RESUMO
Effortful tasks are generally experienced as costly, but the value of work varies greatly across individuals and populations. While most mental health conditions are characterized by amotivation and effort avoidance, individuals with anorexia nervosa (AN) persistently engage in effortful behaviors that most people find unrewarding (food restriction, excessive exercise). Current models of AN differentially attribute such extreme weight-control behavior to altered reward responding and exaggerated cognitive control. In a novel test of these theoretical accounts, we employed an established cognitive effort discounting paradigm in combination with fMRI in young acutely underweight female patients with AN (n = 48) and age-matched healthy controls (HC; n = 48). Contrary to the hypothesis that individuals with AN would experience cognitive effort (operationalized as N-back task performance) as less costly than HC participants, groups did not differ in the subjective value (SV) of discounted rewards or in SV-related activation of brain regions involved in reward valuation. Rather, all group differences in both behavior (superior N-back performance in AN and associated effort ratings) and fMRI activation (increased SV-related frontoparietal activation during decision-making in AN even for easier choices) were more indicative of increased control. These findings suggest that while effort discounting may be relatively intact in AN, effort investment is high both when performing demanding tasks and during effort-based decision-making; highlighting cognitive overcontrol as an important therapeutic target. Future research should establish whether exaggerated control during effort-based decision-making persists after weight-recovery and explore learning the value of effort in AN with tasks involving disorder-relevant effort demands and rewards.
RESUMO
BACKGROUND: Physical sequelae of anorexia nervosa (AN) include a marked reduction in whole brain volume and subcortical structures such as the hippocampus. Previous research has indicated aberrant levels of inflammatory markers and growth factors in AN, which in other populations have been shown to influence hippocampal integrity. METHODS: Here we investigated the influence of concentrations of two pro-inflammatory cytokines (tumor necrosis factor-alpha [TNF-α] and interleukin-6 [IL-6]) and brain-derived neurotrophic factor (BDNF) on the whole hippocampal volume, as well as the volumes of three regions (the hippocampal body, head, and tail) and 18 subfields bilaterally. Investigations occurred both cross-sectionally between acutely underweight adolescent/young adult females with AN (acAN; n = 82) and people recovered from AN (recAN; n = 20), each independently pairwise age-matched with healthy controls (HC), and longitudinally in acAN after partial renourishment (n = 58). Hippocampal subfield volumes were quantified using FreeSurfer. Concentrations of molecular factors were analyzed in linear models with hippocampal (subfield) volumes as the dependent variable. RESULTS: Cross-sectionally, there was no evidence for an association between IL-6, TNF-α, or BDNF and between-group differences in hippocampal subfield volumes. Longitudinally, increasing concentrations of BDNF were positively associated with longitudinal increases in bilateral global hippocampal volumes after controlling for age, age2, estimated total intracranial volume, and increases in body mass index (BMI). CONCLUSIONS: These findings suggest that increases in BDNF may contribute to global hippocampal recovery over and above increases in BMI during renourishment. Investigations into treatments targeted toward increasing BDNF in AN may be warranted.
RESUMO
BACKGROUND: Anorexia nervosa (AN) is a mental disorder characterized by dietary restriction, fear of gaining weight, and distorted body image. Recent studies indicate that the hippocampus, crucial for learning and memory, may be affected in AN, yet subfield-specific effects remain unclear. We investigated hippocampal subfield alterations in acute AN, changes following weight restoration, and their associations with leptin levels. METHODS: T1-weighted magnetic resonance imaging scans were processed using FreeSurfer. We compared 22 left and right hemispheric hippocampal subfield volumes cross-sectionally and longitudinally in females with acute AN (n = 165 at baseline, n = 110 after partial weight restoration), healthy female controls (HCs; n = 271), and females after long-term recovery from AN (n = 79) using linear models. RESULTS: We found that most hippocampal subfield volumes were significantly reduced in patients with AN compared with HCs (~-3.9%). Certain areas such as the subiculum exhibited no significant reduction in the acute state of AN, while other areas, such as the hippocampal tail, showed strong decreases (~-9%). Following short-term weight recovery, most subfields increased in volume. Comparisons between participants after long-term weight-recovery and HC yielded no differences. The hippocampal tail volume was positively associated with leptin levels in AN independent of body mass index. CONCLUSIONS: Our study provides evidence of differential volumetric differences in hippocampal subfields between individuals with AN and HC and almost complete normalization after weight rehabilitation. These alterations are spatially inhomogeneous and more pronounced compared with other major mental disorders (e.g. major depressive disorder and schizophrenia). We provide novel insights linking hypoleptinemia to hippocampal subfield alterations hinting towards clinical relevance of leptin normalization in AN recovery.
Assuntos
Anorexia Nervosa , Transtorno Depressivo Maior , Transtornos Psicóticos , Humanos , Feminino , Transtorno Depressivo Maior/patologia , Leptina , Anorexia Nervosa/diagnóstico por imagem , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Transtornos Psicóticos/patologia , Imageamento por Ressonância Magnética/métodos , Tamanho do ÓrgãoRESUMO
BACKGROUND: Anorexia nervosa (AN) is characterized by sizable, widespread gray matter (GM) reductions in the acutely underweight state. However, evidence for persistent alterations after weight-restoration has been surprisingly scarce despite high relapse rates, frequent transitions to other psychiatric disorders, and generally unfavorable outcome. While most studies investigated brain regions separately (univariate analysis), psychiatric disorders can be conceptualized as brain network disorders characterized by multivariate alterations with only subtle local effects. We tested for persistent multivariate structural brain alterations in weight-restored individuals with a history of AN, investigated their putative biological substrate and relation with 1-year treatment outcome. METHODS: We trained machine learning models on regional GM measures to classify healthy controls (HC) (N = 289) from individuals at three stages of AN: underweight patients starting intensive treatment (N = 165, used as baseline), patients after partial weight-restoration (N = 115), and former patients after stable and full weight-restoration (N = 89). Alterations after weight-restoration were related to treatment outcome and characterized both anatomically and functionally. RESULTS: Patients could be classified from HC when underweight (ROC-AUC = 0.90) but also after partial weight-restoration (ROC-AUC = 0.64). Alterations after partial weight-restoration were more pronounced in patients with worse outcome and were not detected in long-term weight-recovered individuals, i.e. those with favorable outcome. These alterations were more pronounced in regions with greater functional connectivity, not merely explained by body mass index, and even increases in cortical thickness were observed (insula, lateral orbitofrontal, temporal pole). CONCLUSIONS: Analyzing persistent multivariate brain structural alterations after weight-restoration might help to develop personalized interventions after discharge from inpatient treatment.
Assuntos
Anorexia Nervosa , Imageamento por Ressonância Magnética , Humanos , Anorexia Nervosa/psicologia , Magreza/psicologia , Encéfalo/diagnóstico por imagem , Índice de Massa CorporalRESUMO
BACKGROUND: The amygdala is a subcortical limbic structure consisting of histologically and functionally distinct subregions. New automated structural magnetic resonance imaging (MRI) segmentation tools facilitate the in vivo study of individual amygdala nuclei in clinical populations such as patients with anorexia nervosa (AN) who show symptoms indicative of limbic dysregulation. This study is the first to investigate amygdala nuclei volumes in AN, their relationships with leptin, a key indicator of AN-related neuroendocrine alterations, and further clinical measures. METHODS: T1-weighted MRI scans were subsegmented and multi-stage quality controlled using FreeSurfer. Left/right hemispheric amygdala nuclei volumes were cross-sectionally compared between females with AN (n = 168, 12-29 years) and age-matched healthy females (n = 168) applying general linear models. Associations with plasma leptin, body mass index (BMI), illness duration, and psychiatric symptoms were analyzed via robust linear regression. RESULTS: Globally, most amygdala nuclei volumes in both hemispheres were reduced in AN v. healthy control participants. Importantly, four specific nuclei (accessory basal, cortical, medial nuclei, corticoamygdaloid transition in the rostral-medial amygdala) showed greater volumetric reduction even relative to reductions of whole amygdala and total subcortical gray matter volumes, whereas basal, lateral, and paralaminar nuclei were less reduced. All rostral-medially clustered nuclei were positively associated with leptin in AN independent of BMI. Amygdala nuclei volumes were not associated with illness duration or psychiatric symptom severity in AN. CONCLUSIONS: In AN, amygdala nuclei are altered to different degrees. Severe volume loss in rostral-medially clustered nuclei, collectively involved in olfactory/food-related reward processing, may represent a structural correlate of AN-related symptoms. Hypoleptinemia might be linked to rostral-medial amygdala alterations.
Assuntos
Anorexia Nervosa , Feminino , Humanos , Anorexia Nervosa/diagnóstico por imagem , Anorexia Nervosa/patologia , Leptina , Tonsila do Cerebelo/diagnóstico por imagem , Tonsila do Cerebelo/patologia , Substância Cinzenta/patologia , Imageamento por Ressonância Magnética/métodosRESUMO
BACKGROUND: Anorexia nervosa (AN) is characterized by severe emaciation and drastic reductions of brain mass, but the underlying mechanisms remain unclear. The present study investigated the putative association between the serum-based protein markers of brain damage neurofilament light (NF-L), tau protein, and glial fibrillary acidic protein (GFAP) and cortical thinning in acute AN. METHODS: Blood samples and magnetic resonance imaging scans were obtained from 52 predominantly adolescent, female patients with AN before and after partial weight restoration (increase in body mass index >14%). The effect of marker levels before weight gain and change in marker levels on cortical thickness (CT) was modeled at each vertex of the cortical surface using linear mixed-effect models. To test whether the observed effects were specific to AN, follow-up analyses exploring a potential general association of marker levels with CT were conducted in a female healthy control (HC) sample (n = 147). RESULTS: In AN, higher baseline levels of NF-L, an established marker of axonal damage, were associated with lower CT in several regions, with the most prominent clusters located in bilateral temporal lobes. Tau protein and GFAP were not associated with CT. In HC, no associations between damage marker levels and CT were detected. CONCLUSIONS: A speculative interpretation would be that cortical thinning in acute AN might be at least partially a result of axonal damage processes. Further studies should thus test the potential of serum NF-L to become a reliable, low-cost and minimally invasive marker of structural brain alterations in AN.
Assuntos
Anorexia Nervosa , Proteínas tau , Adolescente , Humanos , Feminino , Anorexia Nervosa/diagnóstico por imagem , Afinamento Cortical Cerebral , Filamentos Intermediários , Encéfalo , BiomarcadoresRESUMO
OBJECTIVE: The amygdaloid complex plays a pivotal role in emotion processing and has been associated with rumination transdiagnostically. In anorexia nervosa (AN), we previously observed differential reductions of amygdala nuclei volumes (rostral-medial cluster substantially affected) and, in another study, elevated food-/weight-related rumination. Both amygdala volumes and rumination frequency correlated with characteristically suppressed leptin levels in AN. Thus, we hypothesized that amygdala nuclei alterations might be associated with AN-related rumination and potentially mediate the leptin-rumination relationship in AN. METHODS: Rumination (food-/weight-related) was assessed using ecological momentary assessment for a 14-day period. We employed frequentist and Bayesian linear mixed effects models in females with AN (n = 51, 12-29 years, majority admitted to inpatient treatment) and age-matched healthy females (n = 51) to investigate associations between rostral-medial amygdala nuclei volume alterations (accessory basal, cortical, medial nuclei, corticoamygdaloid transitions) and rumination. We analyzed mediation effects using multi-level structural equation models. RESULTS: Reduced right accessory basal and cortical nuclei volumes predicted more frequent weight-related rumination in AN; both nuclei fully mediated the effect of leptin on weight-related rumination. In contrast, we found robust evidence for the absence of amygdala nuclei volume effects on rumination in healthy females. CONCLUSION: This study provides first evidence for the relevance of specific amygdala substructure reductions regarding cognitive symptom severity in AN and points toward novel mechanistic insight into the relationship between hypoleptinemia and rumination, which might involve the amygdaloid complex. Our findings in AN may have important clinical value with respect to understanding the beneficial neuropsychiatric effects of leptin (treatment) in AN and potentially other psychiatric conditions such as depression.
Assuntos
Anorexia Nervosa , Feminino , Humanos , Leptina , Teorema de Bayes , Tonsila do Cerebelo/diagnóstico por imagem , Avaliação Momentânea EcológicaRESUMO
BACKGROUND: Previous studies have suggested that individuals recovered from anorexia nervosa (AN) are characterized by increased serotonergic (5-HT) activity that might be related to elevated levels of anxiety. Assuming these traits to be also present in individuals at risk for AN, it was further hypothesized that restricting food intake might be a means to temporarily alleviate dysphoric affective states by reducing central nervous availability of tryptophan (TRP), the sole precursor of 5-HT. One study that supported this hypothesis found anxiolytic effects in individuals with a history of AN during an experimentally induced short-term depletion of TRP supply to the brain. METHODS: In this placebo-controlled, double-blind cross-over study, 22 patients weight-recovered from AN (recAN) and 25 healthy control participants (HC) completed questionnaires assessing anxiety and momentary mood during acute tryptophan depletion (ATD), a dietary intervention that lowers central 5-HT synthesis. RESULTS: The ATD procedure effectively reduced the ratio of TRP to competing for large neutral amino acids in the peripheral blood, indicating decreased TRP supply to the brain. Effects of ATD on anxiety and mood did not differ between recAN and HC. Bayesian null hypothesis testing confirmed these initial results. DISCUSSION: Our results do not support the hypothesis that short-term depletion of TRP and its impact on the brain 5-HT reduces anxiety or improves mood in AN. As the evidence for the role of 5-HT dysfunction on affective processes in patients with AN is limited, further studies are needed to assess its relevance in the pathophysiology of AN.
Assuntos
Anorexia Nervosa , Triptofano , Humanos , Feminino , Triptofano/metabolismo , Serotonina/metabolismo , Teorema de Bayes , Estudos Cross-Over , Ansiedade , Método Duplo-CegoRESUMO
OBJECTIVE: The capacity of individuals with anorexia nervosa (AN) to forgo immediate food rewards in their long-term pursuit of thinness is thought to reflect elevated self-control and/or abnormal reward sensitivity. Prior research attempted to capture an increased tendency to delay gratification in AN using delay-discounting tasks that assess how rapidly the subjective value of rewards decreases as a function of time until receipt. However, significant effects were mostly subtle or absent. Here, we tested whether the process leading to such decisions might be altered in AN. METHOD: We recorded mouse-cursor movement trajectories leading to the final choice in a computerized delay-discounting task (238 trials) in 55 acutely underweight females with AN and pairwise age-matched female healthy controls (HC). We tested for group differences in deviations from a direct choice path, a measure of conflict strength in decision making, and whether group moderated the effect of several predictors of conflict strength (e.g., choice difficulty, consistency). We also explored reaction times and changes in trajectory directions (X-flips). RESULTS: No group differences in delay-discounting parameters or movement trajectories were detected. However, the effect of the aforementioned predictors on deviations (and to a lesser extent reaction times) was reduced in AN. DISCUSSION: These findings suggest that while delay discounting and conflict strength in decision making are generally unaltered in AN, conflict strength was more stable across different decisions in the disorder. This might enable individuals with AN to pursue (maladaptive) long-term body-weight goals, because particularly conflicting choices may not be experienced as such. PUBLIC SIGNIFICANCE: The deviations from a direct path of mouse-cursor movements during a computerized delay-discounting task varied less in people with anorexia nervosa. Assuming such deviations measure decision conflict, we speculate that this increased stability might help people with anorexia nervosa achieve their long-term weight goals, as for them the struggle with the decision to eat high-calorie meals when hungry will be milder, so they would be more likely to skip them.
RESUMO
Background: Extreme restrictive food choice in anorexia nervosa is thought to reflect excessive self-control and/or abnormal reward sensitivity. Studies using intertemporal choice paradigms have suggested an increased capacity to delay reward in anorexia nervosa, and this may explain an unusual ability to resist immediate temptation and override hunger in the long-term pursuit of thinness. It remains unclear, however, whether altered delay discounting in anorexia nervosa constitutes a state effect of acute illness or a trait marker observable after recovery. Methods: We repeated the analysis from our previous fMRI investigation of intertemporal choice in acutely underweight patients with anorexia nervosa in a sample of weight-recovered women with anorexia nervosa (n = 36) and age-matched healthy controls (n = 36) who participated in the same study protocol. Follow-up analyses explored functional connectivity separately in both the weight-recovered/healthy controls sample and the acute/healthy controls sample. Results: In contrast to our previous findings in acutely underweight patients with anorexia nervosa, we found no differences between weight-recovered patients with anorexia nervosa and healthy controls at either behavioural or neural levels. New analysis of data from the acute/healthy controls sample sample revealed increased coupling between dorsal anterior cingulate cortex and posterior brain regions as a function of decision difficulty, supporting the hypothesis of altered neural efficiency in the underweight state. Limitations: This was a cross-sectional study, and the results may be task-specific. Conclusion: Although our results underlined previous demonstrations of divergent temporal reward discounting in acutely underweight patients with anorexia nervosa, we found no evidence of alteration in patients with weight-recovered anorexia nervosa. Together, these findings suggest that impaired valuebased decision-making may not constitute a defining trait variable or "scar" of the disorder.
Assuntos
Anorexia Nervosa/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Tomada de Decisões , Doença Aguda , Adolescente , Adulto , Anorexia Nervosa/fisiopatologia , Encéfalo/fisiopatologia , Estudos de Casos e Controles , Criança , Comportamento de Escolha , Feminino , Neuroimagem Funcional , Giro do Cíngulo/diagnóstico por imagem , Giro do Cíngulo/fisiopatologia , Humanos , Imageamento por Ressonância Magnética , Recuperação da Saúde Mental , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiopatologia , Indução de Remissão , Magreza/fisiopatologia , Adulto JovemRESUMO
Background: Patients with anorexia nervosa forgo eating despite emaciation and severe health consequences. Such dysfunctional decision-making might be explained by an excessive level of self-control, alterations in homeostatic and hedonic regulation, or an interplay between these processes. We aimed to understand value-based decision-making in anorexia nervosa and its association with the gut hormone ghrelin. Besides its homeostatic function, ghrelin has been implicated in the hedonic regulation of appetite and reward via the modulation of phasic dopamine signalling. Methods: In a cross-sectional design, we studied acutely underweight (n = 94) and recovered (n = 37) patients with anorexia nervosa of the restrictive subtype, as well as healthy control participants (n = 119). We assessed plasma concentrations of desacyl ghrelin and parameters of delay discounting, probability discounting for gains and losses, and loss aversion. Results: Recovered patients displayed higher risk aversion for gains, but we observed no group differences for the remaining decision-making parameters. Desacyl ghrelin was higher in acutely underweight and recovered participants with anorexia nervosa relative to healthy controls. Moreover, we found a significant group × desacyl ghrelin interaction in delay discounting, indicating that in contrast to healthy controls, acutely underweight patients with anorexia nervosa who had high desacyl ghrelin concentrations preferably chose the delayed reward option. Limitations: We probed decision-making using monetary rewards, but patients with anorexia nervosa may react differently to disorder-relevant stimuli. Furthermore, in contrast to acyl ghrelin, the functions of desacyl ghrelin are unclear. Therefore, the interpretation of the results is preliminary. Conclusion: The propensity for risk aversion as found in recovered patients with anorexia nervosa could help them successfully complete therapy, or it could reflect sequelae of the disorder. Conversely, ghrelin findings might be related to a mechanism contributing to disease maintenance; that is, in acutely underweight anorexia nervosa, a hungry state may facilitate the ability to forgo an immediate reward to achieve a (dysfunctional) long-term goal.
Assuntos
Anorexia Nervosa/psicologia , Tomada de Decisões , Desvalorização pelo Atraso , Grelina/metabolismo , Doença Aguda , Adolescente , Adulto , Anorexia Nervosa/metabolismo , Estudos de Casos e Controles , Criança , Estudos Transversais , Feminino , Humanos , Recuperação da Saúde Mental , Adulto JovemRESUMO
BACKGROUND: Gray matter (GM) 'pseudoatrophy' is well-documented in patients with anorexia nervosa (AN), but changes in white matter (WM) are less well understood. Here we investigated the dynamics of microstructural WM brain changes in AN patients during short-term weight restoration in a combined longitudinal and cross-sectional study design. METHODS: Diffusion-weighted images were acquired in young AN patients before (acAN-Tp1, n = 56) and after (acAN-Tp2, n = 44) short-term weight restoration as well as in age-matched healthy controls (HC, n = 60). Images were processed using Tract-Based-Spatial-Statistics to compare fractional anisotropy (FA) across groups and timepoints. RESULTS: In the cross-sectional comparison, FA was significantly reduced in the callosal body in acAN-Tp1 compared with HC, while no differences were found between acAN-Tp2 and HC. In the longitudinal arm, FA increased with weight gain in acAN-Tp2 relative to acAN-Tp1 in large parts of the callosal body and the fornix, while it decreased in the right corticospinal tract. CONCLUSIONS: Our findings reveal that dynamic, bidirectional changes in WM microstructure in young underweight patients with AN can be reversed with brief weight restoration therapy. These results parallel those previously observed in GM and suggest that alterations in WM in non-chronic AN are also state-dependent and rapidly reversible with successful intervention.
Assuntos
Anorexia Nervosa/patologia , Anorexia Nervosa/terapia , Corpo Caloso/patologia , Magreza/patologia , Magreza/terapia , Aumento de Peso , Substância Branca/patologia , Adolescente , Adulto , Anorexia Nervosa/diagnóstico por imagem , Criança , Corpo Caloso/diagnóstico por imagem , Estudos Transversais , Imagem de Tensor de Difusão , Feminino , Humanos , Estudos Longitudinais , Reabilitação Psiquiátrica , Magreza/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Adulto JovemRESUMO
Structural magnetic resonance imaging studies have documented reduced gray matter in acutely ill patients with anorexia nervosa to be at least partially reversible following weight restoration. However, few longitudinal studies exist and the underlying mechanisms of these structural changes are elusive. In particular, the relative speed and completeness of brain structure normalization during realimentation remain unknown. Here we report from a structural neuroimaging study including a sample of adolescent/young adult female patients with acute anorexia nervosa (n=47), long-term recovered patients (n=34), and healthy controls (n=75). The majority of acutely ill patients were scanned longitudinally (n=35): at the beginning of standardized weight restoration therapy and again after partial weight normalization (>10% body mass index increase). High-resolution structural images were processed and analyzed with the longitudinal stream of FreeSurfer software to test for changes in cortical thickness and volumes of select subcortical regions of interest. We found globally reduced cortical thickness in acutely ill patients to increase rapidly (0.06 mm/month) during brief weight restoration therapy (≈3 months). This significant increase was predicted by weight restoration alone and could not be ascribed to potentially mediating factors such as duration of illness, hydration status, or symptom improvements. By comparing cortical thickness in partially weight-restored patients with that measured in healthy controls, we confirmed that cortical thickness had normalized already at follow-up. This pattern of thinning in illness and rapid normalization during weight rehabilitation was largely mirrored in subcortical volumes. Together, our findings indicate that structural brain insults inflicted by starvation in anorexia nervosa may be reversed at a rate much faster than previously thought if interventions are successful before the disorder becomes chronic. This provides evidence drawing previously speculated mechanisms such as (de-)hydration and neurogenesis into question and suggests that neuronal and/or glial remodeling including changes in macromolecular content may underlie the gray matter alterations observed in anorexia nervosa.
Assuntos
Anorexia Nervosa/dietoterapia , Anorexia Nervosa/patologia , Córtex Cerebral/patologia , Adolescente , Índice de Massa Corporal , Peso Corporal , Criança , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Estudos Longitudinais , Imageamento por Ressonância Magnética , Aumento de Peso , Adulto JovemRESUMO
A massive but reversible reduction of cortical thickness and subcortical gray matter (GM) volumes in Anorexia Nervosa (AN) has been recently reported. However, the literature on alterations in white matter (WM) volume and microstructure changes in both acutely underweight AN (acAN) and after recovery (recAN) is sparse and results are inconclusive. Here, T1-weighted and diffusion-weighted MRI data in a sizable sample of young and medication-free acAN (n = 35), recAN (n = 32), and age-matched female healthy controls (HC, n = 62) were obtained. For analysis, a well-validated global probabilistic tractography reconstruction algorithm including rigorous motion correction implemented in FreeSurfer: TRACULA (TRActs Constrained by UnderLying Anatomy) were used. Additionally, a clustering algorithm and a multivariate pattern classification technique to WM metrics to predict group membership were applied. No group differences in either WM volume or WM microstructure were detected with standard analysis procedures either in acAN or recAN relative to HC after controlling for the number of performed statistical tests. These findings were not affected by age, IQ, or psychiatric symptoms. While cluster analysis was unsuccessful at discriminating between groups, multivariate pattern classification showed some ability to separate acAN from HC (but not recAN from HC). However, these results were not compatible with a straightforward hypothesis of impaired WM microstructure. The current findings suggest that WM integrity is largely preserved in non-chronic AN. This finding stands in contrast to findings in GM, but may help to explain the relatively intact cognitive performance of young patients with AN and provide the basis for the fast recovery of GM structures. Hum Brain Mapp 37:4069-4083, 2016. © 2016 Wiley Periodicals, Inc.
Assuntos
Anorexia Nervosa/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Adolescente , Adulto , Envelhecimento/patologia , Algoritmos , Anorexia Nervosa/psicologia , Anorexia Nervosa/terapia , Índice de Massa Corporal , Criança , Análise por Conglomerados , Imagem de Tensor de Difusão , Feminino , Humanos , Processamento de Imagem Assistida por Computador/métodos , Inteligência , Imageamento por Ressonância Magnética , Análise Multivariada , Tamanho do Órgão , Magreza/diagnóstico por imagem , Magreza/psicologia , Magreza/terapia , Aumento de Peso , Adulto JovemRESUMO
BACKGROUND: We have previously shown increased resting-state functional connectivity (rsFC) in the frontoparietal network (FPN) and the default mode network (DMN) in patients with acute anorexia nervosa. Based on these findings we investigated within-network rsFC in patients recovered from anorexia nervosa to examine whether these abnormalities are a state or trait marker of the disease. To extend the understanding of functional connectivity in patients with anorexia nervosa, we also estimated rsFC between large-scale networks. METHODS: Girls and women recovered from anorexia nervosa and pair-wise, age- and sex-matched healthy controls underwent a resting-state fMRI scan. Using independent component analyses (ICA), we isolated the FPN, DMN and salience network. We used standard comparisons as well as a hypothesis-based approach to test the findings of our previous rsFC study in this recovered cohort. Temporal correlations between network time-course pairs were computed to investigate functional network connectivity (FNC). RESULTS: Thirty-one patients recovered from anorexia nervosa and 31 controls participated in our study. Standard group comparisons revealed reduced rsFC between the dorsolateral prefrontal cortex (dlPFC) and the FPN in the recovered group. Using a hypothesis-based approach we extended the previous finding of increased rsFC between the angular gyrus and the FPN in patients recovered from anorexia nervosa. No group differences in FNC were revealed. LIMITATIONS: The study design did not allow us to conclude that the difference found in rsFC constitutes a scar effect of the disease. CONCLUSION: This study suggests that some abnormal rsFC patterns found in patients recovered from anorexia nervosa normalize after long-term weight restoration, while distorted rsFC in the FPN, a network that has been associated with cognitive control, may constitute a trait marker of the disorder.
Assuntos
Anorexia Nervosa/fisiopatologia , Encéfalo/fisiopatologia , Anorexia Nervosa/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Estudos Transversais , Feminino , Humanos , Imageamento por Ressonância Magnética , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiopatologia , Descanso , Adulto JovemRESUMO
In anorexia nervosa (AN), volitional inhibition of rewarding behaviors, such as eating, involves a conflict between the desire to suppress appetite and the inherent motive to consume. This conflict is thought to have costs that carry over into daily life, e.g., triggering negative affect and/or recurring ruminations, which may ultimately impact long term outcome. Hence, increasing research effort is being dedicated to understand the link between emotional and ruminative processes in the etiology and maintenance of AN. We investigated whether affective states influence disorder-related rumination in AN applying "ecological momentary assessment", a method which allows the experimenter to gain insight into psychological processes in the natural environment and assess data in real time. Participants (AN = 37, healthy controls = 33) were given a smartphone for 14 days. A ringtone signaled at six random time-points each day to fill in a questionnaire, which gauged disorder-typical thoughts about food and weight as well as affective state. Analyses, applying hierarchical linear models confirmed that AN patients spend more time thinking about food, body shape and weight than controls (p < 0.001). Additionally, the results support the hypothesis that momentary negative affect (but not baseline depression (p = 0.56) or anxiety symptoms (p = 0.60) are positively associated with a higher amount of disorder-related rumination in patients (p < 0.001). Our findings are in line with theories which claim that ruminative thinking induces a vulnerability to negative stimuli which, in turn, fosters heightened negative affect. Thus, therapeutic interventions could be improved by implementing modules that specifically target disorder-related rumination.
Assuntos
Afeto/fisiologia , Anorexia Nervosa/fisiopatologia , Pensamento/fisiologia , Adolescente , Adulto , Criança , Avaliação Momentânea Ecológica , Feminino , Humanos , Adulto JovemRESUMO
BACKGROUND: Steatotic liver disease (SLD) is characterized by excessive accumulation of lipids in the liver. It is associated with elevated risk of hepatic and cardiometabolic diseases, as well as mental disorders such as depression. Previous studies revealed global gray matter reduction in SLD. To investigate a possible shared neurobiology with depression, we examined liver fat-related regional gray matter alterations in SLD and its most significant clinical subgroup metabolic dysfunction-associated steatotic liver disease (MASLD). METHODS: We analyzed regional cortical thickness and area obtained from brain MRI in 29,051 participants in UK Biobank. Liver fat amount was computed as proton density fat fraction (PDFF) from liver MRI scans. We examined the relationship between brain structure and PDFF, adjusting for sociodemographic, physical, lifestyle, and environmental factors, as well as alcohol intake and a spectrum of cardiometabolic covariates. Finally, we compared patterns of brain alterations in SLD/MASLD and major depressive disorder (MDD) using previously published results. RESULTS: PDFF-related gray matter alterations were region-specific, involving both increases and decreases in cortical thickness, and increased cortical area. In several regions, PDFF effects on gray matter could also be attributed to cardiometabolic covariates. However, PDFF was consistently associated with lower cortical thickness in middle and superior temporal regions and higher cortical thickness in pericalcarine and right frontal pole regions. PDFF-related alterations for the SLD and the MASLD group correlated with those observed in MDD (Pearson r = 0.45-0.54, p < 0.01). CONCLUSION: These findings suggest the presence of shared biological mechanisms linking MDD to SLD and MASLD. They might explain the well-known elevated risk of depression in these groups and support early lifestyle interventions and treatment of metabolic risk factors for the successful management of the interconnected diseases depression and SLD/MASLD.
RESUMO
Previous studies of brain structure in anorexia nervosa (AN) have reported reduced gray matter in underweight patients, which largely normalizes upon weight gain. One underlying biological mechanism may be glial cell alterations related to low-grade inflammation. Here, we investigated relationships between brain structure as measured by magnetic resonance imaging and serum concentrations of two pro-inflammatory cytokines (interleukin-6 and tumor necrosis factor alpha) cross-sectionally in 82 underweight adolescent and young adult female patients (mean age 16.8 years; 59 of whom were observed longitudinally after short-term weight restoration; mean duration 2.8 months), 20 individuals long-term weight-recovered from AN (mean age 22.7 years) and 105 healthy control (HC) participants (mean age 17.2 years). We measured cortical thickness, subcortical volumes and local gyrification index, a measure of cortical folding. In contrast to most previous studies of cytokine concentrations in AN, we found no cross-sectional group differences (interleukin-6: p = 0.193, tumor necrosis factor alpha: p = 0.057) or longitudinal changes following weight restoration (interleukin-6: p = 0.201, tumor necrosis factor alpha: p = 0.772). As expected, widespread gray matter reductions (cortical thickness, subcortical volumes, cortical folding) were observed in underweight patients with AN compared to HC. However, we found no evidence of associations between cytokine concentrations and structural brain measures in any participant group. Furthermore, longitudinal changes in cytokine concentrations were unrelated to changes in gray matter. In conclusion, we did not identify any association between (sub-)inflammatory processes and structural brain changes in AN. Future studies are needed to elucidate which other factors besides nutritional status may contribute to brain morphological alterations.
Assuntos
Anorexia Nervosa , Encéfalo , Interleucina-6 , Fator de Necrose Tumoral alfa , Adolescente , Adulto , Feminino , Humanos , Adulto Jovem , Anorexia Nervosa/sangue , Anorexia Nervosa/patologia , Anorexia Nervosa/diagnóstico por imagem , Encéfalo/patologia , Encéfalo/diagnóstico por imagem , Estudos Transversais , Interleucina-6/sangue , Estudos Longitudinais , Imageamento por Ressonância Magnética , Fator de Necrose Tumoral alfa/sangueRESUMO
OBJECTIVE: The amygdaloid complex is a subcortical limbic group of distinct nuclei. In a previous patient-control study, differential amygdala nuclei alterations were found in acute anorexia nervosa (AN); rostral-medial nuclei involved in fear and reward processing were substantially reduced in volume and associated with hypoleptinemia, a key neuroendocrine characteristic of AN. Here, longitudinal amygdala nuclei alterations in AN were investigated in relation to weight status and their associations with leptin levels. METHOD: T1-weighted structural magnetic resonance imaging scans were longitudinally processed with FreeSurfer. Amygdala nuclei volumes in young female patients with acute AN before and after short-term weight restoration (n = 110, >14% body mass index increase over 3 months) and female participants with a history of AN (n = 79, long-term [mean 5 years] weight recovered) were compared with female healthy control participants (n = 271) using linear mixed effects models. RESULTS: Rostral-medially clustered amygdala nuclei volumes, accessory basal, cortical, medial nuclei, and corticoamygdaloid transition, increased during short-term weight restoration (Cohen's d range 0.18-0.30). However, volumetric normalization across nuclei was heterogeneous. Right cortical, medial nuclei, bilateral corticoamygdaloid transitions, and anterior amygdaloid areas were only partially normalized following short-term weight restoration. Right anterior amygdaloid area remained reduced after long-term weight recovery compared with control participants (d = 0.36). Leptin increase, accompanying short-term weight restoration, mediated the effect of weight gain on volumetric increase in left corticoamygdaloid transition and bilateral medial nuclei. CONCLUSION: Rostral-medially clustered amygdala nuclei show pronounced volumetric increase but incomplete normalization in AN during and after short-term weight restoration. Leptin increase may be relevant for the recovery of specific amygdala nuclei in addition to nutritional rehabilitation, indicating links between amygdala substructure and leptin dynamics of potential pathophysiological and clinical relevance in AN. PLAIN LANGUAGE SUMMARY: The amygdala plays a critical role in processing fearful and rewarding stimuli, and alterations in the amygdala are associated with anorexia nervosa. In this study, the authors measured amygdala nuclei volumes in female patients with acute anorexia nervosa undergoing weight-restoration treatment (n = 110), long-term weight-recovered individuals with anorexia (n = 79), and healthy control participants (n = 271). Structural magnetic resonance imaging revealed that volumes of specific nuclei, clustered in the rostral-medial amygdala, were substantially reduced in acute anorexia nervosa and only partially normalized following weight restoration treatment. Residual reductions in volume persisted even after long-term weight-recovery, compared to healthy control participants. Short-term weight restoration was associated with increases in the neurohormone leptin, and increasing leptin levels were found to mediate the positive impact of weight gain on increased amygdala volume over the treatment course. DIVERSITY & INCLUSION STATEMENT: We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. One or more of the authors of this paper received support from a program designed to increase minority representation in science. We actively worked to promote sex and gender balance in our author group. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. While citing references scientifically relevant for this work, we also actively worked to promote sex and gender balance in our reference list. While citing references scientifically relevant for this work, we also actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our reference list. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work.
RESUMO
The diagnostic process of attention deficit hyperactivity disorder (ADHD) is complex and relies on criteria sensitive to subjective biases. This may cause significant delays in appropriate treatment initiation. An automated analysis relying on subjective and objective measures might not only simplify the diagnostic process and reduce the time to diagnosis, but also improve reproducibility. While recent machine learning studies have succeeded at distinguishing ADHD from healthy controls, the clinical process requires differentiating among other or multiple psychiatric conditions. We trained a linear support vector machine (SVM) classifier to detect participants with ADHD in a population showing a broad spectrum of psychiatric conditions using anonymized data from clinical records (N = 299 participants). We differentiated children and adolescents with ADHD from those not having the condition with an accuracy of 66.1%. SVM using single features showed slight differences between features and overlapping standard deviations of the achieved accuracies. An automated feature selection achieved the best performance using a combination 19 features. Real-world clinical data from medical records can be used to automatically identify individuals with ADHD among help-seeking individuals using machine learning. The relevant diagnostic information can be reduced using an automated feature selection without loss of performance. A broad combination of symptoms across different domains, rather than specific domains, seems to indicate an ADHD diagnosis.