great East Japan Earthquake, as well as the resulting tsunami and Fukushima nuclear power plant accident, it is not sufficient to focus interventions solely on individuals experiencing mental health issues. The situation demands a comprehensive approach that includes programs that target improvements to mental health literacy among residents in areas affected by the disaster, the rebuilding of relationships between residents themselves, collaboration with recovery and support activities, and mental health support for people participating in recovery and support efforts. From a medium- to long-term perspective, suicide prevention is an important issue. Comprehensive suicide prevention efforts are being promoted in areas of Iwate Prefecture affected by the disaster. In suicide prevention programs, it is crucial to foster the development of human resources in the local community. In order to expand community supports, it is necessary to provide education on ways of supporting those affected by a disaster to local medical personnel, people staffing inquiry and consultation offices, and people in fields related to mental health. Suicide prevention and disaster relief efforts are both approaches that target people in difficulty, and they share commonalities in principles, systems, and approaches to human resource development. "Mental health first aid" is a program developed in Australia that defines methods of early intervention by non-professionals who encounter someone experiencing a mental health problem. The mental health first aid-based gatekeeper training program of the Japanese government's Cabinet Office, which the author's research team helped to develop, allows participants to obtain the knowledge and skills required of gatekeepers. In 2012, a module for disaster-affected areas was developed and added to the program, with additional content that provides program participants with the skills to respond in crisis situations encountered during advice/counseling work in evacuation centers and temporary housing facilities. In addition, since 2011 the Cabinet Office has offered a facilitator training program that was developed based on the gatekeeper training program. Program text materials may be downloaded from the Web site of the Cabinet Office, and it is hoped that they will be used in the education of those involved in caring for people affected by a disaster.

[Paliperidone, risperidone].

Risperidone, a serotonin-dopamine antagonist, is effective in preventing delusions and hallucinations by D2 receptor antagonism and treating negative symptoms by 5-HT2A receptor antagonism. It is less likely to produce extrapyramidal symptoms than conventional antipsychotics, enabling safe drug therapy for schizophrenia. Paliperidone, based on 9OH-risperidone(major metabolite of risperidone), was developed to make the best use of the high therapeutic efficacy of Risperdal and enable continued treatment with lower prevalence of adverse events. Its mechanism of action as an extended-release tablet ensures slow release of the active ingredient, contributing to the lower prevalence of adverse events. With these pharmacological characteristics in mind, the two drugs can serve as safe and effective drug therapy.

[Mental health activities following the Great East Japan Earthquake in the stricken coastal area of Iwate Prefecture].

Since the Great East Japan Earthquake, many survivors have experienced psychological crises because of the immense damage in the coastal area of Iwate Prefecture. Mental care teams started activities in March 2011 along the coast of Iwate. We employed a mid- to long-term care model. In February 2012, we set up the Iwate Mental Care Center and built a long-term support system in Iwate Prefecture.

Usefulness of reminiscence therapy for community mental health.

Reminiscence therapy workshops for health-care professionals (total, n = 105: four trainees in their 20, seven in their 30s, 13 in their 40s, 30 in their 50s, 41 in their 60, five in their 70s, one in their 80s, and four of unknown age) were held, and group work with reminiscence therapy was provided to local residents (total, n = 151; mean age, 73.6 ± 10.6 years). Comparison of pre- and post-workshop questionnaires showed that rates of interest and understanding of trainees increased after the workshop. Concerning group work, 89.2% of the participants felt that reminiscence therapy would prove helpful in their life. Reminiscence therapy may be useful in improving mental health in local residents.

The impact of inpatient suicide on psychiatric nurses and their need for support.

BACKGROUND: The nurses working in psychiatric hospitals and wards are prone to encounter completed suicides. The research was conducted to examine post-suicide stress in nurses and the availability of suicide-related mental health care services and education. METHODS: Experiences with inpatient suicide were investigated using an anonymous, self-reported questionnaire, which was, along with the Impact of Event Scale-Revised, administered to 531 psychiatric nurses. RESULTS: The rate of nurses who had encountered patient suicide was 55.0%. The mean Impact of Event Scale-Revised (IES-R) score was 11.4. The proportion of respondents at a high risk (≥ 25 on the 88-point IES-R score) for post-traumatic stress disorder (PTSD) was 13.7%. However, only 15.8% of respondents indicated that they had access to post-suicide mental health care programmes. The survey also revealed a low rate of nurses who reported attending in-hospital seminars on suicide prevention or mental health care for nurses (26.4% and 12.8%, respectively). CONCLUSIONS: These results indicated that nurses exposed to inpatient suicide suffer significant mental distress. However, the low availability of systematic post-suicide mental health care programmes for such nurses and the lack of suicide-related education initiatives and mental health care for nurses are problematic. The situation is likely related to the fact that there are no formal systems in place for identifying and evaluating the psychological effects of patient suicide in nurses and to the pressures stemming from the public perception of nurses as suppliers rather than recipients of health care.

Visual discrimination among patients with depression and schizophrenia and healthy individuals using semiquantitative color-coded fast spin-echo T1-weighted magnetic resonance imaging.

INTRODUCTION: Fast spin-echo (FSE) T1-weighted (T1W) magnetic resonance imaging (MRI) at 3T, which is sensitive to neuromelanin-related contrast, can quantitatively detect signal alterations in the locus ceruleus (LC) and the substantia nigra pars compacta (SNc) of depressive and schizophrenic patients; however, its qualitative diagnostic performance remains unknown. We investigated whether visual interpretation of semiquantitative color maps can be used for discriminating between depressive and schizophrenic patients and healthy individuals. METHODS: We retrospectively examined 23 patients with major depression, 23 patients with schizophrenia, and 23 age-matched healthy controls by using a FSE-T1W MRI technique. Semiquantitative color maps of sections through the LC and SNc were visually interpreted by nine raters using a continuous confidence rating scale for receiver operating characteristic (ROC) analysis. RESULTS: The area under the ROC curve (Az), which reflects the performance in differentiating between depressive patients and controls, was 0.88, and the sensitivity and specificity at the maximum likelihood were 76% and 83%, respectively. In contrast, the Az value, sensitivity, and specificity values between schizophrenics and controls and between depressives and schizophrenics were 0.66 and 0.69, 42% and 48%, and 82% and 84%, respectively. CONCLUSION: Semiquantitative, color-coded FSE-T1W MRI at 3T can be used for visually differentiating depressive patients from healthy individuals with a substantially high likelihood, but this technique cannot be applied to distinguish schizophrenic patients from the other two groups.

Study of the outcome of suicide attempts: characteristics of hospitalization in a psychiatric ward group, critical care center group, and non-hospitalized group.

BACKGROUND: The allocation of outcome of suicide attempters is extremely important in emergency situations. Following categorization of suicidal attempters who visited the emergency room by outcome, we aimed to identify the characteristics and potential needs of each group. METHODS: The outcomes of 1348 individuals who attempted suicide and visited the critical care center or the psychiatry emergency department of the hospital were categorized into 3 groups, "hospitalization in the critical care center (HICCC)", "hospitalization in the psychiatry ward (HIPW)", or "non-hospitalization (NH)", and the physical, mental, and social characteristics of these groups were compared. In addition, multiple logistic analysis was used to extract factors related to outcome. RESULTS: The male-to-female ratio was 1:2. The hospitalized groups, particularly the HICCC group, were found to have biopsychosocially serious findings with regard to disturbance of consciousness (JCS), general health performance (GAS), psychiatric symptoms (BPRS), and life events (LCU), while most subjects in the NH group were women who tended to repeat suicide-related behaviors induced by relatively light stress. The HIPW group had the highest number of cases, and their symptoms were psychologically serious but physically mild. On multiple logistic analysis, outcome was found to be closely correlated with physical severity, risk factor of suicide, assessment of emergent medical intervention, and overall care. CONCLUSION: There are different potential needs for each group. The HICCC group needs psychiatrists on a full-time basis and also social workers and clinical psychotherapists to immediately initiate comprehensive care by a medical team composed of multiple professionals. The HIPW group needs psychological education to prevent repetition of suicide attempts, and high-quality physical treatment and management skill of the staff in the psychiatric ward. The NH group subjects need a support system to convince them of the risks of attempting suicide and to take a problem-solving approach to specific issues.

A randomized controlled multicenter trial of post-suicide attempt case management for the prevention of further attempts in Japan (ACTION-J).

BACKGROUND: A previous suicide attempt is a potent risk factor for suicide later on. Crisis intervention, psychiatric and psychosocial evaluation at emergency medical facilities, and follow-up care for suicide attempters are considered important components for suicide prevention. The Japanese Multimodal Intervention Trials for Suicide Prevention (J-MISP) includes a randomized, controlled, multicenter trial of post-suicide attempt case management for the prevention of further attempts (ACTION-J) to address the continuing increase in suicides in Japan. The primary aim of ACTION-J is to examine the effectiveness of an extensive intervention for suicide attempters in prevention of recurrent suicidal behavior, as compared with standard intervention. This paper describes the rationale and protocol of the ACTION-J trial. METHODS/DESIGN: In this clinical trial, case management intervention will be provided at 19 emergency medical facilities in Japan. After crisis intervention including psychiatric evaluation, psychosocial assessment, and psychological education, subjects will be randomly assigned to either a group receiving continuous case management or a control group receiving standard care. Suicidal ideation, depressive symptoms, and general health condition will be evaluated as secondary measures. The intervention was initiated in July 2006. By December, 2009, 842 subjects will be randomized. Subject follow-up will continue for 1.5 to 5 years. DISCUSSION: Suicide is a complex phenomenon that encompasses multiple factors. Case management by multi-sector collaboration is needed. ACTION-J may provide valuable information on suicide attempters and may develop effective case management to reduce future risk for suicide attempters. TRIAL REGISTRATION: UMIN Clinical Trials Registry number, UMIN000000444. ClinicalTrials.gov number, NCT00736918.

A community intervention trial of multimodal suicide prevention program in Japan: a novel multimodal community intervention program to prevent suicide and suicide attempt in Japan, NOCOMIT-J.

BACKGROUND: To respond to the rapid surge in the incidence of suicide in Japan, which appears to be an ongoing trend, the Japanese Multimodal Intervention Trials for Suicide Prevention (J-MISP) have launched a multimodal community-based suicide prevention program, NOCOMIT-J. The primary aim of this study is to examine whether NOCOMIT-J is effective in reducing suicidal behavior in the community. METHODS/DESIGN: This study is a community intervention trial involving seven intervention regions with accompanying control regions, all with populations of statistically sufficient size. The program focuses on building social support networks in the public health system for suicide prevention and mental health promotion, intending to reinforce human relationships in the community. The intervention program components includes a primary prevention measures of awareness campaign for the public and key personnel, secondary prevention measures for screening of, and assisting, high-risk individuals, after-care for individuals bereaved by suicide, and other measures. The intervention started in July 2006, and will continue for 3.5 years. Participants are Japanese and foreign residents living in the intervention and control regions (a total of population of 2,120,000 individuals). DISCUSSION: The present study is designed to evaluate the effectiveness of the community-based suicide prevention program in the seven participating areas. TRIAL REGISTRATION: UMIN Clinical Trials Registry (UMIN-CTR) UMIN000000460.

Reduced signal of locus ceruleus in depression in quantitative neuromelanin magnetic resonance imaging.

We used a neuromelanin-magnetic resonance imaging technique to investigate abnormalities in the locus ceruleus in depression. We examined 20 patients with major depression and 43 age-matched controls using a 3 T scanner with a neuromelanin-sensitive sequence. The signal intensities of the areas corresponding to the rostral, middle, and caudal portions of the locus ceruleus were measured, and the contrast ratio relative to the adjacent pontine tegmentum was calculated. In controls, the contrast ratio in the middle portion was higher than in the rostral and caudal areas. In patients, contrast ratios in the rostral and middle portions were significantly decreased in comparison with controls, suggesting dysfunction of the ascending noradrenergic system. Neuromelanin-magnetic resonance imaging can be used to visualize abnormalities in the locus ceruleus of depressive patients.

Reduced pulmonary vascular reactivity after cold exposure to acute hypoxia: a role of nitric oxide (NO).

Exposure to high altitude causes pulmonary hypertension and alterations in pulmonary vascular reactivity. Among the environmental factors, cold exposure has been suggested to be involved in the development of pulmonary hypertension. However, little information is available about pulmonary vascular reactivity after cold exposure. We examined whether cold exposure can cause changes in pulmonary vascular reactivity to acute hypoxia and the possible participation of endogenous nitric oxide. We measured mean systemic (Psa) and pulmonary artery pressures (Ppa) in conscious rats after 1-week cold exposure (3.5 +/- 1.0 degrees C). Subsequently, we investigated hypoxic pulmonary vasoconstriction (HPV) with and without endogenous NO inhibition using N(G)-nitro-L-arginine methyl ester (3 mg/kg) or 7-nitroindazole (1 mg/kg). Cold exposure for 1 week caused a small but significant increase in Ppa, but not in Psa. Neither Ppa nor Psa showed significant changes after both NO inhibitions in rats exposed to cold. However, cold exposure caused a blunted HPV and an increase in plasma nitrite-nitrate concentration compared with rats kept in a neutral environment (24.0 +/- 1.0 degrees C). In addition, NO inhibition by N(G)-nitro-L-arginine methyl ester partially restored the blunted HPV in rats exposed to cold, but not 7-nitroindazole, a selective inhibitor of neuronal NO synthase. We concluded that cold exposure alters pulmonary vascular reactivity to acute hypoxia, and augmented endothelial NO bioactivity plays a counterregulatory role in response to acute hypoxia during cold exposure in rats.

Neuromelanin magnetic resonance imaging of locus ceruleus and substantia nigra in Parkinson's disease.

We carried out an investigation to identify neuromelanin-containing noradrenergic and dopaminergic neurons in the locus ceruleus and substantia nigra pars compacta of healthy volunteers and patients with Parkinson's disease using a newly developed magnetic resonance imaging technique that can demonstrate neuromelanin-related contrast. The high-resolution neuromelanin images obtained by a 3-T scanner revealed high signal areas in the brain stem and these corresponded well with the location of the locus ceruleus and substantia nigra pars compacta in gross specimens. In Parkinson's disease patients, the signal intensity in the locus ceruleus and substantia nigra pars compacta was greatly reduced, suggesting depletion of neuromelanin-containing neurons. We conclude that neuromelanin magnetic resonance imaging can be used for direct visualization of the locus ceruleus and substantia nigra pars compacta, and may help in detecting pathological changes in Parkinson's disease and related disorders.

Age-related changes in locus ceruleus on neuromelanin magnetic resonance imaging at 3 Tesla.

PURPOSE: To investigate age-related changes in the locus ceruleus (LC) in healthy subjects using neuromelanin magnetic resonance (MR) imaging at 3 Tesla. METHODS: We examined 64 healthy volunteers (aged 23 to 80 years) using neuromelanin-sensitive T1-weighted images and measured the contrast of areas of high signal intensity corresponding to the LC. RESULTS: A pair of punctate areas of high signal intensity that represented neuromelanin within the noradrenergic neurons of the LC was easily recognized in all subjects. The contrast ratio of the LC to the adjacent pontine tegmentum increased to the age of 40 to 59 years and gradually and significantly decreased in elderly subjects. This correlates well with pathologically proven age-related changes in neuromelanin content within the LC. CONCLUSION: Age-related variance should be considered when determining the existence of abnormalities in the LC.