Dynamics of depressive states among university students in Japan during the COVID-19 pandemic: an interrupted time series analysis.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic was reported to have increased depression among university students which was associated with impairments in their campus lives. This study examined changes in depressive states among Japanese university students during the COVID-19 pandemic. METHODS: A secondary data analysis from a factorial randomized controlled trial involving smartphone-based cognitive-behavioral therapy was performed. Six cohorts (N = 1626) underwent an 8-week intervention during the spring or autumn of 2019-2021, with a 9-month follow-up. We evaluated participants' depressive states weekly using the Patient Health Questionnaire-9 (PHQ-9) during the intervention, with monthly evaluations thereafter. The follow-up periods included Japan's four states of emergency (SOEs) to control COVID-19. Hypothesizing that SOEs caused a sudden worsening of depressive states, Study 1 compared the cohorts' PHQ-9 scores, and Study 2 employed time series analysis with a mixed-effects model to estimate identified changes in PHQ-9 scores. RESULTS: Although no changes in depressive states were observed in relation to the SOEs, Study 1 identified sudden increases in PHQ-9 scores at the 28-week evaluation point, which corresponded to the beginning of the new academic year for the three autumn cohorts. In contrast, the three spring cohorts did not exhibit similar changes. Study 2 showed that, for all three autumn cohorts (n = 522), the 0.60-point change was significant (95% CI 0.42-0.78; p < .001) at 28 weeks; that is, when their timeline was interrupted. CONCLUSIONS: While the results do not indicate any notable impact of the SOEs, they highlight the influence of the new academic year on university students' mental health during COVID-19. Trial registration UMIN, CTR-000031307. Registered on February 14, 2018.

g Factor of the

The gyromagnetic factor of the low-lying E=251.96(9) keV isomeric state of the nucleus ^{99}Zr was measured using the time-dependent perturbed angular distribution technique. This level is assigned a spin and parity of J^{π}=7/2^{+}, with a half-life of T_{1/2}=336(5) ns. The isomer was produced and spin aligned via the abrasion-fission of a ^{238}U primary beam at RIKEN RIBF. A magnetic moment |µ|=2.31(14)µ_{N} was deduced showing that this isomer is not single particle in nature. A comparison of the experimental values with interacting boson-fermion model IBFM-1 results shows that this state is strongly mixed with a main νd_{5/2} composition. Furthermore, it was found that monopole single-particle evolution changes significantly with the appearance of collective modes, likely due to type-II shell evolution.

No benefit from flexible titration above minimum licensed dose in prescribing antidepressants for major depression: systematic review.

BACKGROUND: In fixed-dose antidepressant trials, the lower range of the licensed dose achieves the optimal balance between efficacy and tolerability. Whether flexible upward titration while side-effects permit provides additional benefits is unknown. METHODS: We did a systematic review of placebo-controlled randomized trials that examined selective serotonin reuptake inhibitors (SSRIs), venlafaxine or mirtazapine in the acute treatment of major depression. Our primary outcome was response, defined as 50% or greater reduction in depression severity. Secondary outcomes included drop-outs due to adverse effects and drop-outs for any reason. We conducted random-effects meta-analyses to calculate the ratios of odds ratios (RORs) between trials comparing the flexible dose titrating above the minimum licensed dose against placebo and those comparing the fixed minimum licensed dose against placebo. RESULTS: We included 123 published and unpublished randomized controlled trials (29 420 participants). There was no evidence supporting efficacy of the flexible dosing over the fixed low dose of SSRIs (ROR 0.96, 95% CI: 0.73 to 1.25), venlafaxine (1.24, 0.96 to 1.60) or mirtazapine (0.77, 0.33 to 1.78). No important differences were noted for tolerability or for any subgroup analyses except the superior efficacy of venlafaxine flexible dosing between 75 and 150 mg over the fixed 75 mg (1.30, 1.02 to 1.65). CONCLUSION: There was no evidence to support added value in terms of efficacy, tolerability or acceptability of flexibly titrating up the dosage over the minimum licensed dose of SSRIs or mirtazapine. For venlafaxine, increased efficacy can be expected by flexibly titrating up to 150 mg.

Trajectory of criterion symptoms of major depression under newly started antidepressant treatment: sleep disturbances and anergia linger on while suicidal ideas and psychomotor symptoms disappear early.

OBJECTIVE: In modern psychiatry, depression is diagnosed with the diagnostic criteria; however, the trajectory of each of the criterion symptoms is unknown. This study aims to examine this. METHODS: We made repeated assessments of the nine diagnostic criterion symptoms with the Patient Health Questionnaire-9 (PHQ-9) among 2011 participants of a 25-week pragmatic randomised controlled trial of sertraline and/or mirtazapine for hitherto untreated major depressive episodes. The changes from baseline were estimated with the mixed-effects model with repeated measures. The time to disappearance of each symptom was modeled using the Kaplan-Meier survival analysis. RESULTS: The total score on PHQ-9 was 18.5 (SD = 3.9, n = 2011) at baseline, which decreased to 15.3 (5.2, n = 2011) at week 1, to 11.5 (5.9, n = 1953) at week 3, to 7.8 (6.0, n = 1927) at week 9, and to 6.0 (5.9, n = 1910) at week 25. Suicidal ideas, psychomotor symptoms decreased rapidly, while anergia and sleep disturbance also decreased but only slowly. The survival analyses confirmed the primary analyses. CONCLUSIONS: Upon initiation of antidepressant treatment, patients with newly treated major depressive episodes can expect their suicidal ideas and psychomotor symptoms to disappear first but sleep disturbances and anergia to linger on.

Radiative cooling of cationic carbon clusters, CN+, N = 8, 10, 13-16.

The radiative cooling of highly excited carbon cluster cations of sizes N = 8, 10, 13-16 has been studied in an electrostatic storage ring. The cooling rate constants vary with cluster size from a maximum at N = 8 of 2.6 × 104 s-1 and a minimum at N = 13 of 4.4 × 103 s-1. The high rates indicate that photon emission takes place from electronically excited ions, providing a strong stabilizing cooling of the molecules.

Guillain-Barré syndrome in a local area in Japan, 2006-2015: an epidemiological and clinical study of 108 patients.

BACKGROUND AND PURPOSE: Many epidemiological studies of Guillain-Barré syndrome (GBS) and Fisher syndrome (FS) have been conducted in Europe and America. In contrast, epidemiological studies are rare in Asia where the GBS subtypes differ from those in Western countries. This study was undertaken to clarify the incidence of GBS and FS in a local area in Japan as well as their seasonal trends. METHOD: Seventy-one GBS and 37 FS patients were recorded from 2006 to 2015 in an area of approximately 1.5 million inhabitants in Japan. The incidence, seasonal trends and clinical features of GBS and FS were examined. RESULTS: The incidence rate of GBS was 0.42 cases per 100 000 person-years and that of FS was 0.22 cases per 100 000 person-years. The incidence of GBS increased with age and FS affected predominantly patients aged from 45 to 64 years old. There was some seasonal clustering of acute motor axonal neuropathy (AMAN) and FS in spring and summer, but it was not significant. AMAN and FS patients had a high frequency of preceding infection (AMAN, 68% gastrointestinal infection; FS, 65% upper respiratory infection). Antecedent respiratory infection was significantly associated with FS as an outcome. Serum antibodies to ganglioside GM1 were detected in 71% of AMAN patients and antibodies to GQ1b were detected in 81% of FS patients. CONCLUSIONS: Our study offers evidence of a lower incidence of GBS and a higher incidence of FS in a local area in Japan than in Western countries.

Differences in the placebo response in duloxetine and venlafaxine trials.

OBJECTIVE: Our analysis aimed at comparing the placebo effect sizes from randomized controlled trials (RCTs) of two widely prescribed antidepressants, namely duloxetine and venlafaxine, and at analysing a potential influence of the investigated drugs on the placebo response. METHOD: We conducted a comprehensive systematic review and meta-analysis of placebo-controlled, double-blind RCTs, which examined the efficacy of duloxetine and venlafaxine in the acute treatment of major depressive disorder. RESULTS: We included 71 studies (29 duloxetine trials and 43 venlafaxine trials; one study provided data for the duloxetine and the venlafaxine data set). The placebo effect sizes, defined as pre-postscore change divided by baseline standard deviation, differed significantly between venlafaxine and duloxetine studies (-2.51 vs. -2.09; test for subgroup differences P = 0.028; high heterogeneity). The analysis of effect modifiers and the metaregression analyses confirmed the drug, next to baseline depression severity and publication status, as the most influential independent predictor. CONCLUSION: Our analyses show a significant difference in the placebo response between venlafaxine and duloxetine trials and suggest that the investigated drug has an influence on the placebo response that is not related to baseline severity, changes over the years or other variables we included.

Initial severity of major depression and efficacy of new generation antidepressants: individual participant data meta-analysis.

OBJECTIVE: The role of baseline severity as effect modifier in various psychiatric disorders is a topic of controversy and of clinical import. This study aims to examine whether baseline severity modifies the efficacy of various antidepressants for major depression through individual participant data (IPD) meta-analysis. METHOD: We identified all placebo-controlled, double-blind randomised trials of new generation antidepressants in the acute phase treatment of major depression conducted in Japan and requested their IPD through the public-private partnerships (PPPs) between the relevant academic societies and the pharmaceutical companies. The effect modification by baseline depression severity was examined through six increasingly complex competing mixed-effects models for repeated measures. RESULTS: We identified eleven eligible trials and obtained IPD from six, which compared duloxetine, escitalopram, mirtazapine, paroxetine or bupropion against placebo (total n = 2464). The best-fitting model revealed that the interaction between baseline severity and treatment was not statistically significant (coefficient = -0.04, 95% confidence interval: -0.16 to 0.08, P = 0.49). Several sensitivity analyses confirmed the robustness of the findings. CONCLUSION: We may expect as much benefit from antidepressant treatments for mild, moderate or severe major depression. Clinical practice guidelines will need to take these findings into consideration.

Quantum Spin Liquid Emerging from Antiferromagnetic Order by Introducing Disorder.

Quantum spin liquids, which are spin versions of quantum matter, have been sought after in systems with geometrical frustration. We show that disorder drives a classical magnet into a quantum spin liquid through conducting NMR experiments on an organic Mott insulator, κ-(ET)_{2}Cu[N(CN)_{2}]Cl. Antiferromagnetic ordering in the pristine crystal, when irradiated by x rays, disappears. Spin freezing, spin gap, and critical slowing down are not observed, but gapless spin excitations emerge, suggesting a novel role of disorder that brings forth a quantum spin liquid from a classical ordered state.

Does Internet-based cognitive behavioral therapy (iCBT) prevent major depressive episode for workers? A 12-month follow-up of a randomized controlled trial.

BACKGROUND: In this study we investigated whether an Internet-based computerized cognitive behavioral therapy (iCBT) program can decrease the risk of DSM-IV-TR major depressive episodes (MDE) during a 12-month follow-up of a randomized controlled trial of Japanese workers. METHOD: Participants were recruited from one company and three departments of another company. Those participants who did not experience MDE in the past month were randomly allocated to intervention or control groups (n = 381 for each). A 6-week, six-lesson iCBT program was provided to the intervention group. While the control group only received the usual preventive mental health service for the first 6 months, the control group was given a chance to undertake the iCBT program after a 6-month follow-up. The primary outcome was a new onset of DSM-IV-TR MDE during the 12-month follow-up, as assessed by means of the web version of the WHO Composite International Diagnostic Interview (CIDI), version 3.0 depression section. RESULTS: The intervention group had a significantly lower incidence of MDE at the 12-month follow-up than the control group (Log-rank χ2 = 7.04, p < 0.01). The hazard ratio for the intervention group was 0.22 (95% confidence interval 0.06-0.75), when estimated by the Cox proportional hazard model. CONCLUSIONS: The present study demonstrates that an iCBT program is effective in preventing MDE in the working population. However, it should be noted that MDE was measured by self-report, while the CIDI can measure the episodes more strictly following DSM-IV criteria.

Protocol registration and selective outcome reporting in recent psychiatry trials: new antidepressants and cognitive behavioural therapies.

OBJECTIVE: The selective reporting of favorable outcomes has a serious influence on our evidence base. However, this problem has not yet been systematically investigated in the field of psychiatry. Our study aimed to evaluate registration and outcome reporting in randomized controlled trials (RCTs) of standard treatments for depression: cognitive behavioural therapy (CBT) or new-generation antidepressants (ADs). METHOD: We searched for reports of RCTs examining the efficacy of CBT or AD for depression that were published between 2011 and 2013. We then compared their primary outcomes in the trial registries and those in publications. RESULTS: We identified 170 trials. Among them, 92 trials (54.1%) were registered, 43 trials (25.3%) were properly registered, and only 32 (18.8%) trials were both properly registered and reported (the primary outcomes as recorded in the registries were reported in publications). There was no statistically significant difference in the proportions of properly registered and reported trials for CBT or AD (relative risk: 0.51, 95% CI: 0.25-1.03). High impact factor journals, commercial funding, publication of protocol, and relatively large sample size were significant predictors of proper registration and reporting. CONCLUSION: The prevalence of proper registration and reporting is still very low in depression trials.

Enthusiasm for homework and improvement of psychological distress in subthreshold depression during behavior therapy: secondary analysis of data from a randomized controlled trial.

BACKGROUND: Cognitive behavioral therapy (CBT) usually involves homework, the completion of which is a known predictor of a positive outcome. The aim of the present study was to examine the session-by-session relationships between enthusiasm to complete the homework and the improvement of psychological distress in depressed people through the course of therapy. METHODS: Working people with subthreshold depression were recruited to participate in the telephone CBT (tCBT) program with demonstrated effectiveness. Their enthusiasm for homework was enhanced with motivational interviewing techniques and was measured by asking two questions: "How strongly do you feel you want to do this homework?" and "How confident do you feel you can actually accomplish this homework?" at the end of each session. The outcome was the K6 score, which was administered at the start of each session. The K6 is an index of psychological distress including depression and anxiety. We used structural equation modeling (SEM) to elucidate the relationships between enthusiasm and the K6 scores from session to session. RESULTS: The best fitting model suggested that, throughout the course of behavior therapy (BT), enthusiasm to complete the homework was negatively correlated with the K6 scores for the subsequent session, while the K6 score measured at the beginning of the session did not influence the enthusiasm to complete the homeworks assigned for that session. CONCLUSIONS: Empirical data now support the practitioners of BT when they try to enhance their patient's enthusiasm for homework regardless of the participant's distress, which then would lead to a reduction in distress in the subsequent week. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT00885014 . April 20, 2009.

Reliability and validity of the Japanese version of the coping inventory for adults for stressful situations in healthy people.

The present study examined the validity and reliability of the Japanese version of the Coping Inventory for Stressful Situations-2nd Edition™ (CISS; hereafter the CISS-J). The participants were 1,268 healthy Japanese individuals. The factor analyses yielded three major scales (task-, emotion-, and avoidance-oriented coping) corresponding to the original version. In addition, the avoidance-oriented scale of the CISS-J contained two subscales (Distraction and Social diversion), as in the original version. Cronbach's α coefficient was found to be .75-.89 for the three scales and two subscales. Results show that the CISS-J is useful for assessing the coping strategies among this sample of Japanese individuals.

Cooling dynamics of photoexcited C6(-) and C6H(-).

We report conclusive evidence of an efficient cooling mechanism via the electronic radiative transitions of hot small molecular anions isolated in vacuum. We stored C6(-) and C6H(-) in an ion storage ring and observed laser-induced electron detachment with delays up to several milliseconds. The terminal hydrogen atom caused a drastic change in the decay profiles. The decay of photoexcited C6H(-) is slow and nonexponential, which can be explained by depletion cooling, whereas that for C6(-) occurs extremely fast, on a time scale below 0.1 ms and can only be explained by electronic radiative cooling via low-lying electronic excited states.

Waiting list may be a nocebo condition in psychotherapy trials: a contribution from network meta-analysis.

OBJECTIVE: Various control conditions have been employed in psychotherapy trials, but there is growing suspicion that they may lead to different effect size estimates. The present study aims to examine the differences among control conditions including waiting list (WL), no treatment (NT) and psychological placebo (PP). METHOD: We comprehensively searched for all randomized controlled trials (RCTs) comparing cognitive-behaviour therapies (CBT) against various control conditions in the acute phase treatment of depression, and applied network meta-analysis (NMA) to combine all direct and indirect comparisons among the treatment and control arms. RESULTS: We identified 49 RCTs (2730 participants) comparing WL, NT, PP and CBT. This network of evidence was consistent, and the effect size estimates for CBT were substantively different depending on the control condition. The odds ratio of response for NT over WL was statistically significant at 2.9 (95% CI: 1.3-5.7). However, the quality of evidence, including publication bias, was less than ideal and none of the preplanned sensitivity analyses limiting to high-quality studies could be conducted, while findings of significant differences did not persist in post hoc sensitivity analyses trying to adjust for publication bias. CONCLUSION: There may be important differences in control conditions currently used in psychotherapy trials.

Radiative cooling of C7⁻.

The spontaneous and photo-induced neutralization of C7⁻ produced in a laser ablation source was measured in an electrostatic storage ring. The measurements provide three independent determinations of the radiative cooling of the ions, based on the short time spontaneous decay and on the integrated amplitude and the shape of the photo-induced neutralization signal. The amplitude of the photo-induced signal was measured between 0.5 ms and 35 ms and found to depend on photon wavelength and ion storage time. All three signals can be reproduced with identical thermal IR radiative cooling rates with oscillator strengths equal to theoretical predictions. In addition, the measurements provide the excitation energy distribution.

Interaction between Habitual Green Tea and Coffee Consumption and ACTN3 Genotype in Association with Skeletal Muscle Mass and Strength in Middle-Aged and Older Adults.

BACKGROUND: Recent studies have suggested the potential benefits of habitual coffee and green tea consumption on skeletal muscle health. However, it remains unclear whether these benefits are modified by genetic factors, particularly the alpha-actinin-3 (ACTN3) genotype, which is associated with the skeletal muscle phenotype. This study aimed to investigate the interaction between habitual coffee or green tea consumption and the ACTN3 genotype in association with skeletal muscle mass (SMM) and strength. METHODS: This cross-sectional study was conducted on 1,023 Japanese middle-aged and older adults (619 females, aged 45-74 years) living in the community. SMM was gauged using a bioelectrical impedance spectroscopy device, and handgrip strength (HGS) was used to measure muscle strength. The ACTN3 genotype (RR, RX, and XX) was determined from blood samples. Sex-specific linear regression models were used to analyze the interactions between coffee or green tea consumption and the ACTN3 genotype in association with SMM and HGS. RESULTS: In females, a significant interaction was observed between green tea consumption and the ACTN3 genotype in association with HGS (P interaction < 0.05). Furthermore, stratified analysis revealed a positive association between green tea consumption and HGS, specifically in females with the ACTN3 XX genotype (P trend < 0.05). In males, no significant interactions were observed between coffee or green tea consumption and the ACTN3 genotype in association with SMM or HGS (P interaction > 0.05). CONCLUSION: Our findings suggest that the skeletal muscle strength benefits associated with habitual green tea consumption may be contingent upon sex and the ACTN3 genotype.

Comprehensive validation of early diagnostic algorithms for myocardial infarction in the emergency department.

OBJECTIVE: To comprehensively evaluate diagnostic algorithms for myocardial infarction using a high-sensitivity cardiac troponin I (hs-cTnI) assay. PATIENTS AND METHODS: We prospectively enrolled patients with suspected myocardial infarction without ST-segment elevation from nine emergency departments in Japan. The diagnostic algorithms evaluated: (i) based on hs-cTnI alone, such as the European Society of Cardiology (ESC) 0/1-h or 0/2-h and High-STEACS pathways; or (ii) used medical history and physical findings, such as the ADAPT, EDACS, HEART, and GRACE pathways. We evaluated the negative predictive value (NPV), sensitivity as safety measures, and proportion of patients classified as low or high-risk as an efficiency measure for a primary outcome of type 1 myocardial infarction or cardiac death within 30 days. RESULTS: We included 437 patients, and the hs-cTnI was collected at 0 and 1 hours in 407 patients and at 0 and 2 hours in 394. The primary outcome occurred in 8.1% (33/407) and 6.9% (27/394) of patients, respectively. All the algorithms classified low-risk patients without missing those with the primary outcome, except for the GRACE pathway. The hs-cTnI-based algorithms classified more patients as low-risk: the ESC 0/1-h 45.7%; the ESC 0/2-h 50.5%; the High-STEACS pathway 68.5%, than those using history and physical findings (15-30%). The High-STEACS pathway ruled out more patients (20.5%) by hs-cTnI measurement at 0 hours than the ESC 0/1-h and 0/2-h algorithms (7.4%). CONCLUSIONS: The hs-cTnI algorithms, especially the High-STEACS pathway, had excellent safety performance for the early diagnosis of myocardial infarction and offered the greatest improvement in efficiency.