A pilot randomised controlled trial of personalised care for depressed patients with symptomatic coronary heart disease in South London general practices: the UPBEAT-UK RCT protocol and recruitment.

ABSTRACT: Background: Community studies reveal people with coronary heart disease (CHD) are twice as likely to be depressed as the general population and that this co-morbidity negatively affects the course and outcome of both conditions. There is evidence for the efficacy of collaborative care and case management for depression treatment, and whilst NICE guidelines recommend these approaches only where depression has not responded to psychological, pharmacological, or combined treatments, these care approaches may be particularly relevant to the needs of people with CHD and depression in the earlier stages of stepped care in primary care settings. Methods: This pilot randomised controlled trial will evaluate whether a simple intervention involving a personalised care plan, elements of case management and regular telephone review is a feasible and acceptable intervention that leads to better mental and physical health outcomes for these patients. The comparator group will be usual general practitioner (GP) care. 81 participants have been recruited from CHD registers of 15 South London general practices. Eligible participants have probable major depression identified by a score of ≥8 on the Hospital Anxiety and Depression Scale depression subscale (HADS-D) together with symptomatic CHD identified using the Modified Rose Angina Questionnaire. Consenting participants are randomly allocated to usual care or the personalised care intervention which involves a comprehensive assessment of each participant’s physical and mental health needs which are documented in a care plan, followed by regular telephone reviews by the case manager over a 6-month period. At each review, the intervention participant’s mood, function and identified problems are reviewed and the case manager uses evidence based behaviour change techniques to facilitate achievement of goals specified by the patient with the aim of increasing the patient’s self efficacy to solve their problems. Depressive symptoms measured by HADS score will be collected at baseline and 1, 6- and 12 months post randomisation. Other outcomes include CHD symptoms, quality of life, wellbeing and health service utilisation. Discussion: This practical and patient-focused intervention is potentially an effective and accessible approach to the health and social care needs of people with depression and CHD in primary care. Trial registration: ISRCTN21615909

Identifying youth-friendly service practices associated with adolescents’ use of reproductive healthcare services in post-conflict Burundi: a cross-sectional study

BACKGROUND: Very little is known about reproductive health service (RHS) availability and adolescents’ use of these services in post-conflict settings. Such information is crucial for targeted community interventions that aim to improve quality delivery of RHS and outcomes in post-conflict settings. The objectives of this study therefore was to examine the density of RHS availability; assess spatial patterns of RHC facilities; and identify youth-friendly practices associated with adolescents’ use of services in post-conflict Burundi. METHODS: A cross-sectional survey was conducted from a full census of all facilities (n = 892) and provider interviews in Burundi. Surveyed facilities included all public, private, religious and community association owned-centers and hospitals. At each facility efforts were made to interview the officer-in-charge and a group of his/her staff. We applied both geospatial and non-spatial analyses, to examine the density of RHS availability and density, and to explore the association between youth-friendly practices and adolescents’ use of RHS in post-conflict Burundi. RESULTS: High spatial patterning of distances of RHC facilities was observed, with facilities clustered predominantly in districts exhibiting persistent violence. But, use of services remained undeterred. We further found a stronger association between use of RHS and facility and programming characteristics. Community outreach, designated check-in/exam rooms, educational materials (posters, print, and pictures) in waiting rooms, privacy and confidentiality were significantly associated with adolescents’ use of RHS across all facility types. Cost was associated with use only at religious facilities and youth involvement at private facilities. No significant association was found between provider characteristics and use of RHS at any facility. CONCLUSIONS: Our findings indicate the need to improve youth-friendly service practices in the provision of RHS to adolescents in Burundi and suggest that current approaches to provider training may not be adequate for improving these vital practices. Our mixed methods approach and results are generalizable to other countries and post-conflict settings. In post-conflict settings, the methods can be used to identify service availability and spatial patterns of RHC facilities to plan for targeted service interventions, to increase demand and uptake of services by youth and young adults

Targeted prevention of common mental health disorders in university students: randomised controlled trial of a transdiagnostic trait-focused web-based intervention

Background: A large proportion of university students show symptoms of common mental disorders, such as depression, anxiety, substance use disorders and eating disorders. Novel interventions are required that target underlying factors of multiple disorders.<p></p> Aims: To evaluate the efficacy of a transdiagnostic trait-focused web-based intervention aimed at reducing symptoms of common mental disorders in university students.<p></p> Method: Students were recruited online (n = 1047, age: M = 21.8, SD = 4.2) and categorised into being at high or low risk for mental disorders based on their personality traits. Participants were allocated to a cognitive-behavioural trait-focused (n = 519) or a control intervention (n = 528) using computerised simple randomisation. Both interventions were fully automated and delivered online (trial registration: ISRCTN14342225). Participants were blinded and outcomes were self-assessed at baseline, at 6 weeks and at 12 weeks after registration. Primary outcomes were current depression and anxiety, assessed on the Patient Health Questionnaire (PHQ9) and Generalised Anxiety Disorder Scale (GAD7). Secondary outcome measures focused on alcohol use, disordered eating, and other outcomes.<p></p> Results: Students at high risk were successfully identified using personality indicators and reported poorer mental health. A total of 520 students completed the 6-week follow-up and 401 students completed the 12-week follow-up. Attrition was high across intervention groups, but comparable to other web-based interventions. Mixed effects analyses revealed that at 12-week follow up the trait-focused intervention reduced depression scores by 3.58 (p<.001, 95%CI [5.19, 1.98]) and anxiety scores by 2.87 (p = .018, 95%CI [1.31, 4.43]) in students at high risk. In high-risk students, between group effect sizes were 0.58 (depression) and 0.42 (anxiety). In addition, self-esteem was improved. No changes were observed regarding the use of alcohol or disordered eating.<p></p> Conclusions This study suggests that a transdiagnostic web-based intervention for university students targeting underlying personality risk factors may be a promising way of preventing common mental disorders with a low-intensity intervention

Detecting depression in patients with coronary heart disease: a diagnostic evaluation of the PHQ-9 and HADS-D in Primary Care, findings from the UPBEAT-UK Study

People with coronary heart disease (CHD) are at heightened risk of depression, and this co-occurrence of conditions is associated with poorer outcomes including raised mortality. This study compares the diagnostic accuracy of two depression case finding instruments in CHD patients relative to a diagnostic standard, the revised Clinical Interview Schedule (CIS-R)

The prevalence of suicidal ideation identified by the Edinburgh Postnatal Depression Scale in postpartum women in primary care: findings from the RESPOND trial

<p>1 Abstract</p> <p>1.1 Background</p> <p>Suicide is a leading cause of perinatal maternal deaths in industrialised countries but there has been little research to investigate prevalence or correlates of postpartum suicidality. The Edinburgh Postnatal Depression Scale is widely used in primary and maternity services to screen for perinatal depressive disorders, and includes a question on suicidal ideation (question 10). We aimed to investigate the prevalence, persistence and correlates of suicidal thoughts in postpartum women in the context of a randomised controlled trial of treatments for postnatal depression.</p> <p>1.2 Methods</p> <p>Women in primary care were sent postal questionnaires at 6 weeks postpartum to screen for postnatal depression before recruitment into an RCT. The Edinburgh Postnatal Depression Scale (EPDS) was used to screen for postnatal depression and in those with high levels of symptoms, a home visit with a standardised psychiatric interview was carried out using the Clinical Interview Schedule-Revised version (CIS-R). Other socio-demographic and clinical variables were measured, including functioning (SF12) and quality of the marital relationship (GRIMS). Women who entered the trial were followed up for 18 weeks.</p> <p>1.3 Results</p> <p>9% of 4,150 women who completed the EPDS question relating to suicidal ideation reported some suicidal ideation (including hardly ever); 4% reported that the thought of harming themselves had occurred to them sometimes or quite often. In women who entered the randomised trial and completed the EPDS question relating to suicidal ideation (n = 253), suicidal ideation was associated with younger age, higher parity and higher levels of depressive symptoms in the multivariate analysis. Endorsement of 'yes, quite often' to question 10 on the EPDS was associated with affirming at least two CIS-R items on suicidality. We found no association between suicidal ideation and SF-12 physical or mental health or the EPDS total score at 18 weeks.</p> <p>1.4 Conclusions</p> <p>Healthcare professionals using the EPDS should be aware of the significant suicidality that is likely to be present in women endorsing 'yes, quite often' to question 10 of the EPDS. However, suicidal ideation does not appear to predict poor outcomes in women being treated for postnatal depression.</p> <p>Trial registration</p> <p>Current Controlled Trials <a href="http://www.controlled-trials.com/ISRCTN16479417">ISRCTN16479417</a>.</p

Depression, Rational Identity and the Educational Imperative: Concordance-Finding in Tricky Diagnostic Moments

It is well-documented, within most medical and much health psychology, that many individuals find diagnoses of depression confusing or even objectionable. Within a corpus of research and practical clinical guidance dominated by the social-cognitive paradigm, the explanation for resistance to a depression diagnosis (or advice pertaining to it) within specific interactions is bordering on the canonical; patients misunderstand depression itself, often as an output of an associated social stigma that distorts public knowledge. The best way to overcome corollary resistance in situ is, logically thus, taken to be a clarification of the true (clinical) nature of depression. In this paper, exploring the diagnosis of depression in UK primary care contexts, the social-cognitive position embedded in contemporary medical reasoning around this matter is critically addressed. It is firstly highlighted how, even in a great deal of extant public health research, the link between an individual holding “correct” medical knowledge and being actively compliant with it is far from inevitable. Secondly, and with respect to concerns around direct communication in clinical contexts, a body of research emergent of Discursive Psychology and Conversation Analysis is explored so as to shed light on how non-cognitive concerns (not least those around the local interactional management of a patient’s social identity) that can inform the manner in which ostensibly “tricky” medical talk plays-out in practice, especially in cases where a mental illness is at stake. Finally, observations are drawn together in a formal Discursive Psychological analysis of a small but highly illustrative sample of three cases where a depression diagnosis is initially questioned or disputed by a patient in primary care but, following further in-consultation activity, concordance with the diagnosis is ultimately reached—a specific issue hitherto unaddressed in either DP or CA fields. These cases specifically reveal the coordinative attention of interlocutors to immediate concerns regarding how the patient might maintain a sense of being an everyday and rational witness to their own lives; indeed, the very act of challenging the diagnosis emerges as a means by which a patient can open up conversational space within the consultation to address such issues. While the veracity of the social-cognitive model is not deemed to be without foundation herein, it is concluded that attention to local interactional concerns might firstly be accorded, such that the practical social concerns and skills of practitioners and patients alike might not be overlooked in the endeavour to produce generally applicable theories

A polygenic resilience score moderates the genetic risk for schizophrenia.

Based on the discovery by the Resilience Project (Chen R. et al. Nat Biotechnol 34:531–538, 2016) of rare variants that confer resistance to Mendelian disease, and protective alleles for some complex diseases, we posited the existence of genetic variants that promote resilience to highly heritable polygenic disorders1,0 such as schizophrenia. Resilience has been traditionally viewed as a psychological construct, although our use of the term resilience refers to a different construct that directly relates to the Resilience Project, namely: heritable variation that promotes resistance to disease by reducing the penetrance of risk loci, wherein resilience and risk loci operate orthogonal to one another. In this study, we established a procedure to identify unaffected individuals with relatively high polygenic risk for schizophrenia, and contrasted them with risk-matched schizophrenia cases to generate the first known “polygenic resilience score” that represents the additive contributions to SZ resistance by variants that are distinct from risk loci. The resilience score was derived from data compiled by the Psychiatric Genomics Consortium, and replicated in three independent samples. This work establishes a generalizable framework for finding resilience variants for any complex, heritable disorder

Transcriptome of iPSC-derived neuronal cells reveals a module of co-expressed genes consistently associated with autism spectrum disorder

Evaluation of expression profile in autism spectrum disorder (ASD) patients is an important approach to understand possible similar functional consequences that may underlie disease pathophysiology regardless of its genetic heterogeneity. Induced pluripotent stem cell (iPSC)-derived neuronal models have been useful to explore this question, but larger cohorts and different ASD endophenotypes still need to be investigated. Moreover, whether changes seen in this in vitro model reflect previous findings in ASD postmortem brains and how consistent they are across the studies remain underexplored questions. We examined the transcriptome of iPSC-derived neuronal cells from a normocephalic ASD cohort composed mostly of high-functioning individuals and from non-ASD individuals. ASD patients presented expression dysregulation of a module of co-expressed genes involved in protein synthesis in neuronal progenitor cells (NPC), and a module of genes related to synapse/neurotransmission and a module related to translation in neurons. Proteomic analysis in NPC revealed potential molecular links between the modules dysregulated in NPC and in neurons. Remarkably, the comparison of our results to a series of transcriptome studies revealed that the module related to synapse has been consistently found as upregulated in iPSC-derived neurons-which has an expression profile more closely related to fetal brain-while downregulated in postmortem brain tissue, indicating a reliable association of this network to the disease and suggesting that its dysregulation might occur in different directions across development in ASD individuals. Therefore, the expression pattern of this network might be used as biomarker for ASD and should be experimentally explored as a therapeutic target

Bupropion Increases Selection of High Effort Activity in Rats Tested on a Progressive Ratio/Chow Feeding Choice Procedure: Implications for Treatment of Effort-Related Motivational Symptoms

Background: Depression and related disorders are characterized by deficits in behavioral activation, exertion of effort, and other psychomotor/motivational dysfunctions. Depressed patients show alterations in effort-related decision making and a bias towards selection of low effort activities. It has been suggested that animal tests of effort-related decision making could be useful as models of motivational dysfunctions seen in psychopathology. Methods: Because clinical studies have suggested that inhibition of catecholamine uptake may be a useful strategy for treatment of effort-related motivational symptoms, the present research assessed the ability of bupropion to increase work output in rats responding on a test of effort-related decision-making (ie, a progressive ratio/chow feeding choice task). With this task, rats can choose between working for a preferred food (high-carbohydrate pellets) by lever pressing on a progressive ratio schedule vs obtaining a less preferred laboratory chow that is freely available in the chamber. Results: Bupropion (10.0–40.0 mg/kg intraperitoneal) significantly increased all measures of progressive ratio lever pressing, but decreased chow intake. These effects were greatest in animals with low baseline levels of work output on the progressive ratio schedule. Because accumbens dopamine is implicated in effort-related processes, the effects of bupropion on markers of accumbens dopamine transmission were examined. Bupropion elevated extracellular dopamine levels in accumbens core as measured by microdialysis and increased phosphorylated dopamine and cyclic-AMP related phosphoprotein 32 kDaltons (pDARPP-32) immunoreactivity in a manner consistent with D1 and D2 receptor stimulation. Conclusion: The ability of bupropion to increase exertion of effort in instrumental behavior may have implications for the pathophysiology and treatment of effort-related motivational symptoms in humans