Ethnic inequalities during clinical placement: A qualitative study of student nurses' experiences within the London National Health Service.

AIM: To understand how student nurse experiences on clinical placement, within National Health Service (NHS) hospitals, differ for ethnic minority and White British groups. DESIGN: A qualitative thematic analysis with an inductive approach. METHODS: Data from semi-structured interviews with 21 London (United Kingdom) hospital-based student nurses were examined using thematic analysis. Participants were interviewed as part of the Tackling Inequalities and Discrimination Experiences in Health Services (TIDES) study and asked about their experiences during clinical placement. RESULTS: Five main themes were identified: (1) Role of mentors, (2) Discrimination and unfair treatment, (3) Speaking up/out, (4) Career progression, and (5) Consequences of adverse experiences. All themes were linked, with the social dynamics and workplace environment (referred to as "ward culture") providing a context that normalizes mistreatment experienced by nursing students. Students from ethnic minority backgrounds reported racism as well as cultural and/or religious microaggressions. While being valued for their race and ethnicity, White British students also experienced discrimination and inequity due to their age, sex, gender, and sexual orientation. Students from both White British and ethnic minority groups acknowledged that being treated badly was a barrier to career progression. Ethnic minority students also noted the lack of diverse representation within senior nursing positions discouraged career progression within the UK NHS. CONCLUSION: These initial experiences of inequality and discrimination are liable to shape a student's perspective of their profession and ability to progress within nursing. The NHS is responsible for ensuring that student nurses' developmental opportunities are equal, irrespective of ethnicity. IMPACT: Ward culture is perpetuated by others who normalize mistreatment and concurrently disadvantage ethnic minority students, making them feel unvalued. This in turn impacts both staff retention and career progression within the NHS. Training assessors should be aware of the existing culture of discrimination within clinical placements and work to eradicate it.

Impact of mental health stigma on help-seeking in the Caribbean: Systematic review.

BACKGROUND: Mental health conditions often go untreated, which can lead to long-term poor emotional, social physical health and behavioural outcomes, and in some cases, suicide. Mental health-related stigma is frequently noted as a barrier to help seeking, however no previous systematic review has considered evidence from the Caribbean specifically. This systematic review aimed to address two research questions: (1) What is the impact of mental health stigma on help-seeking in the Caribbean? (2) What factors underlie the relationship between stigma and help-seeking in the Caribbean? METHODS: A systematic search was conducted across six electronic databases (Medline, Embase, Global Health, PsychInfo, Scopus and LILACS). The search included articles published up to May 2022. Experts in the field were consulted to provide publication recommendations and references of included studies were checked. Data synthesis comprised of three components: a narrative synthesis of quantitative findings, a thematic analysis of qualitative findings, and a meta-synthesis combining these results. RESULTS: The review included nine articles (reflecting eight studies) totaling 1256 participants. A conceptual model was derived from the meta-synthesis, identifying three themes in relation to mental health stigma and help-seeking in the Caribbean: (i) Making sense of mental health conditions'; (ii) Anticipated/Experienced stigma-related experiences and (iii) Individual characteristics. CONCLUSION: This review provides insights into the relationship between mental health stigma and help-seeking in the Caribbean based upon the current research evidence. This can be applied in the design of culturally appropriate future research, and to support policy and practice towards stigma reduction, and improved mental care help-seeking in the Caribbean.

Race, ethnicity and COVID-19 vaccination: a qualitative study of UK healthcare staff.

OBJECTIVE: COVID-19-related inequities experienced by racial and ethnic minority groups including healthcare professionals mirror wider health inequities, which risk being perpetuated by lower uptake of vaccination. We aim to better understand lower uptake among racial and ethnic minority staff groups to inform initiatives to enhance uptake. DESIGN: Twenty-five semi-structured interviews were conducted (October 2020-January 2021) with UK-based healthcare staff. Data were inductively and thematically analysed. RESULTS: Vaccine decision-making processes were underpinned by an overarching theme, 'weighing up risks of harm against potential benefits to self and others'. Sub-themes included 'fear of harm', 'moral/ethical objections', 'potential benefits to self and others', 'information and misinformation', and 'institutional or workplace pressure'. We identified ways in which these were weighted more heavily towards vaccine hesitancy for racial and ethnic minority staff groups influenced by perceptions about institutional and structural discrimination. This included suspicions and fear around institutional pressure to be vaccinated, racial injustices in vaccine development and testing, religious or ethical concerns, and legitimacy and accessibility of vaccine messaging and communication. CONCLUSIONS: Drawing on a critical race perspective, we conclude that acknowledging historical and contemporary abuses of power is essential to avoid perpetuating and aggravating mistrust by de-contextualising hesitancy from the social processes affecting hesitancy, undermining efforts to increase vaccine uptake.

DNA methylation meta-analysis reveals cellular alterations in psychosis and markers of treatment-resistant schizophrenia.

We performed a systematic analysis of blood DNA methylation profiles from 4483 participants from seven independent cohorts identifying differentially methylated positions (DMPs) associated with psychosis, schizophrenia, and treatment-resistant schizophrenia. Psychosis cases were characterized by significant differences in measures of blood cell proportions and elevated smoking exposure derived from the DNA methylation data, with the largest differences seen in treatment-resistant schizophrenia patients. We implemented a stringent pipeline to meta-analyze epigenome-wide association study (EWAS) results across datasets, identifying 95 DMPs associated with psychosis and 1048 DMPs associated with schizophrenia, with evidence of colocalization to regions nominated by genetic association studies of disease. Many schizophrenia-associated DNA methylation differences were only present in patients with treatment-resistant schizophrenia, potentially reflecting exposure to the atypical antipsychotic clozapine. Our results highlight how DNA methylation data can be leveraged to identify physiological (e.g., differential cell counts) and environmental (e.g., smoking) factors associated with psychosis and molecular biomarkers of treatment-resistant schizophrenia.

Evaluating the Efficacy of a Mobile App (Drinks:Ration) and Personalized Text and Push Messaging to Reduce Alcohol Consumption in a Veteran Population: Protocol for a Randomized Controlled Trial.

BACKGROUND: Alcohol misuse is higher in the UK Armed Forces than in the general population. Previous research has shown that interventions delivered via smartphones are efficacious in promoting self-monitoring of alcohol use, have utility in reducing alcohol consumption, and have a broad reach. OBJECTIVE: This single-blinded randomized controlled trial (RCT) aims to assess the efficacy of a 28-day brief alcohol intervention delivered via a smartphone app (Drinks:Ration) in reducing weekly self-reported alcohol consumption between baseline and 3-month follow-up among veterans who drink at a hazardous or harmful level and receive or have received support for mental health symptoms in a clinical setting. METHODS: In this two-arm, single-blinded RCT, a smartphone app that includes interactive features designed to enhance participants' motivation and personalized messaging is compared with a smartphone app that provides only government guidance on alcohol consumption. The trial will be conducted in a veteran population that has sought help through Combat Stress, a UK veteran's mental health charity. Recruitment, consent, and data collection will be carried out automatically through the Drinks:Ration platform. The primary outcome is the change in self-reported weekly alcohol consumption between baseline (day 0) and 3-month follow-up (day 84) as measured using the Time-Line Follow back for Alcohol Consumption. Secondary outcome measures include (1) change in the baseline to 3-month follow-up (day 84) Alcohol Use Disorder Identification Test score and (2) change in the baseline to 3-month follow-up (day 84) World Health Organization Quality of Life-BREF score to assess the quality of adjusted life years. Process evaluation measures include (1) app use and (2) usability ratings as measured by the mHealth App Usability Questionnaire. The primary and secondary outcomes will also be reassessed at the 6-month follow-up (day 168) to assess the longer-term benefits of the intervention, which will be reported as a secondary outcome. RESULTS: The study will begin recruitment in October 2020 and is expected to require 12 months to complete. The study results will be published in 2022. CONCLUSIONS: This study assesses whether a smartphone app is efficacious in reducing self-reported alcohol consumption in a veteran population that has sought help through Combat Stress using personalized messaging and interactive features. This innovative approach, if successful, may provide a means to deliver a low-cost health promotion program that has the potential to reach large groups, in particular those who are geographically dispersed, such as military personnel. TRIAL REGISTRATION: ClinicalTrials.gov NCT04494594; https://clinicaltrials.gov/ct2/show/NCT04494594. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/19720.

Young Muslim Pakistani Women's Lived Experiences of Izzat, Mental Health, and Well-Being.

This article explores how six Pakistani Muslim women interpret cultural concepts of izzat (honor and self-respect); what role, if any, it has in their lives; and whether there is interplay between upholding izzat and the participants' help-seeking strategies for mental health and well-being. Semistructured interviews were conducted and analyzed with an interpretative phenomenological analytic framework. Three themes were identified: (a) "the rules of izzat," (b) "negotiating tensions," and (c) "speaking out/breaking the 'rules.'" Findings highlighted new insights into the understanding of izzat and the implications these cultural concepts have for strategies in managing or silencing of psychological distress. Interviews illustrated tensions the participants experience when considering izzat, how these are negotiated to enable them to self-manage or seek help, and possible life experiences that might lead to self-harm and attempted suicide. Notably, cultural codes, in particular izzat, appear to vary over the life course and are influenced by migration.

Debt, common mental disorders and mental health service use.

BACKGROUND: Uncertainty remains as to whether the effects of debt on common mental disorder (CMD) are persistent over time and what impact it has on mental health service use (MHSU). AIMS: To determine the distribution of debt across sociodemographic and socioeconomic statuses; to examine whether debt influences CMD recovery over time; and to determine the effects of episodic and/or long-term debt and CMD on MHSU outcomes. METHODS: Data were collected from phase 1 (N = 1698) and phase 2 (N = 1052) of the South East London Community Health (SELCoH) study, a population-based survey. RESULTS: 37.2% of participants who reported debt at SELCoH 1 and 46.6% at SELCoH 2 experienced concurrent CMD. Those with concurrent exposure to debt and CMD at SELCoH 1 were at greater risk of CMD at SELCoH 2. Debt accumulation was strongly associated with CMD cross-sectionally; however, this somewhat dissipated over time. Reporting any debt at SELCoH 2 or debt at both time-points were strongly associated with MHSU in the past year in the fully adjusted model adjusting for prior mental health. CONCLUSIONS: More focus is needed on concurrent exposure to debt and CMD with regards to subsequent psychological impact and consequences for MHSU.

DNA modification study of major depressive disorder: beyond locus-by-locus comparisons.

BACKGROUND: Major depressive disorder (MDD) exhibits numerous clinical and molecular features that are consistent with putative epigenetic misregulation. Despite growing interest in epigenetic studies of psychiatric diseases, the methodologies guiding such studies have not been well defined. METHODS: We performed DNA modification analysis in white blood cells from monozygotic twins discordant for MDD, in brain prefrontal cortex, and germline (sperm) samples from affected individuals and control subjects (total N = 304) using 8.1K CpG island microarrays and fine mapping. In addition to the traditional locus-by-locus comparisons, we explored the potential of new analytical approaches in epigenomic studies. RESULTS: In the microarray experiment, we detected a number of nominally significant DNA modification differences in MDD and validated selected targets using bisulfite pyrosequencing. Some MDD epigenetic changes, however, overlapped across brain, blood, and sperm more often than expected by chance. We also demonstrated that stratification for disease severity and age may increase the statistical power of epimutation detection. Finally, a series of new analytical approaches, such as DNA modification networks and machine-learning algorithms using binary and quantitative depression phenotypes, provided additional insights on the epigenetic contributions to MDD. CONCLUSIONS: Mapping epigenetic differences in MDD (and other psychiatric diseases) is a complex task. However, combining traditional and innovative analytical strategies may lead to identification of disease-specific etiopathogenic epimutations.

A voxel-based morphometry comparison of the 3.0T ADNI-1 and ADNI-2 volumetric MRI protocols.

OBJECTIVES: The Alzheimer's Disease Neuroimaging Initiative 3.0 T MRI image acquisition scheme changed between the original ADNI-1 grant and the two subsequent grants (ADNI-GO and ADNI-2). The aim of the current study was to investigate the compatibility of the 3.0 T ADNI-1 and ADNI-2 T1-weighted volumes using voxel-based morphometry (VBM). METHODS: T1-weighted images of 30 subjects were acquired using a 3T GE Signa HDx using the ADNI-1 and ADNI-2 T1-weighted volume sequences. Images were pre-processed and analysed using SPM8. Global grey matter (GM), white matter (WM) and cerebrospinal fluid (CSF) volumes were compared, as well as voxel-by-voxel differences in GM and WM. RESULTS: Correlation coefficients and percentage differences for each tissue type between ADNI-1 and ADNI-2 were as follows: ((GM: intraclass correlation coefficient (ICC) = 0.86, ADNI-1 3.09% < ADNI-2) (WM: ICC = 0.91, ADNI-1 2.92% > ADNI-2) (CSF: ICC = 0.90, ADNI-1 1.94% > ADNI-2)). For ADNI-2, widespread increases in GM were found relative to ADNI-1 (cerebellum and pre-central gyrus), with localised decreases along the midline and temporal lobes. For ADNI-1, widespread increases in WM were found relative to ADNI-2 (cerebellum and pre-central gyrus), together with localised decreases in the temporal gyrus. CONCLUSIONS: The widespread increase in GM and localised decrease in WM in ADNI-2 compared to ADNI-1 images suggests that the image acquisition protocols are not directly comparable using SPM-8. Total volumes of GM, WM and CSF also differed between the protocols in the following order of magnitude: GM > WM > CSF. This has implications for studies aiming to analyse images acquired using the ADNI-1 and ADNI-2 protocols under VBM.

CYP2C19 genotype predicts steady state escitalopram concentration in GENDEP.

In vitro work shows CYP2C19 and CYP2D6 contribute to the metabolism of escitalopram to its primary metabolite, N-desmethylescitalopram. We report the effect of CYP2C19 and CYP2D6 genotypes on steady state morning concentrations of escitalopram and N-desmethylescitalopram and the ratio of this metabolite to the parent drug in 196 adult patients with depression in GENDEP, a clinical pharmacogenomic trial. Subjects who had one CYP2D6 allele associated with intermediate metabolizer phenotype and one associated with poor metabolizer (i.e. IM/PM genotypic category) had a higher mean logarithm escitalopram concentration than CYP2D6 extensive metabolizers (EMs) (p = 0.004). Older age was also associated with higher concentrations of escitalopram. Covarying for CYP2D6 and age, we found those homozygous for the CYP2C19*17 allele associated with ultrarapid metabolizer (UM) phenotype had a significantly lower mean escitalopram concentration (2-fold, p = 0.0001) and a higher mean metabolic ratio (p = 0.0003) than EMs, while those homozygous for alleles conferring the PM phenotype had a higher mean escitalopram concentration than EMs (1.55-fold, p = 0.008). There was a significant overall association between CYP2C19 genotypic category and escitalopram concentration (p = 0.0003; p = 0.0012 Bonferroni corrected). In conclusion, we have demonstrated an association between CYP2C19 genotype, including the CYP2C19*17 allele, and steady state escitalopram concentration.

OPCRIT+: an electronic system for psychiatric diagnosis and data collection in clinical and research settings.

BACKGROUND: The increasingly large sample size requirements of modern adult mental health research suggests the need for a data collection and diagnostic application that can be used across a broad range of clinical and research populations. Aims To develop a data collection and diagnostic application that can be used across a broad range of clinical and research settings. METHOD: We expanded and redeveloped the OPCRIT system into a broadly applicable diagnostic and data-collection package and carried out an interrater reliability study of this new tool. RESULTS: OPCRIT+ performed well in an interrater reliability study with relatively inexperienced clinicians, giving a combined, weighted kappa of 0.70 for diagnostic reliability. CONCLUSIONS: OPCRIT+ showed good overall interrater reliability scores for diagnoses. It is now incorporated in the electronic patient record of the Maudsley and associated hospitals. OPCRIT+ can be downloaded free of charge at http://sgdp.iop.kcl.ac.uk/opcritplus.

Utility of the pooling approach as applied to whole genome association scans with high-density Affymetrix microarrays.

BACKGROUND: We report an attempt to extend the previously successful approach of combining SNP (single nucleotide polymorphism) microarrays and DNA pooling (SNP-MaP) employing high-density microarrays. Whereas earlier studies employed a range of Affymetrix SNP microarrays comprising from 10 K to 500 K SNPs, this most recent investigation used the 6.0 chip which displays 906,600 SNP probes and 946,000 probes for the interrogation of CNVs (copy number variations). The genotyping assay using the Affymetrix SNP 6.0 array is highly demanding on sample quality due to the small feature size, low redundancy, and lack of mismatch probes. FINDINGS: In the first study published so far using this microarray on pooled DNA, we found that pooled cheek swab DNA could not accurately predict real allele frequencies of the samples that comprised the pools. In contrast, the allele frequency estimates using blood DNA pools were reasonable, although inferior compared to those obtained with previously employed Affymetrix microarrays. However, it might be possible to improve performance by developing improved analysis methods. CONCLUSIONS: Despite the decreasing costs of genome-wide individual genotyping, the pooling approach may have applications in very large-scale case-control association studies. In such cases, our study suggests that high-quality DNA preparations and lower density platforms should be preferred.

The Bipolar Association Case-Control Study (BACCS) and meta-analysis: No association with the 5,10-Methylenetetrahydrofolate reductase gene and bipolar disorder.

Bipolar disorder (BD) is a complex genetic disease for which the underlying pathophysiology has yet to be fully explained. 5,10-Methylenetetrahydrofolate reductase (MTHFR) is a crucial enzyme in folate-mediated one-carbon metabolism and folate deficiency can be associated with psychiatric symptoms. A single base variant in MTHFR gene (C677T) results in the production of a mildly dysfunctional thermolabile enzyme and has recently been implicated in BD. We conducted an association study of this polymorphism in 897 patients with bipolar I or bipolar II disorder, and 1,687 healthy control subjects. We found no evidence for genotypic or allelic association in this sample. We also performed a meta-analysis of our own, and all published data, and report no evidence for association. Our findings suggest that the MTHFR C677T polymorphism is not involved in the genetic etiology of clinically significant BD.

Suicidal ideation during treatment of depression with escitalopram and nortriptyline in genome-based therapeutic drugs for depression (GENDEP): a clinical trial.

BACKGROUND: Suicidal thoughts and behaviours during antidepressant treatment, especially during the first weeks of treatment, have prompted warnings by regulatory bodies. The aim of the present study is to investigate the course and predictors of emergence and worsening of suicidal ideation during tricyclic antidepressant and serotonin reuptake inhibitor treatment. METHODS: In a multicentre part-randomised open-label study, 811 adult patients with moderate to severe unipolar depression were allocated to flexible dosage of escitalopram or nortriptyline for 12 weeks. The suicidality items of three standard measures were integrated in a suicidal ideation score. Increases in this score were classified as treatment emergent suicidal ideation (TESI) or treatment worsening suicidal ideation (TWOSI) according to the absence or presence of suicidal ideation at baseline. RESULTS: Suicidal ideation decreased during antidepressant treatment. Rates of TESI and TWOSI peaked in the fifth week. Severity of depression predicted TESI and TWOSI. In men, nortriptyline was associated with a 9.8-fold and 2.4-fold increase in TESI and TWOSI compared to escitalopram, respectively. Retirement and history of suicide attempts predicted TWOSI. CONCLUSION: Increases in suicidal ideation were associated with depression severity and decreased during antidepressant treatment. In men, treatment with escitalopram is associated with lower risk of suicidal ideation compared to nortriptyline. Clinicians should remain alert to suicidal ideation beyond the initial weeks of antidepressant treatment. TRIAL REGISTRATION: EudraCT (No.2004-001723-38) and ISRCTN (No. 03693000).

Body weight as a predictor of antidepressant efficacy in the GENDEP project.

BACKGROUND: Being overweight or obese may be associated with poor response to antidepressants. The present report explores the moderation of antidepressant response by body weight to establish the specificity to antidepressant mode of action, type of depressive symptoms and gender. METHODS: Height and weight were measured in 797 men and women with major depression treated with escitalopram or nortriptyline for twelve weeks as part of the Genome Based Therapeutic Drugs for Depression (GENDEP) project. Body mass index (BMI) and obesity (BMI>30) were tested as predictors of change in depressive symptoms using mixed linear models. RESULTS: Higher BMI and obesity predicted poor response to nortriptyline but did not significantly influence response to escitalopram. The moderation of response by body weight was due to differential improvement in neurovegetative symptoms, including sleep and appetite. The relationship between body weight and change in neurovegetative symptoms was moderated by gender with obese men responding less to nortriptyline and obese women having poorer response to both antidepressants. LIMITATIONS: As no placebo arm was included, the specificity of findings to antidepressants is relative. Lack of specific measures precluded accounting for differences in body fat distribution. CONCLUSIONS: Body weight should be considered in the assessment of depression as it may inform the selection of antidepressant treatment.

Depression Case Control (DeCC) Study fails to support involvement of the muscarinic acetylcholine receptor M2 (CHRM2) gene in recurrent major depressive disorder.

It has been suggested that alteration in the muscarinic-cholinergic system is involved in modulation of mood. Three studies have reported linkage on chromosome 7 with major depressive disorder (MDD) in or close to a region containing the muscarinic receptor CHRM2 gene. A haplotype of SNPs located in CHRM2 (rs1824024-rs2061174-rs324650) has been significantly associated with MDD in a previous study. We report the first study investigating this gene in a large, adequately powered, clinical depression case-control sample (n = 1420 cases, 1624 controls). Our data fail to support association with the CHRM2 polymorphisms previously implicated in the genetic aetiology of depression. It is possible our failure to replicate may be a consequence of differences in definition of the MDD phenotype and/or ethnic differences.

Personality and the bipolar spectrum: normative and classification data for the Eysenck Personality Questionnaire-Revised.

BACKGROUND: Personality traits dispose individuals toward particular affective states and may therefore have an important role in the etiology of affective disorders in particular. Despite being one of the most widely used and well-researched personality instruments, few studies have studied bipolar spectrum disorders using the revised Eysenck Personality Questionnaire (EPQ-R) (Eysenck HJ, Eysenck SBG. The Eysenck Personality Questionnaire-Revised. Sevenoaks: UK; Hodder & Stoughton, 1992). METHODS: The EPQ-R was administered to 50 bipolar patients, 50 unipolar patients, and 50 controls matched on age and sex. Participants in clinical groups were euthymic, and participants in the control groups were screened for symptoms of depression. RESULTS: The EPQ-R scores were most effective at discriminating unipolar patients from controls, such that unipolar patients were higher on neuroticism and lower on extraversion. Bipolar patients showed a similar personality profile to, but were not clearly distinguished from, unipolar patients. CONCLUSIONS: This research provides preliminary normative data for the EPQ-R that complement previous theoretical and empirical work in this area and suggests the usefulness of this tool in a clinical setting.