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Risk Factors for Perinatal Arterial Ischemic Stroke: A Machine Learning Approach
Srivastava R, Cole L, Amador K, Forkert ND, Dunbar M, Shevell MI, Oskoui M, Basu AP, Rivkin MJ, Shany E, de Vries LS, Dewey D, Letourneau N, Mouches P, Hill MD and Kirton A
Perinatal arterial ischemic stroke (PAIS) is a focal vascular brain injury presumed to occur between the fetal period and the first 28 days of life. It is the leading cause of hemiparetic cerebral palsy. Multiple maternal, intrapartum, delivery, and fetal factors have been associated with PAIS, but studies are limited by modest sample sizes and complex interactions between factors. Machine learning approaches use large and complex data sets to enable unbiased identification of clinical predictors but have not yet been applied to PAIS. We combined large PAIS data sets and used machine learning methods to identify clinical PAIS factors and compare this data-driven approach with previously described literature-driven clinical prediction models.
Impact of air pollution and climate change on mental health outcomes: an umbrella review of global evidence
Radua J, De Prisco M, Oliva V, Fico G, Vieta E and Fusar-Poli P
The impact of air pollution and climate change on mental health has recently raised strong concerns. However, a comprehensive overview analyzing the existing evidence while addressing relevant biases is lacking. This umbrella review systematically searched the PubMed/Medline, Scopus and PsycINFO databases (up to June 26, 2023) for any systematic review with meta-analysis investigating the association of air pollution or climate change with mental health outcomes. We used the R metaumbrella package to calculate and stratify the credibility of the evidence according to criteria (i.e., convincing, highly suggestive, suggestive, or weak) that address several biases, complemented by sensitivity analyses. We included 32 systematic reviews with meta-analysis that examined 284 individual studies and 237 associations of exposures to air pollution or climate change hazards and mental health outcomes. Most associations (n=195, 82.3%) involved air pollution, while the rest (n=42, 17.7%) regarded climate change hazards (mostly focusing on temperature: n=35, 14.8%). Mental health outcomes in most associations (n=185, 78.1%) involved mental disorders, followed by suicidal behavior (n=29, 12.4%), access to mental health care services (n=9, 3.7%), mental disorders-related symptomatology (n=8, 3.3%), and multiple categories together (n=6, 2.5%). Twelve associations (5.0%) achieved convincing (class I) or highly suggestive (class II) evidence. Regarding exposures to air pollution, there was convincing (class I) evidence for the association between long-term exposure to solvents and a higher incidence of dementia or cognitive impairment (odds ratio, OR=1.139), and highly suggestive (class II) evidence for the association between long-term exposure to some pollutants and higher risk for cognitive disorders (higher incidence of dementia with high vs. low levels of carbon monoxide, CO: OR=1.587; higher incidence of vascular dementia per 1 μg/m increase of nitrogen oxides, NO: hazard ratio, HR=1.004). There was also highly suggestive (class II) evidence for the association between exposure to airborne particulate matter with diameter ≤10 μm (PM) during the second trimester of pregnancy and the incidence of post-partum depression (OR=1.023 per 1 μg/m increase); and for the association between short-term exposure to sulfur dioxide (SO) and schizophrenia relapse (risk ratio, RR=1.005 and 1.004 per 1 μg/m increase, respectively 5 and 7 days after exposure). Regarding climate change hazards, there was highly suggestive (class II) evidence for the association between short-term exposure to increased temperature and suicide- or mental disorders-related mortality (RR=1.024), suicidal behavior (RR=1.012), and hospital access (i.e., hospitalization or emergency department visits) due to suicidal behavior or mental disorders (RR=1.011) or mental disorders only (RR=1.009) (RR values per 1°C increase). There was also highly suggestive (class II) evidence for the association between short-term exposure to increased apparent temperature (i.e., the temperature equivalent perceived by humans) and suicidal behavior (RR=1.01 per 1°C increase). Finally, there was highly suggestive (class II) evidence for the association between the temporal proximity of cyclone exposure and severity of symptoms of post-traumatic stress disorder (r=0.275). Although most of the above associations were small in magnitude, they extend to the entire world population, and are therefore likely to have a substantial impact. This umbrella review classifies and quantifies for the first time the global negative impacts that air pollution and climate change can exert on mental health, identifying evidence-based targets that can inform future research and population health actions.
A polygenic risk score for alcohol-associated cirrhosis among heavy drinkers with European ancestry
Schwantes-An TH, Whitfield JB, Aithal GP, Atkinson SR, Bataller R, Botwin G, Chalasani NP, Cordell HJ, Daly AK, Darlay R, Day CP, Eyer F, Foroud T, Gawrieh S, Gleeson D, Goldman D, Haber PS, Jacquet JM, Lammert CS, Liang T, Liangpunsakul S, Masson S, Mathurin P, Moirand R, McQuillin A, Moreno C, Morgan MY, Mueller S, Müllhaupt B, Nagy LE, Nahon P, Nalpas B, Naveau S, Perney P, Pirmohamed M, Seitz HK, Soyka M, Stickel F, Thompson A, Thursz MR, Trépo E, Morgan TR, Seth D and
Polygenic Risk Scores (PRS) based on results from genome-wide association studies offer the prospect of risk stratification for many common and complex diseases. We developed a PRS for alcohol-associated cirrhosis by comparing single-nucleotide polymorphisms among patients with alcohol-associated cirrhosis (ALC) versus drinkers who did not have evidence of liver fibrosis/cirrhosis.
Behavioral Problems and Family Impact in Congenital Cytomegalovirus Infection
Rodríguez-Molino P, Alarcón A, Martínez-Biarge M, Cabrera-Lafuente M, Aldecoa V, Fernández-Sánchez A, Fernández-Jiménez E, Baquero-Artigao F and García-Alix A
We examined behavior (Child Behavior Checklist) and family functioning (Family Impact Questionnaire) in 65 children with congenital cytomegalovirus. Behavioral problems were present in 30.8%. Parents of children with moderate/severe outcomes reported strain on all areas of family functioning. Behavioral problems were associated with negative impact on parental feelings and marital/partnership relationship. Our findings inform planning support services.
From "online brains" to "online lives": understanding the individualized impacts of Internet use across psychological, cognitive and social dimensions
Firth J, Torous J, López-Gil JF, Linardon J, Milton A, Lambert J, Smith L, Jarić I, Fabian H, Vancampfort D, Onyeaka H, Schuch FB and Firth JA
In response to the mass adoption and extensive usage of Internet-enabled devices across the world, a major review published in this journal in 2019 examined the impact of Internet on human cognition, discussing the concepts and ideas behind the "online brain". Since then, the online world has become further entwined with the fabric of society, and the extent to which we use such technologies has continued to grow. Furthermore, the research evidence on the ways in which Internet usage affects the human mind has advanced considerably. In this paper, we sought to draw upon the latest data from large-scale epidemiological studies and systematic reviews, along with randomized controlled trials and qualitative research recently emerging on this topic, in order to now provide a multi-dimensional overview of the impacts of Internet usage across psychological, cognitive and societal outcomes. Within this, we detail the empirical evidence on how effects differ according to various factors such as age, gender, and usage types. We also draw from new research examining more experiential aspects of individuals' online lives, to understand how the specifics of their interactions with the Internet, and the impact on their lifestyle, determine the benefits or drawbacks of online time. Additionally, we explore how the nascent but intriguing areas of culturomics, artificial intelligence, virtual reality, and augmented reality are changing our understanding of how the Internet can interact with brain and behavior. Overall, the importance of taking an individualized and multi-dimensional approach to how the Internet affects mental health, cognition and social functioning is clear. Furthermore, we emphasize the need for guidelines, policies and initiatives around Internet usage to make full use of the evidence available from neuroscientific, behavioral and societal levels of research presented herein.
The efficacy, acceptability and safety of acceptance and commitment therapy for fibromyalgia - a systematic review and meta-analysis
Eastwood F and Godfrey E
Fibromyalgia (FM) is a chronic pain disorder characterised by widespread pain, fatigue and cognitive symptoms. Acceptance and commitment therapy (ACT) aims to improve psychological flexibility and has been found to be beneficial in treating chronic pain; however, there are few studies evaluating its efficacy in treating FM.
Evaluating the feasibility of delivering a pain management programme for adults living with sickle cell disease
McLoughlin R, Love J, Smith JG, Scott W and Noblet T
Pain is the prominent feature of sickle cell disease (SCD) and negatively affects quality of life. Delivery of pain management programmes (PMPs) has been suggested in clinical guidelines for pain management in SCD; however, further evidence of the feasibility and effectiveness of PMPs in this population is needed. This study explored the feasibility of delivering a sickle cell pain management programme (SCPMP) for adults within a haemoglobinopathies service.
Real-world effectiveness of antidepressants, antipsychotics and their combinations in the maintenance treatment of psychotic depression. Evidence from within-subject analyses of two nationwide cohorts
Taipale H, Lieslehto J, Lähteenvuo M, Hamina A, Tanskanen A, Mittendorfer-Rutz E, Paljärvi T, Solmi M, Cipriani A, Correll CU and Tiihonen J
Psychotic depression (PD) is a severe mental disorder leading to functional disability and high risk of suicide, but very little is known about the comparative effectiveness of medications used in its maintenance treatment. The objective of this study was to investigate the comparative effectiveness of specific antipsychotics and antidepressants, and their combinations, on the risk of psychiatric hospitalization among persons with PD in routine care. Persons aged 16-65 years with a first-time diagnosis of PD were identified from Finnish (years 2000-2018) and Swedish (years 2006-2021) nationwide registers of inpatient care, specialized outpatient care, sickness absence, and disability pension. The main exposures were specific antipsychotics and antidepressants, and the main outcome measure was psychiatric hospitalization as a marker of severe relapse. The risk of hospitalization associated with periods of use vs. non-use of medications (expressed as adjusted hazard ratio, aHR) was assessed by a within-individual design, using each individual as his/her own control, and analyzed with stratified Cox models. The two national cohorts were first analyzed separately, and then combined using a fixed-effect meta-analysis. The Finnish cohort included 19,330 persons (mean age: 39.8±14.7 years; 57.9% women) and the Swedish cohort 13,684 persons (mean age: 41.3±14.0 years; 53.5% women). Individual antidepressants associated with a decreased risk of relapse vs. non-use of antidepressants were bupropion (aHR=0.73, 95% CI: 0.63-0.85), vortioxetine (aHR=0.78, 95% CI: 0.63-0.96) and venlafaxine (aHR=0.92, 95% CI: 0.86-0.98). Any long-acting injectable antipsychotic (LAI) (aHR=0.60, 95% CI: 0.45-0.80) and clozapine (aHR=0.72, 95% CI: 0.57-0.91) were associated with a decreased risk of relapse vs. non-use of antipsychotics. Among monotherapies, only vortioxetine (aHR=0.67, 95% CI: 0.47-0.95) and bupropion (aHR=0.71, 95% CI: 0.56-0.89) were associated with a significantly decreased risk of relapse vs. non-use of both antidepressants and antipsychotics. In an exploratory analysis of antidepressant-antipsychotic combinations, a decreased relapse risk was found for amitriptyline-olanzapine (aHR=0.45, 95% CI: 0.28-0.71), sertraline-quetiapine (aHR=0.79, 95% CI: 0.67-0.93) and venlafaxine-quetiapine (aHR=0.82, 95% CI: 0.73-0.91) vs. non-use of antidepressants and antipsychotics. Benzodiazepines and related drugs (aHR=1.29, 95% CI: 1.24-1.34) and mirtazapine (aHR=1.17, 95% CI: 1.07-1.29) were associated with an increased risk of relapse. These data indicate that, in the maintenance treatment of PD, bupropion, vortioxetine, venlafaxine, any LAI, clozapine, and only few specific antidepressant-antipsychotic combinations are associated with a decreased risk of relapse. These findings challenge the current recommendation by treatment guidelines to combine an antipsychotic with an antidepressant (without further specification) as standard treatment in PD.
The lived experience of mental disorders in adolescents: a bottom-up review co-designed, co-conducted and co-written by experts by experience and academics
Fusar-Poli P, Estradé A, Esposito CM, Rosfort R, Basadonne I, Mancini M, Stanghellini G, Otaiku J, Olanrele O, Allen L, Lamba M, Alaso C, Ieri J, Atieno M, Oluoch Y, Ireri P, Tembo E, Phiri IZ, Nkhoma D, Sichone N, Siadibbi C, Sundi PRIO, Ntokozo N, Fusar-Poli L, Floris V, Mensi MM, Borgatti R, Damiani S, Provenzani U, Brondino N, Bonoldi I, Radua J, Cooper K, Shin JI, Cortese S, Danese A, Bendall S, Arango C, Correll CU and Maj M
We provide here the first bottom-up review of the lived experience of mental disorders in adolescents co-designed, co-conducted and co-written by experts by experience and academics. We screened first-person accounts within and outside the medical field, and discussed them in collaborative workshops involving numerous experts by experience - representing different genders, ethnic and cultural backgrounds, and continents - and their family members and carers. Subsequently, the material was enriched by phenomenologically informed perspectives and shared with all collaborators. The inner subjective experience of adolescents is described for mood disorders, psychotic disorders, attention-deficit/hyperactivity disorder, autism spectrum disorders, anxiety disorders, eating disorders, externalizing disorders, and self-harm behaviors. The recollection of individuals' past histories also indexes the prodromal (often transdiagnostic) features predating the psychiatric diagnosis. The experience of adolescents with mental disorders in the wider society is described with respect to their family, their school and peers, and the social and cultural context. Furthermore, their lived experience of mental health care is described with respect to receiving a diagnosis of mental disorder, accessing mental health support, receiving psychopharmacological treatment, receiving psychotherapy, experiencing peer support and mental health activism, and achieving recovery. These findings can impact clinical practice, research, and the whole society. We hope that this co-designed, co-conducted and co-written journey can help us maintain our commitment to protecting adolescents' fragile mental health, and can help them develop into a healthy, fulfilling and contributing adult life.
The prescription of valproate: risk of harm
Rugg-Gunn F and Hunt D
European Stroke Organisation (ESO) Guidelines on the diagnosis and management of patent foramen ovale (PFO) after stroke
Caso V, Turc G, Abdul-Rahim AH, Castro P, Hussain S, Lal A, Mattle H, Korompoki E, Søndergaard L, Toni D, Walter S and Pristipino C
Patent foramen ovale (PFO) is frequently identified in young patients with cryptogenic ischaemic stroke. Potential stroke mechanisms include paradoxical embolism from a venous clot which traverses the PFO, in situ clot formation within the PFO, and atrial arrhythmias due to electrical signalling disruption. The purpose of this guideline is to provide recommendations for diagnosing, treating, and long-term managing patients with ischaemic stroke and PFO. Conversely, Transient Ischaemic Attack (TIA) was not considered an index event in this context because only one RCT involved TIA patients. However, this subgroup analysis showed no significant differences between TIA and stroke outcomes. The working group identified questions and outcomes, graded evidence, and developed recommendations following the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach and the European Stroke Organisation (ESO) standard operating procedure for guideline development. This document underwent peer-review by independent experts and members of the ESO Guideline Board and Executive Committee. The working group acknowledges the current evidentiary gap in delineating an unequivocal diagnostic algorithm for the detection of PFO. Although transoesophageal echocardiography is conventionally held as the most accurate diagnostic tool for PFO identification, its status as the 'gold standard' remains unsubstantiated by rigorously validated evidence. We found high-quality evidence to recommend PFO closure plus antiplatelet therapy in selected patients aged 18-60 years in whom no other evident cause of stroke is found but a PFO (i.e. PFO-associated stroke). The PASCAL classification system can be used to select such candidates for PFO closure. Patients with both a large right-to-left shunt and an atrial septal aneurysm benefit most from PFO closure. There is insufficient evidence to make an evidence-based recommendation on PFO closure in patients older than 60 and younger than 18 years. We found low quality evidence to suggest against PFO closure in patients with unlikely PFO-related stroke according to the PASCAL classification, except in specific scenarios (Expert Consensus). We suggest against long-term anticoagulation in patients with PFO-associated stroke unless anticoagulation is indicated for other medical reasons. Regarding the long-term AF monitoring after PFO closure, the working group concluded that there remains significant uncertainty regarding the risks and benefits associated with the use of long-term cardiac monitoring, such as implantable loop recorders. This document provides additional guidance, in the form of evidence-based recommendations or expert consensus statements, on diagnostic methods for PFO detection, and medical management after PFO closure.
Comparing the symptom presentation similarities and differences of complex posttraumatic stress disorder and borderline personality disorder: A systematic review
Atkinson JR, Kristinsdottir KH, Lee T and Freestone MC
Complex posttraumatic stress disorder (CPTSD) is characterized in the by affect dysregulation, negative self-concept, and relationship impairments, symptoms also presented in borderline personality disorder (BPD). Some research shows CPTSD as a distinct disorder, others as a subgroup or a replacement for BPD. No review currently amalgamates the findings on whether CPTSD presents too similarly to BPD to be a standalone disorder. This article systematically reviewed similarities and differences in symptom presentations of the two disorders. Six databases were searched (PsycINFO, EMBASE, PubMed, Web of Science, PsycEXTRA, and Open Access Theses and Dissertations) and identified papers were summarized narratively. The majority of studies found distinct profiles for CPTSD and BPD. One study found no differences between the constructs; however, this used a population without severe trauma. CPTSD and BPD can present comorbidly, these individuals will have likely experienced earlier and more frequent interpersonal trauma and display greater functional impairment. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
Clinical effectiveness and cost-effectiveness of a brief accessible cognitive behavioural therapy programme for stress in school-aged adolescents (BESST): a cluster randomised controlled trial in the UK
Brown J, James K, Lisk S, Shearer J, Byford S, Stallard P, Deighton J, Saunders D, Yarrum J, Fonagy P, Weaver T, Sclare I, Day C, Evans C and Carter B
Depression and anxiety are increasingly prevalent in adolescents. The Brief Educational Workshops in Secondary Schools Trial investigated the effectiveness of a brief accessible stress workshop programme for 16-18-year-olds. We aimed to investigate the clinical effectiveness and cost-effectiveness of the DISCOVER cognitive behavioural therapy (CBT) workshop on symptoms of depression in 16-18-year-olds at 6 months compared with treatment-as-usual.
Psychological distress over 12 months post-diagnosis in an early inflammatory arthritis cohort
Zhao L, Galloway J, Ledingham J, Gallagher S, Garnavos G, Amlani-Hatcher P, Wilson N, Carpenter L, Bannister K and Norton S
People with inflammatory arthritis (IA) experience worsened mental wellbeing alongside disease progression. Using the National Early Inflammatory Arthritis Audit (NEIAA), we assessed trends in psychological distress during 12-months following IA diagnosis, mapping these against clinical outcomes to identify associations.
Neural responses to facial emotions and subsequent clinical outcomes in difficult-to-treat depression
Fennema D, Barker GJ, O'Daly O, Duan S, Godlewska BR, Goldsmith K, Young AH, Moll J and Zahn R
Amygdala and dorsal anterior cingulate cortex responses to facial emotions have shown promise in predicting treatment response in medication-free major depressive disorder (MDD). Here, we examined their role in the pathophysiology of clinical outcomes in more chronic, difficult-to-treat forms of MDD.
Approaches to improving mental health care for autistic children and young people: a systematic review and meta-analysis
Pemovska T, Loizou S, Appleton R, Spain D, Stefanidou T, Kular A, Cooper R, Greenburgh A, Griffiths J, Barnett P, Foye U, Baldwin H, Minchin M, Brady G, Saunders KRK, Ahmed N, Jackson R, Olive RR, Parker J, Timmerman A, Sapiets S, Driskell E, Chipp B, Parsons B, Totsika V, Mandy W, Pender R, Clery P, Lloyd-Evans B, Simpson A and Johnson S
Autistic children and young people (CYP) experience mental health difficulties but face many barriers to accessing and benefiting from mental health care. There is a need to explore strategies in mental health care for autistic CYP to guide clinical practice and future research and support their mental health needs. Our aim was to identify strategies used to improve mental health care for autistic CYP and examine evidence on their acceptability, feasibility, and effectiveness. A systematic review and meta-analysis were carried out. All study designs reporting acceptability/feasibility outcomes and empirical quantitative studies reporting effectiveness outcomes for strategies tested within mental health care were eligible. We conducted a narrative synthesis and separate meta-analyses by informant (self, parent, and clinician). Fifty-seven papers were included, with most investigating cognitive behavioral therapy (CBT)-based interventions for anxiety and several exploring service-level strategies, such as autism screening tools, clinician training, and adaptations regarding organization of services. Most papers described caregiver involvement in therapy and reported adaptations to communication and intervention content; a few reported environmental adjustments. In the meta-analyses, parent- and clinician-reported outcomes, but not self-reported outcomes, showed with moderate certainty that CBT for anxiety was an effective treatment compared to any comparison condition in reducing anxiety symptoms in autistic individuals. The certainty of evidence for effectiveness, synthesized narratively, ranged from low to moderate. Evidence for feasibility and acceptability tended to be positive. Many identified strategies are simple, reasonable adjustments that can be implemented in services to enhance mental health care for autistic individuals. Notable research gaps persist, however.
Methylphenidate Versus Placebo for Treating Fatigue in Patients With Advanced Cancer: Randomized, Double-Blind, Multicenter, Placebo-Controlled Trial
Stone PC, Minton O, Richardson A, Buckle P, Enayat ZE, Marston L and Freemantle N
To compare effects and side effects of 6 weeks of individually dose-titrated methylphenidate or placebo on fatigue in palliative care patients with advanced cancer.
Methodological Quality of Clinical Trials in Amyotrophic Lateral Sclerosis: A systematic Review
Pupillo E, Al-Chalabi A, Sassi S, Arippol E, Tinti L, Vitelli E, Copetti M, Leone MA and Bianchi E
More than 200 clinical trials have been performed worldwide in ALS so far, but no agents with substantial efficacy on disease progression have been found.
Early life stress unravels epistatic genetic associations of cortisol pathway genes with depression
Pereira SC, Coeli-Lacchini FB, Pereira DA, Ferezin LP, Menezes IC, Baes CVW, Luizon MR, Juruena MF, Cleare AJ, Young AH and Lacchini R
Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis represents one of the most consistent pathophysiological findings in depressive disorders. Cortisol signaling is affected by proteins that mediate its cellular responses or alters its availability to mineralocorticoid and glucocorticoid receptors. In our study, we evaluated candidate genes that may influence the risk for depression and suicide due to its involvement in cortisol signaling. The aim of the study was to assess whether the genotypes of these genes are associated with the risk for depression, severity of depressive symptoms, suicidal ideation, and suicide attempts. And whether there is interaction between genes and early-life stress. In this study, 100 healthy controls and 140 individuals with depression were included. The subjects were clinically assessed using the 21-item GRID-Hamilton questionnaires (GRID-HAMD-21), Beck Scale for Suicidal Ideation (BSI), and the Childhood Trauma Questionnaire (CTQ). A robust multifactorial dimensionality reduction analysis was used to characterize the interactions between the genes HSD11B1, NR3C1, NR3C2, and MDR1 and early-life stress. It was found a significant association of the heterozygous genotype of the MDR1 gene rs1128503 polymorphism with reduced risk of at least one suicide attempt (OR: 0.08, p = 0.003*) and a reduction in the number of suicide attempts (β = -0.79, p = 0.006*). Furthermore, it was found that the MDR1 rs1228503 and NR3C2 rs2070951 genes interact with early-life stress resulting in a strong association with depression (p = 0.001). Our findings suggest that polymorphisms in the MDR1 and NR3C2 genes and their interaction with childhood trauma may be important biomarkers for depression and suicidal behaviors.
Investigating the impact of the COVID-19 pandemic on recovery colleges: multi-site qualitative study
McPhilbin M, Stepanian K, Yeo C, Elton D, Dunnett D, Jennings H, Hunter-Brown H, Grant-Rowles J, Cooper J, Barrett K, Hamie M, Bates P, McNaughton R, Trickett S, Bishop S, Takhi S, Lawrence S, Kotera Y, Hayes D, Davidson L, Ronaldson A, Jebara T, Hall C, Brophy L, Jepps J, Meddings S, Henderson C, Slade M and Lawrence V
During the COVID-19 pandemic, mental health problems increased as access to mental health services reduced. Recovery colleges are recovery-focused adult education initiatives delivered by people with professional and lived mental health expertise. Designed to be collaborative and inclusive, they were uniquely positioned to support people experiencing mental health problems during the pandemic. There is limited research exploring the lasting impacts of the pandemic on recovery college operation and delivery to students.
Analysis and evaluation of peer group support for doctors in postgraduate training following workplace violence and aggression
Carter R, Paphitis S, Oram S, McMullen I and Curtis V
Workplace violence and aggression toward healthcare staff has a significant impact on the individual, causing self-blame, isolation and burnout. Timely and appropriate support can mitigate harm, but there is little research into how this should be delivered. We conducted multi-speciality peer groups for London doctors in postgraduate training (DPT), held over a 6-week period. Pre- and post-group burnout questionnaires and semi-structured interviews were used to evaluate peer support. Thematic analysis and descriptive statistical methods were used to describe the data.
Process evaluation of a Structured E-parenting Support (STEPS) in the OPTIMA randomised controlled trial: a protocol
Hedstrom E, Kostyrka-Allchorne K, French B, Glazebrook C, Hall CL, Kovshoff H, Lean N and Sonuga-Barke E
(STEPS) is a digital application (app) designed to help parents manage behaviour of their children who are referred to mental health services and are waiting for an assessment or treatment. STEPS is currently being evaluated in the Online Parent Training for the Initial Management of Attention-Deficit/Hyperactivity Disorder randomised controlled trial. Alongside the examination of STEPS' clinical and cost-effectiveness, we are conducting a process evaluation to better understand the contextual factors that may influence study outcomes. The purpose of this protocol is to describe the aims, objectives and methodology of the process evaluation prior to it taking place to add to the fidelity and rigour of the trial process and outcomes. Our goal is to adapt STEPS to optimise its benefits in future applications.
Comparison of plasma and neuroimaging biomarkers to predict cognitive decline in non-demented memory clinic patients
Mendes AJ, Ribaldi F, Lathuiliere A, Ashton NJ, Zetterberg H, Abramowicz M, Scheffler M, Assal F, Garibotto V, Blennow K and Frisoni GB
Plasma biomarkers of Alzheimer's disease (AD) pathology, neurodegeneration, and neuroinflammation are ideally suited for secondary prevention programs in self-sufficient persons at-risk of dementia. Plasma biomarkers have been shown to be highly correlated with traditional imaging biomarkers. However, their comparative predictive value versus traditional AD biomarkers is still unclear in cognitively unimpaired (CU) subjects and with mild cognitive impairment (MCI).
Problematic pornography use and novel patterns of escalating use: A cross-sectional network analysis with two independent samples
Ince C, Albertella L, Liu C, Tiego J, Fontenelle LF, Chamberlain SR, Yücel M and Rotaru K
Modern internet pornography allows users to harness sexual novelty in numerous ways, which can be used to overcome desensitisation through increasing volume of use (quantitative tolerance), progressing to more stimulating genres (qualitative escalation), skipping between stimuli (tab-jumping), delaying orgasm ('edging'), and engaging in pornographic binges. However, existing research has not yet evaluated how these potentially reciprocal consumption patterns relate to problematic pornography use (PPU). To this end, we recruited two independent samples of male pornography users (N = 1,356, M = 36.86, SD = 11.26; N = 944, M = 38.69, SD = 12.26) and examined the relationships between these behavioural dimensions and self-reported difficulties in controlling one's pornography use. Data were analysed through the network analysis approach (using Gaussian graphical models). As hypothesised, i) quantitative tolerance was centrally placed within the overall network, and ii) acted as a statistical bridge node between other patterns of pornography use (e.g., pornographic binges), and all measured facets of PPU. Our results are consistent with other emerging literature suggesting that tolerance, pornographic binges, tab-jumping, and edging behaviours as relevant features ofPPU, and that upscaling overall usage may connect broader patterns of use with problematic engagement. Clinical and theoretical implications, as well as future research directions, are discussed.
Blood biomarkers of neurodegeneration associate differently with amyloid deposition, medial temporal atrophy, and cerebrovascular changes in APOE ε4-enriched cognitively unimpaired elderly
Koivumäki M, Ekblad L, Lantero-Rodriguez J, Ashton NJ, Karikari TK, Helin S, Parkkola R, Lötjönen J, Zetterberg H, Blennow K, Rinne JO and Snellman A
Alzheimer's disease (AD) is characterized by the accumulation of amyloid-β (Aβ) plaques, neurofibrillary tau tangles, and neurodegeneration in the brain parenchyma. Here, we aimed to (i) assess differences in blood and imaging biomarkers used to evaluate neurodegeneration among cognitively unimpaired APOE ε4 homozygotes, heterozygotes, and non-carriers with varying risk for sporadic AD, and (ii) to determine how different cerebral pathologies (i.e., Aβ deposition, medial temporal atrophy, and cerebrovascular pathology) contribute to blood biomarker concentrations in this sample.
Generalisation of Social Communication Skills by Autistic Children During Play-Based Assessments Across Home, School and an Unfamiliar Research Setting
Carruthers S, Charman T, Leadbitter K, Ellis C, Taylor L, Moore H, Taylor C, James K, Balabanovska M, Langhorne S, Aldred C, Slonims V, Grahame V, Howlin P, McConachie H, Parr J, Emsley R, Le Couteur A, Green J, Pickles A and
We investigated autistic children's generalisation of social communication over time across three settings during a play-based assessment with different adults and explore the potential moderating effects on generalisation of age, nonverbal IQ and level of restricted and repetitive behaviours. The social communication abilities of 248 autistic children (2-11 years, 21% female, 22% single parent, 60% white) from three UK sites were assessed from 1984 video interactions in three contexts with three different interaction partners (parent/home, teaching assistant/school, researcher/clinic) at baseline, midpoint (+ 7m) and endpoint (+ 12m) within the Paediatric Autism Communication Trial-Generalised (PACT-G), a parent-mediated social communication intervention. Children's midpoint social communication at home generalised to school at midpoint and to clinic at endpoint. Generalisation was stronger from home to school and clinic than school to home and clinic. Generalisation was not moderated by age, nonverbal IQ or restricted and repetitive behaviour. Broader child development did not explain the pattern of results. The current study is the largest study to date to explore generalisation with autistic children and provides novel insight into their generalisation of social communication skills. Further research is needed to gain a more comprehensive understanding of facilitators of generalisation across settings and interaction partners in order to develop targeted strategies for interventions to enhance outcomes for young autistic children.
Combining endpoint and change data did not affect the summary standardised mean difference in pairwise and network meta-analyses: An empirical study in depression
Ostinelli EG, Efthimiou O, Luo Y, Miguel C, Karyotaki E, Cuijpers P, Furukawa TA, Salanti G and Cipriani A
When studies use different scales to measure continuous outcomes, standardised mean differences (SMD) are required to meta-analyse the data. However, outcomes are often reported as endpoint or change from baseline scores. Combining corresponding SMDs can be problematic and available guidance advises against this practice. We aimed to examine the impact of combining the two types of SMD in meta-analyses of depression severity. We used individual participant data on pharmacological interventions (89 studies, 27,409 participants) and internet-delivered cognitive behavioural therapy (iCBT; 61 studies, 13,687 participants) for depression to compare endpoint and change from baseline SMDs at the study level. Next, we performed pairwise (PWMA) and network meta-analyses (NMA) using endpoint SMDs, change from baseline SMDs, or a mixture of the two. Study-specific SMDs calculated from endpoint and change from baseline data were largely similar, although for iCBT interventions 25% of the studies at 3 months were associated with important differences between study-specific SMDs (median 0.01, IQR -0.10, 0.13) especially in smaller trials with baseline imbalances. However, when pooled, the differences between endpoint and change SMDs were negligible. Pooling only the more favourable of the two SMDs did not materially affect meta-analyses, resulting in differences of pooled SMDs up to 0.05 and 0.13 in the pharmacological and iCBT datasets, respectively. Our findings have implications for meta-analyses in depression, where we showed that the choice between endpoint and change scores for estimating SMDs had immaterial impact on summary meta-analytic estimates. Future studies should replicate and extend our analyses to fields other than depression.
Action sequence learning, habits, and automaticity in obsessive-compulsive disorder
Banca P, Herrojo Ruiz M, Gonzalez-Zalba MF, Biria M, Marzuki AA, Piercy T, Sule A, Fineberg NA and Robbins TW
This study investigates the goal/habit imbalance theory of compulsion in obsessive-compulsive disorder (OCD), which postulates enhanced habit formation, increased automaticity, and impaired goal/habit arbitration. It directly tests these hypotheses using newly developed behavioral tasks. First, OCD patients and healthy participants were trained daily for a month using a smartphone app to perform chunked action sequences. Despite similar procedural learning and attainment of habitual performance (measured by an objective automaticity criterion) by both groups, OCD patients self-reported higher subjective habitual tendencies via a recently developed questionnaire. Subsequently, in a re-evaluation task assessing choices between established automatic and novel goal-directed actions, both groups were sensitive to re-evaluation based on monetary feedback. However, OCD patients, especially those with higher compulsive symptoms and habitual tendencies, showed a clear preference for trained/habitual sequences when choices were based on physical effort, possibly due to their higher attributed intrinsic value. These patients also used the habit-training app more extensively and reported symptom relief post-study. The tendency to attribute higher intrinsic value to familiar actions may be a potential mechanism leading to compulsions and an important addition to the goal/habit imbalance hypothesis in OCD. We also highlight the potential of smartphone app training as a habit reversal therapeutic tool.
New trends of drug abuse in custodial settings: A systematic review on the misuse of over-the-counter drugs, prescription-only-medications, and new psychoactive substances
Chiappini S, Vaccaro G, Mosca A, Miuli A, Stigliano G, Stefanelli G, Giovannetti G, Carullo R, d'Andrea G, Di Carlo F, Cavallotto C, Pettorruso M, Di Petta G, Corkery JM, Guirguis A, Stair JL, Martinotti G, Fazel S and Schifano F
The article presents a systematic literature review on the use and the psychiatric implications of over-the-counter drugs (OTC), prescription-only-medications (POM), and new psychoactive substances (NPS) within custodial settings. The searches wer carried out on 2 November 2022 on PubMed, Scopus, and Web of Science in line with PRISMA guidelines. A total of 538 records were identified, of which 37 met the inclusion criteria. Findings showed the most prevalent NPS and OTC and POM classes reported in prisons were synthetic cannabinoids receptor agonists (SCRAs) and opioids, respectively. NPS markets were shown to be in constant evolution following the pace of legislations aimed to reduce their spread. The use of such substances heavily impacts the conditions and rehabilitation of persons in custody, with consequent physical and mental health risks. It is important to raise awareness of the use and misuse of such substances in prisons (i) from an early warning perspective for law enforcement and policy makers (ii) to prompt doctors to cautiously prescribe substances that may be misused with caution (iii) to improve and increase access to treatment provided (iv) to add such substances to routine toxicological screening procedures (v) to improve harm reduction programmes.
Deep brain stimulation of the amygdala for treatment-resistant combat post-traumatic stress disorder: Long-term results
Koek RJ, Avecillas-Chasin J, Krahl SE, Chen JW, Sultzer DL, Kulick AD, Mandelkern MA, Malpetti M, Gordon HL, Landry HN, Einstein EH and Langevin JP
Deep brain stimulation (DBS) holds promise for neuropsychiatric conditions where imbalance in network activity contributes to symptoms. Treatment-resistant Combat post-traumatic stress disorder (TR-PTSD) is a highly morbid condition and 50% of PTSD sufferers fail to recover despite psychotherapy or pharmacotherapy. Reminder-triggered symptoms may arise from inadequate top-down ventromedial prefrontal cortex (vmPFC) control of amygdala reactivity. Here, we report long-term data on two TR-PTSD participants from an investigation utilizing high-frequency amygdala DBS. The two combat veterans were implanted bilaterally with quadripolar electrodes targeting the basolateral amygdala. Following a randomized staggered onset, patients received stimulation with adjustments based on PTSD symptom severity for four years while psychiatric and neuropsychiatric symptoms, neuropsychological performance, and electroencephalography were systematically monitored. Evaluation of vmPFC-Amygdala network engagement was assessed with FDG positron emission tomography (PET). CAPS-IV scores varied over time, but improved 55% from 119 at baseline to 53 at 4-year study endpoint in participant 1; and 44%, from 68 to 38 in participant 2. Thereafter, during 5 and 1.5 years of subsequent clinical care respectively, long-term bilateral amygdala DBS was associated with additional, clinically significant symptomatic and functional improvement. There were no serious stimulation-related adverse psychiatric, neuropsychiatric, neuropsychological, neurological, or neurosurgical effects. In one subject, symptomatic improvement was associated with an intensity-dependent reduction in amygdala theta frequency power. In our two participants, FDG-PET findings were inconclusive regarding the hypothesized mechanism of suppression of amygdala hyperactivity. Our findings encourage further research to confirm and extend our preliminary observations.
Impact of and research priorities in early onset epilepsy: An investigation of parental concerns
Lindsay N, Martin J, Adegboye D, Absoud M, Charman T and Tye C
[Background and aim] Early onset epilepsy is a neurological condition with significant developmental consequences, and presents affected children and families with challenges which pervade many aspects of family life. Whilst the concerns of parents and the impact on quality of life is well documented in qualitative research, little emphasis has been placed on the context of 'early onset', and the implications of these concerns for research priority setting. We aimed to explore parental perspectives regarding concerns and the impact of early onset epilepsy on the child and family, and to identify priorities for future paediatric epilepsy research. [Methods] The Brain development in Early Epilepsy: Parent Priorities (BEE-PP) project employed a mixed methods approach to collect information on parents' experience of having a child diagnosed with early onset epilepsy before 36 months old and aged up to 16 years old. Parents completed an online survey (n = 15) followed by a focus group (n = 5) to explore their main concerns regarding early onset epilepsy, the impact on family life and research priorities. [Results] A thematic analysis of the focus group data generated eight themes related to concerns of parents, the impact on the family and research priorities. The three main concerns identified were the expected trajectory of their child's development, a lack of seizure control following diagnosis and adverse behavioural side effects of medication. Within family life, early onset epilepsy had an impact on sibling autonomy and psychosocial adaptation, poorer parental wellbeing and restricted social and personal activities. The need for clearer information regarding their child's developmental trajectory, and managing the side effects of medication and their interactions with behaviour over time were topics of priority for future epilepsy research. [Interpretation] The impact of early onset epilepsy on the family is pervasive and requires the provision of appropriate healthcare service-led support for families to improve quality of life and children's adjustment to epilepsy. Regular monitoring of the concerns of parents and the impact of the diagnosis would be beneficial for addressing epilepsy-related and psychosocial needs of the wider family throughout their child's development. Implications for future research priority setting with regards to improved clinician-to-parent information sharing and managing the behavioural side effects of medication are discussed.
Plasma biomarkers increase diagnostic confidence in patients with Alzheimer's disease or frontotemporal lobar degeneration
Altomare D, Libri I, Alberici A, Rivolta J, Padovani A, Ashton NJ, Zetterberg H, Blennow K and Borroni B
The recent development of techniques to assess plasma biomarkers has changed the way the research community envisions the future of diagnosis and management of Alzheimer's disease (AD) and other neurodegenerative disorders. This work aims to provide real world evidence on the clinical impact of plasma biomarkers in an academic tertiary care center.
Effect of childhood emotional abuse on depression and anxiety in adulthood is partially mediated by neuroticism: Evidence from a large online sample
Alnassar JS, Juruena MF, Macare C, Perkins AM and Young AH
Childhood trauma is widely recognized as a potential risk factor for psychiatric illness in adulthood, yet the precise mechanisms underlying this relationship remain incompletely understood. One proposed mechanism involves the impact of childhood trauma on personality development, particularly in relation to neuroticism, which may subsequently heighten susceptibility to psychiatric disorders. In this study, we aimed to investigate this hypothesis through an online survey involving 1116 participants (232 male, 21 %). Participants completed the Childhood Trauma Questionnaire (CTQ), assessing emotional abuse, physical abuse, sexual abuse, emotional neglect, and physical neglect, along with the Trait Self-Description Inventory (TSDI) for personality assessment and the PHQ-9 and GAD-7 clinical questionnaires for depression and anxiety symptoms evaluation, respectively. Our analyses revealed significant positive correlations between all facets of childhood trauma and neuroticism (all p < .01). Linear regression analysis demonstrated that emotional abuse significantly contributed to neuroticism (β = 0.267, p < .05), openness (β = 0.142, p < .05), and agreeableness (β = 0.089, p < .05), while sexual abuse was associated with agreeableness (β = 0.137, p < .01) Emotional neglect was negatively correlated with conscientiousness (β = -0.090, p < .01), extroversion (β = -0.109, p < .01) and agreeableness (β = -0.154, p < .01). Furthermore, linear regression analysis revealed that emotional abuse was positively and significantly correlated with PHQ-9 and GAD-7 scores (r = 0.330, p < .01 and r = 0.327, p < .01, respectively). Mediation analysis supported a significant mediating role of neuroticism in the association between childhood emotional abuse and both depression (PHQ-9) (z = 8.681, p < .01) and anxiety (GAD-7) (z = 9.206, p < .01). Notably, the correlation between childhood emotional abuse and psychiatric symptoms was attenuated but not eliminated after controlling for neuroticism, suggesting partial mediation. While our cross-sectional design precludes causal inference, our findings support the notion that childhood emotional abuse may contribute to increased neuroticism, thereby elevating vulnerability to affective disorders in adulthood. These results underscore the importance of considering personality factors in understanding the long-term consequences of childhood trauma on mental health outcomes.
Acceptance and Commitment Therapy plus usual care for improving quality of life in people with motor neuron disease (COMMEND): a multicentre, parallel, randomised controlled trial in the UK
Gould RL, McDermott CJ, Thompson BJ, Rawlinson CV, Bursnall M, Bradburn M, Kumar P, Turton EJ, White DA, Serfaty MA, Graham CD, McCracken LM, Goldstein LH, Al-Chalabi A, Orrell RW, Williams T, Noad R, Baker I, Faull C, Lambert T, Chhetri SK, Ealing J, Hanratty A, Radunovic A, Gunawardana N, Meadows G, Gorrie GH, Young T, Lawrence V, Cooper C, Shaw PJ, Howard RJ and
Motor neuron disease is a progressive, fatal neurodegenerative disease for which there is no cure. Acceptance and Commitment Therapy (ACT) is a psychological therapy incorporating acceptance, mindfulness, and behaviour change techniques. We aimed to evaluate the effectiveness of ACT plus usual care, compared with usual care alone, for improving quality of life in people with motor neuron disease.
Proximity to high streets, social isolation and social support in British adolescents: A longitudinal analysis of sociospatial influences on social connectedness using geospatial data
Fernandez CC, Maddock J, Patalay P, Fett AK, Pitman A, Vaughan L and Krenz K
High streets have been shown to be central to socio-economic activity, given their diverse residential, leisure, and commercial activities. This study explores the link between adolescent social isolation and proximity to, and land use mix in, high streets. Hypothesising that greater distance from high streets might increase social isolation, measured via social activities, friend contact frequency, and social support, we used multilevel modelling with data from the Millennium Cohort Study. We did not observe a relationship between proximity to high streets and these social isolation indicators, suggesting that high streets may either not significantly influence adolescent social engagement or that young people are willing to travel greater distances.
Scoping Review: Digital Mental Health Interventions for Children and Adolescents Affected by War
Danese A, Martsenkovskyi D, Remberk B, Khalil MY, Diggins E, Keiller E, Masood S, Awah I, Barbui C, Beer R, Calam R, Gagliato M, Jensen TK, Kostova Z, Leckman JF, Lewis SJ, Lorberg B, Myshakivska O, Pfeiffer E, Rosner R, Schleider JL, Shenderovich Y, Skokauskas N, Tolan PH, Caffo E, Sijbrandij M, Ougrin D, Leventhal BL, Weisz JR and
Over 200 million children and adolescents live in countries affected by violent conflict, are likely to have complex mental health needs, and struggle to access traditional mental health services. Digital mental health interventions have the potential to overcome some of the barriers in accessing mental health support. We performed a scoping review to map existing digital mental health interventions relevant for children and adolescents affected by war, examine the strength of the evidence base, and inform the development of future interventions.
Prevalence and co-occurrence of cognitive impairment in children and young people up to 12-months post infection with SARS-CoV-2 (Omicron variant)
Foret-Bruno P, Shafran R, Stephenson T, Nugawela MD, Chan D, Ladhani S, McOwat K, Mensah A, Simmons R, Fox Smith L, D'oelsnitz A, Xu L, Dalrymple E, Heyman I, Ford T, Segal T, Chalder T, Rojas N and Pinto Pereira SM
Cognitive impairment is often reported after SARS-CoV-2 infection, yet evidence gaps remain. We aimed to (i) report the prevalence and characteristics of children and young people (CYP) reporting "brain fog" (i.e., cognitive impairment) 12-months post PCR-proven SARS-CoV-2 infection and determine whether differences by infection status exist and (ii) explore the prevalence of CYP experiencing cognitive impairment over a 12-month period post-infection and investigate the relationship between cognitive impairment and poor mental health and well-being, mental fatigue and sleep problems.
Health, behavior, and social outcomes among offspring of parents with criminal convictions: a register-based study from Sweden
Järvinen A, Lichtenstein P, D'Onofrio BM, Fazel S, Kuja-Halkola R and Latvala A
There is currently insufficient understanding of the health and behavior of children whose parents engage in criminal behavior. We examined associations between parental criminal convictions and wide range of offspring health, behavioral, and social outcomes by age 18 in a large, national sample, aiming to get a comprehensive picture of the risks among children of offending parents.
Emotion-induced frontal α asymmetry as a candidate predictor of relapse after discontinuation of antidepressant medication
Berwian IM, Tröndle M, de Miquel C, Ziogas A, Stefanics G, Walter H, Stephan KE and Huys QJM
One in three patients relapse after antidepressant discontinuation. Thus, the prevention of relapse after achieving remission is an important component in the long-term management of Major Depressive Disorder (MDD). However, no clinical or other predictors are established. Frontal reactivity to sad mood as measured by fMRI has been reported to relate to relapse independently of antidepressant discontinuation and is an interesting candidate predictor.
Diagnostic accuracy of transvaginal ultrasonography and hysterosalpingography in the detection of uterine cavity pathologies among infertile women
Okonkwo IO, Eleje GU, Obiechina NJ, Ugboaja JO, Okafor CO, Mbachu II, Obiagwu HI, Okwuosa AO, Onwusulu DN, Okeke CF, Ofojebe CJ, Okafor CC, Ogabido CA, Olisa CL and Okafor CG
Uterine cavity pathology may affect the endometrium or myometrium, resulting in distortion of the uterine cavity, and is responsible for 2%-5% of infertility. The methods for its assessment usually involve imaging modalities like pelvic ultrasonography, often transvaginal-(TVS), and hysterosalpingography-(HSG), with hysteroscopy-(HSC) as the gold standard. However, HSC is not readily available in resource-poor-settings.
Predicting patients with dementia most at risk of needing psychiatric in-patient or enhanced community care using routinely collected clinical data: retrospective multi-site cohort study
London SR, Chen S, Sidhom E, Lewis JR, Wolverson E, Cardinal RN, Roalf D, Mueller C and Underwood BR
Dementia is a common and progressive condition whose prevalence is growing worldwide. It is challenging for healthcare systems to provide continuity in clinical services for all patients from diagnosis to death.
The management of sleep disturbances in children with attention-deficit/hyperactivity disorder (ADHD): an update of the literature
Cortese S, Fusetto Veronesi G, Gabellone A, Margari A, Marzulli L, Matera E, Petruzelli MG, Piarulli FM, Tarantino F, Bellato A, Parlatini V, Rietz ED, Larsson H, Hornsey S, Hill C and Margari L
Sleep disorders represent an important comorbidity in individuals with ADHD. While the links between ADHD and sleep disturbances have been extensively investigated, research on the management of sleep disorders in individuals with ADHD is relatively limited, albeit expanding.
Implementation of the International Classification of Diseases 11th revision behavioural indicators for disorders of intellectual development with co-occurring autism spectrum disorder
Lemay KR, Kogan CS, Rebello T, Keeley JW, Bhargava R, Buono S, Cooray S, Ginige P, Kishore MT, Kommu JVS, Recupero M, Roy A, Sharan P and Reed GM
The classification of mental, behavioural and neurodevelopmental disorders in the World Health Organization's International Classification of Diseases 11th revision (ICD-11) includes a comprehensive set of behavioural indicators (BIs) within the neurodevelopmental disorders grouping. BIs can be used to assess the severity of disorders of intellectual development in situations in which standardised measures of intellectual functioning and adaptive behaviours are not available or feasible. This international study examines the implementation characteristics of the BIs and compares them to standardised measures for assessing the severity of intellectual impairment and adaptive behaviours in disorders of intellectual development and autism spectrum disorder (ASD). The clinical utility of the ICD-11 and the fidelity of its application in international clinical settings were also assessed.
Non-parental Childcare During Early Childhood and Problem Behaviour Trajectories from Ages 5 to 14 Years
Burdenski K, Johnson W, Petherick E and Costa S
Using data from the nationally representative Millennium Cohort Study, this study examined the association between age of starting and weekly hours in formal childcare between birth and 5 years with internalising and externalising behaviour trajectories from ages 5 to 14 years in England (N = 6194 children). Associations were analysed using multilevel general linear regression models, with adjustment for socio-economic position, maternal mental health, demographics, and child temperament. Later entry was associated with more internalising behaviours at age 14 years. Children who spent > 40 h per week in childcare between birth and 3 years displayed more externalising behaviour at 5 years than children who did not attend childcare. Controlling for socio-economic position and parental mental health attenuated findings.
Perspectives on the diagnosis and management of functional cognitive disorder: An international Delphi study
Cabreira V, Alty J, Antic S, Araújo R, Aybek S, Ball HA, Baslet G, Bhome R, Coebergh J, Dubois B, Edwards M, Filipović SR, Frederiksen KS, Harbo T, Hayhow B, Howard R, Huntley J, Isaacs J, LaFrance WC, Larner AJ, Di Lorenzo F, Main J, Mallam E, Marra C, Massano J, McGrath ER, McWhirter L, Moreira IP, Nobili F, Pennington C, Tábuas-Pereira M, Perez DL, Popkirov S, Rayment D, Rossor M, Russo M, Santana I, Schott J, Scott EP, Taipa R, Tinazzi M, Tomic S, Toniolo S, Tørring CW, Wilkinson T, Frostholm L, Stone J and Carson A
Current proposed criteria for functional cognitive disorder (FCD) have not been externally validated. We sought to analyse the current perspectives of cognitive specialists in the diagnosis and management of FCD in comparison with neurodegenerative conditions.
Investigating practice integration of independent prescribing by community pharmacists using normalization process theory: a cross-sectional survey
Karim L, McIntosh T, Jebara T, Pfleger D, Osprey A and Cunningham S
Independent prescribing (IP) has not been extensively investigated in community pharmacy (CP). Normalization process theory (NPT) constructs help explain how interventions are integrated into practice and include: 'coherence' (understanding), 'cognitive participation' (what promotes engagement), 'collective action' (integration with existing systems), and 'reflexive monitoring' (evaluation).
Targeting durable remission of fatigue in inflammatory bowel disease
Moulton CD, Young AH and Hart AL
Role of Inflammation in Short Sleep Duration Across Childhood and Psychosis in Young Adulthood
Morales-Muñoz I, Marwaha S, Upthegrove R and Cropley V
Short sleep duration over a prolonged period in childhood could have a detrimental impact on long-term mental health, including the development of psychosis. Further, potential underlying mechanisms of these associations remain unknown.
Linkage of routinely collected NHS data to evaluate liaison mental health services: challenges and lessons learned
Guthrie E, House A, Smith C, Relton S, Romeu D, Saraiva S, Trigwell P, West R, Shuweihdi F, Crawford M, Fossey M, Hewison J, Hulme C and Tubeuf S
Liaison mental health services provide mental health care to patients in acute hospital settings. Evaluation of liaison services is challenging due to their heterogeneous organisation and delivery, high case throughput and varied patient case mix. We aimed to link routinely collected National Health Service data from secondary care settings, chosen for their service characteristics, to data from primary care to evaluate hospital-based liaison mental health services in England.
CIDP trials and tribulations
Rinaldi S
Ask the consultant: old age psychiatry
Vedavanam K, Warner J and Zaidman S
Qatar's National Mental Health Study-The World Mental Health Qatar
Khaled SM, Al-Abdulla M, Tulley I, Al-Thani SM and Woodruff PW
We provide an overview of Qatar's first epidemiological study on prevalence, predictors, and treatment contact for mood and anxiety disorders.
Post-task responses following working memory and movement are driven by transient spectral bursts with similar characteristics
Coleman SC, Seedat ZA, Pakenham DO, Quinn AJ, Brookes MJ, Woolrich MW and Mullinger KJ
The post-movement beta rebound has been studied extensively using magnetoencephalography (MEG) and is reliably modulated by various task parameters as well as illness. Our recent study showed that rebounds, which we generalise as "post-task responses" (PTRs), are a ubiquitous phenomenon in the brain, occurring across the cortex in theta, alpha, and beta bands. Currently, it is unknown whether PTRs following working memory are driven by transient bursts, which are moments of short-lived high amplitude activity, similar to those that drive the post-movement beta rebound. Here, we use three-state univariate hidden Markov models (HMMs), which can identify bursts without a priori knowledge of frequency content or response timings, to compare bursts that drive PTRs in working memory and visuomotor MEG datasets. Our results show that PTRs across working memory and visuomotor tasks are driven by pan-spectral transient bursts. These bursts have very similar spectral content variation over the cortex, correlating strongly between the two tasks in the alpha (R = .89) and beta (R = .53) bands. Bursts also have similar variation in duration over the cortex (e.g., long duration bursts occur in the motor cortex for both tasks), strongly correlating over cortical regions between tasks (R = .56), with a mean over all regions of around 300 ms in both datasets. Finally, we demonstrate the ability of HMMs to isolate signals of interest in MEG data, such that the HMM probability timecourse correlates more strongly with reaction times than frequency filtered power envelopes from the same brain regions. Overall, we show that induced PTRs across different tasks are driven by bursts with similar characteristics, which can be identified using HMMs. Given the similarity between bursts across tasks, we suggest that PTRs across the cortex may be driven by a common underlying neural phenomenon.
Clinical reappraisal of the composite international diagnostic interview version 3.3 in Qatar's National Mental Health Study
Khaled SM, Amro I, Abdelkader M, Al Bahari D, Al Shawwaf M, Alabdulla M, Alhassan A, Ali A, Aly S, Amin A, Chiu WT, Currie J, El Fakki H, First MB, Hassan MHO, Hijawi Z, Mohammed R, Nofal M, Salman S, Sampson NA, Woodruff PW and Kessler RC
Lifetime DSM-5 diagnoses generated by the lay-administered Composite International Diagnostic Interview for DSM-5 (CIDI) in the World Mental Health Qatar (WMHQ) study were compared to diagnoses based on blinded clinician-administered reappraisal interviews.
Lifetime prevalence, risk, and treatment of mood and anxiety disorders in Qatar's national mental health study
Khaled SM, Alhussaini NWZ, Alabdulla M, Sampson NA, Kessler RC, Woodruff PW and Al-Thani SM
To estimate lifetime prevalence, risk, and treatment for mental disorders and their correlates in Qatar's general population for the first time.
A comprehensive examination of mental health in patients with head and neck cancer: Systematic review and meta-analysis
Jimenez-Labaig P, Aymerich C, Braña I, Rullan A, Cacicedo J, González-Torres MÁ, Harrington KJ and Catalan A
Patients with head and neck cancer (HNC) present particularly significant levels of emotional distress. However, the actual rates of clinically relevant mental health symptoms and disorders among this population remain unknown.
Brief Educational Workshops in Secondary Schools Trial (BESST trial), a school-based cluster randomised controlled trial of the DISCOVER workshop for 16-18-year-olds: recruitment and baseline characteristics
James K, Lisk S, Payne-Cook C, Farishta Z, Farrelly M, Sheikh A, Slusarczyk M, Byford S, Day C, Deighton J, Evans C, Fonagy P, Saunders D, Sclare I, Shearer J, Stallard P, Weaver T, Yarrum J, Carter B and Brown JSL
The Brief Educational Workshops in Secondary Schools Trial (BESST) is an England-wide school-based cluster randomised controlled trial assessing the clinical and cost-effectiveness of an open-access psychological workshop programme (DISCOVER) for 16-18-year-olds. This baseline paper describes the self-referral and other recruitment processes used in this study and the baseline characteristics of the enrolled schools and participants.
"": A qualitative exploration of the experiences of young people with Long COVID
Newlands F, Lewis C, d'Oelsnitz A, Pinto Pereira SM, Stephenson T, Chalder T, Coughtrey A, Dalrymple E, Heyman I, Harnden A, Ford T, Ladhani SN, Powell C, McOwat K, Bhopal R, Dudley J, Kolasinska P, Muhid MZ, Nugawela M, Rojas NK, Shittu A, Simmons R and Shafran R
Young people living with Long COVID are learning to navigate life with a constellation of poorly understood symptoms. Most qualitative studies on experiences living with Long COVID focus on adult populations. This study aimed to understand the experiences of young people living with Long COVID. Qualitative, semi-structured interviews were conducted ( = 16); 11 young people (aged 13-19) and five parents were recruited from the Children and Young People with Long COVID (CLoCk) study ( = 11) or its patient and public involvement and engagement (PPIE) group ( = 5). Thematic analysis generated four themes: (i) Unravelling Long COVID: Exploring Symptom Journeys and Diagnostic Dilemmas; (ii) Identity Disruption and Adjustment; (iii) Long COVID's Ripple Effect: the impact on Mental Health, Connections, and Education; and (iv) Navigating Long COVID: barriers to support and accessing services. Treatment options were perceived as not widely available or ineffective, emphasising the need for viable and accessible interventions for young people living with Long COVID.
Predictive coding and phenomenological approaches of delusions: convergence and differences - Authors' reply
Harding JN, Wolpe N, Brugger SP, Navarro V, Teufel C and Fletcher PC
Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021
Understanding the health consequences associated with exposure to risk factors is necessary to inform public health policy and practice. To systematically quantify the contributions of risk factor exposures to specific health outcomes, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 aims to provide comprehensive estimates of exposure levels, relative health risks, and attributable burden of disease for 88 risk factors in 204 countries and territories and 811 subnational locations, from 1990 to 2021.
Updates from the third residential course on child and adolescent psychiatry endorsed by the European Society for Child and Adolescent mental health-ESCAP
Riccioni A, Siracusano M, Davico C, Klauser P, Morcillo C, Ougrin D, Vitiello B, Plessen KJ, Armando M, Mazzone L and Cortese S
The evolving profile of eating disorders and their treatment in a changing and globalised world
Himmerich H, Keeler JL, Davies HL, Tessema SA and Treasure J
How the coronavirus pandemic affected the lives of people with ALS and their spouses in the UK from spouses' perspectives: a qualitative study
Didcote L, Al-Chalabi A and Goldstein LH
This study set out to investigate, using qualitative methodology, the experiences of spouses of people with Amyotrophic Lateral Sclerosis (ALS) during the coronavirus pandemic, with particular focus on spouse distress and cognitive and behavioral change in people with ALS (pwALS).
Practitioner Review: Assessment and treatment of body dysmorphic disorder in young people
Krebs G, Rautio D, Fernández de la Cruz L, Hartmann AS, Jassi A, Martin A, Stringaris A and Mataix-Cols D
Body dysmorphic disorder (BDD) is a relatively common and highly impairing mental disorder that is strikingly underdiagnosed and undertreated in Child and Adolescent Mental Health Services (CAMHS). The only clinical guidelines for the management of BDD in youth were published nearly 20 years ago, when empirical knowledge was sparse. Fortunately, there has been a surge in research into BDD over the last 10 years, shedding important insights into the phenomenology, epidemiology, assessment and treatment of the disorder in young people. This review aimed to provide an overview of recent research developments of relevance to clinicians and healthcare policymakers. We summarise key findings regarding the epidemiology of BDD in youth, which indicate that the disorder usually develops during teenage years and affects approximately 2% of adolescents at any one point in time. We provide an overview of aetiological research, highlighting that BDD arises from an interplay between genetic and environmental influences. We then focus on screening and assessment strategies, arguing that these are crucial to promote detection and diagnosis of this under-recognised condition. Additionally, we summarise the recommended treatment approaches for BDD in youth, namely cognitive behaviour therapy with or without selective serotonin reuptake inhibitors. The review concludes by highlighting key knowledge gaps and priorities for future research including, but not limited to, better understanding aetiological factors, long-term consequences and treatment.
Exploring decision-making performance in young adults with mental health disorders: a comparative study using the Cambridge gambling task
Effah R, Ioannidis K, Grant JE and Chamberlain SR
Decision-making deficits, assessed cognitively, are often associated with mental health symptoms, however, this relationship is not fully understood. This paper explores the relationship between mental health disorders and decision-making, using the Cambridge Gambling Task (CGT). Our study investigated how decision-making varied across 20 different mental health conditions compared to controls in a sample of 572 young adults from the Minneapolis and Chicago metropolitan areas, using a computerized laboratory-based task. Almost all mental health conditions were associated with at least mild (i.e. at least small effect size) impairment in all three studied parameters of the CGT (risk adjustment, quality of decision-making and overall proportion of bet). Notably, binge eating disorder had the largest cognitive impairment and gambling disorder had moderate impairment. Post-traumatic stress disorder (PTSD) was associated with impaired decision-making while obsessive-compulsive disorder (OCD) and depression showed moderate impairment. Additionally, half of the disorders assessed had moderate to large impairment in risk adjustment.These findings suggest that mental health conditions may have a more complex cognitive profile than previously thought, and a better understanding of these impairments may aid in risk assessment and targeted clinical interventions. This study underscores the need for further research to determine the causal pathways between mental health conditions and cognition, as well as to better understand the day-to-day impact of such deficits.
Examining the unique relationships between problematic use of the internet and impulsive and compulsive tendencies: network approach
Liu C, Rotaru K, Ren L, Chamberlain SR, Christensen E, Brierley ME, Richardson K, Lee RSC, Segrave R, Grant JE, Kayayan E, Hughes S, Fontenelle LF, Lowe A, Suo C, Freichel R, Wiers RW, Yücel M and Albertella L
Both impulsivity and compulsivity have been identified as risk factors for problematic use of the internet (PUI). Yet little is known about the relationship between impulsivity, compulsivity and individual PUI symptoms, limiting a more precise understanding of mechanisms underlying PUI.
Associations of Testosterone and Related Hormones With All-Cause and Cardiovascular Mortality and Incident Cardiovascular Disease in Men : Individual Participant Data Meta-analyses
Yeap BB, Marriott RJ, Dwivedi G, Adams RJ, Antonio L, Ballantyne CM, Bauer DC, Bhasin S, Biggs ML, Cawthon PM, Couper DJ, Dobs AS, Flicker L, Handelsman DJ, Hankey GJ, Hannemann A, Haring R, Hsu B, Martin SA, Matsumoto AM, Mellström D, Ohlsson C, O'Neill TW, Orwoll ES, Quartagno M, Shores MM, Steveling A, Tivesten Å, Travison TG, Vanderschueren D, Wittert GA, Wu FCW and Murray K
Whether circulating sex hormones modulate mortality and cardiovascular disease (CVD) risk in aging men is controversial.
Digital Mental Health for Schizophrenia and Other Severe Mental Illnesses: An International Consensus on Current Challenges and Potential Solutions
Smith KA, Hardy A, Vinnikova A, Blease C, Milligan L, Hidalgo-Mazzei D, Lambe S, Marzano L, Uhlhaas PJ, Ostinelli EG, Anmella G, Zangani C, Aronica R, Dwyer B, Torous J and Cipriani A
Digital approaches may be helpful in augmenting care to address unmet mental health needs, particularly for schizophrenia and severe mental illness (SMI).
Sexually transmitted infections, sexual life and risk behaviours of people living with schizophrenia: systematic review and meta-analysis
Aymerich C, Pedruzo B, Salazar de Pablo G, Madaria L, Goena J, Sanchez-Gistau V, Fusar-Poli P, McGuire P, González-Torres MÁ and Catalan A
Sexually transmitted infections (STIs), along with sexual health and behaviour, have received little attention in schizophrenia patients.
Shorter night-time sleep duration and later sleep timing from infancy to adolescence
Manitsa I, Gregory AM, Broome MR, Bagshaw AP, Marwaha S and Morales-Muñoz I
Here, we (a) examined the trajectories of night-time sleep duration, bedtime and midpoint of night-time sleep (MPS) from infancy to adolescence, and (b) explored perinatal risk factors for persistent poor sleep health.
Investigating cortical excitability and inhibition in patients with schizophrenia: A TMS-EEG study
Santoro V, Hou MD, Premoli I, Belardinelli P, Biondi A, Carobin A, Puledda F, Michalopoulou PG, Richardson MP, Rocchi L and Shergill SS
Transcranial magnetic stimulation (TMS) combined with electromyography (EMG) has widely been used as a non-invasive brain stimulation tool to assess excitation/inhibition (E/I) balance. E/I imbalance is a putative mechanism underlying symptoms in patients with schizophrenia. Combined TMS-electroencephalography (TMS-EEG) provides a detailed examination of cortical excitability to assess the pathophysiology of schizophrenia. This study aimed to investigate differences in TMS-evoked potentials (TEPs), TMS-related spectral perturbations (TRSP) and intertrial coherence (ITC) between patients with schizophrenia and healthy controls.
Effects of ebselen addition on emotional processing and brain neurochemistry in depressed patients unresponsive to antidepressant medication
Ramli FF, Singh N, Emir UE, Villa LM, Waters S, Harmer CJ, Cowen PJ and Godlewska BR
Lithium is an effective augmenting agent for depressed patients with inadequate response to standard antidepressant therapy, but numerous adverse effects limit its use. We previously reported that a lithium-mimetic agent, ebselen, promoted a positive emotional bias-an indicator of potential antidepressant activity in healthy participants. We therefore aimed to investigate the effects of short-term ebselen treatment on emotional processing and brain neurochemistry in depressed patients with inadequate response to standard antidepressants. We conducted a double-blind, placebo-controlled 7-day experimental medicine study in 51 patients with major depressive disorder who were currently taking antidepressants but had an inadequate response to treatment. Participants received either ebselen 600 mg twice daily for seven days or identical matching placebo. An emotional testing battery, magnetic resonance spectroscopy and depression and anxiety rating scales were conducted at baseline and after seven days of treatment. Ebselen did not increase the recognition of positive facial expressions in the depressed patient group. However, ebselen increased the response bias towards fear emotion in the signal detection measurement. In the anterior cingulate cortex, ebselen significantly reduced the concentrations of inositol and Glx (glutamate+glutamine). We found no significant differences in depression and anxiety rating scales between visits. Our study did not find any positive shift in emotional bias in depressed patients with an inadequate response to antidepressant medication. We confirmed the ability of ebselen to lower inositol and Glx in the anterior cingulate cortex. These latter effects are probably mediated through inhibition of inositol monophosphatase and glutaminase respectively.
A transdiagnostic prodrome for severe mental disorders: an electronic health record study
Arribas M, Oliver D, Patel R, Kornblum D, Shetty H, Damiani S, Krakowski K, Provenzani U, Stahl D, Koutsouleris N, McGuire P and Fusar-Poli P
Effective prevention of severe mental disorders (SMD), including non-psychotic unipolar mood disorders (UMD), non-psychotic bipolar mood disorders (BMD), and psychotic disorders (PSY), rely on accurate knowledge of the duration, first presentation, time course and transdiagnosticity of their prodromal stages. Here we present a retrospective, real-world, cohort study using electronic health records, adhering to RECORD guidelines. Natural language processing algorithms were used to extract monthly occurrences of 65 prodromal features (symptoms and substance use), grouped into eight prodromal clusters. The duration, first presentation, and transdiagnosticity of the prodrome were compared between SMD groups with one-way ANOVA, Cohen's f and d. The time course (mean occurrences) of prodromal clusters was compared between SMD groups with linear mixed-effects models. 26,975 individuals diagnosed with ICD-10 SMD were followed up for up to 12 years (UMD = 13,422; BMD = 2506; PSY = 11,047; median[IQR] age 39.8[23.7] years; 55% female; 52% white). The duration of the UMD prodrome (18[36] months) was shorter than BMD (26[35], d = 0.21) and PSY (24[38], d = 0.18). Most individuals presented with multiple first prodromal clusters, with the most common being non-specific ('other'; 88% UMD, 85% BMD, 78% PSY). The only first prodromal cluster that showed a medium-sized difference between the three SMD groups was positive symptoms (f = 0.30). Time course analysis showed an increase in prodromal cluster occurrences approaching SMD onset. Feature occurrence across the prodromal period showed small/negligible differences between SMD groups, suggesting that most features are transdiagnostic, except for positive symptoms (e.g. paranoia, f = 0.40). Taken together, our findings show minimal differences in the duration and first presentation of the SMD prodromes as recorded in secondary mental health care. All the prodromal clusters intensified as individuals approached SMD onset, and all the prodromal features other than positive symptoms are transdiagnostic. These results support proposals to develop transdiagnostic preventive services for affective and psychotic disorders detected in secondary mental healthcare.
Exploring causal mechanisms of psychosis risk
Oliver D, Chesney E, Cullen AE, Davies C, Englund A, Gifford G, Kerins S, Lalousis PA, Logeswaran Y, Merritt K, Zahid U, Crossley NA, McCutcheon RA, McGuire P and Fusar-Poli P
Robust epidemiological evidence of risk and protective factors for psychosis is essential to inform preventive interventions. Previous evidence syntheses have classified these risk and protective factors according to their strength of association with psychosis. In this critical review we appraise the distinct and overlapping mechanisms of 25 key environmental risk factors for psychosis, and link these to mechanistic pathways that may contribute to neurochemical alterations hypothesised to underlie psychotic symptoms. We then discuss the implications of our findings for future research, specifically considering interactions between factors, exploring universal and subgroup-specific factors, improving understanding of temporality and risk dynamics, standardising operationalisation and measurement of risk and protective factors, and developing preventive interventions targeting risk and protective factors.
Sickness absence and associations with sociodemographic factors, health risk behaviours, occupational stressors and adverse mental health in 40,343 UK police employees
Parkes S, Irizar P, Greenberg N, Wessely S, Fear NT, Hotopf M and Stevelink SAM
Police employees may experience high levels of stress due to the challenging nature of their work which can then lead to sickness absence. To date, there has been limited research on sickness absence in the police. This exploratory analysis investigated sickness absence in UK police employees.
Perceived expressed emotion in individuals with a first episode of psychosis from a south Asian background
Ramanathan A, Miah SK, Nagularaj L, Sharif HS and Shaikh M
To explore perceived expressed emotion in the south Asian context for individuals with a first episode of psychosis (FEP).
Sustaining attention in affective contexts during adolescence: age-related differences and association with elevated symptoms of depression and anxiety
Dunning DL, Parker J, Griffiths K, Bennett M, Archer-Boyd A, Bevan A, Ahmed S, Griffin C, Foulkes L, Leung J, Sakhardande A, Manly T, Kuyken W, Williams JMG, Blakemore SJ and Dalgleish T
Sustained attention, a key cognitive skill that improves during childhood and adolescence, tends to be worse in some emotional and behavioural disorders. Sustained attention is typically studied in non-affective task contexts; here, we used a novel task to index performance in affective versus neutral contexts across adolescence (= 465; ages 11-18). We asked whether: (i) performance would be worse in negative versus neutral task contexts; (ii) performance would improve with age; (iii) affective interference would be greater in younger adolescents; (iv) adolescents at risk for depression and higher in anxiety would show overall worse performance; and (v) would show differential performance in negative contexts. Results indicated that participants performed more poorly in negative contexts and showed age-related performance improvements. Those at risk of depression performed more poorly than those at lower risk. However, there was no difference between groups as a result of affective context. For anxiety there was no difference in performance as a function of severity. However, those with higher anxiety showed less variance in their reaction times to negative stimuli than those with lower anxiety. One interpretation is that moderate levels of emotional arousal associated with anxiety make individuals less susceptible to the distracting effects of negative stimuli.
LGI1-antibody encephalitis: how to approach this highly treatable dementia mimic in memory and mental health services
Binks SNM, Al-Diwani A, Handel AE, Bajorek T, Manohar S, Husain M, Irani SR and Koychev I
Leucine-rich glioma-inactivated 1-antibody-encephalitis is a treatable and potentially reversible cause of cognitive and psychiatric presentations, and may mimic cognitive decline, rapidly progressive dementia and complex psychosis in older patients. This aetiology is of immediate relevance given the alternative treatment pathway required, compared with other conditions presenting with cognitive deficits.
Personalized whole-brain neural mass models reveal combined Aβ and tau hyperexcitable influences in Alzheimer's disease
Sanchez-Rodriguez LM, Bezgin G, Carbonell F, Therriault J, Fernandez-Arias J, Servaes S, Rahmouni N, Tissot C, Stevenson J, Karikari TK, Ashton NJ, Benedet AL, Zetterberg H, Blennow K, Triana-Baltzer G, Kolb HC, Rosa-Neto P and Iturria-Medina Y
Neuronal dysfunction and cognitive deterioration in Alzheimer's disease (AD) are likely caused by multiple pathophysiological factors. However, mechanistic evidence in humans remains scarce, requiring improved non-invasive techniques and integrative models. We introduce personalized AD computational models built on whole-brain Wilson-Cowan oscillators and incorporating resting-state functional MRI, amyloid-β (Aβ) and tau-PET from 132 individuals in the AD spectrum to evaluate the direct impact of toxic protein deposition on neuronal activity. This subject-specific approach uncovers key patho-mechanistic interactions, including synergistic Aβ and tau effects on cognitive impairment and neuronal excitability increases with disease progression. The data-derived neuronal excitability values strongly predict clinically relevant AD plasma biomarker concentrations (p-tau217, p-tau231, p-tau181, GFAP) and grey matter atrophy obtained through voxel-based morphometry. Furthermore, reconstructed EEG proxy quantities show the hallmark AD electrophysiological alterations (theta band activity enhancement and alpha reductions) which occur with Aβ-positivity and after limbic tau involvement. Microglial activation influences on neuronal activity are less definitive, potentially due to neuroimaging limitations in mapping neuroprotective vs detrimental activation phenotypes. Mechanistic brain activity models can further clarify intricate neurodegenerative processes and accelerate preventive/treatment interventions.
Delivering a sleep intervention across a youth mental health service using non-expert practitioners: A service evaluation
Rollinson R, Cole A, Gee B, Tofan I, Graham A, Hatton J, Lyons J, Reeve S, Wilson J, Beardsworth K and Clarke T
Poor sleep is highly prevalent in young people and increases risk of mental health difficulties, yet access to sleep interventions remains limited. This paper evaluates the use of a sleep intervention delivered by non-expert practitioners in a secondary care youth mental health service.
Cost-effectiveness of surgery for degenerative cervical myelopathy in the United Kingdom
Goacher E, Yardanov S, Phillips R, Budu A, Dyson E, Ivanov M, Barton G, Hutton M, Gardner A, Quraishi NA, Grahovac G, Jung J, Demetriades AK, Vergara P, Pereira E, Arzoglou V, Francis J, Trivedi R, Davies BM and Kotter MRN
Degenerative cervical myelopathy (DCM) is the commonest cause of adult spinal cord dysfunction worldwide, for which surgery is the mainstay of treatment. At present, there is limited literature on the costs associated with the surgical management of DCM, and none from the United Kingdom (UK). This study aimed to evaluate the cost-effectiveness of DCM surgery within the National Health Service, UK.
The relationship between cognitive phenotypes of compulsivity and impulsivity and clinical variables in obsessive-compulsive disorder: A systematic review and Meta-analysis
Clarke AT, Fineberg NA, Pellegrini L and Laws KR
This systematic review and meta-analysis explored the relationship between cognitive phenotypes of compulsivity and impulsivity and clinical variables in obsessive-compulsive disorder (OCD).
Genome sequence analyses identify novel risk loci for multiple system atrophy
Chia R, Ray A, Shah Z, Ding J, Ruffo P, Fujita M, Menon V, Saez-Atienzar S, Reho P, Kaivola K, Walton RL, Reynolds RH, Karra R, Sait S, Akcimen F, Diez-Fairen M, Alvarez I, Fanciulli A, Stefanova N, Seppi K, Duerr S, Leys F, Krismer F, Sidoroff V, Zimprich A, Pirker W, Rascol O, Foubert-Samier A, Meissner WG, Tison F, Pavy-Le Traon A, Pellecchia MT, Barone P, Russillo MC, Marín-Lahoz J, Kulisevsky J, Torres S, Mir P, Periñán MT, Proukakis C, Chelban V, Wu L, Goh YY, Parkkinen L, Hu MT, Kobylecki C, Saxon JA, Rollinson S, Garland E, Biaggioni I, Litvan I, Rubio I, Alcalay RN, Kwei KT, Lubbe SJ, Mao Q, Flanagan ME, Castellani RJ, Khurana V, Ndayisaba A, Calvo A, Mora G, Canosa A, Floris G, Bohannan RC, Moore A, Norcliffe-Kaufmann L, Palma JA, Kaufmann H, Kim C, Iba M, Masliah E, Dawson TM, Rosenthal LS, Pantelyat A, Albert MS, Pletnikova O, Troncoso JC, Infante J, Lage C, Sánchez-Juan P, Serrano GE, Beach TG, Pastor P, Morris HR, Albani D, Clarimon J, Wenning GK, Hardy JA, Ryten M, Topol E, Torkamani A, Chiò A, Bennett DA, De Jager PL, Low PA, Singer W, Cheshire WP, Wszolek ZK, Dickson DW, Traynor BJ, Gibbs JR, Dalgard CL, Ross OA, Houlden H and Scholz SW
Multiple system atrophy (MSA) is an adult-onset, sporadic synucleinopathy characterized by parkinsonism, cerebellar ataxia, and dysautonomia. The genetic architecture of MSA is poorly understood, and treatments are limited to supportive measures. Here, we performed a comprehensive analysis of whole genome sequence data from 888 European-ancestry MSA cases and 7,128 controls to systematically investigate the genetic underpinnings of this understudied neurodegenerative disease. We identified four significantly associated risk loci using a genome-wide association study approach. Transcriptome-wide association analyses prioritized USP38-DT, KCTD7, and lnc-KCTD7-2 as novel susceptibility genes for MSA within these loci, and single-nucleus RNA sequence analysis found that the associated variants acted as cis-expression quantitative trait loci for multiple genes across neuronal and glial cell types. In conclusion, this study highlights the role of genetic determinants in the pathogenesis of MSA, and the publicly available data from this study represent a valuable resource for investigating synucleinopathies.
Telemedicine and Neurology: A Survey of Neurology Patients in a Nigerian Tertiary Hospital
Yakubu AO, Olalude O, Salami M, Amuta AC, Amusa A, Salaudeen HA and Awoyemi AJ
Background Telemedicine has been recognized as a viable solution for addressing the shortage of medical professionals in developing countries such as Nigeria. Tele-neurology has the potential to provide remote consultations and care for patients with neurological conditions, thereby reducing the burden of travel and improving access to medical care. Despite its growing popularity, there is a lack of research on patient's views on this mode of care delivery in Nigeria. This study was conducted to investigate patient's perspectives on the use of tele-neurology in Nigeria. Methodology A descriptive cross-sectional study was conducted among 398 neurology patients at Olabisi Onabanjo University Teaching Hospital, Sagamu, Ogun State, Nigeria. The data obtained were analyzed using descriptive statistics and a chi-square test using p < 0.05. Results Only 3% of our respondents had previously used telemedicine, with 78.1% of the respondents open to using telemedicine as a means of consultation. The disadvantages of telemedicine noted include limitations in assessing neurological status (94.7%), difficulty in explaining health conditions (84.4%), and lack of technical support (14.6%). The majority of respondents (96.5%) believed telemedicine will help in saving time. There was a statistically significant association between propensity to use telemedicine and time spent in the hospital (0.045) and time off work (<0.001). The propensity to use telemedicine was statistically significant to the use of email (0.001) and type of email address (0.001). Conclusion The findings suggested that there is a need for healthcare providers and policymakers to invest in developing telemedicine to improve access to care.
Role of Inflammation in Depressive and Anxiety Disorders, Affect, and Cognition: Genetic and Non-Genetic Findings in the Lifelines Cohort Study
Giollabhui NM, Slaney C, Hemani G, Foley ÉM, van der Most PJ, Nolte IM, Snieder H, Smith GD, Khandaker G and Hartman CA
Low-grade systemic inflammation is implicated in the pathogenesis of various neuropsychiatric conditions affecting mood and cognition. While much of the evidence concerns depression, large-scale population studies of anxiety, affect, and cognitive function are scarce. Importantly, causality remains unclear. We used complementary non-genetic, genetic risk score (GRS), and Mendelian randomization (MR) analyses to examine whether inflammatory markers are associated with affect, depressive and anxiety disorders, and cognitive performance in the Lifelines Cohort; and whether associations are likely to be causal.
Rectified Latent Variable Model-Based EMG Factorization of Inhibitory Muscle Synergy Components Related to Aging, Expertise and Force-Tempo Variations
Huang S, Guo X, Xie JJ, Lau KYS, Liu R, Mak ADP, Cheung VCK and Chan RHM
Muscle synergy has been widely acknowledged as a possible strategy of neuromotor control, but current research has ignored the potential inhibitory components in muscle synergies. Our study aims to identify and characterize the inhibitory components within motor modules derived from electromyography (EMG), investigate the impact of aging and motor expertise on these components, and better understand the nervous system's adaptions to varying task demands. We utilized a rectified latent variable model (RLVM) to factorize motor modules with inhibitory components from EMG signals recorded from ten expert pianists when they played scales and pieces at different tempo-force combinations. We found that older participants showed a higher proportion of inhibitory components compared with the younger group. Senior experts had a higher proportion of inhibitory components on the left hand, and most inhibitory components became less negative with increased tempo or decreased force. Our results demonstrated that the inhibitory components in muscle synergies could be shaped by aging and expertise, and also took part in motor control for adapting to different conditions in complex tasks.
Genome-wide association study identifies 30 obsessive-compulsive disorder associated loci
Strom NI, Gerring ZF, Galimberti M, Yu D, Halvorsen MW, Abdellaoui A, Rodriguez-Fontenla C, Sealock JM, Bigdeli T, Coleman JR, Mahjani B, Thorp JG, Bey K, Burton CL, Luykx JJ, Zai G, Alemany S, Andre C, Askland KD, Banaj N, Barlassina C, Nissen JB, Bienvenu OJ, Black D, Bloch MH, Boberg J, Børte S, Bosch R, Breen M, Brennan BP, Brentani H, Buxbaum JD, Bybjerg-Grauholm J, Byrne EM, Cabana-Dominguez J, Camarena B, Camarena A, Cappi C, Carracedo A, Casas M, Cavallini MC, Ciullo V, Cook EH, Crosby J, Cullen BA, De Schipper EJ, Delorme R, Djurovic S, Elias JA, Estivill X, Falkenstein MJ, Fundin BT, Garner L, German C, Gironda C, Goes FS, Grados MA, Grove J, Guo W, Haavik J, Hagen K, Harrington K, Havdahl A, Höffler KD, Hounie AG, Hucks D, Hultman C, Janecka M, Jenike E, Karlsson EK, Kelley K, Klawohn J, Krasnow JE, Krebs K, Lange C, Lanzagorta N, Levey D, Lindblad-Toh K, Macciardi F, Maher B, Mathes B, McArthur E, McGregor N, McLaughlin NC, Meier S, Miguel EC, Mulhern M, Nestadt PS, Nurmi EL, O'Connell KS, Osiecki L, Ousdal OT, Palviainen T, Pedersen NL, Piras F, Piras F, Potluri S, Rabionet R, Ramirez A, Rauch S, Reichenberg A, Riddle MA, Ripke S, Rosário MC, Sampaio AS, Schiele MA, Skogholt AH, Sloofman LGSG, Smit J, Soler AM, Thomas LF, Tifft E, Vallada H, van Kirk N, Veenstra-VanderWeele J, Vulink NN, Walker CP, Wang Y, Wendland JR, Winsvold BS, Yao Y, Zhou H, , , , , , Agrawal A, Alonso P, Berberich G, Bucholz KK, Bulik CM, Cath D, Denys D, Eapen V, Edenberg H, Falkai P, Fernandez TV, Fyer AJ, Gaziano JM, Geller DA, Grabe HJ, Greenberg BD, Hanna GL, Hickie IB, Hougaard DM, Kathmann N, Kennedy J, Lai D, Landén M, Le Hellard S, Leboyer M, Lochner C, McCracken JT, Medland SE, Mortensen PB, Neale BM, Nicolini H, Nordentoft M, Pato M, Pato C, Pauls DL, Piacentini J, Pittenger C, Posthuma D, Ramos-Quiroga JA, Rasmussen SA, Richter MA, Rosenberg DR, Ruhrmann S, Samuels JF, Sandin S, Sandor P, Spalletta G, Stein DJ, Stewart SE, Storch EA, Stranger BE, Turiel M, Werge T, Andreassen OA, Børglum AD, Walitza S, Hveem K, Hansen BK, Rück CP, Martin NG, Milani L, Mors O, Reichborn-Kjennerud T, Ribasés M, Kvale G, Mataix-Cols D, Domschke K, Grünblatt E, Wagner M, Zwart JA, Breen G, Nestadt G, Kaprio J, Arnold PD, Grice DE, Knowles JA, Ask H, Verweij KJ, Davis LK, Smit DJ, Crowley JJ, Scharf JM, Stein MB, Gelernter J, Mathews CA, Derks EM and Mattheisen M
Obsessive-compulsive disorder (OCD) affects ~1% of the population and exhibits a high SNP-heritability, yet previous genome-wide association studies (GWAS) have provided limited information on the genetic etiology and underlying biological mechanisms of the disorder. We conducted a GWAS meta-analysis combining 53,660 OCD cases and 2,044,417 controls from 28 European-ancestry cohorts revealing 30 independent genome-wide significant SNPs and a SNP-based heritability of 6.7%. Separate GWAS for clinical, biobank, comorbid, and self-report sub-groups found no evidence of sample ascertainment impacting our results. Functional and positional QTL gene-based approaches identified 249 significant candidate risk genes for OCD, of which 25 were identified as putatively causal, highlighting , , and genes in the MHC region. Tissue and single-cell enrichment analyses highlighted hippocampal and cortical excitatory neurons, along with D1- and D2-type dopamine receptor-containing medium spiny neurons, as playing a role in OCD risk. OCD displayed significant genetic correlations with 65 out of 112 examined phenotypes. Notably, it showed positive genetic correlations with all included psychiatric phenotypes, in particular anxiety, depression, anorexia nervosa, and Tourette syndrome, and negative correlations with a subset of the included autoimmune disorders, educational attainment, and body mass index.. This study marks a significant step toward unraveling its genetic landscape and advances understanding of OCD genetics, providing a foundation for future interventions to address this debilitating disorder.
A qualitative investigation of the Montgomery-Åsberg depression rating scale: discrepancies in rater perceptions and data trends in remote assessments of rapid-acting antidepressants in treatment resistant depression
Capodilupo G, Blattner R, Must A, Navarro SG and Opler M
Despite the development of many successful pharmaceutical interventions, a significant subset of patients experience treatment-resistant depression (TRD). Ketamine and its derivatives constitute a novel therapeutic approach to treat TRD; however, standard tools, such as the Montgomery-Åsberg Depression Rating Scale (MADRS) are still being used to measure symptoms and track changes.
Assessing the patient's affective perception of their psychotherapist: validation of the
Stefana A, Fusar-Poli P, Vieta E and Youngstrom EA
Psychotherapists need effective tools to monitor changes in the patient's affective perception of the therapist and the therapeutic relationship during sessions to tailor therapeutic interventions and improve treatment outcomes. This study aims to evaluate the factor structure, reliability, and validity of the (SPARQ), a concise self-report measure designed for practical application in real-world psychotherapy settings.
COVID-19 experience of people with severe mental health conditions and families in South Africa
Brooke-Sumner C, Rapiya B, Myers B, Petersen I, Hanlon C, Repper J and Asher L
People with severe mental health conditions, such as schizophrenia, and their family caregivers are underserved in low- and middle-income countries where structured psychosocial support in the community is often lacking. This can present challenges to recovery and for coping with additional strains, such as a pandemic.
Spontaneous haemoperitoneum in pregnancy in women with endometriosis: Diagnostic challenges and management strategies
Mamah JE, Ruth Otu C, Okafor CC and Okafor CG
Spontaneous haemoperitoneum in pregnancy is a rare but potentially life-threatening condition that requires prompt recognition and management to avert a catastrophic outcome for the mother and baby. The main aim of this review is to summarise the current knowledge on this topic, including its incidence and clinical presentation, highlight the diagnostic challenges, and suggest management strategies. To achieve our objective, we examine the existing literature to provide insights into this complex clinical presentation to enhance our understanding and, in so doing, contribute to the existing body of knowledge on the subject of spontaneous haemoperitoneum in pregnancy.
CSF neurofilament light chain profiling and quantitation in neurological diseases
Leckey CA, Coulton JB, Giovannucci TA, He Y, Aslanyan A, Laban R, Heslegrave A, Doykov I, Ammoscato F, Chataway J, De Angelis F, Gnanapavan S, Byrne LM, Schott JM, Wild EJ, Barthelémy NR, Zetterberg H, Wray S, Bateman RJ, Mills K and Paterson RW
Neurofilament light chain is an established marker of neuroaxonal injury that is elevated in CSF and blood across various neurological diseases. It is increasingly used in clinical practice to aid diagnosis and monitor progression and as an outcome measure to assess safety and efficacy of disease-modifying therapies across the clinical translational neuroscience field. Quantitative methods for neurofilament light chain in human biofluids have relied on immunoassays, which have limited capacity to describe the structure of the protein in CSF and how this might vary in different neurodegenerative diseases. In this study, we characterized and quantified neurofilament light chain species in CSF across neurodegenerative and neuroinflammatory diseases and healthy controls using targeted mass spectrometry. We show that the quantitative immunoprecipitation-tandem mass spectrometry method developed in this study strongly correlates to single-molecule array measurements in CSF across the broad spectrum of neurodegenerative diseases and was replicable across mass spectrometry methods and centres. In summary, we have created an accurate and cost-effective assay for measuring a key biomarker in translational neuroscience research and clinical practice, which can be easily multiplexed and translated into clinical laboratories for the screening and monitoring of neurodegenerative disease or acute brain injury.
Prevalence and Determinants of Diagnosed Dementia: A Registry Linkage Study Linking Diagnosis of Dementia in the Population-Based HUNT Study to Registry Diagnosis of Dementia in Primary Care and Hospitals in Norway
Gjøra L, Strand BH, Bergh S, Bosnes I, Johannessen A, Livingston G, Skjellegrind HK and Selbæk G
A timely diagnosis of dementia can be beneficial for providing good support, treatment, and care, but the diagnostic rate remains unknown and is probably low.
Investigating light sensitivity in bipolar disorder (HELIOS-BD)
Roguski A, Needham N, MacGillivray T, Martinovic J, Dhillon B, Riha RL, Armstrong L, Campbell IH, Ferguson A, Hilgen G, Lako M, Ritter P, Santhi N, von Schantz M, Spitschan M and Smith DJ
Many people with bipolar disorder have disrupted circadian rhythms. This means that the timing of sleep and wake activities becomes out-of-sync with the standard 24-hour cycle. Circadian rhythms are strongly influenced by light levels and previous research suggests that people with bipolar disorder might have a heightened sensitivity to light, causing more circadian rhythm disruption, increasing the potential for triggering a mood switch into mania or depression. Lithium has been in clinical use for over 70 years and is acknowledged to be the most effective long-term treatment for bipolar disorder. Lithium has many reported actions in the body but the precise mechanism of action in bipolar disorder remains an active area of research. Central to this project is recent evidence that lithium may work by stabilising circadian rhythms of mood, cognition and rest/activity. Our primary hypothesis is that people with bipolar disorder have some pathophysiological change at the level of the retina which makes them hypersensitive to the visual and non-visual effects of light, and therefore more susceptible to circadian rhythm dysfunction. We additionally hypothesise that the mood-stabilising medication lithium is effective in bipolar disorder because it reduces this hypersensitivity, making individuals less vulnerable to light-induced circadian disruption. We will recruit 180 participants into the HELIOS-BD study. Over an 18-month period, we will assess visual and non-visual responses to light, as well as retinal microstructure, in people with bipolar disorder compared to healthy controls. Further, we will assess whether individuals with bipolar disorder who are being treated with lithium have less pronounced light responses and attenuated retinal changes compared to individuals with bipolar disorder not being treated with lithium. This study represents a comprehensive investigation of visual and non-visual light responses in a large bipolar disorder population, with great translational potential for patient stratification and treatment innovation.
A retrospective multicenter study on clinical and serological parameters in patients with MuSK myasthenia gravis with and without general immunosuppression
Koneczny I, Mané-Damas M, Zong S, De Haas S, Huda S, van Kruining D, Damoiseaux J, De Rosa A, Maestri M, Guida M, Molenaar P, Van Damme P, Fichtenbaum A, Perkmann T, De Baets M, Lazaridis K, Zouvelou V, Tzartos S, Ricciardi R, Losen M and Martinez-Martinez P
Muscle-specific kinase (MuSK)- myasthenia gravis (MG) is caused by pathogenic autoantibodies against MuSK that correlate with disease severity and are predominantly of the IgG4 subclass. The first-line treatment for MuSK-MG is general immunosuppression with corticosteroids, but the effect of treatment on IgG4 and MuSK IgG4 levels has not been studied.
A systematic review of pharmacogenetic testing to guide antipsychotic treatment
Saadullah Khani N, Hudson G, Mills G, Ramesh S, Varney L, Cotic M, Abidoph R, Richards-Belle A, Carrascal-Laso L, Franco-Martin M, Kaas-Hansen BS, Jürgens G, Barrett B, Jin H and Bramon E
Pharmacogenomics could optimize antipsychotic treatment by preventing adverse drug reactions, improving treatment efficacy or relieving the cost burden on the healthcare system. Here we conducted a systematic review to investigate whether pharmacogenetic testing in individuals undergoing antipsychotic treatment influences clinical or economic outcomes. On 12 January 2024, we searched MEDLINE, EMBASE, PsycINFO and Cochrane Centrale Register of Controlled Trials. The results were summarized using a narrative approach and summary tables. In total, 13 studies were eligible for inclusion in the systematic review. The current evidence base is either in favor of pharmacogenetics-guided prescribing or showed no difference between pharmacogenetics and treatment as usual for clinical and economic outcomes. In the future, we require randomized controlled trials with sufficient sample sizes that provide recommendations for patients who take antipsychotics based on a broad, multigene panel, with consistent and comparable clinical outcomes.
Number and nature of psychiatric emergency department visits in a tertiary hospital before, during, and after coronavirus pandemic
Aymerich C, Pedruzo B, Salazar de Pablo G, Olazabal N, Catalan A and González-Torres MÁ
The COVID-19 pandemic has significantly impacted mental health globally, leading to a deterioration in the overall mental health of the population and changes across all healthcare levels, including emergency departments (ED). However, the evolution of the quantity and nature of psychiatric ED visits in the post-pandemic period remains uncertain.
A comparison of visual attention to pictures in the Autism Diagnostic Observation Schedule in children and adolescents with ADHD and/or autism
Kochhar P, Arora I, Bellato A, Ropar D, Hollis C and Groom MMJ
Attention-Deficit/Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) are neurodevelopmental conditions which frequently co-occur. The Autism Diagnostic Observation Schedule (ADOS) is commonly used to aid with diagnostic assessment of ASD but was not originally designed for use in those with comorbid ADHD. Visual attention to social stimuli has been often studied in ASD using eye-tracking, to obtain quantitative indices of how attention is deployed to different parts of a social image/scene. As the ADOS includes tasks that rely on attending to and processing images of social scenes, these measures of visual attention could provide useful additional objective measurement alongside ADOS scores to enhance the characterisation of autistic symptoms in those with ADHD.
Interstitial lung disease: a review of classification, etiology, epidemiology, clinical diagnosis, pharmacological and non-pharmacological treatment
Althobiani MA, Russell AM, Jacob J, Ranjan Y, Folarin AA, Hurst JR and Porter JC
Interstitial lung diseases (ILDs) refer to a heterogeneous and complex group of conditions characterized by inflammation, fibrosis, or both, in the interstitium of the lungs. This results in impaired gas exchange, leading to a worsening of respiratory symptoms and a decline in lung function. While the etiology of some ILDs is unclear, most cases can be traced back to factors such as genetic predispositions, environmental exposures (including allergens, toxins, and air pollution), underlying autoimmune diseases, or the use of certain medications. There has been an increase in research and evidence aimed at identifying etiology, understanding epidemiology, improving clinical diagnosis, and developing both pharmacological and non-pharmacological treatments. This review provides a comprehensive overview of the current state of knowledge in the field of interstitial lung diseases.
Public perception of psychiatry, psychology and mental health professionals: a 15-year analysis
Domingo-Espiñeira J, Varaona A, Montero M, Lara-Abelenda FJ, Gutierrez-Rojas L, Fernández Del Campo EA, Rodriguez-Jimenez R, Pinto da Costa M, Ortega MA, Alvarez-Mon M and Alvarez-Mon MA
X (previously known as "Twitter") serves as a platform for open discussions on mental health, providing an avenue for scrutinizing public perspectives regarding psychiatry, psychology and their associated professionals.
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