Green Light-Triggered Photocatalytic Anticancer Activity of Terpyridine-Based Ru(II) Photocatalysts.

The relentless increase in drug resistance of platinum-based chemotherapeutics has opened the scope for other new cancer therapies with novel mechanisms of action (MoA). Recently, photocatalytic cancer therapy, an intrusive catalytic treatment, is receiving significant interest due to its multitargeting cell death mechanism with high selectivity. Here, we report the synthesis and characterization of three photoresponsive Ru(II) complexes, viz., [Ru(ph-tpy)(bpy)Cl]PF6 (Ru1), [Ru(ph-tpy)(phen)Cl]PF6 (Ru2), and [Ru(ph-tpy)(aip)Cl]PF6 (Ru3), where, ph-tpy = 4'-phenyl-2,2':6',2″-terpyridine, bpy = 2,2'-bipyridine, phen = 1,10-phenanthroline, and aip = 2-(anthracen-9-yl)-1H-imidazo[4,5-f][1,10] phenanthroline, showing photocatalytic anticancer activity. The X-ray crystal structures of Ru1 and Ru2 revealed a distorted octahedral geometry with a RuN5Cl core. The complexes showed an intense absorption band in the 440-600 nm range corresponding to the metal-to-ligand charge transfer (MLCT) that was further used to achieve the green light-induced photocatalytic anticancer effect. The mitochondria-targeting photostable complex Ru3 induced phototoxicity with IC50 and PI values of ca. 0.7 µM and 88, respectively, under white light irradiation and ca. 1.9 µM and 35 under green light irradiation against HeLa cells. The complexes (Ru1-Ru3) showed negligible dark cytotoxicity toward normal splenocytes (IC50s > 50 µM). The cell death mechanistic study revealed that Ru3 induced ROS-mediated apoptosis in HeLa cells via mitochondrial depolarization under white or green light exposure. Interestingly, Ru3 also acted as a highly potent catalyst for NADH photo-oxidation under green light. This NADH photo-oxidation process also contributed to the photocytotoxicity of the complexes. Overall, Ru3 presented multitargeting synergistic type I and type II photochemotherapeutic effects.

Highly Stable Self-Regenerating Organic Multi-Redox Systems derived from Bicyclic (Alkyl)(amino)carbenes (BICAACs).

An extended class of organic multi-redox systems was derived from bicyclic(alkyl)amino carbenes (BICAACs). The highly-conjugated system undergoes a total of 4 redox events spanning a 1.8 V redox range. These organic compounds exhibited four different stable redox states (dication, radical cation, neutral and radical anion), and all of them were characterized either by single crystal X-ray study and/or various spectroscopic studies. Three of the four redox states are stable to air and moisture. The availability of stable multiple redox states demonstrated promise towards their efficacy in the symmetric H-cell charge/discharge cycling. Among various redox states, the dication/neutral state works efficiently and continuously for 1500 cycles in 2e- charge/discharge process outside glovebox in commercially available DMF with minimum capacity loss (retaining nearly 90 % Coulombic efficiency). Surprisingly, the efficiency of the redox cycle was retained even if the system was exposed to air for 30 days when it slowly regenerated to the initial deep blue radical cation, and it exhibited another 100 charge/discharge cycles with a minimal capacity loss. Such a stable H-cell cycling ability is not well known among organic molecule-based systems.

Cat Ownership and Schizophrenia-Related Disorders and Psychotic-Like Experiences: A Systematic Review and Meta-Analysis.

BACKGROUND: It has been proposed that cat ownership may be a risk-modifying factor for schizophrenia-related disorders and psychotic-like experiences (PLE). This study aimed to systematically review and meta-analyze publications that reported the relationship between cat ownership and schizophrenia-related outcomes. METHODOLOGY: We searched Medline, Embase, CINAHL, Web of Science, and gray literature for publications between January 1, 1980, and May 30, 2023, regardless of geographical location and language. Backward citation search methods were used to locate additional articles. We included studies that reported original data on cat ownership and schizophrenia-related outcomes. We meta-analyzed estimates based on broad definitions (cat ownership, cat bites, and cat contact) with estimates with or without covariate adjustments. We pooled comparable estimates using random-effects models and assessed the risk of bias, heterogeneity, and study quality. RESULTS: We identified 1915 studies, of which 106 were chosen for full-text review, ultimately resulting in the inclusion of 17 studies. We found an association between broadly defined cat ownership and increased odds of developing schizophrenia-related disorders. The unadjusted pooled odds ratio (OR) was 2.35 (95% CI: 1.38-4.01), while the adjusted pooled estimate was 2.24 (95% CI: 1.61-3.12). We were unable to aggregate the estimates for the PLE outcomes because of the broad range of measures. CONCLUSIONS: Our findings support an association between cat exposure and an increased risk of broadly defined schizophrenia-related disorders; however, the findings related to PLE as an outcome are mixed. There is a need for more high-quality studies in this field. PROSPERO REGISTRATION: PROSPERO 2023 CRD42023426974. Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023426974.

Polypyridyl-based Co(III) complexes of vitamin B6 Schiff base for photoactivated antibacterial therapy.

Herein, five novel polypyridyl-based Co(III) complexes of Schiff bases, viz., [Co(dpa)(L1)]Cl (1), [Co(dpa)(L2)]Cl (2), [Co(L3)(L2)]Cl (3), [Co(L3)(L1)]Cl (4), and [Co(L4)(L1)]Cl (5), where dpa (dipicolylamine) = bis(2-pyridylmethyl)amine; H2L1 = (E)-2-((2-hydroxybenzylidene)amino)phenol; H2L2 = (E)-5-(hydroxymethyl)-4-(((2-hydroxyphenyl)imino)methyl)-2-methylpyridin-3-ol; L3 = 4'-phenyl-2,2':6',2''-terpyridine (ph-tpy); and L4 = 4'-ferrocenyl-2,2':6',2''-terpyridine (Fc-tpy), were synthesized and characterized. Complexes 1, 3, and 4 were structurally characterized by single-crystal XRD, indicating an octahedral CoIIIN4O2 coordination core. The absorption bands of these complexes were observed in the visible range with a λmax at ∼430-485 nm. Complex 5 displayed an extra absorption band near 545 nm because of a ferrocene moiety. These absorptions in the visible region reflect the potential of the complexes to act as visible-light antimicrobial photodynamic therapy (aPDT) agents. All of these complexes showed reactive oxygen species (ROS)-mediated antibacterial effects against S. aureus (Gram-positive) and E. coli (Gram-negative bacteria) upon low-energy visible light (0.5 J cm-2, 400-700 nm) exposure. Additionally, 1-5 did not show any toxicity toward A549 (Human Lung adenocarcinoma) cells, reflecting their selective bacteria-killing abilities.

Density Functional Theory-Guided Photo-Triggered Anticancer Activity of Curcumin-Based Zinc(II) Complexes.

Photodynamic therapy (PDT) has evolved as a new therapeutic modality for cancer treatment with fewer side effects and drug resistance. Curcumin exhibits PDT activity, but its low bioavailability restricts its clinical application. Here, the bioavailability of curcumin was increased by its complex formation with the Zn(II) center. For a structure-activity relationship study, Zn(II)-based complexes (1-3) comprising N^N-based ligands (2,2'-bipyridine in 1 and 2 or 1,10-phenanthroline in 3) and O^O-based ligands (acetylacetone in 1, monoanionic curcumin in 2 and 3) were synthesized and thoroughly characterized. The X-ray structure of the control complex, 1, indicated a square pyramidal shape of the molecules. Photophysical and TD-DFT studies indicated the potential of 2 and 3 as good visible light type-II photosensitizers for PDT. Guided by the TD-DFT studies, the low-energy visible light-triggered singlet oxygen (1O2) generation efficacy of 2 and 3 was explored in solution and in cancer cells. As predicted by the TD-DFT calculations, these complexes produced 1O2 efficiently in the cytosol of MCF-7 cancer cells and ultimately displayed excellent apoptotic anticancer activity in the presence of light. Moreover, the molecular docking investigation showed that complexes 2 and 3 have very good binding affinities with caspase-9 and p-53 proteins and could activate them for cellular apoptosis. Further molecular dynamics simulations confirmed the stability of 3 in the caspase-9 protein binding site.

PHASTEST: faster than PHASTER, better than PHAST.

PHASTEST (PHAge Search Tool with Enhanced Sequence Translation) is the successor to the PHAST and PHASTER prophage finding web servers. PHASTEST is designed to support the rapid identification, annotation and visualization of prophage sequences within bacterial genomes and plasmids. PHASTEST also supports rapid annotation and interactive visualization of all other genes (protein coding regions, tRNA/tmRNA/rRNA sequences) in bacterial genomes. Given that bacterial genome sequencing has become so routine, the need for fast tools to comprehensively annotate bacterial genomes has become progressively more important. PHASTEST not only offers faster and more accurate prophage annotations than its predecessors, it also provides more complete whole genome annotations and much improved genome visualization capabilities. In standardized tests, we found that PHASTEST is 31% faster and 2-3% more accurate in prophage identification than PHASTER. Specifically, PHASTEST can process a typical bacterial genome in 3.2 min (raw sequence) or in 1.3 min when given a pre-annotated GenBank file. Improvements in PHASTEST's ability to annotate bacterial genomes now make it a particularly powerful tool for whole genome annotation. In addition, PHASTEST now offers a much more modern and responsive visualization interface that allows users to generate, edit, annotate and interactively visualize (via zooming, rotating, dragging, panning, resetting), colourful, publication quality genome maps. PHASTEST continues to offer popular options such as an API for programmatic queries, a Docker image for local installations, support for multiple (metagenomic) queries and the ability to perform automated look-ups against thousands of previously PHAST-annotated bacterial genomes. PHASTEST is available online at https://phastest.ca.

PlasMapper 3.0-a web server for generating, editing, annotating and visualizing publication quality plasmid maps.

PlasMapper 3.0 is a web server that allows users to generate, edit, annotate and interactively visualize publication quality plasmid maps. Plasmid maps are used to plan, design, share and publish critical information about gene cloning experiments. PlasMapper 3.0 is the successor to PlasMapper 2.0 and offers many features found only in commercial plasmid mapping/editing packages. PlasMapper 3.0 allows users to paste or upload plasmid sequences as input or to upload existing plasmid maps from its large database of >2000 pre-annotated plasmids (PlasMapDB). This database can be searched by plasmid names, sequence features, restriction sites, preferred host organisms, and sequence length. PlasMapper 3.0 also supports the annotation of new or never-before-seen plasmids using its own feature database that contains common promoters, terminators, regulatory sequences, replication origins, selectable markers and other features found in most cloning plasmids. PlasMapper 3.0 has several interactive sequence editors/viewers that allow users to select and view plasmid regions, insert genes, modify restriction sites or perform codon optimization. The graphics for PlasMapper 3.0 have also been substantially upgraded. It now offers an interactive, full-color plasmid viewer/editor that allows users to zoom, rotate, re-color, linearize, circularize, edit annotated features and modify plasmid images or labels to improve the esthetic qualities of their plasmid map and textual displays. All the plasmid images and textual displays are downloadable in multiple formats. PlasMapper 3.0 is available online at https://plasmapper.ca.

MiMeDB: the Human Microbial Metabolome Database.

The Human Microbial Metabolome Database (MiMeDB) (https://mimedb.org) is a comprehensive, multi-omic, microbiome resource that connects: (i) microbes to microbial genomes; (ii) microbial genomes to microbial metabolites; (iii) microbial metabolites to the human exposome and (iv) all of these 'omes' to human health. MiMeDB was established to consolidate the growing body of data connecting the human microbiome and the chemicals it produces to both health and disease. MiMeDB contains detailed taxonomic, microbiological and body-site location data on most known human microbes (bacteria and fungi). This microbial data is linked to extensive genomic and proteomic sequence data that is closely coupled to colourful interactive chromosomal maps. The database also houses detailed information about all the known metabolites generated by these microbes, their structural, chemical and spectral properties, the reactions and enzymes responsible for these metabolites and the primary exposome sources (food, drug, cosmetic, pollutant, etc.) that ultimately lead to the observed microbial metabolites in humans. Additional, extensively referenced data about the known or presumptive health effects, measured biosample concentrations and human protein targets for these compounds is provided. All of this information is housed in richly annotated, highly interactive, visually pleasing database that has been designed to be easy to search, easy to browse and easy to navigate. Currently MiMeDB contains data on 626 health effects or bioactivities, 1904 microbes, 3112 references, 22 054 reactions, 24 254 metabolites or exposure chemicals, 648 861 MS and NMR spectra, 6.4 million genes and 7.6 billion DNA bases. We believe that MiMeDB represents the kind of integrated, multi-omic or systems biology database that is needed to enable comprehensive multi-omic integration.

Comorbidity between mood and substance-related disorders: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: Evidence indicates that mood disorders often co-occur with substance-related disorders. However, pooling comorbidity estimates can be challenging due to heterogeneity in diagnostic criteria and in the overall study design. The aim of this study was to systematically review and, where appropriate, meta-analyse estimates related to the pairwise comorbidity between mood disorders and substance-related disorders, after sorting these estimates by various study designs. METHODS: We searched PubMed (MEDLINE), Embase, CINAHL and Web of Science for publications between 1980 and 2017 regardless of geographical location and language. We meta-analysed estimates from original articles in 4 broadly defined mood and 35 substance-related disorders. RESULTS: After multiple eligibility steps, we included 120 studies for quantitative analysis. In general, regardless of variations in diagnosis type, temporal order or use of adjustments, there was substantial comorbidity between mood and substance-related disorders. We found a sixfold elevated risk between broadly defined mood disorder and drug dependence (odds ratio = 5.7) and fivefold risk between depression and cannabis dependence (odds ratio = 4.9) while the highest pooled estimate, based on period prevalence risk, was found between broadly defined dysthymic disorder and drug dependence (odds ratio = 11.3). Based on 56 separate meta-analyses, all pooled odds ratios were above 1, and 46 were significantly greater than 1 (i.e. the 95% confidence intervals did not include 1). CONCLUSION: This review found robust and consistent evidence of an increased risk of comorbidity between many combinations of mood and substance-related disorders. We also identified a number of under-researched mood and substance-related disorders, suitable for future scrutiny. This review reinforces the need for clinicians to remain vigilant in order to promptly identify and treat these common types of comorbidity.

Co-morbidity between mood and anxiety disorders: A systematic review and meta-analysis.

There is consistent evidence that mood disorders often co-occur with anxiety disorders, however, the strength of the association of these two broad groups of disorders has been challenging to summarize across different studies. The aim was to conduct a meta-analysis of publications reporting on the pairwise comorbidity between mood and anxiety disorders after sorting into comparable study types. We searched MEDLINE, Embase, CINAHL, Web of Science, and the grey literature for publications between 1980 and 2017 regardless of geographical locations and languages. We meta-analyzed estimates from original articles after sorting by: (a) broad or narrow diagnostic criteria, (b) study time-frame, and (c) estimates with or without covariate adjustments. Over 43 000 unique studies were identified through electronic searches, of which 391 were selected for full-text review. Finally, 171 studies were eligible for inclusion, including 53 articles from additional snowball searching. In general, regardless of variations in diagnosis type, study time-frame, temporal order, or use of adjustments, there was substantial comorbidity between mood and anxiety disorders. Based on the entire 90 separate meta-analyses, the median OR was 6.1 (range 1.5-18.7). Of these estimates, all 90 were above 1, and 87 were significantly greater than 1 (i.e., the 95% confidence intervals did not include 1). Fourteen of the 90 pooled estimates had ORs that were greater than 10. This systematic review found robust and consistent evidence of comorbidity between broadly defined mood and anxiety disorders. Clinicians should be vigilant for the prompt identification and treatment of this common type of comorbidity.

Effect of Sodium Benzoate vs Placebo Among Individuals With Early Psychosis: A Randomized Clinical Trial.

Importance: There is evidence that sodium benzoate (BZ) may be an effective adjunctive treatment for schizophrenia. The clinical efficacy of BZ has been investigated in chronic schizophrenia; however, the efficacy of this agent has not been studied in individuals with early psychosis. Objective: To examine the clinical efficacy of the adjunctive use of BZ for symptoms in people with early psychosis. Design, Setting, and Participants: Using a placebo-controlled double-masked parallel-group design, this randomized clinical trial was conducted from August 2015 to July 2018. Participants aged between 15 and 45 years experiencing early psychosis were enrolled from 5 major clinical sites in Queensland, Australia. Data analysis was conducted from October 2018 to February 2020. Interventions: Participants were randomized 1:1 (50 participants in each group) to receive 500 mg of sodium benzoate twice daily or placebo for 12 weeks. Main Outcomes and Measures: The primary efficacy outcome was the Positive and Negative Syndrome Scale (PANSS) total score at 12 weeks. The key secondary efficacy measures were (1) the Clinical Global Impression score, (2) the Hamilton Depression Rating Scale for depression, (3) functioning as assessed by the clinician-rated Global Assessment of Function, and (4) the Assessment of Quality of Life Scale. The PANSS subscale scores and impact on selected amino acid concentrations were also assessed. Results: The study comprised 100 participants with a mean (SD) age of 21.4 (4.1) years, of whom 73 (73%) were male individuals. The mean (SD) baseline PANSS score was 75.3 (15.4). We found no improvement in total PANSS score in the BZ group compared with the placebo group. The end result of least-squares mean difference (SE) for total PANSS was -1.2 (2.4) (P = .63). There were no differences in any subscales of the PANSS, any secondary measures, nor any amino acid concentrations. The dose of BZ was well tolerated without any clinically significant treatment-emergent adverse event differences between BZ and placebo groups. Conclusions and Relevance: In this randomized clinical trial, there was no evidence that adjunctive use of 500 mg of BZ twice daily is an effective treatment for individuals with early psychosis. Trial Registration: anzctr.org.au Identifier: ACTRN12615000187549.

Association between Mental Disorders and Subsequent Medical Conditions.

BACKGROUND: Persons with mental disorders are at a higher risk than the general population for the subsequent development of certain medical conditions. METHODS: We used a population-based cohort from Danish national registries that included data on more than 5.9 million persons born in Denmark from 1900 through 2015 and followed them from 2000 through 2016, for a total of 83.9 million person-years. We assessed 10 broad types of mental disorders and 9 broad categories of medical conditions (which encompassed 31 specific conditions). We used Cox regression models to calculate overall hazard ratios and time-dependent hazard ratios for pairs of mental disorders and medical conditions, after adjustment for age, sex, calendar time, and previous mental disorders. Absolute risks were estimated with the use of competing-risks survival analyses. RESULTS: A total of 698,874 of 5,940,299 persons (11.8%) were identified as having a mental disorder. The median age of the total population was 32.1 years at entry into the cohort and 48.7 years at the time of the last follow-up. Persons with a mental disorder had a higher risk than those without such disorders with respect to 76 of 90 pairs of mental disorders and medical conditions. The median hazard ratio for an association between a mental disorder and a medical condition was 1.37. The lowest hazard ratio was 0.82 for organic mental disorders and the broad category of cancer (95% confidence interval [CI], 0.80 to 0.84), and the highest was 3.62 for eating disorders and urogenital conditions (95% CI, 3.11 to 4.22). Several specific pairs showed a reduced risk (e.g., schizophrenia and musculoskeletal conditions). Risks varied according to the time since the diagnosis of a mental disorder. The absolute risk of a medical condition within 15 years after a mental disorder was diagnosed varied from 0.6% for a urogenital condition among persons with a developmental disorder to 54.1% for a circulatory disorder among those with an organic mental disorder. CONCLUSIONS: Most mental disorders were associated with an increased risk of a subsequent medical condition; hazard ratios ranged from 0.82 to 3.62 and varied according to the time since the diagnosis of the mental disorder. (Funded by the Danish National Research Foundation and others; COMO-GMC ClinicalTrials.gov number, NCT03847753.).

Protocol update and statistical analysis plan for CADENCE-BZ: a randomized clinical trial to assess the efficacy of sodium benzoate as an adjunctive treatment in early psychosis.

BACKGROUND: CADENCE-BZ is a multi-centre, parallel-group, double-blind randomized controlled trial designed to examine the clinical efficacy and safety of an accessible food preservative, sodium benzoate, as an add-on treatment for patients with early psychosis. The original study protocol was published in 2017. Here, we describe the updated protocol along with the Statistical Analysis Plan (SAP) for the CADENCE-BZ trial prior to study completion. METHODS AND MATERIALS: Two important changes were made to the original protocol: (1) improvements to our statistical analysis plan permitted a reduction in sample size; and (2) a revision in the secondary outcomes with the intent of reducing redundancy and excluding those measures that were not appropriate as outcomes. CONCLUSIONS: We provide the updated SAP prior to the completion of the study with the intent of increasing the transparency of the data analyses for CADENCE-BZ. The final participants are currently completing the study and the results will be published in the near future. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ( ACTRN12615000187549 ). Registered on 26th February 2015.

Exploring Comorbidity Within Mental Disorders Among a Danish National Population.

Importance: Individuals with mental disorders often develop comorbidity over time. Past studies of comorbidity have often restricted analyses to a subset of disorders and few studies have provided absolute risks of later comorbidity. Objectives: To undertake a comprehensive study of comorbidity within mental disorders, by providing temporally ordered age- and sex-specific pairwise estimates between the major groups of mental disorders, and to develop an interactive website to visualize all results and guide future research and clinical practice. Design, Setting, and Participants: This population-based cohort study included all individuals born in Denmark between January 1, 1900, and December 31, 2015, and living in the country between January 1, 2000, and December 31, 2016. The analyses were conducted between June 2017 and May 2018. Main Outcomes and Measures: Danish health registers were used to identify mental disorders, which were examined within the broad 10-level International Statistical Classification of Diseases and Related Health Problems, 10th Revision, subchapter groups (eg, codes F00-F09 and F10-F19). For each temporally ordered pair of disorders, overall and lagged hazard ratios and 95% CIs were calculated using Cox proportional hazards regression models. Absolute risks were estimated using competing risks survival analyses. Estimates for each sex were generated. Results: A total of 5 940 778 persons were included in this study (2 958 293 men and 2 982 485 women; mean [SD] age at beginning of follow-up, 32.1 [25.4] years). They were followed up for 83.9 million person-years. All mental disorders were associated with an increased risk of all other mental disorders when adjusting for sex, age, and calendar time (hazard ratios ranging from 2.0 [95% CI, 1.7-2.4] for prior intellectual disabilities and later eating disorders to 48.6 [95% CI, 46.6-50.7] for prior developmental disorders and later intellectual disabilities). The hazard ratios were temporally patterned, with higher estimates during the first year after the onset of the first disorder, but with persistently elevated rates during the entire observation period. Some disorders were associated with substantial absolute risks of developing specific later disorders (eg, 30.6% [95% CI, 29.3%-32.0%] of men and 38.4% [95% CI, 37.5%-39.4%] of women with a diagnosis of mood disorders before age 20 years developed neurotic disorders within the following 5 years). Conclusions and Relevance: Comorbidity within mental disorders is pervasive, and the risk persists over time. This study provides disorder-, sex-, and age-specific relative and absolute risks of the comorbidity of mental disorders. Web-based interactive data visualization tools are provided for clinical utility.

Yoga as a Therapeutic Intervention for the Management of Type 2 Diabetes Mellitus.

PURPOSE: This study aimed to investigate the effects of 12 weeks yogic intervention on blood sugar and lipid profile in elder women with Type 2 diabetes mellitus (T2DM). SUBJECTS AND METHODS: Twenty elderly (age range 55-70 years) T2DM women were divided into two groups, namely, yogic intervention group (YIG: n = 10, age 64.70 ± 4.03, body mass index [BMI] 24.26 ± 3.40) and control group (CG: n = 10, age 64.40 ± 4.79, BMI 24.28 ± 2.36). YIG underwent yoga practice (Asanas, Kriyas, Pranayamas) for 12 weeks (3 sessions/week), while the CG continued their usual routine activities. Standing height, body weight, BMI, blood sugar, and lipid profile were measured before commencement and after 6 and 12 weeks of yogic intervention in both groups. RESULTS: There was a significant (P < 0.01) decrease in fasting plasma glucose, postprandial blood sugar, total cholesterol, triglycerides, low-density lipoprotein, and very low density lipoprotein, with a significant (P < 0.01) increase in high-density lipoprotein level from its initial value in YIG, while showing insignificant result in CG. CONCLUSION: It can be said that yogic intervention may have the beneficial effects on blood sugar and lipid profile in elderly women with T2DM.

The association between psychotic experiences and health-related quality of life: a cross-national analysis based on World Mental Health Surveys.

Psychotic experiences (PEs) are associated with a range of mental and physical disorders, and disability, but little is known about the association between PEs and aspects of health-related quality of life (HRQoL). We aimed to investigate the association between PEs and five HRQoL indicators with various adjustments. Using data from the WHO World Mental Health surveys (n = 33,370 adult respondents from 19 countries), we assessed for PEs and five HRQoL indicators (self-rated physical or mental health, perceived level of stigma (embarrassment and discrimination), and social network burden). Logistic regression models that adjusted for socio-demographic characteristics, 21 DSM-IV mental disorders, and 14 general medical conditions were used to investigate the associations between the variables of interest. We also investigated dose-response relationships between PE-related metrics (number of types and frequency of episodes) and the HRQoL indicators. Those with a history of PEs had increased odds of poor perceived mental (OR = 1.5, 95% CI = 1.2-1.9) and physical health (OR = 1.3, 95% CI = 1.0-1.7) after adjustment for the presence of any mental or general medical conditions. Higher levels of perceived stigma and social network burden were also associated with PEs in the adjusted models. Dose-response associations between PE type and frequency metrics and subjective physical and mental health were non-significant, except those with more PE types had increased odds of reporting higher discrimination (OR = 2.2, 95% CI = 1.3-3.5). Our findings provide novel insights into how those with PEs perceive their health status.

Psychotic experiences and general medical conditions: a cross-national analysis based on 28 002 respondents from 16 countries in the WHO World Mental Health Surveys.

BACKGROUND: Previous work has identified associations between psychotic experiences (PEs) and general medical conditions (GMCs), but their temporal direction remains unclear as does the extent to which they are independent of comorbid mental disorders. METHODS: In total, 28 002 adults in 16 countries from the WHO World Mental Health (WMH) Surveys were assessed for PEs, GMCs and 21 Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) mental disorders. Discrete-time survival analyses were used to estimate the associations between PEs and GMCs with various adjustments. RESULTS: After adjustment for comorbid mental disorders, temporally prior PEs were significantly associated with subsequent onset of 8/12 GMCs (arthritis, back or neck pain, frequent or severe headache, other chronic pain, heart disease, high blood pressure, diabetes and peptic ulcer) with odds ratios (ORs) ranging from 1.3 [95% confidence interval (CI) 1.1-1.5] to 1.9 (95% CI 1.4-2.4). In contrast, only three GMCs (frequent or severe headache, other chronic pain and asthma) were significantly associated with subsequent onset of PEs after adjustment for comorbid GMCs and mental disorders, with ORs ranging from 1.5 (95% CI 1.2-1.9) to 1.7 (95% CI 1.2-2.4). CONCLUSIONS: PEs were associated with the subsequent onset of a wide range of GMCs, independent of comorbid mental disorders. There were also associations between some medical conditions (particularly those involving chronic pain) and subsequent PEs. Although these findings will need to be confirmed in prospective studies, clinicians should be aware that psychotic symptoms may be risk markers for a wide range of adverse health outcomes. Whether PEs are causal risk factors will require further research.

The associations between psychotic experiences and substance use and substance use disorders: findings from the World Health Organization World Mental Health surveys.

BACKGROUND AND AIMS: Prior research has found bidirectional associations between psychotic experiences (PEs) and selected substance use disorders. We aimed to extend this research by examining the bidirectional association between PEs and various types of substance use (SU) and substance use disorders (SUDs), and the influence of antecedent mental disorders on these associations. DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS: We used data from the World Health Organization World Mental Health surveys. A total of 30 902 adult respondents across 18 countries were assessed for (a) six types of life-time PEs, (b) a range of types of SU and DSM-IV SUDs and (c) mental disorders using the Composite International Diagnostic Interview. Discrete-time survival analyses based on retrospective age-at-onset reports examined the bidirectional associations between PEs and SU/SUDs controlling for antecedent mental disorders. FINDINGS: After adjusting for demographics, comorbid SU/SUDs and antecedent mental disorders, those with prior alcohol use disorders [odds ratio (OR) = 1.6, 95% confidence interval (CI) = 1.2-2.0], extra-medical prescription drug use (OR = 1.5, 95% CI = 1.1-1.9), alcohol use (OR = 1.4, 95% CI = 1.1-1.7) and tobacco use (OR = 1.3, 95% CI = 1.0-1.8) had increased odds of subsequent first onset of PEs. In contrast, those with temporally prior PEs had increased odds of subsequent onset of tobacco use (OR = 1.5, 95% CI = 1.2-1.9), alcohol use (OR = 1.3, 95% CI = 1.1-1.6) or cannabis use (OR = 1.3, 95% CI = 1.0-1.5) as well as of all substance use disorders (ORs ranged between 1.4 and 1.5). There was a dose response relationship between both count and frequency of PEs and increased subsequent odds of selected SU/SUDs. CONCLUSIONS: Associations between psychotic experiences (PEs) and substance use/substance use disorders (SU/SUDs) are often bidirectional, but not all types of SU/SUDs are associated with PEs. These findings suggest that it is important to be aware of the presence of PEs within those with SUDs or at risk of SUDs, given the plausibility that they may each impact upon the other.

Trauma and psychotic experiences: transnational data from the World Mental Health Survey.

BackgroundTraumatic events are associated with increased risk of psychotic experiences, but it is unclear whether this association is explained by mental disorders prior to psychotic experience onset.AimsTo investigate the associations between traumatic events and subsequent psychotic experience onset after adjusting for post-traumatic stress disorder and other mental disorders.MethodWe assessed 29 traumatic event types and psychotic experiences from the World Mental Health surveys and examined the associations of traumatic events with subsequent psychotic experience onset with and without adjustments for mental disorders.ResultsRespondents with any traumatic events had three times the odds of other respondents of subsequently developing psychotic experiences (OR = 3.1, 95% CI 2.7-3.7), with variability in strength of association across traumatic event types. These associations persisted after adjustment for mental disorders.ConclusionsExposure to traumatic events predicts subsequent onset of psychotic experiences even after adjusting for comorbid mental disorders.

Association Between Psychotic Experiences and Subsequent Suicidal Thoughts and Behaviors: A Cross-National Analysis From the World Health Organization World Mental Health Surveys.

Importance: Community-based studies have linked psychotic experiences (PEs) with increased risks of suicidal thoughts and behaviors (STBs). However, it is not known if these associations vary across the life course or if mental disorders contribute to these associations. Objective: To examine the temporal association between PEs and subsequent STBs across the life span as well as the influence of mental disorders (antecedent to the STBs) on these associations. Design, Setting, and Participants: A total of 33 370 adult respondents across 19 countries from the World Health Organization World Mental Health Surveys were assessed for PEs, STBs (ie, ideation, plans, and attempts), and 21 DSM-IV mental disorders. Discrete-time survival analysis was used to investigate the associations of PEs with subsequent onset of STBs. Main Outcomes and Measures: Prevalence and frequency of STBs with PEs, and odds ratios and 95% CIs. Results: Of 33 370 included participants, among those with PEs (n = 2488), the lifetime prevalence (SE) of suicidal ideation, plans, and attempts was 28.5% (1.3), 10.8% (0.7), and 10.2% (0.7), respectively. Respondents with 1 or more PEs had 2-fold increased odds of subsequent STBs after adjusting for antecedent or intervening mental disorders (suicidal ideation: odds ratio, 2.2; 95% CI, 1.8-2.6; suicide plans: odds ratio, 2.1; 95% CI, 1.7-2.6; and suicide attempts: odds ratio, 1.9; 95% CI, 1.5-2.5). There were significant dose-response relationships of number of PE types with subsequent STBs that persisted after adjustment for mental disorders. Although PEs were significant predictors of subsequent STB onset across all life stages, associations were strongest in individuals 12 years and younger. After adjustment for antecedent mental disorders, the overall population attributable risk proportions for lifetime suicidal ideation, plans, and attempts associated with temporally prior PEs were 5.3%, 5.7%, and 4.8%, respectively. Conclusions and Relevance: Psychotic experiences are associated with elevated odds of subsequent STBs across the life course that cannot be explained by antecedent mental disorders. These results highlight the importance of including information about PEs in screening instruments designed to predict STBs.