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Recovery and chronicity in anorexia nervosa: brain activity associated with differential outcomes
Abstract
The course of anorexia nervosa varies from rapid recovery to a chronic debilitating illness. This study aimed to identify functional neural correlates associated with differential outcomes.
Brain reactions to food and emotional visual stimuli were measured with functional magnetic resonance imaging in nine women who had long-term recovery from restricting anorexia nervosa. These were compared with age- and education-matched groups of eight women chronically ill with restricting anorexia nervosa and nine healthy control women.
In response to food stimuli, increased medial prefrontal and anterior cingulate activation, as well as a lack of activity in the inferior parietal lobule, differentiated the recovered group from the healthy control subjects. Increased activation of the right lateral prefrontal, apical prefrontal, and dorsal anterior cingulate cortices differentiated these recovered subjects from chronically ill patients. Group differences were specific to food stimuli, whereas processing of emotional stimuli did not differ between groups.
Separate neural correlates underlie trait and state characteristics of anorexia nervosa. The medial prefrontal response to disease-specific stimuli may be related to trait vulnerability. Lateral and apical prefrontal involvement is associated with a good outcome.
... Findings of functional magnetic resonance imaging (fMRI) studies comparing REC and non-patients (NP) show divergent results. With respect to visual food cues, some authors reported no alteration in brain activation in REC (when compared to NP) [21][22][23], while Uher et al. [24] detected increased activation of prefrontal and anterior cingulate cortices (ACC) and a reduction of activity in parietal regions in a small group of REC. Further studies found hypoactivation of the insula [25] or increased caudate activation [26] in response to food pictures. ...
... In this context, the comparison of NP and REC is of particular interest. It complements previous studies on disease-specific food stimuli in REC [21][22][23][24][25][26]. The paradigm has already been employed previously in a study of AN with some REC participants [24,43] and a study focusing on NP versus AN [44]. ...
... It complements previous studies on disease-specific food stimuli in REC [21][22][23][24][25][26]. The paradigm has already been employed previously in a study of AN with some REC participants [24,43] and a study focusing on NP versus AN [44]. Data from the current study comparing NP and AN has been reported previously, with a focus on replicability issues [45]: Group comparisons yielded higher blood oxygenation-level dependent (BOLD) responses of AN compared to NP in midcingulate, pre/postcentral and parietal areas when using a lenient initial threshold, and no significant group differences with a conservative initial threshold. ...
Background
The understanding of the cerebral neurobiology of anorexia nervosa (AN) with respect to state- versus trait-related abnormalities is limited. There is evidence of restitution of structural brain alterations with clinical remission. However, with regard to functional brain abnormalities, this issue has not yet been clarified.
Methods
We compared women with AN (n = 31), well-recovered female participants (REC) (n = 18) and non-patients (NP) (n = 27) cross-sectionally. Functional magnetic resonance imaging was performed to compare neural responses to food versus non-food images. Additionally, affective ratings were assessed.
Results
Functional responses and affective ratings did not differ between REC and NP, even when applying lenient thresholds for the comparison of neural responses. Comparing REC and AN, the latter showed lower valence and higher arousal ratings for food stimuli, and neural responses differed with lenient thresholds in an occipital region.
Conclusions
The data are in line with some previous findings and suggest restitution of cerebral function with clinical recovery. Furthermore, affective ratings did not differ from NP. These results need to be verified in intra-individual longitudinal studies.
... Uher and coworkers (Uher, Brammer, et al., 2003;Uher, Murphy, et al., 2004) have extensively studied the neural correlates of the processing of visual food stimuli in EDs and found that both AN and BN showed decreased activation in areas that are associated with appetitive behavior (inferior parietal lobe, occipital cortex) and increased activation in areas that are associated with cognitive control (medial prefrontal cortex), compared with non-eating-disordered controls. Gordon et al. (2001) used positron emission tomographic measurements of regional cerebral blood flow (rCBF) to compare responses of AN and healthy participants while viewing pictures of high-and low-calorie foods, and nonfood items. ...
... Nevertheless, the causal relationships between brain alterations and the clinical syndrome are unclear because primary neural disturbances cannot be differentiated from phenomena secondary to the disorder. In an effort to overcome this problem, Uher et al. (2003) investigated responses to food stimuli and pictures from the International Affective Picture System (IAPS) with fMRI in chronically ill AN-R and in long-term recovered AN-R and healthy controls. Instead of a prospective design, which would be difficult to realize, Uher et al. (2003) argued that by obtaining evidence from people fully recovered from AN trait factors could be identified without the confounding evidence from acute starvation, metabolic alterations, and treatment-related stress. ...
... In an effort to overcome this problem, Uher et al. (2003) investigated responses to food stimuli and pictures from the International Affective Picture System (IAPS) with fMRI in chronically ill AN-R and in long-term recovered AN-R and healthy controls. Instead of a prospective design, which would be difficult to realize, Uher et al. (2003) argued that by obtaining evidence from people fully recovered from AN trait factors could be identified without the confounding evidence from acute starvation, metabolic alterations, and treatment-related stress. The main finding of this study was that food-related brain activity in recovered AN-R was a combination of responses seen in currently ill AN-R (increased activity in the medial frontal and anterior cingulated cortices) and those recorded in healthy controls (increased activity in the apical and lateral prefrontal cortices). ...
... Research has consistently highlighted that people with a diagnosed Eating Disorder (ED) or sub-threshold symptoms self-report higher negative emotions (e.g. disgust, anxiety, fear) in response to food stimuli compared to Healthy Controls (HCs) [1][2][3][4][5]. Harvey et al. (2002) found that levels of disgust and fear in response to high calorie food images increased with abnormal eating attitudes [6]. ...
... Findings of the current study only in part support the results of a systematic review by [8] in which HCs showed greater activation in occipital cortex and inferior parietal lobule compared to AN participants [3,5]. However, some studies have not shown greater activation in HCs compared to ANs in specific areas of the brain [3][4][5] and in this study participants with AN had higher activation of the visual cortex (occipital lobe) to high energy happy and fear foods compared to the HCs. The observed differences may reflect the methodological variations in the design of the studies, including studies of not satiated participants [3], different experimental paradigms such as instructing participants to think about their perception of hunger when viewing the images [47] and sample differences (e.g. ...
... However, satiation status alone is insufficient to explain differences as enhanced activation in visual areas of the brain (e.g. occipital cortex) in response to motivationally relevant images (food and tools) have been reported by other investigators in HCs when not satiated [48][49][50] or as in the Uher et al. studies [4,5] where participants were in an intermediate state between hunger and satiety. Further research is needed to determine the extent of reduced food-related somatosensory processing in people with AN when satiated and when not satiated. ...
To compare neural responses to high and low-energy food images in patients with Anorexia Nervosa (AN) and an age-matched Healthy Control (HC) group. 25 adolescents with AN and 21 HCs completed a diagnostic interview, self-report questionnaires and fMRI, during which they viewed food images evoking responses of disgust, happiness, or fear. Following whole brain analyses, neural responses in six regions of interest were examined in a series of between-group contrasts, across the three emotive categories. Compared to the HCs, people in the AN group showed increased responsivity to high-energy (1) disgust images in temporal lobe, frontal lobe, insula, and cerebellum anterior lobe; (2) fear images in occipital lobe, temporal, and frontal lobes and (3) happy images in frontal lobe, cerebellum anterior lobe, sub-lobar, and cuneus. More activity was observed in response to low-energy (1) disgust food images in the temporal lobe, frontal lobe, insula, cerebellum anterior and posterior lobes, parietal lobe, occipital lobe, and limbic lobe; (2) and happy food images in frontal lobes. Few correlations were found with levels of eating disorder symptoms. The findings highlight the emotional impact of diverse high and low-energy foods for people with AN. People without AN may have a better capacity to filter salient from non-salient information relating to the current task when viewing high energy foods. In summary, for those with AN, it would seem their ability to efficiently ‘sort-out’ information (especially information pertaining to disorder-relevant stimuli such as food images) to complete the task at hand, may be diminished.
... Individuals with AN exhibit less activation in reward-related brain regions (e.g., ventral tegmental area, dorsal striatum) in response to palatable food cues compared to those with bulimia nervosa [21,34]. Paralleling the literature on reward anticipation, individuals with AN also show greater activation of cognitive control circuitry (e.g., medial or dorsolateral prefrontal cortex) during the receipt of food [35][36][37], social [38], and monetary [25] rewards compared to HC participants. Further, while hunger enhances reward experiencing among HC participants, reflecting a biological tendency to seek rewards (such as food) in a deprived state, reward-related brain activation is unaffected by hunger in AN [39]. ...
... Therefore, they are informed that treatment will emphasize identifying other sources of positive emotion that do not involve engaging in eating-disorder behaviors. The importance of increasing cognitive flexibility around rewards is especially highlighted to individuals with AN, who appear to demonstrate enhanced cognitive control and rigidity surrounding rewards [24,25,[35][36][37][38]. ...
... Given the evidence suggesting heightened or rigid cognitive control over reward in AN [24,25,[35][36][37][38], increasing cognitive flexibility to enhance positive affect is likely to be an especially important skill in this population. Additionally, because self-conscious positive emotions have been especially linked to eating-disorder behaviors in AN [23,[53][54][55], the "Taking Ownership" skill may be particularly important to emphasize in order to build a sense of agency disconnected from eating-disorder symptoms. ...
Accumulating psychobiological data implicate reward disturbances in the persistence of anorexia nervosa (AN). Evidence suggests that individuals with AN demonstrate decision-making deficits similar to those with mood and anxiety disorders that cause them to under-respond to many conventionally rewarding experiences (e.g., eating, interacting socially). In contrast, unlike individuals with other psychiatric disorders, individuals with AN simultaneously over-respond to rewards associated with eating-disorder behaviors (e.g., restrictive eating, exercising). This pattern of reward processing likely perpetuates eating-disorder symptoms, as the rewards derived from eating-disorder behaviors provide temporary relief from the anhedonia associated with limited responsivity to other rewards. Positive Affect Treatment (PAT) is a cognitive-behavioral intervention designed to target reward deficits that contribute to anhedonia in mood and anxiety disorders, including problems with reward anticipation, experiencing, and learning. PAT has been found to promote reward responsivity and clinical improvement in mood and anxiety disorders. This manuscript will: (1) present empirical evidence supporting the promise of PAT as an intervention for AN; (2) highlight nuances in the maintaining processes of AN that necessitate adaptations of PAT for this population; and (3) suggest future directions in research on PAT and other reward-based treatments that aim to enhance clinical outcomes for AN.
... Ob es sich bei den gefundenen Veränderungen um Ursache oder Folge der Erkrankung handelt, ist jedoch durch Untersuchungen an Patientinnen schwer auszumachen. In dieser Frage kann die Untersuchung von remittierten Patientinnen mehr Klarheit schaffen, denn sie tragen weiterhin ihre spezifischen Persönlichkeitszüge, ohne dass durch das Hungern akute metabolische Veränderungen mit im Spiel sind (Uher et al., 2003). ...
... Angst vor dem Essen bleibt neuronal jedoch weiter bestehen, obwohl Essensbilder in gleicher Weise als angenehm oder angstauslösend bewertet werden wie von Gesunden (Uher et al., 2003). Hat sich die gelernte Verknüpfung von Essen, Nahrungsaufnahme und Angst so stark in das Gehirn der Erkrankten "eingebrannt", dass sie auch trotz normalem ...
... Es ist also durchaus denkbar, dass eine adäquate Psychotherapie auch bei AN zu einer Normalisierung der neuronalen Aktivitätsmuster führt.Auch für die Anorexie gibt es schon Untersuchungen, wie es sich um die neurobiologischen funktionellen Veränderungen bei Remission verhält. Im Gegensatz zu unseren Ergebnissen wurden insbesondere bei der Konfrontation mit krankheitsspezifischen negativen Stimuli (Essensbilder, Geschmack etc.) persistierende abweichende Aktivierungsmuster bei Remittierten festgestellt(Bang et al., 2017;Uher et al., 2003;Wagner et al., 2007).Uher et al. (2003) machten jedoch eine Unterscheidung zwischen krankheitsspezifischen und allgemein emotionalen Stimuli, um herauszufinden welche neuronalen Verarbeitungsprozesse speziell durch Essens-bezogene Stimuli ausgelöst werden. Sie fanden eine Hyperaktivierung im mPFC und ACC bei AN und RE während der Konfrontation mit Essens-Bildern, jedoch keine signifikanten Unterschiede der RE zu den HC bei der Konfrontation mit aversiven IAPS-Bildern, unter denen sich auch angstauslösende Bilder befanden. ...
Die Angst, die ein zentraler Bestandteil der Anorexia Nervosa ist, ist bei den Patientinnen extrem gesteigert – Angst vor Nahrungsaufnahme, Angst vor Gewichtszunahme, Angst davor schlechte Leistung zu erbringen. Durch unsere Studie wollen wir herausfinden, ob AN-Patientinnen zu einem erleichtertem Angstlernen neigen und wie sich die gefundenen Ergebnisse bei remittierten Probandinnen verhalten (state vs. trait).
Wir verwenden das IF-Paradigma und psychometrische Fragebögen, um die neuronalen Prozesse beim Angstlernen und das subjektive Angstempfinden, bzw. vorhandene Persönlichkeitsstrukturen der beiden Probandengruppen im Vergleich zu Gesunden darzustellen.
... Although the functional relevance of regional structural abnormalities in AN is largely unknown, studies have explored the neural processes underlying visuospatial ability (Palazidou et al. 1990, Jones et al. 1991, Szmukler et al. 1992, Kingston et al. 1996, Favaro et al. 2012, attention and memory (Jones et al. 1991, Szmukler et al. 1992, Green et al. 1996, Kingston et al. 1996, Seed et al. 2000, Nikendei et al. 2011, reward processing, emotional regulation (Jänsch et al. 2009, Joos et al. 2009, Cowdrey et al. 2012, social cognition (McAdams and Krawczyk 2011), cognitive flexibility (Uher et al. 2003, Garret et al 2014 and perfectionism (Tchanchuria et al. 2004, Roberts et al. 2007, Zastrow et al. 2009, Sato et al. 2013) in acute and recovered AN patients. These studies examining the neurofunctional aspects of AN indicate aberrations in activity within the cortico-limbo-striatal system, including but not limited to DLPFC, ACC, OFC, insula, ventral and dorsal striatum, and the thalamus (Friederich et al. 2006, Wagner et al. 2007, Zastrow et al. 2009, Frank et al. 2012, Kaye et al. 2013). ...
... In line with the reductions in regional blood flow and volume in ACC (Kojima et al. 2005), functional alterations in the ACC in both the acute and weight-restored AN patients have been reported (Frank et al. 2002, Uher et al. 2003, Pieters et al. 2007, Zastrow et al. 2009). Hypoactivation in the ACC in AN compared to healthy persons has been reported during a Stroop test -a task requiring response flexibility (Ferro et al. 2005) via SPECT and during a target detection task (using geometric shapes) measuring cognitive shifts in AN which persisted after recovery (via fMRI) (Zastrow et al. 2009). ...
... healthy controls) (Wagner et al. 2008). Conversely, several fMRI studies reported abnormally elevated ACC activity AN patients, in response to food stimuli in (Uher et al. 2003, Sanders et al. 2015, and in a Wisconsin Card Sorting Test (Sato et al. 2013), a frequently used task for measuring cognitive flexibility and problem-solving ability (Stuss et al. 2000). The inconsistency may be partially explained by the multimodal and heterogeneous feature of ACC with potential heterogeneous functions (e.g. ...
The findings from neuroscience have shaped our understanding in the past decade regarding the way we perceive psychiatric illness. In addition to the more conventional theories that are based solely on the psychological and sociocultural factors to explain psychiatric disorders, there is growing evidence supporting a multifactorial etiology with genetic and neurological components. Anorexia nervosa, a life-threatening psychiatric disorder with relentless restrictive eating resulting in extremely low body weight, is one such illness that may be categorized as a brain disorder based on the recent findings. Although inconsistencies exist, several studies investigated the structural and the neurochemical alterations in the brain as well as the functional significance and the cognitive manifestations of these abnormalities in anorexia nervosa patient. This review aims to summarize the current literature on the neural aberrations and several treatment approaches targeting these abnormalities in anorexia nervosa.
... Visual stimuli comprised food images representing categories such as savoury, sweet, low and high caloric content, as well as non-food images (including neutral, emotional, social stimuli), along with food and non-food words. The potential effects of visual stimuli were mostly explored through passive viewing tasks 9,[17][18][19]22,23,25,26,28,37,39,40 , but also through a food choice task 21 , an affective Go/No-Go task 31 , an anticipation task viewing food or object images 33 , an appetitive reversal learning task 24 , a cue-reactivity task 30,35 , a memory task 38 , a rating task 36 , and, in combination with taste-based stimuli, an associative taste reward learning paradigm 34 . Most of the studies employing taste-based stimuli focused solely on the presentation of the tastants (food and non-food): participants were presented with chocolate milk or water 41 , ionic water or sucrose solution 29 , sucrose solution compared with a bitter solution and water 32 . ...
... The (See Fig. 2). A qualitative analysis of the results revealed that this cluster was primarily in uenced by three experiments: two focusing on the HC > AN contrast 37,40 , whereas the third experiment involved the HC > REC contrast 39 . Conversely, the analysis carried out on the reverse contrast (i.e., AN + REC > HC) included 21 experiments and 86 foci, but did not yield any signi cant clusters. ...
Despite the increased interest in understanding the neural underpinnings of Anorexia Nervosa (AN), its neurobiology is poorly understood. This activation likelihood estimation (ALE) meta-analysis aimed to explore brain activity during food stimuli processing among individuals with AN and those who have recovered (REC). Following the PRISMA guidelines, we searched throughout PubMed and PsycInfo, until the 28th of June 2023. Twenty-six publications were included, encompassing data from 403 AN, 141 REC, and 472 HC. The findings indicated significant convergence in the left Inferior Parietal Lobule (IPL) in the HC > AN + REC contrast, whereas the AN + REC > HC contrast did not yield any significant cluster. From the sensitivity analyses confined to studies encompassing solely visual stimuli, the same significant cluster (left IPL) emerged for the HC > AN + REC contrast and no significant convergence was found for the reverse contrast, showing that the stimulation employed (visual, taste-based or olfactory cues) does not affect the food stimuli processing. Furthermore, when limited to studies involving only AN participants, the sensitivity analyses found no significant convergence for either the HC > AN or the reverse contrast. The fact that no significant cluster emerged when excluding REC participants from the analyses, together with a qualitative analysis of the results from the merged sample (i.e., HC > AN + REC contrast), suggests that REC individuals maintain the dysfunctional pattern. The hypoactivation of the left IPL supports its role in body image disturbance, diminished somatosensory-gustatory processing related to fasting, and fear with weight gain, three core symptoms of AN.
... One important circuit that may play a role in the clinical effects of DBS in AN is the reward system which has been proposed as a key brain circuit in the pathophysiology of AN [8][9][10][11][12][13][14][15][16][17]. The reward circuit encompasses multiple brain regions including the ventral striatum, insula and prefrontal cortex. ...
... A region of interest (ROI) analysis was performed for the ventral striatum (VS) and the medial orbitofrontal cortex (mOFC). These regions were chosen a-priori based on their strong relation to reward processing [13], their role in AN pathology and their previous use in AN-fMRI-studies [14][15][16]. Furthermore, the VS was also the target of DBS. The VS was based on peak-coordinates from a previous study using a similar monetary reward task [17]. ...
Background
Anorexia nervosa (AN) is a severe and life-threatening psychiatric disorder. Initial studies on deep brain stimulation (DBS) in severe, treatment-refractory AN have shown clinical effects. However, the working mechanisms of DBS in AN remain largely unknown. Here, we used a task-based functional MRI approach to understand the pathophysiology of AN.
Methods
We performed functional MRI on four AN patients that participated in a pilot study on the efficacy, safety, and functional effects of DBS targeted at the ventral limb of the capsula interna (vALIC). The patients and six gender-matched healthy controls (HC) were investigated at three different time points. We used an adapted version of the monetary incentive delay task to probe generic reward processing in patients and controls, and a food-specific task in patients only.
Results
At baseline, no significant differences for reward anticipation were found between AN and HC. Significant group (AN and HC) by time (pre- and post-DBS) interactions were found in the right precuneus, right putamen, right ventral and medial orbitofrontal cortex (mOFC). No significant interactions were found in the food viewing task, neither between the conditions high-calorie and low-calorie food images nor between the different time points. This could possibly be due to the small sample size and the lack of a control group.
Conclusion
The results showed a difference in the response of reward-related brain areas post-DBS. This supports the hypotheses that the reward circuitry is involved in the pathogenesis of AN and that DBS affects responsivity of reward-related brain areas.
Trial registration Registered in the Netherlands Trial Register (https://www.trialregister.nl/trial/3322): NL3322 (NTR3469).
... A recent review 13 has outlined the main neural alterations observed in adults with full-threshold AN in response to active viewing of food pictures; in particular, participants were required to either imagine eating the food shown, or to rate food cues according to their pleasantness 13 . Full-threshold AN patients showed lower activity compared with controls during visual processing of food in the inferior parietal lobule and lateral prefrontal cortex 14,15 ; this was hypothesized to be possibly reflective of food-induced weight and body shape concerns [16][17][18] . Moreover, the simultaneous hyperactivation of medial prefrontal regions was suggested to indicate topdown control efforts aimed at restraining eating and food avoidance 16,17,19,20 . ...
... Moreover, the simultaneous hyperactivation of medial prefrontal regions was suggested to indicate topdown control efforts aimed at restraining eating and food avoidance 16,17,19,20 . In addition, lower activation in the medial orbitofrontal cortex and insula during visual processing of food cues has been linked to lower hedonic reactivity in patients with AN compared with controls 14,18 . However, a recent study on adolescents with full-threshold AN showed higher bottom-up, as well as top-down activity in patients in response to high calories food compared with controls 21 . ...
Atypical anorexia nervosa (AN) usually occurs during adolescence. Patients are often in the normal-weight range at diagnosis; however, they often present with signs of medical complications and severe restraint over eating, body dissatisfaction, and low self-esteem. We investigated functional circuitry underlying the hedonic response in 28 female adolescent patients diagnosed with atypical AN and 33 healthy controls. Participants were shown images of food with high (HC) or low (LC) caloric content in alternating blocks during functional MRI. The HC > LC contrast was calculated. Based on the previous literature on full-threshold AN, we hypothesized that patients would exhibit increased connectivity in areas involved in sensory processing and bottom-up responses, coupled to increased connectivity from areas related to top-down inhibitory control, compared with controls. Patients showed increased connectivity in pathways related to multimodal somatosensory processing and memory retrieval. The connectivity was on the other hand decreased in patients in salience and attentional networks, and in a wide cerebello-occipital network. Our study was the first investigation of food-related neural response in atypical AN. Our findings support higher somatosensory processing in patients in response to HC food images compared with controls, however HC food was less efficient than LC food in engaging patients’ bottom-up salient responses, and was not associated with connectivity increases in inhibitory control regions. These findings suggest that the psychopathological mechanisms underlying food restriction in atypical AN differ from full-threshold AN. Elucidating the mechanisms underlying the development and maintenance of eating behavior in atypical AN might help designing specific treatment strategies.
... When instructing participants to imagine eating the depicted food stimuli or to rate stimuli according to their pleasantness, patients with AN commonly display aberrant activation in different regions of the prefrontal cortex [25][26][27][28][29]. Specifically, as outlined in two recent reviews [20,21], hypoactivity during food picture processing in regions such as the inferior parietal lobule and lateral prefrontal cortex may indicate weight and body shape concerns induced by the exposure to visual food stimuli [27,30,31]. The cooccurring increased activation of medial prefrontal regions during picture processing may be related to increased top-down control and efforts to restrain eating and food avoidance [27,30,32,33]. ...
... These results are in line with eye-tracking data showing avoidance of food pictures by patients with AN [34]. Finally, decreased activation in the medial orbitofrontal cortex and insula during food picture processing has been interpreted as reduced hedonic reactivity to food stimuli in in patients with AN [20,31]. ...
Abnormalities and alterations in brain function are commonly associated with the etiology and maintenance of anorexia nervosa (AN). Different symptom categories of AN have been correlated with distinct neurobiological patterns in previous studies. The aim of this literature review is to provide a narrative overview of the investigations into neural correlates of disorder-specific stimuli in patients with AN. Although findings vary across studies, a summary of neuroimaging results according to stimulus category allows us to account for methodological differences in experimental paradigms. Based on the available evidence, the following conclusions can be made: (a) the neural processing of visual food cues is characterized by increased top-down control, which enables restrictive eating, (b) increased emotional and reward processing during gustatory stimulation triggers disorder-specific thought patterns, (c) hunger ceases to motivate food foraging but instead reinforces disorder-related behaviors, (d) body image processing is related to increased emotional and hedonic reactions, (e) emotional stimuli provoke increased saliency associated with decreased top-down control and (f) neural hypersensitivity during interoceptive processing reinforces avoidance behavior. Taken together, studies that investigated symptom-specific neural processing have contributed to a better understanding of the underlying mechanisms of AN.
... This equilibrium seems to be altered in eating disorders (ED) [7]. While several study results [8][9][10] suggest increased activity in the dorsolateral prefrontal cortex (DLPFC) in AN, possibly representing increased TD control, the results on the involvement of BU regions are not as unequivocal: either increased or blunted reward responses to food Table 1. Examples for areas involved in "bottom-up" and "top-down" brain circuits. ...
... Contrary to our hypothesis H2 and unlike two studies which found no specific brain response patterns to emotionally aversive stimuli in AN [10,24], our results yielded many brain regions which were differently involved in AN patients and controls. Specifically, cerebellar regions were less activated in adolescent AN patients than in controls; within the adult group a mixed pattern emerged in AN patients with increased activity in some subregions and decreased activity in others. ...
Background
A constant preoccupation with food and restrictive eating are main symptoms of anorexia nervosa (AN). Imaging studies revealed aberrant neural activation patterns in brain regions processing hedonic and reward reactions as well as–potentially aversive–emotions. An imbalance between so called “bottom-up” and “top-down” control areas is discussed. The present study is focusing on neural processing of disease-specific food stimuli and emotional stimuli and its developmental course in adolescent and adult AN patients and could offer new insight into differential mechanisms underlying shorter or more chronic disease.
Methods
33 adolescents aged 12–18 years (15 AN patients, 18 control participants) and 32 adult women (16 AN patients, 16 control participants) underwent functional magnetic resonance imaging (fMRI, 3T high-field scanner) while watching pictures of high and low-calorie food and affective stimuli. Afterwards, they rated subjective valence of each picture. FMRI data analysis was performed using a region of interest based approach.
Results
Pictures of high-calorie food items were rated more negatively by AN patients.
Differences in activation between patients and controls were found in “bottom up” and “top down” control areas for food stimuli and in several emotion processing regions for affective stimuli which were more pronounced in adolescents than in adults.
Conclusion
A differential pattern was seen for food stimuli compared to generally emotion eliciting stimuli. Adolescents with AN show reduced processing of affective stimuli and enhanced activation of regions involved in “bottom up” reward processing and “top down” control as well as the insula with regard to food stimuli with a focus on brain regions which underlie changes during adolescent development. In adults less clear and less specific activation differences were present, pointing towards a high impact that regions undergoing maturation might have on AN symptoms.
... Hypoactivity in the right inferior parietal lobe (Kim et al., 2012;Santel et al., 2006), orbitofrontal cortex (OFC) Uher et al., 2003) and lateral Prefrontal cortex (PFC) (Gizewski et al., 2010;Uher et al., 2003). Hyperactivity in the right ACC, left and right insula (Schienle et al., 2009), right Middle frontal gyrus and right Cerebellum (Kim et al., 2012). ...
... Hypoactivity in the right inferior parietal lobe (Kim et al., 2012;Santel et al., 2006), orbitofrontal cortex (OFC) Uher et al., 2003) and lateral Prefrontal cortex (PFC) (Gizewski et al., 2010;Uher et al., 2003). Hyperactivity in the right ACC, left and right insula (Schienle et al., 2009), right Middle frontal gyrus and right Cerebellum (Kim et al., 2012). ...
Real-time functional magnetic resonance imaging based brain-computer interfacing (fMRI neurofeedback) has shown encouraging outcomes in the treatment of psychiatric and behavioural disorders. However, its use in the treatment of eating disorders is very limited. Here, we give a brief overview of how to design and implement fMRI neurofeedback intervention for the treatment of eating disorders, considering the basic and essential components. We also attempt to develop potential adaptations of fMRI neurofeedback intervention for the treatment of anorexia nervosa, bulimia nervosa and binge eating disorder.
... However, other studies suggest hyperactivity in reward-related regions such as the ventral striatum (Cowdrey et al., 2011) and amygdala (Vocks et al., 2010) in response to palatable food cues, despite those with AN implicitly and explicitly stating "liking" and "wanting" these foods less than controls (Cowdrey et al., 2013). In concert, heightened activity in prefrontal regions including the medial prefrontal cortex and dorsolateral prefrontal cortex following exposure to palatable food cues has driven several hypotheses suggesting elevated top-down inhibition of reward processing (Kerr et al., 2017;Uher et al., 2003;Uher et al., 2004). ...
Introduction
Anorexia nervosa (AN) is a debilitating and potentially chronic eating disorder, characterized by low hedonic drive toward food, which has been linked with perturbations in both reward processing and dopaminergic activity. Neuromelanin‐sensitive magnetic resonance imaging (MRI) is an emerging method to index midbrain neuromelanin—a by‐product of dopaminergic synthesis. The assessment of midbrain neuromelanin, and its association with AN psychopathology and reward‐related processes, may provide critical insights into reward circuit function in AN.
Methods
This study will incorporate neuromelanin‐sensitive MRI into an existing study of appetitive conditioning in those with AN. Specifically, those with acute and underweight AN (N = 30), those with weight‐restored AN (N = 30), and age‐matched healthy controls (N = 30) will undergo clinical assessment of current and previous psychopathology, in addition to structural neuromelanin‐sensitive MRI, diffusion MRI, and functional MRI (fMRI) during appetitive conditioning.
Conclusion
This study will be among the first to interrogate midbrain neuromelanin in AN—a disorder characterized by altered dopaminergic activity. Results will help establish whether abnormalities in the midbrain synthesis of dopamine are evident in those with AN and are associated with symptomatic behavior and reduced ability to experience pleasure and reward.
... Most research about food perception and reasoning in AN has focused on the reward system and has revealed a decreased preference for high-fat/calorie foods at explicit and implicit levels [23,24]. Studies have also shown that anxiety traits and fear of gaining weight lead to food avoidance and limitation of caloric intake, specifically calories derived from fat [23,25]. ...
Purpose
The present study aimed to explore the implicit associations between food and bodily stimuli in patients with anorexia nervosa (AN) and control subjects (HC).
Methods
A Go/No-Go Association Task was administrated to 55 participants (28 AN and 27 HC), using food stimuli (low-calorie food vs. high-calorie food) and body stimuli (underweight vs. overweight bodies).
Results
We evidenced an implicit association between food and body stimuli in the AN group, whereas the HC group only showed a tendency. AN and HC groups also exhibited different categorization strategies: the AN group tended to categorize stimuli as low-calorie foods and underweight bodies less than the HC group, and they tended to categorize stimuli as high-calorie foods and overweight bodies more than the HC group.
Conclusion
The present study revealed for the first time specificities of the AN population’s implicit association between food and body stimuli in terms of association strength and categorization strategy. Furthermore, the results suggest that combining implicit methodologies with other methods could contribute to a better characterization of the physiopathology of AN.
Level of evidence
Level I, experimental study.
... First, although we used mixed-model analyses, which allows for larger degrees of freedom, the sample size of the present study was small. Second, though custom-created meal is an appropriate methodology that allows to avoid cultural bias [37,38] when comparing patients across cultures, the food stimuli used cannot be considered as standardized and may not be generalizable. Furthermore, the stimuli are computerized pictures presented on a computer screen, it is here important to consider, that this is a clear abstraction away from real food conditions. ...
Purpose
Bulimia nervosa (BN) and anorexia nervosa (AN) are potentially life-threatening eating disorders (ED) that primarily affect young people, mostly women. The central common pathology is linked to the relationship with food and with abnormalities in food intake. A previous study indicated that individuals with AN tend to overestimate food portion sizes compared to healthy controls (HC), but no study has investigated these patterns in BN, which was the objective of this study.
Methods
Women with BN (27), AN (28), and HC (27) were asked to rate different meal portion sizes in two conditions: as if they were supposed to eat them (intent-to-eat condition) or in general (general condition). BN results were compared to HC and AN using mixed model analyses.
Results
BN showed larger estimations compared to HC, while smaller estimations compared to AN. These differences were found mostly for intermediate portion sizes. No difference for conditions (intent-to-eat; general) was found between groups.
Conclusion
When estimating food portion sizes, individuals with BN seem to fall intermediately between HC and AN. ED symptoms in BN were most strongly associated with higher portion estimation. This might therefore reflect one aspect of the cognitive distortions typically seen also in AN. A therapeutic option could include the frequent visual exposure to increasing portions of food, what may serve to recalibrate visual perceptions of what a “normal-sized” portion of food looks like.
Level of evidence
Level II: Evidence obtained from well-designed controlled trials without randomization.
... Individuals with BN or BED commonly report consuming high energy, highly palatable, or pleasurable foods during a binge episode, likely to be linked to the caloric restriction that often precedes the binge episodes (Fairburn, 2008;Zunker et al., 2011). Research has consistently highlighted that people with a diagnosed ED or sub-threshold symptoms self-report higher negative emotions (e.g., disgust, anxiety, and fear) in response to food stimuli compared to healthy controls (HCs; Uher et al., 2003Uher et al., , 2004Santel et al., 2006;Rodríguez et al., 2007;Foroughi et al., 2018). Harvey et al. (2002) found levels of disgust and fear in response to high-calorie food images increased with abnormal eating attitudes and in a later study of non-ED women, as eating concerns increased, so too did the degree of fear response to food images (McNamara et al., 2008). ...
Objective
Bulimia nervosa (BN) and binge eating disorder (BED) are eating disorders (EDs) characterized by recurrent binge eating (BE) episodes. Overlap exists between ED diagnostic groups, with BE episodes presenting one clinical feature that occurs transdiagnostically. Neuroimaging of the responses of those with BN and BED to disorder-specific stimuli, such as food, is not extensively investigated. Furthermore, to our knowledge, there have been no previous published studies examining the neural response of individuals currently experiencing binge eating, to low energy foods. Our objective was to examine the neural responses to both low energy and high energy food images in three emotive categories (disgust; fear; and happy) in BN and BED participants.
Methods
Nineteen females with BN (n = 14) or BED (n = 5), comprising the binge eating group (BEG; N = 19), and 19 age-matched healthy control (HC)’s completed thorough clinical assessment prior to functional MRI (fMRI). Neural response to low energy and high energy foods and non-food images was compared between groups using whole-brain exploratory analyses, from which six regions of interest (ROI) were then selected: frontal, occipital, temporal, and parietal lobes; insula and cingulate.
Results
In response to low energy food images, the BEG demonstrated differential neural responses to all three low energy foods categories (disgust; fear; and happy) compared to HCs. Correlational analyses found a significant association between frequency of binge episodes and diminished temporal lobe and greater occipital lobe response. In response to high energy food images, compared to HC’s, the BEG demonstrated significantly decreased neural activity in response to all high energy food images. The HC’s had significantly greater neural activity in the limbic system, occipital lobe, temporal lobe, frontal lobe, and limbic system in response to high energy food images.
Conclusion
Results in the low energy food condition indicate that binge frequency may be related to increased aberrant neural responding. Furthermore, differences were found between groups in all ROI’s except the insula. The neural response seen in the BEG to disgust food images may indicate disengagement with this particular stimuli. In the high energy food condition, results demonstrate that neural activity in BN and BED patients may decrease in response to high energy foods, suggesting disengagement with foods that may be more consistent with those consumed during a binge eating episode.
... food) as well as disorder-unrelated (e.g. money) stimuli in typical regions of the brain reward system such as the ventral striatum (VS; Cowdrey, Park, Harmer, & McCabe, 2011;Decker, Figner, & Steinglass, 2015;Fladung et al. 2010;Wagner et al. 2008;Wierenga et al. 2015) and the medial orbitofrontal cortex (mOFC; Uher et al., 2003). ...
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.
... This study has also some limitations. First, although we used mixedmodel analyses, which allows for larger degrees of freedom, the sample size of the present study was small.Second,though custom-created meal is an appropriate methodology that allows to avoid cultural bias [37,38] when comparing patients across cultures, the food stimuli used cannot be considered as standardized and may not be generalizable. Furthermore the stimuli are computerized pictures presented on a computer screen, it is here important to consider, that this is a clear abstraction away from real food conditions. ...
Purpose: Bulimia nervosa (BN) and anorexia nervosa (AN) are potentially life-threatening eating disorders (ED) that primarily affect young people, mostly women. The central common pathology is linked to the relationship with food and with abnormalities in food intake.A previous study indicated that individuals with ANtend to overestimate food portion sizes compared to healthy controls (HC), but no study has investigated these patterns in BN, which was the objective of this study.
Methods: Women with BN (27), AN (28), and HC (27) were asked to rate different meal portion sizes in two conditions: as if they were supposed to eat them (intent-to-eat condition) or in general (general condition). BN results were compared to HC and AN using mixed model analyses.
Results: BN showed larger estimations compared to HC, while smaller estimations compared to AN. These differences were found mostly for intermediate portion sizes. No difference for conditions (intent-to-eat; general) was found between groups.
Conclusion: When estimating food portion sizes, individuals with BN seem to fall intermediately between HC and AN. ED symptoms in BN were most strongly associated with higher portion estimation. This might therefore reflect one aspect of the cognitive distortions typically seen also in AN.A therapeutic option could include the frequent visual exposure to increasing portions of food, what may serve to recalibrate visual perceptions of what a “normal-sized” portion of food looks like.
Level of evidence
Level II: Evidence obtained from well-designed controlled trials without randomization.
... Our result indicative of equivalent neural activation between recAN and HC is consistent with work on other emotional disorder-unrelated stimuli, which found intact neural processing of emotional stimuli in recAN [36,70]. However, the results deviate from other neuroimaging studies in recAN that show blunted amygdala activity in response to disorder-unrelated (facial) stimuli [71] or have employed disorder-related stimuli such as food pictures [72][73][74], taste [75][76][77][78], or body stimuli [79]. ...
Altered emotion processing and regulation mechanisms play a key role in eating disorders. We recently reported increased fMRI responses in brain regions involved in emotion processing (amygdala, dorsolateral prefrontal cortex) in acutely underweight anorexia nervosa (AN) patients while passively viewing negatively valenced images. We also showed that patients’ ability to downregulate activity elicited by positively valenced pictures in a brain region involved in reward processing (ventral striatum) was predictive of worse outcomes (increased rumination and negative affect). The current study tries to answer the question of whether these alterations are only state effects associated with undernutrition or whether they constitute a trait characteristic of the disorder that persists after recovery. Forty-one individuals that were weight-recovered from AN (recAN) and 41 age-matched healthy controls (HC) completed an established emotion regulation paradigm using negatively and positively valenced visual stimuli. We assessed behavioral (arousal) and fMRI measures (activity in the amygdala, ventral striatum, and dorsolateral prefrontal cortex) during emotion processing and regulation. Additionally, measures of disorder-relevant rumination and affect were collected several times daily for 2 weeks after scanning via ecological momentary assessment. In contrast to our previous findings in acute AN patients, recAN showed no significant alterations either on a behavioral or neural level. Further, there were no associations between fMRI responses and post-scan momentary measures of rumination and affect. Together, these results suggest that neural responses to emotionally valenced stimuli as well as relationships with everyday rumination and affect likely reflect state-related alterations in AN that improve following successful weight-recovery.
... Genes concerned with serotonin (Bergen et al., 2003;Klump et al., 2007), opioid systems (Bergen et al., 2003) and brain-derived neurotrophic factor (Klump et al., 2007;Ribases et al., 2004Ribases et al., & 2005 might contribute to the risk for developing anorexia nervosa whereas chromosomal sites 1, 4 and 10 might hold risk genes for both anorexia and bulimia nervosa (Grice et al., 2002). It was also noted that in anorexic individuals even after recovery from illness disordered functioning of brain serotonin Steiger et al., 2005), neuro-circuitry (Uher et al., 2003;Wagner et al., 2007Wagner et al., & 2008 and neuropeptide systems continued. The below stated genes are involved in the modulation of metabolism, appetite, autonomic and hormonal systems, cognition, impulse control and mood. ...
Anorexia nervosa has emerged as a prominent eating disorder affecting young women. This disorder's fundamental characteristic is an abnormally low weight achieved by severe calorie restriction and refusal to maintain body weight at or above the minimally normal weight for age and height. It is a complex disorder with its origins still not explicitly defined. In anorexic individuals, an imbalance in the molecular signalling and hypothalamic neuropeptides is believed to be significantly responsible for alterations in the biological mechanisms associated with body weight, appetite and energy homeostasis. The imbalance between the genetic systems such as serotonin, dopamine, brain-derived neurotrophic factor, estrogen and their interactions are significantly observed in anorexic as well as recovered anorexic individuals. The dopaminergic pathway is involved in reward mechanisms but its dysfunction might cause weight loss, food aversion, hyperactivity, obsessive compulsive behaviours, distorted body image. An abnormal serotonin function reveals personality traits such as rigidity, inhibition, anxiety, inflexibility, perfectionism and harm avoidance. The Met66 variant of brain derived neurotrophic factor is strongly associated with the development of restricting-type anorexia nervosa. The development of anorexia has been linked to estrogen receptor beta gene variants, which also regulate food intake and states of anxiety and depression.This review discusses the neurobiological dysregulations because of which anorexics tend to have a distinct personality profile characterized by behaviour patterns comprising perfectionism, obsessive-compulsive disorder, harm avoidance, alexithymia, anger suppression, anxiety, rigidity, novelty seeking, anhedonia, depression, impulsivity, substance abuse, self harm etc. Heterogeneities in the characteristic profile are observed based on the subdivisions of anorexia nervosa. The impact of malnutrition has also been scrutinized.
... To the best of our knowledge, there is no data in the literature on this subject. The hypothalamus, limbic system, and amygdala are thought to play an important role in the pathogenesis of eating disorders 35, 36 . It has been reported that hypothalamic or limbic dysfunction may lead to prodromal symptoms such as nausea, depressive mood, irritability, and hypersomnia prior to migraine episodes 37,38 . ...
Background:
Few studies have explored the coexistence of migraine and disordered eating attitudes. Furthermore, the underlying pathophysiological mechanisms of migraine and disordered eating attitude comorbidity are not clearly understood.
Objective:
This study aimed to investigate the association between migraine and disordered eating attitudes in relation to personality traits, obesity, quality of life, migraine severity, depression, and anxiety.
Methods:
This study included 91 patients with episodic migraine and 84 healthy control subjects. Self-report questionnaires were used to evaluate anxiety, depression, migraine-related disability, personality traits, quality of life, and eating disorders.
Results:
The Eating Attitude Test (EAT) showed disordered eating attitudes in 21 patients (23.1%) in the migraine group and eight patients (9.5%) in the control group. Migraine-related disability, anxiety, depression, neuroticism, and quality of life scores were significantly worse in migraine patients with disordered eating attitudes compared to migraine patients without disordered eating attitudes. In migraine patients, eating attitude test scores were positively correlated with migraine-related disability, anxiety, depression, and neuroticism scores, and negatively correlated with quality of life scores.
Conclusion:
The association of migraine and disordered eating attitudes was shown to be related to depression, anxiety, quality of life and personality traits and may also indicate a more clinically severe migraine. To the best of our knowledge, there is no literature study that deals with all these relevant data together. However, neuropsychiatry-based biological studies are required to better understand this multifaceted association.
... Reward-and anxiety-related alterations associated with anorexia nervosa persist after symptom remission and may even be present in childhood (4,47); we therefore hypothesized that our study would detect trait-like alterations in neural activation. Changes in other circuits not studied here (e.g., executive control circuits [48]) may be required to compensate for these persistent reward-or anxiety-related alterations to promote normalized behavior. In our sample, BOLD response was not associated with duration of illness or remission, providing further support for trait-like alterations; however, longitudinal research among individuals at risk for developing anorexia nervosa is needed to understand alterations that may predispose individuals to anorexia nervosa and persist after remission. ...
Objective:
Anorexia nervosa has the highest mortality rate of any psychiatric condition, yet the pathophysiology of this disorder and its primary symptom, extreme dietary restriction, remains poorly understood. In states of hunger relative to satiety, the rewarding value of food stimuli normally increases to promote eating, yet individuals with anorexia nervosa avoid food despite emaciation. This study's aim was to examine potential neural insensitivity to these effects of hunger in anorexia nervosa.
Methods:
At two scanning sessions scheduled 24 hours apart, one after a 16-hour fast and one after a standardized meal, 26 women who were in remission from anorexia nervosa (to avoid the confounding effects of malnutrition) and 22 matched control women received tastes of sucrose solution or ionic water while functional MRI data were acquired. Within a network of interest responsible for food valuation and transforming taste signals into motivation to eat, the authors compared groups across conditions on blood-oxygen-level-dependent (BOLD) signal and task-based functional connectivity.
Results:
Participants in the two groups had similar BOLD responses to sucrose and water tastants. A group-by-condition interaction in the ventral caudal putamen indicated that hunger had opposite effects on tastant response in the control group and the remitted anorexia nervosa group, with an increase and a decrease, respectively, in BOLD response when hungry. Hunger had a similar opposite effect on insula-to-ventral caudal putamen functional connectivity in the remitted anorexia nervosa group compared with the control group. Exploratory analyses indicated that lower caudate response to tastants when hungry was associated with higher scores on harm avoidance among participants in the remitted anorexia nervosa group.
Conclusions:
Reduced recruitment of neural circuitry that translates taste stimulation to motivated eating behavior when hungry may facilitate food avoidance and prolonged periods of extremely restricted food intake in anorexia nervosa.
... To the best of our knowledge, no study has yet investigated attentional processing of disorder-relevant stimuli using traditional attentional bias paradigms in women recovered from AN. Few brain imaging studies report on processing of food-related information in women recovered from AN, and they find evidence for an approximation of brain activity to those patterns found in healthy women, at least to a certain extent (Cowdrey, Park, Harmer, & McCabe, 2011;Godier, Scaife, Braeutigam, & Park, 2016;Uher et al., 2003). In a paradigm assessing motivated behavior toward stimuli depicting physical activity, women recovered from AN still showed increased appetitive responses toward these stimuli as compared to control women, indicating that they experienced those stimuli as rewarding (O'Hara et al., 2016). ...
Objective:
Biased attention for disorder-relevant information plays a crucial role in the maintenance of different mental disorders including eating disorders and might be of use to define recovery beyond symptom-related criteria.
Method:
We assessed attention deployment using eye tracking in a cued choice viewing paradigm to two different categories of disorder-relevant stimuli in 24 individuals with acute anorexia nervosa (AN), 20 weight-recovered individuals with a history of AN (WRAN) and 23 healthy control participants (CG). Picture pairs consisted of a food stimulus or a picture depicting physical activity and a matched control stimulus (household item/physical inactivity). Participants rated the valence of stimuli afterwards.
Results:
The groups did not differ in initial attention deployment. In later processing stages, AN patients showed a generalized attentional avoidance of food and control pictures as compared to CG, while WRAN individuals were in between. AN patients showed an attentional bias toward physical activity pictures as compared to WRAN individuals, but not the CG. AN individuals rated the food pictures and the pictures showing physical inactivity as less pleasant than the CG, while WRAN individuals were in between.
Discussion:
Attention deployment is partly changed in WRAN as compared to the acute AN group, especially with regard to a shift away from illness-compatible stimuli (physical activity), and this might be a useful recovery criterion. Valence rating of food stimuli might be an additional useful tool to distinguish between acutely ill and weight-recovered individuals. Attentional biases for illness-compatible stimuli might qualify as a valuable approach to defining recovery in AN.
... For instance, fMRI studies focusing on responses to body-related images suggest that AN, when compared to HC, show: (a) divergent brain signal patterns to self-referential images (Mohr et al., 2010;Suda et al., 2013) and other human bodies (Friederich et al., 2010;Suchan et al., 2013;Suda et al., 2013); (b) lower attentional resources (e.g., insula and/or prefrontal cortex, or PFC) devoted to processing their own image as opposed to ideal underweight images (Castellini et al., 2013;Mohr et al., 2010); and (c) less effective connectivity of the visual system network (including the occipital cortex), which is argued to alter body-size processing and contribute to body-size overestimation (Mohr et al., 2010;Suchan et al., 2013). Similarly, another fMRI study investigating responses to food images demonstrates that underweight AN exhibit lower PFC activation to food than recovered AN and HC, who did not differ from each other (Uher et al., 2003). Similar to AN findings for body pictures, results suggest heightened visual attention paid to disorder-salient stimuli (food) unless one is in an actively undernourished state. ...
Objective:
The current systematic and methodological review aimed to critically review existing literature utilizing implicit processing, or automatic approach- and/or avoidance-related attentional biases between eating disorder (ED) and nonclinical samples, which (a) highlights how psychophysiological methods advance knowledge of ED implicit bias; (b) explains how findings fit into transdiagnostic versus disorder-specific ED frameworks; and (c) suggests how research can address perfectionism-related ED biases.
Method:
Three databases were systematically searched to identify studies: PubMed, Scopus, and PsychInfo electronic databases. Peer-reviewed studies of 18- to 39-year-olds with both clinical ED and healthy samples assessing visual attentional biases using pictorial and/or linguistic stimuli related to food, body, and/or perfectionism were included.
Results:
Forty-six studies were included. While behavioral results were often similar across ED diagnoses, studies incorporating psychophysiological measures often revealed disease-specific attentional biases. Specifically, women with bulimia nervosa (BN) tend to approach food and other body types, whereas women with anorexia nervosa (AN) tend to avoid food as well as overweight bodies.
Conclusions:
Further integration of psychophysiological and behavioral methods may identify subtle processing variations in ED, which may guide prevention strategies and interventions, and provide important clinical implications. Few implicit bias studies include male participants, investigate binge-eating disorder, or evaluate perfectionism-relevant stimuli, despite the fact that perfectionism is implicated in models of ED.
... On the other hand, two studies found deactivation in the VS when monetary rewards where presented to acAN 22 and taste stimuli to recAN patients 23 . As for the mOFC, increased activation was found in both acAN and recAN using food pictures 24 as well as in acAN using taste stimuli 21 . Interestingly, lateral prefrontal cortex hyperactivation to reward stimuli was predominantly found in acAN when exposing them to taste stimuli 21 , food pictures 25 , body pictures 26 and exercise cues 27 , which may indicate elevated cognitive control over rewarding stimuli during the acute phase of the disorder. ...
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.
... In line with this putative alteration of neuronal wiring, genome-wide association studies in AN have identified genetic variants in neurodevelopmental genes regulating synapse and neuronal network formation [50]. administration of metabolically active molecules on appetite and brain activation in healthy volunteers [51,52], and of the neural responses to the passive viewing of food [53][54][55] or food choice in AN [56]. Our results raise the provocative idea that the origin of the disconnect between the body's needs and behavioral choices in patients with AN could lie in the hypothalamus, the metabolic window to the brain, which could fail to accurately sense circulating metabolic signals [57,58] and post-ingestive cues [59,60], and thus relay erroneous information to higher decision centers. ...
The hypothalamus contains integrative systems that support life, including physiological processes such as food intake, energy expenditure and reproduction. Here, we show that anorexia nervosa patients, contrary to normal weight and constitutionally lean individuals, respond with a paradoxical reduction in hypothalamic levels of glutamate/glutamine (Glx) upon feeding. This reversal of the Glx response is associated with decreased wiring in the arcuate nucleus and increased connectivity in the lateral hypothalamic area, which are involved in the regulation on a variety of physiological and behavioral functions including the control of food intake and energy balance. The identification of distinct hypothalamic neurochemical dysfunctions and associated structural variations in anorexia nervosa paves the way for the development of new diagnostic and treatment strategies in conditions associated with abnormal body mass index and a maladaptive response to negative energy balance.
... Distinct brain systems for cognitive and affective empathy have been described: the ventromedial prefrontal cortex is involved in cognitive empathy, while the inferior frontal gyrus is involved in affective empathy (75). Neuroimaging studies have reported differences in the ventromedial prefrontal cortex in those with AN (76,77), thus providing a possible explanation for lowered cognitive empathy abilities. fMRI studies utilizing performance-based measures of empathy could be useful in testing this hypothesis. ...
Background: Recent models of eating disorders (EDs) have proposed social and emotional difficulties as key factors in the development and maintenance of the illness. While a number of studies have demonstrated difficulties in theory of mind and emotion recognition, little is known about empathic abilities in those with EDs. Further, few studies have examined the cognitive-affective empathy profile in EDs. The aim of this systematic review and meta-analysis was to provide a synthesis of empathy studies in EDs, and examine whether those with EDs differ from healthy controls (HC) on self-reported total, cognitive, and affective empathy.
Methods: Electronic databases were systematically searched for studies using self-report measures of empathy in ED populations. In total, 17 studies were identified, 14 of which could be included in the total empathy meta-analysis. Eight of the 14 studies were included in the cognitive and affective empathy meta-analyses.
Results: Meta-analyses showed that while total empathy and affective empathy scores did not differ between those with anorexia nervosa (AN) and HC, those with AN had significantly lower cognitive empathy scores compared to HCs (small effect size). Meta-analyses of Interpersonal Reactivity Index sub-scores revealed that AN had significantly lower Fantasy scores than HC (small effect size), indicating that those with AN have more difficulty in identifying themselves with fictional characters. Only 3 studies examined empathy in those with bulimia nervosa (BN) or binge eating disorder (BED).
Conclusions: The lowered cognitive empathy and intact affective empathy profile found in AN is similar to that found in other psychiatric and neurodevelopmental conditions, such as autism spectrum disorder (ASD). These findings add to the literature characterizing the socio-emotional phenotype in EDs. Future research should examine the influence of comorbid psychopathology on empathy in EDs.
... First, there is literature demonstrating higher prevalence of anxiety-related personality traits like harm avoidance and intolerance of uncertainty and increased anxiety comorbidity in AN, and to a lesser degree in BN (Atiye et al., 2015;Fassino et al., 2002;Kaye et al., 2004). Second, there is work suggesting activation of cognitive control or conflict-oriented circuitry during reward processing in patients with ED (Brooks et al., 2011;Uher et al., 2003;Uher et al., 2004), which raises the question of whether reward paradigms may elicit distinct higher order cognitive processes in patient populations, thus enabling them to experience a greater sense of control during tasks (Keating, 2010;Shenhav et al., 2013). This notion would also connect to the difficulty tolerating uncertainty seen in certain populations with ED (Frank et al., 2012b). ...
Individuals with eating disorders (ED) make extreme food choices, raising the possibility of altered food-value computation. We utilized an associative taste reward learning paradigm to test whether value signaling differs between participants with EDs vs. healthy controls (HC). We followed up on previous work examining prediction error (PE) signaling, which is a brain response to violation of a learned reward contingency. Expected value (EV) signal is a trial-by-trial assessment of reward significance accounting for error signaling, reward-likelihood, and learning rate. Adult female participants (N = 111) performed a temporal difference (TD) fMRI taste task, which is a specific type of associative reward learning paradigm, to determine EV signal: Anorexia Nervosa-ill (N = 28), Anorexia Nervosa-recovered (N = 20), Bulimia Nervosa (BN) (N = 20), and HC (N= 43). Anatomical region-of-interest (ROI) analyses were performed utilizing EV regressors derived via algorithm, with ROIs based on prior EV analyses: orbitofrontal cortex, anterior cingulate (ACC), amygdala, and striatum. EV signal was elevated in the bilateral ACC in AN-ill vs. HC and BN. Intolerance of uncertainty negatively correlated with EV in AN-ill. BMI and EV were negatively-correlated across groups. Altered ACC EV computation in response to food stimuli could contribute to food restriction in AN-ill.
... 1,2 Less pleasurable emotions towards food stimuli are consistently reported in patients with EDs compared with healthy controls (HCs). [3][4][5][6][7][8] These responses may be more pronounced in people with anorexia nervosa (AN) compared with other EDs, 9 and it has been suggested that negative emotional arousal impacts the cognitive processing bias to food and body stimuli in EDs. [10][11][12][13][14] We have reported similarly that participants with EDs showed greater aversive emotion and less positive responses to food in comparison to HCs, and furthermore compared with a clinical control group (with depression and anxiety). ...
Objectives:
To investigate emotional responses to food images in women with eating disorders (EDs) and healthy controls (HCs); and in underweight individuals post weight-restoration.
Methods:
Women (>14 years) with ( n = 139) and without ( n = 41) an ED rated food images evoking fear, disgust and happiness on a three-visual-analogue scale. Underweight participants viewed the images at two time-points; pre- and post-weight-restoration.
Results:
HCs were significantly happier, less fearful/anxious prior to viewing the images compared with EDs. Negative emotional responses when viewing images were significantly greater ( p < .001) in EDs compared with HCs; however, groups did not differ in happiness. Emotional responses were not significantly different within the ED groups. At post weight-restoration, individuals were significantly less anxious/disgusted when viewing the images.
Conclusions:
The importance of considering emotional responses when discussing food consumption in EDs trans-diagnostically is highlighted. Weight recovery reduces negative food responses, although responses remained high in comparison to HCs.
... It is also supported by many psychophysiological studies that have demonstrated that exposure of AN women to food stimuli elicits an increase in their arousal level, as measured by heart rate, skin conductance and eye blink startle response (e.g., Perpiña et al., 1998;Gordon et al., 2001;Gorini et al., 2010), suggesting an automatic and unconscious reaction of anxiety. Similarly, fMRI researches have revealed that presentation of food pictures to women with AN increases their amygdala, medial prefrontal cortex (including the anterior cingulate) and insula activations (Ellison et al., 1998;Uher et al., 2003Uher et al., , 2004, three cerebral areas related to innate signals of fear (for review, see Damasio, 1994;Adolphs, 2013;Silva et al., 2016). Finally, the time distortions caused by a fear reaction in participants with AN is not without reminding those of spider-fearful people for which the durations of phobic stimuli are overestimated (Watts and Sharrock, 1984;Buetti and Lleras, 2012). ...
The present study used the presentation of food pictures and judgements about their duration to assess the emotions elicited by food in women suffering from an eating disorder (ED). Twenty-three women diagnosed with an ED, namely anorexia (AN) or bulimia nervosa (BN), and 23 healthy controls (HC) completed a temporal bisection task and a duration discrimination task. Intervals were marked with emotionally pre-rated pictures of joyful and disgusting food, and pictures of neutral objects. The results showed that, in the bisection task, AN women overestimated the duration of food pictures in comparison to neutral ones. Also, compared to participants with BN, they perceived the duration of joyful food pictures as longer, and tended to overestimate the duration of the disgusting ones. These effects on perceived duration suggest that AN women experienced an intense reaction of fear when they were confronted to food pictures. More precisely, by having elevated the arousal level and activated the defensive system, food pictures seemed to have speeded up the rhythm of the AN participants’ internal clock, which led to an overestimation of images’ duration. In addition, the results revealed that, in both tasks, ED women presented a lower temporal sensitivity than HC, which was related to their ED symptomatology (i.e., BMI, restraint and concern) and, particularly, to their weaker cognitive abilities in terms of attention, processing speed and working memory. Considered all together, the findings of the present experiment highlight the role of fear and anxiety in the manifestations of AN and point out the importance of considering non-temporal factors in the interpretation of time perception performance.
... Many brain regions have been reported to function abnormally in AN [1][2][3][4][5][6]. However, it remains unclear whether the brain's response to fear stimuli is the same in AN as in controls. ...
PurposeTo determine whether the fear response is the same in AN as in controls. Method
We recorded the EEG in 10 participants with a history of AN and in 10 controls during a fear stimulus. The response of the brain was recorded using EEG LORETA. The recording was analyzed for a marked increase in activity in the amygdala, uncus, insula, and anterior cingulate from 300 to 500 ms following the stimulus. ResultsThe order or response of the amygdala, uncus, insula, and anterior cingulate was not significantly different in AN and controls. Conclusion
These results suggest that the brain’s response to a fear stimulus is not significantly different in AN and controls. Level of evidenceLevel 3, case-control study.
... 41 Findings from functional neuroimaging studies as well as positron emission tomography highlight the role of ACC in AN patients. [42][43] Recently, these outcomes were supported by several structural studies using voxel-wise analysis. For example, patients recovered from AN showed a reduced GMV in the anterior cingulum. ...
Objective
Structural studies have reported anorexia nervosa (AN) patients with abnormal gray matter in several brain regions and dysfunction in some connected neural circuits. However, the role of white matter (WM) in AN patients has rarely been investigated. The present study aimed to assess alterations in WM microstructure of the entire brain in females with AN using a voxel-based method on diffusion tensor imaging (DTI) data.
Materials and methods
The study enrolled 8 female patients with AN and 14 age-matched females as controls (CW). The DTI data was collected from each subject to calculate the fractional anisotropy (FA) maps of the whole brain by the DTI-Studio software. Subsequently, a 2-sample t-test (P<0.05, corrected) was performed to detect the difference in FA maps of AN and CW group, and a Pearson’s correlation analyzed the relationship between mean FA value of brain regions and body mass index (BMI).
Results
Compared with CW, AN patients revealed a significant decrease in FA maps in the left superior frontal gyrus, medial frontal gyrus, anterior cingulate cortex, middle frontal gyrus, inferior frontal gyrus, thalamus, and bilateral insula. Moreover, significantly positive correlations were established between the mean FA value of the left inferior frontal gyrus, insula as well as thalamus and BMI in AN patients.
Conclusions
Our findings supported the presence of WM abnormality in patients with AN. The significant differences of FA maps, in patients with AN, were associated with their aberrant BMI. The results further improved our understanding of the pathophysiological mechanisms underlying AN.
... Similarly, a recent study by Boehm et al. (2016) demonstrates that passive (e.g., not engaged in a perception or cognitive task during the scan) functional resting state connectivity was reduced between the DLPFC and frontoparietal network in people who had recovered from AN, suggesting that aberrant WM and cognitive control is a trait marker for the risk of developing an ED. Similarly, increased DLPFC activation while perceiving and responding to images of food (e.g., "how disgusting do you find the images?") in recovered patients who previously had chronic AN, may not be an indication of 'good outcome' (Uher et al., 2003), but rather, a reflection that underlying core cognitive symptoms of aberrant WM are recalcitrant. Taken together, these data suggest that the disruptive influence of non-conscious processes on WM and related attentional bias (Brooks et al., 2011b) increases as AN progresses, which in turn promotes epigenetic changes within the cognitive-affective neural interplay underlying the cognitive control of appetite. ...
Prefrontal cortex executive functions, such as working memory (WM) interact with limbic processes to foster impulse control. Such an interaction is referred to in a growing body of publications by terms such as cognitive control, cognitive inhibition, affect regulation, self-regulation, top-down control, and cognitive–emotion interaction. The rising trend of research into cognitive control of impulsivity, using various related terms reflects the importance of research into impulse control, as failure to employ cognitions optimally may eventually result in mental disorder. Against this background, we take a novel approach using an impulse control spectrum model – where anorexia nervosa (AN) and substance use disorder (SUD) are at opposite extremes – to examine the role of WM for cognitive control. With this aim, we first summarize WM processes in the healthy brain in order to frame a systematic review of the neuropsychological, neural and genetic findings of AN and SUD. In our systematic review of WM/cognitive control, we found n = 15 studies of AN with a total of n = 582 AN and n = 365 HC participants; and n = 93 studies of SUD with n = 9106 SUD and n = 3028 HC participants. In particular, we consider how WM load/capacity may support the neural process of excessive epistemic foraging (cognitive sampling of the environment to test predictions about the world) in AN that reduces distraction from salient stimuli. We also consider the link between WM and cognitive control in people with SUD who are prone to ‘jumping to conclusions’ and reduced epistemic foraging. Finally, in light of our review, we consider WM training as a novel research tool and an adjunct to enhance treatment that improves cognitive control of impulsivity.
... Also, the dorsolateral prefrontal cortex, which has increased ADC values in PCOS patients, has been shown to be associated with early satiety [9]. In particular, the visual occipital cortex is of significant importance in patients with eating disorders (anorexia nervosa, bulimia nervosa) [25,26]. In the light of these results, we also suggest that various eating disorders in PCOS patients may be explained as the result microstructural damage in these brain regions. ...
Background
Current psychological and pharmacological treatments for Anorexia Nervosa (AN) provide only moderate effective support, and there is an urgent need for research to improve therapies, especially in developing age. Non-invasive brain stimulation has suggested to have the potential to reducing AN symptomatology, via targeting brain alterations, such as hyperactivity of right prefrontal cortex (PFC). We suppose that transcranial direct current stimulation (tDCS) to the PFC may be effective in children and adolescents with AN.
Methods
We will conduct a randomized, double blind, add-on, placebo-controlled trial to investigate the efficacy of tDCS treatment on clinical improvement. We will also investigate brain mechanisms and biomarkers changes acting in AN after tDCS treatment. Eighty children or adolescent with AN (age range 10–18 years) will undergo treatment-as-usual including psychiatric, nutritional and psychological support, plus tDCS treatment (active or sham) to PFC (F3 anode/F4 cathode), for six weeks, delivered three times a week. Psychological, neurophysiological and physiological measures will be collected at baseline and at the end of treatment. Participants will be followed-up one, three, six months and one year after the end of treatment. Psychological measures will include parent- and self-report questionnaires on AN symptomatology and other psychopathological symptoms. Neurophysiological measures will include transcranial magnetic stimulation (TMS) with electroencephalography and paired pulse TMS and repetitive TMS to investigate changes in PFC connectivity, reactivity and plasticity after treatment. Physiological measures will include changes in the functioning of the endogenous stress response system, body mass index (BMI) and nutritional state.
Discussion
We expect that tDCS treatment to improve clinical outcome by reducing the symptoms of AN assessed as changes in Eating Disorder Risk composite score of the Eating Disorder Inventory-3. We also expect that at baseline there will be differences between the right and left hemisphere in some electrophysiological measures and that such differences will be reduced after tDCS treatment. Finally, we expect a reduction of endogenous stress response and an improvement in BMI and nutritional status after tDCS treatment. This project would provide scientific foundation for new treatment perspectives in AN in developmental age, as well as insight into brain mechanisms acting in AN and its recovery.
Trial registration The study was registered at ClinicalTrials.gov (ID: NCT05674266) and ethical approval for the study was granted by the local research ethics committee (process number 763_OPBG_2014).
This article summarizes the results of studies in which functional magnetic resonance imaging (fMRI) was performed to investigate the neurofunctional activations involved in processing visual stimuli from food in individuals with anorexia nervosa (AN), bulimia nervosa (BN) and binge eating disorder (BED). A systematic review approach based on the PRISMA guidelines was used. Three databases-Scopus, PubMed and Web of Science (WoS)-were searched for brain correlates of each eating disorder. From an original pool of 688 articles, 30 articles were included and discussed. The selected studies did not always overlap in terms of research design and observed outcomes, but it was possible to identify some regularities that characterized each eating disorder. As if there were two complementary regulatory strategies, AN seems to be associated with general hyperactivity in brain regions involved in top-down control and emotional areas, such as the amygdala, insula and hypothalamus. The insula and striatum are hyperactive in BN patients and likely involved in abnormalities of impulsivity and emotion regulation. Finally, the temporal cortex and striatum appear to be involved in the neural correlates of BED, linking this condition to use of dissociative strategies and addictive aspects. Although further studies are needed, this review shows that there are specific activation pathways. Therefore, it is necessary to pay special attention to triggers, targets and maintenance processes in order to plan effective therapeutic interventions. Clinical implications are discussed.
Introduction
Episodes of eating great quantities of extremely sweet and often aversive tasting food are a hallmark of bulimia nervosa. This unique eating pattern led researchers to seek and find differences in taste perception between patients and healthy control subjects. However, it is currently not known if these originate from central or peripheral impairment in the taste perception system. In this cross sectional study, we compare brain response to sweet and sour stimuli in 5 bulimic and 8 healthy women using functional magnetic resonance imaging (fMRI).
Materials and methods
Sweet, sour and neutral (colorless and odorless) taste solutions were presented to subjects while undergoing fMRI scanning. Data were analyzed using a block design paradigm.
Results
Between-group differences in brain activation in response to both sweet and sour tastes were found in 11 brain regions, including operculum, anterior cingulate cortex, midbrain, and cerebellum. These are all considered central to perception and processing of taste.
Conclusion
Our data propose that sweet and sour tastes may have reward or aversion eliciting attributes in patients suffering from bulimia nervosa not found in healthy subjects, suggesting that alteration in taste processing may be a core dysfunction in bulimia nervosa (BN).
Objective:
Functional neuroimaging studies have found differential neural activation patterns during anticipation-related paradigms in participants with eating disorders (EDs) compared to controls. However, publications reported conflicting results on the directionality and location of the abnormal activations. There is an urgent need to integrate our existing knowledge of anticipation, both rewarding and aversive, to elucidate these differences.
Method:
We conducted an activation likelihood estimation (ALE) meta-analysis to quantitatively review functional neuroimaging studies that evaluated differences between brain correlates of anticipation in participants with and without disordered eating. PubMed, Web of Sciences, PsycINFO, Medline and EMBASE were searched for studies published up to November 2022. Exploratory sub-analyses to check for differences between reward and non-reward anticipation among all anticipation paradigms.
Results:
Twenty-one references met the inclusion criteria for meta-analysis. The meta-analysis across anticipation all tasks identified a significant hyperactivation cluster in the right putamen in participants with disordered eating (n = 17 experiments) and a significant hypoactivation cluster in the left inferior parietal lobule (n = 13 experiments), in participants with disordered eating compared to controls.
Conclusions:
These findings and sub-analyses of reward- and non-reward-related cues suggest potential pathophysiological mechanisms underlying anticipatory responses to rewarding and aversive cues in ED.
Background
The present study examines the relationship between obesity, executive functions, and body image in a nonclinical population from southern Italy.
Methods
General executive functioning (Frontal Assessment Battery–15), and body image disturbances (Body Uneasiness Test) were assessed in a sample including 255 participants (138 females, M age = 43.51 years, SD = 17.94, range = 18–86 years; M body mass index (BMI) = 26.21, SD = 4.32, range = 18.03–38.79).
Findings
Multiple Linear Regression Analysis indicated that age, years of education, FAB15 score, body image concerns, and avoidance predicted the variance of BMI. A subsequent mediation analysis highlighted that the indirect effect of FAB15 on BMI through avoidance was statistically significant.
Interpretation
Our results suggest that more performing executive functioning predicts a decrease in BMI that is partially due to the mitigation of avoidance behaviors.
Background
Anorexia nervosa (AN) is a chronic and disabling psychiatric condition characterized by low hedonic drive towards food, and is thought to be inclusive of altered dimensions of reward processing. Whether there exists a fundamental aberrancy in the capacity to acquire and maintain de novo hedonic associations—a critical component of hedonic responding—has never been studied in AN.
Methods
This multi-modal study will employ a 2-day Pavlovian appetitive conditioning paradigm to interrogate the (1) acquisition, (2) extinction, (3) spontaneous recovery and (4) reinstatement of appetitive learning in adolescents and young adults with AN. Participants will be 30 currently ill, underweight individuals with AN; 30 weight-restored individuals with AN; and 30 age-matched healthy controls, all aged 12–22 years. All subjects will undergo clinical assessment, followed by the 2-day appetitive conditioning task during which fMRI, pupillometry, heart rate deceleration, and subjective ratings will be acquired.
Discussion
This study will be the first to interrogate appetitive conditioning in AN—a disorder characterized by altered hedonic responding to food. Results will help establish objective biomarkers of appetitive conditioning in AN and lay the groundwork for developing novel lines of treatment for AN and other psychiatric disorders involving diminished ability to experience pleasure and reward.
Trial registration : Pending.
Intended registry
Clinicaltrials.gov.
"Profilaktyka i leczenie zaburzeń odżywiania – wiedza ekspercka”, powstała jako zwieńczenie realizacji zadania Narodowego Programu Zdrowia w 2017 roku.
Po raz pierwszy w Polsce modele leczenia zaburzeń odżywiania zostały opisane przez ekspertów – kierowników klinik i oddziałów ukierunkowanych na terapię pacjentów z zaburzeniami odżywiania, którzy podzielili się swoimi długoletnimi doświadczeniami w zakresie struktury organizacyjnej oddziałów oraz programu terapii. Książka prezentuje dużą wartość naukową i jest wnikliwym przeglądem współczesnych koncepcji i doniesień naukowych w Polsce i zagranicą. Ze względu na limitowany nakład wydawniczy pozostaje mało dostępna dla środowisk naukowych i klinicznych.
Kompendium wiedzy dla psychiatrów, psychoterapeutów i psychologów
Models of anorexia nervosa (AN) posit that symptoms are maintained through deficient reward and enhanced punishment processing. However, theoretical and empirical inconsistencies highlight the need for a more nuanced conceptualization of this literature. Our goal was to comprehensively review the research on reward and punishment responding in AN from a cue-specific lens to determine which stimuli evoke or discourage reward and punishment responses in this population, and, ultimately, what properties these rewarding and punishing cues might share. A systematic review interrogating reward and punishment responses to specific cues yielded articles (n = 92) that examined responses to disorder relevant (e.g., food) and irrelevant (e.g., money) stimuli across self-report, behavioral, and biological indices. Overall, in most studies individuals with AN exhibited aversive responses to cues signaling higher body weights, social contexts, and monetary losses, and appetitive responses to cues for weight loss behaviors and thinness. Findings were more mixed on responses to palatable food and monetary gains. Results highlight that reward and punishment responding in AN are context specific and may be affected by varied stimulus qualities (e.g., predictability, controllability, delay, effort). Increasing specificity in future research on reward and punishment mechanisms in AN will better inform development of precisely-targeted interventions.
Objective:
Emotional processing dysfunction evident in eating disorders (ED) such as anorexia nervosa (AN) and bulimia nervosa (BN), is considered relevant to the development and maintenance of these disorders. The purpose of the current functional magnetic resonance imaging (fMRI) study was to pilot a comparison of the activity of the fronto-limbic and fronto-striatal brain areas during an emotion processing task in persons with ED.
Methods:
24 women patients with ED were scanned, while showing emotionally stimulating (pleasant, unpleasant) and neutral images from the International Affective Picture System (IAPS).
Results:
During the pleasant condition, significant differences in Dorsolateral Prefrontal Cortex (DLPFC) activations were found with AN participants presenting greater activation compared to BN and ED comorbid groups (EDc) and healthy controls also showing greater activation of this brain area compared to BN and EDc. Left putamen was less activated in EDc compared to both controls (C) and AN. During the unpleasant condition, AN participants showed hyperactivation of the Orbito-frontal Cortex (OFC) when compared to EDc.
Conclusion:
This study highlights the potential functional relevance of brain areas that have been associated with self-control. These findings should help advance understanding the neural substrate of ED, though they should be considered as preliminary and be cautiously interpreted.
Les troubles du comportement alimentaire (TCA) sont des maladies mentales fréquentes qui représentent la deuxième cause de mortalité chez les jeunes de 15 à 25 ans. L’anorexie mentale représente la maladie mentale la plus létale et sa prise en charge reste difficile. Les études récentes mettent en avant un profil neurocognitif particulier chez les patients souffrant d’anorexie mentale, profil retrouvé également chez leur apparentés. Ce sont notamment des difficultés de cohérence centrale et une difficulté de synthèse de l’information dans son ensemble. La facilitation graphique est un outil de médiation qui pourrait aider à la synthèse globale de l’information et à la facilitation des interactions dans un groupe de personne. Cet outil pourrait donc venir renforcer les outils psychothérapeutiques, notamment dans la thérapie multi familiale. Nous avons donc proposé un protocole de trois entretiens familiaux avec de la facilitation graphique lors des prises en charge pluridisciplinaires sur la clinique Saint Vincent de Paul à Lyon.
Notre série de cas rétrospective a porté sur deux groupes de huit patientes de 12 à 16 ans souffrant d’anorexie mentale restrictive. L’un bénéficiant d’entretiens familiaux avec facilitation graphique et l’autre d’entretiens familiaux classiques. L’objectif principal était d’évaluer l’impact d’un outil de médiation sur la qualité de vie des participants.
Les résultats ont témoigné d’une amélioration de l’ensemble des critères étudiés pour les deux groupes. L’amélioration de la qualité de vie et de la sous échelle « ascétisme » de l’EDI a été significativement plus importante (p<0,05) pour les patientes ayant bénéficié de la facilitation graphique. L’amélioration a été tendancielle (p<0,1) pour la sous échelle « perfectionnisme » de l’EDI 2 et pour la flexibilité mentale pour ce même groupe. Les résultats des questionnaires qualitatifs ont été témoins de retours très positifs des entretiens familiaux par l’ensemble des participants. La facilitation des interactions familiales et le rôle psychoéducatif étant mis en avant par les participants.
Notre travail témoigne de la faisabilité et de l’intérêt d’adapter les psychothérapies aux données actuelles de la science et plus particulièrement aux profils neurocognitifs des patients souffrant de troubles psychiques. Le développement de ce type d’outils pourrait à terme aider à améliorer la qualité de vie des patients que l’on sait fortement affectée dans les troubles psychiques.
Abstract A salient feature of anorexia nervosa (AN) is the persistent and severe restriction of food, such that dietary intake is inadequate to maintain a healthy body weight. Experimental tasks and paradigms have used illness-relevant stimuli, namely food images, to study the eating-specific neurocognitive mechanisms that promote food avoidance. This systematic review, completed in accordance with PRISMA guidelines, identified and critically evaluated paradigms involving images of food that have been used to study AN. There were 50 eligible studies, published before March 10th 2018, identified from Medline and PsychINFO searches, and reference screening. Studies using food image-based paradigms were categorised into three methodologic approaches: neuropsychology, neurophysiology, and functional magnetic resonance imaging (fMRI). Paradigms were reviewed with a focus on how well they address phenomena central to AN. Across tasks, differences between individuals with AN and healthy peers have been identified, with the most consistent findings in the area of reward processing. Measuring task performance alongside actual eating behaviour, and using experimental manipulations to probe causality, may advance understanding of the mechanisms of illness in AN.
Anorexia nervosa (AN) ist eine schwere psychische Störung, wobei eine gestörte Emotionsregulation pathophysiologisch relevant ist. Pathologische Muster für das Erlernen und das Verarbeiten von Furcht bei Patientinnen mit AN könnten hinweisgebend auf die Furcht vor Gewichtszunahme und einem entsprechenden Vermeidungsverhalten sein. Die anhaltende Restriktion der Nahrungsaufnahme
hat Studien zufolge einen angstmindernden Effekt, während das Risiko an einer Angststörung zu erkranken bei Patientinnen mit AN signifikant erhöht ist.
In einem sogenannten „Instruierten Furchtparadigma“ wurden funktionelle zerebrale und physiologische Korrelate des Furchtlernenes bei 31 Frauen mit AN und 32 gesunden Kontrollen mittels funktioneller Magnetresonanztomografie untersucht. Die Probandinnen wurden instruiert, dass beim Erscheinen eines anfänglich neutralen Bildes, in Form eines farbigen Rechtecks, ein aversiver
Stimulus appliziert werden könnte („Furchtbedingung“), wohingegen während der Präsentation eines anders farbigen Rechtecks zu keiner Zeit ein aversiver Stimulus gegeben wird („Sicherheitsbedingung“). Als Maß für die Furchtakquisition mittels Instruktion dienten ein Stimulus-Erwartungsrating sowie die Messung der elektrodermalen Antwort.
Die Ergebnisse zeigen bei gesunden Probandinnen Aktivität in aus früheren Studien bekannten Furchtassoziierten Arealen, wie unter anderem der Inselrinde, dem anterioren Cingulum und dem dorsomedialen präfrontalen Cortex. Dies ist beweisend für die gelungene Durchführung des „Instruierten Furchtparadigmas“ (sogenanntes „proof of concept“). Frauen mit AN zeigten eine umfassende Hyporesponsivität in Arealen des zerebralen „Furchtnetzwerkes“, einschließlich
Inselrinde, anteriorem Gyrus cinguli, dorsomedialem und dorsolateralem Präfrontalcortex, wobei sie ihren Angstzustand, als auch ihre ängstlichen Persönlichkeitseigenschaften als signifikant höher bewerteten. Auch der Zeitverlauf der physiologischen Furchtsignale zeigte sich signifikant verändert.
Die funktionelle Hyporesponsivität des „Furchtnetzwerkes“ bei Frauen mit AN steht im Kontrast zu der vergleichsweise hohen Ängstlichkeit dieser Frauen. Dies könnte ein Hinweis auf eine Beeinträchtigung der neurobiologischen Furchtverarbeitung und Furchtregulation sein. Hierbei könnte ein, durch starke Unterernährung hervorgerufener, anxiolytischer Effekt eine zentrale Rolle spielen. Studien die krankheitsspezifisch aversiv wahrgenommene Stimuli (Körperbild und hoch-kalorische Lebensmittel) untersuchten berichten hingegen von einer erhöhten Aktivität des „Furchtnetzwerkes“.
Somit scheint das „Furchtnetzwerk“ bei AN nicht generell hyporesponsiv zu sein. Es wäre hingegen möglich, dass Patientinnen mit AN emotional auf krankheitsspezifische Inhalte fokussiert sind. Diese erste Studie zur Furchtkonditionierung bei AN zeigt somit erhebliche Störungen hinsichtlich
zerebraler Korrelate der Furcht sowie eine Dissoziation zwischen subjektivem Empfinden und neurobiologischer Aktivität.
Disordered eating behavior is the core symptom of the complex disorders anorexia nervosa and bulimia nervosa. Twin and family studies derive high heritability estimates. Hence, substantial genetic influences on the etiology can be assumed for both. Initially, candidate gene studies pertaining to the monoaminergic neurotransmitter systems and to body weight regulation comprised the core of the genetic analyses. Unfortunately, confirmed, solid findings substantiated in meta-analyses are rare, so that eventually none of these associations is unequivocal. Thus, systematic, genome-wide approaches emerged to identify genes with no a priori evidence for their involvement in eating disorders. Genome-wide association studies have hinted to formerly unknown genetic regions. However, significant genome-wide findings have not yet been reported.
Cognitive functions were investigated in four groups of women: 30 underweight anorexics, 38 normal-weight bulimics, 20 long-term weight-restored anorexics, and 39 normal controls. A MANOVA was used to examine performance on five neuropsychological domains derived from prior principal components analyses of a comprehensive neuropsychological battery. Underweight anorexics performed more poorly than normal controls in four of five neuropsychological domains (focusing/execution, verbal, memory, and visuospatial), while normal-weight bulimics showed poorer performances only in focusing/execution. The absolute differences in scores between eating disorder groups and normal controls were for the most part small, suggesting subtle rather than frank cognitive difficulties. Poorer neuropsychological test performance was associated with anxiety but not depression as measured by the Tryon, Stein, and Chu Tension scale and scale 2 of the MMPI respectively. The findings support previous reports of attentional difficulties in eating disorders but do not support the hypothesis of differential right-hemisphere dysfunction in eating disorders.
Personality characteristics were assessed in women who had physically and, in the majority, psychologically recovered from restricting anorexia nervosa at an 8- to 10-year follow-up. Personality dimensions were evaluated using the Multidimensional Personality Questionnaire, the California Personality Inventory, and the Reid-Ware Scale. Women who had recovered from anorexia nervosa rated higher on risk avoidance, displayed greater restraint in emotional expression and initiative, and showed greater conformance to authority than age-matched normal women. On comparison with their sisters, the recovered women reported a greater degree of self- and impulse control and less enterprise and spontaneity; sisters, however, endorsed equally high moral standards. The differences in personality characteristics remained significant after statistically controlling for depressive symptoms and eating behavior. The results suggest that a temperamental disposition toward emotional and behavioral restraint combined with a strong sense for traditional values may be psychological risk factors for the development of the restricting type of anorexia nervosa.
It is well recognized that patients with anorexia nervosa have perfectionistic and obsessive behaviors. This study investigated whether such behaviors persist after recovery.
Twenty subjects who had recovered from anorexia nervosa were recruited for the study. They had been at normal weight and their menses had been regular for more than a year. These subjects were compared with 16 healthy women with the use of the Eating Disorder Inventory, the Frost Multidimensional Perfectionism Scale, and the Yale-Brown Obsessive Compulsive Scale.
The recovered anorexic patients had significantly higher scores than the comparison women on the measures of perfectionism on the Eating Disorder Inventory and on overall perfectionism on the Frost scale. Moreover, the recovered patients had higher scores on the Yale-Brown scale, with target symptoms suggesting that many had specific concerns with symmetry and exactness.
Certain characteristics of anorexia nervosa, such as a need for order and precision, persist after good outcome and recovery, raising the question of whether these behaviors are traits that contribute to the pathogenesis of this illness.
Assessments of anterior cingulate cortex in experimental animals and humans have led to unifying theories of its structural organization and contributions to mammalian behaviour. The anterior cingulate cortex forms a large region around the rostrum of the corpus callosum that is termed the anterior executive region. This region has numerous projections into motor systems, however, since these projections originate from different parts of anterior cingulate cortex and because functional studies have shown that it does not have a uniform contribution to brain functions, the anterior executive region is further subdivided into 'affect' and 'cognition' components. The affect division includes areas 25, 33 and rostral area 24, and has extensive connections with the amygdala and periaqueductal grey, and parts of it project to autonomic brainstem motor nuclei. In addition to regulating autonomic and endocrine functions, it is involved in conditioned emotional learning, vocalizations associated with expressing internal states, assessments of motivational content and assigning emotional valence to internal and external stimuli, and maternal-infant interactions. The cognition division includes caudal areas 24' and 32', the cingulate motor areas in the cingulate sulcus and nociceptive cortex. The cingulate motor areas project to the spinal cord and red nucleus and have premotor functions, while the nociceptive area is engaged in both response selection and cognitively demanding information processing. The cingulate epilepsy syndrome provides important support of experimental animal and human functional imaging studies for the role of anterior cingulate cortex in movement, affect and social behaviours. Excessive cingulate activity in cases with seizures confirmed in anterior cingulate cortex with subdural electrode recordings, can impair consciousness, alter affective state and expression, and influence skeletomotor and autonomic activity. Interictally, patients with anterior cingulate cortex epilepsy often display psychopathic or sociopathic behaviours. In other clinical examples of elevated anterior cingulate cortex activity it may contribute to tics, obsessive-compulsive behaviours, and aberrent social behaviour. Conversely, reduced cingulate activity following infarcts or surgery can contribute to behavioural disorders including akinetic mutism, diminished self-awareness and depression, motor neglect and impaired motor initiation, reduced responses to pain, and aberrent social behaviour. The role of anterior cingulate cortex in pain responsiveness is suggested by cingulumotomy results and functional imaging studies during noxious somatic stimulation. The affect division of anterior cingulate cortex modulates autonomic activity and internal emotional responses, while the cognition division is engaged in response selection associated with skeletomotor activity and responses to noxious stimuli. Overall, anterior cingulate cortex appears to play a crucial role in initiation, motivation, and goal-directed behaviours.(ABSTRACT TRUNCATED AT 400 WORDS)
This study was undertaken to determine whether the increased cerebrospinal fluid (CSF) volumes found in anorexia nervosa (AN) are the result of differences in gray matter or white matter volumes or both.
Thirteen adolescent girls with AN who were receiving inpatient care at a tertiary-care university children's hospital and eight healthy female control subjects were studied by using magnetic resonance imaging. Images were processed by means of software developed to classify all pixels as either CSF, gray matter, or white matter. Pixels of each class were then summed across all sections.
The AN group had larger total CSF volumes in association with deficits in both total gray matter and total white matter volumes. Lowest reported body mass index was inversely correlated with total CSF volume and positively correlated with total gray matter volume. Urinary free cortisol levels were positively correlated with total CSF volume and inversely correlated with central gray matter volume.
These findings add support to the view that the brain abnormalities found in AN are in large part the result of the effects of the illness. The extent to which these differences in gray matter and white matter volumes are reversible with recovery remains to be established.
This study assessed brain function in 20 adolescent females with anorexia nervosa (AN) and 20 controls using event-related potentials (ERPs) and a battery of neuropsychological tests. In the AN group, N4 latencies for a nonverbal memory task were significantly longer than for a verbal task, and P3 latencies for the verbal task were significantly longer among anorexics as compared to controls. On the nonverbal task, the AN group failed to show a right > left hemispheric asymmetry for P3 amplitudes which was observed for controls. These group differences for P3 latency and amplitude were particularly pronounced in the central-parietal region of the head. Body Mass Index (BMI) in the anorexic group significantly predicted N4 amplitudes for the verbal task in the left hemisphere and P3 amplitudes for the nonverbal task in the right hemisphere. The two groups did not differ on any of the tests used to assess neuropsychological functioning. Eight nutritionally recovered patients and their matched controls were retested using the same procedures. Anorexics showed larger P3 amplitudes for the verbal as compared to the nonverbal task at follow-up. These findings provide evidence for localized brain dysfunction in anorexia nervosa that only partially normalizes with weight gain.
Structural changes have been observed in the brains of low-weight patients with anorexia nervosa (AN), including increased cerebrospinal fluid (CSF) volumes and decreased gray matter and white matter volumes. We hypothesized that subjects who are weight-recovered from AN would show elevated CSF volumes and reduced gray matter volumes compared with controls.
We used magnetic resonance imaging to compare the brains of 12 subjects who are weight-recovered from AN (time since weight recovery, 1-23 years) with those of 18 healthy control subjects and 13 low-weight patients with AN. Axial, dual-echo scans of the whole brain were segmented into gray matter, white matter, and CSF compartments by means of a computerized volumetric approach. Brain measures were corrected for the significant effects of intracranial volume and age, based on regression analysis of a larger group of 30 healthy female controls.
Tests showed that the weight-recovered group had significantly greater CSF volumes and smaller gray matter volumes than the control group. By comparison with low-weight patients, the weight-recovered subjects had significantly smaller CSF volumes and significantly larger gray matter and white matter volumes. In the weight-recovered group, neither the CSF elevations nor gray matter deficits were correlated with the length of time since weight recovery.
The persistent gray matter volume deficits in subjects who are weight-recovered from AN suggest that there may be an irreversible component to the brain changes associated with the illness. The neuropathological features of this irreversible component have yet to be characterized.
To assess whether the cerebral gray and white matter volume deficits described in patients with anorexia nervosa (AN) are fully reversible with weight rehabilitation.
A prospective cohort study using magnetic resonance imaging to examine the brains of female adolescents after weight recovery from AN.
An adolescent eating disorder program located in a tertiary care children's hospital.
Of 13 patients who underwent a previous magnetic resonance imaging study at a low weight, 6 patients were weight recovered and underwent rescanning. All brain measures were corrected for the effects of intracranial volume and age, based on a regression analysis of a group of 34 healthy female control subjects. Scans from the patients with AN were also compared with scans from an age-matched subset of 16 healthy female controls.
White matter volumes, gray matter volumes, and cerebrospinal fluid volumes in the weight-recovered AN group.
Quantitative analysis showed that white matter and ventricular cerebrospinal fluid volumes changed significantly (P = .03 for both) on weight recovery from AN. The weight-recovered patients had significant gray matter volume deficits (P = .01) and elevated cerebrospinal fluid volumes (P = .005) compared with those of the age-matched controls. They no longer had significant (P = .30) white matter volume deficits.
The finding of persistent gray matter volume deficits in patients who have recovered their weight after AN suggests an irreversible component to the structural brain changes associated with AN, in addition to a component that resolves on weight recovery.
We describe almost entirely automated procedures for estimation of global, voxel, and cluster-level statistics to test the null hypothesis of zero neuroanatomical difference between two groups of structural magnetic resonance imaging (MRI) data. Theoretical distributions under the null hypothesis are available for 1) global tissue class volumes; 2) standardized linear model [analysis of variance (ANOVA and ANCOVA)] coefficients estimated at each voxel; and 3) an area of spatially connected clusters generated by applying an arbitrary threshold to a two-dimensional (2-D) map of normal statistics at voxel level. We describe novel methods for economically ascertaining probability distributions under the null hypothesis, with fewer assumptions, by permutation of the observed data. Nominal Type I error control by permutation testing is generally excellent; whereas theoretical distributions may be over conservative. Permutation has the additional advantage that it can be used to test any statistic of interest, such as the sum of suprathreshold voxel statistics in a cluster (or cluster mass), regardless of its theoretical tractability under the null hypothesis. These issues are illustrated by application to MRI data acquired from 18 adolescents with hyperkinetic disorder and 16 control subjects matched for age and gender.
It is possible that psychopathological differences exist between the restricting and bulimic forms of anorexia nervosa. We investigated localized differences of brain blood flow of anorexia nervosa patients using SPECT image analysis with statistic parametric mapping (SPM) in an attempt to link brain blood flow patterns to neurophysiologic characteristics.
The subjects enrolled in this study included the following three groups: pure restrictor anorexics (AN-R), anorexic bulimics (AN-BP), and healthy volunteers (HV). All images were transformed into the standard anatomical space of the stereotactic brain atlas, then smoothed. After statistical analysis of each brain image, the relationships among images were evaluated. Results: SPM analysis of the SPECT images revealed that the blood flow of frontal area mainly containing bilateral anterior cingulate gyri (ACC) was significantly decreased in the AN-R group compared to the AN-BP and HV groups.
These findings suggest that some localized functions of the ACCare possibly relevant to the psychopathological aspects of AN-R.
Dorsal anterior cingulate cortex (dACC) is a brain region that subserves cognition and motor control, but the mechanisms of these functions remain unknown. Human neuroimaging and monkey electrophysiology studies have provided valuable insights, but it has been difficult to link the two literatures. Based on monkey single-unit recordings, we hypothesized that human dACC is comprised of a mixture of functionally distinct cells that variously anticipate and detect targets, indicate novelty, influence motor responses, encode reward values, and signal errors. As an initial test of this conceptualization, the current event-related functional MRI study used a reward-based decision-making task to isolate responses from a subpopulation of dACC cells sensitive to reward reduction. As predicted, seven of eight subjects showed significant (P < 10(-4)) dACC activation when contrasting reduced reward (REDrew) trials to fixation (FIX). Confirmatory group analyses then corroborated the predicted ordinal relationships of functional MRI activation expected during each trial type (REDrew > SWITCH > CONrew > or = FIX). The data support a role for dACC in reward-based decision making, and by linking the human and monkey literatures, provide initial support for the existence of heterogeneity within dACC. These findings should be of interest to those studying reward, cognition, emotion, motivation, and motor control.
The authors retrospectively examined a spectrum of childhood traits that reflect obsessive-compulsive personality in adult women with eating disorders and assessed the predictive value of the traits for the development of eating disorders.
In a case-control design, 44 women with anorexia nervosa, 28 women with bulimia nervosa, and 28 healthy female comparison subjects were assessed with an interview instrument that asked them to recall whether they had experienced various types of childhood behavior suggesting traits associated with obsessive-compulsive personality. The subjects also completed a self-report inventory of obsessive-compulsive disorder (OCD) symptoms.
Childhood obsessive-compulsive personality traits showed a high predictive value for development of eating disorders, with the estimated odds ratio for eating disorders increasing by a factor of 6.9 for every additional trait present. Subjects with eating disorders who reported perfectionism and rigidity in childhood had significantly higher rates of obsessive-compulsive personality disorder and OCD comorbidity later in life, compared with eating disorder subjects who did not report those traits.
Childhood traits reflecting obsessive-compulsive personality appear to be important risk factors for the development of eating disorders and may represent markers of a broader phenotype for a specific subgroup of patients with anorexia nervosa.
An unresolved question in neuroscience and psychology is how the brain monitors performance to regulate behavior. It has been proposed that the anterior cingulate cortex (ACC), on the medial surface of the frontal lobe, contributes to performance monitoring by detecting errors. In this study, event-related functional magnetic resonance imaging was used to examine ACC function. Results confirm that this region shows activity during erroneous responses. However, activity was also observed in the same region during correct responses under conditions of increased response competition. This suggests that the ACC detects conditions under which errors are likely to occur rather than errors themselves.
IntroductionHeritability Family StudiesTwin StudiesDevelopmental DifferencesComorbidity PsychopathologyPersonality and Physical CharacteristicsShared Transmission Between AN and BNSummaryMolecular Genetic Studies Association StudiesLinkage StudiesConclusions
References Family StudiesTwin StudiesDevelopmental Differences PsychopathologyPersonality and Physical CharacteristicsShared Transmission Between AN and BNSummary Association StudiesLinkage Studies
Objective
To assess the long-term course of recovery and relapse and predictors of outcome in anorexia nervosa. Method: A naturalistic, longitudinal prospective design was used to assess recovery and relapse in patients ascertained through a university-based specialty treatment program. Patients were assessed semiannually for 5 years and annually thereafter over 10–15 years from the time of their index admission. Recovery was defined in terms of varying levels of symptom remission maintained for no fewer than 8 consecutive weeks. Results: Nearly 30% of patients had relapses following hospital discharge, prior to clinical recovery. However, most patients were weight recovered and menstruating regularly by the end of follow-up, with nearly 76% of the cohort meeting criteria for full recovery. Relapse after recovery was relatively uncommon. Of note, time to recovery was protracted, ranging from 57–79 months depending on definition of recovery. Among restrictors at intake, nearly 30% developed binge eating, occurring within 5 years of intake. A variety of predictors of chronic outcome and binge eating were identified. There were no deaths in the cohort. Conclusion: The course of anorexia nervosa is protracted. Predictors of outcome are surprisingly few, but those identified are in keeping with previous accounts. The intensive treatment received by these patients may account for the lower levels of morbidity and mortality when considered in relation to other reports in the follow-up literature. © 1997 by John Wiley & Sons, Inc. J Eat Disord 22: 339–360 1997.
Abstract Sixty-one subjects with anorexia nervosa (AN) were followed for a minimum of 4 years after discharge (mean 8.3 years). They were evaluated using the Morgan-Russell Outcome Assessment Scale. Thirty-one (51%) were categorized as having good outcome, eight (13%) as intermediate, 15 (25%) as poor, and seven (11%) had died. As predictors of outcome, later onset (after 20 years of age) and low minimum body mass index were associated with poor prognosis. The outcome of AN in Japan is relatively similar to those in Western countries, irrespective of different sociocultural backgrounds and health systems.
Two questions arising In the analysis of functional magnetic resonance imaging (fMRI) data acquired during periodic sensory stimulation are: i) how to measure the experimentally determined effect in fMRI time series; and ii) how to decide whether an apparent effect is significant Our approach is first to fit a time series regression model, including sine and cosine terms at the (fundamental) frequency of experimental stimulation, by pseudogeneralized least squares (PGLS) at each pixel of an image. Sinusoidal modeling takes account of locally variable hemodynamic delay and dispersion, and PGLS fitting corrects for residual or endogenous autocorrelation in fMRI time series, to yield best unbiased estimates of the amplitudes of the sine and cosine terms at fundamental frequency; from these parameters the authors derive estimates of experimentally determined power and its standard error. Randomization testing is then used to create inferential brain activation maps (BAMs) of pixels significantly activated by the experimental stimulus. The methods are illustrated by application to data acquired from normal human subjects during periodic visual and auditory stimulation.
Even in the absence of an experimental effect, functional magnetic resonance imaging (fMRI) time series generally demonstrate serial dependence. This colored noise or endogenous autocorrelation typically has disproportionate spectral power at low frequencies, i.e., its spectrum is -like. Various pre-whitening and pre-coloring strategies have been proposed to make valid inference on standardised test statistics estimated by time series regression in this context of residually autocorrelated errors. Here we introduce a new method based on random permutation after orthogonal transformation of the observed time series to the wavelet domain. This scheme exploits the general whitening or decorrelating property of the discrete wavelet transform and is implemented using a Daubechies wavelet with four vanishing moments to ensure exchangeability of wavelet coefficients within each scale of decomposition. For -like or fractal noises, e.g., realisations of fractional Brownian motion (fBm) parameterised by Hurst exponent 0 < H < 1, this resampling algorithm exactly preserves wavelet-based estimates of the second order stochastic properties of the (possibly nonstationary) time series. Performance of the method is assessed empirically using -like noise simulated by multiple physical relaxation processes, and experimental fMRI data. Nominal type 1 error control in brain activation mapping is demonstrated by analysis of 13 images acquired under null or resting conditions. Compared to autoregressive pre-whitening methods for computational inference, a key advantage of wavelet resampling seems to be its robustness in activation mapping of experimental fMRI data acquired at 3 Tesla field strength. We conclude that wavelet resampling may be a generally useful method for inference on naturally complex time series. Hum. Brain Mapping 12:61–78, 2001. © 2001 Wiley-Liss, Inc.
We used single photon emission computed tomography (SPECT) with Tc-99m-HMPAO to examine the characteristics of regional cerebral blood flow (rCBF) in five patients with bulimia nervosa (BN), eight patients with anorexia nervosa (AN), and in nine healthy controls. The SPECT examinations were performed before and attar food intake stimulus, and the values of the corrected ratio (R) for rCBF in 10 cerebral cortical regions before (Rbefore) and after eating (Rafter) were calculated. The asymmetry indices (AI) of the R values for the left and right side of each cortical region and the percent change from Rbefore to Rafter (%change) were computed. In comparison with the other two groups, BN patients showed significantly higher Rbefore values in the bilateral inferior frontal and left temporal regions. The AN patients showed significantly lower Rbefore values in the left parietal region than the control group. There were no significant differences in Rafter values among the three groups. The %change values in the AN group showed the greatest increase in 9 out of the 10 regions. In contrast to the positive values obtained from the 10 regions observed in the AN group, 5 out of the 10 regions in the BN group showed negative values. Among the three groups, significant differences in %change were observed on both sides of the inferior frontal, temporal, parietal, and occipital regions. These findings indicate that differences in cerebral function of BN and AN patients can be characterized through SPECT imaging.
A simple questionnaire was developed as an instrument for assessing the existence and extent of different obsessional-compulsive complaints. Two major types of complaint, checking and washing compulsions, and two minor types, slowness and doubting, were established. The final form of the questionnaire, and major properties, are presented.
No definitive therapy exists for anorexia nervosa (AN) or bulimia nervosa (BN). Nevertheless, biologic and psychologic research into these disorders has increased over the last decade. We examine the various drugs available for treatment. Advances in pharmacotherapy for AN have been modest and have reflected efforts either to stimulate hunger and weight gain or to control complications of the starvation process. Food remains the "drug" of choice. Antidepressants have been found to be beneficial in the treatment of BN. The meaning of this in the context of a relation between BN and mood disorders remains unclear, since coexistent depression does not predict a positive response to these drugs. Pharmacotherapy represents a single but important dimension of the management of patients with eating disorders. The optimal integration of drug therapy and psychotherapy and the identification of predictors of a positive response to drugs have yet to be addressed by clinical research.
The selective processing of food- and body size-related information was investigated using a modified version of the Stroop task. Anorexic subjects were generally slower than controls in colour-naming all words, and particularly slow with food-related words. This interference effect appeared to operate maximally amongst subjects who fell into the higher end of the anorexic weight range. The findings appeared to be a reflection of current concerns with food and eating.