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.

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.

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.

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.

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.

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).

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.

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.

Rapid neurogenesis through transcriptional activation in human stem cells.

Advances in cellular reprogramming and stem cell differentiation now enable ex vivo studies of human neuronal differentiation. However, it remains challenging to elucidate the underlying regulatory programs because differentiation protocols are laborious and often result in low neuron yields. Here, we overexpressed two Neurogenin transcription factors in human-induced pluripotent stem cells and obtained neurons with bipolar morphology in 4 days, at greater than 90% purity. The high purity enabled mRNA and microRNA expression profiling during neurogenesis, thus revealing the genetic programs involved in the rapid transition from stem cell to neuron. The resulting cells exhibited transcriptional, morphological and functional signatures of differentiated neurons, with greatest transcriptional similarity to prenatal human brain samples. Our analysis revealed a network of key transcription factors and microRNAs that promoted loss of pluripotency and rapid neurogenesis via progenitor states. Perturbations of key transcription factors affected homogeneity and phenotypic properties of the resulting neurons, suggesting that a systems-level view of the molecular biology of differentiation may guide subsequent manipulation of human stem cells to rapidly obtain diverse neuronal types.

Brief report: serpin Spi2A as a novel modulator of hematopoietic progenitor cell formation.

Prime regulation over hematopoietic progenitor cell (HPC) production is exerted by hematopoietins (HPs) and their Janus kinase-coupled receptors (HP-Rs). For HP/HP-R studies, one central challenge in determining specific effects involves the delineation of nonredundant signal transduction factors and their lineage restricted actions. Via loss-of-function studies, we define roles for an HP-regulated Serpina3g/Spi2A intracellular serpin during granulomyelocytic, B-cell, and hematopoietic stem cell (HSC) formation. In granulomyelocytic progenitors, granulocyte macrophage colony stimulating factor (GMCSF) strongly induced Serpina3g expression with Stat5 dependency. Spi2A-knockout (KO) led to 20-fold decreased CFU-GM formation, limited GMCSF-dependent granulocyte formation, and compromised neutrophil survival upon tumor necrosis factor alpha (TNF-α) exposure. In B-cell progenitors, Serpina3g was an interleukin-7 (IL7) target. Spi2A-KO elevated CFU-preB greater than sixfold and altered B-cell formation in competitive bone marrow transplant (BMT), and CpG challenge experiments. In HSCs, Serpina3g/Spi2A expression was also elevated. Spi2A-KO compromised LT-HSC proliferation (as well as lineage(neg) Sca1(pos) Kit(pos) (LSK) cell lysosomal integrity), and skewed LSK recovery post 5-FU. Spi2A therefore functions to modulate HP-regulated immune cell and HSC formation post-5-FU challenge.

Therapist adherence in the strong without anorexia nervosa (SWAN) study: A randomized controlled trial of three treatments for adults with anorexia nervosa.

OBJECTIVE: To develop a psychotherapy rating scale to measure therapist adherence in the Strong Without Anorexia Nervosa (SWAN) study, a multi-center randomized controlled trial comparing three different psychological treatments for adults with anorexia nervosa. The three treatments under investigation were Enhanced Cognitive Behavioural Therapy (CBT-E), the Maudsley Anorexia Nervosa Treatment for Adults (MANTRA), and Specialist Supportive Clinical Management (SSCM). METHOD: The SWAN Psychotherapy Rating Scale (SWAN-PRS) was developed, after consultation with the developers of the treatments, and refined. Using the SWAN-PRS, two independent raters initially rated 48 audiotapes of treatment sessions to yield inter-rater reliability data. One rater proceeded to rate a total of 98 audiotapes from 64 trial participants. RESULTS: The SWAN-PRS demonstrated sound psychometric properties, and was considered a reliable measure of therapist adherence. The three treatments were highly distinguishable by independent raters, with therapists demonstrating significantly more behaviors consistent with the actual allocated treatment compared to the other two treatment modalities. There were no significant site differences in therapist adherence observed. DISCUSSION: The findings provide support for the internal validity of the SWAN study. The SWAN-PRS was deemed suitable for use in other trials involving CBT-E, MANTRA, or SSCM.

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.

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.

Cathepsin B controls the persistence of memory CD8+ T lymphocytes.

The persistence of memory T lymphocytes confers lifelong protection from pathogens. Memory T cells survive and undergo homeostatic proliferation (HSP) in the absence of Ag, although the cell-intrinsic mechanisms by which cytokines drive the HSP of memory T cells are not well understood. In this study we report that lysosome stability limits the long-term maintenance of memory CD8(+) T cell populations. Serine protease inhibitor (Spi) 2A, an anti-apoptotic cytosolic cathepsin inhibitor, is induced by both IL-15 and IL-7. Mice deficient in Spi2A developed fewer memory phenotype CD44(hi)CD8(+) T cells with age, which underwent reduced HSP in the bone marrow. Spi2A was also required for the maintenance of central memory CD8(+) T cell populations after acute infection with lymphocytic choriomeningitis virus. Spi2A-deficient Ag-specific CD8(+) T cell populations declined more than wild-type competitors after viral infection, and they were eroded further after successive infections. Spi2A protected memory cells from lysosomal breakdown by inhibiting cathepsin B. The impaired maintenance of Spi2A-deficient memory CD8(+) T cells was rescued by concomitant cathepsin B deficiency, demonstrating that cathepsin B was a physiological target of Spi2A in memory CD8(+) T cell survival. Our findings support a model in which protection from lysosomal rupture through cytokine-induced expression of Spi2A determines the long-term persistence of memory CD8(+) T cells.

Risk factors for binge eating and purging eating disorders: differences based on age of onset.

OBJECTIVE: To (1) determine whether childhood risk factors for early onset binge eating and purging eating disorders also predict risk for later-onset binge eating and purging disorders, and (2) compare the utility of childhood and early adolescent variables in predicting later-onset disorders. METHOD: Participants (N = 1,383) were drawn from the Western Australian Pregnancy Cohort (Raine) Study, which has followed children from pre-birth to age 20. Eating disorders were assessed when participants were aged 14, 17, and 20. Risk factors for early onset eating disorders have been reported previously (Allen et al., J Am Acad Child Psychiat, 48, 800-809, 2009). This study used logistic regression to determine whether childhood risk factors for early onset disorders, as previously identified, would also predict risk for later-onset disorders (n = 145). Early adolescent predictors of later-onset disorders were also examined. RESULTS: Consistent with early onset cases, female sex and parent-perceived child overweight at age 10 were significant multivariate predictors of binge eating and purging disorders with onset in later adolescence. Eating, weight, and shape concerns at age 14 were also significant in predicting later-onset disorders. In the final stepwise multivariate model, female sex and eating, weight, and shape concerns at age 14 were significant in predicting later-onset eating disorders, while parent-perceived child overweight at age 10 was not. DISCUSSION: There is overlap between risk factors for binge eating and purging disorders with early and later onset. However, childhood exposures may be more important for early than later onset cases.

Low vitamin D levels are associated with symptoms of depression in young adult males.

OBJECTIVE: Results from studies examining associations between serum 25-hydroxyvitamin D (25(OH)D) concentrations and depressive symptoms are equivocal. We investigated the relationship between serum 25(OH)D concentrations and symptoms of depression, anxiety and stress in a cross-sectional analysis of a population-based sample of young adults participating in the Western Australian Pregnancy Cohort (Raine) Study. METHODS: Participants provided a blood sample at the 20-year follow-up (March 2010-April 2012) for the measurement of serum 25(OH)D concentrations. Mental health symptoms were assessed using the 21-item Depression Anxiety Stress Scales (DASS-21). Associations between serum 25(OH)D concentrations and total DASS-21 scores and subscale scores of depression, anxiety and stress were explored in males and females using negative binomial regression, adjusting for age, race, body mass index (BMI) and physical activity (n=735). Models examining subscale scores were also adjusted for the other subscale scores. RESULTS: After adjusting for confounders, an increase in serum 25(OH)D concentrations of 10 nmol/L decreased total DASS-21 scores in males by 9% (rate ratio (RR) 0.91; 95%CI 0.87,0.95; p<0.001) and depression subscale scores in males by 8% (RR 0.92; 95%CI 0.87,0.96; p=0.001). However, in adjusted models there were no significant associations between serum 25(OH)D concentrations and symptoms of anxiety and stress in males. There were no significant associations between serum 25(OH)D concentrations and symptoms of depression, anxiety and stress in females. CONCLUSIONS: We found an association between serum 25(OH)D concentrations and symptoms of depression, but not anxiety and stress, in males. Randomised controlled trials are necessary to determine any benefit of vitamin D supplementation in the prevention and treatment of depressive symptoms in young adults.

Reconsidering do-not-resuscitate orders in the perioperative setting.

Many of our elderly have now signed advance directives or physicians' order sets of life-sustaining treatment forms. Frequently, choices have been made for no life-sustaining interventions at the end of life or do-not-resuscitate (DNR) orders. As the proportion of elderly grows and more patients seek surgical intervention for comfort or to improve their quality of life, the medical and ethical issues of DNR orders in the perioperative setting become increasingly more complex. Many health care providers neither recognize the complexity and significance of the DNR order during the perioperative period nor have hospitals established actions toward resolution of this situation. This article will discuss how this complex issue should be explored, definitions established, and positions recommended.

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.

Cognitive Behavioral Therapy and Hypnosis in the Treatment of Major Depressive Disorder: A Randomized Control Trial.

We investigated whether adding hypnosis to CBT (CBTH) improved treatment outcomes for MDD with a two-armed, parallel-treated, randomized-controlled trial using anonymous self-report and clinician-blinded assessments. Expectancy, credibility, and attitude to hypnosis were also examined. Participants (n = 66) were randomly allocated to 10-weekly sessions of group-based CBT or CBTH. LMM analyses of ITT and Completer data at post-treatment, six-month and 12-month follow-up showed that both treatments were probably efficacious but we did not find significant differences between them. Analyses of remission and response to treatment data revealed that the CBTH Completer group significantly outperformed CBT at 12-month follow-up (p = .011). CBTH also displayed significantly higher associations between credibility, expectancy and mood outcomes up to 12-month follow-up (all p < .05 or better), while attitude to hypnosis showed one significant association (r = -0.57, p < .05). These results suggest that hypnosis shows promise as an adjunct in the treatment of MDD but a larger sample size is required to fully test its merits.

Prognostic value of rapid response to enhanced cognitive behavioral therapy in a routine clinic sample of eating disorder outpatients.

OBJECTIVE: This study examined whether rapid response to enhanced cognitive behavioral therapy (CBT-E) was associated with superior treatment outcomes in a transdiagnostic sample of patients with an eating disorder. METHOD: Participants were 105 patients with a primary eating disorder diagnosis who received individual CBT-E at a community-based outpatient clinic. Patients completed measures of eating disorder and related pathology at baseline and post-treatment. The Eating Disorder Examination-Questionnaire (EDE-Q) was administered at baseline and again, on average, 4.6 weeks after commencing treatment to assess rapid response to CBT-E. Patients achieving reliable change on the EDE-Q at this point were classified as rapid responders. RESULTS: No baseline differences distinguished rapid and nonrapid responders. Rapid responders had significantly lower scores on EDE-Q global at post-treatment, were more likely to achieve full remission, and required significantly fewer treatment sessions than nonrapid responders. One-quarter of the nonrapid responders went on to achieve full remission. There were no group differences on measures of anxiety and depression symptoms at the end of treatment. DISCUSSION: Early change in treatment is encouraged to achieve the best possible prognosis in CBT-E. Those who did not achieve rapid response still had an overall significant improvement in symptoms from pretreatment to post-treatment, but a lower rate of full remission. Nonrapid responders are an important group of patients to study because they offer researchers an opportunity to improve clinical decision-making and treatment outcomes for patients who are at risk of suboptimal response.