What kind of illness is anorexia nervosa? Revisited: some preliminary thoughts to finding a cure.

Two decades have elapsed since our publication of 'What kind of illness is anorexia nervosa?'. The question remains whether our understanding of anorexia nervosa and its treatment thereof has evolved over this time. The verdict is disappointing at best. Our current gold standard treatments remain over-valued and clinical outcomes are modest at best. Those in our field are haunted by the constant reminder that anorexia nervosa carries the highest mortality rate of any psychiatric disorder. This cannot continue and demands immediate action. In this essay, we tackle the myths that bedevil our field and explore a deeper phenotyping of anorexia nervosa. We argue that we can no longer declare agnostic views of the disorder or conceive treatments that are "brainless": it is incumbent upon us to challenge the prevailing zeitgeist and reconceptualise anorexia nervosa. Here we provide a roadmap for the future.

Identifying eating disorders at the earliest opportunity: Testing the reliability of an online eating disorder screener (IOI-S) in primary care and youth mental health settings.

AIM: Eating disorders (EDs) are associated with significant disease burden and unacceptably high mortality rates. Early intervention significantly improves prognosis and can prevent chronic suffering; however, large numbers of people with the illness are not being identified or managed in primary healthcare. The current study aimed to test the reliability of the face-to-face, clinician delivery of a previously validated, co-designed, online screening tool for eating disorders. METHODS: Individuals aged 14 and over who read, English were recruited from the community in either primary care (general practice) settings or headspace youth mental health centres. They completed the InsideOut Institute Screener (IOI-S) face-to-face, delivered verbally by the study researcher clinician and then online by self-report. The primary outcome was test-retest reliability as measured by two-way mixed effects model Intraclass Correlation Coefficient (ICC) with absolute agreement. RESULTS: A total of 83 participants aged 14-81 (M 36.2) completed the study in New South Wales and the Northern Territory, Australia, between April and November 2022. The ICC between successive iterations of the test was significantly positive (0.980), demonstrating strong internal validity and test-retest reliability of the scale. CONCLUSIONS: The IOI-S is an adaptive 6-item screening tool designed to 'start a conversation' and determine risk using gentle language conceived by individuals with lived experience. Originally designed for online use, the current study broadens its versatility to clinical settings. The screener performs equally well when delivered face-to-face in clinical practice. In conjunction with increased practitioner education and improved treatment referral pathways, broad implementation of the screener in early healthcare settings can support timely identification and intervention for those with EDs.

Mortality and mental health funding-do the dollars add up? Eating disorder research funding in Australia from 2009 to 2021: a portfolio analysis.

Background: Eating Disorders (EDs) are among the deadliest of the mental disorders and carry a sizeable public health burden, however their research and treatment is consistently underfunded, contributing to protracted illness and ongoing paucity of treatment innovation. Methods: We compare absolute levels and growth rates of Australian mental health research funding by illness group for the years 2009-2021, with a specific focus on eating disorders analysed at the portfolio level. Findings: Actual and adjusted data obtained from Australia's three national medical research funding bodies (NHMRC, ARC and MRFF) shows eating disorders receive a disproportionately low allocation of mental health research funding despite having amongst the highest mortality rates. Forty-one category one research grants totalling $AUD28.1 million were funded for eating disorders over the period. When adjusted for inflation, this equates to $2.05 per affected individual, compared with $19.56 for depression, $32.11 for autism, and $176.19 for schizophrenia. Half of all research funded for eating disorders was 'basic' research (e.g., illness underpinning), with little investment in the development of innovative treatment models, novel therapeutics or translation, well reflected by recovery rates of less than 50% in individuals with Anorexia Nervosa. Interpretation: Significant discrepancy remains between research funding dollars and disease burden associated with the mental health disorders. The extent to which eating disorders are underfunded may in part be attributable to inaccuracies in epidemiological and burden of disease data. Funding: This work was in-part funded by the Australian Government Department of Health and the National Eating Disorder Research & Translation Strategy. The funder was not directly involved in informing the development of the current study.

Public perceptions of people with eating disorders: Commentary on results from the 2022 Australian national survey of mental health-related stigma and discrimination.

Mental illness is highly prevalent in the community. As such, significant attention has been paid in recent years to raising awareness of the mental health disorders (including eating disorders). This includes efforts to normalise help-seeking, campaigns to reduce stigma and discrimination, targeted research funding and advocacy for improved and accessible mental health service provision. But have these initiatives changed public attitude? The 2022 National Survey of Mental Health-Related Stigma and Discrimination is the first of four national surveys canvassing the general public's perceptions of people with mental health disorders (including stigmatising and discriminatory beliefs) conducted since 1995 to include eating disorders. It finds significant prejudice against those with mental health disorders still exists within the community, particularly among younger Australians. For eating disorders, this is primarily related to attributions of blame and personal weakness. Findings from the survey are discussed in this commentary.

Exploring the psychometric properties of the Intellectual Disability versions of the Short Warwick-Edinburgh Mental Wellbeing Scale and Kidscreen10, self-reported by adolescents with intellectual disability.

BACKGROUND: There are no validated self-report measures that can be used to assess health and wellbeing in adolescents with intellectual disability (ID). METHOD: The aim of this study was to explore the psychometric properties of two newly adapted self-report health-related quality of life (HRQoL) and mental wellbeing measures: the Intellectual Disability versions of the Short Warwick-Edinburgh Mental Wellbeing Scale (ID-SWEMWBS) and Kidscreen10 (ID-Kidscreen10). For this, we used data from a sample of 427 adolescents (aged 11-19) with ID recruited from special school settings. RESULTS: Confirmatory factor analysis (CFA) was conducted to validate the factor structure of both measures. Internal consistency was assessed using Cronbach's alpha and test-retest reliability was analysed using intra-class correlation coefficients. The internal consistency measured using Cronbach's alpha was found to be in the range of 0.70-0.78, test-retest reliabilities were expressed using intra-class correlation coefficients that were found to be high for both measures (ID-SWEMWBS, 0.758; ID-Kidscreen10, 0.723), and the CFA supported the unidimensional structure of both measures. CONCLUSIONS: The results of this study indicate that the ID-SWEMWBS and ID-Kidscreen10 have very good psychometric properties and can be used as self-report measures to assess HRQoL and mental wellbeing in adolescents with ID.

Worse scores but similar patterns of disease activity: interpreting outcomes in women with axial spondyloarthropathy.

OBJECTIVE: The aim of this study was to evaluate the impact of sex on disease activity in axial spondylitis (axSpA). METHOD: Data were extracted from the Ankylosing Spondylitis Registry of Ireland (ASRI). In this cross-sectional study, patients were analysed on the basis of sex, with a series of comparison analyses performed. RESULTS: Overall, 886 participants were enrolled in the ASRI [232 (26.2%) women, 644 (72.6%) men]. Females recorded significantly worse Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) (4.57 vs 3.83, p < 0.01) and Ankylosing Spondylitis Quality of Life questionnaire (ASQoL) (7.51 vs 6.12, p < 0.01) scores than males. There was a stronger correlation in the Bath Ankylosing Spondylitis Functional and Metrology Indices (BASFI and BASMI) in females (rs = 0.619, p < 0.01) than in males (rs = 0.572, p < 0.01). Analysis of factors in BASDAI revealed that the higher total scores in females compared to males were due not to any single component, but to worse scores in all six components of the BASDAI combined. Ranking of components by severity between sexes revealed identical ranking in four of the six components of the BASDAI. CONCLUSIONS: Women with axSpA reported significantly worse disease activity, quality of life, and functional ability than men. However, the BASDAI capturedsimilar patterns of disease activity. Limitation of spinal mobility in women with axSpA corresponded to greater impairment in functional ability. Further evaluation of disease monitoring tools is required to ensure that disease activity is accurately captured in men and women with axSpA.

Involving adolescents with intellectual disability in the adaptation of self-reported subjective well-being measures: participatory research and methodological considerations.

BACKGROUND: The measurement of subjective well-being is challenging with samples of adolescents with intellectual disability (ID) given the cognitive and linguistic difficulties they face in comprehending standardised measures, and as such is primarily based on proxy reports. The lack of appropriate tools needs to be addressed so that adolescents with ID can self-report on their own well-being. The current study reports on the use of participatory research methods to adapt and modify two standardised self-report measures of subjective well-being suitable for completion by adolescents with ID. METHOD: Two special schools were recruited for this study. At each school, staff (n = 15) and pupils aged 11-17 years (n = 35) participated. A series of co-design workshops were conducted to adapt two standardised subjective well-being measures: Kidscreen-10 and short-form Warwick-Edinburgh Mental Well-being Scale. RESULTS: Specific aspects for measure adaption were identified: simplifying the item wording and phrasing; inclusion of pictorial communication symbols and visual prompts to represent the meaning of items; changing of tense of questions from past to present; asking questions rather than statements; reducing 5-point Likert scales to 3-point or dichotomous; presenting one item at a time during administration; and developing alternate formats of the survey to ensure inclusivity. CONCLUSIONS: This paper illustrates the value of using participatory research methods when working alongside adolescents with ID and offers methodological, as well as practical, guidance in the context of adapting subjective self-report measures for this target group, serving as a guide to fellow researchers and clinicians interested in modifying or developing self-report measures for adolescents with ID.

The toll of unemployment in axial spondyloarthropathy: high prevalence and negative impact on outcomes captured in a national registry.

OBJECTIVE: Axial spondyloarthropathy (axSpA) is an inflammatory arthritis of the axial skeleton. Persistent disease activity can result in significant disability and affect the ability to maintain employment. This study aimed to determine the prevalence of unemployment in axSpA and the impact on patient outcomes. METHOD: Data from the Ankylosing Spondylitis Registry of Ireland (ASRI) were cleaned, and information on employment, demographics, and disease characteristics was extracted. Patients were analysed on the basis of employment and categorized as employed or unemployed. RESULTS: Of the 759 participants included in the analysis, 23.5% (178) were unemployed, higher than national averages of 6.2-13.1% during the study period. Unemployed participants reported significantly worse Bath Ankylosing Spondylitis Disease Activity Index (BASDAI; 5.1 vs 3.6), Metrology Index (BASMI; 4.8 vs 3.4), Functional Index (BASFI; 5.2 vs 3.0), Health Assessment Questionnaire (HAQ; 0.82 vs 0.40), and Ankylosing Spondylitis Quality of Life (ASQoL; 9.4 vs 5.4) scores compared to employed (all p < 0.01). Male gender (odds ratio, 95% confidence interval: 2.65, 1.46-4.83), worse BASMI (1.16, 1.02-1.33), and worse HAQ scores (2.18, 1.13-4.19) were significantly associated with unemployment. CONCLUSION: The prevalence of unemployment in axSpA patients is higher than in the general population, and is associated with worse quality of life, poorer levels of function, and higher levels of disease activity. Predictors of unemployment in axSpA were male gender, worse spinal mobility, and poorer level of function. Recognition of patients at risk of unemployment will improve opportunities for intervention and maintain participation in the workforce.

Evaluation of microcalcification contrast in clinical images for digital mammography and synthetic mammography.

PURPOSE: The aim of this work was to compare, in a clinical study, digital mammography and synthetic mammography imaging by evaluating the contrast in microcalcifications of different sizes. METHODS: A retrospective review of microcalcifications from 46 patients was undertaken. A Hologic 3-Dimensions mammography system and a HD Combo protocol was used for simultaneous acquisition of the digital and synthetic images. Microcalcifications were classified in accordance with their size, and patient breast images were classified in accordance with their density as adipose, moderately dense and dense. The contrast of the microcalcifications was measured and the contrast ratio between synthetic and digital images was compared. An additional qualitative assessment of the images was presented to correlate the conspicuity of the microcalcifications with the suppression of the structure noise. RESULTS: Microcalcifications in adipose background always exhibit a comparable or better contrast on synthetic images, regardless their size. For moderately dense background, synthetic images show a better contrast in 91.2 % of cases for small microcalcifications and in 90.9 % of cases for large microcalcifications. For a dense background, better contrast is seen in 89.5 % of cases for small microcalcifications, and in 85.7 % of cases for large microcalcifications. The contrast ratio increases with increasing breast glandularity. The suppression of structure noise also contributes to the enhancement of microcalcifications in the synthetic images. CONCLUSIONS: Synthetic mammography imaging is superior to digital mammography imaging in terms of microcalcification contrast, regardless their size and breast density.

Assessment of structural chromosomal instability phenotypes as biomarkers of carboplatin response in triple negative breast cancer: the TNT trial.

BACKGROUND: In the TNT trial of triple negative breast cancer (NCT00532727), germline BRCA1/2 mutations were present in 28% of carboplatin responders. We assessed quantitative measures of structural chromosomal instability (CIN) to identify a wider patient subgroup within TNT with preferential benefit from carboplatin over docetaxel. PATIENTS AND METHODS: Copy number aberrations (CNAs) were established from 135 formalin-fixed paraffin-embedded primary carcinomas using Illumina OmniExpress SNP-arrays. Seven published [allelic imbalanced CNA (AiCNA); allelic balanced CNA (AbCNA); copy number neutral loss of heterozygosity (CnLOH); number of telomeric allelic imbalances (NtAI); BRCA1-like status; percentage of genome altered (PGA); homologous recombination deficiency (HRD) scores] and two novel [Shannon diversity index (SI); high-level amplifications (HLAMP)] CIN-measurements were derived. HLAMP was defined based on the presence of at least one of the top 5% amplified cytobands located on 1q, 8q and 10p. Continuous CIN-measurements were divided into tertiles. All nine CIN-measurements were used to analyse objective response rate (ORR) and progression-free survival (PFS). RESULTS: Patients with tumours without HLAMP had a numerically higher ORR and significantly longer PFS in the carboplatin (C) than in the docetaxel (D) arm [56% (C) versus 29% (D), PHLAMP,quiet = 0.085; PFS 6.1 months (C) versus 4.1 months (D), Pinteraction/HLAMP = 0.047]. In the carboplatin arm, patients with tumours showing intermediate telomeric NtAI and AiCNA had higher ORR [54% (C) versus 20% (D), PNtAI,intermediate = 0.03; 62% (C) versus 33% (D), PAiCNA,intermediate = 0.076]. Patients with high AiCNA and PGA had shorter PFS in the carboplatin arm [3.4 months (high) versus 5.7 months (low/intermediate); and 3.8 months (high) versus 5.6 months (low/intermediate), respectively; Pinteraction/AiCNA = 0.027, Padj.interaction/AiCNA = 0.125 and Pinteraction/PGA = 0.053, Padj.interaction/PGA = 0.176], whilst no difference was observed in the docetaxel arm. CONCLUSIONS: Patients with tumours lacking HLAMP and demonstrating intermediate CIN-measurements formed a subgroup benefitting from carboplatin relative to docetaxel treatment within the TNT trial. This suggests a complex and paradoxical relationship between the extent of genomic instability in primary tumours and treatment response in the metastatic setting.

Translating evidence-based treatment for digital health delivery: a protocol for family-based treatment for anorexia nervosa using telemedicine.

BACKGROUND: Family-based treatment (FBT) is an efficacious outpatient intervention for young people diagnosed with Anorexia Nervosa (AN). To date, treatment to protocol has relied on standard face-to-face delivery. Face-to-face therapy is subject to geographic, temporal and human factors, rendering it particularly susceptible to inequities and disruption. This has resulted in poorer service provision for rural and regional families, and recently a significant challenge to providing face-to-face services during the COVID-19 global pandemic. The present study examines whether FBT for AN can be successfully translated to a digital delivery platform to address these access issues. METHOD: Forty young people aged 12 to 18 years who meet DSM-5 diagnostic criteria for AN, and live in a rural or regional setting, will along with their family be recruited to the study. Trained therapists will provide 18 sessions of FBT over 9 months via telemedicine to the home of the young person and their family. The analysis will examine treatment effectiveness, feasibility, acceptability, and cost-effectiveness. DISCUSSION: The study addresses the treatment needs of families not able to attend face-to-face clinical services for evidence-based treatment for eating disorders. This might be due to several barriers, including a lack of local services or long travel distances to services. There has been a recent and unprecedented demand for telemedicine to facilitate the continuity of care during COVID-19 despite geographical circumstances. If delivering treatment in this modality is clinically and economically effective and feasible, it will facilitate access to potentially lifesaving, evidence-based treatments for families formerly unable to access such care and provide evidence for the continuity of services when and where face-to-face treatment is not feasible.

Does prehabilitation modify muscle mass in patients with rectal cancer undergoing neoadjuvant therapy? A subanalysis from the REx randomised controlled trial.

BACKGROUND: Patients with rectal cancer who present with sarcopenia (low muscle mass) are at significantly greater risk of postoperative complications and reduction in disease-free survival. We performed a subanalysis of a randomised controlled study [the REx trial; www.isrctn.com ; 62859294] to assess the potential of prehabilitation to modify muscle mass in patients having neoadjuvant chemoradiotherapy (NACRT). METHODS: Patients scheduled for NACRT, then potentially curative surgery (August 2014-March 2016) had baseline physical assessment and psoas muscle mass measurement (total psoas index using computed tomography-based measurements). Participants were randomised to either the intervention (13-17-week telephone-guided graduated walking programme) or control group (standard care). Follow-up testing was performed 1-2 weeks before surgery. RESULTS: The 44 patients had a mean age of 66.8 years (SD 9.6) and were male (64%); white (98%); American Society of Anesthesiologists class 2 (66%); co-morbid (58%); overweight (72%) (body mass index ≥ 25 kg/m2). At baseline, 14% were sarcopenic. At follow-up, 13 (65%) of patients in the prehabilitation group had increased muscle mass versus 7 (35%) that experienced a decrease. Conversely, 16 (67%) controls experienced a decrease in muscle mass and 8 (33%) showed an increase. An adjusted linear regression model estimated a mean treatment difference in Total Psoas Index of 40.2mm2/m2 (95% CI - 3.4 to 83.7) between groups in change from baseline (p = 0.07). CONCLUSIONS: Prehabilitation improved muscle mass in patients with rectal cancer who had NACRT. These results need to be explored in a larger trial to determine if the poorer short- and long-term patient outcomes associated with low muscle mass can be minimised by prehabilitation.

The relationship between sarcopenia and survival at 1 year in patients having elective colorectal cancer surgery.

BACKGROUND: Colorectal cancer remains a common cause of cancer death in the UK, with surgery being the mainstay of treatment. An objective measurement of the suitability of each patient for surgery, and their risk-benefit calculation, would be of great utility. We postulate that sarcopenia (low muscle mass) could fulfil this role as a prognostic indicator. The aim of this study was to determine the relationship between sarcopenia and long-term outcomes in patients undergoing elective bowel resection for colorectal cancer. METHODS: One hundred and sixty-three consecutive patients who had elective curative colorectal resection for cancer were eligible for inclusion in the study. Psoas muscle mass was assessed on preoperative computed tomography scan at the level of the L3 vertebra and standardised for patient height (total psoas index, TPI). Sarcopenia (low muscle mass) was defined as < 524 mm2/m2 in males and 385 mm2/m2 in females. In addition to clinical-pathological parameters, postoperative complications were recorded and patients were followed up for mortality for 1 year after surgery. RESULTS: Sarcopenia was present in 19.6% of the study participants and was significantly related to body mass index (p = 0.007), 30-day mortality (p = 0.042) and 1-year mortality (p = 0.046). In univariate analysis, American Society of Anesthesiologists grade (p = 0.016), tumour stage (p = 0.018) and sarcopenia (p = 0.043) were found to be significant independent predictors of 1-year mortality. CONCLUSIONS: This study has found sarcopenia to be prevalent in patients with colorectal cancer having elective surgery. Independent of age, sarcopenia was associated with poorer 30-day mortality and survival at 1 year. Measurement of muscle mass preoperatively could be used to stratify a patient's risk, allowing targeted strategies such as prehabilitation, to be implemented to modify sarcopenia and improve long-term outcomes for patients.

A comparison of four different imaging modalities - Conventional, cross polarized, infra-red and ultra-violet in the assessment of childhood bruising.

BACKGROUND: It is standard practice to image concerning bruises in children. We aim to compare the clarity and measurements of bruises using cross polarized, infra-red (IR) and ultra-violet (UV) images to conventional images. METHODS: Children aged <11 years with incidental bruising were recruited. Demographics, skin and bruise details were recorded. Bruises were imaged by standard protocols in conventional, cross-polarized, IR and UV lights. Bruises were assessed in vivo for contrast, uniformity and diffuseness, and these characteristics were then compared across image modalities. Color images (conventional, cross polarized) were segmented and measured by ImageJ. Bruises of grey scale images (IR, UV) were measured by a 'plug in' of ImageJ. The maximum and minimum Feret's diameter, area and aspect ratio, were determined. Comparison of measurements across imaging modalities was conducted using Wilcoxon rank sum tests and modified Bland-Altman graphs. Significance was set at p < 0.05. RESULTS: Twenty five children had 39 bruises. Bruises that were of low contrast, i.e. difficult to distinguish from surrounding skin, were also more diffuse, and less uniformity in vivo. Low contrast bruises were best seen on conventional and cross-polarized images and less distinctive on IR and UV images. Of the 19 bruises visible in all modalities, the only significant difference was maximum and minimum Feret's diameters and area were smaller on IR compared to conventional images. Aspect ratios were not affected by the modality. CONCLUSIONS: Conventional and cross-polarized imaging provides the most consistent bruise measurement, particularly in bruises that are not easily distinguished from surrounding skin visually.

Optimising the measurement of bruises in children across conventional and cross polarized images using segmentation analysis techniques in Image J, Photoshop and circle diameter measurements.

BACKGROUND: Bruising is a common abusive injury in children, and it is standard practice to image and measure them, yet there is no current standard for measuring bruise size consistently. We aim to identify the optimal method of measuring photographic images of bruises, including computerised measurement techniques. METHODS: 24 children aged <11 years (mean age of 6.9, range 2.5-10 years) with a bruise were recruited from the community. Demographics and bruise details were recorded. Each bruise was measured in vivo using a paper measuring tape. Standardised conventional and cross polarized digital images were obtained. The diameter of bruise images were measured by three computer aided measurement techniques: Image J (segmentation with Simple Interactive Object Extraction (maximum Feret diameter), 'Circular Selection Tool' (Circle diameter), & the Photoshop 'ruler' software (Photoshop diameter)). Inter and intra-observer effects were determined by two individuals repeating 11 electronic measurements, and relevant Intraclass Correlation Coefficient's (ICC's) were used to establish reliability. Spearman's rank correlation was used to compare in vivo with computerised measurements; a comparison of measurement techniques across imaging modalities was conducted using Kolmogorov-Smirnov tests. Significance was set at p < 0.05 for all tests. RESULTS: Images were available for 38 bruises in vivo, with 48 bruises visible on cross polarized imaging and 46 on conventional imaging (some bruises interpreted as being single in vivo appeared to be multiple in digital images). Correlation coefficients were >0.5 for all techniques, with maximum Feret diameter and maximum Photoshop diameter on conventional images having the strongest correlation with in vivo measurements. There were significant differences between in vivo and computer-aided measurements, but none between different computer-aided measurement techniques. Overall, computer aided measurements appeared larger than in vivo. Inter- and intra-observer agreement was high for all maximum diameter measurements (ICC's > 0.7). CONCLUSIONS: Whilst there are minimal differences between measurements of images obtained, the most consistent results were obtained when conventional images, segmented by Image J Software, were measured with a Feret diameter. This is therefore proposed as a standard for future research, and forensic practice, with the proviso that all computer aided measurements appear larger than in vivo.

Agents, mechanisms and clinical features of non-scald burns in children: A prospective UK study.

AIMS: To inform childhood burn prevention by identifying demographics, clinical features and circumstances of unintentional non-scald burns. METHODS: A prospective cross-sectional study was conducted across Cardiff, Bristol and Manchester, including six emergency departments, three minor injury units and one burns unit between 13/01/2013-01/10/2015. Data collected for children aged <16 years with any burn (scald, contact, flame, radiation, chemical, electrical, friction) included: demographics, circumstances of injury and clinical features. Scalds and burns due to maltreatment were excluded from current analysis. RESULTS: Of 564 non-scald cases, 60.8% were boys, 51.1% were <3 years old, 90.1% (472/524) of burns affected one anatomical site. Contact burns accounted for 86.7% (489/564), 34.8% (137/394) of which were from objects placed at >0.6m and 76.5% (349/456) affected the hands. Hairstyling devices were the most common agent of contact burns (20.5%, 100/487); 34.1% (30/88) of hairstyling devices were on the floor. Of children aged 10-15 years, 63.7% (65/102), sustained contact burns of which 23.2% (13/56) were preparing food, and when burnt from hairstyling devices, 73.3% (11/15) were using them at the time of injury. CONCLUSIONS: Parents of toddlers must learn safe storage of hazardous items. Older children should be taught skills in safe cooking and hairstyling device use.

Methylation of avpr1a in the cortex of wild prairie voles: effects of CpG position and polymorphism.

DNA methylation can cause stable changes in neuronal gene expression, but we know little about its role in individual differences in the wild. In this study, we focus on the vasopressin 1a receptor (avpr1a), a gene extensively implicated in vertebrate social behaviour, and explore natural variation in DNA methylation, genetic polymorphism and neuronal gene expression among 30 wild prairie voles (Microtus ochrogaster). Examination of CpG density across 8 kb of the locus revealed two distinct CpG islands overlapping promoter and first exon, characterized by few CpG polymorphisms. We used a targeted bisulfite sequencing approach to measure DNA methylation across approximately 3 kb of avpr1a in the retrosplenial cortex, a brain region implicated in male space use and sexual fidelity. We find dramatic variation in methylation across the avrp1a locus, with pronounced diversity near the exon-intron boundary and in a genetically variable putative enhancer within the intron. Among our wild voles, differences in cortical avpr1a expression correlate with DNA methylation in this putative enhancer, but not with the methylation status of the promoter. We also find an unusually high number of polymorphic CpG sites (polyCpGs) in this focal enhancer. One polyCpG within this enhancer (polyCpG 2170) may drive variation in expression either by disrupting transcription factor binding motifs or by changing local DNA methylation and chromatin silencing. Our results contradict some assumptions made within behavioural epigenetics, but are remarkably concordant with genome-wide studies of gene regulation.

Characteristics of non-vitreoretinal ocular injury in child maltreatment: a systematic review.

PurposeTo identify the spectrum of non-vitreoretinal ocular injury due to child maltreatment.MethodsAll language search of MEDLINE, PsychINFO, EMBASE, AMED, Web of Science, and CINAHL databases, 1950-2015, was conducted. INCLUSION CRITERIA: explicit confirmation of injury aetiology, age <18 years, examination conducted by an ophthalmologist. Exclusion: post-mortem data, organic diseases, review articles. Standardised critical appraisal and narrative synthesis was conducted of included publications by two independent reviewers.ResultsOf 1492 studies identified, 153 full texts were assessed, 49 underwent full review, resulting in five included studies: three case series and two case reports. The 26 included cases describe a wide variety of ocular, facial and skeletal injuries occurring as a consequence of child maltreatment. Ocular signs included periorbital oedema, chemosis, injection, abrasion, hyphaema, and cataract. Of interest all children that had suffered physical abuse with ocular injury had subconjunctival haemorrhages. Children presenting with abusive ocular injuries had a mean age of 13.9 months (range 1-68), while those who suffered violent corporal punishment were considerably older (mean 96 months). All cases, apart from severe corporal punishment, underwent screening for occult fractures, but neuroimaging only apparent in 2/5 eligible cases.ConclusionAlthough, the face is the most common site of abusive injury, there is a paucity of high-quality data on non-vitreoretinal ocular abusive injury. Thus, while subconjunctival haemorrhages are a potential sentinel injury of maltreatment, and may warrant further evaluation, the lack of large-scale published data limits our ability to highlight further specific characteristics of non-vitreoretinal ocular injury indicative of child abuse.

Ask Me! self-reported features of adolescents experiencing neglect or emotional maltreatment: a rapid systematic review.

BACKGROUND: Neglect is often overlooked in adolescence, due in part to assumptions about autonomy and misinterpretation of behaviors being part of normal adolescent development. Emotional maltreatment (abuse or neglect) has a damaging effect throughout the lifespan, but is rarely recognized amongst adolescents. Our review aims to identify features that adolescents experiencing neglect and/ or emotional maltreatment report. METHOD: A rapid review methodology searched 8 databases (1990-2014), supplemented by hand searching journals, and references, identifying 2,568 abstracts. Two independent reviews were undertaken of 279 articles, by trained reviewers, using standardised critical appraisal. Eligible studies: primary studies of children aged 13-17 years, with substantiated neglect and/ or emotional maltreatment, containing self-reported features. RESULTS: 19 publications from 13 studies were included, demonstrating associations between both neglect and emotional maltreatment with internalising features (9 studies) including depression, post traumatic symptomatology and anxiety; emotional maltreatment was associated with suicidal ideation, while neglect was not (1 study); neglect was associated with alcohol related problems (3 studies), substance misuse (2 studies), delinquency for boys (1 study), teenage pregnancy (1 study), and general victimization for girls (1 study), while emotionally maltreated girls reported more externalising symptoms (1 study). Dating violence victimization was associated with neglect and emotional maltreatment (2 studies), while emotional abuse of boys, but not neglect, was associated with dating violence perpetration (1 study), and neither neglect nor emotional maltreatment had an association with low self-esteem (2 studies). Neither neglect nor emotional maltreatment had an effect on school performance (1 study), but neglected boys showed greater school engagement than neglected girls (1 study). CONCLUSIONS: If asked, neglected or emotionally maltreated adolescents describe significant difficulties with their mental health, social relationships, and alcohol or substance misuse. Practitioners working with youths who exhibit these features should recognize the detrimental impact of maltreatment at this developmental stage, and identify whether maltreatment is a contributory factor that should be addressed.