The effects of acute tryptophan depletion on instrumental reward learning in anorexia nervosa - an fMRI study.

BACKGROUND: The serotonin (5-HT) hypothesis of anorexia nervosa (AN) posits that individuals predisposed toward or recovered from AN (recAN) have a central nervous hyperserotonergic state and therefore restrict food intake as a means to reduce 5-HT availability (via diminished tryptophan-derived precursor supply) and alleviate associated negative mood states. Importantly, the 5-HT system has also been generally implicated in reward processing, which has also been shown to be altered in AN. METHODS: In this double-blind crossover study, 22 individuals recAN and 25 healthy control participants (HC) underwent functional magnetic resonance imaging (fMRI) while performing an established instrumental reward learning paradigm during acute tryptophan depletion (ATD; a dietary intervention that lowers central nervous 5-HT availability) as well as a sham depletion. RESULTS: On a behavioral level, the main effects of reward and ATD were evident, but no group differences were found. fMRI analyses revealed a group × ATD × reward level interaction in the ventral anterior insula during reward anticipation as well as in the medial orbitofrontal cortex during reward consumption. DISCUSSION: The precise pattern of results is suggestive of a 'normalization' of reward-related neural responses during ATD in recAN compared to HC. Our results lend further evidence to the 5-HT hypothesis of AN. Decreasing central nervous 5-HT synthesis and availability during ATD and possibly also by dieting may be a means to normalize 5-HT availability and associated brain processes.

No effects of acute tryptophan depletion on anxiety or mood in weight-recovered female patients with anorexia nervosa.

BACKGROUND: Previous studies have suggested that individuals recovered from anorexia nervosa (AN) are characterized by increased serotonergic (5-HT) activity that might be related to elevated levels of anxiety. Assuming these traits to be also present in individuals at risk for AN, it was further hypothesized that restricting food intake might be a means to temporarily alleviate dysphoric affective states by reducing central nervous availability of tryptophan (TRP), the sole precursor of 5-HT. One study that supported this hypothesis found anxiolytic effects in individuals with a history of AN during an experimentally induced short-term depletion of TRP supply to the brain. METHODS: In this placebo-controlled, double-blind cross-over study, 22 patients weight-recovered from AN (recAN) and 25 healthy control participants (HC) completed questionnaires assessing anxiety and momentary mood during acute tryptophan depletion (ATD), a dietary intervention that lowers central 5-HT synthesis. RESULTS: The ATD procedure effectively reduced the ratio of TRP to competing for large neutral amino acids in the peripheral blood, indicating decreased TRP supply to the brain. Effects of ATD on anxiety and mood did not differ between recAN and HC. Bayesian null hypothesis testing confirmed these initial results. DISCUSSION: Our results do not support the hypothesis that short-term depletion of TRP and its impact on the brain 5-HT reduces anxiety or improves mood in AN. As the evidence for the role of 5-HT dysfunction on affective processes in patients with AN is limited, further studies are needed to assess its relevance in the pathophysiology of AN.

Acute tryptophan depletion balances altered resting-state functional connectivity of the salience network in female patients recovered from anorexia nervosa.

BACKGROUND: It has been suggested that individuals predisposed to or recovered from anorexia nervosa experience a hyperserotonergic state associated with anxiety that might be mitigated by restricted food intake, because diminished levels of the tryptophan precursor lower the central availability of serotonin (5-HT). At the neural level, the salience network is a system of functionally connected brain regions; it has been closely associated with 5-HT functioning and mental disorders (including anorexia nervosa). The aim of the present study was to investigate the effect on the salience network of a temporary dietary manipulation of 5-HT synthesis in patients with anorexia nervosa. METHODS: In this double-blind crossover study, we obtained data on resting-state functional connectivity from 22 weight-recovered female patients with a history of anorexia nervosa, and 22 age-matched female healthy controls. The study procedure included acute tryptophan depletion (a dietary intervention that lowers the central 5-HT synthesis rate) and a sham condition. RESULTS: We identified an interaction of group and experimental condition in resting-state functional connectivity between the salience network and the orbitofrontal cortex extending to the frontal pole (F 1,42 = 12.52; p FWE = 0.026). Further analysis revealed increased resting-state functional connectivity during acute tryptophan depletion in patients recovered from anorexia nervosa, resembling that of healthy controls during the sham condition (T 42 = -0.66; p = 0.51). LIMITATIONS: The effect of acute tryptophan depletion on the central availability of 5-HT can be judged only indirectly using plasma ratios of tryptophan to large neutral amino acids. Moreover, the definition of anorexia nervosa recovery varies widely across studies, limiting comparability. CONCLUSION: Taken together, our findings support the notion of 5-HT dysregulation in anorexia nervosa and indicate that reduced 5-HT synthesis and availability during acute tryptophan depletion (and possibly with food restriction) may balance hyperserotonergic functioning and the associated resting-state functional connectivity of the salience network.

Metabolic state and value-based decision-making in acute and recovered female patients with anorexia nervosa

Background: Patients with anorexia nervosa forgo eating despite emaciation and severe health consequences. Such dysfunctional decision-making might be explained by an excessive level of self-control, alterations in homeostatic and hedonic regulation, or an interplay between these processes. We aimed to understand value-based decision-making in anorexia nervosa and its association with the gut hormone ghrelin. Besides its homeostatic function, ghrelin has been implicated in the hedonic regulation of appetite and reward via the modulation of phasic dopamine signalling. Methods: In a cross-sectional design, we studied acutely underweight (n = 94) and recovered (n = 37) patients with anorexia nervosa of the restrictive subtype, as well as healthy control participants (n = 119). We assessed plasma concentrations of desacyl ghrelin and parameters of delay discounting, probability discounting for gains and losses, and loss aversion. Results: Recovered patients displayed higher risk aversion for gains, but we observed no group differences for the remaining decision-making parameters. Desacyl ghrelin was higher in acutely underweight and recovered participants with anorexia nervosa relative to healthy controls. Moreover, we found a significant group × desacyl ghrelin interaction in delay discounting, indicating that in contrast to healthy controls, acutely underweight patients with anorexia nervosa who had high desacyl ghrelin concentrations preferably chose the delayed reward option. Limitations: We probed decision-making using monetary rewards, but patients with anorexia nervosa may react differently to disorder-relevant stimuli. Furthermore, in contrast to acyl ghrelin, the functions of desacyl ghrelin are unclear. Therefore, the interpretation of the results is preliminary. Conclusion: The propensity for risk aversion as found in recovered patients with anorexia nervosa could help them successfully complete therapy, or it could reflect sequelae of the disorder. Conversely, ghrelin findings might be related to a mechanism contributing to disease maintenance; that is, in acutely underweight anorexia nervosa, a hungry state may facilitate the ability to forgo an immediate reward to achieve a (dysfunctional) long-term goal.

Intact value-based decision-making during intertemporal choice in women with remitted anorexia nervosa? An fMRI study

Background: Extreme restrictive food choice in anorexia nervosa is thought to reflect excessive self-control and/or abnormal reward sensitivity. Studies using intertemporal choice paradigms have suggested an increased capacity to delay reward in anorexia nervosa, and this may explain an unusual ability to resist immediate temptation and override hunger in the long-term pursuit of thinness. It remains unclear, however, whether altered delay discounting in anorexia nervosa constitutes a state effect of acute illness or a trait marker observable after recovery. Methods: We repeated the analysis from our previous fMRI investigation of intertemporal choice in acutely underweight patients with anorexia nervosa in a sample of weight-recovered women with anorexia nervosa (n = 36) and age-matched healthy controls (n = 36) who participated in the same study protocol. Follow-up analyses explored functional connectivity separately in both the weight-recovered/healthy controls sample and the acute/healthy controls sample. Results: In contrast to our previous findings in acutely underweight patients with anorexia nervosa, we found no differences between weight-recovered patients with anorexia nervosa and healthy controls at either behavioural or neural levels. New analysis of data from the acute/healthy controls sample sample revealed increased coupling between dorsal anterior cingulate cortex and posterior brain regions as a function of decision difficulty, supporting the hypothesis of altered neural efficiency in the underweight state. Limitations: This was a cross-sectional study, and the results may be task-specific. Conclusion: Although our results underlined previous demonstrations of divergent temporal reward discounting in acutely underweight patients with anorexia nervosa, we found no evidence of alteration in patients with weight-recovered anorexia nervosa. Together, these findings suggest that impaired valuebased decision-making may not constitute a defining trait variable or "scar" of the disorder.

Peptide YY3-36 concentration in acute- and long-term recovered anorexia nervosa.

PURPOSE: The gut-brain axis could be a possible key factor in the pathophysiology of anorexia nervosa. The neuropeptide peptide YY3-36, secreted by endocrine L cells of the gastrointestinal tract, is a known regulator of appetite and food intake. The objective of this study was to investigate peptide YY3-36 plasma concentrations at different stages of anorexia nervosa in a combined cross-sectional and longitudinal design to differentiate between effects of acute undernutrition and more enduring characteristics. METHODS: We measured fasting plasma peptide YY3-36 concentrations in young patients with acute anorexia nervosa (n = 47) and long-term recovered patients (n = 35) cross-sectionally in comparison to healthy control participants (n = 58), and longitudinally over the course of inpatient treatment. Physical activity was controlled as it may modulate peptide YY secretion. RESULTS: There was no group difference in peptide YY3-36 concentration among young acutely underweight anorexia nervosa patients, long-term recovered anorexia nervosa patients, and healthy control participants. Longitudinally, there was no change in peptide YY3-36 concentration after short-term weight rehabilitation. For acute anorexia nervosa patients at admission to treatment, there was a negative correlation between peptide YY3-36 concentration and body mass index. CONCLUSIONS: The current study provides additional evidence for a normal basal PYY3-36 concentration in AN. Future studies should study multiple appetite-regulating peptides and their complex interplay and also use research designs including a food challenge.

Dynamic changes in white matter microstructure in anorexia nervosa: findings from a longitudinal study.

BACKGROUND: Gray matter (GM) 'pseudoatrophy' is well-documented in patients with anorexia nervosa (AN), but changes in white matter (WM) are less well understood. Here we investigated the dynamics of microstructural WM brain changes in AN patients during short-term weight restoration in a combined longitudinal and cross-sectional study design. METHODS: Diffusion-weighted images were acquired in young AN patients before (acAN-Tp1, n = 56) and after (acAN-Tp2, n = 44) short-term weight restoration as well as in age-matched healthy controls (HC, n = 60). Images were processed using Tract-Based-Spatial-Statistics to compare fractional anisotropy (FA) across groups and timepoints. RESULTS: In the cross-sectional comparison, FA was significantly reduced in the callosal body in acAN-Tp1 compared with HC, while no differences were found between acAN-Tp2 and HC. In the longitudinal arm, FA increased with weight gain in acAN-Tp2 relative to acAN-Tp1 in large parts of the callosal body and the fornix, while it decreased in the right corticospinal tract. CONCLUSIONS: Our findings reveal that dynamic, bidirectional changes in WM microstructure in young underweight patients with AN can be reversed with brief weight restoration therapy. These results parallel those previously observed in GM and suggest that alterations in WM in non-chronic AN are also state-dependent and rapidly reversible with successful intervention.

Preserved white matter microstructure in young patients with anorexia nervosa?

A massive but reversible reduction of cortical thickness and subcortical gray matter (GM) volumes in Anorexia Nervosa (AN) has been recently reported. However, the literature on alterations in white matter (WM) volume and microstructure changes in both acutely underweight AN (acAN) and after recovery (recAN) is sparse and results are inconclusive. Here, T1-weighted and diffusion-weighted MRI data in a sizable sample of young and medication-free acAN (n = 35), recAN (n = 32), and age-matched female healthy controls (HC, n = 62) were obtained. For analysis, a well-validated global probabilistic tractography reconstruction algorithm including rigorous motion correction implemented in FreeSurfer: TRACULA (TRActs Constrained by UnderLying Anatomy) were used. Additionally, a clustering algorithm and a multivariate pattern classification technique to WM metrics to predict group membership were applied. No group differences in either WM volume or WM microstructure were detected with standard analysis procedures either in acAN or recAN relative to HC after controlling for the number of performed statistical tests. These findings were not affected by age, IQ, or psychiatric symptoms. While cluster analysis was unsuccessful at discriminating between groups, multivariate pattern classification showed some ability to separate acAN from HC (but not recAN from HC). However, these results were not compatible with a straightforward hypothesis of impaired WM microstructure. The current findings suggest that WM integrity is largely preserved in non-chronic AN. This finding stands in contrast to findings in GM, but may help to explain the relatively intact cognitive performance of young patients with AN and provide the basis for the fast recovery of GM structures. Hum Brain Mapp 37:4069-4083, 2016. © 2016 Wiley Periodicals, Inc.

Partially restored resting-state functional connectivity in women recovered from anorexia nervosa.

BACKGROUND: We have previously shown increased resting-state functional connectivity (rsFC) in the frontoparietal network (FPN) and the default mode network (DMN) in patients with acute anorexia nervosa. Based on these findings we investigated within-network rsFC in patients recovered from anorexia nervosa to examine whether these abnormalities are a state or trait marker of the disease. To extend the understanding of functional connectivity in patients with anorexia nervosa, we also estimated rsFC between large-scale networks. METHODS: Girls and women recovered from anorexia nervosa and pair-wise, age- and sex-matched healthy controls underwent a resting-state fMRI scan. Using independent component analyses (ICA), we isolated the FPN, DMN and salience network. We used standard comparisons as well as a hypothesis-based approach to test the findings of our previous rsFC study in this recovered cohort. Temporal correlations between network time-course pairs were computed to investigate functional network connectivity (FNC). RESULTS: Thirty-one patients recovered from anorexia nervosa and 31 controls participated in our study. Standard group comparisons revealed reduced rsFC between the dorsolateral prefrontal cortex (dlPFC) and the FPN in the recovered group. Using a hypothesis-based approach we extended the previous finding of increased rsFC between the angular gyrus and the FPN in patients recovered from anorexia nervosa. No group differences in FNC were revealed. LIMITATIONS: The study design did not allow us to conclude that the difference found in rsFC constitutes a scar effect of the disease. CONCLUSION: This study suggests that some abnormal rsFC patterns found in patients recovered from anorexia nervosa normalize after long-term weight restoration, while distorted rsFC in the FPN, a network that has been associated with cognitive control, may constitute a trait marker of the disorder.

Abnormal functional global and local brain connectivity in female patients with anorexia nervosa.

BACKGROUND: Previous resting-state functional connectivity studies in patients with anorexia nervosa used independent component analysis or seed-based connectivity analysis to probe specific brain networks. Instead, modelling the entire brain as a complex network allows determination of graph-theoretical metrics, which describe global and local properties of how brain networks are organized and how they interact. METHODS: To determine differences in network properties between female patients with acute anorexia nervosa and pairwise matched healthy controls, we used resting-state fMRI and computed well-established global and local graph metrics across a range of network densities. RESULTS: Our analyses included 35 patients and 35 controls. We found that the global functional network structure in patients with anorexia nervosa is characterized by increases in both characteristic path length (longer average routes between nodes) and assortativity (more nodes with a similar connectedness link together). Accordingly, we found locally decreased connectivity strength and increased path length in the posterior insula and thalamus. LIMITATIONS: The present results may be limited to the methods applied during preprocessing and network construction. CONCLUSION: We demonstrated anorexia nervosa-related changes in the network configuration for, to our knowledge, the first time using resting-state fMRI and graph-theoretical measures. Our findings revealed an altered global brain network architecture accompanied by local degradations indicating wide-scale disturbance in information flow across brain networks in patients with acute anorexia nervosa. Reduced local network efficiency in the thalamus and posterior insula may reflect a mechanism that helps explain the impaired integration of visuospatial and homeostatic signals in patients with this disorder, which is thought to be linked to abnormal representations of body size and hunger.

A naturalistic examination of negative affect and disorder-related rumination in anorexia nervosa.

In anorexia nervosa (AN), volitional inhibition of rewarding behaviors, such as eating, involves a conflict between the desire to suppress appetite and the inherent motive to consume. This conflict is thought to have costs that carry over into daily life, e.g., triggering negative affect and/or recurring ruminations, which may ultimately impact long term outcome. Hence, increasing research effort is being dedicated to understand the link between emotional and ruminative processes in the etiology and maintenance of AN. We investigated whether affective states influence disorder-related rumination in AN applying "ecological momentary assessment", a method which allows the experimenter to gain insight into psychological processes in the natural environment and assess data in real time. Participants (AN = 37, healthy controls = 33) were given a smartphone for 14 days. A ringtone signaled at six random time-points each day to fill in a questionnaire, which gauged disorder-typical thoughts about food and weight as well as affective state. Analyses, applying hierarchical linear models confirmed that AN patients spend more time thinking about food, body shape and weight than controls (p < 0.001). Additionally, the results support the hypothesis that momentary negative affect (but not baseline depression (p = 0.56) or anxiety symptoms (p = 0.60) are positively associated with a higher amount of disorder-related rumination in patients (p < 0.001). Our findings are in line with theories which claim that ruminative thinking induces a vulnerability to negative stimuli which, in turn, fosters heightened negative affect. Thus, therapeutic interventions could be improved by implementing modules that specifically target disorder-related rumination.

Reduced functional connectivity in the thalamo-insular subnetwork in patients with acute anorexia nervosa.

The neural underpinnings of anorexia nervosa (AN) are poorly understood. Results from existing functional brain imaging studies using disorder-relevant food- or body-stimuli have been heterogeneous and may be biased due to varying compliance or strategies of the participants. In this study, resting state functional connectivity imaging was used. To explore the distributed nature and complexity of brain function we characterized network patterns in patients with acute AN. Thirty-five unmedicated female acute AN patients and 35 closely matched healthy female participants underwent resting state functional magnetic resonance imaging. We used a network-based statistic (NBS) approach [Zalesky et al., 2010a] to identify differences between groups by isolating a network of interconnected nodes with a deviant connectivity pattern. Group comparison revealed a subnetwork of connections with decreased connectivity including the amygdala, thalamus, fusiform gyrus, putamen and the posterior insula as the central hub in the patient group. Results were not driven by changes in intranodal or global connectivity. No network could be identified where AN patients had increased coupling. Given the known involvement of the identified thalamo-insular subnetwork in interoception, decreased connectivity in AN patients in these nodes might reflect changes in the propagation of sensations that alert the organism to urgent homeostatic imbalances and pain-processes that are known to be severely disturbed in AN and might explain the striking discrepancy between patient's actual and perceived internal body state.

Elevated cognitive control over reward processing in recovered female patients with anorexia nervosa.

BACKGROUND: Individuals with anorexia nervosa are thought to exert excessive self-control to inhibit primary drives. METHODS: This study used functional MRI (fMRI) to interrogate interactions between the neural correlates of cognitive control and motivational processes in the brain reward system during the anticipation of monetary reward and reward-related feedback. In order to avoid confounding effects of undernutrition, we studied female participants recovered from anorexia nervosa and closely matched healthy female controls. The fMRI analysis (including node-to-node functional connectivity) followed a region of interest approach based on models of the brain reward system and cognitive control regions implicated in anorexia nervosa: the ventral striatum, medial orbitofrontal cortex (mOFC) and dorsolateral prefrontal cortex (DLPFC). RESULTS: We included 30 recovered patients and 30 controls in our study. There were no behavioural differences and no differences in hemodynamic responses of the ventral striatum and the mOFC in the 2 phases of the task. However, relative to controls, recovered patients showed elevated DLPFC activity during the anticipation phase, failed to deactivate this region during the feedback phase and displayed greater functional coupling between the DLPFC and mOFC. Recovered patients also had stronger associations than controls between anticipation-related DLPFC responses and instrumental responding. LIMITATIONS: The results we obtained using monetary stimuli might not generalize to other forms of reward. CONCLUSION: Unaltered neural responses in ventral limbic reward networks but increased recruitment of and connectivity with lateral-frontal brain circuitry in recovered patients suggests an elevated degree of selfregulatory processes in response to rewarding stimuli. An imbalance between brain systems subserving bottom-up and top-down processes may be a trait marker of the disorder.

[Anorexia nervosa - from a neuroscience perspective]. / Anorexia nervosa. Aktuelle neurowissenschaftliche Befunde.

Anorexia nervosa is a frequent disorder especially among adolescent girls and young women, with high morbidity, mortality, and relapse rates. To date, no single therapeutic approach has proved to be superior to others (Herpertz et al., 2011). It remains unclear how its etiology and pathology are encoded within cognitive, neural, and endocrinological processes that modulate important mechanisms in appetitive processing and weight regulation. Yet, several trait characteristics have been identified in AN which might reflect predisposing factors. Further, altered levels of neuropeptides and hormones that regulate appetite and feeding behavior have been found during both the acute and the recovered state, pointing to dysfunctional mechanisms in AN that persist even after malnutrition has ceased. Researchers are also hoping that brain imaging techniques will allow for a more detailed investigation of the neural basis of reward and punishment sensitivity that appears to be altered in AN. The integration and extension of recent findings in these areas will hopefully provide a more comprehensive understanding of the disorder and hence enable the development of more effective treatments.

Hair endocannabinoid concentrations in individuals with acute and weight-recovered anorexia nervosa.

BACKGROUND: The endocannabinoid system has been suggested to modulate energy metabolism and stress response and could be an important factor in the pathophysiology of anorexia nervosa (AN). In the context of AN, excessive physical activity may influence endocannabinoid concentrations. The objective of this study was to investigate hair endocannabinoid concentrations at different stages of the disorder. Measurement in hair allows for a cumulative assessment of endocannabinoid concentrations independent of circadian rhythms. METHODS: In a combined cross-sectional and longitudinal design, we measured hair concentrations of the endocannabinoids anandamide and 2-arachidonoylglycerol and the endocannabinoid-related compounds palmitoylethanolamide, oleoylethanolamide, and stearoylethanolamide in female underweight patients with acute AN (n = 67, reassessment of n = 47 after short-term weight restoration with a body mass index increase of at least 14%), individuals long-term recovered from AN (n = 27), and healthy control participants (n = 84). RESULTS: Hair concentrations of anandamide and all endocannabinoid-related compounds were elevated in acute AN and decreased over the course of short-term weight restoration. Anandamide concentrations remained elevated in long-term recovered AN patients. In long-term recovered patients, physical activity correlated positively with the concentrations of all endocannabinoid-related compounds. CONCLUSION: The current study provides evidence for a significant alteration of the endocannabinoid system in acute AN, which may partly persist into long-term recovery. The endocannabinoid system may be a possible target for pharmaceutical interventions in AN, which should be explored in further preclinical and subsequently clinical randomized controlled trials.

More by stick than by carrot: A reinforcement learning style rooted in the medial frontal cortex in anorexia nervosa.

Anorexia nervosa (AN) is characterized by a relentless pursuit of thinness, despite serious implications for health and social relations. In a previous study wielding the power of computational psychiatry, we found alterations in learning from negative feedback and in neural activity in the posterior medial frontal cortex (pMFC) in young acutely underweight AN patients (acAN). Here we ask whether these abnormalities are merely a state-related consequence of the illness or whether they might constitute a trait marker predisposing individuals to AN. To address this question, we employed the same reinforcement learning paradigm during fMRI with 31 female former AN patients after complete weight-recovery (recAN) and 31 age-matched healthy volunteers (15-28 years). Participants performed a decision task that required adaptation to changing reward contingencies. Data were analyzed within a hierarchical Gaussian filter model, which captures interindividual variability in feedback learning and decision-making under uncertainty. Similar to acute patients, individuals recovered from AN appear to emphasize negative over positive feedback when updating expectations regarding changing reward-punishment contingencies (difference in learning rate between punished and rewarded trials was increased in recAN: p = .006, d = .70. This behavioral pattern was mirrored in hyperactivation of the pMFC following negative feedback (FWE p < .001). Because the previously observed alterations in acANs are also evident after recovery and do not correlate with state variables like weight, altered feedback learning might be a trait marker of AN. The neural underpinnings of these alterations may lie in the pMFC. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Cognitive overcontrol as a trait marker in anorexia nervosa? Aberrant task- and response-set switching in remitted patients.

Individuals with anorexia nervosa (AN) often present inflexible behaviors and rigid thinking styles, which may contribute to disorder maintenance. Studies of set shifting have documented impairments in AN, but results have varied across samples. Moreover, the hypothesis that deficient set shifting may constitute an endophenotype rests largely on observations made with neuropsychological tests with limited ability to isolate component cognitive control processes. The current behavioral study used a task switching paradigm with a demonstrated ability to fractionate the hierarchical organization underlying task- and response-set shifting in 22 weight-recovered women with a history of AN (recAN) relative to 22 age-matched healthy controls. Whereas recAN performed generally more accurately than healthy controls, they also responded more slowly. Despite slower performance, however, recAN error rates did not exhibit the characteristic improvement in task switching on trials with a concurrent response switch-an interaction thought to index efficient action sequencing and the hierarchical control of behavior. These results were not mediated by comorbid symptoms, but no relationships with clinical measures were detected. Inefficient set shifting in AN may be related to a general tendency to sustain a high level of cognitive control (as evident here in a robust speed-accuracy trade-off), which interferes with context-sensitive regulation of processing priorities (as evident here in an atypical interaction between task and response switching). Although scarring effects cannot be excluded and the generalizability of our findings needs to be tested, the current observations in recAN provide novel evidence that altered set shifting may be a trait marker of the disorder. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Goal-directed vs. habitual instrumental behavior during reward processing in anorexia nervosa: an fMRI study.

Previous studies have proposed that altered reward processing and elevated cognitive control underlie the etiology of anorexia nervosa (AN). A newly debated notion suggests altered habit learning and an overreliance on habits may contribute to the persistence of AN. In weight-recovered AN patients, we previously found neuroimaging-based evidence for unaltered reward processing, but elevated cognitive control. In order to differentiate between state versus trait factors, we here contrast the aforementioned hypotheses in a sample of acutely underweight AN (acAN) patients. 37 acAN patients and 37 closely matched healthy controls (HC) underwent a functional MRI while performing an established instrumental motivation task. We found no group differences with respect to neural responses during the anticipation or receipt of reward. However, the behavioral response data showed a bimodal distribution, indicative for a goal-directed (gAN) and a habit-driven (hAN) patient subgroup. Additional analyses revealed decreased mOFC activation during reward anticipation in hAN, which would be in line with a habit-driven response. These findings provide a new perspective on the debate regarding the notion of increased goal-directed versus habitual behavior in AN. If replicable, the observed dissociation between gAN and hAN might help to tailor therapeutic approaches to individual patient characteristics.

Is hypercortisolism in anorexia nervosa detectable using hair samples?

Anorexia nervosa (AN) is a severe mental disorder accompanied by extensive metabolic and endocrine abnormalities. It has been associated with hypercortisolism using short-term measurement methods such as 24 h-urine, saliva, and blood. The aim of this study was to examine whether the proposed hypercortisolism in acutely underweight AN (acAN) is also reflected in a long-term measure: hair cortisol (HCC). To gain further insight, we compared hair cortisol to a well-established classical cortisol measure (24 h-urine; UCC) longitudinally in acAN. Hair samples were collected and analyzed using a LC-MS/MS-based method to provide a monthly cortisol value. We compared HCC in samples of 40 acAN with 40 pairwise age-matched healthy controls (HC) as well as 23 long-term recovered AN participants (recAN) with 23 pairwise age-matched HC (cross-sectional design). In the second part, UCC collected weekly during 14 weeks of weight-restoration therapy in 16 acAN was compared with the (time-corresponding) HCC using linear mixed models and bivariate correlations (longitudinal design). No group differences in HCC occurred comparing acAN and recAN to HC (cross-sectional study). The longitudinal analysis revealed a decrease of UCC but not HCC with weight gain. Furthermore, there was no overall significant association between UCC and HCC. Only in the last four weeks of weight-restoration therapy we found a significant moderate correlation between UCC and HCC. HCC did not reflect the expected hypercortisolism in acAN and did not decrease during short-term weight-restoration. Time-corresponding measurements of UCC and HCC were not consistently associated in our longitudinal analysis of acAN undergoing inpatient treatment. Given the drastic metabolic disturbances in acutely underweight AN our findings could be interpreted as disturbed cortisol incorporation or altered activity of 11-ß-HSD-enzymes in the hair follicle.

Processing and regulation of negative emotions in anorexia nervosa: An fMRI study.

Theoretical models and recent advances in the treatment of anorexia nervosa (AN) have increasingly focused on the role of alterations in the processing and regulation of emotions. To date, however, our understanding of these changes is still limited and reports of emotional dysregulation in AN have been based largely on self-report data, and there is a relative lack of objective experimental evidence or neurobiological data. The current functional magnetic resonance imaging (fMRI) study investigated the hemodynamic correlates of passive viewing and voluntary downregulation of negative emotions by means of the reappraisal strategy detachment in AN patients. Detachment is regarded as adaptive regulation strategy associated with a reduction in emotion-related amygdala activity and increased recruitment of prefrontal brain regions associated with cognitive control processes. Emotion regulation efficacy was assessed via behavioral arousal ratings and fMRI activation elicited by an established experimental paradigm including negative images. Participants were instructed to either simply view emotional pictures or detach themselves from feelings triggered by the stimuli. The sample consisted of 36 predominantly adolescent female AN patients and a pairwise age-matched healthy control group. Behavioral and neuroimaging data analyses indicated a reduction of arousal and amygdala activity during the regulation condition for both patients and controls. However, compared with controls, individuals with AN showed increased activation in the amygdala as well as in the right dorsolateral prefrontal cortex (dlPFC) during the passive viewing of aversive compared with neutral pictures. These results extend previous findings indicative of altered processing of salient emotional stimuli in AN, but do not point to a general deficit in the voluntary regulation of negative emotions. Increased dlPFC activation in AN during passive viewing of negative stimuli is in line with the hypothesis that the disorder may be characterized by excessive self-control. Taken together, the data seem to suggest that reappraisal via detachment may be an effective strategy to reduce negative arousal for individuals with AN.