Investigating the shared genetic basis and causal relationships between mucosa-associated lymphoid tissue inflammation and psychiatric disorders.

Background: Chronic and acute inflammation of the mucosa-associated lymphoid tissue have been positively linked to the development of psychiatric disorders in observational studies. However, it remains unclear whether this association is causal. In the present study, we investigated this association, using as proxies genetically predicted tonsillectomy, appendectomy and appendicitis on psychiatric disorders including major depressive disorder (MDD), schizophrenia (SCZ), bipolar depression (BD) and anxiety (ANX) via a two-sample Mendelian randomization (MR) analysis. Methods: Genetic association summary statistics for tonsillectomy, appendectomy and appendicitis were sourced from FinnGen Consortium, comprising data from 342,000 participants. Genetic correlations between all exposures and outcome were calculated with Linkage Disequilibrium Score (LDSC) Regression analysis. MR estimates were then calculated to assess their impact on the risk of developing psychiatric disorders. Sensitivity analysis was employed to test for any directional pleiotropy. Results: Our results suggest that there is no direct causal association between tonsillectomy, appendectomy or appendicitis with a heightened risk for development of psychiatric disorders. The robustness of the results of the main MR analysis was further confirmed with additional sensitivity analyses. However, a moderate inverse genetic correlation was observed between tonsillectomy and MDD traits (rg=-0.39, p-value (P)=7.5x10-5). Conclusion: Our findings provide, for the first time, evidence that there is no causal association between tonsillectomy or appendectomy on subsequent vulnerability of developing psychiatric disorders. Future studies using larger sample size GWAS should focus on unraveling the confounding factors and mediators to investigate this relationship further.

Patients' perspectives related to ethical issues and risks in precision medicine: a systematic review.

Background: Precision medicine is growing due to technological advancements including next generation sequencing techniques and artificial intelligence. However, with the application of precision medicine many ethical and potential risks may emerge. Although, its benefits and potential harms are relevantly known to professional societies and practitioners, patients' attitudes toward these potential ethical risks are not well-known. The aim of this systematic review was to focus on patients' perspective on ethics and risks that may rise with the application of precision medicine. Methods: A systematic search was conducted on 4/1/2023 in the database of PubMed, for the period 1/1/2012 to 4/1/2023 identifying 914 articles. After initial screening, only 50 articles were found to be relevant. From these 50 articles, 24 articles were included in this systematic review, 2 articles were excluded as not in English language, 1 was a review, and 23 articles did not include enough relevant qualitative data regarding our research question to be included. All full texts were evaluated following PRISMA guidelines for reporting systematic reviews following the Joanna Briggs Institute criteria. Results: There were eight main themes emerging from the point of view of the patients regarding ethical concerns and risks of precision medicine: privacy and security of patient data, economic impact on the patients, possible harms of precision medicine including psychosocial harms, risk for discrimination of certain groups, risks in the process of acquiring informed consent, mistrust in the provider and in medical research, issues with the diagnostic accuracy of precision medicine and changes in the doctor-patient relationship. Conclusion: Ethical issues and potential risks are important for patients in relation to the applications of precision medicine and need to be addressed with patient education, dedicated research and official policies. Further research is needed for validation of the results and awareness of these findings can guide clinicians to understand and address patients concerns in clinical praxis.

Insights into suicidal behavior among psoriatic arthritis patients: A systematic review and a genetic linkage disequilibrium analysis.

OBJECTIVES: To systematically assess the magnitude of suicidal behavior among PsA patients and identify associated risk factors. Also identify common genes or coinherited single nucleotide polymorphisms (SNPs) implicated in suicidal behavior and PsA. METHODS: Based on the PRISMA guidelines, we conducted a systematic literature review of the online databases PubMed/Medline, Web of Science, and EMBASE from inception to May 2022. Full-text original articles that describe suicidal behavior in PsA patients were eligible. All registered genome-wide association study (GWAS) data in the GWAS catalog database for PsA and psychiatric traits, such as suicidal behavior, and depression, were downloaded for further analysis. RESULTS: A total of 48 articles were identified, and 6 were relevant to the study question .Among the 122,160 PsA patients, 700 had suicidal behavior (0,57%). The range of age in one study was between 30 and 49 years, and 64% of PsA patients with suicidal behavior were female. Among 13,899 PsA patients 74 had suicidal ideation (0.53%) and 125 suicide attempts occurred (0.9%). In two studies, among 17,383 patients, 13 complete suicides occurred (0.07%). A genetic haplotype on chromosomal region 6p21.1, spanning from 29,597,596 to 32,251,264 Mb, contains predisposing SNPs for PsA and depression. 6p21.1-6p21.3 is the chromosomal region containing the HLA genes of classes I, II and III. CONCLUSION: Suicide behavior in PsA patients was associated with depression and other psychiatric comorbidities. Further evidence supports a genetic origin, at least partly. Awareness of these findings can help clinicians to recognize suicide behavior and prevent suicide attempts.

Cognitive impairment in adults under compulsory psychiatric care: association with psychotic symptoms and high-dose antipsychotics.

BACKGROUND: There is limited evidence on the association between cognitive function, psychotic symptoms and doses of antipsychotics in adults under compulsory psychiatric care. AIMS: We assessed (a) the degree of cognitive impairment in adults involuntarily hospitalised for compulsory psychiatric care and (b) correlation of Montreal Cognitive Assessment (MoCA) score with psychotic symptoms, polypharmacy and prescription of high-dose antipsychotics. METHOD: This was a nationwide, cross-sectional study, conducted at the only referral state hospital for compulsory psychiatric care in Cyprus (December 2016-February 2018). Τhe MoCA was applied for the assessment of cognitive functioning. The Positive and Negative Syndrome Scale (PANSS) was applied for the assessment of psychotic symptoms. RESULTS: The sample comprised 187 men and 116 women. The mean MoCA score was 22.09 (reported scale range (RSR): 3-30); the mean PANSS general symptoms subscale score was 49.60 (RSR = 41-162). The participants who reported positive psychiatric history (mean 21.71, s.d. 5.37), non-adherence to pharmacotherapy (mean 21.32, s.d. 5.56) and prescription of high-dose antipsychotics (with medication prescribed as needed: mean 21.31, s.d. 5.70; without medication prescribed as needed: mean 20.71, s.d. 5.78) had lower mean MoCA scores compared with those who reported negative psychiatric history (mean 23.42, s.d. 4.51; P = 0.017), adherence to pharmacotherapy (mean 23.10, s.d. 6.61; P = 0.003) and no prescription of high-dose antipsychotics (with medication prescribed as needed: mean 22.56, s.d. 4.90; without medication prescribed as needed: mean 22.60 s.d. 4.94; P = 0.045-0.005), respectively. Mean MoCA score was mildly and inversely associated with total PANSS score (r = -0.15, P = 0.03), PANSS general (r = -0.18, P = 0.002) and PANSS negative (r = -0.16, P = 0.005) symptoms subscales, respectively. CONCLUSIONS: Our findings support the evaluation of cognitive functioning in adults under compulsory psychiatric care via the MoCA tool, with focus on those prescribed high-dose antipsychotics, with positive mental health history and non-adherence to pharmacotherapy.

Genome-wide association studies reveal shared genetic haplotypes of autoimmune rheumatic and endocrine diseases with psychiatric disorders.

BACKGROUND: Several studies have shown that autoimmune diseases are associated with psychiatric diseases like depression and psychosis. Genetic evidence supports this association. The aim of this study was to investigate if genetic variants predisposing to autoimmune diseases and psychiatric disorders are genetically linked, constructing the common haplotypes. METHODS: All registered single nucleotide polymorphisms (SNPs) in the Genome-wide association studies ("GWAS catalog") having been associated with autoimmune rheumatic and endocrine diseases were investigated for being in linkage disequilibrium with any psychiatric disorders' associated SNPs. Analysis was performed by the LDtrait and LDhap bioinformatics tools. RESULTS: Multiple chromosomal regions have been detected containing rheumatic/endocrine diseases' predisposing SNPs and psychiatric disorders' predisposing SNPs. The genetic haplotypes have been constructed for some of these genetic regions. Six of the autoimmune rheumatic and endocrine diseases examined here share a common haplotype with psychiatric diseases at the HLA locus 6p21-22. CONCLUSION: Our study shows that autoimmune diseases and psychiatric diseases are genetically linked. Genetic haplotypes have been constructed, showing in detail this genetic linkage.

Work-Related Traumatic Stress Response in Nurses Employed in COVID-19 Settings.

Nurses may be at a higher risk of experiencing work-related traumatic stress response during the COVID-19 pandemic compared to other clinicians. This study aimed to investigate the correlations between work-related trauma symptoms and demographic factors, psychosocial hazards and stress response in a census sample of nurses working in COVID-19 settings in Cyprus. In this nationwide descriptive and cross-sectional study, data were collected between April and May 2020 using a questionnaire that included sociodemographic, educational and employment and work-related variables, as well as a modified version of the Secondary Traumatic Stress Scale (STSS) for the assessment of work-related trauma symptoms during the pandemic. Overall, 233 nurses participated (with a response rate of 61.3%) and 25.7% of them reported clinical work-related trauma symptoms (STSS-M > 55; actual scale range: 17-85). The mean value for emotional exhaustion was 7.3 (SD: 2.29; visual scale range: 1-10), while the value for distress that was caused by being avoided due to work in COVID-19 units was 6.98 (SD: 2.69; visual scale range: 1-10). Positive associations were noted between trauma symptoms and both emotional exhaustion and distress from being avoided by others due to work in a COVID-19 setting and a negative association was also found between trauma symptoms and satisfaction from organizational support variables (all p < 0.002). Working in COVID-19 settings during the pandemic is a stressful experience that has been linked to psychologically traumatic symptoms Thus, supportive measures are proposed for healthcare personnel, even in countries with low COVID-19 burden.

Accelerated epigenetic aging in suicide attempters uninfluenced by high intent-to-die and choice of lethal methods.

Suicide attempts (SA) are associated with excess non-suicidal mortality, putatively mediated in part by premature cellular senescence. Epigenetic age (EA) estimators of biological age have been previously demonstrated to strongly predict physiological dysregulation and mortality risk. Herein, we investigate if violent SA with high intent-to-die is predictive of epigenetics-derived estimates of biological aging. The genome-wide methylation pattern was measured using the Illumina Infinium Methylation EPIC BeadChip in whole blood of 88 suicide attempters. Subjects were stratified into two groups based on the putative risk of later committed suicide (low- [n = 58] and high-risk [n = 30]) in dependency of SA method (violent or non-violent) and/or intent-to-die (high/low). Estimators of intrinsic and extrinsic EA acceleration, one marker optimized to predict physiological dysregulation (DNAmPhenoAge/AgeAccelPheno) and one optimized to predict lifespan (DNAmGrimAge/AgeAccelGrim) were investigated for associations to severity of SA, by univariate and multivariate analyses. The study was adequately powered to detect differences of 2.2 years in AgeAccelGrim in relation to SA severity. Baseline DNAmGrimAge exceeded chronological age by 7.3 years on average across all samples, conferring a mean 24.6% increase in relation to actual age. No individual EA acceleration marker was differentiated by suicidal risk group (p > 0.1). Thus, SA per se but not severity of SA is related to EA, implicating that excess non-suicidal mortality in SA is unrelated to risk of committed suicide. Preventative healthcare efforts aimed at curtailing excess mortality after SA may benefit from acting equally powerful to recognize somatic comorbidities irrespective of the severity inherent in the act itself.

HPA-axis dysregulation is not associated with accelerated epigenetic aging in patients with hypersexual disorder.

BACKGROUND: Hypersexual disorder (HD) - a nonparaphilic sexual desire disorder with impulsivity component - was evaluated for inclusion as a diagnosis in the DSM-5 and the diagnosis compulsive sexual behavior disorder is included as an impulse control disorder in the ICD-11. Hypothalamic-pituitary-adrenal (HPA)-axis hyperactivity is believed to affect cellular senescence and has been implicated in HD. No previous study investigated HD or HPA-axis dysregulation in relation to measures of epigenetic age (EA) acceleration. METHODS: This study reports on a case-control study set-up from a well-characterized cohort, contrasting EA predictors in relation to 60 HD patients and 33 healthy volunteers (HV) and 19 mixed HD/HV exhibiting dexamethasone suppression test (DST) non-suppression to 73 mixed HD/HV DST controls. The genome-wide methylation pattern was measured in whole blood from 94 subjects using the Illumina Infinium Methylation EPIC BeadChip and preprocessed according to specialized protocols suitable for epigenetic age estimation. The online DNAm Age Calculator (https://dnamage. GENETICS: ucla.edu/) was implemented to retrieve various EA predictors, which were compared between the in-silico generated subgroups. RESULTS: Quality control analyses indicated strong correlations between the EA measure DNA methylation GrimAge (DNAm GrimAge - the EA clock most reliably associated with mortality risk) and chronological age in all sub-groups. The study was adequately powered to detect differences of 2.5 and 3.0 years in DNAm GrimAge minus age in relation to both HD and HPA-axis dysregulation, respectively. Baseline DNAm GrimAge exceeded chronological age by 2.8 years on average across all samples. No EA acceleration marker was associated with HD or DST suppression status (p > 0.05). CONCLUSION: EA acceleration markers shown to be strongly predictive of physiological dysregulation and mortality-risk, are not related to HD or DST non-suppression status (measured after 0.5 mg dexamethasone). The independency of HPA-axis dysregulation to EA acceleration does not support the biological relevance of this dosage-regimen when applied to patients with HD. These findings do not support the notion of accelerated cellular senescence in HD. Studies stratifying DST non-suppressors according to established dosage-regimens in somatic settings are needed to fully elucidate the putative contribution of HPA-axis dysregulation to EA.

Depressive symptoms in higher education students during the COVID-19 pandemic: the role of containment measures.

BACKGROUND: Students are a vulnerable group for the indirect impact of the COVID-19 pandemic, particularly their mental health. This paper examined the cross-national variation in students' depressive symptoms and whether this can be related to the various protective measures implemented in response to the initial stage of the COVID-19 outbreak. METHODS: Student data stem from the COVID-19 International Student Well-being Study, covering 26 countries during the first wave of the COVID-19 pandemic. Country-level data on government responses to the COVID-19 pandemic were retrieved from the Oxford COVID-19 Tracker. Multilevel analyses were performed to estimate the impact of the containment and economic support measures on students' depressive symptoms (n = 78 312). RESULTS: School and workplace closures, and stay-at-home restrictions were positively related to students' depressive symptoms during the COVID-19 pandemic, while none of the economic support measures significantly related to depressive symptoms. Countries' scores on the index of these containment measures explained 1.5% of the cross-national variation in students' depressive symptoms (5.3%). This containment index's effect was stable, even when controlling for the economic support index, students' characteristics, and countries' epidemiological context and economic conditions. CONCLUSIONS: Our findings raise concerns about the potential adverse effects of existing containment measures (especially the closure of schools and workplaces and stay-at-home restrictions) on students' mental health.

Suicidal behavior in patients with systematic lupus erythematosus: Systematic literature review and genetic linkage disequilibrium analysis.

BACKGROUND: Previous studies suggested that patients with Systematic Lupus Erythematosus (SLE) have a higher risk of suicidal behavior, including suicidal ideation, attempt and complete suicide. Systematic data describing the SLE patients' clinical characteristics and risk factors of suicidal behavior are lacking. OBJECTIVES: To determine the magnitude of suicidal behavior among SLE patients and to examine predictors associated with suicidal behavior. An additional aim was to identify common genes or coinherited single nucleotide polymorphisms (SNP) implicated in suicidal behavior and SLE. METHODS: We conducted a systematic literature review based on PRISMA guidelines using the online databases PubMed/Medline, EMBASE and Web of Science, from inception to August 2021. Full-text original articles that examined the relationship between SLE patients with suicidal behavior were eligible for our review. Two reviewers independently reviewed articles to assess eligibility using the Newcastle-Ottawa Scale and the Joanna Briggs Institute criteria. Systematic reviews, metanalysis, narrative review, case reports, case series, including less than 10 patients, and conference abstracts, were excluded. All registered genome-wide association study (GWAS) data in the GWAS catalog database for SLE and psychiatric traits (suicidal behavior, depression, anxiety, psychosis) were downloaded for further analysis. Special in silico tools were used to examine if any genetic polymorphisms (SNPs) that predispose for SLE or psychiatric traits can be inherited together as a single haplotype. This could be posing a risk factor for a coexisting psychiatric condition in SLE patients. RESULTS: Of the 64 articles identified, 22 were relevant to the study question; cross-sectional (n = 8) and prospective cohorts (n = 6) were the most frequently retrieved studies. Among the 27,106 SLE patients with SLE, 802 had suicidal behavior (2.9%), and of those, 87.9% were female. Suicide attempt occurred in 573/802 (71.4%) and complete suicide in 18/802 (3%). Major depressive disorder was the most frequently reported coexisting psychiatric condition associated with suicidal behavior, followed by psychosis and social phobia. In addition, several clinical manifestations were linked to suicidal behavior, particularly neuropsychiatric lupus, serositis, mucocutaneous, and renal involvement. Further, high scores in disease activity and damage indices were associated with suicidal behavior. A haplotype in chromosomal region 6p21.33 was found to contain a combination of risk alleles predisposing for SLE and depression, the most common psychiatric disorder associated with suicidal behavior. CONCLUSION: Suicide behavior in SLE patients was associated with depression, neuropsychiatric lupus, active disease and damage. Further evidence supports a genetic origin of psychiatric symptoms in SLE patients. Awareness of these findings can guide clinicians to recognize suicide behavior promptly and prevent suicide attempts.

High Plasma Oxytocin Levels in Men With Hypersexual Disorder.

CONTEXT: Hypersexual disorder (HD) involves excessive, persistent sexual behaviors related to various mood states and the diagnosis compulsive sexual behavior disorder is included as an impulse control disorder in the 11th revision of the International Classification of Diseases. Although the neurobiology behind the disorder is not clear, some studies suggest dysregulated hypothalamic-pituitary-adrenal axis. Oxytocin acts as counterregulatory neuroendocrine hormone to cortisol and is also involved in sexual behavior. OBJECTIVE: We hypothesized that oxytocin may play a role in the pathophysiology of HD with compensatory actions to cortisol. DESIGN: Longitudinal. SETTING: ANOVA clinic (Karolinska University Hospital). PATIENTS OR OTHER PARTICIPANTS: 64 males with HD and 38 age-matched healthy volunteers. MAIN OUTCOME MEASURES: Plasma oxytocin levels, measured with radioimmunoassay; Hypersexual Disorder Screening Inventory; and Hypersexual Disorder: Current Assessment Scale for assessing hypersexual symptoms. INTERVENTIONS: A patient subgroup (n = 30) completed the manual-based group-administered cognitive-behavioral therapy (CBT) program for HD, and posttreatment oxytocin levels were measured. RESULTS: Hypersexual men (n = 64) exhibited significantly higher oxytocin plasma levels (mean ±â€…SD: 31.0 ±â€…9.9 pM) compared with healthy volunteers (16.9 ±â€…3.9 pM; P < 0.001). There were significant positive correlations between oxytocin levels and the rating scales measuring hypersexual behavior. Patients who completed CBT treatment (n = 30) had a significant reduction of oxytocin plasma levels from pretreatment (30.5 ±â€…10.1 pM) to posttreatment (20.2 ±â€…8.0 pM; P < 0.001). CONCLUSIONS: The results suggest that the hyperactive oxytocinergic system in hypersexual men may be a compensatory mechanism to attenuate hyperactive stress.

Mental Health and Adherence to COVID-19 Protective Behaviors among Cancer Patients during the COVID-19 Pandemic: An International, Multinational Cross-Sectional Study.

A population-based cross-sectional study was conducted during the first COVID-19 wave, to examine the impact of COVID-19 on mental health using an anonymous online survey, enrolling 9565 individuals in 78 countries. The current sub-study examined the impact of the pandemic and the associated lockdown measures on the mental health, and protective behaviors of cancer patients in comparison to non-cancer participants. Furthermore, 264 participants from 30 different countries reported being cancer patients. The median age was 51.5 years, 79.9% were female, and 28% had breast cancer. Cancer participants reported higher self-efficacy to follow recommended national guidelines regarding COVID-19 protective behaviors compared to non-cancer participants (p < 0.01). They were less stressed (p < 0.01), more psychologically flexible (p < 0.01), and had higher levels of positive affect compared to non-cancer participants. Amongst cancer participants, the majority (80.3%) reported COVID-19, not their cancer, as their priority during the first wave of the pandemic and females reported higher levels of stress compared to males. In conclusion, cancer participants appeared to have handled the unpredictable nature of the first wave of the pandemic efficiently, with a positive attitude towards an unknown and otherwise frightening situation. Larger, cancer population specific and longitudinal studies are warranted to ensure adequate medical and psychological care for cancer patients.

Prescription patterns in psychiatric compulsory care: polypharmacy and high-dose antipsychotics.

BACKGROUND: Antipsychotic polypharmacy and prescription of high-dose antipsychotics are often used for the treatment of psychotic symptoms, especially in compulsory psychiatric care although there is lack of evidence to support this practice and related risks for patients. AIMS: We aimed to investigate prescription patterns in patients with psychosis under compulsory psychiatric treatment in Cyprus and to identify predictors for pharmaceutic treatment patterns. METHOD: This was a nationwide, descriptive correlational study with cross-sectional comparisons, including 482 patients with compulsory admission to hospital. Sociodemographic and clinical data were collected. Psychotic symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS). Prescribed medication patterns, including use of medication pro re nata (PRN, when required), were recorded. RESULTS: Antipsychotic polypharmacy with a PRN schema was reported in 33.2% (n = 160) of the participants. Polypharmacy without a PRN schema was reported in 5.6% (n = 27) of the participants. We found that 27.2% (n = 131) of the participants were prescribed high-dose antipsychotics without PRN included; and 39.2% (n = 189) prescribed high-dose antipsychotics with PRN included. In the logistic regression analyses, predictors for prescription of high-dose antipsychotics were male gender, positive psychiatric history, receiving state benefits and a negative history of substance use. Male gender was the only predictor for polypharmacy without a PRN schema whereas male gender, negative family psychiatric history, receiving state benefits and the total score on the positive symptoms PANSS subscale were predictors for polypharmacy with a PRN schema included. CONCLUSIONS: A high frequency of polypharmacy and use of medication PRN beyond clinical guidelines has been reported for the first time in psychiatric compulsory care in Cyprus; revision in antipsychotic prescription is needed.

The Role of Perceived Organizational Support in Mental Health of Healthcare Workers During the COVID-19 Pandemic: A Cross-Sectional Study.

Background: Data support the link between the coronavirus disease 2019 (COVID-19) pandemic and mental distress in healthcare workers (HCWs). Although previous studies have documented the association between organizational policies and employees' psychological and mental status, there is still scant evidence regarding the effect of perceived organizational support (POS) on mental distress in HCWs during the pandemic. Aims: The present study aimed to assess the association between POS and mental distress in HCWs during the COVID-19 pandemic. The role of POS in stress, depressive and trauma symptoms in HCWs was investigated. Methods: This was an online cross-sectional study in 424 HCWs. Data were collected during the first wave of the pandemic, and included demographics, a 7-item questionnaire assessing POS, the "Patient Health Questionnaire" assessing depressive symptoms, the "Impact of Events Scale Revised," measuring post-traumatic stress disorder (PTSD) symptoms and the "Perceived Stress Scale" assessing perceived stress. Results: The mean POS score was 3.33 [standard deviation:1.85; range 0-7]. Younger (p < 0.001), less experienced (p < 0.001), female (p = 0.002), and non-physician HCWs (p = 0.031) were more likely to report lower self-perceived organizational support than older, male, more experienced physicians. Self-perceived organizational support was significantly and negatively associated with and self-assessed intensity of stress, depressive and traumatic symptoms, after adjusting for putative confounders (p < 0.001). Discussion: Self-perceived organizational support was significantly associated with HCWs' self-assessed mental status during the pandemic. Organizational support and mental distress should be addressed simultaneously in HCWs during the COVID-19 pandemic to increase resilience among them.

HPA axis dysregulation is associated with differential methylation of CpG-sites in related genes.

DNA methylation shifts in Hypothalamic-pituitary-adrenal (HPA) axis related genes is reported in psychiatric disorders including hypersexual disorder. This study, comprising 20 dexamethasone suppression test (DST) non-suppressors and 73 controls, examined the association between the HPA axis dysregulation, shifts in DNA methylation of HPA axis related genes and importantly, gene expression. Individuals with cortisol level ≥ 138 nmol/l, after the low dose (0.5 mg) dexamethasone suppression test (DST) were classified as non-suppressors. Genome-wide methylation pattern, measured in whole blood using the EPIC BeadChip, investigated CpG sites located within 2000 bp of the transcriptional start site of key HPA axis genes, i.e.: CRH, CRHBP, CRHR-1, CRHR-2, FKBP5 and NR3C1. Regression models including DNA methylation M-values and the binary outcome (DST non-suppression status) were performed. Gene transcripts with an abundance of differentially methylated CpG sites were identified with binomial tests. Pearson correlations and robust linear regressions were performed between CpG methylation and gene expression in two independent cohorts. Six of 76 CpG sites were significantly hypermethylated in DST non-suppressors (nominal P < 0.05), associated with genes CRH, CRHR1, CRHR2, FKBP5 and NR3C1. NR3C1 transcript AJ877169 showed statistically significant abundance of probes differentially methylated by DST non-suppression status and correlated with DST cortisol levels. Further, methylation levels of cg07733851 and cg27122725 were positively correlated with gene expression levels of the NR3C1 gene. Methylation levels of cg08636224 (FKBP5) correlated with baseline cortisol and gene expression. Our findings revealed that DNA methylation shifts are involved in the altered mechanism of the HPA axis suggesting that new epigenetic targets should be considered behind psychiatric disorders.

Combined Use of Web-Based and In-Person Education on Ill Health Self-management Skills in Adults With Bipolar Disorder: Protocol for a Mixed Methods Study.

BACKGROUND: Addressing the enhancement of ill health self-management skills in adults diagnosed with bipolar disorder may be considered an important intervention for health care systems worldwide. OBJECTIVE: This protocol describes the study "Management of my Bipolarity" (MoB), which aims to develop an educational intervention for adults with bipolar disorder and assess its effectiveness. The objectives include (a) a literature review on bipolar disorder educational interventions; (b) a qualitative exploration of the educational needs of people with bipolar disorder; (c) development of an educational intervention based on objectives (a) and (b) (ie, the MoB educational intervention); and (d) exploration of the effectiveness of the intervention regarding participants' knowledge of their mental health condition and enhancement of their ill health self-management skills. The MoB educational intervention will consist of an in-person and a web-based intervention in the form of a digital platform. METHODS: The proposed interventional study is a combination of a qualitative and a quantitative design (mixed methods study). A focus group and content analysis will be implemented for the qualitative assessment of the educational needs of adults with bipolar disorder. The intervention will be developed based on the qualitative data of the study and relevant literature. The effectiveness of the acquired knowledge and self-management skills will be assessed according to (a) substance use behavior, (b) health locus of control, (c) impulse control, (d) adherence to pharmacotherapy, (e) relapse prevention, (f) improvement of quality of life, and (g) bipolar disorder knowledge level via structured instruments in the quantitative part of the study using descriptive and inferential statistics (SPSS version 24.0). RESULTS: A total of 13 patients with bipolar disorder have been interviewed (8 women, 5 men) to identify educational needs to be covered through the intervention. Moreover, a literature review on bipolar disorder educational interventions has been completed. These data have been incorporated in the design of the MoB in-person intervention and the digital platform. The digital platform is live, and the development of the MoB in-person intervention was completed at the end of 2020. The recruitment of the participants for the intervention (40 patients) and the control group (40 patients) began during the first semester of 2021. Moreover, by tracking the platform for 1.5 years, we have recorded that 2180 users have visited the platform with an average session duration of almost 2 minutes. Mobile and tablet devices are being used by 70% of the visitors. CONCLUSIONS: Since new parameters regarding educational interventions will be explored, these findings are expected to provide evidence that participation in structured educational interventions offers patients the opportunity to improve adherence to pharmacotherapy and increase their quality of life. TRIAL REGISTRATION: ClinicalTrials.gov NCT04643210; https://clinicaltrials.gov/ct2/show/NCT04643210. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/25168.

Correction: Combined Use of Web-Based and In-Person Education on Ill Health Self-management Skills in Adults With Bipolar Disorder: Protocol for a Mixed Methods Study.

[This corrects the article DOI: 10.2196/25168.].

Depressive symptoms in involuntary hospitalized patients in Cyprus: Socio-demographic and psychopathological characteristics.

Τhe severity and variation of depressive symptoms (DS), among psychotic individuals under involuntary hospitalization is unclear. We investigated the socio-demographic and clinical characteristics of psychotic adults with DS involuntarily hospitalized for compulsory treatment in Cyprus. We also evaluated the psychometric properties (internal consistency, known-group and discriminant validity) of the HDRS-17 and HAM-A for the assessment of depressive and anxiety symptoms, respectively. A descriptive correlational study with cross-sectional comparisons was applied. Data on demographics, cognitive functioning (MoCA scale), depressive (HDRS-17 scale), anxiety (HAM-A scale) and psychotic (PANSS scale) symptoms were collected (December 2016 -February 2018). Following informed consent, the sample included 406 patients. Among them, 21 males and 23 females reported DS (HDRS-17 total score ≥8). The latter were mainly Greek-Cypriots (61.4%), 45-65 years old (38.6%), single (77.3%), unemployed (72.7%), mainly admitted due to aggressiveness towards others (47.7%), most frequently diagnosed with a bipolar disorder (59.1%). The mean score (M) in the HDRS-17 was 30.72 (scale range: 8-50; Standard Deviation [SD]: 10.42). The highest mean score (M) per item was in the variables "Suicide behavior"'(M:3.09; SD:1.09) and "Depressive mood" (M=2.95; SD=1.07). The DS group (HDRS-17 score≥8) reported higher PANSS positive symptoms subscale score (t-test, p=0.003) and HAM-A total score (t-test, p=0.05) compared to the non-DS group (HDRS-17 score<8). In multivariable logistic regression analysis only female sex [OR (95%CI) = 3.28 (1.33.-8.04), p=0.01)] and a mood disorder diagnosis [OR95% CI: 15.22(4.13.-56.14), p<0.0001)] retained a statistically significant association with DS. Cronbach' s alpha was 0.827 for the HDRS, and 0.763 for the HAM-A. The present findings partially support the known-group validity of the HDRS-17 and the ΗΑΜ-Α, and the discriminant validity of the HDRS-17 in psychotic patients under involuntary hospitalization. Additionally, the most frequent diagnosis in the DS group was a bipolar disorder, and the most frequent admission cause was aggressiveness towards others; it is possible that the majority of the DS group participants were patients with a bipolar disorder in episodes with mixed features, presenting simultaneously depressive symptoms and aggressiveness. Further studies on relapse prevention regarding this clinical group are proposed, as well as studies on specificity and sensitivity of the HDRS-17 and HAM-A.

Impact of the COVID-19 Pandemic on the Mental Health of Healthcare Workers.

The coronavirus disease 2019 (COVID-19) has a great impact on healthcare workers (HCWs) that includes negative mental health outcomes, such as post-traumatic stress, anxiety and depressive symptoms. In this cross-sectional study, we report on mental health outcomes among HCWs in Cyprus. Data were collected between 3 May and 27 May 2020, with the use of an online questionnaire that included demographics (sex, age, occupation, education, work sector, years of work experience), the 9-item Patient Health Questionnaire (PHQ-9) which assesses depressive symptoms, the Impact of Events Scale Revised (IES-R), which measures post-traumatic stress disorder (PTSD) symptoms, and the-10 item Perceived Stress Scale (PSS-10) which quantifies stress responses. Participants (42% physicians, 24% nurses, 18% physiotherapists, 16% classified as "other") were 58% of female gender and aged 21-76. A total of 79 (18.6%) and 62 HCWs (14.6%) reported clinically significant depressive (PHQ-9 ≥ 10) and post-traumatic stress (IES-R > 33) symptoms respectively. Nurses were more likely than physicians to suffer from depression (adjusted prevalence ratio 1.7 (1.06-2.73); p = 0.035) and PTSD (adjusted prevalence ratio 2.51 (1.49-4.23); p = 0.001). Even in a country with a rather low spread of the COVID-19, such as Cyprus, HCWs reported a substantial mental health burden, with nurses reporting increased depressive and PTSD symptoms compared to other HCWs.