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Background: Depression and obesity are associated with impaired inhibitory control. Behavioral evidence indicates an exacerbating additive effect when both conditions co-occur. However, the underlying neural mechanisms remain unclear. Moreover, systemic inflammation affects neurocognitive performance in both individuals with depression and obesity. Here, we investigate additive effects of depression and obesity on neural correlates of inhibitory control, and examine inflammation as a connecting pathway. Methods: We assessed inhibitory control processing in 64 individuals with obesity and varying degrees of depressed mood by probing neural activation and connectivity during an fMRI Stroop task. Additionally, we explored associations of altered neural responses with individual differences in systemic inflammation. Data were collected as part of the BARICO (Bariatric surgery Rijnstate and Radboudumc neuroimaging and Cognition in Obesity) study. Results: Concurrent depression and obesity were linked to increased functional connectivity between the supplementary motor area and precuneus and between the inferior occipital and inferior parietal gyrus. Exploratory analysis revealed that circulating inflammation markers, including plasma leptin, IL-6, IL-8, and CCL-3 correlated with the additive effect of depression and obesity on altered functional connectivity. Limitations: The observational design limits causal inferences. Future research employing longitudinal or intervention designs is required to validate these findings and elucidate causal pathways. Conclusion: These findings suggest increased neural crosstalk underlying impaired inhibitory control in individuals with concurrent obesity and depressed mood. Our results support a model of an additive detrimental effect of concurrent depression and obesity on neurocognitive functioning, with a possible role of inflammation.

Background and Objectives: Bariatric surgery (BS) is an effective treatment for obesity. However, some individuals experience insufficient weight loss after surgery. Therefore, we investigated whether cognitive control affects weight loss after Roux-en-Y gastric bypass (RYGB). Methods: Within this exploratory observational study, part of the BARICO study (BAriatric surgery Rijnstate and Radboudumc neuroImaging and Cognition in Obesity), participants aged between 35 and 55 years eligible for RYGB were included. Before and after BS, body weight, (delta) BMI and percentage total body weight loss (%TBWL) were determined. Additionally, at baseline, Stroop task-performance, -activation and -connectivity were assessed by a color-word paradigm task during functional neuroimaging to determine the ability of participants to inhibit cognitive interference. Results: Seventy-six participants were included, of whom 14 were excluded from fMRI analysis, leaving 62 participants. Participants were aged 45.0 ± 5.9 years with a mean pre-surgery BMI of 40.2 ± 3.3 kg/m2, and 86% were women. Mean decrease in BMI was 13.8 ± 2.5 kg/m2, and mean %TBWL was 34.9 ± 6.3% 1 year after BS. Stroop task performance did not correlate with (delta) BMI and %TBWL. The inferior parietal/middle occipital gyrus, inferior frontal gyrus, and supplementary motor cortex were involved in cognitive interference, although activity in these regions did not predict weight loss after surgery. Lastly, generalized psychophysiological interaction did not provide evidence for (delta) BMI- and %TBWL-dependent connectivity modulation. Discussion: Cognitive control did not predict weight loss after surgery. Future studies should focus on longer follow-up periods to understand the relation between cognitive control and weight loss. Trial Registration: NL7090 (https://www.clinicaltrialregister.nl/nl/trial/28949 ) Graphical Abstract: [Figure not available: see fulltext.].

Altered intrinsic brain connectivity of patients with anorexia nervosa has been observed in the acute phase of the disorder, but it remains unclear to what extent these alterations recover during weight normalization. In this study, we used functional imaging data from three time points to probe longitudinal changes in intrinsic connectivity patterns in patients with severe anorexia nervosa (BMI ≤ 15.5 kg/m$^{2}$) over the course of weight normalization. At three distinct stages of inpatient treatment, we examined resting-state functional connectivity in 27 women with severe anorexia nervosa and 40 closely matched healthy controls. Using network-based statistics and graph-theoretic measures, we examined differences in global network strength, subnetworks with altered intrinsic connectivity, and global network topology. Patients with severe anorexia nervosa showed weakened intrinsic connectivity and altered network topology which did not recover during treatment. The persistent disruption of brain networks suggests sustained alterations of information processing in weight-recovered severe anorexia nervosa.

BACKGROUND: The pattern of structural brain abnormalities in anorexia nervosa (AN) is still not well understood. While several studies report substantial deficits in gray matter volume and cortical thickness in acutely underweight patients, others find no differences, or even increases in patients compared with healthy control subjects. Recent weight regain before scanning may explain some of this heterogeneity. To clarify the extent, magnitude, and de-pendencies of gray matter changes in AN, we conducted a prospective, coordinated meta-analysis of multicenter neuroimaging data. METHODS: We analyzed T1-weighted structural magnetic resonance imaging scans assessed with standardized methods from 685 female patients with AN and 963 female healthy control subjects across 22 sites worldwide. In addition to a case-control comparison, we conducted a 3-group analysis comparing healthy control subjects with acutely underweight AN patients (n = 466) and partially weight-restored patients in treatment (n = 251). RESULTS: In AN, reductions in cortical thickness, subcortical volumes, and, to a lesser extent, cortical surface area were sizable (Cohen's d up to 0.95), widespread, and colocalized with hub regions. Highlighting the effects of un-dernutrition, these deficits were associated with lower body mass index in the AN sample and were less pronounced in partially weight-restored patients. CONCLUSIONS: The effect sizes observed for cortical thickness deficits in acute AN are the largest of any psychiatric disorder investigated in the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Consortium to date. These results confirm the importance of considering weight loss and renutrition in biomedical research on AN and underscore the importance of treatment engagement to prevent potentially long-lasting structural brain changes in this population.

Agroecology has been proposed as a strategy to improve food system sustainability, but has also been criticised for using land inefficiently. We compared five explorative storylines, developed in a stakeholder process, for future food systems in the EU to 2050. We modelled a range of biophysical (e.g., land use and food production), environmental (e.g., greenhouse gas emissions) and social indicators, and potential for regional food self-sufficiency, and investigated the economic policy needed to reach these futures by 2050. Two contrasting storylines for upscaling agroecological practices emerged. In one, agroecology was implemented to produce high-value products serving high-income consumers through trade but, despite 40 of agricultural area being under organic management, only two out of eight EU environmental policy targets were met. As diets followed current trends in this storyline, there were few improvements in environmental indicators compared with the current situation, despite large-scale implementation of agroecological farming practices. This suggests that large-scale implementation of agroecological practices without concurrent changes on the demand side could aggravate existing environmental pressures. However, our second agroecological storyline showed that if large-scale diffusion of agroecological farming practices were implemented alongside drastic dietary change and waste reductions, major improvements on environmental indicators could be achieved and all relevant EU policy targets met. An alternative storyline comprising sustainable intensification in combination with dietary change and waste reductions was efficient in meeting targets related to climate, biodiversity, ammonia emissions, and use of antibiotics, but did not meet targets for reductions in pesticide and fertiliser use. These results confirm the importance of dietary change for food system climate change mitigation. Economic modelling showed a need for drastic changes in consumer pr

The European Commission recently embraced the concept of agroecology as a pathway to reduce negative impacts from agri-food systems on the environment. So far, it remains unclear whether agroecology can deliver on these high hopes if implemented on a large scale. We here assess socio-economic and environmental implications of multiple agroecological futures in the European Union in 2050, based on a novel diagnostic scenario approach, i.e. the biomass balancing model BioBaM-GHG 2.0. We find that agroecological measures from the plot to the food systems level can indeed reduce environmental pressures while maintaining domestic food availability within the EU. Such measures are, for example, more hedgerows on croplands or reduced biomass harvest on high natural value – HNV grasslands. However, a key prerequisite is an overall reduction of the food system's size (based on the reduction of animal production, food wastes, and export production) and an optimised crop-livestock integration. Only then does the transformation towards an agroecological agri-food system in the EU not risk overstretching domestic land availability or produce insufficient agricultural commodities. Mitigating the accompanied trade-off of reduced farm income is a central mandate for policy development aimed at re-designing agriculture in Europe to align with the Green Deal goals.

The European Commission recently embraced the concept of agroecology as a pathway to reduce negative impacts from agri-food systems on the environment. So far, it remains unclear whether agroecology can deliver on these high hopes if implemented on a large scale. We here assess socio-economic and environmental implications of multiple agroecological futures in the European Union in 2050, based on a novel diagnostic scenario approach, i.e. the biomass balancing model BioBaM-GHG 2.0. We find that agroecological measures from the plot to the food systems level can indeed reduce environmental pressures while maintaining domestic food availability within the EU. Such measures are, for example, more hedgerows on croplands or reduced biomass harvest on high natural value – HNV grasslands. However, a key prerequisite is an overall reduction of the food system's size (based on the reduction of animal production, food wastes, and export production) and an optimised crop-livestock integration. Only then does the transformation towards an agroecological agri-food system in the EU not risk overstretching domestic land availability or produce insufficient agricultural commodities. Mitigating the accompanied trade-off of reduced farm income is a central mandate for policy development aimed at re-designing agriculture in Europe to align with the Green Deal goals.

Agroecology has been proposed as a strategy to improve food system sustainability, but has also been criticised for using land inefficiently. We compared five explorative storylines, developed in a stakeholder process, for future food systems in the EU to 2050. We modelled a range of biophysical (e.g., land use and food production), environmental (e.g., greenhouse gas emissions) and social indicators, and potential for regional food self-sufficiency, and investigated the economic policy needed to reach these futures by 2050. Two contrasting storylines for upscaling agroecological practices emerged. In one, agroecology was implemented to produce high-value products serving high-income consumers through trade but, despite 40 of agricultural area being under organic management, only two out of eight EU environmental policy targets were met. As diets followed current trends in this storyline, there were few improvements in environmental indicators compared with the current situation, despite large-scale implementation of agroecological farming practices. This suggests that large-scale implementation of agroecological practices without concurrent changes on the demand side could aggravate existing environmental pressures. However, our second agroecological storyline showed that if large-scale diffusion of agroecological farming practices were implemented alongside drastic dietary change and waste reductions, major improvements on environmental indicators could be achieved and all relevant EU policy targets met. An alternative storyline comprising sustainable intensification in combination with dietary change and waste reductions was efficient in meeting targets related to climate, biodiversity, ammonia emissions, and use of antibiotics, but did not meet targets for reductions in pesticide and fertiliser use. These results confirm the importance of dietary change for food system climate change mitigation. Economic modelling showed a need for drastic changes in consumer pr

The European Commission recently embraced the concept of agroecology as a pathway to reduce negative impacts from agri-food systems on the environment. So far, it remains unclear whether agroecology can deliver on these high hopes if implemented on a large scale. We here assess socio-economic and environmental implications of multiple agroecological futures in the European Union in 2050, based on a novel diagnostic scenario approach, i.e. the biomass balancing model BioBaM-GHG 2.0. We find that agroecological measures from the plot to the food systems level can indeed reduce environmental pressures while maintaining domestic food availability within the EU. Such measures are, for example, more hedgerows on croplands or reduced biomass harvest on high natural value – HNV grasslands. However, a key prerequisite is an overall reduction of the food system's size (based on the reduction of animal production, food wastes, and export production) and an optimised crop-livestock integration. Only then does the transformation towards an agroecological agri-food system in the EU not risk overstretching domestic land availability or produce insufficient agricultural commodities. Mitigating the accompanied trade-off of reduced farm income is a central mandate for policy development aimed at re-designing agriculture in Europe to align with the Green Deal goals.

The European Commission recently embraced the concept of agroecology as a pathway to reduce negative impacts from agri-food systems on the environment. So far, it remains unclear whether agroecology can deliver on these high hopes if implemented on a large scale. We here assess socio-economic and environmental implications of multiple agroecological futures in the European Union in 2050, based on a novel diagnostic scenario approach, i.e. the biomass balancing model BioBaM-GHG 2.0. We find that agroecological measures from the plot to the food systems level can indeed reduce environmental pressures while maintaining domestic food availability within the EU. Such measures are, for example, more hedgerows on croplands or reduced biomass harvest on high natural value – HNV grasslands. However, a key prerequisite is an overall reduction of the food system's size (based on the reduction of animal production, food wastes, and export production) and an optimised crop-livestock integration. Only then does the transformation towards an agroecological agri-food system in the EU not risk overstretching domestic land availability or produce insufficient agricultural commodities. Mitigating the accompanied trade-off of reduced farm income is a central mandate for policy development aimed at re-designing agriculture in Europe to align with the Green Deal goals.

Agroecology has been proposed as a strategy to improve food system sustainability, but has also been criticised for using land inefficiently. We compared five explorative storylines, developed in a stakeholder process, for future food systems in the EU to 2050. We modelled a range of biophysical (e.g., land use and food production), environmental (e.g., greenhouse gas emissions) and social indicators, and potential for regional food self-sufficiency, and investigated the economic policy needed to reach these futures by 2050. Two contrasting storylines for upscaling agroecological practices emerged. In one, agroecology was implemented to produce high-value products serving high-income consumers through trade but, despite 40 of agricultural area being under organic management, only two out of eight EU environmental policy targets were met. As diets followed current trends in this storyline, there were few improvements in environmental indicators compared with the current situation, despite large-scale implementation of agroecological farming practices. This suggests that large-scale implementation of agroecological practices without concurrent changes on the demand side could aggravate existing environmental pressures. However, our second agroecological storyline showed that if large-scale diffusion of agroecological farming practices were implemented alongside drastic dietary change and waste reductions, major improvements on environmental indicators could be achieved and all relevant EU policy targets met. An alternative storyline comprising sustainable intensification in combination with dietary change and waste reductions was efficient in meeting targets related to climate, biodiversity, ammonia emissions, and use of antibiotics, but did not meet targets for reductions in pesticide and fertiliser use. These results confirm the importance of dietary change for food system climate change mitigation. Economic modelling showed a need for drastic changes in consumer pr

The European Commission recently embraced the concept of agroecology as a pathway to reduce negative impacts from agri-food systems on the environment. So far, it remains unclear whether agroecology can deliver on these high hopes if implemented on a large scale. We here assess socio-economic and environmental implications of multiple agroecological futures in the European Union in 2050, based on a novel diagnostic scenario approach, i.e. the biomass balancing model BioBaM-GHG 2.0. We find that agroecological measures from the plot to the food systems level can indeed reduce environmental pressures while maintaining domestic food availability within the EU. Such measures are, for example, more hedgerows on croplands or reduced biomass harvest on high natural value – HNV grasslands. However, a key prerequisite is an overall reduction of the food system's size (based on the reduction of animal production, food wastes, and export production) and an optimised crop-livestock integration. Only then does the transformation towards an agroecological agri-food system in the EU not risk overstretching domestic land availability or produce insufficient agricultural commodities. Mitigating the accompanied trade-off of reduced farm income is a central mandate for policy development aimed at re-designing agriculture in Europe to align with the Green Deal goals.

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. Keywords: Anorexia nervosa; Bulimia nervosa; Eating disorders; Estimation; Meal portions; Portion size.

Anorexia nervosa (AN) is difficult to treat with up to half of patients failing to gain weight during treatment. Neurobiological factors predicting treatment response in AN are poorly understood. In this longitudinal study, we aimed to identify morphological characteristics in the grey matter which predict treatment success in patients with AN. Fifty patients with severe AN participated in an eating disorder-specific inpatient treatment. On admission, T1-weighted magnetic resonance images were acquired from all patients. Half of the patients successfully gained weight, reaching a body-mass index ≥ 17.5 kg/m2. Using voxel-based morphometry, local grey matter volumes were compared between the two groups of patients who gained weight and those who did not. This approach allowed us to identify anatomical characteristics which predict treatment success in terms of post-treatment weight status. Patients who did not reach the weight threshold at discharge had a smaller volume in the right cerebellar crus I at the time of admission. In this group, smaller volume was associated with a greater alexithymia score. The findings suggest that a trophic state within the cerebellum before treatment might be prognostic for treatment success. Consistent with previous reports, this result further substantiates the possible role of the cerebellum in the psychopathology of AN.

The pattern of structural brain abnormalities in anorexia nervosa (AN) is still not well understood. While several studies report substantial deficits in grey matter volume and cortical thickness in acutely underweight patients, others find no differences, or even increases in patients compared with healthy controls. Recent weight regain before scanning may explain some of this heterogeneity across studies. To clarify the extent, magnitude, and dependencies of grey matter changes in AN, we conducted a prospective, coordinated meta-analysis of multicenter neuroimaging data. We analyzed T1-weighted structural MRI scans assessed with standardized methods from 685 female AN patients and 963 female healthy controls across 22 sites worldwide. In addition to a case-control comparison, we conducted a three-group analysis comparing healthy controls to acutely underweight AN patients (n = 466), and to those in treatment and partially weight-restored (n = 251). In AN, reductions in cortical thickness, subcortical volumes, and, to a lesser extent, cortical surface area, were sizable (Cohen’s d up to 0.95), widespread and co-localized with hub regions. Highlighting the effects of undernutrition, these deficits associated with lower BMI in the AN sample and were less pronounced in partially weight-restored patients. Notably, the effect sizes observed for cortical thickness deficits in acute AN are the largest of any psychiatric disorder investigated in the ENIGMA consortium to date. These results confirm the importance of considering weight loss and renutrition in biomedical research on AN and underscore the importance of treatment engagement to prevent potentially long-lasting structural brain changes in this population.Competing Interest StatementThe authors have declared no competing interest.Funding StatementThis work was supported by the Carus Promotionskolleg (KB), the Ministerio de Igualdad, Spain (grant number 234/09) and by the Generalitat de Catalunya (2009 SGR 1119) (S

Background: The body mass index is a key predictor of treatment outcome in patients with anorexia nervosa. In adolescents, higher premorbid BMI is a strong predictor of a favorable treatment outcome. It is unclear whether this relationship holds true for adults with anorexia nervosa. Here, we examine adult patients with AN and investigate the lowest and highest lifetime BMI and weight suppression as predisposing factors for treatment outcome. Methods: We included 107 patients aged 17-56 with anorexia nervosa and tracked their BMI from admission to inpatient treatment, through discharge, to follow-up at 1-6 years. Illness history, including lowest and highest lifetime BMI were assessed prior to admission. We used multiple linear regression models with minimal or maximal lifetime BMI or weight suppression at admission as independent variables to predict BMI at admission, discharge and follow-up, while controlling for patients' age, sex, and duration of illness. Results: Low minimal BMI had a negative influence on the weight at admission, which in turn resulted in a lower BMI at discharge. Higher maximal BMI had a substantial positive influence on BMI at discharge and follow-up. Weight suppression was highly correlated with maximal BMI and showed similar effects to maximal BMI. Conclusion: Our findings strongly support a relationship between low minimal lifetime BMI and lower BMI at admission, and between higher maximal lifetime BMI or weight suppression and a positive treatment outcome, even years after discharge. Overall, maximal BMI emerged as the most important factor in predicting the weight course in adults with AN. Keywords: anorexia nervosa; hospitalization; treatment outcome; weight characteristics; weight suppression.

To examine the hypothesis that normalization of low circulating leptin levels in patients with anorexia nervosa ameliorates hyperactivity, three seriously ill females with hyperactivity were treated off-label with metreleptin (recombinant human leptin) for up to 14 days. Drive for activity, repetitive thoughts of food, inner restlessness, and weight phobia decreased in two patients. Surprisingly, depression improved rapidly in all patients. No serious adverse events occurred. Due to obvious limitations of uncontrolled case series, placebo-controlled clinical trials are mandatory to confirm the observed rapid onset of beneficial effects. Our findings suggest an important role of hypoleptinemia in the mental and behavioral phenotype of anorexia nervosa.

Neuroimaging studies on anorexia nervosa (AN) have consistently reported globally reduced gray matter in patients with acute AN. While first studies on adolescent AN patients provide evidence for the reversibility of these impairments after weight gain, longitudinal studies with detailed regional analysis for adult AN patients are lacking and factors associated with brain restitution are poorly understood. We investigated structural changes in anorexia nervosa using T1-weighted magnetic resonance images with surface-based morphometry. The sample consisted of 26 adult women with severe AN and 30 healthy controls. The longitudinal design comprised three time points, capturing the course of weight-restoration therapy in AN patients at distinct stages of weight gain (BMI ≤ 15.5 kg/m2; 15.5 < BMI < 17.5 kg/m2; BMI ≥ 17.5 kg/m2). Compared to controls, AN patients showed globally decreased cortical thickness and subcortical volumes at baseline. Linear mixed effect models revealed the reversibility of these alterations, with brain restoration being most pronounced during the first half of treatment. The restoration of cortical thickness of AN patients negatively correlated with age, but not duration of illness. After weight restoration, residual group differences of cortical thickness remained in the superior frontal cortex. These findings indicate that structural brain alterations of adult patients with severe AN recuperate independently of the duration of illness during weight-restoration therapy. The temporal pattern of brain restoration suggests a decrease in restoration rate over the course of treatment, with patients' age as a strong predictor of brain restitution, possibly reflecting decreases of brain plasticity as patients grow older.

vorgelegt von Lisa Maria Kaufmann, Universität Innsbruck, Diplomarbeit, 2019, (VLID)4548867

Psychotherapy has been shown to be effective, but efforts to prove specific effects by placebo-controlled trials have been practically and conceptually hampered. We propose that adopting open/hidden designs from placebo research would offer a possible way to establish specificity in psychotherapy. Therefore, we tested the effects of providing opposing treatment rationales in an online expressive writing intervention on affect in healthy subjects. Results indicate that it was possible to conduct the expressive writing intervention both covertly and openly, but that participants in the hidden administration condition did not fully benefit from the otherwise effective expressive writing intervention in the long-run. Effect sizes between open and hidden administration groups were comparable to pre-post effect sizes of the intervention. While this finding is important for the understanding of psychotherapy's effects per se, it also proves that alternative research approaches to establish specificity are feasible and informative in psychotherapy research. TRIAL REGISTRATION: German Clinical Trials Register DRKS00009428.