Sex-dependent association of DNA methylation of HPA axis-related gene FKBP5 with obsessive-compulsive disorder.

AIMS: Although hypothalamic-pituitary-adrenal (HPA) axis dysregulation in obsessive-compulsive disorder (OCD) has been reported, epigenetic changes in HPA axis-related genes have not been well studied in OCD. The present study investigated whether the epigenetic regulation of FK506-binding protein 51 gene (FKBP5) intron 7 is associated with OCD status in each sex. In addition, relationships among the DNA methylation levels of FKBP5 intron 7, OCD status and early-life trauma were explored. METHODS: A total of 267 patients with OCD and 201 controls aged between 18 and 40 years were recruited. Demographic and clinical assessment, FKBP5 rs1360780 genotyping, and pyrosequencing of FKBP5 intron 7 were conducted. DNA was extracted from peripheral blood leucocytes. First, multivariate analysis of covariance for differential DNA methylation levels between OCD patients and controls was conducted with adjustment for FKBP5 rs1360780 genotype, early-life trauma, depressive symptoms, and age as covariates in each sex. Next, path analysis was conducted to determine the mediation effects of DNA methylation levels of FKBP5 between early-life trauma and OCD status. In addition, sensitivity analyses for medication and lifetime major depression were also performed. RESULTS: DNA methylation at the FKBP5 intron 7 CpG site was significantly lower in men with OCD, compared to controls (mean difference -1.33%, 95% CI -2.11 to -0.55, p < 0.001). The results remained significant for drug naïve or free subjects (mean difference -1.27%, 95% CI -2.18 to -0.37, p = 0.006, in men) and for subjects without lifetime major depressive disorder (mean difference -1.60%, 95% CI -2.54 to -0.66, p < 0.001, in men). The mediation effect of DNA methylation levels was not significant between early-life trauma and OCD status. CONCLUSION: These findings suggest that epigenetic factors of HPA axis-related gene FKBP5 may play a role in the pathogenesis of OCD. Further studies are needed to determine how altered DNA methylation of FKBP5 intron 7 and HPA axis function are involved in OCD.

Microbiome analysis of circulating bacterial extracellular vesicles in obsessive-compulsive disorder.

AIM: The present study examined the microbiome abundance and composition of drug-naive or drug-free patients with obsessive-compulsive disorder (OCD) compared with healthy controls. In addition, in the OCD group, the microbiome composition was compared between early-onset and late-onset OCD. METHODS: Serum samples were collected from 89 patients with OCD and 107 age- and sex-matched healthy controls. Bacterial DNA was isolated from bacteria-derived extracellular vesicles in serum and then amplified and quantified using primers specific to the V3-V4 hypervariable region of the 16S ribosomal RNA gene. The 16S ribosomal DNA gene amplicon sequencing was performed. RESULTS: The pooled estimate showed that α-diversity was significantly reduced in patients with OCD compared with that in healthy controls (PShannon = 0.00015). In addition, a statistically significant difference was observed in ß-diversity between patients with OCD and healthy controls at the order (P = 0.012), family (P = 0.003), genus (P < 0.001), and species (P = 0.005) levels. In the microbiome composition, Pseudomonas, Caulobacteraceae (f), Streptococcus, Novosphingobium, and Enhydrobacter at the genus level were significantly less prevalent in patients with OCD than in controls. In addition, among patients with OCD, the microbial composition in the early-onset versus late-onset types was significantly different with respect to the genera Corynebacterium and Pelomonas. CONCLUSION: The present study showed an aberrant microbiome in patients with OCD, suggesting a role of the microbiota-brain interaction in the pathophysiology of OCD. Further longitudinal studies with larger sample sizes adjusting for various confounders are warranted.

Psychological factors associated with COVID-19 related anxiety and depression in young adults during the COVID-19 pandemic.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic and the corresponding lockdown have drastically changed our lives and led to high psychological distress and mental health problems. This study examined whether psychological factors such as loneliness, perfectionism, and health anxiety are associated with COVID-19 related anxiety and depression during the pandemic in young Korean adults, after controlling for various socio-demographic factors and early life stress. METHODS: A total of 189 participants (58.2% women) completed a cross-sectional online survey including the Fear of COVID-19 Scale, Center for Epidemiologic Studies Depression Scale, 3-item Revised UCLA Loneliness Scale, Frost Multidimensional Perfectionism Scale, and Whiteley Index-6. Hierarchical linear regression analyses with three blocks were employed to identify the factors that contributed to COVID-19 related anxiety and depressive symptoms. RESULTS: Hierarchical regression analyses showed that higher health anxiety was significantly associated with more severe COVID-19 related anxiety (standardized regression coefficient, ß = 0.599, p < 0.001). Additionally, higher levels of loneliness (ß = 0.482, p < 0.001), perfectionism (ß = 0.124, p = 0.035), and health anxiety (ß = 0.228, p < 0.001) were significantly associated with higher depression scores. The three psychological factors explained 32.8% of the total variance in depressive symptom scores, after taking all covariates into account. CONCLUSION: The results showed that health anxiety was a risk factor for both COVID-19 related anxiety and depression in young adults. Loneliness was the strongest predictor of depressive symptoms during the COVID-19 pandemic. These findings highlight the importance of identifying vulnerable individuals and encouraging psychological counselling and social connections to reduce the burden of psychiatric disorders during the pandemic.

COVID-19 pandemic's impact on networks of depression and anxiety in naturalistic transdiagnostic sample of outpatients with non-psychotic mental illness.

Background: The 2019 coronavirus disease (COVID-19) pandemic has caused an unprecedented disruption of daily lives and a mental health crisis. The present study examined how the depression and anxiety symptom network changed during the COVID-19 pandemic in a naturalistic transdiagnostic sample with non-psychotic mental illness. Materials and methods: A total of 224 psychiatric outpatients before the pandemic and 167 outpatients during the pandemic were included in the study and were assessed for the Patient Health Questionnaire and the Beck Anxiety Inventory. The network of depression and anxiety symptoms before and during the pandemic were estimated separately and were assessed differences. Results: The network comparison analysis showed a significant structural difference between the networks before and during the pandemic. Before the pandemic, the most central symptom in the network was feelings of worthlessness, while in the during pandemic network, somatic anxiety emerged as the most central node. Somatic anxiety, which showed the highest strength centrality during the pandemic, showed significantly increased correlation with suicidal ideation during the pandemic. Limitations: The two cross-sectional network analyses of individuals at one point in time cannot demonstrate causal relationships among measured variables and cannot be assumed to generalize to the intraindividual level. Conclusion: The findings indicate that the pandemic has brought a significant change in the depression and anxiety network and somatic anxiety may serve as a target for psychiatric intervention in the era of the pandemic.

Core clinical symptoms and suicidal ideation in patients with obsessive-compulsive disorder: A network analysis.

INTRODUCTION: Suicidality in obsessive-compulsive disorder (OCD) is underestimated and it is important for clinicians to understand the factors that contribute to suicidal ideation. The present study aimed to estimate a network of the core clinical symptoms of OCD including obsessions, compulsions, and obsessive-compulsive (OC) symptom dimensions, depressive symptoms, and psychological traits, and to examine which symptoms contribute to suicidal ideation in patients with a primary diagnosis of obsessive-compulsive disorder. METHODS: A total of 444 patients with OCD were assessed with the Yale-Brown Obsessive-Compulsive Scale, the Montgomery-Asberg Depression Rating Scale, and various other measures. Network analysis was conducted to estimate the network of obsessive-compulsive and depressive symptoms, psychological traits including alexithymia and impulsivity, and demographic covariates. Symptoms directly related to suicidal ideation in the network were examined for their relative contribution to suicidal ideation. RESULTS: Suicidal ideation was directly related to degree of control over compulsive behaviors, distress associated with compulsive behaviors, time spent performing compulsive behaviors, and unacceptable thoughts, along with depressive symptoms and alexithymia. In the network of OC and depressive symptoms the most central symptoms among the former were interference due to compulsive behaviors and interference due to obsessive thoughts, and among the latter were pessimistic thoughts and reported sadness. CONCLUSION: The findings suggest that along with depressive symptoms and alexithymia, compulsions and unacceptable thoughts dimension may contribute to suicidality, and thus, should be carefully monitored in patients with OCD.

Dysfunctional coronavirus anxiety in nonpsychotic psychiatric outpatients during the COVID-19 pandemic: A network analysis.

BACKGROUND: The 2019 coronavirus disease (COVID-19) pandemic has had a profound impact on the mental health of people worldwide. This study examined dysfunctional coronavirus anxiety in nonpsychotic psychiatric outpatients during the pandemic using the coronavirus anxiety scale (CAS) and examined the relationship between coronavirus anxiety and clinical symptoms using network analysis. METHODS: In this cross-sectional study, 192 patients who first visited the psychiatric outpatient clinic of Severance Hospital during the COVID-19 pandemic with chief complaints of depressed mood, anxiety, somatic symptoms, or insomnia were included. We compared the clinical characteristics of patients with and without dysfunctional coronavirus anxiety. Network analysis was conducted to estimate the network of coronavirus anxiety and depressive, anxious, and hypochondriacal psychopathology. RESULTS: The results showed that 7.8% of patients exhibited dysfunctional coronavirus anxiety (CAS ≥ 5). Patients with dysfunctional coronavirus anxiety showed higher levels of health worry, somatic preoccupation, and subjective anxiety compared to patients without dysfunctional coronavirus anxiety. In the network analysis, the health worry node (Item 6 of the WI) showed the greatest number of connections with coronavirus anxiety nodes. CONCLUSIONS: These findings suggest that health worry may be an important bridge symptom that connects coronavirus anxiety and other clinical psychopathology. Patients with elevated health worries should be carefully monitored during the COVID-19 pandemic for exacerbation of previous symptoms and COVID-19-related psychopathology. Understanding the psychological factors in the face of the pandemic and their relationships with clinical psychiatric symptoms would help people prevent and overcome mental health problems during the pandemic.

Association between social phobia and the risk of arrhythmia using the Korean National Sample Cohort: a retrospective cohort study.

BACKGROUND: Social phobia shares symptoms with arrhythmias, such as palpitations and chest discomfort. However, it is unclear how social phobia is associated with the actual risk of arrhythmia. This study aimed to investigate whether social phobia is associated with the risk of arrhythmia using a nationally representative sample cohort. METHODS: This retrospective cohort study assessed data from the 2002-2013 Korean National Health Insurance Service National Sample Cohort. Using 1:3 propensity score matching for sex, age, income, and insurance status, 1514 patients with social phobia and 4542 control group patients were included in the study. Social phobia and arrhythmia were defined per the International Classification of Diseases, 10th revision. Using cox proportional hazard regression, hazard ratios (HRs) were calculated to estimate the risk of arrhythmia in patients with social phobia. RESULTS: There were statistically significant associations between social phobia history and elevated risks of arrhythmia. Patients with social phobia had a higher risk of arrhythmia after adjusting with covariates (HR = 1.78, 95%CI = 1.25-2.55). Among different types of arrhythmias, atrial fibrillation and flutter presented the highest risk (HR = 2.20, CI = 1.06-4.57) compared to paroxysmal tachycardia (HR = 1.07, CI = 0.39-2.91) and other cardiac arrhythmias (HR = 1.83, CI = 1.16-2.89). CONCLUSION: This study identified the association between social phobia and the risk of arrhythmia in a South Korean representative cohort. These results suggest that social phobia should be treated properly to reduce arrhythmia risks.

Spin-Orbit Torque Switching in an All-Van der Waals Heterostructure.

Current-induced control of magnetization in ferromagnets using spin-orbit torque (SOT) has drawn attention as a new mechanism for fast and energy efficient magnetic memory devices. Energy-efficient spintronic devices require a spin-current source with a large SOT efficiency (ξ) and electrical conductivity (σ), and an efficient spin injection across a transparent interface. Herein, single crystals of the van der Waals (vdW) topological semimetal WTe2  and vdW ferromagnet Fe3 GeTe2 are used to satisfy the requirements in their all-vdW-heterostructure with an atomically sharp interface. The results exhibit values of ξ ≈ 4.6 and σ ≈ 2.25 × 105  Ω-1 m-1 for WTe2 . Moreover, the significantly reduced switching current density of 3.90 × 106 A cm-2 at 150 K is obtained, which is an order of magnitude smaller than those of conventional heavy-metal/ferromagnet thin films. These findings highlight that engineering vdW-type topological materials and magnets offers a promising route to energy-efficient magnetization control in SOT-based spintronics.

Possible Association of Polymorphisms in Ubiquitin Specific Peptidase 46 Gene With Post-traumatic Stress Disorder.

Introduction: Dynamic proteolysis, through the ubiquitin-proteasome system, has an important role in DNA transcription and cell cycle, and is considered to modulate cell stress response and synaptic plasticity. We investigated whether genetic variants in the ubiquitin carboxyl-terminal hydrolase 46 (USP46) would be associated with post-traumatic stress disorder (PTSD) in people with exposure to combat trauma using a case-control candidate gene association design. Methods: Korean male veterans exposed to the Vietnam War were grouped into those with (n = 128) and without (n = 128) PTSD. Seven tagging SNPs of USP46 were selected, and single-marker and haplotype-based association analyses were performed. All analyses were adjusted for sociodemographic factors and levels of combat exposure severity and alcohol problem. Results: One single-marker (rs2244291) showed nominal evidence of association with PTSD status and with the "re-experiencing" cluster, although the association was not significant after Bonferroni correction. No significant association with the other SNPs or the haplotypes was detected. Conclusion: The present finding suggests preliminarily that genetic vulnerability regarding the ubiquitin-proteasome system may be related to fear memory processes and the development of PTSD symptoms after trauma exposure. Further studies with a larger sample size will be needed to examine the role of the ubiquitin-proteasome system including USP46 in PTSD.

A Novel Robot-Assisted Kinematic Measure for Children with Attention-Deficit/Hyperactivity Disorder: A Preliminary Study.

OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by inattention, hyperactivity, and impulsivity. In contrast to neurocognitive measurements of inattention and impulsivity, there has been limited research regarding the objective measurement of hyperactivity in youths with ADHD. The purpose of the present study was to investigate the clinical effectiveness of a newly developed Robot-assisted Kinematic Measure for ADHD (RAKMA) in children with ADHD. METHODS: In total, 35 children with ADHD aged 5 to 12 years and 50 healthy controls (HCs) were recruited, and the parents completed the Child Behavior Checklist and the Korean ADHD Diagnostic Scale. RAKMA performance was represented by RAKMA stimulus-response and hyperactivity variables. We compared the RAKMA performance of those with ADHD and with that of HCs and also investigated the correlation between the RAKMA variables and ADHD clinical scale scores. RESULTS: Significant differences between the ADHD and HC groups were observed regarding most RAKMA variables, including correct reactions, commission errors, omission errors, reaction times, migration distance, and migration speed scores. Significant correlations were detected between various ADHD clinical scale scores and RAKMA variables. CONCLUSION: The RAKMA was a clinically useful tool for objectively measuring hyperactivity symptoms in children with ADHD. Further studies with larger samples are warranted.

Impact of the COVID-19 pandemic on mental health service use among psychiatric outpatients in a tertiary hospital.

BACKGROUND: The aim was to explore the impact of the COVID-19 pandemic on mental health service use according to mental disorder diagnosis among psychiatric outpatients. METHODS: Psychiatric outpatient visits and patient diagnostic information were extracted from the EHR(electronic health records) of a Korean tertiary hospital during 3 months of the COVID-19 pandemic and 3 months before the COVID-19 outbreak. Visit rates of psychiatric outpatients according to primary psychiatric diagnosis category before and after the COVID-19 pandemic were compared using an over-dispersed Poisson regression model. The temporal associations between the number of daily outpatient visits and the daily number of newly confirmed cases were examined by time-series analysis within each diagnosis category. RESULTS: Total daily outpatient visit rate was significantly reduced during the pandemic. Among the nine most prevalent diagnosis categories, the daily visit rates for anxiety disorders, depressive disorders, and schizophrenia-spectrum disorders were significantly reduced by about 29.8%, 14.8%, and 13.3% respectively. Time-series analysis showed significant temporal correlations between the daily number of newly confirmed cases and the daily visit rates for anxiety disorders and depressive disorders, whereas patients with schizophrenia-spectrum disorders showed no significant temporal association. LIMITATIONS: Potential confounding factors unrelated to the pandemic might have influenced the results. CONCLUSIONS: The present findings suggest that patients with anxiety or depressive disorders may have concerns regarding the spread of COVID-19, and may be more reluctant to visit psychiatry outpatient clinics. Delivery strategies for mental healthcare services, such as telepsychiatry, would be helpful to enhance continuity of care during the pandemic.

Non-membrane solvent extraction desalination (SED) technology using solubility-switchable amine.

Solvent extraction desalination (SED) is one of the liquid-liquid separation techniques that selectively uptake freshwater from high saline water, and then separate the absorbed freshwater from the solvent through temperature swing. This study evaluated the desalination performance of seven different amine solvents. Among these solvents, dipropylamine (DPA) was selected as the best solvent for SED, with higher potential of water recovery and salt removal efficiency in batch screening experiment. A continuous SED process was operated using DPA as the solvent, and its desalination performance, i.e. water recovery and salt removal efficiency, was investigated under varied retention time, mixing intensity, and separation temperature. Increase in mixing time, mixing intensity, and separation temperature led to better efficiency of water recovery. On the other hand, salt removal efficiency tended to depend on the inherent characteristics of the solvent, rather than the operating conditions. When the retention time, mixing intensity, and separation temperature were 30 min, 600 rpm, and 80 °C, respectively, the continuous SED process showed 11.05% of water recovery, and 95.5% of salt removal efficiency. Under these conditions, the total thermal energy consumption was estimated at 5.0-6.9 kW h/m3, which is significantly lower than the evaporation process 14.1-27.3 kW h/m3, and comparable to the membrane process 4.0-6.0 kW h/m3.

Aluminum-doped zinc oxide nanoparticles attenuate the TSLP levels via suppressing caspase-1 in activated mast cells.

Zinc oxide nanoparticles (ZO-NPs) are used as antimicrobials, anti-inflammatories, and to treat cancer. However, although ZO-NPs have excellent efficiency and specificity, their cytotoxicity is higher than that of micron-sized zinc oxide. Doping ZO-NPs with aluminum can improve therapeutic efficacy, but the biological effects and mechanisms involved have not been elucidated. Here, we reported the efficacy of aluminum-doped ZO-NP (AZO) on thymic stromal lymphopoietin (TSLP) production and caspase-1 activation in human mast cell line, HMC-1 cells. AZO significantly reduced TSLP levels as well as interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α without inducing cytotoxicity. Furthermore, AZO more effectively reduced TSLP, IL-6, IL-8, and TNF-α levels than ZO-NP. The levels of inflammatory cytokine mRNA were also reduced by AZO treatment. AZO blocked production of IL-1ß and activations of caspase-1 and nuclear factor-κB by inhibiting IκB kinase ß and receptor interacting protein 2. In addition, AZO attenuated phosphorylation of mitogen-activated protein kinases, such as extracellular signal-regulated kinase, c-Jun N-terminal kinases, and p38. These findings provide evidence that AZO improves anti-inflammatory properties and offer a safe and effective potential treatment option.

The therapeutic efficacy of α-pinene in an experimental mouse model of allergic rhinitis.

In the present study, the therapeutic effect and underlying mechanism of α-pinene (α-PN) in the ovalbumin (OVA)-sensitized allergic rhinitis (AR) model were investigated. Our results showed that pretreatment with α-PN caused a decrease in clinical symptoms, including a decrease in the number of nasal, eye, and ear rubs, and spleen weight in the OVA-sensitized mice. The level of interleukin (IL)-4 was decreased on the spleen tissue of α-PN treated mice. Pretreatment with α-PN significantly decreased levels of nasal immunoglobulin E. Protein levels of tumor necrosis factor-α, intercellular adhesion molecule-1, and macrophage inflammatory protein-2 were decreased by the administration of α-PN in the nasal mucosa of the OVA-sensitized mice. The increased numbers of eosinophils and mast cells infiltrating the nasal mucosal tissue of mice with AR were decreased following oral administration of α-PN. Post-treatment with α-PN 1h after OVA challenge also resulted in a significant reduction of clinical symptoms and IgE levels. In addition, the expression and phosphorylation of receptor-interacting protein 2 (RIP2) and IκB kinase (IKK)-ß and activation of nuclear factor-κB (NF-κB), and caspase-1 were all increased in the activated human mast cell line, HMC-1 cells, however, increased activations of RIP2, IKK-ß, NF-κB, and caspase-1 were inhibited by treatment with α-PN. Taken together, we suggest that α-PN is a promising anti-allergic agent and may be useful in the clinical management of AR.

Zinc oxide nanoparticles, a novel candidate for the treatment of allergic inflammatory diseases.

Zinc (Zn) is an essential trace metal for eukaryotes. The roles of Zn in the numerous physiological functions have been elucidated. Bamboo salt contains Zn that was shown to have anti-inflammatory effect and other health benefits. Nanoparticles of various types have found application in the biology, medicine, and physics. Here we synthesized tetrapod-like, zinc oxide nanoparticles (ZO-NP; diameter 200 nm, source of Zn) using a radio frequency thermal plasma system and investigated its effects on mast cell-mediated allergic inflammatory reactions. ZO-NP was found to inhibit the productions and mRNA expressions of inflammatory cytokines such as interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α on the phorbol 12-myristate 13-acetate plus A23187 (PMACI)-stimulated human mast cell line, HMC-1 cells. In these stimulated cells, caspase-1 and nuclear factor-κB activations were abolished by ZO-NP, and the expressions of receptor interacting protein2 (RIP2) and IκB kinaseß (IKKß) induced by PAMCI were reduced. On the other hand, ZO-NP alone increased the expressions of RIP2 and IKKß in normal condition. ZO-NP inhibited the phosphorylation of extracellular signal-regulated protein kinase in the PMACI-stimulated HMC-1 cells. Furthermore, ZO-NP significantly inhibited passive cutaneous anaphylaxis activated by anti-dinitrophenyl IgE. These findings indicate that ZO-NP effectively ameliorates mast cell-mediated allergic inflammatory reaction, and suggest that ZO-NP be considered a potential therapeutic for the treatment of mast cell-mediated allergic diseases.