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Functional impairment in daily activities, such as work and socializing, is part of the diagnostic criteria for major depressive disorder and most anxiety disorders. Despite evidence that symptom severity and functional impairment are partially distinct, functional impairment is often overlooked. To assess whether functional impairment captures diagnostically relevant genetic liability beyond that of symptoms, we aimed to estimate the heritability of, and genetic correlations between, key measures of current depression symptoms, anxiety symptoms, and functional impairment.
Methods
In 17,130 individuals with lifetime depression or anxiety from the Genetic Links to Anxiety and Depression (GLAD) Study, we analyzed total scores from the Patient Health Questionnaire-9 (depression symptoms), Generalized Anxiety Disorder-7 (anxiety symptoms), and Work and Social Adjustment Scale (functional impairment). Genome-wide association analyses were performed with REGENIE. Heritability was estimated using GCTA-GREML and genetic correlations with bivariate-GREML.
Results
The phenotypic correlations were moderate across the three measures (Pearson’s r = 0.50–0.69). All three scales were found to be under low but significant genetic influence (single-nucleotide polymorphism-based heritability [h2SNP] = 0.11–0.19) with high genetic correlations between them (rg = 0.79–0.87).
Conclusions
Among individuals with lifetime depression or anxiety from the GLAD Study, the genetic variants that underlie symptom severity largely overlap with those influencing functional impairment. This suggests that self-reported functional impairment, while clinically relevant for diagnosis and treatment outcomes, does not reflect substantial additional genetic liability beyond that captured by symptom-based measures of depression or anxiety.
Trace amine-associated receptor 1 (TAAR1) agonists offer a new approach, but there is uncertainty regarding their effects, exact mechanism of action and potential role in treating psychosis.
Aims
To evaluate the available evidence on TAAR1 agonists in psychosis, using triangulation of the output of living systematic reviews (LSRs) of animal and human studies, and provide recommendations for future research prioritisation.
Method
This study is part of GALENOS (Global Alliance for Living Evidence on aNxiety, depressiOn and pSychosis). In the triangulation process, a multidisciplinary group of experts, including those with lived experience, met and appraised the first co-produced living systematic reviews from GALENOS, on TAAR1 agonists.
Results
The animal data suggested a potential antipsychotic effect, as TAAR1 agonists reduced locomotor activity induced by pro-psychotic drug treatment. Human studies showed few differences for ulotaront and ralmitaront compared with placebo in improving overall symptoms in adults with acute schizophrenia (four studies, n = 1291 participants, standardised mean difference (SMD) 0.15, 95% CI −0.05 to 0.34). Large placebo responses were seen in ulotaront phase three trials. Ralmitaront was less efficacious than risperidone (one study, n = 156 participants, SMD = −0.53, 95% CI −0.86 to −0.20). The side-effect profile of TAAR1 agonists was favourable compared with existing antipsychotics. Priorities for future studies included (a) using different animal models of psychosis with greater translational validity; (b) animal and human studies with wider outcomes including cognitive and affective symptoms and (c) mechanistic studies and investigations of other potential applications, such as adjunctive treatments and long-term outcomes. Recommendations for future iterations of the LSRs included (a) meta-analysis of individual human participant data, (b) including studies that used different methodologies and (c) assessing other disorders and symptoms.
Conclusions
This co-produced, international triangulation examined the available evidence and developed recommendations for future research and clinical applications for TAAR1 agonists in psychosis. Broader challenges included difficulties in assessing the risk of bias, reproducibility, translation and interpretability of animal models to clinical outcomes, and a lack of individual and clinical characteristics in the human data. The research will inform a separate, independent prioritisation process, led by lived experience experts, to prioritise directions for future research.
We recently reported on the radio-frequency attenuation length of cold polar ice at Summit Station, Greenland, based on bi-static radar measurements of radio-frequency bedrock echo strengths taken during the summer of 2021. Those data also allow studies of (a) the relative contributions of coherent (such as discrete internal conducting layers with sub-centimeter transverse scale) vs incoherent (e.g. bulk volumetric) scattering, (b) the magnitude of internal layer reflection coefficients, (c) limits on signal propagation velocity asymmetries (‘birefringence’) and (d) limits on signal dispersion in-ice over a bandwidth of ~100 MHz. We find that (1) attenuation lengths approach 1 km in our band, (2) after averaging 10 000 echo triggers, reflected signals observable over the thermal floor (to depths of ~1500 m) are consistent with being entirely coherent, (3) internal layer reflectivities are ≈–60$\to$–70 dB, (4) birefringent effects for vertically propagating signals are smaller by an order of magnitude relative to South Pole and (5) within our experimental limits, glacial ice is non-dispersive over the frequency band relevant for neutrino detection experiments.
Understanding the distribution and extent of suitable habitats is critical for the conservation of endangered and endemic taxa. Such knowledge is limited for many Central African species, including the rare and globally threatened Grey-necked Picathartes Picathartes oreas, one of only two species in the family Picathartidae endemic to the forests of Central Africa. Despite growing concerns about land-use change resulting in fragmentation and loss of forest cover in the region, neither the extent of suitable habitat nor the potential species’ distribution is well known. We combine 339 (new and historical) occurrence records of Grey-necked Picathartes with environmental variables to model the potential global distribution. We used a Maximum Entropy modelling approach that accounted for sampling bias. Our model suggests that Grey-necked Picathartes distribution is strongly associated with steeper slopes and high levels of forest cover, while bioclimatic, vegetation health, and habitat condition variables were all excluded from the final model. We predicted 17,327 km2 of suitable habitat for the species, of which only 2,490 km2 (14.4%) are within protected areas where conservation designations are strictly enforced. These findings show a smaller global distribution of predicted suitable habitat forthe Grey-necked Picathartes than previously thought. This work provides evidence to inform a revision of the International Union for Conservation of Nature (IUCN) Red List status, and may warrant upgrading the status of the species from “Near Threatened” to “Vulnerable”.
Melanie Fennell’s (1997) seminal cognitive approach to low self-esteem was published in Behavioural and Cognitive Psychotherapy. The current paper proposes a refined model, drawing on social theories, and research with people with socially devalued characteristics. This model emphasises how self-esteem relates to perceptions of one’s value in the eyes of others. It is proposed that core beliefs typical of low self-esteem relate to one’s value in relation to personal adequacy (e.g. having worth or status) and/or to social connection (e.g. being liked, loved, accepted or included). In each of these value domains, beliefs about both the self (e.g. ‘I am a failure’, ‘I am unlovable’) and others (e.g. ‘Others look down on me’, ‘Others don’t care about me’) are considered important. The model suggests that everyone monitors their value but in people with low self-esteem, cognitive biases associated with underlying beliefs occur. In the context of trigger situations, this results in a greater likelihood of negative appraisals of perceived threat to one’s value. Such appraisals activate underlying negative beliefs, resulting in negative mood (e.g. low mood, anxiety, shame, disgust) and other responses that maintain low self-esteem. Responses which can be used excessively or in unhelpful ways include (a) corrective behaviours; (b) compensatory strategies; (c) increased value monitoring; (d) safety-seeking behaviours; (e) rumination; (f) unhelpful mood regulation responses. These responses can adversely impact daily functioning or health, having the counterproductive effect of maintaining negative beliefs about one’s value. Examples are provided for low self-esteem in lesbian, gay and bisexual individuals.
‘E-learning’ can be defined broadly as the use of internet technologies to deliver teaching and to enhance knowledge and performance. It is also referred to as web-based, online, distributed or internet-based learning (Ruiz et al. 2006). Many sites use ‘blended learning’, where e-learning is combined with in-person or virtual face-to-face instructor-led training.
The increase in portability, power and connectivity of devices means that most smartphones can easily access information in real time (Marzano et al. 2017) and, of internet users worldwide, 93% access the internet via mobile devices (Johnson 2021). This means that access to the internet to gather information about mental health is immediate, but the vast number of information sites can easily become overwhelming for both patients and clinicians. A simple search for a single mental health topic generates a huge number and range of results. These vary from reviews of the evidence and primary research articles, to news articles and advertisements for treatment centres. The internet user is swamped with an array of sites of variable (and often unknown) quality, which are neither necessarily relevant to the original question nor ranked in order of reliability.
Network meta-analysis (NMA) is a statistical method that allows comparison of multiple treatments against each other. The use of NMA, and its advantages and potential limitations, is discussed here in the context of this issue's Cochrane review of psychological treatments for panic disorder. The review showed benefits for psychological treatment when compared to a waiting list, particularly for cognitive behavioural therapy in both the short and longer term. The findings were limited by the primary studies available, but despite these, this analysis using NMA presents the best evidence to date of the relative benefits of different types of psychological treatments in panic disorder.
Over the past 30 years, the number of US doctoral anthropology graduates has increased by about 70%, but there has not been a corresponding increase in the availability of new faculty positions. Consequently, doctoral degree-holding archaeologists face more competition than ever before when applying for faculty positions. Here we examine where US and Canadian anthropological archaeology faculty originate and where they ultimately end up teaching. Using data derived from the 2014–2015 AnthroGuide, we rank doctoral programs whose graduates in archaeology have been most successful in the academic job market; identify long-term and ongoing trends in doctoral programs; and discuss gender division in academic archaeology in the US and Canada. We conclude that success in obtaining a faculty position upon graduation is predicated in large part on where one attends graduate school.
Psychotic depression is a severe condition. Drug treatment (antipsychotics, antidepressants or the combination) or electroconvulsive therapy (ECT) are both effective. However, a 2005 Cochrane review of drug treatments could not find a clear benefit for combination treatment with antidepressant and antipsychotic medication over antidepressants alone. The current updated Cochrane review (2015) incorporated two larger studies and found evidence of superiority for combination treatment. The review was constrained by the small number of available studies and could not address key questions such as the relative merits of antipsychotics and/or antidepressants compared with ECT or ketamine in acute treatment, and which treatments are best for long-term maintenance and prevention of recurrence. However, the methodology used was rigorous and the review gives the best summary to date of the evidence, as well as providing a platform for informing future research.
NHS Education for Scotland (NES) has developed a suite of training to address the learning and development needs of supervisors of psychological therapies in the National Health Service (NHS) in Scotland and to support quality of evidence-based practice in psychological therapies, in light of the recent expansion in this area of healthcare. In parallel with the structure of the recently developed supervisory competency frameworks, an initial training package addressing generic (cross-modality) supervision competences was supplemented by the development of a training package to meet the specific needs of supervisors of CBT: NES Specialist Supervision Training in CBT (NESSST CBT). A blended learning package was developed, in light of the emerging evidence around the effectiveness of e-learning, to produce a flexible and learner-centred training package. This paper describes the development, delivery and planned evaluation methods of NESSST CBT. Lessons learned during implementation are outlined, along with key challenges regarding the future of supervision training in Scotland and the UK.
Glutamate receptor modulators, including ketamine, are possible candidates for new antidepressants with a novel mode of action. The pair of reviews discussed in this month's Round the Corner considered their use in treating unipolar major depression and bipolar depression. Promising results were seen for ketamine, but further studies are needed, in particular to investigate whether the benefits are sustained or can be extended by repeated or adjunctive treatment, whether ketamine is effective in treatment resistance, whether other modes of administration are as effective as the intravenous route and the long-term adverse effects of use.
Keeping up to date with the best evidence on treatment interventions is an essential part of clinical practice, but it can seem an overwhelming task for busy clinicians. Systematic reviews and meta-analyses provide a useful and convenient summary of knowledge and form an essential part of an evidence-based approach to clinical practice. However, these reviews vary in methodology and therefore in the quality of the recommendations they provide. Clinicians need to feel confident in their skills of critical appraisal, so that they can assess the relative merits of systematic reviews. In this article we discuss the strengths and limitations of different types of evidence synthesis to enable the reader to feel more confident in assessing the scientific information to use in clinical practice.
Plutonium metal is a very unusual element, exhibiting six allotropes at ambient pressure, between room temperature and its melting point, a complicated phase diagram, and a complex electronic structure. Many phases of plutonium metal are unstable with changes in temperature, pressure, chemical additions, or time. This strongly affects structure and properties, and becomes of high importance, particularly when considering effects on structural integrity over long periods of time [1]. This paper presents a time-dependent neutron total scattering study of the local and average structure of naturally aging δ-phase 239Pu-Ga alloys, together with preliminary results on neutron tomography characterization.
Self-harm is a significant social and healthcare problem, with substantial morbidity and healthcare costs. It has strong links to further self-harm and to suicide. The current review is one of three that investigate interventions in preventing recurrence of self-harm, and it focuses on pharmacological treatment. The conclusions are limited by the small number and size of trials identified, and the low quality of evidence. No benefit on recurrence of self-harm was detected in three small trials of antidepressants, but the types studied are ones that are now less commonly used. A small trial of flupentixol suggested a possible benefit on repetition, but this has not been replicated. One small trial of lithium showed no benefit, but this was in contrast to a recent large meta-analysis showing a significant anti-suicidal effect of lithium when used to treat mood disorder. The review highlights important areas for further research.
The internet provides access to what is often a bewildering array of medical knowledge on mental health, some (but not all) of which is evidence based. As well as information for clinicians, there has been a dramatic increase in the variety and quality of information available for patients and carers. In this article we discuss the advantages and limitations of the types of information available, with suggested sites and strategies for assessing their relative merits.
Anxiety disorders are common, often have a chronic course and frequentlycoexist with other psychiatric disorders. Psychological therapy isrecommended as first-line treatment, but equitable access remains achallenge. This month's Cochrane Corner review assesses the evidence for theefficacy of therapist-supported cognitive-behavioural therapy (CBT) foranxiety disorders delivered via the internet. Although internet delivery oftherapy is attractive for many reasons, and the results of this preliminaryreview suggest that it is efficacious, this is a rapidly expanding field.Further updates of this review will include more evidence to support orrefute the use of this new method of treatment delivery, either alongside orin preference to standard face-to-face CBT.