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After years of slow and fragmented implementation of telemental health (TMH), the coronavirus disease (COVID-19) pandemic necessitated widespread adoption. With the initial state of public health emergency behind us, we are at a decision point on whether to continue with TMH or return to a largely in-person care model. In this qualitative study, we investigated clinicians' perspectives on advantages and disadvantages of TMH in outpatient mental healthcare as well as considerations for future implementation. We conducted 29 semistructured interviews with outpatient mental health providers. Data were analyzed using rapid qualitative analysis methodology. Advantages included increased utilization of services, improved therapeutic processes, and improved provider wellbeing. Providers, however, also noted that TMH has some disadvantages in terms of therapeutic processes and provider wellbeing, and they reported technology issues as an additional disadvantage. Overall providers reported they can provide high quality care via TMH, but indicated some patient populations and appointment types are a better fit for in-person services. Most providers preferred a hybrid model of care moving forward with reimbursement discrepancies and out-of-state licensure restrictions as barriers. They indicated that, as TMH becomes a mainstay in psychiatric care, training and professional guidelines will be important. Continued implementation of TMH alongside in-person care is likely to offer improved access and enhanced service quality when applied to the right patient populations and appointment types. Effective implementation may require policy and systems level support on equitable reimbursement rates, out-of-state licensure restrictions and professional guidelines for delivering TMH. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Virtual human technologies are now being widely explored as therapy tools for mental health disorders including depression and anxiety. These technologies leverage the ability of the virtual agents to engage in naturalistic social interactions with a user to elicit behavioural expressions which are indicative of depression and anxiety. Research efforts have focused on optimising the human-like expressive capabilities of the virtual human, but less attention has been given to investigating the effect of virtual human mediation on the expressivity of the user. In addition, it is still not clear what an optimal task is or what task characteristics are likely to sustain long term user engagement. To this end, this paper describes the design and evaluation of virtual human-mediated tasks in a user study of 56 participants. Half the participants complete tasks guided by a virtual human, while the other half are guided by text on screen. Self-reported PHQ9 scores, biosignals and participants' ratings of tasks are collected. Findings show that virtual-human mediation influences behavioural expressiveness and this observation differs for different depression severity levels. It further shows that virtual human mediation improves users' disposition towards tasks.

ObjectivesTo investigate changes in daily mental health (MH) service use and mortality in response to the introduction and the lifting of the COVID-19 ‘lockdown’ policy in Spring 2020.DesignA regression discontinuity in time (RDiT) analysis of daily service-level activity.Setting and participantsMental healthcare data were extracted from 10 UK providers.Outcome measuresDaily (weekly for one site) deaths from all causes, referrals and discharges, inpatient care (admissions, discharges, caseloads) and community services (face-to-face (f2f)/non-f2f contacts, caseloads): Adult, older adult and child/adolescent mental health; early intervention in psychosis; home treatment teams and liaison/Accident and Emergency (A&E). Data were extracted from 1 Jan 2019 to 31 May 2020 for all sites, supplemented to 31 July 2020 for four sites. Changes around the commencement and lifting of COVID-19 ‘lockdown’ policy (23 March and 10 May, respectively) were estimated using a RDiT design with a difference-in-difference approach generating incidence rate ratios (IRRs), meta-analysed across sites.ResultsPooled estimates for the lockdown transition showed increased daily deaths (IRR 2.31, 95% CI 1.86 to 2.87), reduced referrals (IRR 0.62, 95% CI 0.55 to 0.70) and reduced inpatient admissions (IRR 0.75, 95% CI 0.67 to 0.83) and caseloads (IRR 0.85, 95% CI 0.79 to 0.91) compared with the pre lockdown period. All community services saw shifts from f2f to non-f2f contacts, but varied in caseload changes. Lift of lockdown was associated with reduced deaths (IRR 0.42, 95% CI 0.27 to 0.66), increased referrals (IRR 1.36, 95% CI 1.15 to 1.60) and increased inpatient admissions (IRR 1.21, 95% CI 1.04 to 1.42) and caseloads (IRR 1.06, 95% CI 1.00 to 1.12) compared with the lockdown period. Site-wide activity, inpatient care and community services did not return to pre lockdown levels after lift of lockdown, while number of deaths did. Between-site heterogeneity most often indicated variation in size rather than direction of effect.ConclusionsMH service delivery underwent sizeable changes during the first national lockdown, with as-yet unknown and unevaluated consequences.

In an effort to better understand the drug metabolism and pharmacokinetics (DMPK) properties of glycopyrronium bromide (1), a muscarinic acetylcholine receptor antagonist, a C-14 labeled isotopologue was required. The compound was prepared in five synthetic steps and 5% overall radiochemical yield from Cu14 CN. During the synthesis, an unexpected decarboxylation of phenylglyoxylate resulted in the loss of much of the radiolabeled compound. Chiral chromatography was utilized to isolate and deliver the proper pair of enantiomers as [14 C]-1.

Background: The Patient Health Questionnaire-9 (PHQ-9) is a widely used instrument for measuring levels of depression in patients in clinical practice and academic research; its factor structure has been investigated in various samples, with limited evidence of measurement equivalence/invariance (ME/I) but not in patients with more severe depression of long duration. This study aims to explore the factor structure of the PHQ-9 and the ME/I between treatment groups over time for these patients. Methods: 187 secondary care patients with persistent major depressive disorder (PMDD) were recruited to a randomised controlled trial (RCT) with allocation to either a specialist depression team arm or a general mental health arm; their PHQ-9 score was measured at baseline, 3, 6, 9 and 12 months. Exploratory Structural Equational Modelling (ESEM) was performed to examine the factor structure for this specific patient group. ME/I between treatment arm at and across follow-up time were further explored by means of multiple-group ESEM approach using the best-fitted factor structure. Results: A two-factor structure was evidenced (somatic and affective factor). This two-factor structure had strong factorial invariance between the treatment groups at and across follow up times. Limitations: Participants were largely white British in a RCT with 40% attrition potentially limiting the study’s generalisability. Not all two-factor modelling criteria were met at every time-point. Conclusion: PHQ-9 has a two-factor structure for PMDD patients, with strong measurement invariance between treatment groups at and across follow-up time, demonstrating its validity for RCTs and prospective longitudinal studies in chronic moderate to severe depression.

BackgroundThe 17-item Hamilton Depression Rating Scale (HDRS17) is used world-wide as an observer-rated measure of depression in randomised controlled trials (RCTs) despite continued uncertainty regarding its factor structure. This study investigated the dimensionality of HDRS17 for patients undergoing treatment in UK mental health settings with moderate to severe persistent major depressive disorder (PMDD).MethodsExploratory Structural Equational Modelling (ESEM) was performed to examine the HDRS17 factor structure for adult PMDD patients with HDRS17 score ≥16. Participants (n = 187) were drawn from a multicentre RCT conducted in UK community mental health settings evaluating the outcomes of a depression service comprising CBT and psychopharmacology within a collaborative care model, against treatment as usual (TAU). The construct stability across a 12-month follow-up was examined through a measurement equivalence/invariance (ME/I) procedure via ESEM.ResultsESEM showed HDRS17 had a bi-factor structure for PMDD patients (baseline mean (sd) HDRS17 22.6 (5.2); 87% PMDD >1 year) with an overall depression factor and two group factors: vegetative-worry and retardation-agitation, further complicated by negative item loading. This bi-factor structure was stable over 12 months follow up. Analysis of the HDRS6 showed it had a unidimensional structure, with positive item loading also stable over 12 months.ConclusionsIn this cohort of moderate-severe PMDD the HDRS17 had a bi-factor structure stable across 12 months with negative item loading on domain specific factors, indicating that it may be more appropriate to multidimensional assessment of settled clinical states, with shorter unidimensional subscales such as the HDRS6 used as measures of change.

Aim Nottinghamshire Healthcare NHS Foundation Trust (NHFT) provides a variety of mental health services across Nottinghamshire. During out-of-hours work, junior doctors cover each of these three main hospital sites. The Health Education East Midlands (HEE) Quality Management visit concluded the handover system in NHFT was not fit for purpose, posing significant risks to both patients and junior doctors. The aim of our quality improvement project was to assess these concerns using a mixed methodology, including local surveys and audit; and secondly to make any necessary quality improvements to the handover process and guidance. The pre-implementation evaluation of the handover system in use consisted of a survey and an audit. Methods The quality improvement strategy involved a two-pronged approach, which included the development of a new IT-based handover recording tool and improving education and training in its use. We used Plan-Do-Study-Act (PDSA) cycles between August 2015 and August 2016 to implement changes. Phase 2 of the project involved audit, education and training to consolidate and reinforce the change to make it sustainable through creation of a white board animation video for junior doctors. Results Percentage of recorded handovers was the main outcome measure. Quality outcomes improved after the phase 1 and were sustained during the phase 2 of the project due to introduction of mandatory recording fields. Conclusion We learnt that the active engagement of end users in the designing and implementation of the new IT handover system was a key factor in optimal development. We learnt that continuous induction, training and monitoring are important to sustain high usage of the system. Also, use of project management tools from the start will improve efficiency and time management. This project demonstrates how existing resources within a NHS Trust can be collaboratively and iteratively deployed to improve patient care.

Summary Background Persistent moderate or severe unipolar depression is common and expensive to treat. Clinical guidelines recommend combined pharmacotherapy and psychotherapy. Such treatments can take up to 1 year to show an effect, but no trials of suitable duration have been done. We investigated the efficacy and cost-effectiveness of outpatient-based, specialist depression services (SDS) versus treatment as usual (TAU) on depression symptoms and function. Methods We did a multicentre, single-blind, patient-level, parallel, randomised controlled trial (RCT), as part of the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) study, in three mental health outpatient settings in England. Eligible participants were in secondary care, were older than 18 years, had unipolar depression (with a current major depressive episode, a 17-item Hamilton Depression Rating Scale [HDRS 17 ] score of ≥16, and a Global Assessment of Function [GAF] score of ≤60), and had not responded to 6 months or more of treatment for depression. Randomisation was stratified by site with allocation conveyed to a trial administrator, with research assessors masked to outcome. Patients were randomised (1:1) using a computer-generated pseudo-random code with random permuted blocks of varying sizes of two, four, or six to either SDS (collaborative care approach between psychiatrists and cognitive behavioural therapists for 12 months, followed by graduated transfer of care up to 15 months) or to the TAU group. Intention-to-treat primary outcome measures were changes in HDRS 17 and GAF scores between baseline and 6, 12, and 18 months' follow-up. We will separately publish follow-up outcomes for months 24 and 36. Clinical efficacy and cost-effectiveness were examined from health and social care persp ectives at 18 months, as recommended by the National Institute for Health and Care Excellence. This trial is registered at ClinicalTrials.gov (NCT01047124) and the ISRCTN registry (ISRCTN10963342); the trial has ended. Findings 307 patients were assessed for eligibility between Dec 21, 2009, and Oct 31, 2012. 94 patients were assigned to TAU and 93 patients to SDS, and were included in intention-to-treat analyses. The changes from baseline to 6 months in HDRS 17 and GAF scores did not significantly differ between treatment groups (mean change difference in HDRS 17 score −1·01 [95% CI −3·30 to 1·28], p=0·385; and in GAF score 1·33 [–2·92 to 5·57], p=0·538). Primary outcome data were available for 134 (72%) patients at 12 months. We noted no differences at 12 months' follow-up between SDS and TAU for mean HDRS 17 score (14·8 [SD 7·9] in the SDS group vs 17·2 [7·3] in the TAU group, p=0·056) or GAF score (60·4 [11·7] vs 55·8 [12·7], p=0·064), and the changes from baseline to 12 months in HDRS 17 and GAF scores did not significantly differ between treatment groups (mean change difference in HDRS 17 score −2·45 [95% CI −5·04 to 0·14], p=0·064; and in GAF score 4·12 [–0·11 to 8·35], p=0·056). The mean change in HDRS 17 score from baseline to 18 months was significantly improved in the SDS group compared with the TAU group (13·6 [SD 8·8] in the SDS group vs 16·1 [6·6] in the TAU group; mean change difference −2·96 [95% CI −5·33 to −0·59], p=0·015), but the GAF scores showed no significant differences between the groups (61·2 [SD 13·0] vs 57·7 [11·9]; mean change difference 3·82 [–9·3 to 8·57], p=0·113). We reported no deaths, but one (1%) patient was admitted to hospital for myocardial infarction, and three episodes of self-harm were reported in three (2%) patients (two receiving TAU, one receiving SDS care). The incremental cost-effectiveness ratio of SDS versus TAU was £43 603 per quality-adjusted life-year. Interpretation Compared with usual specialist mental health secondary care, SDS might improve depression symptoms for patients with persistent moderate to severe depression, but functional outcomes and economic benefits are equivocal. Funding National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care, UK Medical Research Council, Nottinghamshire Healthcare NHS Foundation Trust, Derbyshire Healthcare NHS Foundation Trust, Cambridgeshire and Peterborough NHS Foundation Trust, University of Nottingham.

BackgroundRecent models of major depressive disorder (MDD) have proposed the rostral anterior cingulate (rACC) and dorsomedial prefrontal cortex (dmPFC) as nexus sites in the dysfunctional regulation of cognitive-affective state. Limited evidence from remitted-state MDD supports these theories by suggesting that aberrant neural activity proximal to the rACC and the dmPFC may play a role in vulnerability to recurrence/relapse within this disorder. Here we present a targeted analysis assessing functional activity within these two regions of interest (ROIs) for groups with identified vulnerability to MDD: first, remitted, high predicted recurrence-risk patients; and second, patients suffering observed 1-year recurrence.MethodBaseline T2* images sensitive to blood oxygen level-dependent (BOLD) contrast were acquired from patients and controls during a Go/No-Go (GNG) task incorporating negative feedback, with 1-year patient follow-up to identify recurrence. BOLD contrast data for error commission (EC) and visual negative feedback (VNF) were used in an ROI analysis based on rACC and dmPFC coordinates from the literature, comparing patientsversuscontrols and recurrenceversusnon-recurrenceversuscontrol groups.ResultsAnalysis of patients (n = 20)versuscontrols (n = 20) showed significant right dmPFC [Brodmann area (BA) 9] hypoactivity within the patient group, co-localized during EC and VNF, with additional significant rACC (BA 32) hypoactivity during EC. The results from the follow-up analysis were undermined by small groups and potential confounders but suggested persistent right dmPFC (BA 9) hypoactivity associated with 1-year recurrence.ConclusionsConvergent hypoactive right dmPFC (BA 9) processing of VNF and EC, possibly impairing adaptive reappraisal of negative experience, was associated most clearly with clinically predicted vulnerability to MDD.

BackgroundPatients in recovery following episodes of major depressive disorder (MDD) remain highly vulnerable to future recurrence. Although psychological determinants of this risk are well established, little is known about associated biological mechanisms. Recent work has implicated the default mode network (DMN) in this vulnerability but specific hypotheses remain untested within the high risk, recovered state of MDD.AimsTo test the hypothesis that there is excessive DMN functional connectivity during task performance within recovered-state MDD and to test for connected DMN cortical gyrification abnormalities.MethodA multimodal structural and functional magnetic resonance imaging (fMRI) study, including task-based functional connectivity and cortical folding analysis, comparing 20 recovered-state patients with MDD with 20 matched healthy controls.ResultsThe MDD group showed significant task-based DMN hyperconnectivity, associated with hypogyrification of key DMN regions (bilateral precuneus).ConclusionsThis is the first evidence of connected structural and functional DMN abnormalities in recovered-state MDD, supporting recent hypotheses on biological-level vulnerability.

The present study employed high-density ERPs to examine the effect of induced sad mood on the spatiotemporal correlates of conflict monitoring and resolution in a colour-word Stroop interference task. Neuroimaging evidence and dipole modelling implicates the involvement of the anterior cingulate cortex (ACC) and medial prefrontal cortex (mPFC) regions in conflict-laden interference control. On the basis that these structures have been found to mediate emotion-cognition interactions in negative mood states, it was predicted that Stroop-related cognitive control, which relies heavily on anterior neural sources, would be affected by effective sad mood provocation. Healthy participants (N=14) were induced into transient sadness via use of autobiographical sad scripts, a well-validated mood induction technique (Liotti et al., 2000a, 2002). In accord with previous research, interference effects were shown at both baseline and sad states while Stroop conflict was associated with early (N450) and late (Late Positive Component; LPC) electrophysiological modulations at both states. Sad mood induction attenuated the N450 effect in line with our expectation that it would be susceptible to modulation by mood, given its purported anterior limbic source. The LPC effect was displayed at the typical posterior lateral sites but, as predicted, was not affected by sad mood. However, frontocentral LPC activity-presumably generated from an additional anterior limbic source-was affected at sad state, hinting a role in conflict monitoring. Although the neurophysiological underpinnings of interference control are yet to be clarified, this study provided further insight into emotion-cognition interactions as indexed by Stroop conflict-laden processing.

Background. We assess claims that the documented rise in psychiatric morbidity during the nineteenth and twentieth centuries was associated with an increasing incidence of schizophrenia.Method. Cross-sectional epidemiological comparison of the incidence of schizophrenia in one urban, industrialized community at three points over more than 100 years using new data from 1881–1902 and two pre-existing datasets, 1978–1980 and 1992–1994. For 1881–1902, 34 cases of schizophrenia were obtained through retrospective diagnosis, using Research Diagnostic Criteria, of a random 14·5% sample of first admissions to Nottingham Asylum (n=330). Inter-rater reliability and leakage analyses were performed. The administrative incidence for all three studies was directly standardized against 1991 census data. Local statistics on total psychiatric morbidity in Nottingham were taken from the asylum superintendent's register and recent data from the Office of National Statistics.Results. Official local and national rates of total psychiatric morbidity increased exponentially. There was no significant change in the incidence of schizophrenia over the 114-year period 1881–1994.Conclusions. The rise in both local and national official statistics of psychiatric morbidity 1881–1994 was not associated with a significant increase in the incidence of schizophrenia. Stability in the epidemiology of schizophrenia at a geographical level is found despite important demographic changes.

Madness: A Very Short Introduction By Andrew Scull. Oxford University Press. 2011. £7.99 (pb). 152 pp. ISBN: 9780199608034 Here, in just over 100 pages, Scull accepts the task of providing a stimulating way into the subject of ‘madness’; a ‘commonsense category, reflecting our culture's...