Hippocampal aggregation signatures of pathogenic UBQLN2 in amyotrophic lateral sclerosis and frontotemporal dementia.

Pathogenic variants in the UBQLN2 gene cause X-linked dominant amyotrophic lateral sclerosis and/or frontotemporal dementia characterised by ubiquilin 2 aggregates in neurons of the motor cortex, hippocampus, and spinal cord. However, ubiquilin 2 neuropathology is also seen in sporadic and familial amyotrophic lateral sclerosis and/or frontotemporal dementia cases not caused by UBQLN2 pathogenic variants, particularly C9orf72-linked cases. This makes the mechanistic role of mutant ubiquilin 2 protein and the value of ubiquilin 2 pathology for predicting genotype unclear. Here we examine a cohort of 44 genotypically diverse amyotrophic lateral sclerosis cases with or without frontotemporal dementia, including eight cases with UBQLN2 variants (resulting in p.S222G, p.P497H, p.P506S, p.T487I (two cases), and p.P497L (three cases)). Using multiplexed (5-label) fluorescent immunohistochemistry, we mapped the co-localisation of ubiquilin 2 with phosphorylated TDP-43, dipeptide repeat aggregates, and p62, in the hippocampus of controls (n = 6), or amyotrophic lateral sclerosis with or without frontotemporal dementia in sporadic (n = 20), unknown familial (n = 3), SOD1-linked (n = 1), FUS-linked (n = 1), C9orf72-linked (n = 5), and UBQLN2-linked (n = 8) cases. We differentiate between i) ubiquilin 2 aggregation together with phosphorylated TDP-43 or dipeptide repeat proteins, and ii) ubiquilin 2 self-aggregation promoted by UBQLN2 pathogenic variants that cause amyotrophic lateral sclerosis/and frontotemporal dementia. Overall, we describe a hippocampal protein aggregation signature that fully distinguishes mutant from wildtype ubiquilin 2 in amyotrophic lateral sclerosis with or without frontotemporal dementia, whereby mutant ubiquilin 2 is more prone than wildtype to aggregate independently of driving factors. This neuropathological signature can be used to assess the pathogenicity of UBQLN2 gene variants and to understand the mechanisms of UBQLN2-linked disease.

Latent profile analysis reveals overlapping ARFID and shape/weight motivations for restriction in eating disorders.

BACKGROUND: DSM-5 differentiates avoidant/restrictive food intake disorder (ARFID) from other eating disorders (EDs) by a lack of overvaluation of body weight/shape driving restrictive eating. However, clinical observations and research demonstrate ARFID and shape/weight motivations sometimes co-occur. To inform classification, we: (1) derived profiles underlying restriction motivation and examined their validity and (2) described diagnostic characterizations of individuals in each profile to explore whether findings support current diagnostic schemes. We expected, consistent with DSM-5, that profiles would comprise individuals endorsing solely ARFID or restraint (i.e. trying to eat less to control shape/weight) motivations. METHODS: We applied latent profile analysis to 202 treatment-seeking individuals (ages 10-79 years [M = 26, s.d. = 14], 76% female) with ARFID or a non-ARFID ED, using the Nine-Item ARFID Screen (Picky, Appetite, and Fear subscales) and the Eating Disorder Examination-Questionnaire Restraint subscale as indicators. RESULTS: A 5-profile solution emerged: Restraint/ARFID-Mixed (n = 24; 8% [n = 2] with ARFID diagnosis); ARFID-2 (with Picky/Appetite; n = 56; 82% ARFID); ARFID-3 (with Picky/Appetite/Fear; n = 40; 68% ARFID); Restraint (n = 45; 11% ARFID); and Non-Endorsers (n = 37; 2% ARFID). Two profiles comprised individuals endorsing solely ARFID motivations (ARFID-2, ARFID-3) and one comprising solely restraint motivations (Restraint), consistent with DSM-5. However, Restraint/ARFID-Mixed (92% non-ARFID ED diagnoses, comprising 18% of those with non-ARFID ED diagnoses in the full sample) endorsed ARFID and restraint motivations. CONCLUSIONS: The heterogeneous profiles identified suggest ARFID and restraint motivations for dietary restriction may overlap somewhat and that individuals with non-ARFID EDs can also endorse high ARFID symptoms. Future research should clarify diagnostic boundaries between ARFID and non-ARFID EDs.

Cognitive-behavioral therapy for avoidant/restrictive food intake disorder: A proof-of-concept for mechanisms of change and target engagement.

BACKGROUND: Cognitive-behavioral therapy for avoidant/restrictive food intake disorder (ARFID; CBT-AR) theoretically targets three prototypic motivations (sensory sensitivity, lack of interest/low appetite, fear of aversive consequences), aligned with three modularized interventions. As an exploratory investigation, we: (1) evaluated change in candidate mechanisms in relationship to change in ARFID severity, and (2) tested if assignment (vs. not) to a module resulted in larger improvements in the corresponding mechanism. METHOD: Males and females (N = 42; 10-55 years) participated in an open trial of CBT-AR. RESULTS: Decreases in scaled scores for each candidate mechanism had medium to large correlations with decreases in ARFID severity-sensory sensitivity: -0.7 decrease (r = .42, p = .01); lack of interest/low appetite: -0.3 decrease (r = .60, p < .0001); and fear of aversive consequences: -1.1 decrease (r = .33, p = .05). Linear mixed models revealed significant weekly improvements for each candidate mechanism across the full sample (ps < .0001). There were significant interactions for the sensory and fear of aversive consequences modules-for each, participants who received the corresponding module had significantly larger decreases in the candidate mechanism than those who did not receive the module. DISCUSSION: Sensory sensitivity and fear of aversive consequences improved more if the CBT-AR module was received, but lack of interest/low appetite may improve regardless of receipt of the corresponding module. Future research is needed to test target engagement in CBT-AR with adaptive treatment designs, and to identify valid and sensitive measures of candidate mechanisms. PUBLIC SIGNIFICANCE: The mechanisms through which components of CBT-AR work have yet to be elucidated. We conducted an exploratory investigation to test if assignment (vs. not) to a CBT-AR module resulted in larger improvements in the corresponding prototypic ARFID motivation that the module intended to target. Measures of the sensory sensitivity and the fear of aversive consequences motivations improved more in those who received the corresponding treatment module, whereas the lack of interest/low appetite measure improved regardless of if the corresponding module was received.

Medical Comorbidities, Nutritional Markers, and Cardiovascular Risk Markers in Youth With ARFID.

OBJECTIVE: Avoidant/restrictive food intake disorder (ARFID) is common among populations with nutrition-related medical conditions. Less is known about the medical comorbidity/complication frequencies in youth with ARFID. We evaluated the medical comorbidities and metabolic/nutritional markers among female and male youth with full/subthreshold ARFID across the weight spectrum compared with healthy controls (HC). METHOD: In youth with full/subthreshold ARFID (n = 100; 49% female) and HC (n = 58; 78% female), we assessed self-reported medical comorbidities via clinician interview and explored abnormalities in metabolic (lipid panel and high-sensitive C-reactive protein [hs-CRP]) and nutritional (25[OH] vitamin D, vitamin B12, and folate) markers. RESULTS: Youth with ARFID, compared with HC, were over 10 times as likely to have self-reported gastrointestinal conditions (37% vs. 3%; OR = 21.2; 95% CI = 6.2-112.1) and over two times as likely to have self-reported immune-mediated conditions (42% vs. 24%; OR = 2.3; 95% CI = 1.1-4.9). ARFID, compared with HC, had a four to five times higher frequency of elevated triglycerides (28% vs. 12%; OR = 4.0; 95% CI = 1.7-10.5) and hs-CRP (17% vs. 4%; OR = 5.0; 95% CI = 1.4-27.0) levels. DISCUSSION: Self-reported gastrointestinal and certain immune comorbidities were common in ARFID, suggestive of possible bidirectional risk/maintenance factors. Elevated cardiovascular risk markers in ARFID may be a consequence of limited dietary variety marked by high carbohydrate and sugar intake.

Characterization of neurofibrillary tangle immunophenotype signatures to classify tangle maturity in Alzheimer's disease.

INTRODUCTION: Tau aggregation into neurofibrillary tangles in Alzheimer's disease (AD) is a dynamic process involving changes in tau phosphorylation, isoform composition, and morphology. To facilitate studies of tangle maturity, we developed an image analysis pipeline to study antibody labeling signatures that can distinguish tangle maturity levels in AD brain tissue. METHODS: Using fluorescent immunohistochemistry, we co-labeled AD brain tissue with four antibodies that bind different tau epitopes. Mean fluorescence intensity of each antibody was measured, and spectral clustering was used to identify tangle immunophenotypes. RESULTS: Five distinct tangle populations were identified, and different tangle maturity immunophenotypes were identified with increasing Braak stage. Early tangle immunophenotypes were more prevalent in later affected regions and advanced immunophenotypes were associated with ghost morphology. DISCUSSION: Our findings indicate that tangle populations characterized by advanced tau immunophenotypes are associated with higher Braak stage and more mature morphology, providing a new framework for defining tangle maturity levels using tau antibody signatures. HIGHLIGHTS: Populations of neurofibrillary tangles exist in Alzheimer's disease. The immunophenotype of neurofibrillary tangle populations relates to their maturity. The most advanced immunophenotypes are associated with higher Braak stage. The most advanced immunophenotypes are associated with ghost morphology. The most immature immunophenotypes are associated with later affected regions.

Validation of the youth-nine item avoidant/restrictive food intake disorder screen.

OBJECTIVE: This study assessed the factorial, divergent, and criterion-related validity of the Youth-Nine Item Avoidant/Restrictive Food Intake Disorder (ARFID) Screen (Y-NIAS) in a paediatric clinical sample at initial evaluation for an eating disorder (ED). METHOD: Participants included 310 patients (82.9% female, 77.4% White, Age M = 14.65) from a tertiary ED clinic. Confirmatory factor analysis (CFA) evaluated the three-factor of the Y-NIAS. One-way analysis of variance compared Y-NIAS scores across diagnoses. A receiver operating curve analysis assessed the ability of each subscale to identify ARFID presentations from the full sample. Two logistic regressions assessed the criterion-related validity of the obtained Y-NIAS cut-scores. RESULTS: CFA supported the original three-factor structure of the Y-NIAS. Clinically-elevated scores were observed in all diagnostic groups except for binge-eating disorder. Subscales were unable to discriminate ARFID cases from other ED diagnoses. Cut scores were identified for picky eating subscale (10) and Fear subscale (9), but not for Appetite subscale. In combination with the ED Examination Questionnaire (EDE-Q), classification accuracy was moderate for ARFID (62.7%) and other EDs (89.4%). DISCUSSION: The Y-NIAS demonstrated excellent factorial validity and internal consistency. Findings were mixed regarding the utility of the Y-NIAS for identifying clinically-significant ARFID presentations from other ED diagnoses.

The Intersection of Disorders of Gut-Brain Interaction With Avoidant/Restrictive Food Intake Disorder.

High rates of overlap exist between disorders of gut-brain interaction (DGBI) and eating disorders, for which common interventions conceptually conflict. There is particularly increasing recognition of eating disorders not centered on shape/weight concerns, specifically avoidant/restrictive food intake disorder (ARFID) in gastroenterology treatment settings. The significant comorbidity between DGBI and ARFID highlights its importance, with 13% to 40% of DGBI patients meeting full criteria for or having clinically significant symptoms of ARFID. Notably, exclusion diets may put some patients at risk for developing ARFID and continued food avoidance may perpetuate preexisting ARFID symptoms. In this review, we introduce the provider and researcher to ARFID and describe the possible risk and maintenance pathways between ARFID and DGBI. As DGBI treatment recommendations may put some patients at risk for developing ARFID, we offer recommendations for practical treatment management including evidence-based diet treatments, treatment risk counseling, and routine diet monitoring. When implemented thoughtfully, DGBI and ARFID treatments can be complementary rather than conflicting.

Evaluation of the MOVE online exercise programme for young people aged 13-30.

PURPOSE: To evaluate the MOVE exercise programme in supporting the recovery of young people affected by cancer. METHODS: Participants in an 8-week exercise rehabilitation programme delivered online by cancer rehabilitation specialists completed self-reported questionnaires at baseline and after programme completion. Assessments included cancer-related fatigue (FACIT fatigue scale) and health-related quality of life (EORTC-QLC-30). Qualitative data were provided through written accounts of participant experiences and underwent content analysis. RESULTS: Seventy-one participants commenced the exercise rehabilitation programme and 57 completed the programme and provided data for analysis (63% female; median age 22 years). Statistically significant improvements were observed in post-programme scores for all measured outcomes (cancer-related fatigue, quality of life, physical functioning, role functioning, emotional functioning). Content analysis of written experiences generated ten unique codes. The highest frequency codes were enjoyment (n = 34), motivation (n = 14) and fitness (n = 13). CONCLUSIONS: These findings indicate feasibility of delivery, acceptability to patients and physical and psychological benefits of a personalised online exercise rehabilitation programme for young people living with and beyond cancer. Further research involving a control arm and long-term follow-up would be beneficial. IMPLICATIONS FOR CANCER SURVIVORS: These results support the inclusion of a personalised exercise programme as part of cancer rehabilitation for young people living with and beyond cancer.

Preliminary data that psychological treatment and baseline anxiety are associated with a decrease in postprandial fullness and early satiation for individuals with bulimia nervosa and related other specified feeding or eating disorder.

OBJECTIVE: Gastrointestinal symptoms, particularly postprandial fullness, are frequently reported in eating disorders. Limited data exist evaluating how these symptoms change in response to outpatient psychological treatment. The current study sought to describe the course of postprandial fullness and early satiation across psychological treatment for adults with bulimia nervosa and related other specified feeding or eating disorders and to test if anxiety moderates treatment response. METHODS: Secondary data analysis was conducted on questionnaire data provided by 30 individuals (80% white, M(SD)age = 31.43(13.44) years; 90% female) throughout treatment and six-month follow-up in a pilot trial comparing mindfulness and acceptance-based treatment with cognitive-behavioral therapy for bulimia nervosa. Participants completed items from the Rome IV Diagnostic Questionnaire for Adult Functional Gastrointestinal Disorders and the State Trait Anxiety Inventory. RESULTS: Postprandial fullness and early satiation both significantly decreased over time (ds = 1.23-1.54; p's < .001). Baseline trait anxiety moderated this outcome, such that greater decreases were observed for those with higher baseline anxiety (p = .02). DISCUSSION: Results extend prior work in inpatient samples by providing preliminary data that postprandial fullness and early satiation decrease with outpatient psychological treatment for bulimia nervosa. Baseline anxiety moderated this effect for postprandial fullness. Future work should replicate findings in a larger sample and test anxiety as a mechanism underlying postprandial fullness in eating disorders. PUBLIC SIGNIFICANCE: The current study found that common gastrointestinal symptoms (postprandial fullness and early satiation) decrease over the course of outpatient psychotherapy for adults with full and subthreshold bulimia nervosa. Postprandial fullness decreased more across time for those high in anxiety.

Development of a brief cognitive-behavioral treatment for avoidant/restrictive food intake disorder in the context of disorders of gut-brain interaction: Initial feasibility, acceptability, and clinical outcomes.

BACKGROUND: Avoidant/restrictive food intake disorder (ARFID) symptoms are common (up to 40%) among adults with disorders of gut-brain interaction (DGBI), but treatments for this population (DGBI + ARFID) have yet to be evaluated. We aimed to identify initial feasibility, acceptability, and clinical effects of an exposure-based cognitive-behavioral treatment (CBT) for adults with DGBI + ARFID. METHODS: Patients (N = 14) received CBT as part of routine care in an outpatient gastroenterology clinic. A two-part investigation of the CBT included a retrospective evaluation of patients who were offered a flexible (8-10) session length and an observational prospective study of patients who were offered eight sessions. Feasibility benchmarks were ≥75% completion of sessions, quantitative measures (for treatment completers), and qualitative interviews. Acceptability was assessed with a benchmark of ≥70% patients reporting a posttreatment satisfaction scores ≥3 on 1-4 scale and with posttreatment qualitative interviews. Mixed model analysis explored signals of improvement in clinical outcomes. RESULTS: All feasibility and acceptability benchmarks were achieved (and qualitative feedback revealed high satisfaction with the treatment and outcomes). There were improvements in clinical outcomes across treatment (all p's < .0001) with large effects for ARFID fear (-52%; Hedge's g = 1.5; 95% CI = 0.6, 2.5) and gastrointestinal-specific anxiety (-42%; Hedge's g = 1.0; 95% CI = 0.5, 16). Among those who needed to gain weight (n = 10), 94%-103% of expected weight gain goals were achieved. DISCUSSION: Initial development and testing of a brief 8-session CBT protocol for DGBI + ARFID showed high feasibility, acceptability, and promising clinical improvements. Findings will inform an NIH Stage 1B randomized control trial. PUBLIC SIGNIFICANCE: While cognitive-behavioral treatments (CBTs) for ARFID have been created in outpatient feeding and eating disorder clinics, they have yet to be developed and refined for other clinic settings or populations. In line with the recommendations for behavioral treatment development, we conducted a two-part investigation of an exposure-based CBT for a patient population with high rates of ARFID-adults with disorders of gut-brain interaction (also known as functional gastrointestinal disorders). We found patients had high satisfaction with treatment and there were promising improvements for both gastrointestinal and ARFID outcomes. The refined treatment includes eight sessions delivered by a behavioral health care provider and the findings reported in this article will be studied next in an NIH Stage 1B randomized controlled trial.

Prefrontal cortex activation by binge-eating status in individuals with obesity while attempting to reappraise responses to food using functional near infrared spectroscopy.

PURPOSE: Difficulty reappraising drives to consume palatable foods may promote poorer inhibition and binge eating (BE) in adults with obesity, but neural underpinnings of food-related reappraisal are underexamined. METHODS: To examine neural correlates of food-related reappraisal, adults with obesity with and without BE wore a portable neuroimaging tool, functional near-infrared spectroscopy (fNIRS). fNIRS measured activity in the prefrontal cortex while participants watched videos of food and attempt to "resist" the food stimuli (i.e., "consider the negative consequences of eating the food"). RESULTS: Participants (N = 32, 62.5% female; BMI 38.6 [Formula: see text] 7.1; 43.5 [Formula: see text] 13.4 y) had a BMI > 30 kg/m2. Eighteen adults (67.0% female; BMI 38.2 [Formula: see text] 7.6) reported BE (≥ 12 BE-episodes in preceding 3 months). The control group comprised 14 adults who denied BE (64.0% female; BMI 39.2 [Formula: see text] 6.6). Among the entire sample, mixed models showed significant, small hyperactivation during crave and resist compared to watch (relax) condition bilaterally in the medial superior frontal gyrus, dorsolateral areas, and middle frontal gyrus (optodes 5, 7, 9, 10, 11, and 12) in the total sample. No statistically significant differences in neural activation were observed between the BE and control group. Moreover, there were no significant group by condition interactions on neural activation. CONCLUSION: Among adults with obesity, BE status was not linked to differential activation in inhibitory prefrontal cortex areas during a food-related reappraisal task. Future research is needed with larger samples, adults without obesity, and inhibition paradigms with both behavioral and cognitive components. LEVEL OF EVIDENCE: Level III: Evidence obtained from well-designed cohort or case-control analytic studies. TRIAL REGISTRATION: # NCT03113669, date April 13, 2017.

Assessing the presence and motivations of orthorexia nervosa among athletes and adults with eating disorders: a cross-sectional study.

PURPOSE: Orthorexia nervosa involves restricting diet based on quality rather than quantity. Although orthorexia is well reported in many at-risk populations, limited data addresses its presence in individuals with eating disorder history (EDs) or athletes. We aimed to identify the presence and potential drivers of orthorexia in adults with EDs and endurance athletes, compared to control subjects. METHODS: Participants ≥ 18y included: people with a diagnosed eating disorder (ED as per DSM-5); endurance athletes (training/competing ≥ 5 h/week); or control subjects. Participants (n = 197) completed an online survey assessing orthorexia (eating habits questionnaire, EHQ), eating motivations (TEMS-B) and compulsive exercise (CET). RESULTS: ED had the highest orthorexia symptom severity (92.0 ± 3.02, n = 32), followed by athletes (76.2 ± 2.74, n = 54) and controls (71.0 ± 1.80, n = 111) (F (2) = 18.2, p < 0.001). A strong positive correlation existed between weight control motives and higher orthorexia symptom severity (r = 0.54, 95% CI [1.35, 2.36], p < 0.001), while a weak negative association existed between Hunger and Pleasure motives and higher orthorexia symptom severity (r = 0.23, 95% CI [- 2.24, - 0.34], p = 0.008; r = 0.26, 95% CI [- 2.11, - 0.47], p = 0.002, respectively). A moderate positive relationship was found between CET and orthorexia symptom severity (95% CI [1.52, 3.12], p < 0.001). CONCLUSION: Adults with ED history and endurance athletes have greater orthorexia symptom severity compared to control. Clinicians working with at-risk populations should screen patients and be aware of red-flags of orthorexic traits, desire to control weight, and compulsive exercise behavior. LEVEL OF EVIDENCE: III: Evidence obtained from cohort studies.

Psychological Considerations in the Dietary Management of Patients With DGBI.

In this article, an expert team of 2 gastro-psychologists, a dietician, and an academic gastroenterologist provides insights into the psychological and social implications of evidence-based and "popular" dietary interventions in disorders of gut-brain interaction (DGBI). We focus on practical approaches for evaluating a patient's appropriateness for a dietary intervention, considering the nutritional, psychological, behavioral, and social context in which a patient may find themselves managing their DGBI with dietary intervention. We also discuss how to identify risk factors for and symptoms of avoidant/restrictive food intake disorder, a growing concern in the DGBI population.

Prevalence and Characteristics of Avoidant/Restrictive Food Intake Disorder in Pediatric Neurogastroenterology Patients.

ABSTRACT: Recent reports document avoidant/restrictive food intake disorder (ARFID) symptoms among 13-40% of adults presenting to neurogastroenterology clinics, but ARFID in pediatrics is understudied. We conducted a retrospective review of charts from 129 consecutive referrals (ages 6-18 years; 57% female) for pediatric neurogastroenterology examination, from January 2016 through December 2018. Eleven cases (8%) met the full criteria for ARFID by the Diagnostic and Statistical Manual of Mental Disorders, 5th edition and 19 cases (15%) had clinically significant avoidant/ restrictive eating behaviors with insufficient information for a definitive ARFID diagnosis. Of patients with ARFID symptoms (n = 30), 20 (67%) cited fear of gastrointestinal symptoms as motivation for their avoidant/ restrictive eating. Compared to patients without ARFID symptoms, patients with ARFID symptoms were older (P  < .001), more likely to be female (51% vs 79%, P  = 0.014), and more frequently presented with eating/weight-related complaints (15% vs 33%, P  = 0.026). This pilot retrospective study showed ARFID symptoms present in 23% of pediatric neurogastroenterology patients; further research is needed to understand risk and maintenance factors of ARFID in the neurogastroenterology setting.

Food neophobia as a mechanism of change in video-delivered cognitive-behavioral therapy for avoidant/restrictive food intake disorder: A case study.

OBJECTIVE: The mechanisms through which cognitive-behavioral therapies (CBTs) for avoidant/restrictive food intake disorder (ARFID) may work have yet to be elucidated. To inform future treatment revisions to increase parsimony and potency of CBT for ARFID (CBT-AR), we evaluated change in food neophobia during CBT-AR treatment of a sensory sensitivity ARFID presentation via a single case study. METHOD: An adolescent male completed 21, twice-weekly sessions of CBT-AR via live video delivery. From pre- to mid- to post-treatment and at 2-month follow-up, we calculated percent change in food neophobia and ARFID symptom severity measures. Via visual inspection, we explored trajectories of week-by-week food neophobia in relation to clinical improvements (e.g., when the patient incorporated foods into daily life). RESULTS: By post-treatment, the patient achieved reductions across food neophobia (45%), and ARFID severity (53-57%) measures and no longer met criteria for ARFID, with sustained improvement at 2-month follow-up. Via visual inspection of week-by-week food neophobia trajectories, we identified that decreases occurred after mid-treatment and were associated with incorporation of a food directly tied to the patient's main treatment motivation. DISCUSSION: This study provides hypothesis-generating findings on candidate CBT-AR mechanisms, showing that changes in food neophobia were related to food exposures most connected to the patient's treatment motivations. PUBLIC SIGNIFICANCE: Cognitive-behavioral therapies (CBTs) can be effective for treating avoidant/restrictive food intake disorder (ARFID). However, we do not yet have evidence to show how they work. This report of a single patient shows that willingness to try new foods (i.e., food neophobia), changed the most when the patient experienced a clinical improvement most relevant to his motivation for seeking treatment.

Validation of the food craving Acceptance and action questionnaire (FAAQ) in a weight loss-seeking sample.

OBJECTIVE: The Food Craving Acceptance and Action Questionnaire (FAAQ) was developed to measure psychological flexibility around food-related internal experiences (e.g., thoughts, feelings, urges) and has two subscales, acceptance and willingness. However, the FAAQ factor structure has not yet been systematically validated with a clinically relevant sample. METHODS: Two weight-loss treatment seeking samples (total N = 462; 80.4% female) ages 18 to 70 (M = 52.6, SD = 9.8) completed the FAAQ before and after group-based treatment of overweight or obesity. RESULTS: Confirmatory factor analysis on the FAAQ's previously observed two-factor model produced poor model fit. An alternative 7-item model removing specific items that contributed to poor fit and were conceptually relevant to remove provided good model fit. The resulting revised 7-item FAAQ (items 1,3,6 removed) had adequate internal consistency and significant predictive validity for the Total score and subscales, and showed initial construct validity for the Total score. CONCLUSIONS: Results from this study suggest researchers and clinicians should now use the 7-item FAAQ-II, which retains the Willingness and Acceptance subscales. Future research is needed with other relevant samples to confirm the FAAQ-II's factor structure and psychometric properties.

fISHing with immunohistochemistry for housekeeping gene changes in Alzheimer's disease using an automated quantitative analysis workflow.

In situ hybridization (ISH) is a powerful tool that can be used to localize mRNA expression in tissue samples. Combining ISH with immunohistochemistry (IHC) to determine cell type provides cellular context of mRNA expression, which cannot be achieved with gene microarray or polymerase chain reaction. To study mRNA and protein expression on the same section we investigated the use of RNAscope® ISH in combination with fluorescent IHC on paraffin-embedded human brain tissue. We first developed a high-throughput, automated image analysis workflow for quantifying RNA puncta across the total cell population and within neurons identified by NeuN+ immunoreactivity. We then applied this automated analysis to tissue microarray (TMA) sections of middle temporal gyrus tissue (MTG) from neurologically normal and Alzheimer's Disease (AD) cases to determine the suitability of three commonly used housekeeping genes: ubiquitin C (UBC), peptidyl-prolyl cis-trans isomerase B (PPIB) and DNA-directed RNA polymerase II subunit RPB1 (POLR2A). Overall, we saw a significant decrease in total and neuronal UBC expression in AD cases compared to normal cases. Total expression results were validated with RT-qPCR using fresh frozen tissue from 5 normal and 5 AD cases. We conclude that this technique combined with our novel automated analysis pipeline provides a suitable platform to study changes in gene expression in diseased human brain tissue with cellular and anatomical context. Furthermore, our results suggest that UBC is not a suitable housekeeping gene in the study of post-mortem AD brain tissue.

Validating the visceral sensitivity index in an eating disorder sample.

OBJECTIVE: Individuals with eating disorders (EDs) often have difficulty tolerating uncomfortable body sensations. As such, anxiety sensitivity specific to gastrointestinal (GI) sensations, has relevance for EDs. However, to date, no validated measures of this construct exist in EDs. Thus, the present study sought to validate the visceral sensitivity index (VSI), a 15-item measure originally validated in an irritable bowel syndrome sample, in an ED sample and explore associations with ED symptoms. METHOD: Two hundred and sixty-six adolescents (n = 116) and adults (n = 150) in an ED partial hospital program completed the VSI and related measures at admission. Confirmatory factor analysis examined the factor structure of the VSI and hierarchical regression analyses explored associations between the VSI and ED symptoms. RESULTS: The original version of the VSI had adequate model fit. An alternative 13-item model removing specific items with poor fit and less theoretical relevance to EDs also demonstrated good fit. The 15-item and 13-item VSI had strong internal consistency (α = .93-.94), and correlation results supported the convergent and divergent validity of both versions. Higher visceral sensitivity was associated with elevated body dissatisfaction, cognitive restraint, purging, restricting, and excessive exercise (p-values <.05), beyond length of illness, body mass index, and trait anxiety. DISCUSSION: Results support the relevance of GI-specific anxiety in EDs and suggest that the original 15-item VSI and modified 13-item VSI have strong psychometric properties in an ED sample. Given comparable model fit and psychometric properties, both versions of the VSI may be used for future ED research.

Validation of the nine item ARFID screen (NIAS) subscales for distinguishing ARFID presentations and screening for ARFID.

OBJECTIVE: The Nine Item Avoidant/Restrictive Food Intake Disorder (ARFID) Screen (NIAS) has three subscales aligned with ARFID presentations but clinically validated cutoff scores have not been identified. We aimed to examine NIAS subscale (picky eating, appetite, fear) validity to: (1) capture clinically-diagnosed ARFID presentations; (2) differentiate ARFID from other eating disorders (other-ED); and (3) capture ARFID symptoms among individuals with ARFID, individuals with other-ED, and nonclinical participants. METHOD: Participants included outpatients (ages 10-76 years; 75% female) diagnosed with ARFID (n = 49) or other-ED (n = 77), and nonclinical participants (ages 22-68 years; 38% female, n = 40). We evaluated criterion-related concurrent validity by conducting receiver operating curve (ROC) analyses to identify potential subscale cutoffs and by testing if cutoffs could capture ARFID with and without use of the Eating Disorder Examination-Questionnaire (EDE-Q). RESULTS: Each NIAS subscale had high AUC for capturing those who fit versus do not fit each ARFID presentation, resulting in proposed cutoffs of ≥10 (sensitivity = .97, specificity = .63), ≥9 (sensitivity = .86, specificity = .70), and ≥ 10 (sensitivity = .68, specificity = .89) on the NIAS-picky eating, NIAS-appetite, and NIAS-fear subscales, respectively. ARFID versus other-ED had high AUC on the NIAS-picky eating (≥10 proposed cutoff), but not NIAS-appetite or NIAS-fear subscales. NIAS subscale cutoffs had a high association with ARFID diagnosis, but only correctly classified other-ED in combination with EDE-Q Global <2.3. DISCUSSION: To screen for ARFID, we recommend using a screening tool for other-ED (e.g., EDE-Q) in combination with a positive score on any NIAS subscale (i.e., ≥10, ≥9, and/or ≥10 on the NIAS-picky eating, NIAS-appetite, and NIAS-fear subscales, respectively).

Mindfulness and acceptance-based behavioral treatment for bulimia-spectrum disorders: A pilot feasibility randomized trial.

OBJECTIVE: Although existing research supports the efficacy of mindfulness- and acceptance-based treatments (MABTs) for eating disorders (EDs), few studies have directly compared outcomes from MABTs to standard CBT. METHOD: Participants (N = 44), treatment-seeking adults with bulimia-spectrum EDs, were screened for eligibility, consented, and randomized to receive 20 sessions of outpatient, individual CBT or MABT treatment. Treatment outcomes (binge eating and compensatory behavior episodes, global ED severity, depressive symptoms, quality of life, emotional awareness/clarity, distress tolerance, values-based decision-making, and emotion modulation) were measured at pre-treatment, post-treatment, and 6-month follow up. Data on feasibility and acceptability are also presented. RESULTS: Treatment and assessment retention rates were comparable between MABT and CBT (p range = .51-.73) and between-group differences on acceptability measures were very small (d range = 0.03-0.19). Both conditions produced notable and generally comparable changes in most treatment outcomes at post-treatment (within group d range = 0.06-1.77). DISCUSSION: The MABT and CBT conditions demonstrated comparable degrees of feasibility, acceptability, and symptom improvement, suggesting that MABTs warrant further evaluation as ED treatments.