New understandings meet old treatments: putting a contemporary face on established protocols.

In the twenty years since the publication of the most widely used treatment manuals describing evidence-based therapies for eating disorders, there have been some substantial advances in the field. New methods of delivering treatments have been trialled and our perception of mental health has advanced; significant cultural changes have led to shifts in our societal landscape; and new technologies have allowed for more in-depth research to be conducted. As a result, our understanding of eating disorders and their treatment has broadened considerably. However, these new insights have not necessarily been translated into improved clinical practice. This paper highlights the changes we consider to have had the greatest impact on our work as experienced clinical psychologists in the field and suggests a list of new learnings that might be incorporated into clinical practice and research design.

In the field of eating disorders the most commonly used manualised treatments are nearly twenty years old. There has been much progress in the field since then in terms of technologies, understandings and social changes. In this paper, two experienced clinical psychologists describe some of the more recent developments in the field and highlight ways to incorporate the new learnings into clinical practice and research design.

Clinical Hypnosis as an Adjunct to Cognitive Behavior Therapy: An Updated Meta-Analysis.

In 1995, Kirsch and colleagues published an influential meta-analysis (k = 20, N = 577) which found that CBT enhanced with hypnosis (CBTH) was superior to CBT alone by at least d = .53. However, a lack of full replication and the emergence of new empirical studies prompted this updated analysis. A total of 48 post- (N = 1,928) and 25 follow-up treatments (N = 1,165) were meta-analyzed. CBTH achieved small to medium but statistically significant advantages over CBT at posttreatment (dIGPP/d = .25 to .41), and specifically in the management of depressed mood and pain. At follow-up, there was a medium sized advantage for CBTH (dIGPP/d = .54 to .59), and specifically for the treatment of obesity. These results further support the adjunctive use of hypnosis as an enhancer of CBT's efficaciousness and endurance as a treatment.

CHD2-Related CNS Pathologies.

Epileptic encephalopathies (EE) are severe epilepsy syndromes characterized by multiple seizure types, developmental delay and even regression. This class of disorders are increasingly being identified as resulting from de novo genetic mutations including many identified mutations in the family of chromodomain helicase DNA binding (CHD) proteins. In particular, several de novo pathogenic mutations have been identified in the gene encoding chromodomain helicase DNA binding protein 2 (CHD2), a member of the sucrose nonfermenting (SNF-2) protein family of epigenetic regulators. These mutations in the CHD2 gene are causative of early onset epileptic encephalopathy, abnormal brain function, and intellectual disability. Our understanding of the mechanisms by which modification or loss of CHD2 cause this condition remains poorly understood. Here, we review what is known and still to be elucidated as regards the structure and function of CHD2 and how its dysregulation leads to a highly variable range of phenotypic presentations.

Evidence That the Clinical Impairment Assessment (CIA) Subscales Should Not Be Scored: Bifactor Modelling, Reliability, and Validity in Clinical and Community Samples.

Aim: The Clinical Impairment Assessment (CIA 3.0) is the most widely used instrument assessing psychosocial impairment secondary to eating disorder symptoms. However, there is conflicting advice regarding the dimensionality and optimal method of scoring the CIA. We sought to resolve this confusion by conducting a comprehensive factor analytic study of the CIA in a community sample (N = 301) and clinical sample comprising patients with a diagnosed eating disorder (N = 209). Convergent and discriminant validity were also assessed. Method: The CIA and measures of eating disorder symptoms were administered to both samples. Results: Factor analyses indicated there is a general impairment factor underlying all items on the CIA that is reliably measured by the CIA Global score. CIA Global demonstrated good convergent and discriminant validity. Conclusions: CIA Global is a reliable and valid measure of psychosocial impairment secondary to eating disorder symptoms; however, subscale scores should not be computed.

The development and validation of a measure of eating disorder-specific interpersonal problems: The Interpersonal Relationships in Eating Disorders (IR-ED) Scale.

Clinical reports suggest that interpersonal problems are associated with the onset and maintenance of eating pathology, but existing measures of such problems have limited links to eating pathology. Therefore, the aim of this study was to develop an eating-specific measure of interpersonal problems. The new measure, the Interpersonal Relationships in Eating Disorders scale (IR-ED), was administered to a large community sample, a nonclinical replication sample, and a clinical group of eating disorder patients. In Study 1, the psychometric properties of the IR-ED were established, and they were tested using confirmatory analyses in Study 2. Study 3 determined the validity of the test score interpretations in a clinical sample. The final 15-item version of the IR-ED demonstrated 3 distinct factors with reliability of test scores-Food-Related Isolation; Avoidance of Body Evaluation; and Food-Related Interpersonal Tension. Study 2 demonstrated that the IR-ED comprises a common Interpersonal Problems factor and a specific group factor-Avoidance of Body Evaluation. Study 3 showed that the clinical group had higher IR-ED scores than a nonclinical group. Across the studies, Avoidance of Body Evaluation was the strongest correlate of eating pathology in this group. The IR-ED has strong psychometric properties and its test scores appear to be more valid than those of a generic measure of interpersonal problems. Avoidance of Body Evaluation is the strongest facet of such interpersonal problems, and has meaningful links to models of eating psychopathology. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

A single session assessment and psychoeducational intervention for eating disorders: Impact on treatment waitlists and eating disorder symptoms.

OBJECTIVE: Long waitlists are common in eating disorder services and can have a detrimental impact on patients. We examined the effect on waitlist length, attendance, and eating disorder symptoms, of a 75-90 min single session intervention (SSI), attended a median of 16 days after referral to a specialist eating disorders clinic. METHOD: Sequential referrals (N = 448) to a public outpatient eating disorders program were tracked from referral until a decision was made on patients entering treatment. One group ("SSI cohort") received a protocol incorporating assessment and psychoeducation about eating disorders before being placed on a waitlist, after which they received further assessment and entered treatment. Data on patient flow indices were collected from this cohort and compared to data from a "Pre-SSI" cohort who had not received the SSI. Symptom change was examined in the SSI cohort. RESULTS: Waitlist length reduced and the proportion of referrals attending assessment and being allocated to treatment increased. Eating disorder symptoms and impairment decreased. Underweight patients (Body Mass Index [BMI] < 18.5 kg/m2 ) gained weight. DISCUSSION: These findings suggest that a single session psychoeducational assessment may reduce waiting times, increase the likelihood of patients entering treatment, and facilitate early reductions in eating disorder symptoms. However, there may be other explanations for the changes observed.

Randomized controlled psychotherapy trials in eating disorders: Improving their conduct, interpretation and usefulness.

BACKGROUND: While randomized controlled trials (RCTs) inform the efficacy and effectiveness of treatments, we need to understand that even RCTs can be associated with sub-optimal execution. This is of special pertinence to eating disorders given the majority of treatment studies involving cognitive behaviour therapy are of poor quality with respect to managing risk of bias adequately. METHODS: The current paper outlines the components of a good RCT for psychotherapy, and examines ways to improve the conduct, interpretation, and usefulness of RCTs. RESULTS: This includes managing reporting bias, recognizing the limits of randomization, applicability, and ethical considerations. CONCLUSIONS: We highlight a number of strategies for future research, including issues related to utilizing a variety of designs to examine treatment outcomes, integrity, openness and reproducibility.

Antiapoptotic serine protease inhibitors contribute to survival of allergenic TH2 cells.

BACKGROUND: The mechanisms that regulate maintenance of persistent TH2 cells and potentiate allergic inflammation are not well understood. OBJECTIVE: The function of serine protease inhibitor 2A (Spi2A) was studied in mouse TH2 cells, and the serine protease inhibitor B3 (SERPINB3) and SERPINB4 genes were studied in TH2 cells from patients with grass pollen allergy. METHODS: Spi2A-deficient TH2 cells were studied in in vitro culture or in vivo after challenge of Spi2A knockout mice with ovalbumin in alum. Expression of SERPINB3 and SERPINB4 mRNA was measured in in vitro-cultured TH2 cells and in ex vivo CD27-CD4+ cells and innate lymphoid cell (ILC) 2 from patients with grass pollen allergy by using quantitative PCR. SERPINB3 and SERPINB4 mRNA levels were knocked down in cultured CD27-CD4+ cells with small hairpin RNA. RESULTS: There were lower levels of in vitro-polarized TH2 cells from Spi2A knockout mice (P < .005) and in vivo after ovalbumin challenge (P < .05), higher levels of apoptosis (Annexin V positivity, P < .005), and less lung allergic inflammation (number of lung eosinophils, P < .005). In vitro-polarized TH2 cells from patients with grass pollen allergy expressed higher levels of both SERPINB3 and SERPINB4 mRNA (both P < .05) compared with unpolarized CD4 T cells. CD27-CD4+ from patients with grass pollen allergy expressed higher levels of both SERPINB3 and SERPINB4 mRNA (both P < .0005) compared with CD27+CD4+ cells. ILC2 expressed higher levels of both SERPINB3 and SERPINB4 mRNA (both P < .0005) compared with ILC1. Knockdown of either SERPINB3 or SERPINB4 mRNA (both P < .005) levels resulted in decreased viability of CD27-CD4+ compared with control transduced cells. CONCLUSION: The Serpins Spi2A in mice and SERPINB3 and SERPINB4 in allergic patients control the viability of TH2 cells. This provides proof of principle for a therapeutic approach for allergic disease through ablation of allergic memory TH2 cells through SERPINB3 and SERPINB4 mRNA downregulation.

The psychosocial burden of childhood overweight and obesity: evidence for persisting difficulties in boys and girls.

There is evidence that overweight and obese children tend to remain overweight or obese into adolescence and adulthood. However, little is known about the long-term psychosocial outcomes of childhood overweight and obesity. This study aimed to investigate the course of psychosocial difficulties over a 2-year period for children who were overweight or obese at baseline, and a sample of children who were a healthy weight at baseline. Participants were 212 children aged 8 to 13 years at baseline, who were participating in the Childhood Growth and Development (GAD) Study. Questionnaire and interview measures were used to assess children's self-esteem, depressive symptoms, body image, eating disorder symptoms, experiences with bullying, family satisfaction and quality of life. Linear mixed models were used to consider longitudinal changes in psychosocial variables. Overweight and obese children reported greater psychosocial distress than healthy weight children, and these differences were more pronounced for girls than boys. Weight and psychosocial impairment showed stability from baseline to 2-year follow-up. CONCLUSION: The results of this study suggest that psychosocial difficulties show considerable stability in childhood, for overweight/obese and healthy weight children. What is Known: • Childhood obesity tracks into adolescence and adulthood. • Physical health problems associated with childhood obesity also persist to adulthood. What is New: • Overweight and obese children are at risk of ongoing psychosocial distress from childhood into early adolescence.

Do universal media literacy programs have an effect on weight and shape concern by influencing media internalization?

The current study examined whether media internalization, found to mediate the relationship between selected prevention programs and outcomes, mediated the impact of two universal prevention programs that targeted risk factors for eating disorders and obesity, namely weight concern, and shape concern. Students randomized to a media literacy (Media Smart) program (N = 269, 65% females, mean age 12.97 years) and a healthy lifestyle (Life Smart) program (N = 347, 69% females, mean age 13.07 years) were included in the analyses. There were four waves of data (baseline, end of intervention, 6- and 12-month follow-up). Latent growth curve modeling was used to explore whether group assignment influenced levels of media internalization, and whether that in turn influenced change over time of our two outcome variables. Being randomly allocated to Media Smart as opposed to Life Smart resulted in less growth of both outcome variables through the influence on decreasing levels of media internalization. Findings provided support for the suggestion that media literacy programs exert an impact on outcomes related to eating disorder risk through changes to media internalization. Future research should examine whether these mechanisms of change differ between girls and boys.

Treatment Success: Investigating Clinically Significant Change in Quality of Life Following Bariatric Surgery.

BACKGROUND: One of the most important outcomes following bariatric surgery is an improvement in health-related quality of life (QOL). This study aimed to explore what degree of weight loss is required after bariatric surgery in order to achieve a clinically significant change in QOL from pre-surgery to 4 to 5 years after surgery. METHODS: Participants were assessed prior to having surgery (N = 280) and were invited to participate in a follow-up study 4 to 5 years after surgery. Sixty-seven of the original participants agreed to take part and completed a Web-based survey, which included the Impact of Weight on Quality of Life-Lite (IWQOL-Lite) questionnaire. Several analyses were conducted to examine the association between weight loss and clinically significant change in QOL. RESULTS: Mean age was 48.13 ± 10.37 years, 51 (76%) were female, 62 (92.5%) Caucasian, and mean baseline body mass index (BMI) was 41.11 ± 6.03 kg/m2. The mean percent of excess weight loss (EWL) was 46% (17% total weight loss), and 64% (n = 43) achieved a clinically significant change in QOL. The majority of those who lost ≥40% EWL had a clinically significant change in QOL, and their odds of achieving this change were 2.81 times higher than those that did not. CONCLUSIONS: Results indicated that an EWL of ≥40% may be sufficient for the majority of patients to achieve clinically significant change, but that ≥50% is a better predictor of clinically significant change.

Eating disorders in the context of preconception care: fertility specialists' knowledge, attitudes, and clinical practices.

OBJECTIVE(S): To gauge fertility specialists' knowledge, clinical practices, and training needs in regard to eating disorders. DESIGN: Cross-sectional study. SETTINGS: Fertility clinics. PARTICIPANTS: Eighty Australian and New Zealand fertility specialists who were members of the Fertility Society of Australia. INTERVENTION(S): None. MAIN OUTCOME MEASURES(S): Responses to an anonymously completed online questionnaire. RESULT(S): Approximately 54% of doctors correctly identified the body mass index relevant to anorexia nervosa, and 30% identified menstrual disturbances for anorexia, while 63.8% of doctors incorrectly nominated maladaptive weight control behaviors as a characteristic of binge eating disorder. While clinicians (83.7%) agreed it was important to screen for eating disorders during preconception assessments, 35% routinely screened for eating disorders and 8.8% indicated that their clinics had clinical practice guidelines for management of eating disorders. A minority of participants (13.8%) felt satisfied with their level of university training in eating disorders, 37.5% of doctors felt confident in their ability to recognize symptoms of an eating disorder, and 96.2% indicated a need for further education and clinical guidelines. On most items examined, knowledge and clinical practices regarding eating disorders did not differ according to doctor gender or years of clinical experience working as a fertility specialist. CONCLUSION(S): Knowledge about eating disorders in the context of fertility treatment is important. This study highlights the uncertainty among fertility specialists in detecting features of eating disorders. The findings point to the importance of further education and training, including the development of clinical guidelines specific to fertility health care providers.

Outcomes of three universal eating disorder risk reduction programs by participants with higher and lower baseline shape and weight concern.

OBJECTIVE: To investigate if baseline shape and weight concern (SWC) moderated outcomes in Prevention Across the Spectrum, a randomized-controlled trial (RCT) of 3 school-based programs aimed at reducing eating disorder and obesity risk factors. METHOD: N = 1,316 Grade 7 and 8 girls and boys (M age = 13.21 years) across three Australian states were randomly allocated to: Media Smart; Life Smart; Helping, Encouraging, Listening and Protecting Peers Initiative (HELPP) or control (usual school class). Moderation was explored by testing interaction effects for group (Media Smart; Life Smart; HELPP; Control) × moderator (SWC: higher-SWC; lower-SWC) × time (post-program; 6-month follow-up; 12-month follow-up), with baseline risk factor scores entered as covariates. RESULTS: Moderation effects were found for shape concern, weight concern, eating concern, regular eating (i.e., meal skipping), physical activity, body dissatisfaction, dieting, and perfectionism. Post-hoc testing found eating concern at post-program was the only variable where higher-SWC Media Smart participants experienced a reduction in risk relative to controls. Both higher-SWC Life Smart and HELPP participants reported an increase in eating concern relative to controls and both groups were skipping more meals than controls at 12-month follow-up. Amongst lower-SWC participants, Media Smart was the only group to experience a benefit relative to controls (physical activity). CONCLUSIONS: This study highlights the need for moderator analyses to become more routinely conducted in universal trials, to ensure that participants across baseline risk levels are benefiting and not harmed from program participation. © 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2017; 50:66-75).

An investigation of young girls' responses to sexualized images.

Evidence suggests that the sexualization of girls has increased and become more explicit in recent years. However, most of the research conducted to date has focused on sexualization in adults. To address this research gap, this study explored how young Australian girls respond to and describe sexualized and non-sexualized depictions of their peers. Results from 42 girls aged 6-11 years revealed that sexualization was a perceptually salient attribute, with participants readily classifying sexualized girls as a subgroup. Participants also made distinct trait attributions based on the differences between sexualized and non-sexualized girls. The results suggest that young girls respond differently to sexualized and non-sexualized depictions of their peers and are beginning to develop stereotypes based on these depictions. As such, the implementation of media literacy programs in adolescence may be too late and efforts may be required to address this issue among younger children.

Testing for interactive and non-linear effects of risk factors for binge eating and purging eating disorders.

Almost no research has tested whether risk factors interact in the prediction of future eating disorder onset, which might suggest qualitatively distinct etiologic pathways. Accordingly, this prospective study tested for possible interactions between risk factors in the prediction of binge eating and purging eating disorders in adolescents. It also examined sex differences in pathways to risk. Two analytical approaches were used: (1) classification tree analysis (CTA), which is ideally suited to identifying non-linear interactions and the optimal cut-points for defining risk, with follow-up random forest analyses; and (2) two-way interaction terms in a series of logistic regression models. Data were drawn from the Western Australian Pregnancy Cohort (Raine) Study, a population-based study that followed participants from pre-birth to young adulthood. This study involved 1297 adolescents (49% male), 146 (11%) of whom developed bulimia nervosa, binge eating disorder or purging disorder in late adolescence. In CTA, sex was the first and most potent predictor of eating disorder risk with females showing a 5-fold increase in risk relative to males. For males and females, weight and eating concerns were the next most potent predictor of risk and three risk groups emerged, reflecting non-linear risk. For females with intermediate weight and eating concerns, externalizing problems emerged as an additional predictor. Interaction terms in logistic regression models did not produce significant results after correcting for multiple testing. Findings advance knowledge on risk pathways to eating disorder onset, highlight non-linear risk processes, and provide cut-points for prospectively identifying high-risk youth for prevention programs.

How perfectionism and ineffectiveness influence growth of eating disorder risk in young adolescent girls.

While perfectionism is widely considered to influence risk for eating disorders, results of longitudinal studies are mixed. The goal of the current study was to investigate a more complex model of how baseline perfectionism (both high personal standards and self-critical evaluative concerns) might influence change in risk status for eating disorders in young adolescent girls, through its influence on ineffectiveness. The study was conducted with 926 girls (mean age of 13 years), and involved three waves of data (baseline, 6- and 12-month follow-up). Latent growth curve modelling, incorporating the average rate at which risk changed over time, the intercept (initial status) of ineffectiveness, and baseline perfectionism, was used to explore longitudinal mediation. Personal standards was not supported as contributing to risk but results indicated that the higher mean scores on ineffectiveness over the three waves mediated the relationship between higher baseline self-critical evaluative concerns and both measures of eating disorder risk. The relationship between concern over mistakes and change in risk was small and negative. These results suggest the usefulness of interventions related to self-criticism and ineffectiveness for decreasing risk for developing an eating disorder in young adolescent girls.

Distinguishing Between Risk Factors for Bulimia Nervosa, Binge Eating Disorder, and Purging Disorder.

Binge eating disorder and purging disorder have gained recognition as distinct eating disorder diagnoses, but risk factors for these conditions have not yet been established. This study aimed to evaluate a prospective, mediational model of risk for the full range of binge eating and purging eating disorders, with attention to possible diagnostic differences. Specific aims were to determine, first, whether eating, weight and shape concerns at age 14 would mediate the relationship between parent-perceived childhood overweight at age 10 and a binge eating or purging eating disorder between age 15 and 20, and, second, whether this mediational model would differ across bulimia nervosa, binge eating disorder, and purging disorder. Participants (N = 1,160; 51 % female) were drawn from the Western Australian Pregnancy Cohort (Raine) Study, which has followed children from pre-birth to age 20. Eating disorders were assessed via self-report questionnaires when participants were aged 14, 17 and 20. There were 146 participants (82 % female) with a binge eating or purging eating disorder with onset between age 15 and 20 [bulimia nervosa = 81 (86 % female), binge eating disorder = 43 (74 % female), purging disorder = 22 (77 % female)]. Simple mediation analysis with bootstrapping was used to test the hypothesized model of risk, with early adolescent eating, weight and shape concerns positioned as a mediator between parent-perceived childhood overweight and later onset of a binge eating or purging eating disorder. Subsequently, a conditional process model (a moderated mediation model) was specified to determine if model pathways differed significantly by eating disorder diagnosis. In the simple mediation model, there was a significant indirect effect of parent-perceived childhood overweight on risk for a binge eating or purging eating disorder in late adolescence, mediated by eating, weight and shape concerns in early adolescence. In the conditional process model, this significant indirect effect was not moderated by eating disorder group. The results support a prospective model of risk that applies to bulimia nervosa, binge eating disorder and purging disorder. Common prevention approaches may be possible for bulimia nervosa, binge eating disorder and purging disorder.

Multi-kilobase homozygous targeted gene replacement in human induced pluripotent stem cells.

Sequence-specific nucleases such as TALEN and the CRISPR/Cas9 system have so far been used to disrupt, correct or insert transgenes at precise locations in mammalian genomes. We demonstrate efficient 'knock-in' targeted replacement of multi-kilobase genes in human induced pluripotent stem cells (iPSC). Using a model system replacing endogenous human genes with their mouse counterpart, we performed a comprehensive study of targeting vector design parameters for homologous recombination. A 2.7 kilobase (kb) homozygous gene replacement was achieved in up to 11% of iPSC without selection. The optimal homology arm length was around 2 kb, with homology length being especially critical on the arm not adjacent to the cut site. Homologous sequence inside the cut sites was detrimental to targeting efficiency, consistent with a synthesis-dependent strand annealing (SDSA) mechanism. Using two nuclease sites, we observed a high degree of gene excisions and inversions, which sometimes occurred more frequently than indel mutations. While homozygous deletions of 86 kb were achieved with up to 8% frequency, deletion frequencies were not solely a function of nuclease activity and deletion size. Our results analyzing the optimal parameters for targeting vector design will inform future gene targeting efforts involving multi-kilobase gene segments, particularly in human iPSC.

Low dietary intake of magnesium is associated with increased externalising behaviours in adolescents.

OBJECTIVE: Adequate Zn and Mg intakes may be beneficial for the prevention and treatment of mental health problems, such as depression, anxiety and attention-deficit hyperactivity disorder. We aimed to investigate the prospective association between dietary intakes of Zn and Mg and internalising and externalising behaviour problems in a population-based cohort of adolescents. DESIGN: Prospective analysis (general linear mixed models) of dietary intakes of Zn and Mg assessed using a validated FFQ and mental health symptoms assessed using the Youth Self-Report (YSR), adjusting for sex, physical activity, family income, supplement status, dietary misreporting, BMI, family functioning and energy intake. SETTING: Western Australian Pregnancy Cohort (Raine) Study. SUBJECTS: Adolescents (n 684) at the 14- and 17-year follow-ups. RESULTS: Higher dietary intake of Mg (per SD increase) was significantly associated with reduced externalising behaviours (ß = -1.45; 95% CI -2.40, -0.50; P = 0.003). There was a trend towards reduced externalising behaviours with higher Zn intake (per SD increase; ß = -0.73; 95% CI -1.57, 0.10; P = 0.085). CONCLUSIONS: The study shows an association between higher dietary Mg intake and reduced externalising behaviour problems in adolescents. We observed a similar trend, although not statistically significant, for Zn intake. Randomised controlled trials are necessary to determine any benefit of micronutrient supplementation in the prevention and treatment of mental health problems in adolescents.

Crispr-mediated Gene Targeting of Human Induced Pluripotent Stem Cells.

CRISPR/Cas9 nuclease systems can create double-stranded DNA breaks at specific sequences to efficiently and precisely disrupt, excise, mutate, insert, or replace genes. However, human embryonic stem or induced pluripotent stem cells (iPSCs) are more difficult to transfect and less resilient to DNA damage than immortalized tumor cell lines. Here, we describe an optimized protocol for genome engineering of human iPSCs using a simple transient transfection of plasmids and/or single-stranded oligonucleotides. With this protocol, we achieve transfection efficiencies greater than 60%, with gene disruption efficiencies from 1-25% and gene insertion/replacement efficiencies from 0.5-10% without any further selection or enrichment steps. We also describe how to design and assess optimal sgRNA target sites and donor targeting vectors; cloning individual iPSC by single cell FACS sorting, and genotyping successfully edited cells.