Recommendations to encourage participation of individuals from diverse backgrounds in psychiatric genetic studies.

We present innovative research practices in psychiatric genetic studies to ensure representation of individuals from diverse ancestry, sex assigned at birth, gender identity, age, body shape and size, and socioeconomic backgrounds. Due to histories of inappropriate and harmful practices against marginalized groups in both psychiatry and genetics, people of certain identities may be hesitant to participate in research studies. Yet their participation is essential to ensure diverse representation, as it is incorrect to assume that the same genetic and environmental factors influence the risk for various psychiatric disorders across all demographic groups. We present approaches developed as part of the Eating Disorders Genetics Initiative (EDGI), a study that required tailored approaches to recruit diverse populations across many countries. Considerations include research priorities and design, recruitment and study branding, transparency, and community investment and ownership. Ensuring representation in participants is costly and funders need to provide adequate support to achieve diversity in recruitment in prime awards, not just as supplemental afterthoughts. The need for diverse samples in genetic studies is critical to minimize the risk of perpetuating health disparities in psychiatry and other health research. Although the EDGI strategies were designed specifically to attract and enroll individuals with eating disorders, our approach is broadly applicable across psychiatry and other fields.

PPA2-associated sudden cardiac death: extending the clinical and allelic spectrum in 20 new families.

PURPOSE: Biallelic hypomorphic variants in PPA2, encoding the mitochondrial inorganic pyrophosphatase 2 protein, have been recently identified in individuals presenting with sudden cardiac death, occasionally triggered by alcohol intake or a viral infection. Here we report 20 new families harboring PPA2 variants. METHODS: Synthesis of clinical and molecular data concerning 34 individuals harboring five previously reported PPA2 variants and 12 novel variants, 11 of which were functionally characterized. RESULTS: Among the 34 individuals, only 6 remain alive. Twenty-three died before the age of 2 years while five died between 14 and 16 years. Within these 28 cases, 15 died of sudden cardiac arrest and 13 of acute heart failure. One case was diagnosed prenatally with cardiomyopathy. Four teenagers drank alcohol before sudden cardiac arrest. Progressive neurological signs were observed in 2/6 surviving individuals. For 11 variants, recombinant PPA2 enzyme activities were significantly decreased and sensitive to temperature, compared to wild-type PPA2 enzyme activity. CONCLUSION: We expand the clinical and mutational spectrum associated with PPA2 dysfunction. Heart failure and sudden cardiac arrest occur at various ages with inter- and intrafamilial phenotypic variability, and presentation can include progressive neurological disease. Alcohol intake can trigger cardiac arrest and should be strictly avoided.

Interspecific hybridization causes long-term phylogenetic discordance between nuclear and mitochondrial genomes in freshwater fishes.

Classification, phylogeography and the testing of evolutionary hypotheses rely on correct estimation of species phylogeny. Early molecular phylogenies often relied on mtDNA alone, which acts as a single linkage group with one history. Over the last decade, the use of multiple nuclear sequences has often revealed conflict among gene trees. This observation can be attributed to hybridization, lineage sorting, paralogy or selection. Here, we use 54 groups of fishes from 48 studies to estimate the degree of concordance between mitochondrial and nuclear gene trees in two ecological grades of fishes: marine and freshwater. We test the hypothesis that freshwater fish phylogenies should, on average, show more discordance because of their higher propensity for hybridization in the past. In keeping with this idea, concordance between mitochondrial and nuclear gene trees (as measured by proportion of components shared) is on average 50% higher in marine fishes. We discuss why this difference almost certainly results from introgression caused by greater historical hybridization among lineages in freshwater groups, and further emphasize the need to use multiple nuclear genes, and identify conflict among them, in estimation of species phylogeny.

Fluorescence Methods for Probing G-Quadruplex Structure in Single- and Double-Stranded DNA.

Interest in exploring G-quadruplex (G4) structures in nucleic acids is growing as it becomes more widely recognized that these structures have many interesting biological roles and chemical properties. Probing the G4-forming potential of DNA with dimethyl sulfate, polymerase stop assays, or nuclease digestion are three commonly used techniques that usually employ radio-isotopic labels for visualization. However, as fluorescent labeling methods have grown in popularity and versatility, many laboratories have moved away from the routine use of radio-isotopic methods. We have adapted traditional procedures for structural analysis of G4-forming DNA sequences by using fluorescent labels and capillary electrophoresis and demonstrate their application to well-studied G4 structures, including c-MYC PU27 G4. The three fluorescent assays described here allow interrogation of G4 structures in double- and single-stranded DNA substrates, using either chemical or enzymatic cleavage. When combined, these techniques can provide valuable information for the investigation of G4 topology and structure, as well as visualizing any structural effects caused by interaction of quadruplexes with the complementary C-rich DNA strand.

Avoidant/restrictive food intake disorder (ARFID) in New Zealand and Australia: a scoping review.

BACKGROUND: Avoidant/restrictive food intake disorder (ARFID) is an eating disorder that involves restrictive or avoidant eating behaviour not related to weight or body image concerns. It was first included in the Diagnostic and Statistical Manual of Mental Disorders-fifth edition (DSM-5) in 2013. ARFID frequently begins in childhood and can have serious psychosocial impacts and detrimental health consequences when nutritional and energy needs are persistently unmet. This systematic scoping review focuses on Australasia, synthesizing the current literature landscape on ARFID, and offering recommendations for targeted, actionable research directions for both funders and researchers. METHODS: Online databases and university thesis repositories were systematically searched for studies examining ARFID in the New Zealand or Australian population since 2013. Database search results were exported to Rayyan software, and two independent reviewers screened all identified sources, prior to extraction of key data. RESULTS: Twenty-nine studies and one thesis from 138 screened sources were eligible for inclusion. Frequent study types were treatment interventions and cross-sectional studies, with populations including individuals with ARFID, ED service populations, parents/caregivers, health professionals, and non-clinical populations. ARFID presents in a range of settings and is associated with poorer quality of life and significant functional impairment. Assessment of ARFID was varied, and no specific treatment guidelines for ARFID have been written as yet. CONCLUSION: This review calls for more accurate prevalence estimates of ARFID in children and larger-scale studies in all ages using validated measures. It emphasizes the need for education and training of healthcare professionals, and interdisciplinary collaboration. Established interventions like behaviour analytics should be considered, and more comprehensive research is needed on interventions for ARFID, including controlled trials and longitudinal studies. Urgent research is needed to improve outcomes for those affected by ARFID.

This scoping review examines all published literature on Avoidant/Restrictive Food Intake Disorder (ARFID) in the Australasian region since the disorder was first recognized in 2013. ARFID is an eating disorder marked by restrictive or avoidant eating behaviour unrelated to weight or body image concerns. The disorder can have serious psychosocial impacts and detrimental health consequences when nutritional and energy needs are persistently unmet. The review identifies the methods, participants, and key findings of the studies on ARFID and suggests targeted and actionable research goals for researchers and funders. It calls for more accurate information on how common ARFID is in children, for larger-scale studies using validated measures, and emphasizes the need for education and training of healthcare professionals, and a collaborative approach to treatment. We also underscore the need for longitudinal studies to better understand the landscape of ARFID in Australasia.

Eating disorders, disordered eating, and body image research in New Zealand: a scoping review.

BACKGROUND: The prevention and treatment of eating disorders relies on an extensive body of research that includes various foci and methodologies. This scoping review identified relevant studies of eating disorders, body image, and disordered eating with New Zealand samples; charted the methodologies, sample characteristics, and findings reported; and identified several gaps that should be addressed by further research. METHODS: Using scoping review methodology, two databases were searched for studies examining eating disorders, disordered eating, or body image with New Zealand samples. Snowball methods were further used to identify additional relevant articles that did not appear in initial searches. Two independent reviewers screened the titles and abstracts of 473 records. Full text assessment of the remaining 251 records resulted in 148 peer-reviewed articles being identified as eligible for the final review. A search of institutional databases yielded 106 Masters and Doctoral theses for assessment, with a total of 47 theses being identified as eligible for the final review. The included studies were classified by methodology, and the extracted information included the study foci, data collected, sample size, demographic information, and key findings. RESULTS: The eligible studies examined a variety of eating disorder categories including binge-eating disorder, bulimia nervosa, and anorexia nervosa, in addition to disordered eating behaviours and body image in nonclinical or community samples. Methodologies included treatment trials, secondary analysis of existing datasets, non-treatment experimental interventions, cross-sectional observation, case-control studies, qualitative and mixed-methods studies, and case studies or series. Across all of the studies, questionnaire and interview data were most commonly utilised. A wide range of sample sizes were evident, and studies often reported all-female or mostly-female participants, with minimal inclusion of males and gender minorities. There was also an underrepresentation of minority ethnicities in many studies, highlighting the need for future research to increase diversity within samples. CONCLUSION: This study provides a comprehensive and detailed overview of research into eating disorders and body image in New Zealand, while highlighting important considerations for both local and international research.

How genetic analysis may contribute to the understanding of avoidant/restrictive food intake disorder (ARFID).

Avoidant/restrictive food intake disorder (ARFID) was introduced in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). Unlike anorexia nervosa, ARFID is characterised by avoidant or restricted food intake that is not driven by weight or body shape-related concerns. As with other eating disorders, it is expected that ARFID will have a significant genetic risk component; however, sufficiently large-scale genetic investigations are yet to be performed in this group of patients. This narrative review considers the current literature on the diagnosis, presentation, and course of ARFID, including evidence for different presentations, and identifies fundamental questions about how ARFID might fit into the fluid landscape of other eating and mental disorders. In the absence of large ARFID GWAS, we consider genetic research on related conditions to point to possible features or mechanisms relevant to future ARFID investigations, and discuss the theoretical and clinical implications an ARFID GWAS. An argument for a collaborative approach to recruit ARFID participants for genome-wide association study is presented, as understanding the underlying genomic architecture of ARFID will be a key step in clarifying the biological mechanisms involved, and the development of interventions and treatments for this serious, and often debilitating disorder.

Avoidant/restrictive food intake disorder (ARFID) can be a severe and debilitating eating disorder, where individuals limit food intake for reasons unrelated to the weight and body image concerns observed in anorexia nervosa. Although genetics is known to play a significant role in other eating disorders such as anorexia nervosa and bulimia nervosa, only one study has investigated the genetic background of ARFID, and this was limited to those with ARFID within an autism cohort. This narrative review describes current knowledge about the clinical characteristics of ARFID and highlights current knowledge gaps, setting the scene for a discussion of how existing research findings about the genetics of related conditions might help guide genetic research about ARFID. A large genome-wide association study (GWAS) is recommended as the first step to addressing some of the fundamental biological questions around ARFID and will lay the framework for development of interventions and treatments that target ARFID at a biological level.