Retina as a potential biomarker in schizophrenia spectrum disorders: a systematic review and meta-analysis of optical coherence tomography and electroretinography.

INTRODUCTION: Abnormal findings on optical coherence tomography (OCT) and electroretinography (ERG) have been reported in participants with schizophrenia spectrum disorders (SSDs). This study aims to reveal the pooled standard mean difference (SMD) in retinal parameters on OCT and ERG among participants with SSDs and healthy controls and their association with demographic characteristics, clinical symptoms, smoking, diabetes mellitus, and hypertension. METHODS: Using PubMed, Scopus, Web of Science, and PSYNDEX, we searched the literature from inception to March 31, 2023, using specific search terms. This study was registered with PROSPERO (CRD4202235795) and conducted according to PRISMA 2020. RESULTS: We included 65 studies in the systematic review and 44 in the meta-analysis. Participants with SSDs showed thinning of the peripapillary retinal nerve fiber layer (pRNFL), macular ganglion cell layer- inner plexiform cell layer, and retinal thickness in all other segments of the macula. A meta-analysis of studies that excluded SSD participants with diabetes and hypertension showed no change in results, except for pRNFL inferior and nasal thickness. Furthermore, a significant difference was found in the pooled SMD of pRNFL temporal thickness between the left and right eyes. Meta-regression analysis revealed an association between retinal thinning and duration of illness, positive and negative symptoms. In OCT angiography, no differences were found in the foveal avascular zone and superficial layer foveal vessel density between SSD participants and controls. In flash ERG, the meta-analysis showed reduced amplitude of both a- and b-waves under photopic and scotopic conditions in SSD participants. Furthermore, the latency of photopic a-wave was significantly shorter in SSD participants in comparison with HCs. DISCUSSION: Considering the prior report of retinal thinning in unaffected first-degree relatives and the results of the meta-analysis, the findings suggest that retinal changes in SSDs have both trait and state aspects. Future longitudinal multimodal retinal imaging studies are needed to clarify the pathophysiological mechanisms of these changes and to clarify their utility in individual patient monitoring efforts.

Kinetics formulation for Two-Dimensional Growth Behavior of Water/Ice Interface on Si Substrate.

Sublimation drying is used in the drying process of semiconductor device manufacturing. However, the solidification behavior mechanics of sublimation agents on substrates has not been clarified. Therefore, the properties of solidified films within substrate surfaces can become nonuniform, leading to their collapse. This study aimed to analyze the interface growth behavior during the cooling and solidification of a water/ice system as a basic case and to clarify the dynamic mechanism of the solidification behavior of liquid films on Si substrates. The solidification behavior of a water/ice system on Si substrates was captured on a video at different cooling rates. The recorded video was subjected to a digital image analysis to examine the crystal morphology and quantify the interface growth rate. The least-squares method with kinetic formulas was used to evaluate the feasibility of fitting the temperature variation to the interface growth rate. A visual examination of the morphology of interfacial growth revealed that it can be classified into four morphologies. The proposed kinetic equation describes the experimental results regarding the temperature dependence of the interfacial growth rate. Through image analysis, the interface growth rate of water and ice was quantified, and an evaluation formula was proposed.

Concomitant use of hydroxyzine and haloperidol did not worsen delirium in patients with cancer: A multicenter, retrospective, observational study.

OBJECTIVES: There is concern that hydroxyzine exacerbates delirium, but a recent preliminary study suggested that the combination of haloperidol and hydroxyzine was effective against delirium. This study examined whether the concomitant use of hydroxyzine and haloperidol worsened delirium in patients with cancer. METHODS: This retrospective, observational study was conducted at 2 general hospitals in Japan. The medical records of patients with cancer who received haloperidol for delirium from July to December 2020 were reviewed. The treatments for delirium included haloperidol alone or haloperidol combined with hydroxyzine. The primary outcome was the duration from the first day of haloperidol administration to the resolution of delirium, defined as its absence for 2 consecutive days. The time to delirium resolution was analyzed to compare the haloperidol group and hydroxyzine combination group using the log-rank test with the Kaplan-Meier method. Secondary outcomes were (1) the total dose of antipsychotic medications, including those other than haloperidol (measured in chlorpromazine-equivalent doses), and (2) the frequencies of detrimental incidents during delirium, specifically falls and self-removal of drip infusion lines. The unpaired t-test and Fisher's exact test were used to analyze secondary outcomes. RESULTS: Of 497 patients who received haloperidol, 118 (23.7%) also received hydroxyzine. No significant difference in time to delirium resolution was found between the haloperidol group and the hydroxyzine combination group (log-rank test, P = 0.631). No significant difference between groups was found in either chlorpromazine-equivalent doses or the frequency of detrimental incidents. SIGNIFICANCE OF RESULTS: This study showed that the concomitant use of hydroxyzine and haloperidol did not worsen delirium in patients with cancer.

Volume Reduction of the Dorsal Lateral Prefrontal Cortex Prior to the Onset of Frank Psychosis in Individuals with an At-Risk Mental State.

Although some individuals with at-risk mental states (ARMS) develop overt psychosis, surrogate markers which can reliably predict a future onset of psychosis are not well established. The dorsal lateral prefrontal cortex (DLPFC) is thought to be involved in psychotic disorders such as schizophrenia. In this study, 73 ARMS patients and 74 healthy controls underwent 1.5-T 3D magnetic resonance imaging scans at three sites. Using labeled cortical distance mapping, cortical thickness, gray matter (GM) volume, and surface area of DLPFC were estimated. These measures were compared across the diagnostic groups. We also evaluated cognitive function among 36 ARMS subjects to clarify the relationships between the DLPFC morphology and cognitive performance. The GM volume of the right DLPFC was significantly reduced in ARMS subjects who later developed frank psychosis (ARMS-P) relative to those who did not (P = 0.042). There was a positive relationship between the right DLPFC volume and the duration prior to the onset of frank psychosis in ARMS-P subjects (r = 0.58, P = 0.018). Our data may suggest that GM reduction of the DLPFC might be a potential marker of future onset of psychosis in individuals with ARMS.

Surface morphology of the orbitofrontal cortex in individuals at risk of psychosis: a multicenter study.

Changes in the surface morphology of the orbitofrontal cortex (OFC), such as a fewer orbital sulci and altered sulcogyral pattern of the 'H-shaped' orbital sulcus, have been reported in schizophrenia, possibly reflecting abnormal neurodevelopment during gestation. However, whether high-risk subjects for developing psychosis also exhibit these gross morphologic anomalies is not well documented. This multicenter MRI study from four scanning sites in Japan investigated the distribution of the number of intermediate and posterior orbital sulci, as well as the OFC sulcogyral pattern, in 125 individuals with an at-risk mental state (ARMS) [of whom 22 later developed psychosis (ARMS-P) and 89 did not (ARMS-NP)] and 110 healthy controls. The ARMS group as a whole had a significantly lower number of intermediate and posterior orbital sulci compared with the controls, which was associated with prodromal symptomatology. However, there was no group difference in OFC pattern distribution. The ARMS-P and -NP groups did not differ in OFC surface morphology. These results suggest that gross morphology of the OFC in high-risk subjects may at least partly reflect neurodevelopmental pathology related to vulnerability to psychosis.

The pitfall of empathic concern with chronic fatigue after a disaster in young adults.

BACKGROUND: Empathic concern (EC) is an important interpersonal resilience factor that represents positive adaptation, such as "relating to others" (a factor of posttraumatic growth [PTG]) after disaster. However, controversy exists regarding whether the changes in EC (e.g., the intra-personal change between the acute phase and the disillusionment phase) positively or negatively affect mental health after a disaster. We hypothesized that increased EC may increase chronic fatigue due to over-adjustment (hypothesis 1). We also hypothesized that increasing the changes in "relating to others" could decrease the changes in chronic fatigue (hypothesis 2). METHODS: Forty-nine young, healthy volunteers (M/F: 36/13; age at 3 months after the disaster [3 months]: mean ± SD: 21.1 ± 1.7 years) underwent assessments of EC using the Japanese version of the Interpersonal Reactivity Index, chronic fatigue using the Japanese version of the Checklist Individual Strength (CIS-J) questionnaire, and "relating to others" using the Japanese version of the PTG inventory during the acute phase (3 months) and the disillusionment phase (1 year after the disaster). Pearson product moment correlations at 3 months and 1 year were determined for all scores related to EC. The changes (delta = degree of change from 3 months to 1 year) or scores at 1 year were entered into linear structural equation systems to test the hypotheses. RESULTS: The delta of EC positively affected the delta of the CIS-J, and the delta of relating to others negatively affected the delta of the CIS-J. Both the EC and relating to others scores were negatively associated with the CIS-J score at 1 year. These results were in accordance with hypothesis 1 and 2. CONCLUSIONS: We demonstrated the opposite effects of 2 types of ECs, i.e., stability (inherent disposition) and flexibility (degree of change), on the degree of chronic fatigue. Increasing EC with increasing chronic fatigue, but not the change in relating to others, may be a red flag for individuals during the disillusionment phase.

Neural Mechanism for Mirrored Self-face Recognition.

Self-face recognition in the mirror is considered to involve multiple processes that integrate 2 perceptual cues: temporal contingency of the visual feedback on one's action (contingency cue) and matching with self-face representation in long-term memory (figurative cue). The aim of this study was to examine the neural bases of these processes by manipulating 2 perceptual cues using a "virtual mirror" system. This system allowed online dynamic presentations of real-time and delayed self- or other facial actions. Perception-level processes were identified as responses to only a single perceptual cue. The effect of the contingency cue was identified in the cuneus. The regions sensitive to the figurative cue were subdivided by the response to a static self-face, which was identified in the right temporal, parietal, and frontal regions, but not in the bilateral occipitoparietal regions. Semantic- or integration-level processes, including amodal self-representation and belief validation, which allow modality-independent self-recognition and the resolution of potential conflicts between perceptual cues, respectively, were identified in distinct regions in the right frontal and insular cortices. The results are supportive of the multicomponent notion of self-recognition and suggest a critical role for contingency detection in the co-emergence of self-recognition and empathy in infants.

Psychological trauma after the Great East Japan Earthquake.

The Great East Japan Earthquake (GEJE) struck the northeastern part of Japan on 11 March 2011 and triggered a devastating tsunami, causing widespread destruction along the coast of northeastern Japan. The tsunami also led to an accident at the Fukushima Daiichi nuclear power plant. Incidents occurring in such major disasters are known to lead to psychological trauma. This paper has summarized English-language documentation regarding GEJE-related psychological trauma or post-traumatic stress disorder (PTSD). Research thus far has reported the possibility of higher probable PTSD prevalence among residents of the GEJE areas than in the average Japanese population during normal times. At the very least, many people have experienced trauma symptoms at self-recognition levels 1 year or longer after the disaster. It appears that the percentage of persons with high PTSD risk was higher in regions with radiation-related impacts than in regions where the main damage was caused by the earthquake and tsunami. Results have not been limited to showing relations between severe exposure to a traumatic event and PTSD symptoms but also show that a variety of factors, including social factors, has been shown to interact with PTSD symptoms. The fact that Japanese society as a whole united against the trauma of the GEJE may have worked to minimize the effects of trauma. To grasp a full picture of the effects of psychological trauma due to the GEJE, further surveys and research are necessary. It will be necessary to continue engagements related to these problems and issues into the future.

Post-traumatic stress disorder and depression prevalence and associated risk factors among local disaster relief and reconstruction workers fourteen months after the Great East Japan Earthquake: a cross-sectional study.

BACKGROUND: Many local workers have been involved in rescue and reconstruction duties since the Great East Japan Earthquake (GEJE) on March 11, 2011. These workers continuously confront diverse stressors as both survivors and relief and reconstruction workers. However, little is known about the psychological sequelae among these workers. Thus, we assessed the prevalence of and personal/workplace risk factors for probable post-traumatic stress disorder (PTSD), probable depression, and high general psychological distress in this population. METHODS: Participants (N = 1294; overall response rate, 82.9%) were workers (firefighters, n = 327; local municipality workers, n = 610; hospital medical workers, n = 357) in coastal areas of Miyagi prefecture. The study was cross-sectional and conducted 14 months after the GEJE using a self-administered questionnaire which included the PTSD Checklist-Specific Version, the Patient Health Questionnaire-9, and the K6 scale. Significant risk factors from bivariate analysis, such as displacement, dead or missing family member(s), near-death experience, disaster related work, lack of communication, and lack of rest were considered potential factors in probable PTSD, probable depression, and high general psychological distress, and were entered into the multivariable logistic regression model. RESULTS: The prevalence of probable PTSD, probable depression, and high general psychological distress was higher among municipality (6.6%, 15.9%, and 14.9%, respectively) and medical (6.6%, 14.3%, and 14.5%, respectively) workers than among firefighters (1.6%, 3.8%, and 2.6%, respectively). Lack of rest was associated with increased risk of PTSD and depression in municipality and medical workers; lack of communication was linked to increased PTSD risk in medical workers and depression in municipality and medical workers; and involvement in disaster-related work was associated with increased PTSD and depression risk in municipality workers. CONCLUSIONS: The present results indicate that at 14 months after the GEJE, mental health consequences differed between occupations. High preparedness, early mental health interventions, and the return of ordinary working conditions might have contributed to the relative mental health resilience of the firefighters. Unlike the direct effects of disasters, workplace risk factors can be modified after disasters; thus, we should develop countermeasures to improve the working conditions of local disaster relief and reconstruction workers.

[Activity to prevent mental diseases after the Great East Japan Earthquake].

Following the Great East Japan Earthquake, we have been supporting psychiatric hospitals and mental health and welfare centers in Miyagi Prefecture. In October 2011, with a grant from Miyagi Prefecture, the Department of Preventive Psychiatry was established in Tohoku University Graduate School of Medicine. The institute aims to promote the prevention of and early intervention for mental diseases. As its members, we carry out our duties in collaboration with the Miyagi Disaster Mental Health Care Center. We refer to our activities as the Great East Japan Earthquake Mental Health Support and Research (GEMS) project. The GEMS project includes both practices and research in the affected areas in Miyagi Prefecture. The focus is on supporting those who provide services for survivors long-term, such as municipal employees, nurses, fire fighters, and staff of the social welfare council. We investigated how much the disaster impaired the functioning of psychiatric hospitals and clinics in Miyagi Prefecture. We also conduct mental health surveys in public organizations. Based on the results, we arrange workshops, consultation, or counseling. Moreover, we promote improvement of the mental health skills of mental health professionals, which are essential for mid and long-term support after the disaster. One of them is "Skills for Psychological Recovery". As members of the support organization in the region, we keep working toward the recovery and development of mental health systems in Miyagi Prefecture.

New Formulas for Evaluation of Cyclohexanol Solidification on Substrates with Surface Nanostructures.

In semiconductor manufacturing, the sublimation drying process is crucial but poorly understood-particularly regarding the solidification of agents such as cyclohexanol on Si substrates. This knowledge gap results in inconsistent film properties and risks such as structural collapse. To address this critical gap in knowledge, the present study focused on an in-depth examination of the nucleation behavior exhibited by cyclohexanol during its cooling and solidification on Si substrates. Using a digital camera (GoPro10), the solidification process in experiments was recorded for a range of cooling rates and using substrates with distinct surface patterns. To evaluate temporal changes in crystal nucleation, video images were visually checked, and the temporal changes in the number of nuclei were examined. For a more quantitative analysis, the least-squares method was successfully employed to correlate mathematical equations to time-dependent nucleation data. Interestingly, the outcomes revealed significant correlations between the nucleation rate, cooling rate, and substrate pattern. In summary, this research offers a robust experimental framework for understanding the complex solidification behavior of cyclohexanol on Si substrates. The study contributes both qualitative and quantitative analyses, enriching our understanding of the variables that govern the solidification process, which has significant implications for enhancing the overall reliability and efficiency of semiconductor manufacturing.

[Challenges faced by psychiatric services in Miyagi Prefecture after the Great East Japan Earthquake].

Following the Great East Japan Earthquake and Tsunami, the number of patients with onset, relapse, and exacerbation of mental disorders was expected to increase in Miyagi Prefecture, one of the worst affected areas. The functioning of almost all psychiatric hospitals sharply declined or even ceased. This situation worsened with traffic congestion and crippled public transportation, hindering many patients with psychiatric disorders from accessing mental health services. Among them, patients with schizophrenia and related disorders were affected the most; some could not reach the hospitals and clinics they had regularly visited and had to become new patients of another hospital or clinic. Moreover, an increasing number of patients with schizophrenia needed to be hospitalized because of acute exacerbations of their disorder, due to the experience of the disaster and the consequent drastic changes in their living environment Unfortunately, the support system for psychiatric institutions after disasters is not yet well structured; the system needs to be rebuilt and strengthened in anticipation of future disasters.

Successful rechallenge with clozapine after discontinuation due to drug-induced pneumonia: A case report.

Background: There have been a limited number of case reports of clozapine-induced pneumonia. Few have reported rechallenging of clozapine after discontinuation due to the side-effect. Case Presentation: A 43-year-old man was diagnosed with schizophrenia after developing auditory hallucinations and delusions of persecution and reference. After diagnosing him with treatment-resistant schizophrenia, clozapine was started. From a starting dose of 12.5 mg/day, we increased it by 25 mg every 2-3 days to reach 150 mg/day by Day 15. On Day 17, his body temperature suddenly rose to 39.6°C (103.3°F) without any other apparent physical symptoms. Blood biochemistry testing showed elevated C-reactive protein (CRP) and high counts of leukocytes and neutrophils, but not eosinophils. Chest computed tomography revealed ground-glass opacities in the lower lobes of both lungs. Suspecting bacterial pneumonia, we started him on levofloxacin 500 mg/day. However, pneumonia exacerbated, and eosinophilia became apparent 5 days after the onset of fever. We suspected acute eosinophilic pneumonia induced by clozapine and discontinued its administration the same day. The patient clinically recovered the next day after stopping clozapine. After stopping clozapine, his psychiatric symptoms, such as persecutory/referential delusions, irritability, and polydipsia, became worse. We decided to rechallenge with clozapine in incremental doses slower than the standard protocol, along with careful monitoring of CRP and eosinophil counts. Pneumonia has not recurred, and his psychiatric symptoms have been well managed. Conclusion: Our experience suggests that some patients with inflammatory reactions to clozapine can still take the drug if it is reintroduced with caution.

Depression is associated with increased disease activity in patients with ulcerative colitis: A propensity score-matched analysis using a nationwide database in Japan.

Background and Aim: The incidence and prevalence of psychiatric disorders are elevated in patients with inflammatory bowel disease (IBD). Whether psychiatric disorders could affect the clinical course of IBD is uncertain and controversial. We aimed to evaluate the impact of psychiatric disorders, particularly depression, on the clinical course of IBD using a nationwide database in Japan. Methods: We collected data on admissions with IBD using the Diagnosis Procedure Combination database system introduced in Japan. We divided eligible admissions into IBD with and without depression groups using propensity score matching and compared the rates of surgery, use of molecular targeted drugs and biologics, systemic steroid administrations, and in-hospital death. We also conducted a logistic regression analysis to identify clinical factors affecting surgery, the use of molecular targeted drugs and biologics, and systemic steroid administrations. Results: The rates of surgery, use of two or more molecular targeted drugs, systemic steroid administrations, and in-hospital deaths in the ulcerative colitis (UC) with depression group were higher than in the UC without depression group. Multivariate analysis of UC showed that depression increased the odds of systemic steroid administrations, use of two or more molecular targeted drugs, and surgery. However, analysis of Crohn's disease showed that only steroid administrations were associated with depression. Conclusion: Our study demonstrated an association between a worse clinical course of UC and depression. Although this result indicates that depression might be associated with increased disease activity in patients with UC, the causal relationship is still unclear. Further prospective studies are warranted.

Reduced cortical thickness of the paracentral lobule in at-risk mental state individuals with poor 1-year functional outcomes.

Although widespread cortical thinning centered on the fronto-temporal regions in schizophrenia has been reported, the findings in at-risk mental state (ARMS) patients have been inconsistent. In addition, it remains unclear whether abnormalities of cortical thickness (CT) in ARMS individuals, if present, are related to their functional decline irrespective of future psychosis onset. In this multicenter study in Japan, T1-weighted magnetic resonance imaging was performed at baseline in 107 individuals with ARMS, who were subdivided into resilient (77, good functional outcome) and non-resilient (13, poor functional outcome) groups based on the change in Global Assessment of Functioning scores during 1-year follow-up, and 104 age- and sex-matched healthy controls recruited at four scanning sites. We measured the CT of the entire cortex and performed group comparisons using FreeSurfer software. The relationship between the CT and cognitive functioning was examined in an ARMS subsample (n = 70). ARMS individuals as a whole relative to healthy controls exhibited a significantly reduced CT, predominantly in the fronto-temporal regions, which was partly associated with cognitive impairments, and an increased CT in the left parietal and right occipital regions. Compared with resilient ARMS individuals, non-resilient ARMS individuals exhibited a significantly reduced CT of the right paracentral lobule. These findings suggest that ARMS individuals partly share CT abnormalities with patients with overt schizophrenia, potentially representing general vulnerability to psychopathology, and also support the role of cortical thinning in the paracentral lobule as a predictive biomarker for short-term functional decline in the ARMS population.

Investigation of the Effect of Inhomogeneous Material on the Fracture Mechanisms of Bamboo by Finite Element Method.

Bamboo is a remarkably strong and sustainable material available for construction. It exhibits optimized mechanical characteristics based on a hollow-inhomogeneous structure which also affects its fracture behavior. In this study, the aim is to investigate the effect of material composition and geometrical attributes on the fracture mechanisms of bamboo in various modes of loading by the finite element method. In the first part of the investigation, the optimized transverse isotropy of bamboo to resist transverse deformation was numerically determined to represent its noticeable orthotropic characteristics which prevail in the axial direction. In the second part of this study, a numerical investigation of fracture mechanisms in four fundamental modes of loading, namely bending, compression, torsion, and shear, were conducted by considering the failure criterion of maximum principal strain. A crack initiation stage was simulated and compared by implementing an element erosion technique. Results showed that the characteristics of bamboo's crack initiation differed greatly from solid geometry and homogeneous material-type models. Splitting patterns, which were discerned in bending and shear modes, differed in terms of location and occurred in the outside-center position and inside-lowermost position of the culm, respectively. The results of this study can be useful in order to achieve optimized strength in bamboo-inspired bionic designs.

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.

Theoretical and Experimental Studies on Thermal Properties of Polyester Nonwoven Fibrous Material.

Polyester nonwoven fibrous material is widely used in construction and automobile industries for thermal insulation purposes. It is worthy and meaningful to understand the effect of structural parameters on the thermal property. Fiber orientation, as one of the most vital parameters, has a significant effect on thermal property. However, there has been little quantitative analysis focusing on this aspect. This paper theoretically and experimentally analyzes the thermal conductivity of samples with varying fiber orientation. Existing models were selected to predict the thermal conductivity of polyester nonwoven samples. Two different apparatus were applied to carry out the experimental measurements. The relative differences between the predicted and measured results were compared. One commonly used model was modified for accurate prediction. It was shown that some existing models under- or overestimate the thermal conductivity compared to the measured values. The results indicate that the modified model can accurately predict the thermal conductivity of polyester nonwoven materials within a 0.2% relative difference.

Machine learning to reveal hidden risk combinations for the trajectory of posttraumatic stress disorder symptoms.

The nature of the recovery process of posttraumatic stress disorder (PTSD) symptoms is multifactorial. The Massive Parallel Limitless-Arity Multiple-testing Procedure (MP-LAMP), which was developed to detect significant combinational risk factors comprehensively, was utilized to reveal hidden combinational risk factors to explain the long-term trajectory of the PTSD symptoms. In 624 population-based subjects severely affected by the Great East Japan Earthquake, 61 potential risk factors encompassing sociodemographics, lifestyle, and traumatic experiences were analyzed by MP-LAMP regarding combinational associations with the trajectory of PTSD symptoms, as evaluated by the Impact of Event Scale-Revised score after eight years adjusted by the baseline score. The comprehensive combinational analysis detected 56 significant combinational risk factors, including 15 independent variables, although the conventional bivariate analysis between single risk factors and the trajectory detected no significant risk factors. The strongest association was observed with the combination of short resting time, short walking time, unemployment, and evacuation without preparation (adjusted P value = 2.2 × 10-4, and raw P value = 3.1 × 10-9). Although short resting time had no association with the poor trajectory, it had a significant interaction with short walking time (P value = 1.2 × 10-3), which was further strengthened by the other two components (P value = 9.7 × 10-5). Likewise, components that were not associated with a poor trajectory in bivariate analysis were included in every observed significant risk combination due to their interactions with other components. Comprehensive combination detection by MP-LAMP is essential for explaining multifactorial psychiatric symptoms by revealing the hidden combinations of risk factors.