Functional connectivity underlying hedonic response to food in female adolescents with atypical AN: the role of somatosensory and salience networks.

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.

Preserved white matter microstructure in adolescent patients with atypical anorexia nervosa.

OBJECTIVE: Patients with atypical anorexia nervosa (AN) are often in the normal-weight range at presentation; however, signs of starvation and medical instability are not rare. White matter (WM) microstructural correlates of atypical AN have not yet been investigated, leaving an important gap in our knowledge regarding the neural pathogenesis of this disorder. METHOD: We investigated WM microstructural integrity in 25 drug-naïve adolescent patients with atypical AN and 25 healthy controls, using diffusion tensor imaging (DTI) with a tract-based spatial statistics (TBSS) approach. Psychological variables related to the eating disorder and depressive symptoms were also evaluated by administering the eating disorder examination questionnaire (EDE-Q) and the Montgomery-Åsberg depression rating scale (MADRS-S) respectively, to all participants. RESULTS: Patients and controls were in the normal-weight range and did not differ from the body mass index standard deviations for their age. No between groups difference in WM microstructure could be detected. DISCUSSION: Our findings support the hypothesis that brain structural alterations may not be associated to early-stage atypical AN. These findings also suggest that previous observations of alterations in WM microstructure in full syndrome AN may constitute state-related consequences of severe weight loss. Whether the preservation of WM structure is a pathogenetically discriminant feature of atypical AN or only an effect of a less severe nutritional disturbance, will have to be verified by future studies on larger samples, possibly directly comparing AN and atypical AN.

Reduced resting-state connectivity in areas involved in processing of face-related social cues in female adolescents with atypical anorexia nervosa.

Atypical anorexia nervosa (AN) has a high incidence in adolescents and can result in significant morbidity and mortality. Neuroimaging could improve our knowledge regarding the pathogenesis of eating disorders (EDs), however research on adolescents with EDs is limited. To date no neuroimaging studies have been conducted to investigate brain functional connectivity in atypical AN. We investigated resting-state functional connectivity using 3 T MRI in 22 drug-naïve adolescent patients with atypical AN, and 24 healthy controls. Psychological traits related to the ED and depressive symptoms have been assessed using the Eating Disorders Examination Questionnaire (EDE-Q) and the Montgomery-Åsberg Depression Rating Scale self-reported (MADRS-S) respectively. Reduced connectivity was found in patients in brain areas involved in face-processing and social cognition, such as the left putamen, the left occipital fusiform gyrus, and specific cerebellar lobules. The connectivity was, on the other hand, increased in patients compared with controls from the right inferior temporal gyrus to the superior parietal lobule and superior lateral occipital cortex. These areas are involved in multimodal stimuli integration, social rejection and anxiety. Patients scored higher on the EDE-Q and MADRS-S questionnaires, and the MADRS-S correlated with connectivity from the right inferior temporal gyrus to the superior parietal lobule in patients. Our findings point toward a role for an altered development of socio-emotional skills in the pathogenesis of atypical AN. Nonetheless, longitudinal studies will be needed to assess whether these connectivity alterations might be a neural marker of the pathology.

Atypical anorexia nervosa is not related to brain structural changes in newly diagnosed adolescent patients.

OBJECTIVE: Patients with atypical anorexia nervosa (AN) have many features overlapping with AN in terms of genetic risk, age of onset, psychopathology and prognosis of outcome, although the weight loss may not be a core factor. While brain structural alterations have been reported in AN, there are currently no data regarding atypical AN patients. METHOD: We investigated brain structure through a voxel-based morphometry analysis in 22 adolescent females newly-diagnosed with atypical AN, and 38 age- and sex-matched healthy controls (HC). ED-related psychopathology, impulsiveness and obsessive-compulsive traits were assessed with the Eating Disorder Examination Questionnaire (EDE-Q), Barratt Impulsiveness Scale (BIS-11) and Obsessive-compulsive Inventory Revised (OCI-R), respectively. Body mass index (BMI) was also calculated. RESULTS: Patients and HC differed significantly on BMI (p < .002), EDE-Q total score (p < .000) and OCI-R total score (p < .000). No differences could be detected in grey matter (GM) regional volume between groups. DISCUSSION: The ED-related cognitions in atypical AN patients would suggest that atypical AN and AN could be part of the same spectrum of restrictive-ED. However, contrary to previous reports in AN, our atypical AN patients did not show any GM volume reduction. The different degree of weight loss might play a role in determining such discrepancy. Alternatively, the preservation of GM volume might indeed differentiate atypical AN from AN.

Family-based intervention in adolescent restrictive eating disorders: early treatment response and low weight suppression is associated with favourable one-year outcome.

BACKGROUND: Family-based treatments are first-line treatments for adolescents with restrictive eating disorders (ED) but have to be improved since outcome is poor for some. We have investigated the one-year outcome of a family-based intervention programme with defined and decisive interventions at the start of treatment. METHOD: Data pertaining 201 adolescents with restrictive ED with features of anorexia nervosa but not fulfilling the weight criterion starting treatment 2010-2015, had a wide range of body mass index (BMI) and of weight loss at presentation, and completed a one-year follow-up was analysed. Recovery from the ED was defined as an Eating Disorder Examination-questionnaire (EDE-Q) score < 2.0 or as not fulfilling criteria for an ED at a clinical interview. RESULTS: By EDE-Q 130 (65%) had recovered at 1 year and by clinical interview 106 (53%). According to the EDE-Q criterion recovery was independently associated with lower EDE-Q score at presentation, higher weight gain after 3 months of treatment and lower weight suppression at follow-up, weight suppression being defined as the difference between premorbid and current BMI. Not fulfilling criteria for an ED was associated with the same factors and also by higher BMI at presentation. CONCLUSION: The observations that low weight and high ED cognitions confer a poor prognosis but that rapid weight gain at the start of treatment predicts a better prognosis are presently extended to adolescents with restrictive ED with a wide range of BMI at presentation. High weight suppression at follow-up is associated with a poor prognosis and indicates the importance of taking premorbid BMI into account when setting weight targets for treatment.

Correction: Limbic-thalamo-cortical projections and reward-related circuitry integrity affects eating behavior: A longitudinal DTI study in adolescents with restrictive eating disorders.

[This corrects the article DOI: 10.1371/journal.pone.0172129.].

Limbic-thalamo-cortical projections and reward-related circuitry integrity affects eating behavior: A longitudinal DTI study in adolescents with restrictive eating disorders.

Few studies have used diffusion tensor imaging (DTI) to investigate the micro-structural alterations of WM in patients with restrictive eating disorders (rED), and longitudinal data are lacking. Twelve patients with rED were scanned at diagnosis and after one year of family-based treatment, and compared to twenty-four healthy controls (HCs) through DTI analysis. A tract-based spatial statistics procedure was used to investigate diffusivity parameters: fractional anisotropy (FA) and mean, radial and axial diffusivities (MD, RD and AD, respectively). Reduced FA and increased RD were found in patients at baseline in the corpus callosum, corona radiata and posterior thalamic radiation compared with controls. However, no differences were found between follow-up patients and controls, suggesting a partial normalization of the diffusivity parameters. In patients, trends for a negative correlation were found between the baseline FA of the right anterior corona radiata and the Eating Disorder Examination Questionnaire total score, while a positive trend was found between the baseline FA in the splenium of corpus callosum and the weight loss occurred between maximal documented weight and time of admission. A positive trend for correlation was also found between baseline FA in the right anterior corona radiata and the decrease in the Obsessive-Compulsive Inventory Revised total score over time. Our results suggest that the integrity of the limbic-thalamo-cortical projections and the reward-related circuitry are important for cognitive control processes and reward responsiveness in regulating eating behavior.

Adolescents newly diagnosed with eating disorders have structural differences in brain regions linked with eating disorder symptoms.

BACKGROUND: Adults with eating disorders (ED) show brain volume reductions in the frontal, insular, cingulate, and parietal cortices, as well as differences in subcortical regions associated with reward processing. However, little is known about the structural differences in adolescents with behavioural indications of early stage ED. AIM: This is the first study to investigate structural brain changes in adolescents newly diagnosed with ED compared to healthy controls (HC), and to study whether ED cognitions correlate with structural changes in adolescents with ED of short duration. METHODS: Fifteen adolescent females recently diagnosed with ED, and 28 age-matched HC individuals, were scanned with structural magnetic resonance imaging (MRI). Whole-brain and region-of-interest analyses were conducted using voxel-based morphometry (VBM). ED cognitions were measured with self-report questionnaires and working memory performance was measured with a neuropsychological computerized test. RESULTS AND CONCLUSIONS: The left superior temporal gyrus had a smaller volume in adolescents with ED than in HC, which correlated with ED cognitions (concerns about eating, weight, and shape). Working memory reaction time correlated positively with insula volumes in ED participants, but not HC. In ED, measurements of restraint and obsession was negatively correlated with temporal gyrus volumes, and positively correlated with cerebellar and striatal volumes. Thus, adolescents with a recent diagnosis of ED had volumetric variations in brain areas linked to ED cognitions, obsessions, and working memory. The findings emphasize the importance of early identification of illness, before potential long-term effects on structure and behaviour occur.

One-year outcome and incidence of anorexia nervosa and restrictive eating disorders among adolescent girls treated as out-patients in a family-based setting.

Aims To study the 1-year outcome and to analyse predictors of outcome of a cohort of adolescent girls with anorexia nervosa (AN) or restrictive eating disorders not otherwise specified (EDNOSr) treated as out-patients in a family-based programme at a specialized eating disorder service. To calculate the incidence of anorexia nervosa among treatment-seeking girls younger than 18 in Uppsala County from 2004 to 2006. Methods A total of 168 female patients were offered treatment, and 141 were followed-up 1 year after starting treatment, 29 with AN and 112 with EDNOSr. Results Of the 29 girls who initially had AN, 6 (20%) had a good outcome and were free of any form of eating disorder at follow-up; only 1 (3%) had AN. Of the patients with EDNOSr, 54 (48%) had a good outcome and were free of eating disorders. Three (3%) had a poor outcome and had developed AN. The incidence of AN was 18/100,000 person-years in girls younger than 12 and 63/100,000 in girls younger than 18. Conclusion Restrictive eating disorders, including AN, in children and adolescents can be successfully treated in a family-based specialized out-patient service without in-patient care.

Obsessive-compulsivity and working memory are associated with differential prefrontal cortex and insula activation in adolescents with a recent diagnosis of an eating disorder.

The role of rumination at the beginning of eating disorder (ED) is not well understood. We hypothesised that impulsivity, rumination and restriction could be associated with neural activity in response to food stimuli in young individuals with eating disorders (ED). We measured neural responses with functional magnetic resonance imaging (fMRI), tested working memory (WM) and administered the eating disorders examination questionnaire (EDE-Q), Barratt impulsivity scale (BIS-11) and obsessive-compulsive inventory (OCI-R) in 15 adolescent females with eating disorder not otherwise specified (EDNOS) (mean age 15 years) and 20 age-matched healthy control females. We found that EDNOS subjects had significantly higher scores on the BIS 11, EDE-Q and OCI-R scales. Significantly increased neural responses to food images in the EDNOS group were observed in the prefrontal circuitry. OCI-R scores in the EDNOS group also significantly correlated with activity in the prefrontal circuitry and the cerebellum. Significantly slower WM responses negatively correlated with bilateral superior frontal gyrus activity in the EDNOS group. We conclude that ruminations, linked to WM, are present in adolescent females newly diagnosed with EDNOS. These may be risk factors for the development of an eating disorder and may be detectable before disease onset.

The importance of genetic and environmental effects for pre-eclampsia and gestational hypertension: a family study.

OBJECTIVES: To determine the importance of genetic effects in the aetiology of pre-eclampsia and gestational hypertension and to investigate whether pre-eclampsia and gestational hypertension share genetic aetiology. DESIGN: Individual record linkage between the population-based Swedish Multi-Generation and the Medical Birth Registers. SETTING: Sweden. POPULATION: 1,188,207 births between 1987 and 1997 and their parents. METHODS: Similarities in relatives were measured by the number of pairs concordant and discordant for disease, the odds ratio (OR) and tetrachoric correlations. Estimates of genetic and environmental effect for gestational hypertension, pre-eclampsia and pregnancy-induced hypertension were calculated from structural equation model fitting. MAIN OUTCOME MEASURES: Pre-eclampsia and gestational hypertension. RESULTS: Full sisters and mother-daughters were more similar for pre-eclampsia (OR 3.3, 95% confidence interval [CI] 3.0-3.6 and OR 2.6, 95% CI 1.6-4.3, respectively) than half-sisters (maternal half-sisters OR 1.4, 95% CI 0.9-2.2 and paternal half-sisters OR 1.0, 95% CI 0.6-1.6). Full sisters and mother-daughters were also more similar for gestational hypertension than half-sisters. A full sister to a woman with pre-eclampsia also had a significantly increased risk of gestational hypertension (OR 2.5, 95% CI 2.2-2.8). In contrast, the risk for half-sisters was not increased. Model fitting suggested heritability estimates for pre-eclampsia of 31%, for gestational hypertension 20% and for pregnancy-induced hypertension 28%. CONCLUSIONS: There is a genetic component in the development of pre-eclampsia and gestational hypertension and the pattern of co-morbidity suggests that they may share part of their genetic aetiology. This could be important for studies of potential susceptibility genes for these diseases.