Trajectories for Post-traumatic Stress Disorder Symptoms Among Local Disaster Recovery Workers Following the Great East Japan Earthquake: Group-based Trajectory Modeling.

BACKGROUND: As many local municipality and medical workers were involved in disaster recovery duties following the Great East Japan Earthquake (GEJE) on March 11, 2011, the aim of this work was to elucidate the distinct trajectories for post-traumatic stress disorder (PTSD) symptoms and associated factors among these personnel. They confronted a diverse range of stressors both as survivors and as relief workers; however, little is known about their longitudinal PTSD symptoms. METHODS: The participants were 745 local municipality and hospital medical workers [average age: 43.6 ± 9.5 years, range: 20 - 66 years; 306 (59%) women] involved in disaster recovery duties following the GEJE. PTSD symptoms were measured using the Japanese version of the PTSD Checklist Specific Version (PCL-S) at four time points: 14, 30, 43, and 54 months after the GEJE. Using group-based trajectory modeling, distinct trajectories were elucidated. RESULTS: We identified five distinct PTSD symptoms profiles: resistance (n = 467, 62.7%), subsyndromal (n = 181, 24.3%), recovery (n = 47, 6.3%), fluctuating (n = 26, 3.5%), and chronic (n = 24, 3.2%). The trajectories differed according to the post-disaster working conditions and personal disaster experiences. LIMITATIONS: Potential selection bias resulting from the limited number of participants who completed all waves. The survey was conducted in one region of the disaster area. CONCLUSIONS: The majority of participants remained stable, with a relatively small group classified as chronic and fluctuating. Our results highlight the importance of improved working conditions and sustained monitoring of workers responding to natural disasters.

A single nucleotide polymorphism (-250 A/C) of the GFAP gene is associated with brain structures and cerebral blood flow.

AIM: Glial fibrillary acidic protein (GFAP), the intermediate filament protein expressed in astrocytes, plays a key role in many aspects of brain function through communication with neurons or blood vessels. A common single nucleotide polymorphism (SNP), GFAP -250 C/A (rs2070935), is associated with the transcriptional regulation of GFAP, which can potentially result in the genotype-specific brain structure. This study aimed to verify the biological effects of the GFAP variants on brain structure and function. METHODS: We investigated the associations between the GFAP variants and magnetic resonance imaging findings, including gray and white matter volumes, white matter integrity, and resting arterial blood flow, from 1212 healthy Japanese subjects. RESULTS: The GFAP -250 C/A genotype was significantly associated with total gray matter volume, total white matter volume, average mean diffusivity, and mean cerebral blood flow. In voxel-by-voxel analyses, the GFAP genotype showed significant associations with the regional gray and white matter volumes in the inferior frontal lobe and corpus callosum, the regional mean diffusivity in the left posterior region, and the regional cerebral blood flow throughout the brain. CONCLUSION: This study revealed a common SNP that is significantly associated with multiple global brain structure parameters.

Neural responses to action contingency error in different cortical areas are attributable to forward prediction or sensory processing.

The contingency of sensory feedback to one's actions is essential for the sense of agency, and experimental violation of this contingency is a standard paradigm in the neuroscience of self-awareness and schizophrenia. However, neural responses to this violation have arbitrarily been interpreted either as activation of the system generating forward prediction (agency-error account) or decreased suppression of processing of predictable input (prediction-error account). In this functional magnetic resonance imaging (fMRI) study, the regions responsive to auditory contingency errors were examined if they exhibited responses to an isolated auditory stimulus and to passive-contingency delay, which the prediction-error account expects. These responses were observed only in the auditory association cortex in the right superior temporal gyrus. Several multimodal and motor-association cortices did not exhibit these responses, suggesting their relevance to the agency-error account. Thus, we formulated the coexistence and dissociation of two accounts in neural contingency-error responses.

Federated multi-site longitudinal study of at-risk mental state for psychosis in Japan.

There has been recent accumulation of evidence and clinical guidance regarding the at-risk mental state (ARMS) for psychosis. However, most studies have been observational cohort and intervention studies of Western populations. To assess the validity of the ARMS concept and the transition rate to psychosis in a non-Western nation, we retrospectively combined and analyzed clinical data of individuals diagnosed with ARMS who were prospectively followed-up at three specialized clinical services for ARMS in Japan. In total, we included 309 individuals with ARMS, of whom 43 developed overt psychosis. We estimated cumulative transition rates to psychosis with the Kaplan-Meier method, obtaining rates of 12% at 12, 16% at 24, 19% at 36, and 20% at 48 months. Only two individuals reported past cannabis use. Despite several differences among the three sites, transition rates did not differ among them. Furthermore, the transition rate of children aged between 14 and 17 years did not differ from that of individuals aged 18 years or older. Regression analysis revealed that meeting the brief limited intermittent psychotic symptoms (BLIPS) criterion was associated with an increased risk of transition to psychosis, whereas genetic risk factors were not. Although antipsychotic prescription was relatively frequent in this cohort, there was no evidence supporting frequent use of antipsychotics for this population. In conclusion, our findings support the assertion that the current concept of ARMS is applicable in Japan. Development of local clinical guidelines and training for clinicians is necessary to disseminate this concept to more clinical settings.

Open-label study of cognitive behavioural therapy for individuals with at-risk mental state: Feasibility in the Japanese clinical setting.

AIM: To date, most cognitive behavioural therapy (CBT) trials for individuals with at-risk metal state (ARMS) have been conducted in few Western countries and its feasibility in other regions, including Japan, has not been established. METHODS: We designed an open-label pilot study. Fourteen ARMS participants received CBT over 6 months and were followed-up for 6 months. RESULTS: Thirteen individuals completed the CBT intervention and assessments. The mean total score on the Positive and Negative Syndrome Scale improved from 60.2 to 46.0 after the intervention (Cohen's d = 1.1). The effects were maintained at the follow-up assessment. One participant transitioned to psychosis after the CBT intervention, and was the only patient who received antipsychotics. CONCLUSIONS: We confirmed the feasibility of the provision of CBT for ARMS in Japan. Since overprescription of antipsychotics is a matter of great concern in Japan, CBT could be a valuable alternative treatment strategy.

No regional gray matter volume reduction observed in young Japanese people at ultra-high risk for psychosis: A voxel-based morphometry study.

OBJECTIVES: Structural brain magnetic resonance imaging studies of individuals at ultra-high risk (UHR) for psychosis have shown subtle but widespread reductions in baseline gray matter volume (GMV) in the frontal, temporal, and limbic regions compared with healthy controls (HC). These regions coincide with regions of reduced GMV in patients with established psychosis and have led to the consideration of structural changes in UHR as a potential biomarker for future transition to psychosis. However, most studies have been from Europe, North America, and Australia, with few reports from other regions, and two recent studies from Asian countries have failed to detect regional GMV reduction in UHR, suggesting the need for further analysis of an Asian sample. In this study, we investigated GMV reduction in Japanese UHR subjects. RESULTS: The study used voxel-based morphometry to compare magnetic resonance imaging brain scans between 45 UHR individuals recruited by a specialist and 33 HCs. This showed no significant GMV reduction in the UHR group compared with the healthy control group. This negative result may be attributable to characteristics of Asian samples, such as a low prevalence of illicit drug use, or to the heterogeneous nature of UHR subjects.

Longitudinal characteristics of resilience among adolescents: A high school student cohort study to assess the psychological impact of the Great East Japan Earthquake.

AIM: Resilience, the ability to cope with disasters and significant life adversity, is an important factor to consider when studying the mental health of populations affected by a disaster. Although high school students in a community affected by a disaster should have specific characteristics of resilience, little has been reported on the issue. This study was designed to provide initial data regarding characteristics of the resilience of high school students affected by a catastrophe. METHODS: A total of 760 high school students in Natori City, which was devastated by the Great East Japan Earthquake in 2011, were profiled, and a 3-year longitudinal study was conducted with 254 students who had entered the school in 2012. Resilience was evaluated with the 10-item Connor-Davidson Resilience Scale. The Quick Inventory of Depressive Symptomatology-Japanese version, the Zung Self-Rating Anxiety Scale, and the Impact of Event Scale-Revised were also administered to assess the students' mental health. RESULTS: Among the students who entered the high school in 2012, 28.6% showed high resilience, and the proportion increased to 42.9% in 2013 and 46.6% in 2014. The Quick Inventory of Depressive Symptomatology-Japanese version and Impact of Event Scale-Revised scores decreased significantly over the 3-year study period, but there were no significant differences in the Zung Self-Rating Anxiety Scale scores over time. CONCLUSION: This initial study profiling the characteristics of resilience among adolescents suggests that resilience is a highly changeable component of mental health among people who have faced adversity. Resilience can be a useful indicator of recovery from adversity and a target of interventions for improving mental health conditions.

Polymorphisms in the microglial marker molecule CX3CR1 affect the blood volume of the human brain.

AIM: CX3CR1, a G-protein-coupled receptor, is involved in various inflammatory processes. Two non-synonymous single nucleotide polymorphisms, V249I (rs3732379) and T280M (rs3732378), are located in the sixth and seventh transmembrane domains of the CX3CR1 protein, respectively. Previous studies have indicated significant associations between T280M and leukocyte functional characteristics, including adhesion, signaling, and chemotaxis, while the function of V249I is unclear. In the brain, microglia are the only proven and widely accepted CX3CR1-expressing cells. This study aimed to specify whether there were specific brain regions on which these two single nucleotide polymorphisms exert their biological impacts through their functional effects on microglia. METHODS: Associations between the single nucleotide polymorphisms and brain characteristics, including gray and white matter volumes, white matter integrity, resting arterial blood volume, and cerebral blood flow, were evaluated among 1300 healthy Japanese individuals. RESULTS: The major allele carriers (V249 and T280) were significantly associated with an increased total arterial blood volume of the whole brain, especially around the bilateral precuneus, left posterior cingulate cortex, and left posterior parietal cortex. There were no significant associations between the genotypes and other brain structural indicators. CONCLUSION: This finding suggests that the CX3CR1 variants may affect arterial structures in the brain, possibly via interactions between microglia and brain microvascular endothelial cells.

The relationship between cognitive insight and cognitive performance among individuals with at-risk mental state for developing psychosis.

Impairments in cognitive insight-the capacity to appraise and modify one's own distorted beliefs-are believed to be associated with the formation of psychosis. Nevertheless, the association between cognitive insight and cognitive function among people with at-risk mental state (ARMS) for developing psychotic illness has not been made clear. In this study, we used the Beck Cognitive Insight Scale (BCIS) to assess cognitive insight and the Brief Assessment of Cognition in Schizophrenia (BACS) and the Wisconsin Card Sorting Test (WCST) to assess cognitive functions. Fifty subjects with ARMS and 29 healthy volunteers were recruited as participants. The scores for the two groups on the BCIS, BACS, and WCST were compared and Spearman's rank correlations between the domains of the BCIS and cognitive performance were examined in each group. No significant differences were found in BCIS scores between these groups, whereas all of the cognitive function scores were poorer in the participants with ARMS. In the ARMS group, higher self-certainty on the BCIS was significantly correlated with lower performance in the mean number of categories achieved (ρ=-0.31, P=0.03) and perseverative errors of the Nelson type (ρ=0.29, P=0.04) on the WCST. This indicates that excessively high self-certainty might be linked with weaknesses in cognitive flexibility or set-shifting ability in people with ARMS.

Increase in the number of admissions to psychiatric hospitals immediately after the Great East Japan Earthquake.

INTRODUCTION: Major natural disasters have a significant impact on the mental health of survivors in affected communities. Although it has been speculated that the number of survivors requiring admission to psychiatric hospital increases immediately after a major disaster, few studies have examined the issue. METHODS: On March 11, 2011, the Great East Japan Earthquake and subsequent tsunami devastated the relatively isolated city of Kesennuma. We therefore compared the weekly number of patients admitted to 2 psychiatric hospitals in Kesennuma in the 4 weeks immediately after the earthquake with those in the 4 weeks immediately preceding the earthquake. We also made comparisons between this 8-week period and the corresponding 8-week periods in 2009, 2010, and 2012. RESULTS: The number of patients admitted to the 2 psychiatric hospitals increased in 4 weeks after the disaster in 2011, with a weekly median (range) of 13 (9-16), compared with 6 (5-9) in the preceding 4 weeks in 2011. The corresponding figures were 5.5 (2-10) in 2009, 6.5 (5-9) in 2010, and 4 (3-7) in 2012 (P = .01, H = 13.05). By diagnostic category, admissions for schizophrenia spectrum disorder and neurotic stress-related disorder increased significantly following the disaster. DISCUSSION: Demands for inpatient psychiatric treatment increased immediately after the Great East Japan Earthquake. Government officials and mental health professionals must strengthen support for survivors with mental illness, especially those with schizophrenia spectrum disorder. This should include support for mental health authorities and medical staff in the affected community.

Criticism by community people and poor workplace communication as risk factors for the mental health of local welfare workers after the Great East Japan Earthquake: A cross-sectional study.

After a large-scale natural disaster, demand for social welfare services increases, and the mental health of local social welfare workers becomes a matter of great concern because of their dual role as support providers and disaster survivors. We examined whether work-related social stressors, including criticism by community people and poor workplace communication, were associated with increased risk of post-traumatic stress disorder (PTSD), depression, or psychological distress 20-22 months after the Great East Japan Earthquake (GEJE; March 11, 2011) in local social welfare workers. Demographic characteristics, disaster-related risk factors (near-death experience, dead/missing family members, loss of housing), and work-related social risk factors (criticism, lack of communication) were obtained 20-22 months after the GEJE from 822 local workers. Questionnaires measured PTSD, depression, and psychological stress. Bivariate and multivariate regression analyses were applied. More local social welfare workers suffered from mental health problems than would be expected. Criticism by community people was significantly associated with probable PTSD and high psychological distress (adjusted odds ratio = 2.31 and 2.55, respectively). Furthermore, lack of workplace communication was associated with probable PTSD, depression, and high psychological distress (adjusted odds ratio = 3.97, 4.27, and 4.65, respectively). Almost 2 years after the disaster, local relief workers still suffered from mental health problems. Because post-disaster work-related social stressors constitute risk factors for these mental health problems, measures to improve working conditions and prevent and treat mental disorders should be a priority.

School-Based Interventions Aimed at the Prevention and Treatment of Adolescents Affected by the 2011 Great East Japan Earthquake: A Three-Year Longitudinal Study.

How natural disasters affect the psychological state of adolescents has not been well studied. Thus, we examined the effect of a natural disaster on high-school-aged youth and considered the most effective forms of support following such a disaster. We examined students from two high schools that were near the epicenter of the 9.0-magnitude Great East Japan Earthquake, which struck the Tohoku coastal area on March 11, 2011, causing severe damage to the region. The questionnaires measuring depression, anxiety, and post-traumatic stress reaction (PTSR) was administered to the students 3 times between July 2012 and August 2014; students who scored above the cut-off values of these measures were considered high-risk students. School teachers, nurses, and counselors provided a school-based intervention for all high-risk students identified in the survey. Data were analyzed using the Kruskal-Wallis H-test. Survey data revealed that 860 of the 1,432 (55.9%) high school students were at high risk of psychological trauma in 2012. This rate did not change substantially in the following 2 years, reaching 1,059 of 1,488 (69.1%) in 2013, and 949 of 1,430 (62.7%) in 2014. Depression and PTSR scores were significantly lower after the intervention (for 2nd and 3rd grade students in 2013 and 2014) compared to before (for the initial 2012 survey). However, there were no significant differences between the 1st grade students for all three years. Thus, school-based interventions involving psychological testing and interviews might reduce the rates of depression and PTSR in high school students.

The associations between quality of life and clinical symptoms in individuals with an at-risk mental state and first-episode psychosis.

Quality of life (QOL) is strongly associated with severity of clinical symptoms and is often compromised in patients with chronic or first-episode psychosis (FEP). However, it remains unclear whether baseline QOL in individuals with an at-risk mental state (ARMS) for psychosis is higher or lower than that in patients with FEP, or what specific clinical symptoms relate to a decreased QOL in individuals with ARMS and FEP. The World Health Organization's WHOQOL-BREF, an instrument assessing QOL, was administered to 104 individuals with ARMS and 53 with FEP. Clinical symptoms were assessed by the Positive and Negative Syndrome Scale and the Beck Depression Inventory-II. We compared the four domain scores of the WHOQOL-BREF between the two groups, and calculated Pearson correlations between each WHOQOL-BREF domain score and the clinical symptoms and compared these correlations between the groups. We observed significant correlations between poor QOL and severity of depressive symptoms in both the FEP and ARMS group. No between-group differences were found in any correlation coefficients between WHOQOL-BREF domains and clinical symptoms. Thus, depressive symptoms should be investigated as a key factor relating to poor QOL in both individuals with ARMS and those with FEP.

Microglial production of TNF-alpha is a key element of sustained fear memory.

The proinflammatory cytokine productions in the brain are altered in a process of fear memory formation, indicating a possibility that altered microglial function may contribute to fear memory formation. We aimed to investigate whether and how microglial function contributes to fear memory formation. Expression levels of M1- and M2-type microglial marker molecules in microglia isolated from each conditioned mice group were assessed by real-time PCR and immunohistochemistry. Levels of tumor necrosis factor (TNF)-α, but not of other proinflammatory cytokines produced by M1-type microglia, increased in microglia from mice representing retention of fear memory, and returned to basal levels in microglia from mice representing extinction of fear memory. Administration of inhibitors of TNF-α production facilitated extinction of fear memory. On the other hand, expression levels of M2-type microglia-specific cell adhesion molecules, CD206 and CD209, were decreased in microglia from mice representing retention of fear memory, and returned to basal levels in microglia from mice representing extinction of fear memory. Our findings indicate that microglial TNF-α is a key element of sustained fear memory and suggest that TNF-α inhibitors can be candidate molecules for mitigating posttraumatic reactions caused by persistent fear memory.

Deficits of cognitive theory of mind and its relationship with functioning in individuals with an at-risk mental state and first-episode psychosis.

Disturbance of theory of mind (ToM) and its relationship with functioning in schizophrenia is well documented; however, this is unclear in spectrum disorders like at-risk mental state (ARMS) and first-episode psychosis (FEP). To assess mental state reasoning ability, the total score of the Theory of Mind Picture Stories Task questionnaire was compared among 36 Japanese individuals with ARMS, 40 with FEP, and 25 healthy controls (HC). Pearson's correlations between ToM performance and global and social functioning indices were examined. ToM performance for FEP and ARMS subjects was significantly lower than that for HC, though the significance of the difference between the ARMS and HC disappeared when controlling for premorbid IQ. ToM deficits in ARMS subjects were confirmed only in the comprehension of higher-order false belief. Only among FEP subjects were ToM performance and global functioning significantly correlated, though the significance disappeared when controlling for neurocognitive performance or dose of antipsychotics. No significant correlation between ToM performance and social functioning was observed in the FEP and ARMS groups. The current findings suggest that ToM deficits emerge in ARMS subjects confined within a higher-order domain, and that the relationship between ToM impairment and functional deterioration might be established after psychosis onset.

Correction: Criticism and Depression among the Caregivers of At-Risk Mental State and First-Episode Psychosis Patients.

[This corrects the article DOI: 10.1371/journal.pone.0149875.].

Criticism and Depression among the Caregivers of At-Risk Mental State and First-Episode Psychosis Patients.

Expressed emotion (EE), especially criticism, is an important predictor of outcomes for the patient for a wide range of mental health problems. To understand complex links between EE and various relevant variables in early phase psychosis, this study examined criticism, distress of caregivers, other patients', and caregivers' variables, and links between criticism and these variables in those with at-risk mental state (ARMS) for psychosis and first-episode psychosis (FEP). The participants were 56 patients (mean age 18.8 ± 4.2 years) with ARMS and their caregivers (49.4 ± 5.8 years) and 43 patients (21.7 ± 5.2 years) with FEP and their caregivers (49.3 ± 7.4 years). We investigated criticisms made by caregivers using the Japanese version of the Family Attitude Scale and caregiver depressive symptoms via the self-report Beck Depression Inventory. We also assessed psychiatric symptoms and functioning of the patients. Approximately one-third of caregivers of patients with ARMS or FEP had depressive symptoms, predominately with mild-to-moderate symptom levels, whereas only a small portion exhibited high criticism. The level of criticism and depression were comparable between ARMS and FEP caregivers. The link between criticism, caregivers' depression, and patients' symptoms were observed in FEP but not in ARMS caregivers. These findings imply that the interaction between criticism and caregivers' and patients' mental states may develop during or after the onset of established psychosis and interventions for the caregivers should be tailored to the patient's specific stage of illness. Interventions for FEP caregivers should target their emotional distress and include education about patient's general symptoms.

Post-traumatic growth of children affected by the Great East Japan Earthquake and their attitudes to memorial services and media coverage.

AIMS: Post-traumatic growth (PTG) refers to positive changes that result from coping with a major life crisis or a traumatic event. Factors influencing PTG in youth have not been well characterized but could have a great impact on overall maturation. METHODS: Fourth to ninth graders (n = 3337) attending elementary or junior high schools located in a district severely damaged by the Great East Japan Earthquake completed a questionnaire, including the revised Posttraumatic Growth Inventory for Children (PTGI-C-R) along with the Post Traumatic Stress Symptoms for Children 15 items (PTSSC-15), 31 months after the event. Experience of the disaster, prior traumatic experiences, and attitudes toward memories of the disaster (rumination) were scored by their caregivers and teachers, and effects of these factors on PTG were evaluated. RESULTS: There were no significant associations between PTGI-C-R and sex or experiences of the disaster. However, PTGI-C-R was negatively correlated with age (r = -0.132, P < 0.001). There was significant but very weak negative correlation between PTGI-C-R and PTSSC-15 among the children (r = -0.096, P < 0.001). PTGI-C-R was significantly associated with positive attitudes to memorial services (P < 0.001) and media coverage (P < 0.05). CONCLUSION: Positive attitudes to deliberate rumination may facilitate PTG in children following natural disasters.

Histamine H1 receptor occupancy by the new-generation antipsychotics olanzapine and quetiapine: a positron emission tomography study in healthy volunteers.

RATIONALE: Histamine H1 antagonists have hypnotic, appetite-promoting, and sedative side effects. Most second-generation antipsychotics have potent antagonistic effects on histamine H1 receptor (H1R). Positron emission tomography (PET) can measure the H1R occupancy (H1RO) in vivo, although there are no reports regarding antipsychotics. OBJECTIVES: We studied the H1RO of olanzapine and quetiapine in vivo with respect to their plasma concentrations and subjective drowsiness by performing human PET imaging studies with [(11)C]doxepin, a potent PET ligand of H1R. METHODS: Six healthy Japanese male volunteers were enrolled. Cross-randomized PET imaging was performed after a single oral administration of olanzapine (2.5 mg), quetiapine (25 mg), or placebo. PET data were analyzed by region of interest and voxel-by-voxel analysis. We concurrently measured plasma drug concentrations by liquid chromatography/tandem mass spectrometry and evaluated subjective sleepiness. RESULTS: The binding potential ratios of olanzapine and quetiapine in the cerebral cortex were significantly lower than that of the placebo. The H1RO values of olanzapine and quetiapine in the cortex were approximately 61-80 and 56-81%, respectively. The binding potential ratios of the drugs were significantly lower than that of the placebo in the dorsolateral prefrontal and lateral temporal cortices, and anterior and posterior cingulate gyri. The H1RO values in the cortex were significantly correlated with subjective sleepiness but not plasma drug concentrations. CONCLUSIONS: Olanzapine and quetiapine have high H1RO values in the human brain under their clinical minimum doses. This study provides a foundation of the properties by which new-generation antipsychotics block the central histaminergic system in humans.

Life and mental health of medical students after the Great East Japan Earthquake.

Students of the Tohoku University School of Medicine experienced the Great East Japan Earthquake on March 11, 2011. We conducted a series of surveys to examine the relationships among their experiences and activities on the day of the earthquake, their physical, mental, and economic problems following the disaster, and how their problems changed over time. The initial survey was performed in April 2011, with three follow-up surveys in July 2011, February 2012, and April 2013. The initial survey focused on students' experiences and living conditions during the disaster, which contained questions on their locations and circumstances, family circumstances, lives after the earthquake, voluntary works, physical or mental health problems, and desire for counseling. The follow-up surveys included new items regarding their circumstances, changes in their health problems, and their desire for economic assistance. Students who answered the first survey to the 4th one, with response rates in the following bracket, were as follows: 472 (28.0%), 640 (29.9%), 681 (36.0%), and 678 (39.0%), respectively. Six months after the earthquake, about 20% having experienced physical and/or mental problems. Although there was a trend toward a reduction in suffering and health problems over time, some students' conditions remained unchanged or worsened. It is notable that students who had participated in voluntary activities, despite their own suffering of harm and distress, were identified as the group that required the closest attention. Our present results can be applied to appropriate supports for students in future large-scale disasters.