Genetics impact risk of Alzheimer's disease through mechanisms modulating structural brain morphology in late life.

BACKGROUND: Alzheimer's disease (AD)-related neuropathological changes can occur decades before clinical symptoms. We aimed to investigate whether neurodevelopment and/or neurodegeneration affects the risk of AD, through reducing structural brain reserve and/or increasing brain atrophy, respectively. METHODS: We used bidirectional two-sample Mendelian randomisation to estimate the effects between genetic liability to AD and global and regional cortical thickness, estimated total intracranial volume, volume of subcortical structures and total white matter in 37 680 participants aged 8-81 years across 5 independent cohorts (Adolescent Brain Cognitive Development, Generation R, IMAGEN, Avon Longitudinal Study of Parents and Children and UK Biobank). We also examined the effects of global and regional cortical thickness and subcortical volumes from the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium on AD risk in up to 37 741 participants. RESULTS: Our findings show that AD risk alleles have an age-dependent effect on a range of cortical and subcortical brain measures that starts in mid-life, in non-clinical populations. Evidence for such effects across childhood and young adulthood is weak. Some of the identified structures are not typically implicated in AD, such as those in the striatum (eg, thalamus), with consistent effects from childhood to late adulthood. There was little evidence to suggest brain morphology alters AD risk. CONCLUSIONS: Genetic liability to AD is likely to affect risk of AD primarily through mechanisms affecting indicators of brain morphology in later life, rather than structural brain reserve. Future studies with repeated measures are required for a better understanding and certainty of the mechanisms at play.

Sex-Based Contributors to and Consequences of Post-traumatic Stress Disorder.

PURPOSE OF REVIEW: Women are twice as likely to develop post-traumatic stress disorder (PTSD) compared to men after a traumatic experience. The purpose of this mini review was to explore recent research on biological contributors to this sex difference. RECENT FINDINGS: We identified 51 studies published since 2019. Studies found that beyond the influence of sex on the prevalence and symptoms of PTSD, there is evidence for and against sex-based differences in genetic and epigenetic factors (n = 8), brain structure and function (n = 11), neuroendocrine and inflammatory responses (n = 5), and in the role of sleep on emotional memory processing (n = 1). Sex differences were also observed in recovery and during PTSD treatment (n = 16). Finally, there is emerging evidence of sex-differentiated risk for medical and psychiatric comorbidities in PTSD (n = 10). Rapid advances are being made using integrated multidisciplinary approaches to understand why females are at a heightened risk for developing PTSD.

Post-traumatic stress disorder symptoms following exposure to acute psychological trauma in children aged 8-16 years in South Africa: protocol for the Sinethemba longitudinal study.

INTRODUCTION: Children exposed to trauma are vulnerable to developing post-traumatic stress disorder (PTSD) and other adverse mental health outcomes. In low-and middle-income countries (LMICs), children are at increased risk of exposure to severe trauma and co-occurring adversities. However, relative to high-income countries, there is limited evidence of the factors that predict good versus poor psychological recovery following trauma exposure in LMIC children, and the role of caregiver support in these high-adversity communities. METHODS AND ANALYSIS: We will conduct a longitudinal, observational study of 250 children aged 8-16 years and their caregivers in South Africa, following child exposure to acute trauma. Dyads will be recruited from community hospitals following a potentially traumatic event, such as a motor vehicle accident or assault. Potential participants will be identified during their hospital visit, and if they agree, will subsequently be contacted by study researchers. Assessments will take place within 4 weeks of the traumatic event, with 3-month and 6-month follow-up assessments. Participants will provide a narrative description of the traumatic event and complete questionnaires designed to give information about social and psychological risk factors. Child PTSD symptoms will be the primary outcome, and wider trauma-related mental health (depression, anxiety, behavioural problems) will be secondary outcomes. Regression-based methods will be used to examine the association of psychosocial factors in the acute phase following trauma, including caregiver support and responding, with child PTSD and wider mental health outcomes. ETHICS AND DISSEMINATION: Ethical approvals have been granted by Stellenbosch University and the University of Bath, with additional approvals to recruit via hospitals and healthcare clinics being granted by the University of Cape Town, the Department of Health and the City of Cape Town. Study findings will be disseminated via publication in journals, workshops for practitioners and policy-makers, and public engagement events.

Data-driven digital health technologies in the remote clinical care of diabetic foot ulcers: a scoping review.

Background: The availability and effectiveness of Digital Health Technologies (DHTs) to support clinicians, empower patients, and generate economic savings for national healthcare systems are growing rapidly. Of particular promise is the capacity of DHTs to autonomously facilitate remote monitoring and treatment. Diabetic Foot Ulcers (DFUs) are characterised by high rates of infection, amputation, mortality, and healthcare costs. With clinical outcomes contingent on activities that can be readily monitored, DFUs present a promising focus for the application of remote DHTs. Objective: This scoping review has been conducted as a first step toward ascertaining fthe data-related challenges and opportunities for the development of more comprehensive, integrated, and individualised sense/act DHTs. We review the latest developments in the application of DHTs to the remote care of DFUs. We cover the types of DHTs in development and their features, technological readiness, and scope of clinical testing. Eligibility criteria: Only peer-reviewed original experimental and observational studies, case series and qualitative studies were included in literature searches. All reviews and manuscripts presenting pre-trial prototype technologies were excluded. Methods: An initial search of three databases (Web of Science, MEDLINE, and Scopus) generated 1,925 English-language papers for screening. 388 papers were assessed as eligible for full-text screening by the review team. 81 manuscripts were found to meet the eligibility criteria. Results: Only 19% of studies incorporated multiple DHTs. We categorised 56% of studies as 'Treatment-Manual', i.e. studies involving technologies aimed at treatment requiring manual data generation, and 26% as 'Prevention-Autonomous', i.e. studies of technologies generating data autonomously through wearable sensors aimed at ulcer prevention through patient behavioural change. Only 10% of studies involved more ambitious 'Treatment-Autonomous' interventions. We found that studies generally reported high levels of patient adherence and satisfaction. Conclusions: Our findings point to a major potential role for DHTs in remote personalised medical management of DFUs. However, larger studies are required to assess their impact. Here, we see opportunities for developing much larger, more comprehensive, and integrated monitoring and decision support systems with the potential to address the disease in a more complete context by capturing and integrating data from multiple sources from subjective and objective measurements.

Psychotherapeutic interventions for childhood posttraumatic stress disorder: an update.

PURPOSE OF THE REVIEW: We review treatment outcome studies and systematic reviews for childhood and adolescent posttraumatic stress disorder (PTSD) between January 2020 and August 2022, including studies involving younger children and different treatment delivery methods and models. We address predictors, moderators, treatment engagement, and attrition. RECENT FINDINGS: Recent randomised controlled trials corroborate earlier trials documenting trauma-focused cognitive behaviour therapy (TF-CBT) as a highly efficacious treatment for PTSD. Evidence for treatment effects in complex PTSD in youth is still sparse. Research on moderators and predictors of treatment continues to be hampered by multiple factors, including a lack of sufficiently large homogeneous trauma samples. SUMMARY: TF-CBT is a very effective treatment for children and adolescents with PTSD. Further work is needed to (i) demonstrate that task-shifting models utilising lay community health counsellors and peer counsellors can effectively and cost-effectively close the mental health treatment gap that exists world-wide in children and adolescents diagnosed with PTSD, but particularly within low- and middle income countries, and (ii) better understand moderators and predictors of treatment which remains a priority.

Population neuroimaging: generation of a comprehensive data resource within the ALSPAC pregnancy and birth cohort.

Neuroimaging offers a valuable insight into human brain development by allowing in vivo assessment of structure, connectivity and function. Multimodal neuroimaging data have been obtained as part of three sub-studies within the Avon Longitudinal Study of Parents and Children, a prospective multigenerational pregnancy and birth cohort based in the United Kingdom. Brain imaging data were acquired when offspring were between 18 and 24 years of age, and included acquisition of structural, functional and magnetization transfer magnetic resonance, diffusion tensor, and magnetoencephalography imaging. This resource provides a unique opportunity to combine neuroimaging data with extensive phenotypic and genotypic measures from participants, their mothers, and fathers.