Genetic diversity fuels gene discovery for tobacco and alcohol use

Tobacco and alcohol use are heritable behaviours associated with 15% and 5.3% of worldwide deaths, respectively, due largely to broad increased risk for disease and injury(1-4). These substances are used across the globe, yet genome-wide association studies have focused largely on individuals of European ancestries(5). Here we leveraged global genetic diversity across 3.4 million individuals from four major clines of global ancestry (approximately 21% non-European) to power the discovery and fine-mapping of genomic loci associated with tobacco and alcohol use, to inform function of these loci via ancestry-aware transcriptome-wide association studies, and to evaluate the genetic architecture and predictive power of polygenic risk within and across populations. We found that increases in sample size and genetic diversity improved locus identification and fine-mapping resolution, and that a large majority of the 3,823 associated variants (from 2,143 loci) showed consistent effect sizes across ancestry dimensions. However, polygenic risk scores developed in one ancestry performed poorly in others, highlighting the continued need to increase sample sizes of diverse ancestries to realize any potential benefit of polygenic prediction.Peer reviewe

Commentary: evaluating Title VII investments in primary care training: drop in the ocean, or levee against the flood?

The Title VII primary care programs have been in place for over thirty years to improve Americans\u27 access to primary care clinicians, especially physicians, through community based, primary care-focused education of students and residents, and preparation of faculty. Despite the long investment in these programs, however, U.S. medical students\u27 interest in primary care has reached new lows. So it might seem obvious why the president\u27s Office of Management and Budget (OMB) declared the Title VII primary care programs ineffective; But the OMB analysis aggregates these into an overall assessment of 40 separate Health Resources and Services Administration health professions programs. Furthermore the OMB evaluation of the Title VII primary care programs did not consider the outcomes most readily affected by these grants-those on the individual students, residents, faculty, and institutions. Accordingly, it does not reflect the important role of Title VII in building and sustaining primary care teaching over the years, an impact extensively documented in the accompanying articles. The Title VII primary care programs have struggled with diminishing levels of funding even as sources of support for specialized education have flooded into medical schools and teaching hospitals. What is most impressive about the successes of the Title VII primary care programs documented in the accompanying articles is not just the impressive record of accomplishment but that it occurred despite the powerful forces driving subspecialty care. Hopefully, the next generation of policy makers will use this important history to recommit to a national investment in primary care education. This commentary is part of a theme issue of Academic Medicine on the Title VII health professions training programs

The interpersonal context of rumination : an investigation of interpersonal antecedents and consequences of the ruminative response style

The thesis aim was to increase understanding of interpersonal antecedents and consequences of rumination, defined as ‘repetitive and passive thinking about one’s symptoms of depression and the possible causes and consequences of those symptoms’ (Nolen-Hoeksema, 2004, p.107). As a proof-of-principle study, rumination predicted diminished relationship satisfaction, three months later, in a sample of remitted depressed adults (N = 57). In the next study, rumination was associated with a maladaptive submissive interpersonal style and rejection sensitivity, controlling for depressive symptoms, other interpersonal styles and gender, in a different sample (N = 103 currently depressed, previously depressed and never depressed adults). Subsequent chapters incorporated a second assessment point of data from this same sample. Longitudinal analyses were undertaken to investigate; a) do rumination and depressogenic interpersonal factors predict future depression?; b) does rumination prospectively predict increased rejection sensitivity and submissive interpersonal behaviours, and, vice-versa, do these interpersonal factors predict increased rumination?; c) does rumination prospectively predict poor social adjustment and interpersonal stress? Consistent with previous findings, Time 1 rumination predicted increased depression six months later. Unexpectedly, the effect of rumination on future depression was mediated by its relationship with the submissive interpersonal style. Partially consistent with the stated predictions, Time 1 rejection sensitivity (but not the submissive interpersonal style) prospectively predicted increased rumination, but rumination did not predict rejection sensitivity or the submissive interpersonal style. As predicted, rumination prospectively predicted increased chronic interpersonal stress and poor social adjustment (but not acute interpersonal stress). In a final study, rumination was manipulated via an applied intervention (concreteness training, CT), within the context of a randomized controlled trial (N = 79 clinically depressed adults). Analyses compared the change in social adjustment and submissive interpersonal behaviour reported in the CT condition compared to a treatment as usual (TAU) condition. There was a significantly greater reduction in rumination in the CT compared to TAU condition, p < .05. Moreover, the reduction in submissive interpersonal behaviours was significantly greater in the CT compared to TAU condition, p < .05. The change in social adjustment was not greater in the CT compared to TAU condition. Thus, a psychological intervention which reduces rumination decreased maladaptive submissive interpersonal behaviour. The implications of the findings are discussed in relation to theory of rumination and interpersonal theories of depression.EThOS - Electronic Theses Online ServiceEconomic and Social Research Council (ESRC) : National Health ServiceGBUnited Kingdo

Rumination-focused cognitive-behavioural therapy for residual depression: phase II randomised controlled trial

BackgroundAbout 20% of major depressive episodes become chronic and medication-refractory and also appear to be less responsive to standard cognitive–behavioural therapy (CBT).AimsTo test whether CBT developed from behavioural activation principles that explicitly and exclusively targets depressive rumination enhances treatment as usual (TAU) in reducing residual depression.MethodForty-two consecutively recruited participants meeting criteria for medication-refractory residual depression were randomly allocated to TAU v. TAU plus up to 12 sessions of individual rumination-focused CBT. The trial has been registered (ISRCTN22782150).ResultsAdding rumination-focused CBT to TAU significantly improved residual symptoms and remission rates. Treatment effects were mediated by change in rumination.ConclusionsThis is the first randomised controlled trial providing evidence of benefits of rumination-focused CBT in persistent depression. Although suggesting the internal validity of rumination-focused CBT for residual depression, the trial lacked an attentional control group so cannot test whether the effects were as a result of the specific content of rumination-focused CBT v. non-specific therapy effects.</jats:sec

Cognitive behavioural therapy competence of Japanese trainees: A comparison with UK trainees

The present study aimed to assess the Cognitive Behavioural Therapy (CBT) competences of trainees enrolled in a two-year accredited master’s course in clinical psychology in Japan, and compare their competence levels with those trainees enrolled in a one-year postgraduate CBT diploma course accredited by the British Association of Behavioural and Cognitive Psychotherapies (BABCP) in the UK. Participants (Japan=162, UK=29) responded to questionnaires assessing their CBT competences. Descriptive data suggested that most Japanese trainees regarded themselves as being able to demonstrate little to none of the required CBT competences. The UK trainees rated their CBT competences to be significantly higher than the Japanese trainees on all competence items. Moreover, the number of counselling cases experienced during the training predicted the generic therapeutic competences among Japanese trainees. Furthermore, the number of initial intake interviews performed by the trainees predicted their basic CBT competences, specific CBT techniques, and meta-competences. The key limitations of the study were differences in participants’ age and their experiences prior to the enrolment in the course reported between the two countries. Future studies should consider the effects of these factors on trainees’ CBT competences

Mindfulness-based cognitive therapy to prevent relapse in recurrent depression

For people at risk of depressive relapse, mindfulness-based cognitive therapy (MBCT) has an additive benefit to usual care (H. F. Coelho, P. H. Canter, and E. Ernst, 2007). This study asked if, among patients with recurrent depression who are treated with antidepressant medication (ADM), MBCT is comparable to treatment with maintenance ADM (m-ADM) in (a) depressive relapse prevention, (b) key secondary outcomes, and (c) cost effectiveness. The study design was a parallel 2-group randomized controlled trial comparing those on m-ADM (N = 62) with those receiving MBCT plus support to taper/discontinue antidepressants (N = 61). Relapse/recurrence rates over 15-month follow-ups in MBCT were 47%, compared with 60% in the m-ADM group (hazard ratio = 0.63; 95% confidence interval: 0.39 to 1.04). MBCT was more effective than m-ADM in reducing residual depressive symptoms and psychiatric comorbidity and in improving quality of life in the physical and psychological domains. There was no difference in average annual cost between the 2 groups. Rates of ADM usage in the MBCT group was significantly reduced, and 46 patients (75%) completely discontinued their ADM. For patients treated with ADM, MBCT may provide an alternative approach for relapse prevention