Emotion coaching skills as an augmentation to family-based therapy for adolescents with anorexia nervosa: A pilot effectiveness study with families with high expressed emotion.

OBJECTIVE: To examine the feasibility and acceptability of augmenting family-based treatment (FBT) for adolescents with anorexia nervosa (AN) or atypical anorexia nervosa (AAN) with a parent emotion coaching intervention (EC) focused on reducing parent expressed emotion. METHOD: In this pilot effectiveness trial, families of adolescents with AN/AAN exhibiting high expressed emotion received standard FBT with either (1) EC group or (2) support group (an attention control condition focused on psychoeducation). RESULTS: Forty-one adolescents with AN or AAN were recruited (88% female, Mage = 14.9 ± 1.6 years, 95% White: Non-Hispanic, 1% White: Hispanic, 1% Bi-racial: Asian). Most study adolescents were diagnosed with AN (59%) while 41% were diagnosed with AAN. Participating parents were predominantly mothers (95%). Recruitment and retention rates were moderately high (76% and 71%, respectively). High acceptability and feasibility ratings were obtained from parents and interventionists with 100% reporting the EC intervention was "beneficial"-"very beneficial." The FBT + EC group demonstrated higher parental warmth scores at post-treatment compared to the control group (standardized effect size difference, d = 1.58), which was maintained at 3-month follow-up. Finally, at post-treatment, the FBT + EC group demonstrated higher rates of full remission from AN/AAN (40%) compared to FBT + support (27%), and were nine times more likely to be weight restored by 3-month follow-up. DISCUSSION: Augmenting FBT with emotion coaching for parents with high expressed emotion is acceptable, feasible, and demonstrates preliminary effectiveness. PUBLIC SIGNIFICANCE: Family based treatment for AN/AAN is the recommended treatment for youth but families with high criticism/low warmth are less likely to respond to this treatment. Adding a parent emotion coaching group (EC) where parents learn to talk to their adolescents about tough emotions is feasible and well-liked by families.

Divergent Histopathological Networks of Frontotemporal Degeneration Proteinopathy Subytpes.

Network analyses inform complex systems such as human brain connectivity, but this approach is seldom applied to gold-standard histopathology. Here, we use two complimentary computational approaches to model microscopic progression of the main subtypes of tauopathy versus TDP-43 proteinopathy in the human brain. Digital histopathology measures were obtained in up to 13 gray matter (GM) and adjacent white matter (WM) cortical brain regions sampled from 53 tauopathy and 66 TDP-43 proteinopathy autopsy patients. First, we constructed a weighted non-directed graph for each group, where nodes are defined as GM and WM regions sampled and edges in the graph are weighted using the group-level Pearson's correlation coefficient for each pairwise node comparison. Additionally, we performed mediation analyses to test mediation effects of WM pathology between anterior frontotemporal and posterior parietal GM nodes. We find greater correlation (i.e., edges) between GM and WM node pairs in tauopathies compared with TDP-43 proteinopathies. Moreover, WM pathology strongly correlated with a graph metric of pathology spread (i.e., node-strength) in tauopathies (r = 0.60, p < 0.03) but not in TDP-43 proteinopathies (r = 0.03, p = 0.9). Finally, we found mediation effects for WM pathology on the association between anterior and posterior GM pathology in FTLD-Tau but not in FTLD-TDP. These data suggest distinct tau and TDP-43 proteinopathies may have divergent patterns of cellular propagation in GM and WM. More specifically, axonal spread may be more influential in FTLD-Tau progression. Network analyses of digital histopathological measurements can inform models of disease progression of cellular degeneration in the human brain.SIGNIFICANCE STATEMENT In this study, we uniquely perform two complimentary computational approaches to model and contrast microscopic disease progression between common frontotemporal lobar degeneration (FTLD) proteinopathy subtypes with similar clinical syndromes during life. Our models suggest white matter (WM) pathology influences cortical spread of disease in tauopathies that is less evident in TDP-43 proteinopathies. These data support the hypothesis that there are neuropathologic signatures of cellular degeneration within neurocognitive networks for specific protienopathies. These distinctive patterns of cellular pathology can guide future efforts to develop tissue-sensitive imaging and biological markers with diagnostic and prognostic utility for FTLD. Moreover, our novel computational approach can be used in future work to model various neurodegenerative disorders with mixed proteinopathy within the human brain connectome.

Associations of phosphorylated tau pathology with whole-hemisphere ex vivo morphometry in 7 tesla MRI.

INTRODUCTION: Neurodegenerative disorders are associated with different pathologies that often co-occur but cannot be measured specifically with in vivo methods. METHODS: Thirty-three brain hemispheres from donors with an Alzheimer's disease (AD) spectrum diagnosis underwent T2-weighted magnetic resonance imaging (MRI). Gray matter thickness was paired with histopathology from the closest anatomic region in the contralateral hemisphere. RESULTS: Partial Spearman correlation of phosphorylated tau and cortical thickness with TAR DNA-binding protein 43 (TDP-43) and α-synuclein scores, age, sex, and postmortem interval as covariates showed significant relationships in entorhinal and primary visual cortices, temporal pole, and insular and posterior cingulate gyri. Linear models including Braak stages, TDP-43 and α-synuclein scores, age, sex, and postmortem interval showed significant correlation between Braak stage and thickness in the parahippocampal gyrus, entorhinal cortex, and Broadman area 35. CONCLUSION: We demonstrated an association of measures of AD pathology with tissue loss in several AD regions despite a limited range of pathology in these cases. HIGHLIGHTS: Neurodegenerative disorders are associated with co-occurring pathologies that cannot be measured specifically with in vivo methods. Identification of the topographic patterns of these pathologies in structural magnetic resonance imaging (MRI) may provide probabilistic biomarkers. We demonstrated the correlation of the specific patterns of tissue loss from ex vivo brain MRI with underlying pathologies detected in postmortem brain hemispheres in patients with Alzheimer's disease (AD) spectrum disorders. The results provide insight into the interpretation of in vivo structural MRI studies in patients with AD spectrum disorders.

Predictors of caregiver burden before starting family-based treatment for adolescent anorexia nervosa and associations with weight gain during treatment.

PURPOSE: Caregivers play a pivotal role in the success of family-based treatment (FBT) for anorexia nervosa (AN). Caregiver burden is frequently demonstrated in eating disorders (EDs) and may impact FBT outcomes. This study examined factors associated with caregiver burden before starting FBT and whether pre-treatment caregiver burden was associated with weight gain during FBT. METHODS: Participants included 114 adolescents with AN or atypical AN (mean age = 15.6 years, SD = 1.4) and a primary caregiver (87.6% mothers) who received FBT in the United States. Before starting treatment, participants completed self-report measures of caregiver burden (via the Eating Disorder Symptom Impact Scale), caregiver anxiety, caregiver depression, and ED symptoms. Clinical characteristics and percentage of target goal weight (%TGW) at FBT session 1 and 3 and 6 months after starting treatment were obtained via retrospective chart review. Hierarchical regressions examined predictors of caregiver burden before FBT initiation. Associations between pre-treatment caregiver burden and %TGW gain at 3 and 6 months after starting FBT were assessed with hierarchical regressions. RESULTS: Caregiver anxiety (p < 0.001), family history of EDs (p = 0.028), adolescent mental health treatment history (p = 0.024), and ED symptoms (p = 0.042) predicted caregiver burden before starting FBT. Pre-treatment caregiver burden was not associated with %TGW gain at 3 or 6 months. Males demonstrated less %TGW gain than females at 3 months (p = 0.010) and 6 months (p = 0.012). CONCLUSION: Proactively evaluating caregiver burden before starting FBT is suggested. Providing recommendations and/or referrals for identified caregiver vulnerabilities could indirectly impact FBT progress. Males in FBT could require longer courses of treatment and extra vigilance to this demographic is suggested. LEVEL OF EVIDENCE: Level III, case-control analytic study.

Caregiver and adolescent intuitive eating behavior: associations with weight change during family-based treatment for anorexia nervosa.

PURPOSE: Intuitive eating (IE) is an adaptive eating construct for which little research exists in eating disorder (ED) samples. IE is negatively correlated with disordered eating behaviors in healthy adolescents and adults, and similar associations have been found in adults with EDs. This study aims to examine IE in a treatment seeking sample of adolescents and their caregivers to understand the role of IE in weight gain during FBT. METHODS: Descriptive statistics and bivariate correlations were calculated in a sample of 47 pairs of adolescent patients and their caregivers who initiated outpatient FBT at a large academic medical center. Analyses examined associations between caregiver and adolescent IE on the Intuitive Eating Scale (IES), change in percent expected body weight (%EBW) by session 4 and end of treatment (EOT), clinical impairment, and ED pathology. RESULTS: Significant correlations were found between aspects of adolescent IE, ED symptoms, and clinical impairment. Caregiver IES scores (Reliance on Hunger and Satiety Cues, Body-Food Choice Congruence, IES Total) were negatively related to adolescent ED symptoms (EDE-Q Weight Concerns, EDE-Q Shape Concerns, EDE-Q Global) at baseline. Caregiver IE (Eating for Physical Rather than Emotional Reasons) was positively associated with adolescent weight gain at FBT session 4 and EOT, even when statistically adjusting for gender and initial level of care. CONCLUSION: Study results were consistent with past research indicating adolescent IE is negatively associated with ED behaviors, cognitions, and impairment. This study is the first to provide evidence that caregiver IE is positively associated with adolescent weight gain in FBT and is the first to provide evidence that caregiver IE is negatively related to adolescent ED symptoms. Future research should examine adolescent and caregiver IE throughout FBT to understand the role of IE in treatment response. LEVEL OF EVIDENCE: Level III: Evidence obtained from cohort or case-control analytic studies.

Regional distribution and maturation of tau pathology among phenotypic variants of Alzheimer's disease.

Alzheimer's disease neuropathologic change (ADNC) is clinically heterogenous and can present with a classic multidomain amnestic syndrome or focal non-amnestic syndromes. Here, we investigated the distribution and burden of phosphorylated and C-terminally cleaved tau pathologies across hippocampal subfields and cortical regions among phenotypic variants of Alzheimer's disease (AD). In this study, autopsy-confirmed patients with ADNC, were classified into amnestic (aAD, N = 40) and non-amnestic (naAD, N = 39) groups based on clinical criteria. We performed digital assessment of tissue sections immunostained for phosphorylated-tau (AT8 detects pretangles and mature tangles), D421-truncated tau (TauC3, a marker for mature tangles and ghost tangles), and E391-truncated tau (MN423, a marker that primarily detects ghost tangles), in hippocampal subfields and three cortical regions. Linear mixed-effect models were used to test regional and group differences while adjusting for demographics. Both groups showed AT8-reactivity across hippocampal subfields that mirrored traditional Braak staging with higher burden of phosphorylated-tau in subregions implicated as affected early in Braak staging. The burden of phosphorylated-tau and TauC3-immunoreactive tau in the hippocampus was largely similar between the aAD and naAD groups. In contrast, the naAD group had lower relative distribution of MN423-reactive tangles in CA1 (ß = - 0.2, SE = 0.09, p = 0.001) and CA2 (ß = - 0.25, SE = 0.09, p = 0.005) compared to the aAD. While the two groups had similar levels of phosphorylated-tau pathology in cortical regions, there was higher burden of TauC3 reactivity in sup/mid temporal cortex (ß = 0.16, SE = 0.07, p = 0.02) and MN423 reactivity in all cortical regions (ß = 0.4-0.43, SE = 0.09, p < 0.001) in the naAD compared to aAD. In conclusion, AD clinical variants may have a signature distribution of overall phosphorylated-tau pathology within the hippocampus reflecting traditional Braak staging; however, non-amnestic AD has greater relative mature tangle pathology in the neocortex compared to patients with clinical amnestic AD, where the hippocampus had greatest relative burden of C-terminally cleaved tau reactivity. Thus, varying neuronal susceptibility to tau-mediated neurodegeneration may influence the clinical expression of ADNC.

Signature laminar distributions of pathology in frontotemporal lobar degeneration.

Frontotemporal lobar degeneration (FTLD) with either tau (FTLD-tau) or TDP-43 (FTLD-TDP) inclusions are distinct proteinopathies that frequently cause similar frontotemporal dementia (FTD) clinical syndromes. FTD syndromes often display macroscopic signatures of neurodegeneration at the level of regions and networks, but it is unclear if subregional laminar pathology display patterns unique to proteinopathy or clinical syndrome. We hypothesized that FTLD-tau and FTLD-TDP accumulate pathology in relatively distinct cortical layers independent of clinical syndrome, with greater involvement of lower layers in FTLD-tau. The current study examined 170 patients with either FTLD-tau (n = 73) or FTLD-TDP (n = 97) spanning dementia and motor phenotypes in the FTD spectrum. We digitally measured the percent area occupied by tau and TDP-43 pathology in upper layers (I-III), lower layers (IV-VI), and juxtacortical white matter (WM) from isocortical regions in both hemispheres where available. Linear mixed-effects models compared ratios of upper to lower layer pathology between FTLD groups and investigated relationships with regions, WM pathology, and global cognitive impairment while adjusting for demographics. We found lower ratios of layer pathology in FTLD-tau and higher ratios of layer pathology in FTLD-TDP, reflecting lower layer-predominant tau pathology and upper layer-predominant TDP-43 pathology, respectively (p < 0.001). FTLD-tau displayed lower ratios of layer pathology related to greater WM tau pathology (p = 0.002) and to earlier involved/severe pathology regions (p = 0.007). In contrast, FTLD-TDP displayed higher ratios of layer pathology not related to either WM pathology or regional severity. Greater cognitive impairment was associated with higher ratios of layer pathology in FTLD-tau (p = 0.018), but was not related to ratios of layer pathology in FTLD-TDP. Lower layer-predominant tau pathology and upper layer-predominant TDP-43 pathology are proteinopathy-specific, regardless of clinical syndromes or regional networks that define these syndromes. Thus, patterns of laminar change may provide a useful anatomical framework for investigating how degeneration of select cells and corresponding laminar circuits influence large-scale networks and clinical symptomology in FTLD.

Associations Between Childhood Trauma Characteristics and Theory of Mind in Adults: Results From a Large, Diverse Sample.

Theory of mind (ToM) is an essential social cognitive process encompassing abilities to represent and understand others' mental states. Although previous reports linked childhood trauma to social cognitive deficits, how characteristics of trauma exposure, such as subtype or timing, affect ToM remains unaddressed. Using data from a diverse adult sample (n = 2200), we tested whether exposure type and first exposure timing of common childhood trauma associated with ToM. Neither interpersonal loss (ß = - 0.25, p = 0.170, [- 0.61, 0.10]) nor child maltreatment (ß = - 0.21, p = 0.369, [- 0.66, 0.25]) was associated with lower ToM. There was no effect of timing of age at which trauma was experienced (F = 2.19, p = 0.087). While we did not identify age-dependent effects, future studies should examine links between timing or chronicity of prospectively reported childhood trauma and social cognition. Understanding of how childhood experiences shape ToM could reveal mechanisms underlying social cognition development and inform prevention efforts.

Modifiable factors associated with mental health symptoms in siblings of adolescents with anorexia nervosa.

PURPOSE: Research demonstrates that anorexia nervosa (AN) takes a significant toll on affected families, yet the well-being of siblings has been largely overlooked. This study examines mental health symptoms in siblings of adolescents with AN and seeks to identify modifiable factors associated with well-being. METHOD: Participants included 34 siblings (aged 11-19) of adolescents with AN and 47 age and sex matched controls. Participants and their caregivers completed assessments of anxiety, depression, internalizing and externalizing problems, and parentification. Siblings of adolescents with AN also completed the Sibling Perception Questionnaire, an assessment of perceptions and attitudes about AN. RESULTS: Analyses indicated that siblings of adolescents with AN reported greater anxiety and parentification than controls. On caregiver reports of participants' internalizing and externalizing symptoms, no significant differences were found across groups. In siblings of adolescents with AN, females were more vulnerable to anxiety, depression, and negative attitudes and perceptions about AN than males. Perceived negative interpersonal interactions, specific to having a brother or sister with AN, were associated with greater anxiety and depression among AN siblings. CONCLUSION: Findings from this pilot study suggest that siblings of adolescents with AN are vulnerable to anxiety and parentification behaviors. Negative interpersonal interactions specific to having a brother or sister with AN may perpetuate risk for poorer well-being. Caregivers may not be attuned to these struggles, highlighting the importance of provider and family education about sibling vulnerabilities. Therapeutic interventions that target siblings of adolescents with AN are also indicated. LEVEL OF EVIDENCE: Level III, case-control analytic study.

Cognitive and Pathological Influences of Tau Pathology in Lewy Body Disorders.

OBJECTIVE: To use digital histology in a large autopsy cohort of Lewy body disorder (LBD) patients with dementia to test the hypotheses that co-occurring Alzheimer disease (AD) pathology impacts the anatomic distribution of α-synuclein (SYN) pathology and that co-occurring neocortical tau pathology in LBDs associates with worse cognitive performance and occurs in a pattern differing from AD. METHODS: Fifty-five autopsy-confirmed LBD (Parkinson disease with dementia, n = 36; dementia with Lewy bodies, n = 19) patients and 25 AD patients were studied. LBD patients were categorized as having moderate/severe AD copathology (SYN + AD = 20) or little/no AD copathology (SYN-AD = 35). Digital measures of tau, ß-amyloid (Aß), and SYN histopathology in neocortical and subcortical/limbic regions were compared between groups and related to antemortem cognitive testing. RESULTS: SYN burden was higher in SYN + AD than SYN-AD in each neocortical region (F1, 54 = 5.6-6.0, p < 0.02) but was equivalent in entorhinal cortex and putamen (F1, 43-49 = 0.7-1.7, p > 0.2). SYN + AD performed worse than SYN-AD on a temporal lobe-mediated naming task (t27 = 2.1, p = 0.04). Antemortem cognitive test scores inversely correlated with tau burden (r = -0.39 to -0.68, p < 0.05). AD had higher tau than SYN + AD in all regions (F1, 43 = 12.8-97.2, p < 0.001); however, SYN + AD had a greater proportion of tau in the temporal neocortex than AD (t41 = 2.0, p < 0.05), whereas AD had a greater proportion of tau in the frontal neocortex than SYN + AD (t41 = 3.3, p < 0.002). SYN + AD had similar severity and distribution of neocortical Aß compared to AD (F1, 40-43 = 1.6-2.0, p > 0.1). INTERPRETATION: LBD patients with AD copathology harbor greater neocortical SYN pathology. Regional tau pathology relates to cognitive performance in LBD dementia, and its distribution may diverge from pure AD. Tau copathology contributes uniquely to the heterogeneity of cognitive impairment in LBD. Ann Neurol 2018; 1-13 ANN NEUROL 2019;85:259-271.

Degeneration of the locus coeruleus is a common feature of tauopathies and distinct from TDP-43 proteinopathies in the frontotemporal lobar degeneration spectrum.

Neurodegeneration of the locus coeruleus (LC) in age-related neurodegenerative diseases such as Alzheimer's disease (AD) is well documented. However, detailed studies of LC neurodegeneration in the full spectrum of frontotemporal lobar degeneration (FTLD) proteinopathies comparing tauopathies (FTLD-tau) to TDP-43 proteinopathies (FTLD-TDP) are lacking. Here, we tested the hypothesis that there is greater LC neuropathology and neurodegeneration in FTLD-tau compared to FTLD-TDP. We examined 280 patients including FTLD-tau (n = 94), FTLD-TDP (n = 135), and two reference groups: clinical/pathological AD (n = 32) and healthy controls (HC, n = 19). Adjacent sections of pons tissue containing the LC were immunostained for phosphorylated TDP-43 (1D3-p409/410), hyperphosphorylated tau (PHF-1), and tyrosine hydroxylase (TH) to examine neuromelanin-containing noradrenergic neurons. Blinded to clinical and pathologic diagnoses, we semi-quantitatively scored inclusions of tau and TDP-43 both inside LC neuronal somas and in surrounding neuropil. We also digitally measured the percent area occupied of neuromelanin inside of TH-positive LC neurons and in surrounding neuropil to calculate a ratio of extracellular-to-intracellular neuromelanin as an objective composite measure of neurodegeneration. We found that LC tau burden in FTLD-tau was greater than LC TDP-43 burden in FTLD-TDP (z = - 11.38, p < 0.0001). Digital measures of LC neurodegeneration in FTLD-tau were comparable to AD (z = - 1.84, p > 0.05) but greater than FTLD-TDP (z = - 3.85, p < 0.0001) and HC (z = - 4.12, p < 0.0001). Both tau burden and neurodegeneration were consistently elevated in the LC across pathologic and clinical subgroups of FTLD-tau compared to FTLD-TDP subgroups. Moreover, LC tau burden positively correlated with neurodegeneration in the total FTLD group (rho = 0.24, p = 0.001), while TDP-43 burden did not correlate with LC neurodegeneration in FTLD-TDP (rho = - 0.01, p = 0.90). These findings suggest that patterns of disease propagation across all tauopathies include prominent LC tau and neurodegeneration that are relatively distinct from the minimal degenerative changes to the LC in FTLD-TDP and HC. Antemortem detection of LC neurodegeneration and/or function could potentially improve antemortem differentiation of underlying FTLD tauopathies from clinically similar FTLD-TDP proteinopathies.

Dialectical behavioral therapy skills group as an adjunct to family-based therapy in adolescents with restrictive eating disorders.

Dialectical behavior therapy (DBT) is commonly used in the treatment of eating disorders (ED), yet few studies have examined the utility of DBT skills groups as an adjunct to evidence-based therapy for ED. Thus, we sought to examine the preliminary efficacy of a DBT skills group as an adjunct to Family-Based Treatment (FBT) for adolescent restrictive ED. Our preliminary pilot study included 18 adolescent girls ages 13-18 (M= 15.3, SD = 1.64) with restrictive ED, including Anorexia Nervosa (AN; N = 10), Atypical Anorexia Nervosa (AAN, N = 5), and Other Specific Feeding or Eating Disorder (OSFED; N = 3). All participants were enrolled in a 6-month, weekly DBT skills group and were concurrently receiving family-based treatment (FBT). Participants who completed the intervention experienced large effect sizes for increases in adaptive skills (Cohen's d = .71) and decreases in general dysfunctional coping strategies (Cohen's d = .85); and small to medium effect sizes for decreases in binge eating (Cohen's d = .40) and increases in percent expected body weight (% EBW; Cohen's d = .32). Finally, small effect sizes were evidenced in decreases in Global EDE-Q scores (Cohen's d = .26), EDE-Q restraint (Cohen's d = .29) and CDI scores (Cohen's d = .28). Our study presents promising preliminary data suggesting that adolescents with restrictive EDs receiving FBT could benefit from an adjunctive DBT skills group. Feasibility of and considerations for tailoring a DBT skills group to an outpatient ED treatment program are discussed.

An intensive family-based treatment guided intervention for medically hospitalized youth with anorexia nervosa: Parental self-efficacy and weight-related outcomes.

Recent studies suggest the efficacy of family-based treatment (FBT) among youth with anorexia nervosa (AN) in intensive treatment settings. This study aimed to assess weight outcomes in youth who received an FBT intervention while hospitalized for medical complications of AN. Parental self-efficacy among participating caregivers was also measured. Post-discharge weights of 49 participants were compared with weights of 44 youth who were hospitalized prior to the provision of the FBT intervention. Youth who received the FBT intervention gained significantly more weight than youth in the retrospective treatment as usual group at 3 and 6 months following discharge. FBT youth were 2.84 times more likely than retrospective treatment as usual youth to achieve at least 95% of treatment goal weight at 6 months post-discharge. Finally, parental self-efficacy significantly increased in caregivers who participated in the FBT intervention. Findings provided preliminary support for the provision of FBT to medically hospitalized youth with AN.

Adolescent males with atypical anorexia nervosa and premorbid obesity: three case reports.

PURPOSE: Premorbid obesity is an identified risk factor for eating disorder (ED) development among adolescent males. However, pervasive gender- and weight-related biases about ED inhibit timely diagnosis and treatment among this demographic. This study examined the psychological and medical characteristics of three adolescent males with premorbid obesity who were not diagnosed with atypical anorexia nervosa (AAN) until medical sequelae of malnutrition warranted emergent hospitalization. Factors associated with diagnostic delays among these cases were identified to facilitate increased awareness of this at-risk demographic. METHODS: Retrospective chart review was conducted on three adolescent males (aged 12-17) with AAN and premorbid obesity who were medically hospitalized for 13-24 days (M = 20.3, SD = 9.7). Demographic variables, psychological characteristics, and physical data were extracted. RESULTS: Each case presented at normal or overweight BMI status (M = 22.7 kg/m2, SD = 3.2) following a significant loss of weight ranging from 19 to 42% of total body mass (M = 31.7%, SD = 9.5) over 5-12 months (M = 8.3, SD = 2.9). Plausible factors associated with diagnostic delays included initial weight loss recommendations by a medical provider, with little support or oversight; limited insight that symptoms were problematic; social reinforcement of dieting behaviors; low prevalence of psychiatric comorbidity; parental obesity; and parental history of bariatric surgery. CONCLUSIONS: These cases elucidate the importance of close follow-up of youth with obesity who are encouraged to lose weight. Further education about AAN among males with premorbid obesity is crucial for timely diagnosis and intervention.

Examination of Psychosocial and Physiological Risk for Bulimic Symptoms in Youth With Type 1 Diabetes Transitioning to an Insulin Pump: A Pilot Study.

Objectives: This study tested hypotheses drawn from a risk model positing that psychosocial risk plus disease-related and treatment factors contribute to bulimic symptoms in youth with type 1 diabetes (T1D) transitioning to an insulin pump. The goal of this study was to examine whether disease-related factors, particularly disease- and treatment-based disruption in hunger and satiety, contribute to report of bulimic symptoms in youth with T1D after accounting for psychosocial risk factors. Methods: 43 youth (ages 10-17, 54% female) with established T1D were recruited before transition from multiple daily injections to insulin-pump therapy from three tertiary pediatric diabetes centers. Participants completed measures of bulimic symptoms, depressive symptoms dietary restraint, and the Diabetes Treatment and Satiety Scale, a diabetes-specific questionnaire assessing hunger and satiety cues and eating behavior in response to blood glucose levels and treatment. Results: Hierarchical multiple regression was used to assess contributions of psychosocial and disease-based risk to report of bulimic symptoms. After assessing the contributions of body mass index, body image dissatisfaction, and dietary restraint, a significant 2-way interaction emerged between depression and diabetes-related uncontrollable hunger related to bulimic symptoms (ß = 1.82, p < .01). Conclusions: In addition to psychosocial risk, disease- and treatment-based hunger and satiety dysregulation appear to be important factors contributing to report of bulimic symptoms in youth with T1D. These preliminary findings have significant treatment implications for bulimic symptoms in youth with T1D.

Reproductive and Appetite Hormones and Bulimic Symptoms during Midlife.

Eating disorders and related symptoms occur during midlife; however, little is known about their aetiology. It has been hypothesised that perimenopause represents a window of vulnerability for the development or exacerbation of eating disorder symptomatology because, like puberty, perimenopause is a period of reproductive hormone change. We compared symptoms of bulimia nervosa (bulimic symptomatology) assessed via mean scores on a self-report questionnaire in premenopausal and perimenopausal women. We also examined the association between hormone concentrations (reproductive/appetite) and bulimic symptomatology. No mean differences in bulimic symptomatology were observed between premenopause and perimenopause. However, there was a significant positive association between leptin and binge eating. Although no significant associations between reproductive hormones and bulimic symptomatology were observed, additional research is needed to provide definitive information. It is essential to learn more about the aetiology of eating disorders and related symptomatology across the lifespan in order to develop age-relevant treatment and prevention programs. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.

Genetic and environmental components to self-induced vomiting.

OBJECTIVE: We examined the association between the genetic and environmental factors contributing to the liability to having ever engaged in self-induced vomiting (SIV initiation) and the genetic and environmental factors contributing to regular SIV behaviors (weekly or daily) for weight control. METHOD: SIV was assessed in 3,942 women from monozygotic twin pairs and 2,790 women from same-sex dizygotic twin pairs, aged 20-47, from the Swedish Twin study of Adults: Genes and Environment. A causal-contingent-common pathway model assessed the extent to which genetic and environmental factors that influence initiation of SIV also influence regular SIV behaviors. RESULTS: In the best-fit model, genetic and individual-specific environmental factors influenced liability to SIV initiation. The genetic factors influencing regular SIV behaviors were the same as the genetic factors influencing SIV initiation. Additional individual-specific environmental factors that were unrelated to SIV initiation influenced regular SIV behaviors. DISCUSSION: Our findings provide evidence that the underlying liabilities for SIV initiation and regular SIV lie on the same continuum given the degree of overlap in risk between SIV initiation and regular SIV behaviors. Further, the lack of specific genetic factors and the importance of individual-specific environmental factors for regular SIV behaviors highlight the significance of environmental factors in the etiology of eating disorder symptomatology and the non-deterministic nature of genetic factors. Finally, our results suggest that when it comes to preventing individuals from developing regular SIV behavior, intervening at an environmental level is warranted.

Impact of short-term refeeding on appetite and meal experiences in new onset adolescent eating disorders.

Restrictive eating disorders (ED) are increasing and represent a serious risk to the health of adolescent females. Restrictive ED in youth are often treated through aggressive short-term refeeding. Although evidence supports that this intervention is the "gold standard" for improving ED outcomes in youth, little research has specifically probed appetite and meal-related responses to this type of intensive, short-term refeeding in newly diagnosed individuals. Information about appetite and meal-related dysfunction could provide valuable insights regarding treatment-interfering features of ED in both acute inpatient and longer-term outpatient treatment. The purpose of this study was to evaluate the hunger, fullness, olfactory, and gustatory responses of adolescents with newly-diagnosed restrictive ED and to probe how and when these responses are altered by refeeding. Using a quasi-experimental ecologically valid methodology, this study described and compared profiles of hunger, fullness, olfactory, and gustatory responses in adolescent females (n = 15) with newly diagnosed restrictive ED at hospital admission (i.e., severe malnutrition) and after medical refeeding, in comparison to healthy controls (n = 15). Results showed that newly diagnosed (i.e., malnourished) adolescents with ED showed significantly different meal-related experiences than controls. Refeeding improved some of these differences, but not all. Following refeeding, females with ED continued to show lower hunger, greater fullness, and lower pleasantness of smell ratings compared to controls. Unpleasantness of taste ratings maladaptively increased, such that females who were re-fed reported more aversive scents than pre-treatment. Profiles of meal-related responses were also identified and compared between groups. The applicability of these findings are discussed within the context of critical periods of change during refeeding treatment and potentially promising intervention targets that might enhance treatment outcomes for adolescents with newly onset, restrictive ED.

Topical review: a comprehensive risk model for disordered eating in youth with type 1 diabetes.

OBJECTIVES: Provide an updated literature review on prevalence, measurement, and correlates of disordered eating in youth with Type 1 diabetes (T1D), present a novel theoretical risk model (i.e., The Modified Dual Pathway Model) for disordered eating in youth with T1D incorporating psychosocial and physiological risk factors, and discuss clinical implications. METHODS: Literature review of prevalence, correlates, risk factors, and outcomes of disordered eating behavior (DEB) in youth with T1D. RESULTS: Insulin treatment, subsequent weight gain, and disruptions to hunger and satiety regulation are hypothesized disease-related mechanisms through which the treatment of T1D may increase vulnerability to development of behavior characterized as DEB. The Modified Dual Pathway Model integrates these factors with a validated psychosocial risk (body dissatisfaction, depression, and abstinence violation) model for DEB in nondiabetic youth. CONCLUSIONS: The Modified Dual Pathway model of DEB in youth with T1D is a comprehensive representation of both psychosocial and T1D-related risk factors with the potential to inform future interventions for this population.

Defining the structure-function relationship of specific lesions in early and advanced age-related macular degeneration.

The objective of this study is to define structure-function relationships of pathological lesions related to age-related macular degeneration (AMD) using microperimetry and multimodal retinal imaging. We conducted a cross-sectional study of 87 patients with AMD (30 eyes with early and intermediate AMD and 110 eyes with advanced AMD), compared to 33 normal controls (66 eyes) recruited from a single tertiary center. All participants had enface and cross-sectional optical coherence tomography (Heidelberg HRA-2), OCT angiography, color and infra-red (IR) fundus and microperimetry (MP) (Nidek MP-3) performed. Multimodal images were graded for specific AMD pathological lesions. A custom marking tool was used to demarcate lesion boundaries on corresponding enface IR images, and subsequently superimposed onto MP color fundus photographs with retinal sensitivity points (RSP). The resulting overlay was used to correlate pathological structural changes to zonal functional changes. Mean age of patients with early/intermediate AMD, advanced AMD and controls were 73(SD = 8.2), 70.8(SD = 8), and 65.4(SD = 7.7) years respectively. Mean retinal sensitivity (MRS) of both early/intermediate (23.1 dB; SD = 5.5) and advanced AMD (18.1 dB; SD = 7.8) eyes were significantly worse than controls (27.8 dB, SD = 4.3) (p < 0.01). Advanced AMD eyes had significantly more unstable fixation (70%; SD = 63.6), larger mean fixation area (3.9 mm2; SD = 3.0), and focal fixation point further away from the fovea (0.7 mm; SD = 0.8), than controls (29%; SD = 43.9; 2.6 mm2; SD = 1.9; 0.4 mm; SD = 0.3) (p ≤ 0.01). Notably, 22 fellow eyes of AMD eyes (25.7 dB; SD = 3.0), with no AMD lesions, still had lower MRS than controls (p = 0.04). For specific AMD-related lesions, end-stage changes such as fibrosis (5.5 dB, SD = 5.4 dB) and atrophy (6.2 dB, SD = 7.0 dB) had the lowest MRS; while drusen and pigment epithelial detachment (17.7 dB, SD = 8.0 dB) had the highest MRS. Peri-lesional areas (20.2 dB, SD = 7.6 dB) and surrounding structurally normal areas (22.2 dB, SD = 6.9 dB) of the retina with no AMD lesions still had lower MRS compared to controls (27.8 dB, SD = 4.3 dB) (p < 0.01). Our detailed topographic structure-function correlation identified specific AMD pathological changes associated with a poorer visual function. This can provide an added value to the assessment of visual function to optimize treatment outcomes to existing and potentially future novel therapies.