Explore the vast range of titles available.

Pituitary adenylate cyclase-activating polypeptide (PACAP), a neuropeptide with survival-promoting actions, has been observed in endocrine organs and is thought to play a role in reproductive functions, including pregnancy. PACAP occurs in two forms, 27 and 38 amino acid residues, with PACAP38 being the predominant form in human tissues. In the present study, we determined the concentrations of PACAP38 and PACAP27 in first-trimester and full-term human placentas using radioimmunoassay. We found high levels of PACAP38 and lower levels of PACAP27 in different parts of the full-term human placenta. PACAP38 content increased in the placenta during pregnancy, both on the maternal side and on the fetal side. The effects of PACAP on the survival of JAR human choriocarcinoma cells were investigated using flow cytometry and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) cell viability assay in cells exposed to the widely used chemotherapeutic agent methotrexate (MTX). It was found that PACAP neither influenced the survival of JAR cytotrophoblast cells nor affected cellular response to the death-inducing effect of the chemotherapeutic agent MTX. The present observations further support the significance of PACAP in the human placenta. The observation that PACAP did not influence the effects of MTX may have future clinical importance, showing that PACAP does not decrease the effects of certain chemotherapeutic agents.

The National i-THRIVE Programme seeks to evaluate the impact of the NHS England-funded whole system transformation on child and adolescent mental health services (CAMHS). This article reports on the design for a model of implementation that has been applied in CAMHS across over 70 areas in England using the ‘THRIVE’ needs-based principles of care. The implementation protocol in which this model, ‘i-THRIVE’ (implementing-THRIVE), will be used to evaluate the effectiveness of the THRIVE intervention is reported, together with the evaluation protocol for the process of implementation. To evaluate the effectiveness of i-THRIVE to improve care for children and young people’s mental health, a cohort study design will be conducted. N = 10 CAMHS sites that adopt the i-THRIVE model from the start of the NHS England-funded CAMHS transformation will be compared to N = 10 ‘comparator sites’ that choose to use different transformation approaches within the same timeframe. Sites will be matched on population size, urbanicity, funding, level of deprivation and expected prevalence of mental health care needs. To evaluate the process of implementation, a mixed-methods approach will be conducted to explore the moderating effects of context, fidelity, dose, pathway structure and reach on clinical and service level outcomes. This study addresses a unique opportunity to inform the ongoing national transformation of CAMHS with evidence about a popular new model for delivering children and young people’s mental health care, as well as a new implementation approach to support whole system transformation. If the outcomes reflect benefit from i-THRIVE, this study has the potential to guide significant improvements in CAMHS by providing a more integrated, needs-led service model that increases access and involvement of patients with services and in the care they receive.

Adolescence is a key time period for the emergence of psychosocial and mental health difficulties. To promote adolescent adaptive ('resilient') psychosocial functioning (PSF), appropriate conceptualisation and quantification of such functioning and its predictors is a crucial first step. Here, we quantify resilient functioning as the degree to which an individual functions better or worse than expected given their self-reported childhood family experiences, and relate this to adolescent family and friendship support. We used Principal Component and regression analyses to investigate the relationship between childhood family experiences and PSF (psychiatric symptomatology, personality traits and mental wellbeing) in healthy adolescents (the Neuroscience in Psychiatry Network; N = 2389; ages 14-24). Residuals from the relation between childhood family experiences and PSF reflect resilient functioning; the degree to which an individual is functioning better, or worse, than expected given their childhood family experiences. Next, we relate family and friendship support with resilient functioning both cross-sectionally and 1 year later. Friendship and family support were positive predictors of immediate resilient PSF, with friendship support being the strongest predictor. However, whereas friendship support was a significant positive predictor of later resilient functioning, family support had a negative relationship with later resilient PSF. We show that friendship support, but not family support, is an important positive predictor of both immediate and later resilient PSF in adolescence and early adulthood. Interventions that promote the skills needed to acquire and sustain adolescent friendships may be crucial in increasing adolescent resilient PSF.

The COVID-19 pandemic and nationally mandated restrictions to control the virus have been associated with increased mental health issues. However, the differential impact of the pandemic and lockdown on groups of individuals, and the personal characteristics associated with poorer outcomes are unknown. Data from 21 938 adults in England who participated in a stratified cohort study were analysed. Trajectories of depression and anxiety symptoms were identified using growth mixture modelling. Multinomial and logistic regression models were constructed to identify sociodemographic and personality-related risk factors associated with trajectory class membership. Four trajectories of depression and five for anxiety were identified. The most common group presented with low symptom severity throughout, other classes were identified that showed: severe levels of symptoms which increased; moderate symptoms throughout; worsening mental health during lockdown but improvements after lockdown ended; and for anxiety only, severe initial anxiety that decreased quickly during lockdown. Age, gender, ethnicity, income, previous diagnoses, living situation, personality factors and sociability were associated with different trajectories. Nearly 30% of participants experienced trajectories with symptoms in the clinical range during lockdown, and did not follow the average curve or majority group, highlighting the importance of differential trajectories. Young, female, outgoing and sociable people and essential workers experienced severe anxiety around the announcement of lockdown which rapidly decreased. Younger individuals with lower incomes and previous mental health diagnoses experienced higher and increasing levels of symptoms. Recognising the likely symptom trajectories for such groups may allow for targeted care or interventions.

Mental health difficulties are common in children and young people with chronic health conditions, but many of those in need do not access evidence-based psychological treatments. The study aim was to evaluate the clinical effectiveness of integrated mental health treatment for children and young people with epilepsy, a common chronic health condition known to be associated with a particularly high rate of co-occurring mental health difficulties. We conducted a parallel group, multicentre, open-label, randomised controlled trial of participants aged 3–18 years, attending epilepsy clinics across England and Northern Ireland who met diagnostic criteria for a common mental health disorder. Participants were randomised (1:1; using an independent web-based system) to receive the Mental Health Intervention for Children with Epilepsy (MICE) in addition to usual care, or assessment-enhanced usual care alone (control). Children and young people in both groups received a full diagnostic mental health assessment. MICE was a modular psychological intervention designed to treat common mental health conditions in children and young people using evidence-based approaches such as cognitive behaviour therapy and behavioural parenting strategies. Usual care for mental health disorders varied by site but typically included referral to appropriate services. Participants, along with their caregivers, and clinicians were not masked to treatment allocation but statisticians were masked until the point of analysis. The primary outcome, analysed by modified intention-to-treat, was the parent-report Strengths and Difficulties Questionnaire (SDQ) at 6 months post-randomisation. The study is complete and registered with ISRCTN (57823197). 1401 young people were potentially deemed eligible for study inclusion. Following the exclusion of 531 young people, 870 participants were assessed for eligibility and completed the SDQ, and 480 caregivers provided consent for study inclusion between May 20, 2019, and Jan 31, 2022. Between Aug 28, 2019, and Feb 21, 2022, 334 participants (mean ages 10·5 years [SD 3·6] in the MICE group vs 10·3 [4·0] in control group at baseline) were randomly assigned to an intervention using minimisation balanced by age, primary mental health disorder, diagnosis of intellectual disability, and autistic spectrum disorder at baseline. 168 (50%) of the participants were female and 166 (50%) were male. 166 participants were randomly assigned to the MICE group and 168 were randomly assigned to the control group. At 6 months, the mean SDQ difficulties for the 148 participants in the MICE group was 17·6 (SD 6·3) and 19·6 (6·1) for the 148 participants in the control group. The adjusted effect of MICE was –1·7 (95% CI –2·8 to –0·5; p=0·0040; Cohen's d, 0·3). 14 (8%) patients in the MICE group experienced at least one serious adverse event compared with 24 (14%) in the control group. 68% percent of serious adverse events (50 events) were admission due to seizures. MICE was superior to assessment-enhanced usual care in improving symptoms of emotional and behavioural difficulties in young people with epilepsy and common mental health disorders. The trial therefore shows that mental health comorbidities can be effectively and safely treated by a variety of clinicians, utilising an integrated intervention across ages and in the context of intellectual disability and autism. The evidence from this trial suggests that such a model should be fully embedded in epilepsy services and serves as a model for other chronic health conditions in young people. UK National Institute for Health Research Programme Grants for Applied Research programme and Epilepsy Research UK Endeavour Project Grant.

Questions concerning the safety of selective serotonin reuptake inhibitors (SSRIs) in the treatment of depression in children led us to compare and contrast published and unpublished data on the risks and benefits of these drugs. We did a meta-analysis of data from randomised controlled trials that evaluated an SSRI versus placebo in participants aged 5–18 years and that were published in a peer-reviewed journal or were unpublished and included in a review by the Committee on Safety of Medicines. The following outcomes were included: remission, response to treatment, depressive symptom scores, serious adverse events, suicide-related behaviours, and discontinuation of treatment because of adverse events. Data for two published trials suggest that fluoxetine has a favourable risk-benefit profile, and unpublished data lend support to this finding. Published results from one trial of paroxetine and two trials of sertraline suggest equivocal or weak positive risk-benefit profiles. However, in both cases, addition of unpublished data indicates that risks outweigh benefits. Data from unpublished trials of citalopram and venlafaxine show unfavourable risk-benefit profiles. Published data suggest a favourable risk-benefit profile for some SSRIs; however, addition of unpublished data indicates that risks could outweigh benefits of these drugs (except fluoxetine) to treat depression in children and young people. Clinical guideline development and clinical decisions about treatment are largely dependent on an evidence base published in peer-reviewed journals. Non-publication of trials, for whatever reason, or the omission of important data from published trials, can lead to erroneous recommendations for treatment. Greater openness and transparency with respect to all intervention studies is needed.

Developing integrated mental health services focused on the needs of children and young people is a key policy goal in England. The THRIVE Framework and its implementation programme, i-THRIVE, are widely used in England. This study examines experiences of staff using i-THRIVE, estimates its effectiveness, and assesses how local system working relationships influence programme success. This evaluation uses a quasi-experimental design (10 implementation and 10 comparison sites.) Measurements included staff surveys and assessment of 'THRIVE-like' features of each site. Additional site-level characteristics were collected from health system reports. The effect of i-THRIVE was evaluated using a four-group propensity-score-weighted difference-in-differences model; the moderating effect of system working relationships was evaluated with a difference-in-difference-in-differences model. Implementation site staff were more likely to report using THRIVE and more knowledgeable of THRIVE principles than comparison site staff. The mean improvement of fidelity scores among i-THRIVE sites was 16.7, and 8.8 among comparison sites; the weighted model did not find a statistically significant difference. However, results show that strong working relationships in the local system significantly enhance the effectiveness of i-THRIVE. Sites with highly effective working relationships showed a notable improvement in 'THRIVE-like' features, with an average increase of 16.41 points (95% confidence interval: 1.69-31.13, P-value: 0.031) over comparison sites. Sites with ineffective working relationships did not benefit from i-THRIVE (-2.76, 95% confidence interval: - 18.25-12.73, P-value: 0.708). The findings underscore the importance of working relationship effectiveness in the successful adoption and implementation of multi-agency health policies like i-THRIVE.

Improving Access to Psychological Therapies (IAPT) services treat most patients in England who present to primary care with major depression. Psychodynamic psychotherapy is one of the psychotherapies offered. Dynamic Interpersonal Therapy (DIT) is a psychodynamic and mentalization-based treatment for depression. 16 sessions are delivered over approximately 5 months. Neither DIT's effectiveness relative to low-intensity treatment (LIT), nor the feasibility of randomizing patients to psychodynamic or cognitive-behavioural treatments (CBT) in an IAPT setting has been demonstrated. 147 patients were randomized in a 3:2:1 ratio to DIT (n = 73), LIT (control intervention; n = 54) or CBT (n = 20) in four IAPT treatment services in a combined superiority and feasibility design. Patients meeting criteria for major depressive disorder were assessed at baseline, mid-treatment (3 months) and post-treatment (6 months) using the Hamilton Rating Scale for Depression (HRSD-17), Beck Depression Inventory-II (BDI-II) and other self-rated questionnaire measures. Patients receiving DIT were also followed up 6 months post-completion. The DIT arm showed significantly lower HRSD-17 scores at the 6-month primary end-point compared with LIT (d = 0.70). Significantly more DIT patients (51%) showed clinically significant change on the HRSD-17 compared with LIT (9%). The DIT and CBT arms showed equivalence on most outcomes. Results were similar with the BDI-II. DIT showed benefit across a range of secondary outcomes. DIT delivered in a primary care setting is superior to LIT and can be appropriately compared with CBT in future RCTs.

Introduction Methodological and ethical arguments support the involvement of individuals with lived experience in research to reduce engagement barriers and ensure those directly affected by studies contribute to knowledge generation. However, there is limited evidence on the impact of including researchers with lived experience of serving a prison or community sentence in clinical trials. This qualitative study aimed to explore the value of involving researchers with lived experience of the criminal justice system as data collectors in the Mentalization for Offending Adult Males (MOAM), a multisite RCT conducted in the National Probation Service in England and Wales. Methods Semi‐structured interviews were conducted with 30 trial participants and 17 key stakeholders, either in person or via telephone. The interviews were transcribed verbatim and analysed thematically. Findings Five themes emerged for trial participants and 11 for key stakeholders. For some, lived experience researchers helped overcome engagement barriers by fostering common ground with participants who were serving a prison or community sentence during recruitment. Participants reported that the involvement of lived experience researchers enhanced the study by facilitating knowledge transfer in certain instances. However, their inclusion did not eliminate all barriers and, for some participants, introduced new challenges to engagement. Conclusion Forensic lived experience researchers bridged the gap by fostering trust between data collectors and participants. Future studies should ensure that lived experience researchers receive adequate clinical supervision to support their role. The adopted methodology challenged assumptions about knowledge generation and stereotypes associated with being an ex‐offender, benefiting both lived experience and traditional researchers. Patient or Public Contribution The study was developed in collaboration with User Voice (charity number: 1136047), who contributed to the study's design and conduct. The service user organisation co‐designed the interview schedule and directed the protocol for participant payments, emphasising a consistent approach to avoid tokenism and ensure equal recognition of all contributions. The dissemination plan was developed in partnership with individuals with lived experience of the criminal justice system.

IntroductionAssessing mentalizing abilities is a complex issue. Only recently an instrument assessing mentalizing capacity as a whole, the Reflective Functioning Questionnaire (RFQ), has been developed.ObjectivesTo reach the purpose of our study, we investigated the psychometric proprieties of the Italian version of the RFQ.MethodsThe study was conducted on a sample including a group of violent offenders and a group of community participants. All subjects fulfilled the RFQ, the Personality Inventory for DSM-5 (PID-5) and the Aggression Questionnaire (AQ).ResultsThe theoretical model was defined and analysed by using Partial Least Squares–Path Modelling with high-order construct definition. Data showed good psychometric proprieties of the Italian version of the RFQ. Also, specific patterns of correlations were identified between the RFQ subscales and both PID-5 and AQ scores. Offenders significantly differed from controls only in relation to one subscale of the RFQ.ConclusionsData supported the factorial structure of the RFQ found in the original validation study. Results also support the existence of a second-order variable, mentalizing, resulting from the convergence of hypomentalizing and hypermentalizing.