Data Analytics and Psychiatry

The stigma of nursing students towards people with mental illness (PMI) creates significant barriers to diagnosis, treatment, and recovery for those with PMI. It can also have a significant impact on the future career choices of nursing students in the field of psychiatry. Current research has found various influencing factors, including personal characteristics and educational influences. However, a comprehensive analysis that encompasses all aspects is lacking. The aim of the study was to conduct a convergent mixed-method systematic review to synthesize the influencing factors of the stigma of nursing students towards PMI according to Framework Integrating Normative Influences on Stigma (FINIS) at micro, meso, and macro levels. PubMed, Web of Science, Cochrane Library, EMBASE, CINAHL and PsycINFO were searched from 1990 to 31 December 2023. The reference lists of the included literature were further checked to identify potentially relevant articles. Two authors independently screened all titles, abstracts, and full-text articles and extracted data. Study quality was assessed by two authors using the Mixed Method Appraisal Tool (MMAT). A total of 4865 articles were initially retrieved, and 73 of these articles were included. The results suggested that the stigma towards PMI by nursing students was influenced by micro, meso and macro levels. At each FINIS level, the most frequent influencing factors are personal characteristics, the treatment system and media images. Numerous interconnected factors exert an influence on the stigma towards PMI among nursing students. Our research can be used to identify barriers and facilitators to nursing students' stigma towards PMI and to provide supporting information for interventions designed to reduce this stigma.

Retinal optical coherence tomography (OCT) provides promising prognostic imaging biomarkers for future disease activity in multiple sclerosis (MS). However, raw OCT-derived measures have multiple dependencies, supporting the need for establishing reference values adjusted for possible confounders. The purpose of this study was to investigate the capacity for age-adjusted scores of OCT-derived measures to prognosticate future disease activity and disability worsening in people with MS (PwMS).

Neuropsychological evaluations can be helpful in the aftermath of traumatic brain injury. Cognitive functioning is assessed using standardized assessment tools and by comparing an individual's scores on testing to normative data. These evaluations examine objective cognitive functioning as well as other factors that have been shown to influence performance on cognitive tests (eg, psychiatric conditions, sleep) in an attempt to answer a specific question from referring providers. Referral questions may focus on the extent of impairment, the trajectory of recovery, or ability to return to work, sport, or the other previous activity.

Chronic pain affects a wide range of physical and psychological aspects of life for those impacted. Psychosocial treatment approaches may be of support, but outreach is still limited.

Prior literature suggests a dose-response relationship between physical activity (PA) and depressive symptoms. The intensity and domain of PA are suggested to be critical to its protective effect against depression; however, existing literature has shown mixed results.

While prior studies have explored the efficacy of Morinda officinalis oligosaccharides (MOs) as a treatment for patients with major depressive disorder (MDD), the mechanistic basis for the effects of MOs on brain function or the default-mode network (DMN) has yet to be characterized. The objective of this was to examine the effects of MOs treatment on functional connectivity in different regions of the DMN.

Individuals with congenital heart disease (CHD) have an increased risk of neurodevelopmental impairments. Given the hypothesized complexity linking genomics, atypical brain structure, cardiac diagnoses and their management, and neurodevelopmental outcomes, unsupervised methods may provide unique insight into neurodevelopmental variability in CHD. Using data from the Pediatric Cardiac Genomics Consortium Brain and Genes study, we identified data-driven subgroups of individuals with CHD from measures of brain structure. Using structural magnetic resonance imaging (MRI; N = 93; cortical thickness, cortical volume, and subcortical volume), we identified subgroups that differed primarily on cardiac anatomic lesion and language ability. In contrast, using diffusion MRI (N = 88; white matter connectivity strength), we identified subgroups that were characterized by differences in associations with rare genetic variants and visual-motor function. This work provides insight into the differential impacts of cardiac lesions and genomic variation on brain growth and architecture in patients with CHD, with potentially distinct effects on neurodevelopmental outcomes.

During the Covid-19 pandemic Germany experienced its first increase in the proportion of heavy cannabis users since 1995. With the expected nationwide decriminalization of cannabis before 2025, we investigate the potential causes for that increase. Data were from the 2021 European Web Survey on Drugs (EWSD) including 762 12-month marijuana users from Germany (72.9% male, mean age = 29.5 years). Both heavy and regular cannabis consumers reported an increase in marijuana consumption during the pandemic, with infrequent users reporting a decrease. Using multinomial logistic regression, we found younger individuals (OR = 0.95 [95% CI = 0.92, 0.98]) and those not pursuing or completing higher education (OR = 1.86 [1.23, 2.81]) had increased use. Additionally, using cannabis to self-medicate (OR = 2.79 [1.56, 4.99]) and purchasing marijuana (OR = 2.26 [1.35, 3.77]) was associated with increased use. We found, relative to infrequent users, both regular (OR = 4.00 [2.39, 6.72]) and notably heavy users (OR = 31.17 [12.10, 80.32]) were more likely to use cannabis to self-medicate. Both regular (OR = 4.09 [2.47, 6.77]) and especially heavy users (OR = 13.53 [6.74, 27.16]) were also more likely to purchase marijuana. Heavy users were also more likely to be past 30-day tobacco users (OR = 5.92 [2.81, 12.45]). We identified the self-reported motivation of using cannabis to self-medicate as well as act of purchasing marijuana as having the strongest relation to being a heavy user and increasing marijuana use during the Covid-19 pandemic.

In the present work we investigate how individual differences in at least occasionally using distinct social media platforms is linked to social networks use disorder (SNUD) tendencies. A final sample of n = 2200 participants filled in the AICA-C-9 measure to get insights into individual differences in overuse of social media and participants also indicated which platforms they used at least once a month.

People with psychotic disorders are at increased risk of experiencing involuntary hospital admissions relative to other psychiatric patients. Within this group, refugees and other minority groups may be at even greater risk. However, little is known about the role of migration background in the risk of involuntary admissions around the time of first psychosis-related treatment.

HIV biomedical intervention uptake is suboptimal among Black sexually minoritized men (SMM) and transgender women (TW). Venues where people meet and interact shape HIV-related risk and prevention behaviors. We aimed to construct GPS-defined venue-based affiliation networks and identify the unique set of venues that could maximize reach of HIV biomedical interventions among Black SMM and TW.

The 15-method is an opportunistic screening and brief intervention tool for alcohol-related problems in primary healthcare. A Danish feasibility study of the 15-method indicated that adjustments were needed to improve its contextual fit to Danish general practice. This adjustment process was conducted in two parts. The first part focused on identifying barriers, facilitators, and user needs for addressing alcohol using the 15-method. The second part will address the identified barriers and user needs to finalize a Danish version of the method. This study reports on part one of the adjustment process.

Translational studies benefit from experimental designs where laboratory organisms use human-relevant behaviors. One such behavior is decision-making, however studying complex decision-making in rodents is labor-intensive and typically restricted to two levels of cost/reward. We design a fully automated, inexpensive, high-throughput framework to study decision-making across multiple levels of rewards and costs: the REward-COst in Rodent Decision-making (RECORD) system. RECORD integrates three components: 1) 3D-printed arenas, 2) custom electronic hardware, and 3) software. We validated four behavioral protocols without employing any food or water restriction, highlighting the versatility of our system. RECORD data exposes heterogeneity in decision-making both within and across individuals that is quantifiably constrained. Using oxycodone self-administration and alcohol-consumption as test cases, we reveal how analytic approaches that incorporate behavioral heterogeneity are sensitive to detecting perturbations in decision-making. RECORD is a powerful approach to studying decision-making in rodents, with features that facilitate translational studies of decision-making in psychiatric disorders.

TikTok (ByteDance) experienced a surge in popularity during the COVID-19 pandemic as a way for people to interact with others, share experiences and thoughts related to the pandemic, and cope with ongoing mental health challenges. However, few studies have explored how youth use TikTok to learn about mental health.

Clinical forecasting models have potential to optimize treatment and improve outcomes in psychosis, but predicting long-term outcomes is challenging and long-term follow-up data are scarce. In this 10-year longitudinal study, we aimed to characterize the temporal evolution of cortical correlates of psychosis and their associations with symptoms.

This study investigated the impact of social activities on cognitive functioning and psychopathological symptoms.

Global health reciprocal innovation emphasizes the movement of technologies or interventions between high- and low-income countries to address a shared public health problem, in contrast to unidirectional models of "development aid" or "reverse innovation". Evidence-based interventions are frequently adapted from the setting in which they were developed and applied in a new setting, presenting an opportunity for learning and partnership across high- and low-income contexts. However, few clear procedures exist to guide researchers and implementers on how to incorporate equitable and learning-oriented approaches into intervention adaptation across settings. We integrated theories from pedagogy, implementation science, and public health with examples from experience adapting behavioral health interventions across diverse settings to develop a procedure for a bidirectional, equitable process of intervention adaptation across high- and low-income contexts. The Mutual capacity building model for adaptation (MCB-MA) is made up of seven steps: 1) Exploring: A dialogue about the scope of the proposed adaptation and situational appraisal in the new setting; 2) Developing a shared vision: Agreeing on common goals for the adaptation; 3) Formalizing: Developing agreements around resource and data sharing; 4) Sharing complementary expertise: Group originating the intervention supporting the adapting group to learn about the intervention and develop adaptations, while gleaning new strategies for intervention implementation from the adapting group; 5) Reciprocal training: Originating and adapting groups collaborate to train the individuals who will be implementing the adapted intervention; 6) Mutual feedback: Originating and adapting groups share data and feedback on the outcomes of the adapted intervention and lessons learned; and 7) Consideration of next steps: Discuss future collaborations. This evidence-informed procedure may provide researchers with specific actions to approach the often ambiguous and challenging task of equitable partnership building. These steps can be used alongside existing intervention adaptation models, which guide the adaptation of the intervention itself.

Caring for those who have been traumatized can place mental health professionals at risk of secondary traumatic stress, particularly in those with their own experience of personal trauma.

Suicidal behaviour is common among medical students, and the prevalence rates might vary across various regions. Even though various systematic reviews have been conducted to assess suicidal behaviours among medical students in general, no review has ever assessed or carried out a sub-analysis to show the burden of suicidal behaviours among Bangladeshi medical students.

A small number of earlier studies have suggested an effect of temporary abstinence campaigns on alcohol consumption. However, all were based on self-reported consumption estimates.

Workplace violence (WPV) is a complex global challenge in healthcare that can only be addressed through a quality improvement initiative composed of a complex intervention. However, multiple WPV-specific quality indicators are required to effectively monitor WPV and demonstrate an intervention's impact. This study aims to determine a set of quality indicators capable of effectively monitoring WPV in healthcare.

This study assessed the impact of migraine and fibromyalgia (FM) in TMD patients, focusing on pain, anxiety, depression, and quality of life (QoL). Additionally, we investigated how these variables relate to the total number of comorbidities to gain insights into their interactions.

Informed by Minority Stress Theory, to investigate disparities in pain intensity, interference, and care in patients with spinal cord injuries (SCI) based on demographic features.

We examined the burden of neuropsychiatric symptoms (NPSs) in early-onset (EO) and late-onset (LO) Alzheimer's disease (AD) and adjusted for age effects via the inclusion of cognitively unimpaired (CU) individuals.

Persistent symptoms after mild traumatic brain injury (mTBI) negatively affect daily functioning and quality of life. Fear avoidance behaviour, a coping style in which people avoid or escape from activities or situations that they expect will exacerbate their symptoms, maybe a particularly potent and modifiable risk factor for chronic disability after mTBI. This study will evaluate the efficacy of graded exposure therapy (GET) for reducing persistent symptoms following mTBI, with two primary aims: (1) To determine whether GET is more effective than usual care; (2) to identify for whom GET is the most effective treatment option, by evaluating whether baseline fear avoidance moderates differences between GET and an active comparator (prescribed aerobic exercise). Our findings will guide evidence-based care after mTBI and enable better matching of mTBI patients to treatments.

The cannabis gray market poses significant public health concerns and remains a major threat to consumer and/or potential consumer uptake of regulated cannabis markets in jurisdictions with legal state-sponsored cannabis programs. In this perspective, we provide an overview of the cannabis gray market, and describe an integrated epidemiological and regulatory science framework to study the gray market. Using tobacco regulatory science as a guide, we introduce example cannabis regulatory science research activities as a means to improve the field's understanding of the cannabis gray market. Cannabis regulatory science is a developing field that can improve our understanding of the cannabis regulatory ecosystem and provide regulatory officials and policymakers alike with much needed data to inform regulatory decision-making and improve the success and uptake of state-sponsored cannabis programs.

Some cohort studies have reported a decline in dementia prevalence and incidence over time, although these findings have not been consistent across studies. We reviewed evidence on changes in dementia prevalence and incidence over time using published population-based cohort studies that had used consistent methods with each wave and aimed to quantify associated changes in risk factors over time using population attributable fractions (PAFs).

Rates of dementia are increasing in migrant populations, however, there is evidence that they remain underrepresented in older adult healthcare services. Barriers and facilitators to accessing dementia care have been explored from the viewpoint of migrants and caregivers, however, no review has synthesised the literature pertaining to clinicians' viewpoints. This review aimed to explore clinician perspectives as to the barriers and facilitators in assessing and diagnosing dementia in migrant populations.

This study derived composite scores for two novel cognitive measures, the No Practice Effect (NPE) battery and the Miami Computerized Functional Skills Assessment and Training system for use in early-stage Alzheimer's disease (AD) clinical trials. Their psychometric properties and associations with AD risk markers were compared to those of well-established measures.

The role of adherence to the recommendations for 24-hour movement behaviors (24-HMB), including physical activity (PA), screen time (ST), and sleep duration (SLP), in relation to emotional and behavioral problems in Chinese adolescents remains uncertain. This study aimed to investigate these associations and explore potential sex differences.

Evidence suggests that having a chronic physical illness (CPI; eg, asthma, diabetes, and epilepsy) is an independent risk factor for suicidality (ie, suicidal ideation or attempts) among youth. Less is known about the mechanisms linking CPI and suicidality. Some evidence suggests that mental illness (eg, depression and anxiety) or neurodevelopmental disorder (eg, attention-deficit/hyperactivity disorder) mediates or moderates the CPI-suicidality association. Missing from the knowledge base is information on the association between having co-occurring CPI and mental illness or neurodevelopmental disorder (MIND) on youth suicidality.

Three meta-analyses suggested that the psychological assessment as a therapeutic intervention approach might have therapeutic effects but had unspecific inclusion criteria.

Behavioral sleep medicine (BSM) is a subspecialty that combines behavioral psychology and sleep medicine specialties. The objective of this study was to analyze referral patterns to a BSM clinic. The three specific aims were: (1) describe factors that predict referral acceptance, (2) identify barriers to attending initial appointment, and (3) describe variables associated with the number of visits attended.

Adults with binge-eating disorder (BED), compared with those without BED, demonstrate higher blood-oxygen-level-dependent (BOLD) response to food cues in reward-related regions of the brain. It is not known whether cognitive behavioral therapy (CBT) can reverse this reward system hyperactivation. This randomized controlled trial (RCT) assessed changes in BOLD response to binge-eating cues following CBT versus wait-list control (WLC).

The fast-growing migrant population in Japan and globally poses challenges in mental healthcare, yet research addressing migrants' mental health treatment engagement remains limited.

To access the attitudes of service users about the sharing of health records for research and to foster collaboration between municipal health services and the specialist health services in Norway.

Patients' online record access (ORA) enables patients to read and use their health data through online digital solutions. One such solution, patient-accessible electronic health records (PAEHRs) have been implemented in Estonia, Finland, Norway, and Sweden. While accumulated research has pointed to many potential benefits of ORA, its application in mental healthcare (MHC) continues to be contested. The present study aimed to describe MHC users' overall experiences with national PAEHR services.

Understanding how social categories like gender, migration background, LGBT status (lesbian/gay/bisexual/transgender), education and their intersections affect health outcomes is crucial. Challenges include avoiding stereotypes and fairly assessing health outcomes. This paper aims to demonstrate how to analyse these aspects.

Cognitive reserve (CR) is considered a protective factor for cognitive function and may explain interindividual differences of cognitive performance given similar levels of neurodegeneration, e.g., in Alzheimer´s disease. Recent evidence suggests that CR is also relevant in Parkinson's disease (PD).

Vascular contributions to cognitive impairment and dementia (VCID) represent a major factor in cognitive decline in older adults. The present study examined the relationship between cerebrovascular reactivity (CVR) measured by magnetic resonance imaging (MRI) and cognitive function in a multi-site study, using a predefined hypothesis.

TikTok is a social media mobile application that is widely used by adolescents, and has the potential to serve as a revolutionary platform for public and mental health discourse, education, and intervention.

Supporting healthy aging is a US public health priority, and gratitude is a potentially modifiable psychological factor that may enhance health and well-being in older adults. However, the association between gratitude and mortality has not been studied.

Medications for opioid use disorder (MOUD) including buprenorphine are effective, but underutilized. Rural patients experience pronounced disparities in access. To reach rural patients, the US Department of Veterans Affairs (VA) has sought to expand buprenorphine prescribing beyond specialty settings and into primary care.

Globally, violence against children poses substantial health and economic challenges, with estimated costs nearing USD 7 trillion. This prompts the urgent call for effective evidence-based interventions in preventing and mitigating violence against children. ParentApp is a mobile, open-source application designed to offer a remote version of the Parenting for Lifelong Health (PLH) programme. ParentApp is the first digital parenting intervention for caregivers of adolescents aged 10-17 years to be tested in low- and middle-income settings.

Persistent olfactory dysfunction (OD) is a common symptom following SARS-CoV-2 infection that can greatly impact quality of life (QoL). Because coping strategies have been shown to moderate the effect of disease symptoms on functional and affective outcomes, this study aims to determine whether specific coping strategies are associated with and moderate QoL outcomes.

In ESCAPE-TRD (NCT04338321), esketamine nasal spray (NS) significantly increased the probability of remission at Week 8, and of being relapse-free through Week 32 after remission at Week 8, versus quetiapine extended release (XR) in patients with treatment resistant depression (TRD). Here, we explore the time course, burden and consequences of treatment emergent adverse events (TEAEs) in the phase IIIb ESCAPE‑TRD trial. Patients with TRD were randomised 1:1 to esketamine NS or quetiapine XR, dosed per label alongside an ongoing selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor. In this secondary publication, safety analyses (comprising patients who received ≥1 dose of study treatment) included incidence, severity and durations (Kaplan‑Meier method) of TEAEs, and subsequent dispositional changes. P values were not adjusted for multiple testing. 336 patients were randomised to esketamine NS and 340 to quetiapine XR; 334 and 336 received ≥1 dose of study treatment, respectively. TEAEs were significantly more common with esketamine NS than quetiapine XR (91.9 % versus 78.0 %; p < 0.001), but were typically mild/moderate and transient in nature: a greater proportion resolved on the same-day (92.0 % versus 12.1 %) and lead to treatment discontinuation in significantly fewer patients (4.2 % versus 11.0 %, respectively; p < 0.001). The proportion of days spent with TEAEs was significantly lower with esketamine NS than quetiapine XR (median: 11.9 % versus 21.3 %; p < 0.001). Although more frequent with esketamine NS, TEAEs were typically transient and mild, with discontinuation less likely versus quetiapine XR. Data were consistent with established safety profiles, with no new safety signals identified. Alongside greater efficacy, the demonstrably more favourable tolerability profile of esketamine NS versus quetiapine XR further supports its use for TRD.

Symptoms of anxiety and attention-deficit/hyperactivity disorder (ADHD) are prospectively related from childhood to adolescence. However, whether the two dimensions of ADHD-inattention and hyperactivity-impulsivity-are differentially related to anxiety and whether there are developmental and sex/gender differences in these relations are unknown.

Lesbian, gay, bisexual, transgender, queer, and/or questioning (LGBTQ+) youth face worse mental health outcomes than non-LGBTQ+ peers. Family support may mitigate this, but sparse evidence demonstrates this in clinical settings.

To describe a learning health care system research process designed to increase buprenorphine prescribing for the treatment of opioid use disorder (OUD) in rural primary care settings within U.S. Department of Veterans Affairs (VA) treatment facilities.

The cerebellum is involved in higher-order mental processing as well as sensorimotor functions. Although structural abnormalities in the cerebellum have been demonstrated in schizophrenia, neuroimaging techniques are not yet applicable to identify them given the lack of biomarkers. We aimed to develop a robust diagnostic model for schizophrenia using radiomic features from T1-weighted magnetic resonance imaging (T1-MRI) of the cerebellum.

Post-COVID-19 condition (PCC), also known as "long COVID," is characterized by persistent symptoms, negatively affecting the well-being of individuals with PCC. Anhedonia (i.e., reduced capacity for pleasure) and compromised psychosocial functioning are notable symptoms in those with PCC. We aimed to provide insights to understand the effects of anhedonia and impaired psychosocial functioning of patients with PCC. This post-hoc analysis used data from an 8-week, double-blind, randomized, placebo-controlled trial which evaluated vortioxetine for cognitive deficits in individuals with PCC (Clinicaltrials.gov Identifier: NCT05047952). A total of 147 eligible participants were randomly assigned to receive vortioxetine or matching placebo over eight weeks of double-blind treatment. Our study investigated the relationship between anhedonia, assessed by the Snaith-Hamilton Pleasure Scale (SHAPS), and psychosocial functioning, measured with the Post-COVID Functional Status (PCFS) scale. The analysis was conducted using a generalized linear model, with adjustments for relevant covariates such as age, sex, education, suspected versus confirmed COVID diagnosis, MDD diagnosis, and alcohol consumption. Of the 147 participants, 143 participants had available baseline data for analysis. We observed that baseline PCFS score was statistically significantly positively correlated to baseline SHAPS score (β = 0.070, p = 0.045, 95% CI). Our analysis revealed a significant relationship between measures of anhedonia and psychosocial functioning in adults with PCC. Strategies that aim to improve patient-reported outcomes with PCC need to prioritize the prevention and treatment of hedonic disturbances in patients experiencing PCC.

Structural neuroimaging data have been used to compute an estimate of the biological age of the brain (brain-age) which has been associated with other biologically and behaviorally meaningful measures of brain development and aging. The ongoing research interest in brain-age has highlighted the need for robust and publicly available brain-age models pre-trained on data from large samples of healthy individuals. To address this need we have previously released a developmental brain-age model. Here we expand this work to develop, empirically validate, and disseminate a pre-trained brain-age model to cover most of the human lifespan. To achieve this, we selected the best-performing model after systematically examining the impact of seven site harmonization strategies, age range, and sample size on brain-age prediction in a discovery sample of brain morphometric measures from 35,683 healthy individuals (age range: 5-90 years; 53.59% female). The pre-trained models were tested for cross-dataset generalizability in an independent sample comprising 2101 healthy individuals (age range: 8-80 years; 55.35% female) and for longitudinal consistency in a further sample comprising 377 healthy individuals (age range: 9-25 years; 49.87% female). This empirical examination yielded the following findings: (1) the accuracy of age prediction from morphometry data was higher when no site harmonization was applied; (2) dividing the discovery sample into two age-bins (5-40 and 40-90 years) provided a better balance between model accuracy and explained age variance than other alternatives; (3) model accuracy for brain-age prediction plateaued at a sample size exceeding 1600 participants. These findings have been incorporated into CentileBrain (https://centilebrain.org/#/brainAGE2), an open-science, web-based platform for individualized neuroimaging metrics.

Delirium is a common complication of older people in hospitals, rehabilitation and long-term facilities.

Despite a two-fold risk, individuals of African ancestry have been underrepresented in Alzheimer's disease (AD) genomics efforts.

Prenatal fish intake is a key source of omega-3 polyunsaturated fatty acids needed for brain development, yet intake is generally low, and studies addressing associations with autism spectrum disorder (ASD) and related traits are lacking.

To date, only 10 of the more than 30 fur colours that had been observed in American mink (Neogale vison) have been linked to specific genes. The Royal pastel fur colour is part of a large family of brownish colours that are quite similar to one another, making breeding and selecting processes more difficult. Here we carried out whole-genome sequencing of five American minks with Royal pastel (b/b) phenotypes originating from two distinct mink populations. We identified an insertion of endogenous retroviral element type 1 (ERV1) into the first intron of the gene encoding the HPS3 protein, which regulates the trafficking of tyrosinase-containing vesicles to maturing melanosomes. With Cas9-targeted nanopore sequencing, we reconstructed the full-length sequence of the 11.7 Kb ERV1 insertion and observed hypermethylation that spread to the HPS3 gene promoter region. These findings highlight the role of HPS3 in the formation of melanosomes and melanin, as well as the genetic process regulating the intensity and spectrum of hair colour. Moreover, in mink breeding projects, these data are also useful for tracking economically important fur qualities.

The objective of this scoping review will be to identify and map the characteristics of participatory research approaches in mental health care services conducted in low- and middle-income countries (LMICs).

Encouraging engagement in rewarding or pleasant activities is one of the most important treatment goals for depression. Mental imagery exercises have been shown to increase the motivation for planned behaviour in the lab but it is unclear whether this is also the case in daily life. Therefore, we aimed to investigate the effect of mental imagery exercises on motivation and behaviour in daily life. Participants with depressive symptoms (N = 59) were randomly assigned to a group receiving mental imagery (MI) exercises or a control group receiving relaxation (RE) exercises via study phones. We employed an experience sampling design with 10 assessments per day for 10 days (three days baseline, four days with two exercises per day and three days post-intervention). Data was analysed using t-tests and multilevel linear regression analyses. As predicted, MI exercises enhanced motivation and reward anticipation during the intervention phase compared to RE. However, MI did not enhance active behaviour or strengthen the temporal association from reward anticipation (t-1) to active behaviour (t). Mental imagery exercises can act as a motivational amplifier but its effects on behaviour and real-life reward processes remain to be elucidated.

Recovery from a COVID-19 infection can lead to post-COVID-19 condition (PCC), which causes a multitude of debilitating symptoms that negatively affect an individual's health-related quality of life, including depressive and anxiety symptoms. We aim to examine the mediatory effects of anxiety on depressive symptoms in persons with PCC receiving vortioxetine.

Previous evidence suggests sex differences in the clinical course of relapsing remitting multiple sclerosis (RRMS), but comprehensive early-stage prospective studies are lacking. We aim to quantify the impact of sex on clinical outcomes in early-stage RRMS.

Studies evaluating the benefits and risks of green spaces on children's health are scarce. The present study aimed to examine the associations between exposure to green spaces during pregnancy and early childhood with respiratory, cardiometabolic, and neurodevelopmental outcomes in school-age children. We performed an Individual-Participant Data (IPD) meta-analysis involving 35,000 children from ten European birth cohorts across eight countries. For each participant, we calculated residential Normalized Difference Vegetation Index (NDVI) within a 300 m buffer and the linear distance to green spaces (meters) during prenatal life and childhood. Multiple harmonized health outcomes were selected: asthma and wheezing, lung function, body mass index, diastolic and systolic blood pressure, non-verbal intelligence, internalizing and externalizing problems, and ADHD symptoms. We conducted a two-stage IPD meta-analysis and evaluated effect modification by socioeconomic status (SES) and sex. Between-study heterogeneity was assessed via random-effects meta-regression. Residential surrounding green spaces in childhood, not pregnancy, was associated with improved lung function, particularly higher FEV (β = 0.06; 95 %CI: 0.03, 0.09 I = 4.03 %, p < 0.001) and FVC (β = 0.07; 95 %CI: 0.04, 0.09 I = 0 %, p < 0.001) with a stronger association observed in females (p < 0.001). This association remained robust after multiple testing correction and did not change notably after adjusting for ambient air pollution. Increased distance to green spaces showed an association with lower FVC (β = -0.04; 95 %CI: -0.07, -0.02, I = 4.8, p = 0.001), with a stronger effect in children from higher SES backgrounds (p < 0.001). No consistent associations were found between green spaces and asthma, wheezing, cardiometabolic, or neurodevelopmental outcomes, with direction of effect varying across cohorts. Wheezing and neurodevelopmental outcomes showed high between-study heterogeneity, and the age at outcome assessment was only associated with heterogeneity in internalizing problems.. This large European meta-analysis suggests that childhood exposure to green spaces may lead to better lung function. Associations with other respiratory outcomes and selected cardiometabolic and neurodevelopmental outcomes remain inconclusive.

Children and adolescents with obsessive-compulsive disorder (OCD) are at risk of long-term adversity, but factors influencing long-term outcomes are unclear. A general factor of psychopathology, often referred to as the p factor, captures variance shared by all mental disorders and has predicted long-term outcomes in youth with anxiety and depressive disorders. The p factor has never been examined in relation to outcomes in pediatric OCD. Here, we examine whether the p factor predicts four important outcomes over both short and long durations in youth with OCD.

Despite the impact of physician-scientists on scientific discovery and translational medicine, several reports have signalled their declining workforce, reduced funding, and insufficient protected research time. Given the paucity of outcome data on Canadian MD/PhD programs, this study presents a national portrait of the sociodemographic characteristics, training trajectories, productivity, and satisfaction in trainees and alumni from Canadian MD/PhD and MD/MSc programs.

This is a process evaluation of a large UK-based randomised controlled trial (RCT) (n = 5602) evaluating the effectiveness of recommending an alcohol reduction app, Drink Less, compared with usual digital care in reducing alcohol consumption in increasing and higher risk drinkers. The aim was to understand whether participants' engagement ('self-reported adherence') and behavioural characteristics were mechanisms of action underpinning the effectiveness of Drink Less. Self-reported adherence with both digital tools was over 70% (Drink Less: 78.0%, 95% CI = 77.6-78.4; usual digital care: 71.5%, 95% CI = 71.0-71.9). Self-reported adherence to the intervention (average causal mediation effect [ACME] = -0.250, 95% CI = -0.42, -0.11) and self-monitoring behaviour (ACME = -0.235, 95% CI = -0.44, -0.03) both partially mediated the effect of the intervention (versus comparator) on alcohol reduction. Following the recommendation (self-reported adherence) and the tracking (self-monitoring behaviour) feature of the Drink Less app appear to be important mechanisms of action for alcohol reduction among increasing and higher risk drinkers.

Spatial normalization is an essential process for comparative analyses that heavily depends on the standard brain template used. Brain morphological differences are observed in different populations due to genetic and environmental factors, causing mismatches in regions when the data are normalized to different population templates. Recent studies have indicated differences between Caucasian and East Asian populations as well as within East Asian populations, suggesting the necessity of population-specific brain templates. Thus, this study aimed to construct a Korean young adult age-specific brain template utilizing an advanced method of template construction to update the currently available Korean template.

This review was performed to determine sleep disturbance prevalence in individuals with mild cognitive impairment (MCI). The MEDLINE, Embase, Cochrane Library, CINAHL, PsycINFO, and Web of Science databases were systematically searched from inception to January 20, 2024. Fifty-two studies fulfilling the eligibility criteria were included. However, six of these studies were excluded from data synthesis due to poor methodological quality. The subjective sleep disturbance prevalence among all individuals with MCI was 35.8 % (95 % CI: 31.9-39.7) across 44 studies, and the objective sleep disturbance prevalence was 46.3 % (95 % CI: 36.3-56.3) across 6 studies. Five studies examined TST and WASO, while three assessed SE. Among all potential objective assessments of sleep disturbance prevalence, only TST, WASO, and SE could be meta-analyzed in MCI because of the limited number of studies available. The estimated sleep disturbance prevalence differed significantly according to measurement method, geographical region, and research design. However, the data source did not significantly influence prevalence estimates. In meta-regression analysis, publication year, participant age, percentage of females, and study quality did not predict prevalence. As subjective and objective sleep disturbances are common in people with MCI, effective intervention strategies should be developed to alleviate them.

Human immunodeficiency virus (HIV) infection is a major global public health issue, affecting millions of people annually. University students are among the risk groups in the community because of their high-risk behaviors. Few studies have been conducted on HIV/AIDS preventive behaviors and associated factors among university students. Therefore, focusing on these target populations is crucial because it will help university managers and different stakeholders be informed about the burden of the problem and take different measures to halt the distribution of the infection.

Medications for opioid use disorder (MOUD) reduce risks for overdose among correctional populations. Among other barriers, daily dosing requirements hinder treatment continuity post-release. Extended-release buprenorphine (XR-BUP) may therefore be beneficial. However, limited evidence exists. To conduct a systematic review examining the feasibility and effectiveness of XR-BUP among correctional populations. Searches were carried out in Pubmed, Embase, and PsychINFO in October 2023. Ten studies reporting on feasibility or effectiveness of XR-BUP were included, representing  = 819 total individuals (81.6% male). Data were extracted and narratively reported under the following main outcomes: 1) Feasibility; 2) Effectiveness; and 3) Barriers and Facilitators. Studies were heterogeneous. Correctional populations were two times readier to try XR-BUP compared to non-correctional populations. XR-BUP was feasible and safe, with no diversion, overdoses, or deaths; several negative side effects were reported. Compared to other MOUD, XR-BUP significantly reduced drug use, resulted in similar or higher treatment retention rates, fewer re-incarcerations, and was cost-beneficial, with a lower overall monthly/yearly cost. Barriers to XR-BUP, such as side effects and a fear of needles, as well as facilitators, such as a lowered risk of opioid relapse, were also identified. XR-BUP appears to be a feasible and potentially effective alternative treatment option for correctional populations with OUD. XR-BUP may reduce community release-related risks, such as opioid use and overdose risk, as well as barriers to treatment retention. Efforts to expand access to and uptake of XR-BUP among correctional populations are warranted.

Heavy alcohol drinking is a major, preventable problem that adversely impacts the physical and mental health of US young adults. Studies seeking drinking risk factors typically focus on young adults who enrolled in 4-year residential college programs (4YCP) even though most high school graduates join the workforce, military, or community colleges. We examined 106 of these understudied young adults (USYA) and 453 4YCPs from the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) by longitudinally following their drinking patterns for 8 years from adolescence to young adulthood. All participants were no-to-low drinkers during high school. Whereas 4YCP individuals were more likely to initiate heavy drinking during college years, USYA participants did so later. Using mental health metrics recorded during high school, machine learning forecasted individual-level risk for initiating heavy drinking after leaving high school. The risk factors differed between demographically matched USYA and 4YCP individuals and between sexes. Predictors for USYA drinkers were sexual abuse, physical abuse for girls, and extraversion for boys, whereas 4YCP drinkers were predicted by the ability to recognize facial emotion and, for boys, greater openness. Thus, alcohol prevention programs need to give special consideration to those joining the workforce, military, or community colleges, who make up the majority of this age group.

Large multi-site studies that combine magnetic resonance imaging (MRI) data across research sites present exceptional opportunities to advance neuroscience research. However, scanner or site variability and non-standardised image acquisition protocols, data processing and analysis pipelines can adversely affect the reliability and repeatability of MRI derived brain measures. We implemented a standardised MRI protocol based on that used in the Adolescent Brain Cognition Development (ABCD) study in two sites, and across four MRI scanners. Twice repeated measurements of a single healthy volunteer were obtained in two sites and in four 3T MRI scanners (vendors: Siemens, Philips, and GE). Imaging data included anatomical scans (T1 weighted, T2 weighted), diffusion weighted imaging (DWI) and resting state functional MRI (rs-fMRI). Standardised containerized pipelines were utilised to pre-process the data and different image quality metrics and test-retest variability of different brain metrics were evaluated. The implementation of the MRI protocols was possible with minor adjustments in acquisition (e.g. repetition time (TR), higher b-values) and exporting (DICOM formats) of images due to different technical performance of the scanners. This study provides practical insights into the implementation of standardised sequences and data processing for multisite studies, showcase the benefits of containerised preprocessing tools, and highlights the need for careful optimisation of multisite image acquisition.

Previous mobile health (mHealth) studies have revealed significant links between depression and circadian rhythm features measured via wearables. However, the comprehensive impact of seasonal variations was not fully considered in these studies, potentially biasing interpretations in real-world settings.

Provisional Tic Disorder (PTD) is common in childhood. The received wisdom among clinicians is that PTD is short-lived and mild, with at most a few tics, and rarely includes complex tics, premonitory phenomena or comorbid illnesses. However, such conclusions come from clinical experience, with biased ascertainment and limited follow-up.

This study aims to assess the effectiveness and safety of mesenchymal stem cell (MSC) transplantation in the treatment of inflammatory arthritis.

We aimed to identify the clinical subtypes in individuals starting long-term care in Japan and examined their association with prognoses. Using linked medical insurance claims data and survey data for care-need certification in a large city, we identified participants who started long-term care. Grouping them based on 22 diseases recorded in the past 6 months using fuzzy c-means clustering, we examined the longitudinal association between clusters and death or care-need level deterioration within 2 years. We analyzed 4,648 participants (median age 83 [interquartile range 78-88] years, female 60.4%) between October 2014 and March 2019 and categorized them into (i) musculoskeletal and sensory, (ii) cardiac, (iii) neurological, (iv) respiratory and cancer, (v) insulin-dependent diabetes, and (vi) unspecified subtypes. The results of clustering were replicated in another city. Compared with the musculoskeletal and sensory subtype, the adjusted hazard ratio (95% confidence interval) for death was 1.22 (1.05-1.42), 1.81 (1.54-2.13), and 1.21 (1.00-1.46) for the cardiac, respiratory and cancer, and insulin-dependent diabetes subtypes, respectively. The care-need levels more likely worsened in the cardiac, respiratory and cancer, and unspecified subtypes than in the musculoskeletal and sensory subtype. In conclusion, distinct clinical subtypes exist among individuals initiating long-term care.

Paranoid ideation is common among adolescents, yet little is known about the precursors. Using a novel immersive virtual reality (VR) paradigm, we tested whether experiences of bullying, and other interpersonal/threatening events, are associated with paranoid ideation to a greater degree than other types of (i) non-interpersonal events or (ii) adverse childhood experiences.

Preventing military sexual assault (SA) is a DoD priority. Building prevention capacity could strengthen the impact of prevention programs and improve outcomes. Capacity was conceptualized as implementation knowledge and skills using the Getting To Outcomes (GTO) process and organizational-level capacities using the Prevention Evaluation Framework, a framework that applies best practices in prevention and implementation science to prevention at the program and organizational level. The present study assesses implementation knowledge and skills currently possessed by SA prevention personnel in one U.S. Army installation with the goal of identifying preexisting proficiencies and potential gaps. The study uses the Prevention Evaluation Framework organizational-level domains to identify organizational capacities that could be improved.

In recent years, smart devices have become an integral part of daily life. However, longitudinal studies, particularly those regarding the relationship between toddlers' smart device usage and behavioral outcomes, are limited. Understanding the impact of parent-child interactions on this relationship is crucial for enhancing toddlers' developmental outcomes. Accordingly, this study examined the influence of early screen time and media content exposure on toddlers' behaviors, as well as the positive effects of mother-child interactions on this influence.

Investigating the genetic underpinnings of human aging is essential for unraveling the etiology of and developing actionable therapies for chronic diseases. Here, we characterize the genetic architecture of the biological age gap (BAG; the difference between machine learning-predicted age and chronological age) across nine human organ systems in 377,028 participants of European ancestry from the UK Biobank. The BAGs were computed using cross-validated support vector machines, incorporating imaging, physical traits and physiological measures. We identify 393 genomic loci-BAG pairs (P < 5 × 10) linked to the brain, eye, cardiovascular, hepatic, immune, metabolic, musculoskeletal, pulmonary and renal systems. Genetic variants associated with the nine BAGs are predominantly specific to the respective organ system (organ specificity) while exerting pleiotropic links with other organ systems (interorgan cross-talk). We find that genetic correlation between the nine BAGs mirrors their phenotypic correlation. Further, a multiorgan causal network established from two-sample Mendelian randomization and latent causal variance models revealed potential causality between chronic diseases (for example, Alzheimer's disease and diabetes), modifiable lifestyle factors (for example, sleep duration and body weight) and multiple BAGs. Our results illustrate the potential for improving human organ health via a multiorgan network, including lifestyle interventions and drug repurposing strategies.

The association of cardiovascular health levels, as measured by the Life's Essential 8 score, with cardiovascular disease (CVD) incidence and mortality among individuals with type 2 diabetes (T2D) has not been fully elucidated.

Brain variations are responsible for developmental impairments, including autism spectrum disorder (ASD). EEG signals efficiently detect neurological conditions by revealing crucial information about brain function abnormalities.

Mosaic chromosomal alterations (mCAs) are implicated in neuropsychiatric disorders, yet the contribution to schizophrenia (SCZ) risk for somatic copy number variations (sCNVs) emerging in early developmental stages is not fully established.

Perioperative mental health of older Black surgical patients is associated with poor surgical outcomes; however, evidence-based perioperative interventions are lacking. Our two study objectives included: first, examine factors affecting perioperative care experiences of older Black surgical patients with mental health problems, and second, ascertain design and implementation requirements for a culturally-adapted perioperative mental health intervention.

The interplay between insomnia and PTSD symptoms remains misunderstood, and seems to be influenced by other factors like individual resilience. Our study examined the moderating role of resilience in the relationship between insomnia and PTSD symptoms among a sample of Lebanese adolescents, in the aftermath of the 2023 earthquake. This cross sectional study, conducted in April, 2 months after the earthquake, enrolled 546 Lebanese adolescents. We used the Sleep Self Report, the Resilience Scale for Adolescents and the 13-item Children's Impact of Event Scale. The interaction insomnia severity by resilience was significantly associated with PTSD scores. At low, moderate and high resilience levels, higher insomnia severity was significantly associated with lower PTSD. Resilience moderated the relationship between insomnia and PTSD, mitigating the detrimental impact of disrupted sleep on PTSD symptoms. This data can guide healthcare administrators and psychiatric caregivers in classifying risk factors and implementing interventions to predict PTSD development.

To use individual participant data meta-analysis (IPDMA) to estimate the minimal detectable change (MDC) of the Geriatric Depression Scale-15 (GDS-15) and to examine whether MDC may differ based on participant characteristics and study-level variables.

Fragile X syndrome (FXS) is a genetic condition associated with increased risk for social anxiety and avoidance. Using functional near-infrared spectroscopy (fNIRS), we previously demonstrated aberrant neural activity responding to faces in young girls with FXS cross-sectionally. Here, we tested the hypothesis that abnormalities in neural activation and sensitization would increase with age in 65 girls with FXS, ages 5-16 years, relative to an age-matched control group of 52 girls who had comparable cognitive function and clinical symptoms.

We aimed to assess the mental health of adults living in Ukraine one year after onset of the Russo-Ukrainian war, along with quality of life and coping strategies. Quota sampling was used to collect online survey data from 2364 adults aged 18-79 years living in Ukraine from April 5, 2023 to May 15, 2023. Among adults living in Ukraine, 14.4 % had probable post-traumatic stress disorder (PTSD), another 8.9 % had complex PTSD (CPTSD), 44.2 % had probable depressive disorder, 23.1 % had anxiety disorder and 38.6 % showed significant loneliness. In adjusted models, the number of trauma events experienced during the war showed a dose-response association with PTSD/CPTSD and was associated with depressive disorder and anxiety disorder. Quality of life domains, particularly physical quality of life, were negatively associated with PTSD/CPTSD, depressive disorder, anxiety disorder, and number of trauma events. Maladaptive coping was positively associated with depressive disorder, anxiety disorder, PTSD/CPTSD and loneliness. All quality of life domains were positively associated with using adaptive coping strategies. Mental health disorders are highly prevalent in adults living in Ukraine one year into the war. Policy and services can promote adaptive coping strategies to improve mental health and quality of life for increased resilience during war.

Despite encouraging multi-generational cohabitation, the population of Japanese people living alone has increased. However, little is known about the association between health and multigenerational cohabitation. This study examined the relationship between self-rated health and living arrangements among Japanese adults using data from the Japan Multi-Institutional Collaborative Cohort Study (2013-2017). The analysis employed multivariate logistic regression to examine the associations. Our results showed no association between living arrangements and self-rated health when stratified by gender. Living alone was found to be associated with poor self-rated health among women aged 65 and above. A similar association may exist among men in the same age group. Among women aged < 65 years, two-generation cohabitation was associated with a good self-rated health, similar to those living alone. Among men aged < 65 years, neither living alone nor two-generation cohabitation was significantly associated with good self-rated health. We found no association between three- or plus-generation cohabitation and self-rated health. Therefore, our findings indicate associations between multigenerational cohabitation and self-rated health, but they vary by gender and age. Invested stakeholders in the public health field should consider the potential impact of living arrangements on health based on gender and age.

Variants in cis-regulatory elements link the noncoding genome to human pathology; however, detailed analytic tools for understanding the association between cell-level brain pathology and noncoding variants are lacking. CWAS-Plus, adapted from a Python package for category-wide association testing (CWAS), enhances noncoding variant analysis by integrating both whole-genome sequencing (WGS) and user-provided functional data. With simplified parameter settings and an efficient multiple testing correction method, CWAS-Plus conducts the CWAS workflow 50 times faster than CWAS, making it more accessible and user-friendly for researchers. Here, we used a single-nuclei assay for transposase-accessible chromatin with sequencing to facilitate CWAS-guided noncoding variant analysis at cell-type-specific enhancers and promoters. Examining autism spectrum disorder WGS data (n = 7280), CWAS-Plus identified noncoding de novo variant associations in transcription factor binding sites within conserved loci. Independently, in Alzheimer's disease WGS data (n = 1087), CWAS-Plus detected rare noncoding variant associations in microglia-specific regulatory elements. These findings highlight CWAS-Plus's utility in genomic disorders and scalability for processing large-scale WGS data and in multiple-testing corrections. CWAS-Plus and its user manual are available at https://github.com/joonan-lab/cwas/ and https://cwas-plus.readthedocs.io/en/latest/, respectively.

Evidence on the association of chronic illnesses with depression among adolescents in the Indian community setting is limited. A simple random sample of 583 adolescents, comprising 56.6% of boys and 43.4% of girls, were interviewed on home visits. Self-reports on chronic illnesses were elicited, followed by administration of Patient Health Questionnaire-9 (PHQ-9) questionnaire to screen for depression, and for confirmation of diagnosis by age-appropriate Mini-International Neuropsychiatric Interview for Children and Adolescents (MINI Kid), or MINI. The prevalence of chronic illnesses was 8.4% (95% confidence interval [CI]: 6.3-11.0). Of these participants, 42.8% screened positive for depression. The prevalence of depression was 10.2% (95% CI: 3.4-22.2) among adolescents with chronic illness. The prevalence of physical-mental multimorbidity was 0.8% (95% CI: 0.3-2.0). The presence of chronic illness was associated with depression identified using both PHQ-9 (adjusted odds ratio [AOR] =3.1 [95% CI: 1.7-5.8], P < 0.001) and MINI Kid/MINI (AOR = 3.2 [95% CI: 1.1-9.4], P = 0.037). Adolescents with chronic illnesses can be targeted for mental morbidity screening in a bid to improve functional outcomes.

The aim of this study was to examine some psychometric characteristics of the Chilean-adapted version of the Quantitative Checklist for Autism in Toddlers (Q-CHAT-24) (24) in a group of unselected children (community sample). This version was administered remotely through an online version during the pandemic period to caregivers of children, aged 18-24 months, registered in four primary care polyclinics of the Health Service Araucanía Sur, Chile.

Major depressive disorder (MDD) is a heterogeneous clinical syndrome with widespread subtle neuroanatomical correlates. Our objective was to identify the neuroanatomical dimensions that characterize MDD and predict treatment response to selective serotonin reuptake inhibitor (SSRI) antidepressants or placebo. In the COORDINATE-MDD consortium, raw MRI data were shared from international samples ( = 1,384) of medication-free individuals with first-episode and recurrent MDD ( = 685) in a current depressive episode of at least moderate severity, but not treatment-resistant depression, as well as healthy controls ( = 699). Prospective longitudinal data on treatment response were available for a subset of MDD individuals ( = 359). Treatments were either SSRI antidepressant medication (escitalopram, citalopram, sertraline) or placebo. Multi-center MRI data were harmonized, and HYDRA, a semi-supervised machine-learning clustering algorithm, was utilized to identify patterns in regional brain volumes that are associated with disease. MDD was optimally characterized by two neuroanatomical dimensions that exhibited distinct treatment responses to placebo and SSRI antidepressant medications. Dimension 1 was characterized by preserved gray and white matter ( = 290 MDD), whereas Dimension 2 was characterized by widespread subtle reductions in gray and white matter ( = 395 MDD) relative to healthy controls. Although there were no significant differences in age of onset, years of illness, number of episodes, or duration of current episode between dimensions, there was a significant interaction effect between dimensions and treatment response. Dimension 1 showed a significant improvement in depressive symptoms following treatment with SSRI medication (51.1%) but limited changes following placebo (28.6%). By contrast, Dimension 2 showed comparable improvements to either SSRI (46.9%) or placebo (42.2%) ( = -18.3, 95% CI (-34.3 to -2.3),  = 0.03). Findings from this case-control study indicate that neuroimaging-based markers can help identify the disease-based dimensions that constitute MDD and predict treatment response.

This study began as a single-blind randomized controlled trial (RCT) to investigate the efficacy and safety of electroconvulsive therapy (ECT) for severe treatment-refractory agitation in advanced dementia. The aims are to assess agitation reduction using the Cohen-Mansfield Agitation Inventory (CMAI), evaluate tolerability and safety outcomes, and explore the long-term stability of agitation reduction and global functioning. Due to challenges encountered during implementation, including recruitment obstacles and operational difficulties, the study design was modified to an open-label format and other protocol amendments were implemented.

: Recent evidence highlights the pivotal role of mitochondrial dysfunction in mood disorders, but the mechanism involved remains unclear. We studied whether the Hippo/YAP/14-3-3η signaling pathway mediates mitochondrial abnormalities that result in the onset of major depressive disorder (MDD) in a mouse model. : The ROC algorithm was used to identify a subpopulation of mice that were exposed to chronic unpredictable mild stress (CUMS) and exhibited the most prominent depressive phenotype (Dep). Electron microscopy, biochemical assays, quantitative PCR, and immunoblotting were used to evaluate synaptic and mitochondrial changes in the basolateral amygdala (BLA). RNA sequencing was used to explore changes in the Hippo pathway and downstream target genes. pharmacological inhibition and immunoprecipitation was used to confirm YAP/14-3-3η interaction and its role in neuronal mitochondrial dysfunction. We used virus-mediated gene overexpression and knockout in YAP transgenic mice to verify the regulatory effect of the Hippo/YAP/14-3-3η pathway on depressive-like behavior. : Transcriptomic data identified a large number of genes and signaling pathways that were specifically altered from the BLA of Dep mice. Dep mice showed notable synaptic impairment in BLA neurons, as well as mitochondrial damage characterized by abnormal mitochondrial morphology, compromised function, impaired biogenesis, and alterations in mitochondrial marker proteins. The Hippo signaling pathway was activated in Dep mice during CUMS, and the transcriptional regulatory activity of YAP was suppressed by phosphorylation of its Ser127 site. 14-3-3η was identified as an important co-regulatory factor of the Hippo/YAP pathway, as it can respond to chronic stress and regulate cytoplasmic retention of YAP. Importantly, the integrated Hippo/YAP/14-3-3η pathway mediated neuronal mitochondrial dysfunction and depressive behavior in Dep mice. : The integrated Hippo/YAP/14-3-3η pathway in the BLA neuron is critical in mediating depressive-like behaviors in mice, suggesting a causal role for this pathway in susceptibility to chronic stress-induced depression. This pathway therefore may present a therapeutic target against mitochondrial dysfunction and synaptic impairment in MDD.

In mediation analysis, the exposure often influences the mediating effect, i.e., there is an interaction between exposure and mediator on the dependent variable. When the mediator is high-dimensional, it is necessary to identify non-zero mediators and exposure-by-mediator ( -by- ) interactions. Although several high-dimensional mediation methods can naturally handle -by- interactions, research is scarce in preserving the underlying hierarchical structure between the main effects and the interactions. To fill the knowledge gap, we develop the XMInt procedure to select and -by- interactions in the high-dimensional mediators setting while preserving the hierarchical structure. Our proposed method employs a sequential regularization-based forward-selection approach to identify the mediators and their hierarchically preserved interaction with exposure. Our numerical experiments showed promising selection results. Further, we applied our method to ADNI morphological data and examined the role of cortical thickness and subcortical volumes on the effect of amyloid-beta accumulation on cognitive performance, which could be helpful in understanding the brain compensation mechanism.

Alzheimer's disease (AD) is influenced by a variety of modifiable risk factors, including a person's dietary habits. While the ketogenic diet (KD) holds promise in reducing metabolic risks and potentially affecting AD progression, only a few studies have explored KD's metabolic impact, especially on blood and cerebrospinal fluid (CSF). Our study involved participants at risk for AD, either cognitively normal or with mild cognitive impairment. The participants consumed both a modified Mediterranean Ketogenic Diet (MMKD) and the American Heart Association diet (AHAD) for 6 weeks each, separated by a 6-week washout period. We employed nuclear magnetic resonance (NMR)-based metabolomics to profile serum and CSF and metagenomics profiling on fecal samples. While the AHAD induced no notable metabolic changes, MMKD led to significant alterations in both serum and CSF. These changes included improved modifiable risk factors, like increased HDL-C and reduced BMI, reversed serum metabolic disturbances linked to AD such as a microbiome-mediated increase in valine levels, and a reduction in systemic inflammation. Additionally, the MMKD was linked to increased amino acid levels in the CSF, a breakdown of branched-chain amino acids (BCAAs), and decreased valine levels. Importantly, we observed a strong correlation between metabolic changes in the CSF and serum, suggesting a systemic regulation of metabolism. Our findings highlight that MMKD can improve AD-related risk factors, reverse some metabolic disturbances associated with AD, and align metabolic changes across the blood-CSF barrier.

Canonical correlation analysis (CCA) and partial least squares correlation (PLS) detect linear associations between two data matrices by computing latent variables (LVs) having maximal correlation (CCA) or covariance (PLS). This study compared the similarity and generalizability of CCA- and PLS-derived brain-behavior relationships. Data were accessed from the baseline Adolescent Brain Cognitive Development (ABCD) dataset ( > 9,000, 9-11 years). The brain matrix consisted of cortical thickness estimates from the Desikan-Killiany atlas. Two phenotypic scales were examined separately as the behavioral matrix; the Child Behavioral Checklist (CBCL) subscale scores and NIH Toolbox performance scores. Resampling methods were used to assess significance and generalizability of LVs. LV for the CBCL brain relationships was found to be significant, yet not consistently stable or reproducible, across CCA and PLS models (singular value: CCA = .13, PLS = .39, < .001). LV for the NIH brain relationships showed similar relationships between CCA and PLS and was found to be stable and reproducible (singular value: CCA = .21, PLS = .43, < .001). The current study suggests that stability and reproducibility of brain-behavior relationships identified by CCA and PLS are influenced by the statistical characteristics of the phenotypic measure used when applied to a large population-based pediatric sample.

Image and Performance-Enhancing Drugs (IPEDs) can enhance mental and physical capabilities and impact one's overall health. Initially confined in sport environments, IPEDs use has become increasingly widespread in a high-performing society. The present study was aimed at profiling IPEDs use during the COVID-19 lockdown among an international sample of young adults.