State-specific alterations in the neural computations underlying inhibitory control in women remitted from bulimia nervosa.

The neurocomputational processes underlying bulimia nervosa and its primary symptoms, out-of-control overeating and purging, are poorly understood. Research suggests that the brains of healthy individuals form a dynamic internal model to predict whether control is needed in each moment. This study tested the hypothesis that this computational process of inhibitory control is abnormally affected by metabolic state (being fasted or fed) in bulimia nervosa. A Bayesian ideal observer model was fit to behavioral data acquired from 22 women remitted from bulimia nervosa and 20 group-matched controls who completed a stop-signal task during two counterbalanced functional MRI sessions, one after a 16 h fast and one after a meal. This model estimates participants' trial-by-trial updating of the probability of a stop signal based on their experienced trial history. Neural analyses focused on control-related Bayesian prediction errors, which quantify the direction and degree of "surprise" an individual experiences on any given trial. Regardless of group, metabolic state did not affect behavioral performance on the task. However, metabolic state modulated group differences in neural activation. In the fed state, women remitted from bulimia nervosa had attenuated prediction-error-dependent activation in the left dorsal caudate. This fed-state activation was lower among women with more frequent past binge eating and self-induced vomiting. When they are in a fed state, individuals with bulimia nervosa may not effectively process unexpected information needed to engage inhibitory control. This may explain the difficulties these individuals have stopping eating after it begins.

Testing the role of associative learning in evidence-based treatments for anorexia nervosa.

Treatments for anorexia nervosa (AN) remain ineffective for many patients. Processes that can account for differential treatment outcomes remain mostly unknown. We propose that the field test the role of associative learning in current psychological treatments. We hold that this line of research could yield actionable information for understanding non-response and improving long-term outcomes. To make this argument, we define associative learning and outline its proposed role in understanding psychiatric disorders and their treatment. We then briefly review data exploring associative learning in AN. We argue that associative learning processes are implicitly implicated in existing treatments; by this rationale, baseline differences in learning may interfere with treatment response. Finally, we outline future research to test our hypotheses. Altogether, future research aimed at better understanding how associative learning may contribute to AN symptom persistence has the potential to inform novel directions in intervention research. PUBLIC SIGNIFICANCE: There is a pressing need to improve outcomes in treatments for anorexia nervosa (AN). We propose that individual differences in associative learning-the ability to form and update associations between cues, contexts, behaviors, and outcomes-may account for differential response to existing treatments. Undertaking this research could provide an understanding of how current treatments work and inform new approaches for those who may be at risk of poor outcomes.

Conceptualizing avoidant/restrictive food intake disorder via an executive functioning lens.

Avoidant/restrictive food intake disorder (ARFID) is a heterogeneous disorder wherein restrictive eating is primarily attributed to non-shape/weight-based reasons (e.g., sensory sensitivity) that empirical research continues to explore. Mounting evidence suggests that ARFID often presents alongside neurodevelopmental diagnoses (NDs) or divergent neurodevelopment broadly. Executive functioning (EF) differences often characterize divergent neurodevelopmental trajectories. Additionally, restrictive eating in anorexia nervosa has been conceptualized as related to EF factors (e.g., set shifting). Given the neurodevelopmental phenotype that may be associated with ARFID and the role of EF in anorexia nervosa, this paper proposes EF as a potentially important, yet understudied factor in ARFID pathology. We posit that various observed ARFID behavioral/cognitive tendencies can be conceptualized in relation to EF differences. We contextualize commonly observed ARFID presentations within "core" EF components (i.e., cognitive flexibility, working memory, inhibitory control), leading to hypotheses about EF in ARFID. Finally, we offer additional considerations/directions for future research on EF in ARFID. Increased research on EF in ARFID is needed to consider this potential common factor in the etiology and maintenance of this heterogeneous disorder. We aim to promote further consideration of EF in ARFID etiology, maintenance, and treatment-outcome research. PUBLIC SIGNIFICANCE: This article proposes that aspects of executive functioning (EF) may play a role in the onset and maintenance of avoidant/restrictive food intake disorder (ARFID), although this notion is largely untested by existing research. Further research on the role of EF in ARFID may assist with refining models and treatments for this heterogeneous disorder.

Change in motivational bias during treatment predicts outcome in anorexia nervosa.

OBJECTIVE: Reward and punishment sensitivity are known to be altered in anorexia nervosa (AN). Most research has examined these constructs separately although motivated behavior is influenced by considering both the potential for reward and risk of punishment. The present study sought to compare the relative balance of reward and punishment sensitivity in AN versus healthy controls (HCs) and examine whether motivational bias is associated with AN symptoms and treatment outcomes. METHODS: Adolescents and adults with AN (n = 262) in a partial hospitalization program completed the Eating Disorders Examination Questionnaire (EDE-Q), Behavioral Inhibition System/Behavioral Activation System (BIS/BAS) scales, and Sensitivity to Punishment/Sensitivity to Reward Questionnaire (SPSRQ) at admission and discharge. HCs (HC; n = 90) completed the BIS/BAS and SPSRQ. Motivational Bias Scores were calculated to reflect the dominance of reward versus punishment sensitivity. RESULTS: Individuals with AN demonstrated significantly greater bias toward punishment sensitivity than HC. In AN, a bias toward punishment was associated with higher EDE-Q Global score at admission. Change in motivational bias during treatment predicted EDE-Q Global scores, but not BMI, at discharge, with greater increases in reward sensitivity or greater decreases in punishment sensitivity during treatment predicting lower eating pathology. Similar findings were observed using the BIS/BAS and SPSRQ. DISCUSSION: Change in motivational bias during treatment is associated with improved outcomes in AN. However, it appears that much of the change in motivational bias can be attributed to changes in punishment sensitivity, rather than reward sensitivity. Future research should examine the mechanisms underlying punishment sensitivity decreases during treatment. PUBLIC SIGNIFICANCE: Sensitivity to reward and punishment may be important treatment targets for individuals with anorexia nervosa (AN). To date, most research has considered reward and punishment sensitivity separately, rather than examining their relationship to each other. We found that the balance of reward and punishment sensitivity (i.e., motivational bias) differs between healthy controls and those with AN and that this bias is associated with eating disorder symptoms and treatment outcome.

Comparing changes in eating disorder psychopathology and comorbid symptoms over treatment in anorexia nervosa and atypical anorexia nervosa in a partial hospitalization program.

OBJECTIVE: The objective of this study is to compare treatment trajectories in anorexia nervosa (AN) and atypical AN. METHOD: Adolescents and adults with AN (n = 319) or atypical AN (n = 67) in a partial hospitalization program (PHP) completed diagnostic interviews and self-report questionnaires measuring eating disorder (ED), depression, and anxiety symptoms throughout treatment. RESULTS: Premorbid weight loss did not differ between diagnoses. Individuals with atypical AN had more comorbid diagnoses, but groups did not differ on specific diagnoses. ED psychopathology and comorbid symptoms of depression/anxiety did not differ at admission between groups nor did rate of change in ED psychopathology and comorbid symptoms of depression/anxiety from admission to 1-month. From admission to discharge, individuals with atypical AN had a faster reduction in ED psychopathology and comorbid symptoms of depression and anxiety (ps < 0.05; rs = 0.01-0.32); however, there were no group differences in ED psychopathology or depression symptoms at discharge (ps>.50; ds = .01-.30). Individuals with atypical AN had lower anxiety at discharge compared to individuals with AN (p = 0.05; d = .4). Length of stay did not differ between groups (p = 0.11; d = .21). DISCUSSION: Groups had similar ED treatment trajectories, suggesting more similarities than differences. PHP may also be effective for AAN. PUBLIC SIGNIFICANCE: This study supports previous research that individuals with AN and atypical AN have more similarities than differences. Results from this study indicate that individuals with AN and atypical AN have similar treatment outcomes for both ED psychopathology and depressive symptoms; however, individuals with atypical AN have lower anxiety symptoms at discharge compared to individuals with AN. AN and atypical AN also have more symptom similarity at admission and throughout treatment, which challenges their current designation as distinct disorders.

Early change in gastric-specific anxiety sensitivity as a predictor of eating disorder treatment outcome.

Eating disorders (EDs) are often accompanied by gastrointestinal (GI) distress. Anxiety sensitivity is the tendency to interpret sensations of anxiety as threatening or dangerous, and includes both broad physical symptoms (e.g., elevated heartrate) and GI-specific symptoms. Physical and GI-specific anxiety sensitivity may be important risk and maintaining factors in EDs. This study tested the hypothesis that greater reductions in both types of anxiety sensitivity during the first month of treatment would predict lower ED symptoms and trait anxiety at discharge and 6-month follow-up. Patients (n = 424) in ED treatment reported physical and GI-specific anxiety sensitivity, ED symptoms, and trait anxiety at treatment admission, 1-month into treatment, discharge, and 6-month follow-up. Analyses were conducted with hierarchical linear regression with imputation, controlling for relevant covariates. Results indicated that early reduction in GI-specific but not general physical anxiety sensitivity predicted both lower ED symptoms and lower trait anxiety at discharge and 6-month follow-up. These findings demonstrate the importance of GI-specific anxiety sensitivity as a potential maintaining factor in EDs. Developing and refining treatments to target GI-specific anxiety sensitivity may have promise in improving the treatment not only of EDs, but also of commonly co-morbid anxiety disorders.

Using clinical cutoff scores on the eating disorder examination-questionnaire to evaluate eating disorder symptoms during and after naturalistic intensive treatment.

Clinical cutoff scores for self-report measures provide a means of evaluating clinically significant pathology during and after treatment. A cutoff of 2.8 on the Eating Disorder Examination-Questionnaire (EDE-Q) has been recommended to screen for eating disorders (ED). We used this cutoff to assess ED symptoms in adolescents (n = 444) and adults (n = 592) through ED treatment and follow-up. Most patients scored above 2.8 at intake (adolescents 67%, M = 3.21; adults 78%, M = 4.20) and below 2.8 at discharge (adolescents 65%, M = 1.87; adults 66%, M = 2.67), with gains often maintained through follow-up (40% of adolescents and 35% of adults at 12-month follow-up). EDE-Q scores were higher in adults than adolescents and in patients with binge/purge disorders. Results suggest a cutoff of 2.8 on the EDE-Q effectively tracks ED symptom improvement through treatment and discharge. This supports the need for the development of culture-specific and empirically developed clinical cutoffs and their widespread use to evaluate program effectiveness.

Altered Reinforcement Learning from Reward and Punishment in Anorexia Nervosa: Evidence from Computational Modeling.

OBJECTIVES: Anorexia nervosa (AN) is associated with altered sensitivity to reward and punishment. Few studies have investigated whether this results in aberrant learning. The ability to learn from rewarding and aversive experiences is essential for flexibly adapting to changing environments, yet individuals with AN tend to demonstrate cognitive inflexibility, difficulty set-shifting and altered decision-making. Deficient reinforcement learning may contribute to repeated engagement in maladaptive behavior. METHODS: This study investigated learning in AN using a probabilistic associative learning task that separated learning of stimuli via reward from learning via punishment. Forty-two individuals with Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 restricting-type AN were compared to 38 healthy controls (HCs). We applied computational models of reinforcement learning to assess group differences in learning, thought to be driven by violations in expectations, or prediction errors (PEs). Linear regression analyses examined whether learning parameters predicted BMI at discharge. RESULTS: AN had lower learning rates than HC following both positive and negative PE (p < .02), and were less likely to exploit what they had learned. Negative PE on punishment trials predicted lower discharge BMI (p < .001), suggesting individuals with more negative expectancies about avoiding punishment had the poorest outcome. CONCLUSIONS: This is the first study to show lower rates of learning in AN following both positive and negative outcomes, with worse punishment learning predicting less weight gain. An inability to modify expectations about avoiding punishment might explain persistence of restricted eating despite negative consequences, and suggests that treatments that modify negative expectancy might be effective in reducing food avoidance in AN.

Changes in anhedonia over the course of eating disorder treatment.

OBJECTIVE: Anhedonia, a transdiagnostic symptom referring to the loss of ability to experience pleasure, is heightened across eating disorder (ED) diagnoses. This study aimed to assess whether anhedonia changes during ED treatment and explore how changes in anhedonia relate to treatment outcome. METHOD: Adults and adolescents in a partial hospitalization program for EDs (N = 499) completed the Eating Disorders Examination Questionnaire (EDE-Q) and the anhedonia subscale of the Beck Depression Inventory (BDI) at admission and discharge. RESULTS: Anhedonia scores significantly decreased from admission to discharge. Anhedonia at admission was also significantly different across ED diagnostic groups. To examine how study variables related to discharge EDE-Q scores, a hierarchical linear regression was conducted with demographic, diagnostic, and medication variables in the first step, anhedonia and EDE-Q scores at admission added to the second step, and anhedonia at discharge added to the final step. Greater anhedonia at discharge was related to higher EDE-Q scores at discharge. DISCUSSION: Our findings suggest that anhedonia changes significantly over the course of intensive treatment and changes in anhedonia relate to ED symptoms at discharge. Future research is needed to determine whether specifically targeting anhedonia in ED treatment may influence treatment outcomes. PUBLIC SIGNIFICANCE: The findings from this study suggest that anhedonia may decrease during eating disorder (ED) treatment, and greater anhedonia may relate to elevated ED symptoms. These results provide support for the continued study of anhedonia in ED samples and indicate that anhedonia should be explored as a potential target for novel ED treatments.

Family functioning and eating disorders treatment in a partial hospitalization program in adolescent females with eating disorders.

OBJECTIVE: Previous research examining family functioning in eating disorder (ED) treatment has focused primarily on outpatient settings. However, few studies have examined this aspect in partial hospitalization programs. To address this gap, this study examined family functioning over the course of an ED partial hospitalization program (PHP) in adolescent females (M(SD) age = 15.66 (1.50)). METHOD: Participants (n = 105) completed the Family Assessment Device and Eating Disorder Examination Questionnaire at treatment admission, 1-month post-admission, and discharge. RESULTS: Results from repeated measures analysis of variance indicated adolescents perceived an improvement in family functioning regarding Communication, Affective Responsiveness, and Behavioral Control through 1-year follow-up (p values < .05). Neither family functioning at admission nor change in family functioning in the first month correlated with any outcomes (weight, ED symptoms, and remission). DISCUSSION: Results support that family functioning does not contribute to ED severity, and that treatment can improve adolescent perception of family functioning. Given the importance of involving the family in ED treatment, identifying mediators of treatment outcomes is critical to improve treatment efficacy. PUBLIC SIGNIFICANCE: Adolescents in a partial hospital program (PHP) for eating disorders (EDs) perceived improvements in their family communication, behavior, and ability to process appropriate emotions from admission to 1-year post-treatment, although these aspects did not significantly predict treatment outcomes. The findings provide helpful information for future research on adolescents with EDs in higher levels of care and underscore the importance of exploring mechanisms of family-based treatment in PHP.

Exploring changes in alexithymia throughout intensive dialectical behavior therapy for eating disorders.

OBJECTIVE: Alexithymia is proposed as a prominent clinical feature of eating disorders (EDs). However, despite theoretical reason to believe that alexithymia could interfere with the success of treatments, few studies have tested whether alexithymia changes over the course of treatment. The goals of the current study were to evaluate (a) changes in alexithymia over the course of intensive Dialectical Behaviour Therapy (DBT) for EDs, and (b) associations between alexithymia and ED symptoms over time. METHOD: A mixed-diagnostic group of patients with EDs (N = 894) completed the Eating Disorders Examination-Questionnaire (EDE-Q) and the Toronto Alexithymia Scale (TAS-20) throughout intensive treatment and at various lengths of follow-up (6, 12, 24 months). RESULTS: Results suggested that even after controlling for relevant covariates, there were significant decreases in alexithymia from intake to discharge and discharge to follow-up. Models exploring changes in self-reported ED symptoms indicated that TAS-20 scores significantly related to ED symptoms across timepoints, such that greater alexithymia was associated with greater severity of symptoms. CONCLUSIONS: Altogether, findings support an association between alexithymia and ED symptoms over treatment and suggest that emotion-focussed therapies like DBT may result in decreases in alexithymia. Future research should explore whether this effect is consistent across therapies without an emotional focus.

Pilot study of a water load test as a measure of gastric interoception in anorexia nervosa.

PURPOSE: Research and clinical experience suggest that individuals with anorexia nervosa (AN) have deficits in gastric interoception, which has been hypothesized to maintain restrictive eating. Behavioral water load tasks (WLTs) have the capability to noninvasively assess gastric interoception; however, to date, no studies have examined WLTs in AN. Thus, the present proof-of-concept pilot study explored the preliminary validity of a WLT in individuals with AN. METHODS: Participants were n = 10 individuals with AN and n = 10 matched-control women (CW). Participants completed self-report questionnaires before and after a WLT, in which participants were asked to drink water until "completely full". RESULTS: Participants with AN drank significantly less water than CW (AN = 240(109.14) milliliters (ml), CW = 398.00(149.21) ml, p = 0.02, Cohen's d = 1.21), but reported greater increases in negative affect pre- to-post-WLT (p = 0.04, partial eta2 = 0.21). Correlations between WLT performance and interoceptive sensibility in AN and CW participants supported the convergent validity of the WLT. CONCLUSION: Preliminary results support the potential utility of the WLT as a behavioral measure of gastric interoception in patients with AN. Future research should examine how response to the WLT changes over the course of intervention and how results are related to treatment outcome. LEVEL OF EVIDENCE: Level IV: Evidence obtained from multiple time series analysis such as case studies. (NB: Dramatic results in uncontrolled trials might also be regarded as this type of evidence).

Associations of elevated weight status with symptom severity and treatment outcomes in binge/purge eating disorders.

OBJECTIVE: Binge-eating and purging behaviors commonly co-occur with overweight. However, little is known about the potential associations of elevated weight status with eating disorder severity or treatment outcomes. Thus, the present study compared binge-eating and purging patients with low, normal, and high weight statuses on eating disorder and mood symptoms at treatment admission, and tested whether weight status was associated with symptom change over treatment. METHOD: The sample included 135 adult female patients in an intensive outpatient program, who completed self-assessments at admission and discharge. MANOVAs compared the groups at treatment admission, and multilevel models examined changes over time. RESULTS: At admission, the high-weight group reported greater fasting frequency than the normal-weight group, and higher shape and weight concerns than the low-weight group. Over time, the high-weight group additionally showed higher eating disorder psychological symptom severity than the normal-weight group. The groups did not differ on mood symptoms at admission. Longitudinal results indicated that the groups showed comparable symptom improvements over treatment. DISCUSSION: These findings highlight the severity of higher-weight patients with bulimia nervosa. Additionally, although these patients may present with more severe symptoms, their response to an intensive treatment may be comparable to that of normal- or lower-weight groups.

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.

Last word: a call to view temperamental traits as dual vulnerabilities and strengths in anorexia nervosa.

Research suggests that individuals with anorexia nervosa (AN) have certain temperamental traits (e.g. perfectionism, anxiety, harm avoidance), which often onset prior to the eating disorder (ED), and may persist following recovery. Although these traits are often represented as vulnerabilities to developing an ED, there is reason to believe that within certain contexts, these traits may serve as assets. We propose that traits can be harnessed within or outside of treatment to promote long-term success, and possibly relate to recovery. To do so, the current paper will: (1) outline literature on traits viewed as strengths; (2) review precedents for strengths-based interventions drawing from other areas of research; (3) propose a framework for future research to assess these strengths in AN; and (4) discuss the implications of the proposed research for the destigmatization of EDs. This last word calls for a shift to a dual consideration of traits as vulnerabilities and strengths.

Evaluating patterns of inconsistent and missing data on the eating disorders examination-questionnaire in a sample of treatment-seeking adults and adolescents.

Missing or inconsistent responses on self-report assessments can have implications for the use of empirically validated measurements in research and clinical practice. However, literature on frequency and systematic patterns of missingness on common measures of eating pathology is lacking. The current study evaluated EDE-Q missing and inconsistent responding in a clinical eating disorders (EDs) sample (N = 739). Thirteen percent (13.4%; n = 99) of the sample failed to provide complete responses on the EDE-Q and 13.8% (n = 101) inconsistently responded to behavioral items of the EDE-Q. Males were more likely to provide missing data, and mean BMI was higher among individuals with missing responses. Inconsistent responders endorsed higher scores on several EDE-Q subscales, were younger, and were more likely to be Hispanic/Latinx. However, many of these differences were not significant following correction for multiple comparisons. Although our results indicated similar rates of missingness and inconsistency to past work in college samples, our results suggest that missing and inconsistent responding on the EDE-Q in clinical samples may not warrant specialized consideration within statistical analyses.

Examining day hospital treatment outcomes for sexual minority patients with eating disorders.

OBJECTIVE: Epidemiological data support that sexual minorities (SM) report higher levels of eating pathology. Theories suggest these disparities exist due to stressors specific to belonging to a minority group; however, few studies have specifically explored differences between SM and heterosexual individuals in clinical eating disorder samples. Thus, the present study compared SM and heterosexual patients with eating disorders on demographic characteristics and eating disorder and psychological outcomes during day hospital treatment. METHOD: Patients (N = 389) completed surveys of eating pathology, mood, anxiety, and skills use at treatment admission, 1-month post-admission, discharge, and 6-month follow-up. Overall, 19.8% of patients (n = 79) identified as SM, while 8.0% (n = 32) reported not identifying with any sexual orientation. SM were more likely to present across genders (17.7% of females, 24.2% of males, 33.3% of transgender patients, and 87.5% of nonbinary patients). RESULTS: SM patients were significantly more likely to endorse major depressive disorder, panic disorder, and self-harm at admission than their heterosexual counterparts. Multilevel models demonstrated that across time, SM patients demonstrated greater eating pathology, emotion dysregulation, depressive symptoms, and anxiety symptoms. Significant interactions between sexual orientation and time were found for eating pathology and emotion dysregulation, such that although SM patients started treatment with higher scores, they improved at a faster rate compared to heterosexual patients. DISCUSSION: Consistent with minority stress theory, SM patients report greater overall eating disorder and comorbid symptoms. Importantly, results do not support that there appear to be significant disparities in treatment outcome for SM patients in this sample of day hospital patients.

Naturalistic outcomes for a day-hospital programme in a mixed diagnostic sample of adolescents with eating disorders.

Despite initial data suggesting positive treatment outcomes for adolescent eating disorder day-hospital programmes (DHPs), existing studies have included limited follow-up, small samples, and a focus on restricting-type eating disorders. To address these gaps, we explored naturalistic outcomes for an adolescent eating disorders DHP. Adolescent participants (N = 265) completed measurements at treatment admission, discharge (n = 170), and various lengths of follow-up (n = 126; Mfollow up = 278.87 days). Results from multilevel models indicated significant increases in body weight for the anorexia nervosa group throughout treatment and maintenance of increased body weight from discharge to follow-up. In bulimic spectrum disorders, binge eating and purging significantly decreased from intake to discharge and did not change from discharge to follow-up. Across the entire sample, eating disorder symptoms decreased from intake to discharge and did not change from discharge to follow-up. Further, anxiety and depression decreased over the course of treatment and continued to decrease over the follow-up period. The current investigation represents the first study to explore longitudinal DHP outcomes within adolescent bulimic spectrum eating disorders. Our findings also highlight many challenges inherent in conducting naturalistic research; it is critical that the field continue to develop solutions to the barriers inherent in conducting longitudinal research on eating disorder treatment.

APOE modifies the interaction of entorhinal cerebral blood flow and cortical thickness on memory function in cognitively normal older adults.

OBJECTIVE: The ε4 allele of the apolipoprotein E (APOE) gene increases risk for cognitive decline in normal and pathologic aging. However, precisely how APOE ε4 exerts its negative impact on cognition is poorly understood. The present study aimed to determine whether APOE genotype (ε4+ vs. ε4-) modifies the interaction of medial temporal lobe (MTL) resting cerebral blood flow (CBF) and brain structure (cortical thickness [CT], volume [Vo]) on verbal memory performance. METHODS: Multiple linear regression models were employed to investigate relationships between APOE genotype, arterial spin labeling MRI-measured CBF and FreeSurfer-based CT and Vo in four MTL regions of interest (left and right entorhinal cortex and hippocampus), and verbal memory performance among a sample of 117 cognitively normal older adults (41 ε4+, 76 ε4-) between the ages of 64 and 89 (mean age â€‹= â€‹73). RESULTS: Results indicated that APOE genotype modified the interaction of CBF and CT on memory in the left entorhinal cortex, such that the relationship between entorhinal CBF and memory was negative (lower CBF was associated with better memory) in non-carriers with higher entorhinal CT, positive (higher CBF was associated with better memory) in non-carriers with lower entorhinal CT, and negative (higher CBF was associated with worse memory) in ε4 carriers with lower entorhinal CT. CONCLUSIONS: Findings suggest that older adult APOE ε4 carriers may experience vascular dysregulation and concomitant morphological alterations in the MTL that interact to negatively affect memory even in the absence overt clinical symptoms, providing potential insight into the mechanistic link between APOE ε4 and detriments in cognition. Moreover, findings suggest a distinct multimodal neural signature in ε4 carriers (higher CBF and lower CT in the entorhinal cortex) that could aid in the identification of candidates for future clinical trials aimed at preventing or slowing cognitive decline. Differential findings with respect to ε4 carriers and non-carriers are discussed in the context of neurovascular compensation.

Task-switching inefficiencies in currently ill, but not remitted anorexia nervosa.

OBJECTIVE: Models of anorexia nervosa (AN) posit that set-shifting deficits may contribute to behavioral inflexibility and extreme dietary restriction. Findings from neurocognitive studies of set-shifting in AN have been somewhat mixed, perhaps due to the use of tasks that cannot distinguish shifting from other processes (i.e., learning). To more precisely characterize cognitive flexibility and selectively assess this process independent of rule learning and feedback sensitivity, we examined task-switching ability in AN. METHOD: Women ill with AN, subthreshold AN or atypical AN (IAN; n = 40), women remitted from AN (RAN; n = 24), and age-matched healthy control women (n = 42) completed a computerized cued color-shape task-switching paradigm. Groups were compared on mix costs (reflecting global cognitive control) and switch costs (reflecting transient cognitive control). RESULTS: Although mix costs were equivalent across groups, switch costs were more pronounced in the IAN group, as indicated by a group-by-trial type interaction for reaction times on stay and switch trials. DISCUSSION: Findings indicate that IAN, but not RAN, have difficulty flexibly switching between cognitive task sets, and suggest that prior findings of set-shifting deficits in AN may reflect difficulty with cognitive flexibility independent of learning deficits. As such, task-switching may represent a promising adjunctive treatment target.