Subcortical volumetric alterations in four major psychiatric disorders: a mega-analysis study of 5604 subjects and a volumetric data-driven approach for classification.

Differential diagnosis is sometimes difficult in practical psychiatric settings, in terms of using the current diagnostic system based on presenting symptoms and signs. The creation of a novel diagnostic system using objective biomarkers is expected to take place. Neuroimaging studies and others reported that subcortical brain structures are the hubs for various psycho-behavioral functions, while there are so far no neuroimaging data-driven clinical criteria overcoming limitations of the current diagnostic system, which would reflect cognitive/social functioning. Prior to the main analysis, we conducted a large-scale multisite study of subcortical volumetric and lateralization alterations in schizophrenia, bipolar disorder, major depressive disorder, and autism spectrum disorder using T1-weighted images of 5604 subjects (3078 controls and 2526 patients). We demonstrated larger lateral ventricles volume in schizophrenia, bipolar disorder, and major depressive disorder, smaller hippocampus volume in schizophrenia and bipolar disorder, and schizophrenia-specific smaller amygdala, thalamus, and accumbens volumes and larger caudate, putamen, and pallidum volumes. In addition, we observed a leftward alteration of lateralization for pallidum volume specifically in schizophrenia. Moreover, as our main objective, we clustered the 5,604 subjects based on subcortical volumes, and explored whether data-driven clustering results can explain cognitive/social functioning in the subcohorts. We showed a four-biotype classification, namely extremely (Brain Biotype [BB] 1) and moderately smaller limbic regions (BB2), larger basal ganglia (BB3), and normal volumes (BB4), being associated with cognitive/social functioning. Specifically, BB1 and BB2-3 were associated with severe and mild cognitive/social impairment, respectively, while BB4 was characterized by normal cognitive/social functioning. Our results may lead to the future creation of novel biological data-driven psychiatric diagnostic criteria, which may be expected to be useful for prediction or therapeutic selection.

Cerebral cortical structural alteration patterns across four major psychiatric disorders in 5549 individuals.

According to the operational diagnostic criteria, psychiatric disorders such as schizophrenia (SZ), bipolar disorder (BD), major depressive disorder (MDD), and autism spectrum disorder (ASD) are classified based on symptoms. While its cluster of symptoms defines each of these psychiatric disorders, there is also an overlap in symptoms between the disorders. We hypothesized that there are also similarities and differences in cortical structural neuroimaging features among these psychiatric disorders. T1-weighted magnetic resonance imaging scans were performed for 5,549 subjects recruited from 14 sites. Effect sizes were determined using a linear regression model within each protocol, and these effect sizes were meta-analyzed. The similarity of the differences in cortical thickness and surface area of each disorder group was calculated using cosine similarity, which was calculated from the effect sizes of each cortical regions. The thinnest cortex was found in SZ, followed by BD and MDD. The cosine similarity values between disorders were 0.943 for SZ and BD, 0.959 for SZ and MDD, and 0.943 for BD and MDD, which indicated that a common pattern of cortical thickness alterations was found among SZ, BD, and MDD. Additionally, a generally smaller cortical surface area was found in SZ and MDD than in BD, and the effect was larger in SZ. The cosine similarity values between disorders were 0.945 for SZ and MDD, 0.867 for SZ and ASD, and 0.811 for MDD and ASD, which indicated a common pattern of cortical surface area alterations among SZ, MDD, and ASD. Patterns of alterations in cortical thickness and surface area were revealed in the four major psychiatric disorders. To our knowledge, this is the first report of a cross-disorder analysis conducted on four major psychiatric disorders. Cross-disorder brain imaging research can help to advance our understanding of the pathogenesis of psychiatric disorders and common symptoms.

Dynamics of corticocortical brain functional connectivity relevant to therapeutic response to biologics in inflammatory arthritis.

Aberrant functional connectivity (FC) of the brain regions, evaluated by functional magnetic resonance imaging (fMRI), affects clinical courses in inflammatory arthritis (IA). The static analysis methods would be simplistic to estimate the whole picture of resting-state brain function because blood oxygen level-dependent (BOLD) signals fluctuate over time. The effects of FC dynamics on clinical course are unknown in IA. Therefore, we aimed to evaluate dynamic FC for therapeutic responsiveness to biologics in IA patients. We analyzed resting-state fMRI data of 64 IA patients in 2 cohorts. Dynamic FC was derived as a correlation coefficient of the windowed BOLD signal time series. We determined representative whole-brain dynamic FC patterns by k-means++ cluster analysis, leading to 4 distinct clusters. In the first cohort, occurrence probability of the distinct cluster was associated with favorable therapeutic response in disease activity and patients' global assessment, which was validated by the second cohort. The whole-brain FC of the distinct cluster indicated significantly increased corticocortical connectivity, and probabilistically decreased after therapy in treatment-effective patients compared with -ineffective patients. Taken together, frequent emergence of corticocortical connections was associated with clinical outcomes in IA. The coherence of corticocortical interactions might affect pain modulation, possibly relevant to therapeutic satisfaction.

Comorbid psychiatric disorders and long-term survival after liver transplantation in transplant facilities with a psychiatric consultation-liaison team: a multicenter retrospective study.

OBJECTIVE: Comorbid psychiatric disorders negatively affect the survival rate of patients with some physical disorders. In liver transplant recipients, various psychiatric disorders have been identified as worsening prognosis. However, little is known about how the presence of any comorbid (overall) disorders affect the survival rate of transplant recipients. In this study, we examined the effect of overall comorbid psychiatric disorders on survival rate in liver transplant recipients. METHODS: A total of 1006 recipients who underwent liver transplantation between September 1997 and July 2017 across eight transplant facilities with a psychiatric consultation-liaison team were identified consecutively. Recipients were categorized into those with comorbid psychiatric disorders and those without comorbid psychiatric disorders. In the comorbid psychiatric disorder group, psychiatric disorder diagnosis and time of diagnosis were investigated retrospectively. RESULTS: Of the 1006 recipients, 294 (29.2%) had comorbid psychiatric disorders. Comorbid psychiatric disorders in the 1006 recipients were insomnia (N = 107, 10.6%), delirium (N = 103, 10.2%), major depressive disorder (N = 41, 4.1%), adjustment disorder (N = 19, 1.9%), anxiety disorder (N = 17, 1.7%), intellectual disability (N = 11, 1.1%), autism spectrum disorder (N = 7, 0.7%), somatic symptom disorder (N = 4, 0.4%) schizophrenia (N = 4, 0.4%), substance use disorder (N = 24, 2.4%) and personality disorder (N = 2, 0.2%). The most common time of psychiatric disorder diagnosis was within the first 3 months after liver transplantation (51.6%). The final mortality in patients with comorbid psychiatric disorder diagnosis during the five periods (pretransplant, transplant to 3 months, months to 1 year, 1 to 3 years, and over 3 years posttransplant) was 16.2%, 18.8%, 39.1%, 28.6%, and 16.2% respectively, and there were no significant differences between the five periods (χ2 = 8.05, df = 4, p = 0.09). Overall comorbid psychiatric disorders were significantly associated with shorter survival time (log-rank test: p = 0.01, hazard ratio: 1.59 [95% confidence interval: 1.14-2.21], survival rate at the endpoint [%]: 62.0 vs. 83.3). However, after adjusting for confounding variables using Cox proportional hazards regression, there was no significant effect of overall comorbid psychiatric disorders on prognosis. CONCLUSION: Comorbid psychiatric disorders did not affect the survival rate of liver transplant recipients in this study.

Neurobiological correlation between phosphorylated tau and mood symptoms in memory clinic patients.

BACKGROUND: Alzheimer's disease (AD) dementia and mild cognitive impairment are characterised by impaired cognition accompanied by neuropsychiatric symptoms (NPS) relating to mood, including depression, anxiety, and apathy. However, the utility of AD biomarkers for predicting mood symptoms of NPS remains controversial. Herein, we analyzed the relationship between phosphorylated tau (p-tau) and depression, anxiety, and apathy of NPS. We also examined the influence of genetic factors such as apolipoprotein E (APOE) ε4 on these relationships. METHODS: We conducted a cross-sectional survey in older patients (n = 122) with normal cognition (n = 12), mild cognitive impairment (n = 46), and AD (n = 64) strictly diagnosed by the board of psychiatrists and neurologists of Hokkaido University. NPS of the patients were assessed using the Neuropsychiatric Inventory Questionnaire (NPI). All patients also received a lumbar puncture to obtain cerebral spinal fluid for assessment of p-tau. The inverse probability weighting method was used to adjust for demographic differences between the p-tau present group and the p-tau absent group. RESULTS: There was an association between p-tau accumulation and decreased incidence of depression and apathy. APOE ε4 non-carriers also showed a trend toward a negative association between p-tau and depression, which was not evident in APOE ε4 carriers. CONCLUSIONS: We provide new evidence for a negative correlation between p-tau and depression and apathy of NPS, which may be influenced by APOE ε4. Future longitudinal studies are required to confirm the utility of p-tau for predicting the course of mood symptoms in patients with cognitive decline.

Unguided Computer-Assisted Self-Help Interventions Without Human Contact in Patients With Obsessive-Compulsive Disorder: Systematic Review and Meta-analysis.

BACKGROUND: Computer-assisted treatment may reduce therapist contact and costs and promote client participation. This meta-analysis examined the efficacy and acceptability of an unguided computer-assisted therapy in patients with obsessive-compulsive disorder (OCD) compared with a waiting list or attention placebo. OBJECTIVE: This study aimed to evaluate the effectiveness and adherence of computer-assisted self-help treatment without human contact in patients with OCD using a systematic review and meta-analysis approach. METHODS: Randomized controlled trials with participants primarily diagnosed with OCD by health professionals with clinically significant OCD symptoms as measured with validated scales were included. The interventions included self-help treatment through the internet, computers, and smartphones. We excluded interventions that used human contact. We conducted a search on PubMed, Cochrane Central Register of Controlled Trials, EMBASE, World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov, as well as the reference lists of the included studies. The risk of bias was evaluated using version 2 of the Cochrane risk-of-bias tool for randomized trials. We calculated the standardized mean differences for continuous outcomes and risk ratios for dichotomous outcomes. The primary outcomes were short-term improvement of OCD symptoms measured by validated scales and dropout for any reason. RESULTS: We included 11 randomized controlled trials with a total of 983 participants. The results indicated that unguided computer-assisted self-help therapy was significantly more effective than a waiting list or psychological placebo (standard mean difference -0.47, 95% CI -0.73 to -0.22). Unguided computer-assisted self-help therapy had more dropouts for any reason than waiting list or psychological placebo (risk ratio 1.98, 95% CI 1.21 to 3.23). However, the quality of evidence was very low because of the risk of bias and inconsistent results among the included studies. The subgroup analysis showed that exposure response and prevention and an intervention duration of more than 4 weeks strengthen the efficacy without worsening acceptability. Only a few studies have examined the interaction between participants and systems, and no study has used gamification. Most researchers only used text-based interventions, and no study has used a mobile device. The overall risk of bias of the included studies was high and the heterogeneity of results was moderate to considerable. CONCLUSIONS: Unguided computer-assisted self-help therapy for OCD is effective compared with waiting lists or psychological placebo. An exposure response and prevention component and intervention duration of more than 4 weeks may strengthen the efficacy without worsening the acceptability of the therapy. TRIAL REGISTRATION: PROSPERO (International Prospective Register of Systematic Reviews) CRD42021264644; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=264644.

White matter microstructural alterations across four major psychiatric disorders: mega-analysis study in 2937 individuals.

Identifying both the commonalities and differences in brain structures among psychiatric disorders is important for understanding the pathophysiology. Recently, the ENIGMA-Schizophrenia DTI Working Group performed a large-scale meta-analysis and reported widespread white matter microstructural alterations in schizophrenia; however, no similar cross-disorder study has been carried out to date. Here, we conducted mega-analyses comparing white matter microstructural differences between healthy comparison subjects (HCS; N = 1506) and patients with schizophrenia (N = 696), bipolar disorder (N = 211), autism spectrum disorder (N = 126), or major depressive disorder (N = 398; total N = 2937 from 12 sites). In comparison with HCS, we found that schizophrenia, bipolar disorder, and autism spectrum disorder share similar white matter microstructural differences in the body of the corpus callosum; schizophrenia and bipolar disorder featured comparable changes in the limbic system, such as the fornix and cingulum. By comparison, alterations in tracts connecting neocortical areas, such as the uncinate fasciculus, were observed only in schizophrenia. No significant difference was found in major depressive disorder. In a direct comparison between schizophrenia and bipolar disorder, there were no significant differences. Significant differences between schizophrenia/bipolar disorder and major depressive disorder were found in the limbic system, which were similar to the differences in schizophrenia and bipolar disorder relative to HCS. While schizophrenia and bipolar disorder may have similar pathological characteristics, the biological characteristics of major depressive disorder may be close to those of HCS. Our findings provide insights into nosology and encourage further investigations of shared and unique pathophysiology of psychiatric disorders.

Microstructural Alterations in Bipolar and Major Depressive Disorders: A Diffusion Kurtosis Imaging Study.

BACKGROUND: Identifying structural and functional abnormalities in bipolar (BD) and major depressive disorders (MDD) is important for understanding biological processes. HYPOTHESIS: Diffusion kurtosis imaging (DKI) may be able to detect the brain's microstructural alterations in BD and MDD and any differences between the two. STUDY TYPE: Prospective. SUBJECTS: In all, 16 BD patients, 19 MDD patients, and 20 age- and gender-matched healthy volunteers. FIELD STRENGTH/SEQUENCE: DKI at 3.0T. ASSESSMENT: The major DKI indices of the brain were compared voxel-by-voxel among the three groups. Significantly different voxels were tested for correlation with clinical variables (ie, Young Mania Rating Scale [YMRS], 17-item Hamilton Depression Rating Scale [17-HDRS], Montgomery-Åsberg Depression Rating Scale, total disease duration, duration of current episode, and the number of past manic/depressive episodes). The performance of the DKI indices in identifying microstructural alterations was estimated. STATISTICAL TESTS: One-way analysis of variance (ANOVA) was used for group comparison of DKI indices. The performance of these indices in detecting microstructural alterations was determined by receiver operating characteristic (ROC) analysis. Pearson's product-moment correlation analyses were used to test the correlations of these indices with clinical variables. RESULTS: DKI revealed widespread microstructural alterations across the brain in each disorder (P < 0.05). Some were significantly different between the two disorders. Mean kurtosis (MK) in the gray matter of the right inferior parietal lobe was able to distinguish BD and MDD with an accuracy of 0.906. A strong correlation was revealed between MK in that region and YMRS in BD patients (r = -0.641, corrected P = 0.042) or 17-HDRS in MDD patients (r = -0.613, corrected P = 0.030). There were also strong correlations between a few other DKI indices and disease duration (r = -0.676 or 0.626, corrected P < 0.05). DATA CONCLUSION: DKI detected microstructural brain alterations in BD and MDD. Its indices may be useful to distinguish the two disorders or to reflect disease severity and duration. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 3 J. Magn. Reson. Imaging 2020;52:1187-1196.

Distinctive Neuroanatomical Substrates for Depression in Bipolar Disorder versus Major Depressive Disorder.

No neuroanatomical substrates for distinguishing between depression of bipolar disorder (dBD) and major depressive disorder (dMDD) are currently known. The aim of the current multicenter study was to identify neuroanatomical patterns distinct to depressed patients with the two disorders. Further analysis was conducted on an independent sample to enable generalization of results. We directly compared MR images of these subjects using voxel-based morphometry (VBM) and a support vector machine (SVM) algorithm using 1531 participants. The VBM analysis showed significantly reduced gray matter volumes in the bilateral dorsolateral prefrontal (DLPFC) and anterior cingulate cortices (ACC) in patients with dBD compared with those with dMDD. Patients with the two disorders shared small gray matter volumes for the right ACC and left inferior frontal gyrus when compared with healthy subjects. Voxel signals in these regions during SVM analysis contributed to an accurate classification of the two diagnoses. The VBM and SVM results in the second cohort also supported these results. The current findings provide new evidence that gray matter volumes in the DLPFC and ACC are core regions in displaying shared and distinct neuroanatomical substrates and can shed light on elucidation of neural mechanism for depression within the bipolar/major depressive disorder continuum.

[A Case of Dilated Cardiomyopathy after 17 Years of Clozapine Treatment].

Clozapine-induced cardiomyopathy is a rare but fatal complication with a reported incidence of 0.4% in Japan. Clozapine-induced cardiomyopathy develops at an average of 14.4 months after initiating clozapine, and to our knowledge, has a duration no longer than seven years. We present a patient who developed dilated cardiomyopathy after 17 years of clozapine treatment and made a full recovery of cardiac function at 40 weeks after clozapine treatment cessation. A 43-year-old male with a 24-year history of schizophrenia was treated with clozapine (600 mg/day) for 17 years. No abnormal findings were revealed at follow up until he pre- sented with dyspnea with no accompanying symptoms while walking. He was suspected of worsening asthma due to his past history and lack of abnormalities of ECG and CXR. However, as he experienced gradually worsening dyspnea accompanied by listlessness and lightheaded- ness, he was referred to a cardiologist. The echocardiogram revealed left ventricular dilatation and systolic dysfunction (left ventricular ejection fraction, LVEF=40%), which made a diagno- sis of dilated cardiomyopathy. We excluded cardiac ischemia and other possible causes of dilated cardiomyopathy with cardiac catheterization and endomyocardial biopsy. Clozapine treatment was stopped and switched to olanzapine along with standard heart failure medica- tions. The symptoms and left ventricular function improved following clozapine discontinua- tion. The symptoms resolved and echocardiogram showed a LVEF of 50% within 11 weeks after treatment with clozapine was ended. LVEF was reported at 59% 40weeks after cessation of clozapine. At the present time, 32 months since ceasing clozapine treatment, no worsening of symptoms has been presented. After ceasing clozapine and inducing standard heart failure medications, the patient presented the excellent recovery and the normalization of his echocar- diogram. Despite this outcome, there is currently insufficient evidence to conclusively establish a causal relationship between clozapine and cardiomyopathy in this case. In addition, this case demonstrates that we cannot exclude cardiomyopathy due to lack of abnormal findings of ECG and CXR. Therefore, we recommend that echocardiograms should be performed annually. The mortality associated with clozapine-induced cardiomyopathy is high, so if patients undergoing therapy with clozapine develop new symptoms or signs suggestive of cardiac dysfunction such as dyspnea, a focused cardiovascular examination should be considered.

Chronic ischemia alters brain microstructural integrity and cognitive performance in adult moyamoya disease.

BACKGROUND AND PURPOSE: The mechanisms underlying frontal lobe dysfunction in moyamoya disease (MMD) are unknown. We aimed to determine whether chronic ischemia induces subtle microstructural brain changes in adult MMD and evaluated the association of changes with neuropsychological performance. METHODS: MRI, including 3-dimensional T1-weighted imaging and diffusion tensor imaging, was performed in 23 adult patients with MMD and 23 age-matched controls and gray matter density and major diffusion tensor imaging indices were compared between them; any alterations in the patients were tested for associations with age, ischemic symptoms, hemodynamic compromise, and neuropsychological performance. RESULTS: Decrease in gray matter density, associated with hemodynamic compromise (P<0.05), was observed in the posterior cingulate cortex of patients with MMD. Widespread reduction in fractional anisotropy and increases in radial diffusivity and mean diffusivity in some areas were also observed in bilateral cerebral white matter. The fractional anisotropy (r=0.54; P<0.0001) and radial diffusivity (r=-0.41; P<0.01) of white matter significantly associated with gray matter density of the cingulate cortex. The mean fractional anisotropy of the white matter tracts of the lateral prefrontal, cingulate, and inferior parietal regions were significantly associated with processing speed, executive function/attention, and working memory. CONCLUSIONS: In adult MMD, there were more white matter abnormalities than gray matter changes. Disruption of white matter may play a pivotal role in the development of cognitive dysfunction.

Vertical and lateral transport of particulate radiocesium off Fukushima.

Transport processes of particulate radiocesium were investigated using a sediment trap deployed at about 100 km east of the Fukushima Daiichi Nuclear Power Plant. A sediment trap was installed at 873 m depth of the station (119 m above the bottom), and time-series sampling of sinking particles was carried out from August, 2011 to June, 2013. The accident-derived radiocesium was detected from sinking particles over two years after the accident. Observed 137Cs flux was highest in September 2011 (98 mBq m(-2) day(-1): decay-corrected to March 11, 2011), and decreased over time with seasonal fluctuations. Particulate fluxes of radiocesium were mainly affected by two principal processes. One was the rapid sinking of radiocesium-bound particles (moderate mode). This mode was dominant especially in the early postaccident stage, and was presumed to establish the distribution of radiocesium in the offshore seabed. Another mode was observed in winter, and secondary transport of particles attributed to turbulence near the seabed increased fluxes of particulate radiocesium (turbulence mode). Although the latter process would not drastically change the distribution of sedimentary radiocesium in the short term, attention should be paid as this key process redistributing the accident-derived radiocesium may cumulatively affect the long-term distribution.

Validity and reliability of the palliative care needs assessment tool in Japanese patients with heart failure.

AIMS: Although patients with heart failure (HF) frequently experience considerable symptom burden and require significant care, most HF patients do not receive timely intervention due to the absence of a standardized method for identifying those in need of palliative care. The Needs Assessment Tool: Progressive Disease-Heart Failure (NAT: PD-HF) assesses the palliative care needs of patients with HF. However, its validity and reliability have yet to be fully examined. We aimed to assess the validity and reliability of the NAT: PD-HF in Japanese patients with HF. METHODS: We prospectively enrolled 106 consecutive patients with chronic HF admitted to our university hospital between February 2023 and July 2023. Their caregivers (n = 95) and healthcare providers (n = 17) were also included. The NAT: PD-HF was translated from English to Japanese using a forward-backward translation procedure and adapted based on Japanese cultural and medical backgrounds by our professional multidisciplinary team. We assessed the internal consistency of the Japanese NAT: PD-HF version with Cronbach's alpha coefficient and the inter-rater and test-retest reliabilities with Cohen's kappa coefficient. After using the tool, all participants were asked to complete a questionnaire about the tool to determine its validity. RESULTS: The proportion of female patients in this study was 47 (44%). The median age was 72 years [interquartile range (IQR) 59-81]. The median time spent assessing the patients' and their caregivers' needs using the Japanese NAT: PD-HF was 14 min (IQR 12-17). The Cronbach's alpha coefficient was 0.82, and the minimum kappa coefficient was 0.77 for inter-rater reliability and 0.88 for test-retest reliability. In total, 103 patients (97%) and all caregivers responded that the tool was easy to understand. One hundred (94%) patients and 89 (94%) caregivers felt that the tool would improve the quality of care, and 102 (96%) patients and 91 (96%) caregivers indicated that the discussions using this tool allowed them to confide in all their burdens and care needs. All healthcare providers expressed that this tool is helpful in understanding the burden and care needs of both patients and caregivers comprehensively. CONCLUSIONS: The NAT: PD-HF is a reliable and valid tool for Japanese patients with HF and their caregivers. This tool was very well accepted by patients, caregivers and healthcare providers to identify burdens and care needs.

Suspected Postpartum Depression Revealed to be CSF1R-Related Leukoencephalopathy: A Case Report.

Introduction: This is a case of a 32-year-old woman who developed postpartum depression (PPD). She became anxious and depressive about caring for her child, and the Edinburgh Postnatal Depression Scale (EPDS) test showed a score of 9 at 2 weeks after delivery, and at 7 months postpartum, she presented with major melancholic depression followed by mild cognitive decline without any neurological symptoms except cluttering speech. Case Presentation: Cerebral magnetic resonance imaging showed confluent fluid-attenuated inversion recovery hyperintensities in the periventricular and frontal deep white matter, with multiple spotty calcifications in the frontal white matter by cerebral CT. Genetic testing revealed a mutation in the colony-stimulating factor 1 receptor (CSF1R). Conclusion: This case report is consistent with evidence that PPD may have organic causes in some cases, including CSF1R mutations. Atypical findings such as mild cognitive decline combined with PPD in psychiatric interview may justify brain imaging to avoid misdiagnosis, since CSF1R-related leukoencephalopathy is probably an under-recognized disease in medical psychiatry. Further investigations are needed to clarify a pathophysiological correlation between CSF1R signaling abnormality and PPD as well as major depression.

Differences in acute outcomes of suicide patients by psychiatric disorder: Retrospective observational study.

Suicide is a social problem with significant economic losses, the victims of which are mainly from the productive population. There are numerous reports on the assessment of suicide risk, but most focus on long-term management. Therefore, factors influencing the severity of physical impairments in the acute phase and the prognosis of suicidal patients have not been sufficiently investigated. This is a single-center retrospective observational study. We collected data on suicidal patients admitted to our emergency department. The effect of age, gender, psychiatric history, method of suicide, alcohol consumption, and hospital admission on the outcome of suicide was assessed. Outcomes were assessed using the hospital mortality scale and the cerebral performance category scale for in-hospital mortality within 28 days. Methods of suicide with a high mortality rate (hanging, jumping, carbon monoxide poisoning, and burns) were defined as lethal methods. A detailed risk assessment of outcomes was performed for patients with schizophrenia, mood disorders, and somatoform disorders. We identified 340 suicide patients from computerized medical records and analyzed 322 records without missing data. The non-survivor group predominantly comprised older adults, men, and patients without a history of psychiatric treatment. Contrastingly, more patients drank alcohol before suicide in the survivor group. In the subgroup analysis, patients with schizophrenia had unfavorable neurological outcomes. Patients with mood disorders had worse in-hospital mortality than other psychiatric patients, as did patients who chose the lethal method. By disease, patients with stress-related and somatoform disorders tended to have higher survival rates, although their psychiatric hospitalization rates were lower. Conversely, patients with mood disorders had a higher rate of hospital visits but a lower survival rate. The results suggest that usual outpatient treatment alone may not be sufficient to reduce suicide mortality in patients with mood disorders who are considered to be at high risk of suicide.

Cardiovascular adverse reactions associated with escitalopram in patients with underlying cardiovascular diseases: a systematic review and meta-analysis.

Background: Despite the anticipated efficacy of escitalopram in treating depression and anxiety in individuals with preexisting cardiovascular conditions, persistent concerns regarding its adverse effects have emerged. In this systematic review, we aimed to evaluate the cardiovascular safety profile of escitalopram compared with that of placebo in patients with underlying cardiovascular disease. Methods: We used a predefined search strategy in PubMed, Cochrane Central Register of Controlled Trials, Embase, International Clinical Trials Registry Platform, and ClinicalTrials.gov to identify studies evaluating adverse cardiovascular reactions to escitalopram in patients with underlying cardiovascular disease. Randomized controlled trials (RCTs) that provided results on cardiovascular safety outcomes were included. Two independent reviewers screened the abstracts and full texts of the individual studies. The risk of bias was assessed using version 2 of the Cochrane risk-of-bias tool for randomized trials. The certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation approach. Results: The primary outcomes were the frequency of major adverse cardiovascular events (MACE), QTc prolongation, and discontinuation of study medication. We identified 5 RCTs with 773 participants who met the inclusion criteria. Escitalopram was not associated with significantly increased risk of MACE (risk ratio [RR] = 1.85; 95% confidence interval [CI] 0.80 to 4.26; I2 0%; 5 RCTs; n = 773, moderate certainty of evidence), discontinuation of study medication (RR = 1.03; 95% CI 0.84-1.26; I2 0%; 5 RCTs; n = 773, low certainty of evidence), and QTc prolongation (RR = 1.20; 95% CI 0.76-1.90; I2 0%; 4 RCTs; n = 646, low certainty of evidence). Conclusion: Escitalopram does not significantly increase the risk of cardiovascular adverse reactions compared with placebo in patients with underlying cardiovascular disease. However, the presence of wide CIs and the limited number of included studies highlight the need for further studies with larger sample sizes to enhance the precision and reliability of these findings.Systematic review registration: International Prospective Register of Systematic Reviews [CRD42022298181].

Aberrant functional connectivity between anterior cingulate cortex and left insula in association with therapeutic response to biologics in inflammatory arthritis.

BACKGROUND: Brain activity is reported to be associated with individual pain susceptibility and inflammatory status, possibly contributing to disease activity assessment in inflammatory arthritis (IA) including rheumatoid arthritis (RA) and spondyloarthritis (SpA). However, what alteration of brain function associated with disease activity and therapeutic effectiveness in IA remains unclear. We aimed to identify the alterations of brain functional connectivity (FC) shared in both RA and SpA, and evaluate its relationship to anti-rheumatic treatment response using functional magnetic resonance imaging (MRI). PATIENTS AND METHODS: Structural and resting-state functional MRI data were acquired from patients with IA, patients with osteoarthritis (OA) and heathy controls (HCs). Two datasets were adopted to derive (51 IA, 56 OA, and 17 HCs) and validate (31 IA) the observations. 33 IA patients in the derivation dataset and all the patients in validation dataset required biological treatment and were clinically evaluated before and after therapy. Via whole-brain pair-wise FC analyses, we analyzed IA-specific FC measures relevant to therapeutic response to biologics. RESULTS: The value of FC between left insular cortex (IC) and anterior cingulate cortex (ACC) was significantly low in IA patients compared with OA patients and HCs. We demonstrated that the FC between left anterior long insular gyrus as a subdivision of IC and ACC was significantly associated with therapeutic response to biologics regarding the improvement of patients' global assessment (PGA) in both derivation and validation datasets. CONCLUSION: Disease-specific resting-state FC provides a means to assess the therapeutic improvement of PGA and would be a clinical decision-making tool with predictability for treatment response in both RA and SpA.

Significance of Fukushima-derived radiocaesium flux via river-estuary-ocean system.

The environmental dynamics of Fukushima-derived radiocaesium from land to ocean and the impact of its flux on the marine environment are matters of concern because radiocaesium will be continually transported to the open ocean for the next several decades, or possibly more than one hundred years. In order to assess the distribution and flux of radiocaesium in a river-estuary-ocean system, we investigated the activity concentration of radiocaesium in Matsukawa-ura Lagoon, the largest lagoon in Fukushima, where it is very easy to carry out observations with a wide salinity gradient. Activity concentrations of dissolved 137Cs are elevated in seawater of low to intermediate salinity. It can thus be inferred that radiocaesium desorbs from suspended particles in an estuarine area. The porewater activity concentration of 137Cs in lagoon sediment was about 10 times higher than that in the overlying lagoon water. This direct measurement indicates that a significant amount of radiocaesium in sediment desorbs into porewater. From the results of a mass balance model, dissolved 137Cs flux from the lagoon's bottom is 15.3 ± 3.7 times greater than the riverine input, including desorption from particles. In the case of the whole Pacific coast of northeastern Japan (Miyagi, Fukushima, and Ibaraki Prefectures), dissolved 137Cs flux into the open ocean, including diffusion of porewater, is estimated to be up to 1.5 times greater than the sum of riverine input and the ongoing release from the Fukushima Dai-ichi Nuclear Power Station's harbor. Consequently, our results suggest that radiocaesium is transported to the open ocean under the control of various processes, not only by desorption from particles but also, for example, by the diffusion of porewater.

Apathy in Alzheimer's Disease Correlates with the Dopamine Transporter Level in the Caudate Nuclei.

INTRODUCTION: Apathy is a common neuropsychiatric symptom in patients with Alzheimer's disease (AD). The striatal binding potential (BP) of 123I-FP-CIT (N-δ-fluoropropyl-2ß-carbomethoxy-3ß-[4-iodophenyl]tropane) single-photon emission computed tomography (SPECT) is correlated with the degree of apathy in patients with Parkinson's disease (PD) and dementia with Lewy bodies (DLB). This study aimed to determine if dopaminergic activity in the basal ganglia is associated with the development of apathy in AD. METHODS: Nineteen subjects with AD were included and underwent 123I-FP-CIT-SPECT. Patients with other types of dementia as a comorbidity, those taking antidepressants, and those with overt parkinsonism were excluded. Apathy was assessed using the Apathy Evaluation Scale Informant-Japanese version (AES-I-J). SPECT images were overlaid with images in striatal regions of interest (ROIs), and the SPECT values in these regions were counted. The relationship between BP values and AES-I-J scores was investigated using Spearman's rank correlation coefficient. RESULTS: Significant inverse correlations were observed between BP values and AES-I-J scores in the left caudate nucleus and there was a marginally significant inverse correlation in the right caudate nucleus. CONCLUSION: The pathological basis of apathy might be the impairment of the dopaminergic nervous system. Further studies on more subjects with AD, healthy controls, and patients with PD and DLB are needed.