Cross-linguistic studies have demonstrated that individuals with schizophrenia-particularly those exhibiting formal thought disorder (FTD)-show distinctive distributions of noun phrases (NPs) in spontaneous speech. NPs (e.g., the picture; a husband) serve to organize the referential structure of meaning. Extracting such referential NP features, however, has traditionally required manual annotations. In this study we applied state-of-the-art large language models (LLMs) to extract these features automatically, using an existing, manually annotated dataset, in which English-speaking participants described a comic strip: 30 individuals with schizophrenia (SZ) (15 with moderate or severe FTD (SZ + FTD), 15 with minimal or no FTD (SZ-FTD), 15 neurotypical controls (NC). We first show that LLM-based analyses replicate the findings based on manual annotation, particularly highlighting that definite NPs tied to prior discourse, markers of grammatical and cognitive complexity and narrative coherence, were underused in the SZ + FTD group. Secondly, we demonstrate that LLMs, especially when used with in-context (few-shot) learning, offer a promising avenue for the automatic extraction of referential features. These results show that a cross-linguistically validated and clinically important linguistic pattern of deviance is accessible to automatized assessment with NLP.

Introduction Bipolar disorder affects around 2% of the population and is linked with reduced life expectancy and socioeconomic burden. Depressive episodes are difficult to treat and typically more prevalent, enduring and burdensome than manic episodes. The use of antidepressants alone has limited effect and is associated with significant clinical risk through polarity switch. Current National Institute for Health and Care Excellence guidelines recommend quetiapine, olanzapine (with or without fluoxetine) and lamotrigine; however, these medications have limited efficacy, tolerability and acceptability. The ASCEnD study aims to assess the clinical and cost-effectiveness of aripiprazole plus sertraline compared with quetiapine, offering potential improvements for outcomes in bipolar depression. The study is funded by the National Institute for Health and Care Research Health Technology Assessment programme (NIHR132773).Methods and analysis ASCEnD is a prospective, two-arm, superiority, individually 1:1 randomised, controlled, pragmatic, parallel group, type A open-label clinical trial of aripiprazole/sertraline medication combination compared with quetiapine for bipolar depression. The study is conducted in the UK National Health Service setting with the aim of recruiting and randomising 270 participants followed-up for 24 weeks. Adults with bipolar disorder self-refer or are recruited through primary and secondary care services. The primary outcome is change in depressive symptoms 12–16 weeks after randomisation. Secondary outcomes include measures of symptom change, treatment satisfaction, tolerability, medication adherence, concomitant medication use, psychosocial functioning, quality of life and cost-effectiveness and informal carer measures of quality of life and costs of caring. The exploratory outcome is change in participant reward and punishment responsiveness. Analysis will follow a prespecified statistical analysis plan. A nested qualitative study is included to examine feasibility and acceptability of the trial design.Ethics and dissemination A Clinical Trial Authorisation from Medicines and Healthcare products Regulatory Agency, and approval from the Health Research Authority (IRAS 1007468) and North East – Newcastle and North Tyneside 1 Research Ethics Committee (23/NE/0132) were obtained. Results will be disseminated through peer-reviewed publications, conference presentations and lay summaries for participants and patient and public groups.Trial registration number ISRCTN63917405.

BACKGROUND:Growing evidence highlights maternal risk factors that can increase the likelihood of traumatic childbirth experience. Yet little is known about the availability of primary antenatal intervention for childbirth trauma to facilitate optimal maternal and infant outcomes. The aim of this study was to conduct a systematic review of the literature and empirical evidence to identify antenatal interventions and their effectiveness for treatment of childbirth trauma, post-traumatic stress disorder (PTSD), subthreshold PTSD, or post-traumatic stress (PTS) from childbirth. METHODS:Four databases were accessed: PUBMED, CINAHL, ProQuest, and EBSCOHOST. PRISMA guidelines were followed for screening and reporting. Inclusion criteria were as follows: (1) peer reviewed articles; (2) samples of pregnant women; (3) published in English; (4) measure of PTSD, PTSD symptoms, PTS or fear of childbirth; (5) variable of childbirth trauma or childbirth experience; (6) antenatal intervention; and (7) human studies. RESULTS:We identified 2034 articles, with 12 articles in the final sample. The most common antenatal intervention in four studies was childbirth plans, which were associated with an increase in positive childbirth experience, childbirth control, mastery, and participation, as well as increased self-efficacy and reduced PTSD symptoms (p < 0.01). Other interventions included antenatal counseling and psychoeducation; eye movement desensitization and reprocessing; counseling; haptotherapy; trauma-informed care; cognitive behavioral therapy; and hypnosis for childbirth trauma. CONCLUSIONS:Methodological limitations as well as a lack of inclusion of women with perinatal mental health difficulties represent gaps in knowledge. Findings suggest promising evidence for the implementation of antenatal interventions in clinical and hospital contexts to treat childbirth trauma.

Despite global recognition of childbirth trauma, as well as identifiable factors in pregnancy that may increase its occurrence, there is an absence of accessible and cost-effective primary (i.e., before childbirth) antenatal intervention. This study describes an antenatal intervention, Sensitive Care Birth Plans (SCBP), currently implemented at the Women and Newborn Health Service (WNHS) in Western Australia and aims to analyse the maternal and infant characteristics of women accessing it for childbirth trauma. Data were drawn from 126 patient files, which was the total number of women identified with SCBPs from January to December 2022 at WNHS in a retrospective file review. Where possible, outcomes of the SCBP cohort are compared to all other women who birthed during the same period at the service. Data were analysed using descriptive and inferential statistics. The SCBP cohort was 14.1–44.4 years of age (M = 30.34 years). Most women were diagnosed with the diagnostic category of a neurotic, stress-related and somatoform disorder (85.3

Objectives Previous studies have established that higher Sense of Coherence (SoC) predicts lower pregnancy-specific distress, fewer delivery complications, and increased birth satisfaction. However, less is known about how SoC typically changes over pregnancy, birth, and postnatally and the risk factors and protective factors contributing to SoC trajectory during the perinatal period. In this study, we aim to describe and predict common trajectories of SoC in the perinatal period.Methods 680 women in the Mercy Pregnancy and Emotional Wellbeing Study completed measures of SoC on four occasions across pregnancy and the postpartum. Predictors included history of childhood trauma, expectations and outcomes from birth and the postpartum, and postpartum social support. Depression was assessed by structured clinical interview in early pregnancy. Growth mixture modeling was used to classify participants into trajectories of SoC, and multinomial logistic regression models predicted class membership.Results Four trajectories were identified: (1) High (67%), (2) Low (21%), (3) Rising (8%), (4) Falling (3%). The strongest predictors of class were depression diagnosis, associated with Low and Rising trajectories, and a history of childhood trauma, associated with Low and Falling trajectories.Conclusion Childhood trauma was thus predictive of a poor SoC at 12 months postpartum, suggesting that pregnancy and birth have a negative impact on women's resilience resources, whereas depression in early pregnancy is more predictive of poorer starting point of SoC. Targeted mental health support in the perinatal period may ensure individuals have adequate coping resources.

BACKGROUND:Depression is a leading cause of disability worldwide, with general practitioners (GPs) playing a crucial role in its identification and management. Despite this central position, GPs face challenges in diagnosing depression. Previous qualitative research has focused on clinical and interactional aspects of depression diagnosis in primary care, including uncertainty and negotiation; this study examines logistical and practical challenges in diagnosis. AIM:To explore GP perspectives of the challenges in diagnosing depression and providing initial support in primary care. DESIGN & SETTING:Qualitative study involving GPs across Scotland, the North-East of England and Northern Ireland. METHOD:Semi-structured interviews were conducted with GPs, recruited through clinical networks of the research team who were contacted via email, followed by a snowball sampling strategy. Interviews were recorded, transcribed and thematically analysed. Themes were developed to explore GPs' perspectives of the challenges in diagnosing depression. RESULTS:Ten GPs from a range of practice locations were interviewed. Three themes were developed highlighting the challenges that GPs face in diagnosing depression: (1) Complexity of presentation; (2) Constraints on access and time; (3) Continuity of care. CONCLUSION:Diagnostic challenges for depression in primary care are shaped by clinical complexity, time constraints, and continuity of care. Addressing these factors may help GPs navigate diagnostic uncertainty and provide earlier support for patients presenting with depressive symptoms.

BACKGROUND:Depression is associated with increased mortality, with underlying causes unclear. We conducted a systematic review and meta-analysis of cardiovascular (CV) mortality in depression and how antidepressant treatments and comorbidities modify this. METHODS:We searched Medline, Embase, Scopus, Web of Science and Cochrane registers (inception to 31 December 2024) for randomised controlled trials (RCTs) and observational studies comparing CV mortality in adults with depression vs without, and receiving antidepressants vs controls. We excluded studies with <12 months follow-up, reporting only all-cause mortality or lacking control groups. Random-effects meta-analyses were conducted with CV mortality as the primary outcome. Risk of bias was assessed with RoB 2 and ROBINS-I. PROSPERO:CRD42020200812. RESULTS:We included 7 RCTs and 47 cohort studies (1,593,722 people). In multivariable-adjusted cohorts (k = 26), depression was associated with a significantly higher CV mortality versus no-depression (hazard ratio (HR): 1.45, 95% CI: 1.25-1.69). Effects were similar in non-selected community-dwelling cohorts and those with CV disease or type 2 diabetes. Antidepressants overall were associated with increased CV mortality in cohorts but after adjustment only tricyclic antidepressants (TCAs) had significantly increased risk vs no antidepressant (k = 4; HR: 1.27, 95% CI: 1.02-1.58). RCT findings were directionally consistent but underpowered. CONCLUSIONS:Depression is associated with increased risk of CV mortality irrespective of comorbid group studied. Antidepressants do not appear to modify this risk, apart from TCAs, which may increase it. The antidepressant models in particular had high heterogeneity, reflecting a knowledge gap on the long-term effects of antidepressants in patients with depression on CV mortality.

BACKGROUND:About 30% of patients with depression treated with antidepressant medication do not respond sufficiently to the first agents used. Pramipexole might usefully augment antidepressant medication in such cases of treatment-resistant depression, but data on its effects and tolerability are scarce. We aimed to assess the efficacy and tolerability of pramipexole augmentation of ongoing antidepressant treatment, over 48 weeks, in patients with treatment-resistant depression. METHODS:We did a multicentre, double-blind, placebo-controlled randomised trial in which adults with resistant major depressive disorder were randomly assigned (1:1; using an online randomisation system) to 48 weeks of pramipexole (titrated to 2·5 mg) or placebo added to their ongoing antidepressant medication. The study was conducted in nine National Health Service Trusts in England. Participants, investigators, and researchers involved in recruitment and assessment were masked to group allocation, and the central pharmacy team dispensing the medication was not masked. The primary outcome was change from baseline to week 12 in the total score of the 16-item Quick Inventory of Depressive Symptomology self-report version (QIDS-SR16). The primary analysis was performed on the intention-to-treat population that included all eligible, randomly assigned participants. People with lived experience were involved in the design, oversight, and interpretation of the study. The trial was registered with ISCTRN (ISRCTN84666271) and EudraCT (2019-001023-13) and is complete. FINDINGS:Between Feb 16 and May 29, 2024, 217 participants attended a screening visit, of whom 66 were excluded due to ineligibility. 151 participants were randomly assigned (75 to the pramipexole group and 75 to the placebo group, after one participant was found to be ineligible after randomisation). 84 (56%) participants were female and 66 (44%) were male and the mean age of participants was 44·9 years (SD 14·0). Ethnicity data were not available. The mean QIDS-SR16 total score at baseline was 16·4 (SD 3·4) in the pramipexole group and 16·2 (3·5) in the placebo group. The mean dose of pramipexole received at week 12 was 2·3 mg (SD 0·45). Adjusted mean decrease from baseline to week 12 of the QIDS-SR16 total score was 6·4 (SD 4·9) for the pramipexole group and 2·4 (4·0) for the placebo group; the mean difference between groups was -3·91 (95% CI -5·37 to -2·45; p<0·0001). Termination of trial treatment due to adverse events was more frequent in the pramipexole group (15 participants [20%]) than in the placebo group (four participants [5%]), with reported adverse events consistent with known side-effects of pramipexole, in particular nausea, headache, and sleep disturbance or somnolence. INTERPRETATION:In this trial involving participants with treatment-resistant depression, pramipexole augmentation of antidepressant treatment, at a target dose of 2·5 mg, demonstrated a reduction in symptoms relative to placebo at 12 weeks but was associated with some adverse effects. These results suggest that pramipexole is a clinically effective option for reducing symptoms in patients with treatment-resistant depression. Future trials directly comparing pramipexole with existing treatments for this disorder are needed. FUNDING:National Institute of Health and Care Research, Efficacy and Mechanism Evaluation Programme.

BACKGROUND:Sustained attention is integral to goal-directed tasks in everyday life. It is a demanding and effortful process prone to failure. Deficits are particularly prevalent in mood disorders. However, conventional methods of assessment, rooted in overall measures of performance, neglect the nuanced temporal dimensions inherent in sustained attention, necessitating alternative analytical approaches. METHODS:This study investigated sustained attention deficits and temporal patterns of attentional fluctuation in a large clinical cohort of patients with bipolar depression (BPd, n = 33), bipolar euthymia (BPe, n = 84), major depression (MDd, n = 38) and controls (HC, n = 138) using a continuous performance task (CPT). Longitudinal and spectral analyses were employed to examine trial-level reaction time (RT) data. RESULTS:Longitudinal analysis revealed a significant worsening of performance over time (vigilance decrement) in BPd, whilst spectral analysis unveiled attentional fluctuations concentrated in the frequency range of 0.077 Hz (1/12.90 s)-0.049 Hz (1/20.24 s), with BPd and MDd demonstrating greater spectral power compared to BPe and controls. CONCLUSIONS:Although speculative, the increased variability in this frequency range may have an association with the dysfunctional activity of the Default Mode Network, which has been shown to oscillate at a similar timescale. These findings underscore the importance of considering the temporal dimensions of sustained attention and show the potential of spectral analysis of RT in future clinical research.

Background:There are limited options currently recommended in National Institute for Health and Care Excellence guidelines for the treatment of bipolar depression. Pramipexole has been shown to improve mood symptoms in two small pilot studies in such patients. Objectives:Primary: to evaluate the clinical effectiveness of pramipexole versus placebo alongside routine mood-stabilising medications over 12 weeks in patients with treatment-resistant bipolar depression. Secondary: evaluate the impact of pramipexole on mood and anxiety, psychosocial function, cost-effectiveness, and safety and tolerability over 48 weeks. Design:Multicentre, randomised, placebo-controlled trial of pramipexole versus placebo in addition to standard-of-care mood stabilisers. Clinicians, researchers and participants were blinded throughout the duration of the study. Pre-randomisation stage (to adjust antipsychotics or commence mood stabilisers where required) before randomisation. Weekly online assessments of mood and anxiety from randomisation to week 52, with psychosocial function, quality of life and healthcare resource utilisation assessments conducted at regular intervals. Setting:Twenty-one National Health Service trusts and Health Boards across England and Scotland. Participants:Patients aged 18 years and over with a diagnosis of treatment-resistant bipolar depression currently under secondary care mental health services. Aim to randomise 290 participants. Interventions:Pramipexole or matched placebo orally once daily, titrated from 0.25 mg to maximum of 2.5 mg (salt weight) depending on efficacy and tolerability. Main outcome measures:Depression - Quick Inventory for Depressive Symptomology; anxiety - Generalised Anxiety Disorder-7-item scale; psychosocial functioning - Work and Social Adjustment Scale; hypomania/mania - Altman Self-rating Scale of Mania; tolerability - Treatment Satisfaction Questionnaire for Medication; well-being and quality of life - EuroQol-5 Dimensions, five-level version, ICEpop CAPability measure for Adults and Oxford CAPabilities questionnaire-Mental Health tools. Results:Thirty-nine participants randomised (18 to pramipexole and 21 to placebo) with 36 providing data for the primary analysis. Pramipexole led to greater reductions in depressive symptoms at 12 weeks compared to placebo [4.4 (4.8) vs. 2.1 (5.1)]: a medium-sized (d = -0.72) but not statistically significant difference (95% confidence interval -0.4 to 6.3; p = 0.087). There were some statistically significant positive effects of pramipexole on secondary outcomes (reduction in depressive symptoms at 36 weeks, response and remission rates at trial exit, psychosocial function). Pramipexole was associated with an increased rate of hypomania/manic symptoms, but this appeared to be reduced by coadministration with an antipsychotic. General tolerability of pramipexole was good. There were significant annual gains in health-related quality of life and capability-well-being and tendency towards reduced health and social care costs. Limitations:Small sample size and variable follow-up period due to recruitment during COVID-19 pandemic and the trial closing early. Participants limited to those in secondary care mental health services. All assessments only available in English. Conclusions:No change in clinical practice can be recommended as there was not a significant difference between pramipexole and placebo on the primary efficacy outcome measure. However, there was evidence of positive effects of pramipexole on mood, psychosocial function and quality of life. Future work:Replication in a larger population and research to investigate the impact of coadministration of antipsychotics alongside pramipexole. Trial registration:This trial is registered as ISRCTN72151939 and EudraCT 2018-2869-18. Funding:This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 16/154/01) and is published in full in Health Technology Assessment; Vol. 29, No. 21. See the NIHR Funding and Awards website for further award information.

Background: Options for ‘treatment-resistant bipolar depression’ (TRBD) are limited. Two small, short-term, trials of pramipexole suggest it might be an option. Aims: To evaluate the clinical effectiveness and safety of pramipexole in the management of TRBD. Methods: A multi-centre randomised, double-blind controlled trial including participants ⩾18 years old with TRBD (failure to respond, tolerate or clinical contraindication/patient refusal of ⩾2 of quetiapine, olanzapine, lamotrigine or lurasidone) randomised 1:1 to pramipexole (max 2.5 mg/day salt weight) or placebo added to ongoing mood stabiliser ( n = 39). Primary outcome: Quick Inventory of Depressive Symptoms, Self-rated (QIDS-SR) at 12 weeks. Up to 48 weeks follow-up. Results: Pramipexole ( n = 18) was associated with a greater reduction in QIDS-SR score at 12 weeks versus placebo ( n = 21, 4.4 (4.8) vs 2.1 (5.1)): a medium sized ( d = −0.72) but not statistically significant difference (95% CI: −0.4 to 6.3, p = 0.087). Similarly, there was a non-significant approximate 2-point ( d = −0.76) improvement in pleasure at 6 weeks (95% CI: −0.11 to 4.20). Significant advantages of pramipexole on QIDS-SR score (6.28 points: 95% CI: 1.85–10.71) and psychosocial function (5.36 points: 95% CI: 0.38–10.35) were seen at 36 weeks post-randomisation, and on the response (46% vs 6%; p = 0.026) and remission (31% vs 0%; p = 0.030) rates at trial exit (48 weeks or last available data after 16 weeks for those affected by the early study closure). Hypomania ratings were significantly higher at 12 weeks. Otherwise, pramipexole was well tolerated. Conclusions: Clinically large, but statistically non-significant, effects of pramipexole on depression at 12 weeks, with significant longer-term benefits on mood and function were observed. Pramipexole use was complicated by dose titration and increased hypomanic symptoms. The small sample size limits interpretation. Furthermore, larger randomised placebo-controlled trials are warranted.

Background There are no licensed pharmacological treatments for people who are at clinical high risk of developing psychosis. Although psychological interventions are well tolerated, they do not appear to reduce the risk of later transition to psychosis. Clinically high-risk people commonly experience low-grade anxiety and psychotic symptoms. Cannabidiol is a non-intoxicating substance present in cannabis that shows promise in terms of its antipsychotic and antianxiety potential. However, no fully powered randomised clinical trial has investigated the efficacy of cannabidiol as a treatment in people with clinical high risk. Further, the mechanisms that may underlie its beneficial effects remain unclear. Objectives To conduct a double-blind, placebo-controlled randomised controlled trial to investigate the efficacy of cannabidiol as a treatment for psychotic and anxiety symptoms in people at clinical high risk, its safety and tolerability, and the neurochemical and neurophysiological basis of its effects. Design We proposed to conduct a parallel-arm, multisite, double-blind randomised control trial to evaluate the efficacy and tolerability of cannabidiol when added to treatment as usual, compared to treatment as usual plus placebo, in 300 clinically high-risk patients (n = 150 per treatment arm). In a subsample of participants (total N = 100; n = 50 per treatment arm), we proposed to use magnetic resonance spectroscopy to measure hippocampal glutamate levels, functional magnetic resonance imaging to measure brain activation (while patients performed verbal memory and emotional processing tasks), and arterial spin labelling to measure blood flow to investigate the neurochemical and neurophysiological basis of the effects of cannabidiol (mechanism substudy). Setting Multicentre study involving early intervention services within the United Kingdom. Participants Three hundred patients aged 18–35 years (N = 300; n = 150 per treatment arm) diagnosed with a clinical high-risk state for psychosis and attenuated psychotic symptoms for the randomised controlled trial. A subsample of participants (total N = 100; n = 50 per treatment arm) for the mechanism substudy. Intervention Participants were to receive a single daily dose of 600 mg cannabidiol or placebo to be taken orally for 6 months. Main outcome measure Severity of psychotic symptoms at 6 months using the Comprehensive Assessment of At-Risk Mental States. In the mechanism substudy, we aimed to compare their effects following 28 days treatment on hippocampal glutamate levels, and on brain activation while performing verbal memory and emotional processing tasks, as well as resting regional cerebral blood flow in the medial temporal cortex and basal ganglia. Results Funding for the research commenced in September 2018, when we entered a planned 6-month study set-up phase. The trial was not able to be delivered in a timely manner due to uncertainty over the drug supply, leading to eventual closure of the study in March 2022. Conclusions Here we summarise the events that led to this decision, reflect on the contributing factors and suggest potential learning points to help other researchers avoid such outcomes in future. Study limitations and future work The CANTOP-RCT did not start owing to challenges in securing supply of the study drug, and therefore addressing this issue is essential for any future definitive study to investigate the efficacy of cannabidiol as a treatment for clinical high-risk patients with attenuated psychotic symptoms. Funding This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation (EME) programme as award number 16/126/53. Plain language summary Psychosis is often preceded by a clinical high-risk state, when people have similar but shorter-lasting and less severe experiences than people with fully developed psychosis. As fully developed psychosis causes a great deal of suffering to patients and their families, there is growing interest in treating people at the clinical high-risk stage. However, current treatments for people in the clinical high-risk state do not work very well and are also not tolerated very well. Hence, at the moment, most people in a clinical high-risk state presenting to the National Health Service typically receive practical help and support from clinicians to address current issues. Cannabidiol, a naturally available chemical found in extracts of the cannabis plant, seems to be a promising candidate. However, we do not know whether cannabidiol treatment will actually be useful in relieving symptoms in clinical high-risk state patients. We received funding to test this in a large clinical trial comparing cannabidiol to placebo (a sugar pill with no active ingredient). We aimed to study 300 clinical high-risk state patients. Half of them were supposed to receive the same dose of cannabidiol (600 mg/day) that we have used before and the other half were supposed to receive a matching dummy capsule. Neither the researchers nor the patients were supposed to know what each person received during the study. At the end of 6-month treatment, we wanted to examine whether those who received cannabidiol were significantly better compared to those who received the sugar pill. We also aimed to use brain scanning in a subgroup of people (50 from each treatment group) to understand how cannabidiol might work. However, despite our best efforts, it was challenging to find a supply of high-quality cannabidiol for the trial. The COVID pandemic also posed challenges. As a result, the study was closed down before the trial could even start.

Linguistic profiles in neurological and psychiatric conditions offer critical insights into the relationship between language and broader cognitive functions. People with aphasia (PwA) can display severe language production and comprehension difficulties, often alongside relatively preserved capacity in other domains. In contrast, people with schizophrenia (PwS) can present with disordered thoughts, delusions and hallucinations, accompanied by atypical language use. We examined microstructural (lexicon, syntax) and macrostructural (narrative) features of comic strip descriptions produced by PwA, PwS, and two respective control samples, using manual annotation and computerized tools. Both clinical groups diverged from controls at microstructural and macrostructural levels. However, PwA showed greater microstructural disruption, while PwS exhibited greater macrostructural impairment. Language production in PwA differed most from PwS in the much higher rate of morphosyntactic errors, more frequent intra-clausal pauses, and a greater reduction of grammatical complexity. In PwA, performance in non-verbal reasoning and semantics tests correlated with macrostructural, but not with microstructural measures. In PwS, non-verbal reasoning scores correlated with both micro- and macrostructural measures. These findings highlight distinct effects of more focal left perisylvian damage associated with aphasia, versus diffuse bihemispheric frontotemporal and parietal dysfunction associated with schizophrenia, on cognition and communication. We propose that verbal disruption with few morphosyntactic errors and intra-clausal pauses reflects broader cognitive dysfunction, whereas a high frequency of these features points to difficulties more specific to language production and comprehension.

Aims: Specialist mood disorder services in the UK are diverse in structure and spread over different clinical-academic centres in the UK. Relationships between these centres are strong but often based on academic projects, with limited opportunities for clinical case discussions. The NIHR Mental Health Translational Research Collaboration, together with the ASCEnD trial team, has set up an online monthly meeting of tertiary mood disorder services: the Mood Disorders Grand Rounds (MDGR). The aims are: 1) to bring together people with expertise and interest from different centres across the UK; 2) to discuss complex and difficult to treat (or interesting) cases; 3) to consider treatment options. The format includes a 20-minute anonymised case presentation by a specialist, covering clinical and thematic aspects, followed by a 40-minute panel discussion focusing on case management, related themes, and relevant research studies. The presentership rotates between centres around the country and encourages a multidisciplinary approach. Following the first 12 months of MDGR, we distributed a survey to evaluate and develop the meetings. Methods: An evaluation form was developed and sent to all registered attendees over the course of six months, on a rolling basis. Participants were asked to both rate the effectiveness of various aspects of the programme and to submit suggestions for improvement, including suggestions for future speakers. Questions included both Likert scored items and free text responses. Results: We received 21 responses (12% of those registered). 75% of respondents had not been to a similar regular collaborative programme previously. 50% of respondents stated that the MDGR had directly influenced their clinical practice, examples being of “Using MAOIs in a case where I hadn’t considered it before” and “identification of a patient with likely autoimmune encephalitis”. The remaining 50% stated that whilst the programme was relevant it had not had a direct result on practice. Conclusion: A high proportion of respondents reported their clinical practice had been directly influenced by attendance. This suggests the MDGR is fulfilling the stated aim of focusing on clinical discussions and is of value to attenders. The rate of response is low and could be biased to those who found it more useful.

BACKGROUND:People with bipolar disorders (BD) frequently experience depressive symptoms that do not respond to available treatment options. The resulting burden for people with BD and society is substantial. This study sought to explore the cost-effectiveness of pramipexole in combination with mood stabilisers for people with treatment-resistant bipolar disorder (TRBD). METHODS:We calculated mean incremental cost-effectiveness ratios (ICER) of pramipexole compared to placebo over 12 and 48 weeks from health and social care (NHS + PSS) and societal perspectives for 36 participants with TRBD. Quality-adjusted life years (QALY) were captured with the EQ-5D-5L as the primary outcome measure. We used capability well-being measures (ICECAP-A, OxCAP-MH) to assess the robustness of the results and multiple imputation and bootstrapping to address missing data and small sample size. RESULTS:We found that pramipexole is dominantly more effective and cost-saving from the NHS + PSS perspective with 86 % probability of being cost-effective at £30,000/QALY gained over 12 weeks and 93 % over 48 weeks. From the societal perspective, pramipexole was more effective but also more expensive with lower probability of cost-effectiveness (36 % over 12 weeks and 48 % over 48 weeks). Uncertainty around the mean ICERs was substantial due to the small sample size. LIMITATIONS:The PAX-BD trial was conducted during the COVID-19 pandemic and terminated early, resulting in a limited generalizability of resource use outside the pandemic context and a small sample size. CONCLUSIONS:Pramipexole is a cost-effective treatment option for TRBD from the NHS + PSS perspective, with statistically significant increases in health-related quality of life and capability well-being over extended periods.

Pre-babbling infants can track nonadjacent dependencies (NADs) in the auditory domain. While this forms a crucial prerequisite for language acquisition, the neurodevelopmental origins of this ability remain unknown. We applied functional near-infrared spectroscopy in neonates and 6- to 7-month-old infants to investigate the neural substrate supporting NAD learning and detection using tone sequences in an artificial grammar learning paradigm. Detection of NADs was indicated by left prefrontal activation in neonates while by left supramarginal gyrus (SMG), superior temporal gyrus (STG), and inferior frontal gyrus activation in 6- to 7-month-olds. Functional connectivity analyses further indicated that the neonate activation pattern during the test phase benefited from a brain network consisting of prefrontal regions, left SMG and STG during the rest and learning phases. These findings suggest a left-hemispheric learning-related functional brain network may emerge at birth and serve as the foundation for the later engagement of these regions for NAD detection, thus, providing a neural basis for language acquisition.