Childhood abuse and deprivation are associated with distinct sex-dependent differences in brain morphology

Childhood adversity (CA) has been associated with long-term structural brain alterations and an increased risk for psychiatric disorders. Evidence is emerging that subtypes of CA, varying in the dimensions of threat and deprivation, lead to distinct neural and behavioral outcomes. However, these specific associations have yet to be established without potential confounders such as psychopathology. Moreover, differences in neural development and psychopathology necessitate the exploration of sexual dimorphism. Young healthy adult subjects were selected based on history of CA from a large database to assess gray matter (GM) differences associated with specific subtypes of adversity. We compared voxel-based morphometry data of subjects reporting specific childhood exposure to abuse (n = 127) or deprivation (n = 126) and a similar sized group of controls (n = 129) without reported CA. Subjects were matched on age, gender, and educational level. Differences between CA subtypes were found in the fusiform gyrus and middle occipital gyms, where subjects with a history of deprivation showed reduced GM compared with subjects with a history of abuse. An interaction between sex and CA subtype was found. Women showed less GM in the visual posterior precuneal region after both subtypes of CA than controls. Men had less GM in the postcentral gyms after childhood deprivation compared with abuse. Our results suggest that even in a healthy population, CA subtypes are related to specific alterations in brain structure, which are modulated by sex. These findings may help understand neurodevelopmental consequences related to C

Meta-analysis and meta-regression of omega-3 polyunsaturated fatty acid supplementation for major depressive disorder

Contains fulltext : 167940.pdf (publisher's version ) (Open Access)Omega-3 polyunsaturated fatty acid (PUFA) supplementation has been proposed as (adjuvant) treatment for major depressive disorder (MDD). In the present meta-analysis, we pooled randomized placebo-controlled trials assessing the effects of omega-3 PUFA supplementation on depressive symptoms in MDD. Moreover, we performed meta-regression to test whether supplementation effects depended on eicosapentaenoic acid (EPA) or docosahexaenoic acid dose, their ratio, study duration, participants' age, percentage antidepressant users, baseline MDD symptom severity, publication year and study quality. To limit heterogeneity, we only included studies in adult patients with MDD assessed using standardized clinical interviews, and excluded studies that specifically studied perinatal/perimenopausal or comorbid MDD. Our PubMED/EMBASE search resulted in 1955 articles, from which we included 13 studies providing 1233 participants. After taking potential publication bias into account, meta-analysis showed an overall beneficial effect of omega-3 PUFAs on depressive symptoms in MDD (standardized mean difference=0.398 (0.114-0.682), P=0.006, random-effects model). As an explanation for significant heterogeneity (I(2)=73.36, P<0.001), meta-regression showed that higher EPA dose (beta=0.00037 (0.00009-0.00065), P=0.009), higher percentage antidepressant users (beta=0.0058 (0.00017-0.01144), P=0.044) and earlier publication year (beta=-0.0735 (-0.143 to 0.004), P=0.04) were significantly associated with better outcome for PUFA supplementation. Additional sensitivity analyses were performed. In conclusion, present meta-analysis suggested a beneficial overall effect of omega-3 PUFA supplementation in MDD patients, especially for higher doses of EPA and in participants taking antidepressants. Future precision medicine trials should establish whether possible interactions between EPA and antidepressants could provide targets to improve antidepressant response and its prediction. Furthermore, potential long-term biochemical side effects of high-dosed add-on EPA supplementation should be carefully monitored

Service provision and barriers to care for homeless people with mental health problems across 14 European capital cities

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Large-scale production of LGR5-positive bipotential human liver stem cells

Background and Aims: The gap between patients on transplant waiting lists and available donor organs is steadily increasing. Human organoids derived from leucine‐rich repeat‐containing G protein‐coupled receptor 5 (LGR5)–positive adult stem cells represent an exciting new cell source for liver regeneration; however, culturing large numbers of organoids with current protocols is tedious and the level of hepatic differentiation is limited. Approach and Results: Here, we established a method for the expansion of large quantities of human liver organoids in spinner flasks. Due to improved oxygenation in the spinner flasks, organoids rapidly proliferated and reached an average 40‐fold cell expansion after 2 weeks, compared with 6‐fold expansion in static cultures. The organoids repopulated decellularized liver discs and formed liver‐like tissue. After differentiation in spinner flasks, mature hepatocyte markers were highly up‐regulated compared with static organoid cultures, and cytochrome p450 activity reached levels equivalent to hepatocytes. Conclusions: We established a highly efficient method for culturing large numbers of LGR5‐positive stem cells in the form of organoids, which paves the way for the application of organoids for tissue engineering and liver transplantation

Mutation-specific reporter for optimization and enrichment of prime editing

Prime editing is a versatile genome-editing technique that shows great promise for the generation and repair of patient mutations. However, some genomic sites are difficult to edit and optimal design of prime-editing tools remains elusive. Here we present a fluorescent prime editing and enrichment reporter (fluoPEER), which can be tailored to any genomic target site. This system rapidly and faithfully ranks the efficiency of prime edit guide RNAs (pegRNAs) combined with any prime editor variant. We apply fluoPEER to instruct correction of pathogenic variants in patient cells and find that plasmid editing enriches for genomic editing up to 3-fold compared to conventional enrichment strategies. DNA repair and cell cycle-related genes are enriched in the transcriptome of edited cells. Stalling cells in the G1/S boundary increases prime editing efficiency up to 30%. Together, our results show that fluoPEER can be employed for rapid and efficient correction of patient cells, selection of gene-edited cells, and elucidation of cellular mechanisms needed for successful prime editing

Towards a New Definition of Return-to-Work Outcomes in Common Mental Disorders from a Multi-Stakeholder Perspective

Objectives: To examine the perspectives of key stakeholders involved in the return-to-work (RTW) process regarding the definition of successful RTW outcome after sickness absence related to common mental disorders (CMD's). Methods: A mixed-method design was used: First, we used qualitative methods (focus groups, interviews) to identify a broad range of criteria important for the definition of successful RTW (N = 57). Criteria were grouped into content-related clusters. Second, we used a quantitative approach (online questionnaire) to identify, among a larger stakeholder sample (N = 178), the clusters and criteria most important for successful RTW. Results: A total of 11 clusters, consisting of 52 unique criteria, were identified. In defining successful RTW, supervisors and occupational physicians regarded "Sustainability'' and "At-work functioning" most important, while employees regarded "Sustainability," "Job satisfaction," "Work-home balance,'' and " Mental Functioning" most important. Despite agreement on the importance of certain criteria, considerable differences among stakeholders were observed. Conclusions: Key stakeholders vary in the aspects and criteria they regard as important when defining successful RTW after CMD-related sickness absence. Current definitions of RTW outcomes used in scientific research may not accurately reflect these key stakeholder perspectives. Future studies should be more aware of the perspective from which they aim to evaluate the effectiveness of a RTW intervention, and define their RTW outcomes accordingly

Mental health care for irregular migrants in Europe: Barriers and how they are overcome

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited