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Dementia in Rare Genetic Neurodevelopmental Disorders: A Systematic Literature Review
Kwetsie H, van Schaijk M, Van Der Lee S, Maes-Festen D, Ten Hoopen LW, van Haelst MM, Coesmans M, Van Den Berg E, De Wit MCY, Pijnenburg Y, Aronica E, Boot E and Van Eeghen AM
Knowledge of young-onset Alzheimer disease in adults with Down syndrome has greatly improved clinical care. However, little is known about dementia in rare genetic neurodevelopmental disorders (RGNDs). In this review, a comprehensive overview is provided of reports on dementia and cognitive/adaptive trajectories in adults with RGNDs.
Abortion and mental health outcomes: A systematic review and meta-analysis
Littell JH, Young S, Pigott TD, Biggs MA, Munk-Olsen T and Steinberg JR
This is a protocol for a systematic review and meta-analysis of research on mental health outcomes of abortion. Does abortion increase the risk of adverse mental health outcomes? That is the central question for this review. Our review aims to inform policy and practice by locating, critically appraising, and synthesizing empirical evidence on associations between abortion and subsequent mental health outcomes. Given the controversies surrounding this topic and the complex social, political, legal, and ideological contexts in which research and reviews on abortion are conducted, it is especially important to conduct this systematic review and meta-analysis with comprehensive, rigorous, unbiased, and transparent methods. We will include a variety of study designs to enhance understanding of studies' methodological strengths and weaknesses and to identify potential explanations for conflicting results. We will follow open science principles, providing access to our methods, measures, and results, and making data available for re-analysis.
Design and Methods of the Early Age-Related Hearing Loss Investigation Randomized Controlled Trial
Denham MW, Arnold ML, Sanchez VA, Lin FR, Tucker LH, Gomez MC, Fernandez K, Arpi P, Neil H, Boyle S, Selevan S, Sussman TJ, Gmelin T, Fine I, Glynn NW, Teresi J, Noble JM, Goldberg T, Luchsinger JA and Golub JS
Hearing loss has been identified as a major modifiable risk factor for cognitive decline. The Early Age-Related Hearing Loss Investigation (EARHLI) study will assess the mechanisms linking early age-related hearing loss (ARHL) and cognitive impairment.
A randomized controlled trial to compare the effects of time-restricted eating versus Mediterranean diet on symptoms and quality of life in bipolar disorder
Johnson SL, Murray G, Kriegsfeld LJ, Manoogian ENC, Mason L, Allen JD, Berk M, Panda S, Rajgopal NA, Gibson JC, Joyner KJ, Villanueva R and Michalak EE
The primary objective of this randomized controlled trial (RCT) is to establish the effectiveness of time-restricted eating (TRE) compared with the Mediterranean diet for people with bipolar disorder (BD) who have symptoms of sleep disorders or circadian rhythm sleep-wake disruption. This work builds on the growing evidence that TRE has benefits for improving circadian rhythms. TRE and Mediterranean diet guidance will be offered remotely using self-help materials and an app, with coaching support.
Network-targeted transcranial direct current stimulation of the hypothalamus appetite-control network: a feasibility study
Ester-Nacke T, Berti K, Veit R, Dannecker C, Salvador R, Ruffini G, Heni M, Birkenfeld AL, Plewnia C, Preissl H and Kullmann S
The hypothalamus is the key regulator for energy homeostasis and is functionally connected to striatal and cortical regions vital for the inhibitory control of appetite. Hence, the ability to non-invasively modulate the hypothalamus network could open new ways for the treatment of metabolic diseases. Here, we tested a novel method for network-targeted transcranial direct current stimulation (net-tDCS) to influence the excitability of brain regions involved in the control of appetite. Based on the resting-state functional connectivity map of the hypothalamus, a 12-channel net-tDCS protocol was generated (Neuroelectrics Starstim system), which included anodal, cathodal and sham stimulation. Ten participants with overweight or obesity were enrolled in a sham-controlled, crossover study. During stimulation or sham control, participants completed a stop-signal task to measure inhibitory control. Overall, stimulation was well tolerated. Anodal net-tDCS resulted in faster stop signal reaction time (SSRT) compared to sham (p = 0.039) and cathodal net-tDCS (p = 0.042). Baseline functional connectivity of the target network correlated with SSRT after anodal compared to sham stimulation (p = 0.016). These preliminary data indicate that modulating hypothalamus functional network connectivity via net-tDCS may result in improved inhibitory control. Further studies need to evaluate the effects on eating behavior and metabolism.
eHealth mindfulness-based music therapy for patients undergoing allogeneic hematopoietic stem cell transplantation: A pilot randomized controlled trial protocol
Fleszar-Pavlovic SE, Esquives BN, Brito AE, Sia AM, Kauffman MA, Lopes M, Moreno PI, Koru-Sengul T, Gong R, Wang T, Wieder ED, Rueda-Lara M, Antoni M, Komanduri K, Lesiuk T and Penedo FJ
Allogeneic stem cell transplantation (allo-SCT) is the preferred therapy for patients with high-risk or relapsed hematologic malignancies, but may be complicated by psychological distress (e.g., depression, anxiety) and symptom burden (e.g., fatigue, pain). Mindfulness-based music therapy (MBMT), a relatively novel integrative medicine intervention that draws from mindfulness and music therapy principles, has shown promise in improving psychosocial outcomes and symptom burden in cancer patients. We outline an eHealth-based MBMT (eMBMT) intervention protocol examining: (1) feasibility, acceptability, and intended effects of eMBMT in improving HRQOL, symptom burden, and clinical markers of disease activity (e.g., infections), and (2) the extent to which eMBMT music therapy component-associated improvements in HRQOL, symptom burden, and disease activity are mediated by improvements in psychosocial and physiological (e.g., systemic inflammation, immune recovery) adaptation.
Long COVID Definitions and Models of Care : A Scoping Review
Chou R, Herman E, Ahmed A, Anderson J, Selph S, Dana T, Williams L and Ivlev I
Definitions of long COVID are evolving, and optimal models of care are uncertain.
Effectiveness of combining prevention psychological interventions with interventions that address the social determinants of mental health in low and middle-income countries: protocol of a systematic review and meta-analysis
Prina E, Bano B, Singh R, Albanese E, Trujillo D, Dedios Sanguineti MC, Sorsdahl K, Luitel NP, Garman EC, Purgato M, Barbui C, Jordans MJD and Lund C
Common mental health conditions (CMHCs), including depression, anxiety and post-traumatic stress disorder (PTSD), are highly prevalent in low and middle-income countries (LMICs). Preventive strategies combining psychological interventions with interventions addressing the social determinants of mental health may represent a key strategy for effectively preventing CMHCs. However, no systematic reviews have evaluated the effectiveness of these combined intervention strategies for preventing CMHCs.
Information-based TMS to mid-lateral prefrontal cortex disrupts action goals during emotional processing
Lapate RC, Heckner MK, Phan AT, Tambini A and D'Esposito M
The ability to respond to emotional events in a context-sensitive and goal-oriented manner is essential for adaptive functioning. In models of behavioral and emotion regulation, the lateral prefrontal cortex (LPFC) is postulated to maintain goal-relevant representations that promote cognitive control, an idea rarely tested with causal inference. Here, we altered mid-LPFC function in healthy individuals using a putatively inhibitory brain stimulation protocol (continuous theta burst; cTBS), followed by fMRI scanning. Participants performed the Affective Go/No-Go task, which requires goal-oriented action during affective processing. We targeted mid-LPFC (vs. a Control site) based on the individualized location of action-goal representations observed during the task. cTBS to mid-LPFC reduced action-goal representations in mid-LPFC and impaired goal-oriented action, particularly during processing of negative emotional cues. During negative-cue processing, cTBS to mid-LPFC reduced functional coupling between mid-LPFC and nodes of the default mode network, including frontopolar cortex-a region thought to modulate LPFC control signals according to internal states. Collectively, these results indicate that mid-LPFC goal-relevant representations play a causal role in governing context-sensitive cognitive control during emotional processing.
Protocol for process evaluation of ARTEMIS cluster randomised controlled trial: an intervention for management of depression and suicide among adolescents living in slums in India
Mukherjee A, Yatirajula SK, Kallakuri S, Paslawar S, Lempp H, Raman U, Kumar A, Essue BM, Sagar R, Singh R, Peiris D, Norton R, Thornicroft G and Maulik PK
There are around 250 million adolescents (10-19 years) in India. The prevalence of mental health-related morbidity among adolescents in India is approximately 7.3%. Vulnerable subpopulations among adolescents such as those living in slum communities are particularly at risk due to poor living conditions, financial difficulty and limited access to support services. Adolescents' Resilience and Treatment nEeds for Mental Health in Indian Slums (ARTEMIS) is a cluster randomised controlled trial of an intervention that intends to improve the mental health of adolescents living in slum communities in India. The aim of this paper is to describe the process evaluation protocol for ARTEMIS trial. The process evaluation will help to explain the intervention outcomes and understand how and why the intervention worked or did not work. It will identify contextual factors, intervention barriers and facilitators and the adaptations required for optimising implementation.
Medical students' attitudes towards well-being and welfare: a systematic review protocol
Mazzoleni A, Garg S, Bhatia S and Kumar NS
Medical education poses serious stressors on medical students, as they report overall higher rates of psychiatric comorbidities compared with students enrolled in other university-level courses. The high rates of poor well-being reported should be considered a concern, as students represent the future workforce of healthcare professionals. Although there has been an increased interest towards well-being and burn-out in medical students, there is still much to be elucidated. Indeed, there is an overall lack of understanding of which attitudes medical students have towards well-being and welfare, something that could be used to develop targeted practice to improve medics' quality of life and reduce overall burn-out.This review will aim at evaluating and reporting the current research available on medical students' attitudes towards well-being and welfare. We will take into account which countries have published data on the topic, and we will analyse papers written during the COVID-19 period separately, giving this particular time frame a separate outlook.
Morning light treatment for inflammatory bowel disease: a clinical trial
Cohen-Mekelburg S, Goldstein CA, Rizvydeen M, Fayyaz Z, Patel PJ, Berinstein JA, Bishu S, Cushing-Damm KC, Kim HM and Burgess HJ
Inflammatory bowel disease (IBD) affects over 3 million Americans and has a relapsing and remitting course with up to 30% of patients experiencing exacerbations each year despite the availability of immune targeted therapies. An urgent need exists to develop adjunctive treatment approaches to better manage IBD symptoms and disease activity. Circadian disruption is associated with increased disease activity and may be an important modifiable treatment target for IBD. Morning light treatment, which advances and stabilizes circadian timing, may have the potential to improve IBD symptoms and disease activity, but no studies have explored these potential therapeutic benefits in IBD. Therefore, in this study, we aim to test the effectiveness of morning light treatment for patients with IBD.
START NOW WebApp-promoting emotion regulation and resilience in residential youth care and correctional institutions: study protocol for a cluster randomized controlled trial
Kersten L, Alfano J, Erlanger TE, Helfenstein F, Lanz L, Weiss S, Chilla C, von Planta B, Kapoor M, Borel N, Rocco T, Papageorgiou A, De Brito CF, Bajrami A, Savary V, Mayor M, Hurschler J, Traut A, Brunner D, Vriends N and Stadler C
Adolescents and young adults in residential care and correctional institutions face various challenges, leading to negative life outcomes. Implementation barriers within these institutions, such as limited financial and spatial resources, pose significant hurdles to providing necessary support. Web-based approaches address these challenges by offering cost-effective, accessible solutions. This study aims to assess the efficacy of a newly developed web-based version of the existing evidence-based START NOW skills training in fostering emotion regulation and resilience among institutionalized adolescents and young adults. We present the study protocol (Version 5, August 2023) of the trial titled "Implementation of an e-version of the skills training START NOW for promoting emotion regulation and resilience in residential youth care and correctional institutions".
Remote family education and support program for parents of patients with adolescent and early adulthood eating disorders based on interpersonal psychotherapy: study protocol for a pilot randomized controlled trial
Katsuki F, Watanabe N, Kondo M, Sawada H and Yamada A
In cases of adolescent and early adulthood eating disorders, despite the importance of the patients' relationship with their parents, conflict and confusion frequently occur among them. Interpersonal psychotherapy (IPT) is a present-focused psychotherapy that emphasizes the interpersonal context of symptoms. We developed a remote family education and support program exclusively for parents of patients with eating disorders, based on the principle of IPT. The use of IPT is expected to reduce conflicts in the patient-parent relationship. Consequently, parents will be better able to listen to patients, and patients will be better able to express their thoughts and desires. In this study, we describe the protocol for a randomized controlled trial designed to examine the effectiveness of this program in promoting effective communication in their home based on active listening skills of parents of patients with adolescent and early adulthood eating disorders.
Success rates of intensive aphasia therapy: real-world data from 448 patients between 2003 and 2020
Peitz D, Schumann-Werner B, Hussmann K, Pinho J, Chen H, Binkofski F, Huber W, Willmes K, Heim S, Schulz JB, Fimm B and Werner CJ
Aphasia is a devastating consequence after stroke, affecting millions of patients each year. Studies have shown that intensive speech and language therapy (SLT) is effective in the chronic phase of aphasia. Leveraging a large single-center cohort of persons with aphasia (PWA) including patients also in the subacute phase, we assessed treatment effects of intensive aphasia therapy in a real-world setting.
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.
Personal growth initiative across the life span: a systematic review protocol of quantitative studies using the Personal Growth Initiative Scale-II
Verdoodt K, Simons M, de Hoog N, Reijnders J and Jacobs N
Personal Growth Initiative (PGI) a multi-dimensional construct, conceptualised as a skill set that helps individuals to intentionally grow is considered an important construct throughout the life span. Coping with the challenges, transitions, experiences and stressors of life requires an active growth orientation. In previous empirical research, the construct has been measured by either the PGIS-I or PGIS-II, of which only the latter takes account of the theoretically established multi-dimensionality of the construct. This paper describes the protocol for conducting a systematic review of published peer-reviewed empirical research articles on the multi-dimensional construct of PGI. The aim of this review is threefold: (1) to better understand the multi-dimensional construct PGI in different contexts and populations, (2) to improve our understanding of the reliability and validity of the PGIS-II in various research populations and (3) to obtain an overview of its associations with relevant psychosocial factors.
The Impact of Microbiome Interventions on the Progression and Severity of Inflammatory Bowel Disease: A Systematic Review
Kasapoglu M, Yadavalli R, Nawaz S, Althwanay A, AlEdani EM, Kaur H and Butt S
Inflammatory bowel disease (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC), is characterized by chronic intestinal inflammation. The dysbiotic gut microbiome likely contributes to IBD pathogenesis. Microbiome-directed therapies such as fecal microbiota transplantation (FMT), probiotics, and synbiotics may help induce and maintain remission. This systematic review aimed to determine the efficacy of microbiome interventions compared to standard therapy or placebo for IBD treatment. PubMed, EMBASE, Cochrane CENTRAL, and Web of Science were searched for randomized controlled trials on microbiome interventions in IBD from inception to October 2023. The risk of bias was assessed using Cochrane tools. Outcomes included disease activity, endoscopy, histology, quality of life, and adverse events. A total of 18 randomized controlled trials were included. Three trials found intensive (i.e., high frequency of administration and/or large volumes of fecal material) multi-donor FMT superior to autologous FMT or glucocorticoids for UC remission induction. Seven placebo-controlled trials demonstrated higher remission rates with FMT, especially intensive protocols, versus control for mild-to-moderate UC. However, a single FMT did not prevent relapses. Seven probiotic trials showed the potential to improve UC activity and maintain remission. One synbiotic trial reported reduced inflammation and symptoms versus placebo. Serious adverse events were rare. Small sample sizes and protocol heterogeneity limited the conclusions. Current evidence indicates the potential benefits of microbiome interventions, particularly intensive multi-donor FMT, for inducing and maintaining remission in UC. Probiotics may also improve outcomes. Adequately powered trials using standardized protocols are still needed to firmly establish efficacy and safety. Microbiome-directed therapies represent a promising approach for improving IBD outcomes.
An Immersive Virtual Reality Intervention for Preoperative Anxiety and Distress Among Adults Undergoing Oncological Surgery: Protocol for a 3-Phase Development and Feasibility Trial
El-Gabalawy R, Sommer JL, Hebbard P, Reynolds K, Logan GS, Smith MSD, Mutter TC, Mutch WA, Mota N, Proulx C, Gagnon Shaigetz V, Maples-Keller JL, Arora RC, Perrin D, Benedictson J and Jacobsohn E
Preoperative state anxiety (PSA) is distress and anxiety directly associated with perioperative events. PSA is associated with negative postoperative outcomes such as longer hospital length of stay, increased pain and opioid use, and higher rates of rehospitalization. Psychological prehabilitation, such as education, exposure to hospital environments, and relaxation strategies, has been shown to mitigate PSA; however, there are limited skilled personnel to deliver such interventions in clinical practice. Immersive virtual reality (VR) has the potential for greater accessibility and enhanced integration into an immersive and interactive experience. VR is rarely used in the preoperative setting, but similar forms of stress inoculation training involving exposure to stressful events have improved psychological preparation in contexts such as military deployment.
Protocol for a randomised controlled trial of ketamine versus ketamine and behavioural activation therapy for adults with treatment-resistant depression in the community
Beaglehole B, Porter R, Douglas K, Lacey CJ, de Bie A, Jordan J, Mentzel C, Thwaites B, Manuel J, Murray G, Frampton C and Glue P
Although short-term benefits follow parenteral ketamine for treatment-resistant major depressive disorder (TR-MDD), there are challenges that prevent routine use of ketamine by clinicians. These include acute dissociative effects of parenteral ketamine, high relapse rates following ketamine dosing and the uncertain role of psychotherapy. This randomised controlled trial (RCT) seeks to establish the feasibility of evaluating repeated oral doses of ketamine and behavioural activation therapy (BAT), compared with ketamine treatment alone, for TR-MDD. We also aim to compare relapse rates between treatment arms to determine the effect size of adding BAT to oral ketamine.
Ketamine-enhanced prolonged exposure therapy in veterans with PTSD: A randomized controlled trial protocol
Shiroma PR, Thuras P, Polusny M, Kehle-Forbes S, Disner S, Pardo J, Tolly B, Voller E, McManus E, King C, Lipinski A, Eng E, Hawkinson F and Wang G
The 2023 VA/DoD Clinical Practice Guideline for the Management of PTSD recommends individual, manualized trauma-focused such as Prolonged Exposure (PE) over pharmacologic interventions for the primary treatment of PTSD. Unfortunately, clinical trials of trauma-based therapies in the military and veteran population showed that 30% to 50% of patients did not demonstrate clinically meaningful symptom change. Ketamine, an FDA-approved anesthetic with potent non-competitive glutamatergic N-methyl-d-aspartate antagonistic properties, has demonstrated to enhance the recall of extinction learning and decrease fear renewal without interference of extinction training in preclinical studies.
Association of type 2 diabetes with family history of diabetes, diabetes biomarkers, mental and physical disorders in a Kenyan setting
Ndetei DM, Mutiso V, Musyimi C, Nyamai P, Lloyd C and Sartorius N
This study aimed to determine the degree of family relations and associated socio-demographics characteristics, clinical/physical and mental disorders in type 2 diabetes mellitus in a Kenyan diabetes clinic. This study was part of a large multicentre study whose protocol and results had been published. It took place at the outpatient diabetes clinic at a County Teaching and Referral Hospital in South East Kenya involving 182 participants. We used a socio-demographic questionnaire, the Hamilton Depression (HAM-D) and PHQ-9 rating scales for depression, the MINI International Neuropsychiatric Interview (MINI; V5 or V6) for DSM-5 diagnoses, the WHO-5 Well-being scale and Problem Areas in Diabetes Scale (PAID). We extracted from the notes all physical conditions. We enquired about similar conditions in 1st and 2nd degree relatives. Descriptive, Chi-square test, Fisher's exact test, one way ANOVA, and Multinomial logistic regression analysis were conducted to test achievements of our specific aims. Of the 182 patients who participated in the study, 45.1% (82/182) reported a family history of diabetes. Conditions significantly (p < 0.05) associated with a degree of family history of diabetes were retinopathy, duration of diabetes (years), hypertension, and depressive disorder. On average 11.5% (21/182) scored severe depression (≥ 10) on PHQ-9 and 85.2% (115/182) scored good well-being (≥ 13 points). All DSM-5 psychiatric conditions were found in the 182 patients in varying prevalence regardless of relations. In addition, amongst the 182 patients, the highest prevalence was poor well-being on the WHO quality of life tool. This was followed by post-traumatic disorders (current), suicidality, and psychotic lifetime on DSM-5. The least prevalent on DSM-5 was eating disorders. Some type 2 diabetes mellitus physical disorders and depression have increased incidence in closely related patients. Overall, for all the patients, the prevalence of all DSM-5 diagnoses varied from 0.5 to 9.9%.
History of Rectal Product Use and Country of Residence Influence Preference for Rectal Microbicide Dosage Forms Among Young Sexual and Gender Minorities: A Multi-country Trial Comparing Placebo Douche, Suppository, and Insert Products
Giguere R, Balán IC, Kutner BA, Choi SK, Tingler R, Johnson S, Macagna N, Webster J, Liu A, Chariyalertsak S, Hoesley C, Gonzales P, Ho K, Kayange N, Palanee-Phillips T, Brown E, Zemanek J, Jacobson CE, Doncel GF, Piper J, Bauermeister JA and
The DESIRE Study (MTN-035) explored product preference among three placebo rectal microbicide (RM) formulations, a rectal douche (RD), a suppository, and an insert, among 210 sexually active transgender people and men who have sex with men in five counties: the United States, Peru, Thailand, South Africa, and Malawi. Participants used each product prior to receptive anal sex (RAS) for 1 month, following a randomly assigned sequence, then selected their preferred product via computer assisted self-interview. In-depth interviews examined reasons for preference. We compared product preference and prior product use by country to explore whether geographic location and experience with the similar products impacted preference. A majority in the United States (56%) and Peru (58%) and nearly half in South Africa (48%) preferred the douche. Most in Malawi (59%) preferred the suppository, while half in Thailand (50%) and nearly half in South Africa (47%) preferred the insert. Participants who preferred the douche described it as quick and easy, already routinized, and serving a dual purpose of cleansing and protecting. Those who preferred the insert found it small, portable, discreet, with quick dissolution. Those who preferred the suppository found the size and shape acceptable and liked the added lubrication it provided. Experience with product use varied by country. Participants with RD experience were significantly more likely to prefer the douche (p = 0.03). Diversifying availability of multiple RM dosage forms can increase uptake and improve HIV prevention efforts globally.
BERNN: Enhancing classification of Liquid Chromatography Mass Spectrometry data with batch effect removal neural networks
Pelletier SJ, Leclercq M, Roux-Dalvai F, de Geus MB, Leslie S, Wang W, Lam TT, Nairn AC, Arnold SE, Carlyle BC, Precioso F and Droit A
Liquid Chromatography Mass Spectrometry (LC-MS) is a powerful method for profiling complex biological samples. However, batch effects typically arise from differences in sample processing protocols, experimental conditions, and data acquisition techniques, significantly impacting the interpretability of results. Correcting batch effects is crucial for the reproducibility of omics research, but current methods are not optimal for the removal of batch effects without compressing the genuine biological variation under study. We propose a suite of Batch Effect Removal Neural Networks (BERNN) to remove batch effects in large LC-MS experiments, with the goal of maximizing sample classification performance between conditions. More importantly, these models must efficiently generalize in batches not seen during training. A comparison of batch effect correction methods across five diverse datasets demonstrated that BERNN models consistently showed the strongest sample classification performance. However, the model producing the greatest classification improvements did not always perform best in terms of batch effect removal. Finally, we show that the overcorrection of batch effects resulted in the loss of some essential biological variability. These findings highlight the importance of balancing batch effect removal while preserving valuable biological diversity in large-scale LC-MS experiments.
Natural Language Processing for Work-Related Stress Detection Among Health Professionals: Protocol for a Scoping Review
Bieri JS, Ikae C, Souissi SB, Müller TJ, Schlunegger MC and Golz C
There is an urgent need worldwide for qualified health professionals. High attrition rates among health professionals, combined with a predicted rise in life expectancy, further emphasize the need for additional health professionals. Work-related stress is a major concern among health professionals, affecting both the well-being of health professionals and the quality of patient care.
Regulatory Issues in Electronic Health Records for Adolescent HIV Research: Strategies and Lessons Learned
Green SS, Lee SJ, Chahin S, Pooler-Burgess M, Green-Jones M, Gurung S, Outlaw AY and Naar S
Electronic health records (EHRs) are a cost-effective approach to provide the necessary foundations for clinical trial research. The ability to use EHRs in real-world clinical settings allows for pragmatic approaches to intervention studies with the emerging adult HIV population within these settings; however, the regulatory components related to the use of EHR data in multisite clinical trials poses unique challenges that researchers may find themselves unprepared to address, which may result in delays in study implementation and adversely impact study timelines, and risk noncompliance with established guidance.
Social Determinants of Health and Health Equity in the Treatment and Rehabilitation of Sport-Related Concussion: A Content Analysis of Intervention Research and Call-To-Action
Cook NE, Kissinger-Knox AM, Iverson IA, Stephenson K, Norman MA, Hunter A, Saadi A and Iverson GL
This review was designed to (i) determine the extent to which the clinical science on sport-related concussion treatment and rehabilitation has considered social determinants of health (SDoH) or health equity and (ii) offer recommendations to enhance the incorporation of SDoH and health equity in concussion treatment research and clinical care. The Concussion in Sport Group consensus statement (2023) was informed by two systematic reviews examining prescribed rest or exercise following concussion and targeted interventions to facilitate concussion recovery. We examined 31 studies, including 2,698 participants, from those two reviews. Race (k=6; 19.4%) and ethnicity (k=4; 12.9%) were usually not reported. Four studies examined ethnicity (i.e., Hispanic), exclusively as a demographic category. Five studies (16.1%) examined race as a demographic category. Three studies (9.7%) examined socioeconomic status (SES; measured as household income) as a demographic category/sample descriptor and one study (3.2%) examined SES in depth, by testing whether the treatment and control groups differed by SES. Five studies examined a SDoH domain in a descriptive manner and four studies in an inferential/intentional manner. No study mentioned SDoH, health equity, or disparities by name. Many studies (61.3%) excluded participants based on demographic, sociocultural, or health factors, primarily due to language proficiency. The new consensus statement includes recommendations for concussion treatment and rehabilitation that rely on an evidence base that has not included SDoH or studies addressing health equity. Researchers are encouraged to design treatment and rehabilitation studies that focus specifically on under-represented groups to determine if they have specific and unique treatment and rehabilitation needs, whether certain practical modifications to treatment protocols might be necessary, and whether completion rates and treatment adherence and response are similar.
Influence of paternal preconception health on pregnancy, intrapartum, postpartum and early childhood outcomes: protocol for a parallel scoping review
Dennis CL, Abbass-Dick J, Birken C, Dennis-Grantham A, Goyal D, Singla D, Letourneau N, McQueen K, Shorey S and Dol J
Preconception care is the provision of behavioural, social or biomedical interventions to women and couples prior to conception. To date, preconception research has primarily focused on maternal health, despite the male partner's contribution before birth to both short-term and long-term child outcomes. The objectives of the reviews are: (1) to identify, consolidate and analyse the literature on paternal preconception health on pregnancy and intrapartum outcomes, and (2) to identify, consolidate and analyse the literature on paternal preconception health on postpartum and early childhood outcomes.
Mentalising imagery therapy for family dementia caregivers: protocol for a scoping review
Jiang X and Jiang H
Dementia is a growing public health concern, and providing long-term care for individuals affected by this condition is challenging for their family caregivers. While researchers have explored various intervention options to provide psychological support for dementia caregivers, mentalising imagery therapy (MIT) has gained significant recognition as an effective programme. Despite its significance and effectiveness, there is a lack of comprehensive scoping reviews of MIT in dementia caregiving. Thus, conducting such a review can provide valuable insights into the status and outcomes of MIT, identify gaps in existing research and provide recommendations for a more effective clinical practice.
Cognitive rehabilitation effects on grey matter volume and Go-NoGo activity in progressive multiple sclerosis: results from the CogEx trial
Rocca MA, Valsasina P, Romanò F, Tedone N, Amato MP, Brichetto G, Boccia VD, Chataway J, Chiaravalloti ND, Cutter G, Dalgas U, DeLuca J, Farrell RA, Feys P, Freeman J, Inglese M, Meza C, Motl RW, Salter A, Sandroff BM, Feinstein A, Filippi M and
Research on cognitive rehabilitation (CR) and aerobic exercise (EX) to improve cognition in progressive multiple sclerosis (PMS) remains limited. CogEx trial investigated the effectiveness of CR and EX in PMS: here, we present MRI substudy volumetric and task-related functional MRI (fMRI) findings.
The prevalence of post traumatic and associated factors among nurses during COVID_19 pandemics: a systematic review and meta-analysis
Karbasi A, Babakhanian M, Ahmadzadeh A and Omranifard V
Despite the negative outcomes, exposure to a crisis may cause people to experience positive changes. This study aims to analyze the prevalence of post-traumatic growth (PTG) and its relevant factors among nurses during the COVID-19 pandemic.
The Prevalence and Influence of New or Worsened Neck Pain After a Sport-Related Concussion in Collegiate Athletes: A Study From the CARE Consortium
King JA, Nelson LD, Cheever K, Brett B, Gliedt J, Szabo A, Dong H, Huber DL, Broglio SP, McAllister TW, McCrea M, Pasquina P, Feigenbaum LA, Hoy A, Mihalik JP, Duma SM, Buckley T, Kelly LA, Miles C, Goldman JT, Benjamin HJ, Master CL, Ortega J, Kontos A, Clugston JR, Cameron KL, Kaminski TW, Chrisman SP, Eckner JT, Port N and McGinty G
Neck pain in a concussion population is an emerging area of study that has been shown to have a negative influence on recovery. This effect has not yet been studied in collegiate athletes.
Implementation Barriers Encountered During a Universal Suicide Screening Program in Pediatric Emergency Departments
Seag DEM, Cervantes PE, Narcisse I, Wiener E, Tay ET, Knapp K and Horwitz SM
Because understanding barriers to universal suicide risk screening in pediatric emergency departments (PEDs) may improve both identification and management of suicidal behaviors and ideation, this study assessed barriers to a quality improvement initiative examining the use of a novel computerized adaptive test (CAT), the Kiddie-CAT, in 2 PEDs.
Noninvasive brain stimulation in autism: review and outlook for personalized interventions in adult patients
Hensel L, Lüdtke J, Brouzou KO, Eickhoff SB, Kamp D and Schilbach L
Noninvasive brain stimulation (NIBS) has been increasingly investigated during the last decade as a treatment option for persons with autism spectrum disorder (ASD). Yet, previous studies did not reach a consensus on a superior treatment protocol or stimulation target. Persons with ASD often suffer from social isolation and high rates of unemployment, arising from difficulties in social interaction. ASD involves multiple neural systems involved in perception, language, and cognition, and the underlying brain networks of these functional domains have been well documented. Aiming to provide an overview of NIBS effects when targeting these neural systems in late adolescent and adult ASD, we conducted a systematic search of the literature starting at 631 non-duplicate publications, leading to six studies corresponding with inclusion and exclusion criteria. We discuss these studies regarding their treatment rationale and the accordingly chosen methodological setup. The results of these studies vary, while methodological advances may allow to explain some of the variability. Based on these insights, we discuss strategies for future clinical trials to personalize the selection of brain stimulation targets taking into account intersubject variability of brain anatomy as well as function.
Comparative electroencephalography analysis: Marathon runners during tapering versus sedentary controls reveals no significant differences
Moussiopoulou J, Handrack-Bonnet M, Pross B, Pogarell O, Keeser D, Halle M, Falkai P, Scherr J, Hasan A and Roeh A
Previous studies described various adaptive neuroplastic brain changes associated with physical activity (PA). EEG studies focused mostly on effects during or shortly after short bouts of exercise. This is the first study to investigate the capability of EEG to display PA-induced long-lasting plasticity in runners compared to a sedentary control group.
Intermittent theta-burst stimulation to the right dorsolateral prefrontal cortex may increase potentiated startle in healthy individuals
Teferi M, Gura H, Patel M, Casalvera A, Lynch KG, Makhoul W, Deng ZD, Oathes DJ, Sheline YI and Balderston NL
Repetitive transcranial magnetic stimulation (rTMS) treatment protocols targeting the right dlPFC have been effective in reducing anxiety symptoms comorbid with depression. However, the mechanism behind these effects is unclear. Further, it is unclear whether these results generalize to non-depressed individuals. We conducted a series of studies aimed at understanding the link between anxiety potentiated startle and the right dlPFC, following a previous study suggesting that continuous theta burst stimulation (cTBS) to the right dlPFC can make people more anxious. Based on these results we hypothesized that intermittent TBS (iTBS), which is thought to have opposing effects on plasticity, may reduce anxiety when targeted at the same right dlPFC region. In this double-blinded, cross-over design, 28 healthy subjects underwent 12 study visits over a 4-week period. During each of their 2 stimulation weeks, they received four 600 pulse iTBS sessions (2/day), with a post-stimulation testing session occurring 24 h following the final iTBS session. One week they received active stimulation, one week they received sham. Stimulation weeks were separated by a 1-week washout period and the order of active/sham delivery was counterbalanced across subjects. During the testing session, we induced anxiety using the threat of unpredictable shock and measured anxiety potentiated startle. Contrary to our initial hypothesis, subjects showed increased startle reactivity following active compared to sham stimulation. These results replicate work from our two previous trials suggesting that TMS to the right dlPFC increases anxiety potentiated startle, independent of both the pattern of stimulation and the timing of the post stimulation measure. Although these results confirm a mechanistic link between right dlPFC excitability and startle, capitalizing upon this link for the benefit of patients will require future exploration.
Prospective and Retrospective Measures of Child Maltreatment and Their Association With Psychopathology: A Systematic Review and Meta-Analysis
Baldwin JR, Coleman O, Francis ER and Danese A
Prospective and retrospective measures of childhood maltreatment identify largely different groups of individuals. However, it is unclear if these measures are differentially associated with psychopathology.
Targeting the left DLPFC and right VLPFC in unmarried romantic relationship breakup (love trauma syndrome) with intensified electrical stimulation: A randomized, single-blind, parallel-group, sham-controlled study
Alizadehgoradel J, Razavi SD, Shirani Z, Barati M, Taherifard M, Nejati V and Nitsche MA
Ending a romantic relationship is one of the most painful losses an adult experience. Neuroimaging studies suggest that there is a neuropsychological link between breakup experiences and bereaved individuals, and that specific prefrontal regions are involved. The aim of this study was to determine whether enhancement of left DLPFC and right VLPFC activity with a novel intensified anodal transcranial direct current stimulation protocol reduces core symptoms of love trauma syndrome (LTS) and improves treatment-related variables.
Exploring early life social and executive function development in infants and risk for autism: a prospective cohort study protocol of NICU graduates and infants at risk for cerebral palsy
Boulton KA, Lee D, Honan I, Phillips NL, Morgan C, Crowle C, Novak I, Badawi N and Guastella AJ
Delays in early social and executive function are predictive of later developmental delays and eventual neurodevelopmental diagnoses. There is limited research examining such markers in the first year of life. High-risk infant groups commonly present with a range of neurodevelopmental challenges, including social and executive function delays, and show higher rates of autism diagnoses later in life. For example, it has been estimated that up to 30% of infants diagnosed with cerebral palsy (CP) will go on to be diagnosed with autism later in life.
Perceptual Dysfunction in Eating Disorders
Reilly EE, Brown TA and Frank GKW
Eating disorders (EDs) are characterized by abnormal responses to food and weight-related stimuli and are associated with significant distress, impairment, and poor outcomes. Because many of the cardinal symptoms of EDs involve disturbances in perception of one's body or abnormal affective or cognitive reactions to food intake and how that affects one's size, there has been longstanding interest in characterizing alterations in sensory perception among differing ED diagnostic groups. Within the current review, we aimed to critically assess the existing research on exteroceptive and interoceptive perception and how sensory perception may influence ED behavior. Overall, existing research is most consistent regarding alterations in taste, visual, tactile, and gastric-specific interoceptive processing in EDs, with emerging work indicating elevated respiratory and cardiovascular sensitivity. However, this work is far from conclusive, with most studies unable to speak to the precise etiology of observed perceptual differences in these domains and disentangle these effects from affective and cognitive processes observed within EDs. Further, existing knowledge regarding perceptual disturbances in EDs is limited by heterogeneity in methodology, lack of multimodal assessment protocols, and inconsistent attention to different ED diagnoses. We propose several new avenues for improving neurobiology-informed research on sensory processing to generate actionable knowledge that can inform the development of innovative interventions for these serious disorders.
A review of the kappa opioid receptor system in opioid use
Cayir S, Zhornitsky S, Barzegary A, Sotomayor-Carreño E, Sarfo-Ansah W, Funaro MC, Matuskey D and Angarita G
The kappa opioid receptor (KOR) system is implicated in dysphoria and as an "anti-reward system" during withdrawal from opioids. However, no clear consensus has been made in the field, as mixed findings have been reported regarding the relationship between the KOR system and opioid use. This review summarizes the studies to date on the KOR system and opioids. A systematic scoping review was reported following PRISMA guidelines and conducted based on the published protocol. Comprehensive searches of several databases were done in the following databases: MEDLINE, Embase, PsycINFO, Web of Science, Scopus, and Cochrane. We included preclinical and clinical studies that tested the administration of KOR agonists/antagonists or dynorphin and/or measured dynorphin levels or KOR expression during opioid intoxication or withdrawal from opioids. One hundred studies were included in the final analysis. Preclinical administration of KOR agonists decreased drug-seeking/taking behaviors and opioid withdrawal symptoms. KOR antagonists showed mixed findings, depending on the agent and/or type of withdrawal symptom. Administration of dynorphins attenuated opioid withdrawal symptoms both in preclinical and clinical studies. In the limited number of available studies, dynorphin levels were found to increase in cerebrospinal fluid (CSF) and peripheral blood lymphocytes (PBL) of opioid use disorder subjects (OUD). In animals, dynorphin levels and/or KOR expression showed mixed findings during opioid use. The KOR/dynorphin system appears to have a multifaceted and complex nature rather than simply functioning as an anti-reward system. Future research in well-controlled study settings is necessary to better understand the clinical role of the KOR system in opioid use.
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).
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.
Using policy codesign to achieve multi-sector alignment in adolescent behavioral health: a study protocol
Walker SC, Ahrens KR, Owens MD, Parnes M, Langley J, Ackerley C, Purtle J, Saldana L, Aarons GA, Hogue A and Palinkas LA
Policymaking is quickly gaining focus in the field of implementation science as a potential opportunity for aligning cross-sector systems and introducing incentives to promote population health, including substance use disorders (SUD) and their prevention in adolescents. Policymakers are seen as holding the necessary levers for realigning service infrastructure to more rapidly and effectively address adolescent behavioral health across the continuum of need (prevention through crisis care, mental health, and SUD) and in multiple locations (schools, primary care, community settings). The difficulty of aligning policy intent, policy design, and successful policy implementation is a well-known challenge in the broader public policy and public administration literature that also affects local behavioral health policymaking. This study will examine a blended approach of coproduction and codesign (i.e., Policy Codesign), iteratively developed over multiple years to address problems in policy formation that often lead to poor implementation outcomes. The current study evaluates this scalable approach using reproducible measures to grow the knowledge base in this field of study.
High-fat diet, microbiome-gut-brain axis signaling, and anxiety-like behavior in male rats
de Noronha SISR, de Moraes LAG, Hassell JE, Stamper CE, Arnold MR, Heinze JD, Foxx CL, Lieb MM, Cler KE, Karns BL, Jaekel S, Loupy KM, Silva FCS, Chianca-Jr DA, Lowry CA and de Menezes RC
Obesity, associated with the intake of a high-fat diet (HFD), and anxiety are common among those living in modern urban societies. Recent studies suggest a role of microbiome-gut-brain axis signaling, including a role for brain serotonergic systems in the relationship between HFD and anxiety. Evidence suggests the gut microbiome and the serotonergic brain system together may play an important role in this response. Here we conducted a nine-week HFD protocol in male rats, followed by an analysis of the gut microbiome diversity and community composition, brainstem serotonergic gene expression (tph2, htr1a, and slc6a4), and anxiety-related defensive behavioral responses. We show that HFD intake decreased alpha diversity and altered the community composition of the gut microbiome in association with obesity, increased brainstem tph2, htr1a and slc6a4 mRNA expression, including in the caudal part of the dorsomedial dorsal raphe nucleus (cDRD), a subregion previously associated with stress- and anxiety-related behavioral responses, and, finally, increased anxiety-related defensive behavioral responses. The HFD increased the Firmicutes/Bacteroidetes ratio relative to control diet, as well as higher relative abundances of Blautia, and decreases in Prevotella. We found that tph2, htr1a and slc6a4 mRNA expression were increased in subregions of the dorsal raphe nucleus in the HFD, relative to control diet. Specific bacterial taxa were associated with increased serotonergic gene expression in the cDRD. Thus, we propose that HFD-induced obesity is associated with altered microbiome-gut-serotonergic brain axis signaling, leading to increased anxiety-related defensive behavioral responses in rats.
Effectiveness of a web-enabled psychoeducational resource for postpartum depression and anxiety among women in British Columbia
Lawrence CG, Breau G, Yang L, Hellerstein OS, Hippman C, Kennedy AL, Ryan D, Shulman B and Brotto LA
Postpartum depression (PPD) and anxiety (PPA) affect nearly one-quarter (23%) of women in Canada. eHealth is a promising solution for increasing access to postpartum mental healthcare. However, a user-centered approach is not routinely taken in the development of web-enabled resources, leaving postpartum women out of critical decision-making processes. This study aimed to evaluate the effectiveness, usability, and user satisfaction of PostpartumCare.ca, a web-enabled psychoeducational resource for PPD and PPA, created in partnership with postpartum women in British Columbia.
Help-seeking processes related to targeted school-based mental health services: systematic review
McPhail L, Thornicroft G and Gronholm PC
One in seven adolescents globally are affected by mental health conditions, yet only a minority receive professional help. School-based mental health services have been endorsed as an effective way to increase access to mental health support for people at risk, or currently presenting with mental health conditions, throughout adolescence. Despite this, low treatment utilisation prevails, therefore the aim of this review is to contribute insights into the processes related to adolescents' accessing and engaging with essential targeted mental health support within schools.
Intensive longitudinal assessment following index trauma to predict development of PTSD using machine learning
Horwitz A, McCarthy K, House SL, Beaudoin FL, An X, Neylan TC, Clifford GD, Linnstaedt SD, Germine LT, Rauch SL, Haran JP, Storrow AB, Lewandowski C, Musey PI, Hendry PL, Sheikh S, Jones CW, Punches BE, Swor RA, Hudak LA, Pascual JL, Seamon MJ, Harris E, Pearson C, Peak DA, Domeier RM, Rathlev NK, Sergot P, Sanchez LD, Bruce SE, Joormann J, Harte SE, Koenen KC, McLean SA and Sen S
There are significant challenges to identifying which individuals require intervention following exposure to trauma, and a need for strategies to identify and provide individuals at risk for developing PTSD with timely interventions. The present study seeks to identify a minimal set of trauma-related symptoms, assessed during the weeks following traumatic exposure, that can accurately predict PTSD. Participants were 2185 adults (Mean age=36.4 years; 64% women; 50% Black) presenting for emergency care following traumatic exposure. Participants received a 'flash survey' with 6-8 varying symptoms (from a pool of 26 trauma symptoms) several times per week for eight weeks following the trauma exposure (each symptom assessed ∼6 times). Features (mean, sd, last, worst, peak-end scores) from the repeatedly assessed symptoms were included as candidate variables in a CART machine learning analysis to develop a pragmatic predictive algorithm. PTSD (PCL-5 ≥38) was present for 669 (31%) participants at the 8-week follow-up. A classification tree with three splits, based on mean scores of nervousness, rehashing, and fatigue, predicted PTSD with an Area Under the Curve of 0.836. Findings suggest feasibility for a 3-item assessment protocol, delivered once per week, following traumatic exposure to assess and potentially facilitate follow-up care for those at risk.
The Neuropsychological Assessment Battery Driving Scenes Test in a Dementia Clinic
Ashendorf L, Withrow S and Gavett BE
In dementia research, the Driving Scenes test from the Neuropsychological Assessment Battery has been shown to relate to memory, dementia diagnosis, and functional impairment. The aim of the current study was to examine Driving Scenes and its component scores, and their relationships with cognition and daily functioning, in a mixed dementia clinic sample.
Digital Interventions to Understand and Mitigate Stress Response: Protocol for Process and Content Evaluation of a Cohort Study
Martin J, Rueda A, Lee GH, Tassone VK, Park H, Ivanov M, Darnell BC, Beavers L, Campbell DM, Nguyen B, Torres A, Jung H, Lou W, Nazarov A, Ashbaugh A, Kapralos B, Litz B, Jetly R, Dubrowski A, Strudwick G, Krishnan S and Bhat V
Staffing and resource shortages, especially during the COVID-19 pandemic, have increased stress levels among health care workers. Many health care workers have reported feeling unable to maintain the quality of care expected within their profession, which, at times, may lead to moral distress and moral injury. Currently, interventions for moral distress and moral injury are limited.
Feasibility and Acceptability of a Mobile App-Based TEAM-CBT (Testing Empathy Assessment Methods-Cognitive Behavioral Therapy) Intervention (Feeling Good) for Depression: Secondary Data Analysis
Bisconti N, Odier M, Becker M and Bullock K
The Feeling Good App is an automated stand-alone digital mobile mental health tool currently undergoing beta testing with the goal of providing evidence-informed self-help lessons and exercises to help individuals reduce depressive symptoms without guidance from a mental health provider. Users work through intensive basic training (IBT) and ongoing training models that provide education regarding cognitive behavioral therapy principles from a smartphone.
Medical comorbidities in bipolar disorder (BIPCOM): clinical validation of risk factors and biomarkers to improve prevention and treatment. Study protocol
de Girolamo G, Andreassen OA, Bauer M, Brambilla P, Calza S, Citerà N, Corcoy R, Fagiolini A, Garcia-Argibay M, Godin O, Klingler F, Kobayashi NF, Larsson H, Leboyer M, Matura S, Martinelli A, De la Peña-Arteaga V, Poli R, Reif A, Ritter P, Rødevand LN, Magno M, Caselani E and
BIPCOM aims to (1) identify medical comorbidities in people with bipolar disorder (BD); (2) examine risk factors and clinical profiles of Medical Comorbidities (MC) in this clinical group, with a special focus on Metabolic Syndrome (MetS); (3) develop a Clinical Support Tool (CST) for the personalized management of BD and medical comorbidities.
Re-awakening the brain: Forcing transitions in disorders of consciousness by external in silico perturbation
Dagnino PC, Escrichs A, López-González A, Gosseries O, Annen J, Sanz Perl Y, Kringelbach ML, Laureys S and Deco G
A fundamental challenge in neuroscience is accurately defining brain states and predicting how and where to perturb the brain to force a transition. Here, we investigated resting-state fMRI data of patients suffering from disorders of consciousness (DoC) after coma (minimally conscious and unresponsive wakefulness states) and healthy controls. We applied model-free and model-based approaches to help elucidate the underlying brain mechanisms of patients with DoC. The model-free approach allowed us to characterize brain states in DoC and healthy controls as a probabilistic metastable substate (PMS) space. The PMS of each group was defined by a repertoire of unique patterns (i.e., metastable substates) with different probabilities of occurrence. In the model-based approach, we adjusted the PMS of each DoC group to a causal whole-brain model. This allowed us to explore optimal strategies for promoting transitions by applying off-line in silico probing. Furthermore, this approach enabled us to evaluate the impact of local perturbations in terms of their global effects and sensitivity to stimulation, which is a model-based biomarker providing a deeper understanding of the mechanisms underlying DoC. Our results show that transitions were obtained in a synchronous protocol, in which the somatomotor network, thalamus, precuneus and insula were the most sensitive areas to perturbation. This motivates further work to continue understanding brain function and treatments of disorders of consciousness.
Internet-Delivered Exposure and Response Prevention for Pediatric Tourette Syndrome: 12-Month Follow-Up of a Randomized Clinical Trial
Andrén P, Sampaio F, Ringberg H, Wachtmeister V, Warnström M, Isomura K, Aspvall K, Lenhard F, Hall CL, Davies EB, Murphy T, Hollis C, Feldman I, Bottai M, Serlachius E, Andersson E, Fernández de la Cruz L and Mataix-Cols D
Behavior therapy is a recommended intervention for Tourette syndrome (TS) and chronic tic disorder (CTD), but availability is limited and long-term effects are uncertain.
Lifestyle management and brain MRI metrics in female Australian adults living with multiple sclerosis: a feasibility and acceptability study
Wills O, Wright B, Greenwood LM, Solowij N, Schira M, Maller JJ, Gupta A, Magnussen J and Probst Y
Limited studies of multiple sclerosis (MS) exist whereby magnetic resonance imaging (MRI) of the brain with consistent imaging protocols occurs at the same time points as collection of healthy lifestyle measures. The aim of this study was to test the feasibility, acceptability and preliminary efficacy of acquiring MRI data as an objective, diagnostic and prognostic marker of MS, at the same time point as brain-healthy lifestyle measures including diet.
Design and rationale of the Botswana Smoking Abstinence Reinforcement Trial: a protocol for a stepped-wedge cluster randomized trial
Bada F, Mansfield ME, Okui L, Montebatsi M, DiClemente C, Tapera R, Ikgopoleng K, Mokonopi S, Magidson JF, Onukwugha E, Ndwapi N, Himelhoch S, Mbongwe B and Charurat M
With expanded and sustained availability of HIV treatment resulting in substantial improvements in life expectancy, the need to address modifiable risk factors associated with leading causes of death among people living with HIV/AIDS (PLWH), such as tobacco smoking, has increased. Tobacco use is highly prevalent among PLWH, especially in southern Africa, where HIV is heavily concentrated, and many people who smoke would like to quit but are unable to do so without assistance. SBIRT (Screening, Brief Intervention and Referral to Treatment) is a well-established evidence-based approach successful at supporting smoking cessation in a variety of settings. Varenicline is efficacious in supporting smoking cessation. We intend to assess the effectiveness of SBIRT and varenicline on smoking cessation among PLWH in Botswana and the effectiveness of our implementation.
An open pilot trial of a behavioural intervention to reduce violence by young adults with early psychosis receiving treatment in an early intervention services setting: A protocol
Rolin SA, Caffrey D, Flores MG, Pope LG, Mootz J, Bello I, Nossel I, Compton MT, Stanley B, Wainberg M, Dixon LB and Appelbaum PS
Despite the public health impact of violence among young adults with psychosis, behavioural interventions to reduce the risk of engaging in violence remain rare. For young adults with early psychosis, cognitive behavioural therapy (CBT)-based psychotherapy has efficacy in reducing impairment and improving functioning. However, no CBT-based intervention to reduce violence has been formally adapted for young adults with early psychosis. This protocol outlines the first clinical trial of a behavioural intervention to reduce violence for young adults with early psychosis. This study is set in an early intervention services (EIS) setting and seeks to adapt and pilot Psychological Intervention for Complex PTSD and Schizophrenia-Spectrum Disorder (PICASSO), a CBT-based intervention, through an iterative process utilizing mixed-methods assessments.
A phase I trial of accelerated intermittent theta burst rTMS for amnestic MCI
Aghamoosa S, Lopez J, Rbeiz K, Fleischmann HH, Horn O, Madden K, Caulfield KA, Antonucci MU, Revuelta G, McTeague LM and Benitez A
Emerging evidence suggests that repetitive transcranial magnetic stimulation (rTMS) enhances cognition in mild cognitive impairment (MCI). Accelerated intermittent theta burst stimulation (iTBS) rTMS protocols are promising as they substantially reduce burden by shortening the treatment course, but the safety, feasibility, and acceptability of iTBS have not been established in MCI.
ØCD: protocol for the development and evaluation of a cognitive-behavioral prevention program for obsessive-compulsive disorder
Cardoș RAI, Dumitru EP and David OA
Obsessive-compulsive disorder (OCD) imposes significant burdens on individuals, families, and healthcare systems and the COVID-19 pandemic appears to have exacerbated OCD symptoms. Currently, there are no validated prevention programs for OCD, highlighting a critical gap in mental health services. This study aims to develop and validate the first ØCD prevention program, for at-risk adults, utilizing cognitive-behavioral therapy (CBT) and exposure response prevention (ERP) techniques.
Diversity, equity and inclusion considerations in mental health apps for young people: protocol for a scoping review
Figueroa CA, Pérez-Flores NJ, Guan KW and Stiles-Shields C
After COVID-19, a global mental health crisis affects young people, with one in five youth experiencing mental health problems worldwide. Delivering mental health interventions via mobile devices is a promising strategy to address the treatment gap. Mental health apps are effective for adolescent and young adult samples, but face challenges such as low real-world reach and under-representation of minoritised youth. To increase digital health uptake, including among minoritised youth, there is a need for diversity, equity and inclusion (DEI) considerations in the development and evaluation of mental health apps. How well DEI is integrated into youth mental health apps has not been comprehensively assessed. This scoping review aims to examine to what extent DEI considerations are integrated into the design and evaluation of youth mental health apps and report on youth, caregiver and other stakeholder involvement.
A scoping review and critique of the Input-Output subtyping dimension of spatial neglect
Aziz JR, Good SR, Horne SC and Eskes GA
Spatial neglect is a common and debilitating disorder after stroke whereby individuals have difficulty reporting, orienting, and/or responding to the contralesional side of space. Given the heterogeneity of neglect symptom presentation, various neglect subtypes have been proposed to better characterize the disorder. This review focuses on the distinction between Input neglect (i.e., difficulty perceiving and/or attending to contralesional stimuli) and Output neglect (i.e., difficulty planning and/or executing movements toward contralesional stimuli). Conceptualizations of Input and Output neglect have varied considerably. We provide a novel summary of the terminology, measurement approaches, and neural correlates of these subtypes. A protocol detailing our systematic scoping review strategy is registered on the Open Science Framework (https://osf.io/bvtxf/). For feasibility and greater comparability across studies, we limited our inclusion criteria to tasks focused on visual stimuli and upper-limb movements. A total of 110 articles were included in the review. Subtyping tasks were categorized based on whether they mainly manipulated aspects of the input (i.e., congruence of visual input with motor output, presence of visual input) or the output (i.e., modality, goal, or direction of output) to produce an Input-Output subtype dissociation. We used our review results to identify four main critiques of this literature: 1) lack of consistency/clarity in conceptual models; 2) methodological issues of dissociating Input and Output subtypes; 3) a need for updated neural theories; and 4) barriers to clinical application. We discuss the lessons learned from this subtyping dimension that can be applied to future research on neglect subtype assessment and treatment.
Testing a new model of telehealth-delivered treatment for primary care patients with alcohol use disorder: A randomized controlled trial protocol
Bonar EE, Goldstick JE, Rostker MJ, Dailey SE, Augustiniak AN, Brin C, Manderachia DA, Bourque C, Girard R, Sulkowski L and Lin LA
The majority of adults suffering from alcohol use disorders (AUD) do not receive treatment. To address this gap in care, we must develop new models to increase identification, engagement and delivery of accessible and effective treatment. This paper describes the protocol for a randomized controlled trial (RCT) testing a novel telehealth treatment model for primary care patients with untreated AUD.
The Pediatric Autism Research Cohort (PARC) Study: protocol for a patient-oriented prospective study examining trajectories of functioning in children with autism
Kata A, McPhee PG, Chen YJ, Zwaigenbaum L, Singal D, Roncadin C, Bennett T, Carter M, Di Rezze B, Drmic I, Duku E, Fournier S, Frei J, Gentles SJ, Georgiades K, Hanlon-Dearman A, Hoult L, Kelley E, Koller J, de Camargo OK, Lai J, Mahoney B, Mesterman R, Ng O, Robertson S, Rosenbaum P, Salt M, Zubairi MS and Georgiades S
The developmentally variable nature of autism poses challenges in providing timely services tailored to a child's needs. Despite a recent focus on longitudinal research, priority-setting initiatives with stakeholders highlighted the importance of studying a child's day-to-day functioning and social determinants of health to inform clinical care. To address this, we are conducting a pragmatic multi-site, patient-oriented longitudinal investigation: the (. In young children (<7 years of age) newly diagnosed with autism, we will: (1) examine variability in trajectories of adaptive functioning from the point of diagnosis into transition to school; and (2) identify factors associated with trajectories of adaptive functioning.
From hallucinations to delusions: A narrative review of psychotic-like experiences and their implications
Logoń K, Świrkosz GJ and Kowalski K
Psychotic-like experiences (PLEs) refer to sub-threshold hallucinations and delusions observed in both clinical samples and the general population. Psychotic-like experiences have far-reaching implications for an individual's coping strategies and daily functioning. They are associated with both psychotic and non-psychotic disorders. This article presents a comprehensive review of the current literature on PLEs, incorporating a detailed exploration of the definition, prevalence, risk factors, functional impairments, and comorbid psychiatric disorders. Medline/PubMed and Embase were searched to establish and identify the literature. A total of 108 studies met our inclusion criteria. The genetic and biochemical backgrounds of PLEs are discussed, focusing on gene polymorphisms, changes in brain gyrification and hypothalamic-pituitary-adrenal (HPA) axis dysfunction. Psychological factors, such as trauma exposure, emotion regulation difficulties, cognitive biases, and attachment issues, were thoroughly examined, especially in terms of their impact on the emergence of PLEs. Here, we show how important the clinical aspects of developmental PLEs are, underlining the significance of an increased risk of self-harm and suicidal behaviors in those individuals and the comorbidity of psychiatric disorders in enabling clinicians to discern specific areas to observe. Although there is limited evidence on effective protocols for PLE management, various treatment approaches are explained. Despite increased research on PLEs in recent years, further investigation is needed to fully understand the nature of PLEs and to optimize therapeutic strategies. This article consolidates the current knowledge by synthesizing information on PLEs, including risk factors, comorbidities, treatments, and their impact on individual's lives.
Digital Self-Management Platform for Adult Asthma: Randomized Attention-Placebo Controlled Trial
Kandola A, Edwards K, Straatman J, Dührkoop B, Hein B and Hayes J
Asthma is one of the most common chronic conditions worldwide, with a substantial individual and health care burden. Digital apps hold promise as a highly accessible, low-cost method of enhancing self-management in asthma, which is critical to effective asthma control.
The impact of low-energy total diet replacement with behavioural support for remission of type 2 diabetes on disordered eating (ARIADNE): Protocol for a non-inferiority randomised controlled trial
Tsompanaki E, Aveyard P, Park RJ and Koutoukidis DA
The National Health Service (NHS) in England is currently piloting a weight loss programme for remission of newly diagnosed type 2 diabetes (T2D), where participants replace all food with low-energy nutritionally complete formula products for 12 weeks (total diet replacement, TDR) and receive behavioural support. In a clinical trial, this programme led to remission in nearly half the participants. However, this weight loss programme might also worsen disordered eating and prompt eating disorders in susceptible people. We aim to investigate if the TDR programme is non-inferior to standard care in terms of disordered eating in susceptible individuals.
Mindfulness-based stress reduction (MBSR) for fibromyalgia patients: The role of pain cognitions as mechanisms of change
Taub R, Agmon-Levin N, Frumer L, Samuel-Magal I, Glick I and Horesh D
Fibromyalgia (FM) is a pain condition characterized by physical and psychological difficulties. This randomized controlled trial aimed to evaluate the effects of a mindfulness-based stress reduction (MBSR) on FM patients and identify the role of two pain cognitions: psychological inflexibility in pain (PIPS) and pain catastrophizing (PCS), as mechanisms of change.
The efficacy of real versus sham external Trigeminal Nerve Stimulation (eTNS) in youth with Attention-Deficit/Hyperactivity Disorder (ADHD) over 4 weeks: a protocol for a multi-centre, double-blind, randomized, parallel-group, phase IIb study (ATTENS)
Rubia K, Johansson L, Carter B, Stringer D, Santosh P, Mehta MA, Conti AA, Bozhilova N, Eraydin IE and Cortese S
Attention Deficit/Hyperactivity Disorder (ADHD), if severe, is usually treated with stimulant or non-stimulant medication. However, users prefer non-drug treatments due to side effects. Alternative non-medication treatments have so far only shown modest effects. External trigeminal nerve stimulation (eTNS) is a minimal risk, non-invasive neuromodulation device, targeting the trigeminal system. It was approved for ADHD in 2019 by the USA Food and Drug administration (FDA) based on a small proof of concept randomised controlled trial (RCT) in 62 children with ADHD showing improvement of ADHD symptoms after 4 weeks of nightly real versus sham eTNS with minimal side effects. We present here the protocol of a larger confirmatory phase IIb study testing efficacy, longer-term persistency of effects and underlying mechanisms of action.
A Low-Intensity Transcranial Focused Ultrasound Parameter Exploration Study of the Ventral Capsule/Ventral Striatum
Chou T, Kochanowski BJ, Hayden A, Borron BM, Barbeiro MC, Xu J, Kim JW, Zhang X, Bouchard RR, Phan KL, Goodman WK and Dougherty DD
Deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) is effective for treatment-resistant obsessive-compulsive disorder (OCD); however, DBS is associated with neurosurgical risks. Transcranial focused ultrasound (tFUS) is a newer form of noninvasive (ie, nonsurgical) stimulation that can modulate deeper regions, such as the VC/VS. tFUS parameters have just begun to be studied and have often not been compared in the same participants. We explored the effects of three VC/VS tFUS protocols and an entorhinal cortex (ErC) tFUS session on the VC/VS and cortico-striato-thalamo-cortical circuit (CSTC) in healthy individuals for later application to patients with 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.
Repurposing of dextromethorphan as an adjunct therapy in patients with major depressive disorder: a randomised, group sequential adaptive design, controlled clinical trial protocol
Maji S, Mohapatra D, Jena M, Srinivasan A and Maiti R
Therapeutic latency, lack of efficacy and adverse drug reactions are the major concerns in current antidepressant therapies. To overcome these treatment hurdles, add-on therapy to conventional antidepressant medications may lead to better therapeutic outcomes. The present randomised controlled trial has been planned to evaluate the efficacy and safety of add-on dextromethorphan to selective serotonin reuptake inhibitors (SSRIs) in major depressive disorder (MDD).
The National Sleep Research Resource: making data findable, accessible, interoperable, reusable and promoting sleep science
Zhang Y, Kim M, Prerau M, Mobley D, Rueschman M, Sparks K, Tully M, Purcell S and Redline S
This paper presents a comprehensive overview of the National Sleep Research Resource (NSRR), a National Heart Lung and Blood Institute-supported repository developed to share data from clinical studies focused on the evaluation of sleep disorders. The NSRR addresses challenges presented by the heterogeneity of sleep-related data, leveraging innovative strategies to optimize the quality and accessibility of available datasets. It provides authorized users with secure centralized access to a large quantity of sleep-related data including polysomnography, actigraphy, demographics, patient-reported outcomes, and other data. In developing the NSRR, we have implemented data processing protocols that ensure de-identification and compliance with FAIR (Findable, Accessible, Interoperable, Reusable) principles. Heterogeneity stemming from intrinsic variation in the collection, annotation, definition, and interpretation of data has proven to be one of the primary obstacles to efficient sharing of datasets. Approaches employed by the NSRR to address this heterogeneity include (1) development of standardized sleep terminologies utilizing a compositional coding scheme, (2) specification of comprehensive metadata, (3) harmonization of commonly used variables, and (3) computational tools developed to standardize signal processing. We have also leveraged external resources to engineer a domain-specific approach to data harmonization. We describe the scope of data within the NSRR, its role in promoting sleep and circadian research through data sharing, and harmonization of large datasets and analytical tools. Finally, we identify opportunities for approaches for the field of sleep medicine to further support data standardization and sharing.
'Nip it in the bud': Low-frequency rTMS of the prefrontal cortex disrupts threat memory consolidation in humans
Battaglia S, Nazzi C, Fullana MA, di Pellegrino G and Borgomaneri S
It is still unclear how the human brain consolidates aversive (e.g., traumatic) memories and whether this process can be disrupted. We hypothesized that the dorsolateral prefrontal cortex (dlPFC) is crucially involved in threat memory consolidation. To test this, we used low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) within the memory stabilization time window to disrupt the expression of threat memory. We combined a differential threat-conditioning paradigm with LF-rTMS targeting the dlPFC in the critical condition, and occipital cortex stimulation, delayed dlPFC stimulation, and sham stimulation as control conditions. In the critical condition, defensive reactions to threat were reduced immediately after brain stimulation, and 1 h and 24 h later. In stark contrast, no decrease was observed in the control conditions, thus showing both the anatomical and temporal specificity of our intervention. We provide causal evidence that selectively targeting the dlPFC within the early consolidation period prevents the persistence and return of conditioned responses. Furthermore, memory disruption lasted longer than the inhibitory window created by our TMS protocol, which suggests that we influenced dlPFC neural activity and hampered the underlying, time-dependent consolidation process. These results provide important insights for future clinical applications aimed at interfering with the consolidation of aversive, threat-related memories.
A Systematic Review and Meta-analysis: Paternal Anxiety and the Emotional and Behavioral Outcomes in Their Offspring
Zecchinato F, Ahmadzadeh YI, Kreppner JM and Lawrence PJ
Anxiety disorders are highly prevalent worldwide; however, the literature lacks a meta-analytic quantification of the risk posed by fathers' anxiety for offspring development. This systematic review and meta-analysis aimed to provide a comprehensive estimate of the magnitude of the association between paternal anxiety and emotional and behavioral problems of offspring.
Autism spectrum disorder (ASD) and sexual offending: A systematic review
Margari A, De Agazio G, Marzulli L, Piarulli FM, Mandarelli G, Catanesi R, Carabellese FF and Cortese S
The relationship between autism spectrum disorder (ASD) and sexual offending (SO) is an overlooked issue, both in clinical practice and in research. Based on a pre-specified protocol (PROSPERO: CRD42024501598), we systematically searched Pubmed and Scopus, between January 1st, 1994 and January 12th, 2024, for articles related to SO in ASD. Study quality was assessed with study design-specific tools (Study Quality Assessment Tools, NHLBI, NIH). We found 19 relevant publications (five cross-sectional studies, two case-control studies, and 12 case reports). Seven of the studies were deemed of "good" quality, the rest as "fair". Included studies addressed three key aspects: 1) psychopathological characteristics of individuals with ASD that increase the risk of committing SO; 2) intervention strategies for individuals with ASD and SO; 3) involvement of individuals with ASD and SO in the justice system. Overall, while there is an increasing interest in this topic, more rigorous study designs, including randomised controlled trials, are needed to inform clinical practice and healthcare and social policies.
Cognitive Training in Obsessive-Compulsive Disorder: A Systematic Review
Bhattacharya M, Kashyap H and Reddy YCJ
Cognitive training (CT) for illness-linked neuropsychological deficits has been attempted in psychiatric disorders and, more recently, in obsessive-compulsive disorder (OCD). However, studies are few and far between, with a limited understanding of factors contributing to efficacy. This article aims to provide a comprehensive critical review of studies employing CT in OCD.
The Effectiveness of Transcranial Direct Current Stimulation (tDCS) and Omega-3 on Food Craving, Executive Functions, Weight, and Depressive Symptoms in Patients with Depression and Overweight: A Randomized Controlled Trial
Tabasi M, Mostafavi SA, Oreyzi H, Mohammadi MR and Khaleghi A
The most important hypothesis of this research was based on the fact that the mechanism of the effect of omega-3 on depression and obesity is formed through its accumulation in the dorsolateral prefrontal cortex (DLPFC), especially in women. Accordingly, we investigated the omega-3 intake and the concurrent stimulation of the DLPFC by tDCS and hypothesized that the synergy of these two treatments can increase the obtained effect size in patients with depression and overweight. This research was a double-blind randomized controlled trial (RCT) with a factorial design consisting of four treatment and control groups. The participants were females with depression and overweight on an outpatient basis. They received 5 ml/day omega-3 syrup (545 mg DHA, 620 mg EPA) or placebo adjunct with 12 sessions sham/tDCS stimulation administered for 3 weeks with anode-left/cathode-right protocol in the prefrontal cortex (1.5 mA, 15 minutes' stimulation / 15-20 minutes' rest intervals/one visit per week, 4 stimulations per visit). tDCS or omega-3 alone did not significantly improve the executive functions, depression, food cravings, and weight in the experimental groups compared to the control group (P > 0.05). However, tDCS adjunct with the omega-3 had a significant and positive effect on improving weight change (P = 0.011; df = 1; F = 1.27; Eta = 0.108) with a power of 0.73 compared to the control group. Furthermore, their interaction led to an improving trend in executive functions and a decreasing trend in food cravings which are clinically important. tDCS could strengthen the omega-3 mechanisms of effect through stimulating its accumulation site in the brain (i.e., the DLPFC) and the synergistic effects of these two treatments result in weight control as well as an improvement trend in the executive functions and food craving in women.
Framework proposal for Role-Playing Games as mental health intervention: the Critical Skills methodology
Otani VHO, Novaes RACB, Pedron J, Nabhan PC, Rodrigues TM, Chiba R, Guedes JVC, Marques LM and Vissoci JRN
Gamified interventions are an emerging approach in mental health treatment and prevention. Their positive effects on managing various clinical conditions stem from enhancing social skills. However, cost-effective options like Table-top Role-Playing Games (TTRPGs), which offer similar benefits to other game-based interventions, lack standardized methods for ensuring replicability. In this regard, the method outlined in this study endeavors, in a structured and guided manner drawing from the Consolidated Framework for Implementation Research (CFIR), to establish a six-step protocol for developing an intervention method utilizing TTRPGs. In all Steps, we aim to anchor ourselves in robust literature concerning social skills training (SST), cognitive behavioral therapy (CBT), and gamification comprehensively. Thus, the method presented encompasses the objectives of SST, the strategies of CBT, and the dynamics of gamification via TTRPGs. Furthermore, we demonstrate a possible application of the method to illustrate its feasibility. Ultimately, the final method is structured, evidence-based, easily applicable, cost-effective, and thus viable. Mental health professionals seeking a structured and instructional tool for protocol development will find support in the method proposed here.
Clinical effectiveness of drop-in mental health services at paediatric hospitals: A non-randomised multi-site study for children and young people and their families - study protocol
Roach A, Bennett S, Heyman I, Coughtrey A, Stokes I, Ndoci X, Balakrishnan S, Astle N, Drinkwater J, Evans R, Frederick U, Groszmann M, Jones S, McDonnell K, Mobley A, Murray A, O'Sullivan H, Ormrod S, Prendegast T, Rajalingam U, Webster E, Webster R, Vinton G and Shafran R
Despite the high prevalence of mental health difficulties in children and young people with long-term health conditions (LTCs), these difficulties and experiences are often overlooked and untreated. Previous research demonstrated the effectiveness of psychological support provided via a drop-in mental health centre located in a paediatric hospital. The aim of this prospective non-randomised single-arm multi-centre interventional study is to determine the clinical effectiveness of drop-in mental health services when implemented at paediatric hospitals in England.
Targeting the adenosinergic system in restless legs syndrome: A pilot, "proof-of-concept" placebo-controlled TMS-based protocol
Lanza G, Salemi M, Mogavero MP, Catania V, Galeano A, Garifoli A, Lanuzza B, Morreale M, Tripodi M, Cantone M, Cappellani F, Concerto C, Rodolico A, Pennisi M, Bella R and Ferri R
Restless Legs Syndrome (RLS) is a common sleep disorder characterized by an urge to move the legs that is responsive to movement (particularly during rest), periodic leg movements during sleep, and hyperarousal. Recent evidence suggests that the involvement of the adenosine system may establish a connection between dopamine and glutamate dysfunction in RLS. Transcranial magnetic stimulation (TMS) is a non-invasive electrophysiological technique widely applied to explore brain electrophysiology and neurochemistry under different experimental conditions. In this pilot study protocol, we aim to investigate the effects of dipyridamole (a well-known enhancer of adenosinergic transmission) and caffeine (an adenosine receptor antagonist) on measures of cortical excitation and inhibition in response to TMS in patients with primary RLS. Initially, we will assess cortical excitability using both single- and paired-pulse TMS in patients with RLS. Then, based on the measures obtained, we will explore the effects of dipyridamole and caffeine, in comparison to placebo, on various TMS parameters related to cortical excitation and inhibition. Finally, we will evaluate the psycho-cognitive performance of RLS patients to screen them for cognitive impairment and/or mood-behavioral dysfunction, thus aiming to correlate psycho-cognitive findings with TMS data. Overall, this study protocol will be the first to shed lights on the neurophysiological mechanisms of RLS involving the modulation of the adenosine system, thus potentially providing a foundation for innovative "pharmaco-TMS"-based treatments. The distinctive TMS profile observed in RLS holds indeed the potential utility for both diagnosis and treatment, as well as for patient monitoring. As such, it can be considered a target for both novel pharmacological (i.e., drug) and non-pharmacological (e.g., neuromodulatory), "TMS-guided", interventions.
Neuromuscular electrical stimulation for physical function maintenance during hematopoietic stem cell transplantation: Study protocol
Anderson LJ, Paulsen L, Miranda G, Syrjala KL, Graf SA, Chauncey TR and Garcia JM
Hematopoietic stem cell transplantation is a common life-saving treatment for hematologic malignancies, though can lead to long-term functional impairment, fatigue, muscle atrophy, with decreased quality of life. Although traditional exercise has helped reduce these effects, it is inconsistently recommended and infrequently maintained, and most patients remain sedentary during and after treatment. There is need for alternative rehabilitation strategies, like neuromuscular electrical stimulation, that may be more amenable to the capabilities of hematopoietic stem cell transplant recipients. Patients receiving autologous HCT are being enroled in a randomized controlled trial with 1:1 (neuromuscular electrical stimulation:sham) design stratified by diagnosis and sex. Physical function, body composition, quality of life, and fatigue are assessed prior to hematopoietic stem cell transplant (prior to initiating preparatory treatment) and 24±5 days post hematopoietic stem cell transplant (Follow-up 1); physical function and quality of life are also assessed 6-months post hematopoietic stem cell transplant (Follow-up 2). The primary outcome is between-group difference in the 6-minute walk test change scores (Follow-up 1-Pre-transplant; final enrolment goal N = 23/group). We hypothesize that 1) neuromuscular electrical stimulation will attenuate hematopoietic stem cell transplant-induced adverse effects on physical function, muscle mass, quality of life, and fatigue compared to sham at Follow-up 1, and 2) Pre-transplant physical function will significantly predict fatigue and quality of life at Follow-up 2. We will also describe feasibility and acceptability of neuromuscular electrical stimulation during hematopoietic stem cell transplant. This proposal will improve rehabilitative patient care and quality of life by determining efficacy and feasibility of a currently underutilized therapeutic strategy aimed at maintaining daily function and reducing the impact of a potent and widely used cancer treatment. This trial is registered with clinicaltrials.gov (NCT04364256).
Effectiveness of mindfulness and Qigong training for self-healing in patients with Hwabyung and depressive disorder: a protocol for a randomized controlled trial
Yoon SI, Park HY, Lee HW, Park C, Chung SY and Kim JW
Hwabyung is a Korean culture-bound syndrome characterized by anger-related physical and psychological symptoms. Depressive disorder is a common mental illness occurring worldwide, and has been reported to have a high comorbidity rate with Hwabyung. For patients with depressive disorders, differential diagnosis and combined treatment for Hwabyung should be considered. Mindfulness and Qigong may be effective alternatives for regulating emotions such as depression, anxiety, and anger. This study aims to investigate whether Mindfulness and Qigong Training for Self-Healing (MQT-SH) would improve emotional problems in patients with Hwabyung and depressive disorder.
Understanding the pubertal, psychosocial, and cognitive developmental trajectories of stunted and non-stunted adolescents: protocol of a multi-site Indonesian cohort study
Medise BE, Julia M, Devaera Y, Sitaresmi MN, Asmarinah , Widjaja NA, Kalalo RT, Soesanti F, Friska D, Sirait WR, Azzopardi P and Sawyer S
The prevalence of stunting among Indonesian children aged 5-12 years decreased from 30.7% in 2013 to 23.6% in 2018 but has remained among the highest rates worldwide. Furthermore, Indonesian children were shorter than the standard reported by the World Health Organization and experienced obesity. The Indonesian government has created many programs to reduce stunting in children under the age of 5 years. An early preventive strategy is necessary because stunting can manifest within the initial 1,000 days of life, including during pregnancy. Therefore, a newer perspective, such as that achieved by addressing stunting in adolescents, has been deemed useful, given that adolescents are in their pubertal stage and are undergoing lifestyle changes. This cohort study was designed to measure these factors comprehensively in stunted and non-stunted children as they pass through adolescence.
Metabolic Syndrome in people treated with Antipsychotics (RISKMet): A multimethod study protocol investigating genetic, behavioural, and environmental risk factors
de Girolamo G, La Cascia C, Macchia PE, Nobile M, Calza S, Camillo L, Mauri M, Pozzi M, Tripoli G, Vetrani C, Caselani E and Magno M
The RISKMet project aims to: (1) identify risk factors for metabolic syndrome (MetS) by comparing patients with and without MetS; (2) characterise patients treated with second-generation antipsychotics (SGAs) about MetS diagnosis; (3) study behavioural patterns, including physical activity (PA) and dietary habits, in patients and healthy individuals using a prospective cohort design.
Study protocol for measuring stigmatization in persistent tic disorders: development and validation of the Tourette discrimination-stigmatization scale
Martindale JM, Ringheanu VM, Pring KA, Norona S, Wiseman K, Strowd RE, Chapman L, Rigdon J, Rapp SR, Storch EA, Ip E and Mink JW
Persistent Tic Disorders such as Tourette Syndrome are common neurodevelopmental disorders that are highly stigmatized. Many individuals with Persistent Tic Disorders experience peer rejection, loneliness, and self-stigma. Experiencing stigmatization during childhood can influence the persistence of moderate-to-severe tics later in life. Additionally, these factors have been associated with increased suicidal ideation, suicide attempts, and psychiatric symptom severity. There is a need for interventions to reduce stigma and stigmatization in Persistent Tic Disorders. Before developing cost-effective interventions to mitigate stigma's profound downstream health impacts, a reliable measure of stigmatization must be created. The overarching goal of this research is to develop and validate the Tourette Discrimination-Stigmatization (TD-STIGMA) Scale.
Retinal Tear Following Low-Frequency Repetitive Transcranial Magnetic Stimulation for Obsessive-Compulsive Disorder
Garip B, Buzkan B and Demir S
Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive form of brain stimulation that uses magnetic pulses to stimulate specific brain regions. Retina is being investigated whether the retina, which is also known as the brain's window to the outside world, is affected by the treatment.
Acceptability, usability, and credibility of a mindfulness-based digital therapeutic for pediatric concussion: A mixed-method study
Sicard V, O'Kane K, Brown O, Butterfield L, Kardish R, Choi E, Healey K, Silverberg N, Smith AM, Goldfield G, Saab BJ, Gray C, Goulet K, Anderson P, Mackie C, Roth S, Osmond M, Zemek R, Cairncross M and Ledoux AA
The ability to cope with concussion symptoms and manage stress is an important determinant of risk for prolonged symptoms.
Researching COVID to enhance recovery (RECOVER) pediatric study protocol: Rationale, objectives and design
Gross RS, Thaweethai T, Rosenzweig EB, Chan J, Chibnik LB, Cicek MS, Elliott AJ, Flaherman VJ, Foulkes AS, Gage Witvliet M, Gallagher R, Gennaro ML, Jernigan TL, Karlson EW, Katz SD, Kinser PA, Kleinman LC, Lamendola-Essel MF, Milner JD, Mohandas S, Mudumbi PC, Newburger JW, Rhee KE, Salisbury AL, Snowden JN, Stein CR, Stockwell MS, Tantisira KG, Thomason ME, Truong DT, Warburton D, Wood JC, Ahmed S, Akerlundh A, Alshawabkeh AN, Anderson BR, Aschner JL, Atz AM, Aupperle RL, Baker FC, Balaraman V, Banerjee D, Barch DM, Baskin-Sommers A, Bhuiyan S, Bind MC, Bogie AL, Bradford T, Buchbinder NC, Bueler E, Bükülmez H, Casey BJ, Chang L, Chrisant M, Clark DB, Clifton RG, Clouser KN, Cottrell L, Cowan K, D'Sa V, Dapretto M, Dasgupta S, Dehority W, Dionne A, Dummer KB, Elias MD, Esquenazi-Karonika S, Evans DN, Faustino EVS, Fiks AG, Forsha D, Foxe JJ, Friedman NP, Fry G, Gaur S, Gee DG, Gray KM, Handler S, Harahsheh AS, Hasbani K, Heath AC, Hebson C, Heitzeg MM, Hester CM, Hill S, Hobart-Porter L, Hong TKF, Horowitz CR, Hsia DS, Huentelman M, Hummel KD, Irby K, Jacobus J, Jacoby VL, Jone PN, Kaelber DC, Kasmarcak TJ, Kluko MJ, Kosut JS, Laird AR, Landeo-Gutierrez J, Lang SM, Larson CL, Lim PPC, Lisdahl KM, McCrindle BW, McCulloh RJ, McHugh K, Mendelsohn AL, Metz TD, Miller J, Mitchell EC, Morgan LM, Müller-Oehring EM, Nahin ER, Neale MC, Ness-Cochinwala M, Nolan SM, Oliveira CR, Osakwe O, Oster ME, Payne RM, Portman MA, Raissy H, Randall IG, Rao S, Reeder HT, Rosas JM, Russell MW, Sabati AA, Sanil Y, Sato AI, Schechter MS, Selvarangan R, Sexson Tejtel SK, Shakti D, Sharma K, Squeglia LM, Srivastava S, Stevenson MD, Szmuszkovicz J, Talavera-Barber MM, Teufel RJ, Thacker D, Trachtenberg F, Udosen MM, Warner MR, Watson SE, Werzberger A, Weyer JC, Wood MJ, Yin HS, Zempsky WT, Zimmerman E, Dreyer BP and
The prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or "Long COVID") in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults.
The PRECISE-DYAD protocol: linking maternal and infant health trajectories in sub-Saharan Africa
Craik R, Volvert ML, Koech A, Jah H, Pickerill K, Abubakar A, D'Alessandro U, Barratt B, Blencowe H, Bone JN, Chandna J, Gladstone MJ, Khalil A, Li L, Magee LA, Makacha L, Mistry HD, Moore SE, Roca A, Salisbury TT, Temmerman M, Toudup D, Vidler M, von Dadelszen P and
PRECISE-DYAD is an observational cohort study of mother-child dyads running in urban and rural communities in The Gambia and Kenya. The cohort is being followed for two years and includes uncomplicated pregnancies and those that suffered pregnancy hypertension, fetal growth restriction, preterm birth, and/or stillbirth.
Effectiveness of short sprint interval training in women with major depressive disorder: a proof-of-concept study
Ribeiro JA, Schuch FB, Tonello L, Meneghel Vargas KF, Oliveira-Junior SA, Müller PT and Boullosa D
High-intensity intermittent training has emerged as an option for treating major depressive disorder (MDD). However, short sprint training (sSIT), an efficient HIIT modality, has not been tested yet for this purpose. The sSIT has been proven to induce the same metabolic adaptations, with the advantage of promoting lower muscle fatigue than other HIIT protocols.
Stress in autism (STREAM): A study protocol on the role of circadian activity, sleep quality and sensory reactivity
Gernert CC, Falter-Wagner CM, Noreika V, Jachs B, Jassim N, Gibbs K, Streicher J, Betts H and Bekinschtein TA
Mental health issues are markedly increased in individuals with autism, making it the number one research priority by stakeholders. There is a crucial need to use personalized approaches to understand the underpinnings of mental illness in autism and consequently, to address individual needs. Based on the risk factors identified in typical mental research, we propose the following themes central to mental health issues in autism: sleep difficulties and stress. Indeed, the prevalence of manifold circadian disruptions and sleep difficulties in autism, alongside stress related to sensory overload, forms an integral part of autistic symptomatology. This proof-of-concept study protocol outlines an innovative, individualised approach towards investigating the interrelationships between stress indices, sleep and circadian activation patterns, and sensory sensitivity in autism. Embracing an individualized methodology, we aim to collect 14 days of data per participant from 20 individuals with autism diagnoses and 20 without. Participants' sleep will be monitored using wearable EEG headbands and a sleep diary. Diurnal tracking of heart rate and electrodermal activity through wearables will serve as proxies of stress. Those objective data will be synchronized with subjective experience traces collected throughout the day using the Temporal Experience Tracing (TET) method. TET facilitates the quantification of relevant aspects of individual experience states, such as stress or sensory sensitivities, by providing a continuous multidimensional description of subjective experiences. Capturing the dynamics of subjective experiences phase-locked to neural and physiological proxies both between and within individuals, this approach has the potential to contribute to our understanding of critical issues in autism, including sleep problems, sensory reactivity and stress. The planned strives to provide a pathway towards developing a more nuanced and individualized approach to addressing mental health in autism.
A Review of Transcranial Magnetic Stimulation and Transcranial Direct Current Stimulation Combined with Medication and Psychotherapy for Depression
Kochanowski B, Kageki-Bonnert K, Pinkerton EA, Dougherty DD and Chou T
After participating in this CME activity, the psychiatrist should be better able to:• Compare and contrast therapies used in combination with transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) for treating MDD.
Emotional Regulation as a Transdiagnostic Process of Emotional Disorders in Therapy: A Systematic Review and Meta-Analysis
Antuña-Camblor C, Gómez-Salas FJ, Burgos-Julián FA, González-Vázquez A, Juarros-Basterretxea J and Rodríguez-Díaz FJ
Several studies have shown that emotional regulation (ER) is a transdiagnostic construct of emotional disorders. Therefore, if therapy improves ER, it would improve psychological distress.
Studying the context of psychoses to improve outcomes in Ethiopia (SCOPE): Protocol paper
Hanlon C, Roberts T, Misganaw E, Malla A, Cohen A, Shibre T, Fekadu W, Teferra S, Kebede D, Mulushoa A, Girma Z, Tsehay M, Kiross D, Lund C, Fekadu A, Morgan C and Alem A
Global evidence on psychosis is dominated by studies conducted in Western, high-income countries. The objectives of the Study of Context Of Psychoses to improve outcomes in Ethiopia (SCOPE) are (1) to generate rigorous evidence of psychosis experience, epidemiology and impacts in Ethiopia that will illuminate aetiological understanding and (2) inform development and testing of interventions for earlier identification and improved first contact care that are scalable, inclusive of difficult-to-reach populations and optimise recovery.
Depression with comorbid borderline personality disorder - could ketamine be a treatment catalyst?
Więdłocha M, Marcinowicz P, Komarnicki J, Tobiaszewska M, Dębowska W, Dębowska M and Szulc A
Borderline personality disorder (BPD) is diagnosed in 10-30% of patients with major depressive disorder (MDD), and the frequency of MDD among individuals with BPD reaches over 80%. The comorbidity of MDD and BPD is associated with more severe depressive symptoms and functional impairment, higher risk of treatment resistance and increased suicidality. The effectiveness of ketamine usage in treatment resistant depression (TRD) has been demonstrated in numerous studies. In most of these studies, individuals with BPD were not excluded, thus given the high co-occurrence of these disorders, it is possible that the beneficial effects of ketamine also extend to the subpopulation with comorbid TRD and BPD. However, no protocols were developed that would account for comorbidity. Moreover, psychotherapeutic interventions, which may be crucial for achieving a lasting therapeutic effect in TRD and BPD comorbidity, were not included. In the article, we discuss the results of a small number of existing studies and case reports on the use of ketamine in depressive disorders with comorbid BPD. We elucidate how, at the molecular and brain network levels, ketamine can impact the neurobiology and symptoms of BPD. Furthermore, we explore whether ketamine-induced neuroplasticity, augmented by psychotherapy, could be of use in alleviating core BPD-related symptoms such as emotional dysregulation, self-identity disturbances and self-harming behaviors. We also discuss the potential of ketamine-assisted psychotherapy (KAP) in BPD treatment. As there is no standard approach to the application of ketamine or KAP in individuals with comorbid TRD and BPD, we consider further research in the field as imperative. The priorities should include development of dedicated protocols, distinguishing subpopulations that may benefit most from such treatment and investigating factors that may influence its effectiveness and safety.
The efficacy of transcranial direct current stimulation in the treatment of anorexia nervosa: a randomized double-blind clinical trial
Rząd Z, Rog J, Kajka N, Szewczyk P, Krukow P and Karakuła-Juchnowicz H
Anorexia nervosa (AN) is a life-threatening disease with a low effectiveness of treatment. The high relapse and mortality rate indicate new treatment approaches are needed. Here, we represent the protocol for randomized clinical trial (RCT) of transcranial direct current stimulation (tDCS) efficiency in the AN treatment. The main purpose of the 3-week RCT is to determine the effect of tDCS on the mental state and advances in nutritional rehabilitation in patients with AN.
Feasibility and acceptability of a community health worker administered behavioral activation intervention for postpartum depression: a single arm pilot study from India
Szajna A, Tekkalaki B, Nandagaon V, Udapi G, Sogalad M, Dandagi S, Kole U, Patil S, Raddi S, Short V and Kelly PJ
Women in India experience high rates of postpartum depression (PPD), with minimal availability of screening or treatment. India has an extensive network of community health workers, known as accredited social health activists (ASHAs). While they are knowledgeable about most maternal-child health problems, they have minimal knowledge about PPD. We trained ASHAs to deliver a simple home-based intervention, behavioral activation (BA), which involves individuals in activities that are sources of positive reinforcement to counter depression. The research questions guiding this study were as follows: 1) What are the feasibility and acceptability of ASHAs screening for and delivering a brief behavioral activation intervention addressing PPD among women in Belagavi, South India? 2) What impact did the brief behavioral activation intervention have on PPD?
The type of inhibition provided by thalamic interneurons alters the input selectivity of thalamocortical neurons
Djama D, Zirpel F, Ye Z, Moore G, Chue C, Edge C, Jager P, Delogu A and Brickley SG
A fundamental problem in neuroscience is how neurons select for their many inputs. A common assumption is that a neuron's selectivity is largely explained by differences in excitatory synaptic input weightings. Here we describe another solution to this important problem. We show that within the first order visual thalamus, the type of inhibition provided by thalamic interneurons has the potential to alter the input selectivity of thalamocortical neurons. To do this, we developed conductance injection protocols to compare how different types of synchronous and asynchronous GABA release influence thalamocortical excitability in response to realistic patterns of retinal ganglion cell input. We show that the asynchronous GABA release associated with tonic inhibition is particularly efficient at maintaining information content, ensuring that thalamocortical neurons can distinguish between their inputs. We propose a model where alterations in GABA release properties results in rapid changes in input selectivity without requiring structural changes in the network.
A confounder controlled machine learning approach: Group analysis and classification of schizophrenia and Alzheimer's disease using resting-state functional network connectivity
Hassanzadeh R, Abrol A, Pearlson G, Turner JA and Calhoun VD
Resting-state functional magnetic resonance imaging (rs-fMRI) has increasingly been used to study both Alzheimer's disease (AD) and schizophrenia (SZ). While most rs-fMRI studies being conducted in AD and SZ compare patients to healthy controls, it is also of interest to directly compare AD and SZ patients with each other to identify potential biomarkers shared between the disorders. However, comparing patient groups collected in different studies can be challenging due to potential confounds, such as differences in the patient's age, scan protocols, etc. In this study, we compared and contrasted resting-state functional network connectivity (rs-FNC) of 162 patients with AD and late mild cognitive impairment (LMCI), 181 schizophrenia patients, and 315 cognitively normal (CN) subjects. We used confounder-controlled rs-FNC and applied machine learning algorithms (including support vector machine, logistic regression, random forest, and k-nearest neighbor) and deep learning models (i.e., fully-connected neural networks) to classify subjects in binary and three-class categories according to their diagnosis labels (e.g., AD, SZ, and CN). Our statistical analysis revealed that FNC between the following network pairs is stronger in AD compared to SZ: subcortical-cerebellum, subcortical-cognitive control, cognitive control-cerebellum, and visual-sensory motor networks. On the other hand, FNC is stronger in SZ than AD for the following network pairs: subcortical-visual, subcortical-auditory, subcortical-sensory motor, cerebellum-visual, sensory motor-cognitive control, and within the cerebellum networks. Furthermore, we observed that while AD and SZ disorders each have unique FNC abnormalities, they also share some common functional abnormalities that can be due to similar neurobiological mechanisms or genetic factors contributing to these disorders' development. Moreover, we achieved an accuracy of 85% in classifying subjects into AD and SZ where default mode, visual, and subcortical networks contributed the most to the classification and accuracy of 68% in classifying subjects into AD, SZ, and CN with the subcortical domain appearing as the most contributing features to the three-way classification. Finally, our findings indicated that for all classification tasks, except AD vs. SZ, males are more predictable than females.
A systematic review of midwives' training needs in perinatal mental health and related interventions
Dubreucq M, Dupont C, Lambregtse-Van den Berg MP, Bramer WM, Massoubre C and Dubreucq J
Midwives may be key stakeholders to improve perinatal mental healthcare (PMHC). Three systematic reviews considered midwives' educational needs in perinatal mental health (PMH) or related interventions with a focus on depression or anxiety. This systematic review aims to review: 1) midwives' educational/training needs in PMH; 2) the training programs in PMH and their effectiveness in improving PMHC.
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