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Brain Structure and Function in Adolescents with Atypical Anorexia Nervosa
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Schiöth: Functional Pharmacology.ORCID iD: 0000-0002-7514-4493
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Atypical anorexia nervosa (AAN) has a high incidence in adolescents, resulting in significant morbidity and mortality. The weight loss is generally less pronounced than that experienced in full-syndrome anorexia nervosa (AN), but the medical consequences can be as severe. Neuroimaging could improve our knowledge regarding the pathogenesis of eating disorders, however research on adolescents is limited, and no neuroimaging studies have been conducted in AAN. In paper I, we investigated brain structure through a voxel-based morphometry analysis in 22 drug-naïve adolescent females newly-diagnosed with AAN, and 38 age- and sex-matched healthy controls. In Paper II, we investigated white matter microstructural integrity on 25 drug-naïve adolescent patients with AAN and 25 healthy controls, using diffusion tensor imaging with a tract-based spatial statistics approach. No differences in brain structure could be detected, indicating preserved regional grey matter volumes and white matter diffusivity in patients with AAN compared to controls. These findings suggest that previous observations of brain structure alterations in full syndrome AN may constitute state-related consequences of severe underweight. Alternatively, the preservation of brain structure might indeed differentiate AAN from AN. In paper III, we investigated resting-state functional connectivity in 22 drug-naïve adolescent patients with AAN, and 24 healthy controls. We report reduced connectivity in patients in brain areas involved in face-processing and social cognition, while an increased connectivity, correlating with depressive symptoms, was found in areas involved in the multimodal integration of sensory stimuli, aesthetic judgment, and social rejection anxiety. These findings point toward a core role for an altered development of socio-emotional skills in the pathogenesis of AAN. In Paper IV, we investigated neural connectivity underlying visual processing of foods with different caloric content in a sample of 28 adolescent females diagnosed with AAN, and 33 age- and sex-matched healthy controls. Our results showed higher connectivity in patients in pathways related to the integration of sensory input and memory retrieval, in response to food with high caloric content. This, however, was coupled to lower connectivity in salience and attentional networks, and lower connectivity between areas involved in visual food cues processing and appetite regulatory regions. Thus, despite food with high caloric content is associated to greater processing of somatosensory information in patients, it is attributed less salience and engages patients’ attention less than food with low caloric content.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2019. , p. 68
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1585
Keywords [en]
MRI, functional MRI, fMRI, magnetic resonance imaging, neuroimaging, brain imaging, anorexia nervosa, eating disorders, neuroscience, adolescents
National Category
Psychiatry Radiology, Nuclear Medicine and Medical Imaging Neurosciences
Research subject
Medical Science; Neuroscience
Identifiers
URN: urn:nbn:se:uu:diva-389865ISBN: 978-91-513-0702-2 (print)OAI: oai:DiVA.org:uu-389865DiVA, id: diva2:1339693
Public defence
2019-09-18, Room B42, Uppsala biomedicinska centrum (BMC), Husargatan 3, Uppsala, 10:00 (English)
Opponent
Supervisors
Available from: 2019-08-28 Created: 2019-07-30 Last updated: 2019-09-17
List of papers
1. Atypical anorexia nervosa is not related to brain structural changes in newly diagnosed adolescent patients.
Open this publication in new window or tab >>Atypical anorexia nervosa is not related to brain structural changes in newly diagnosed adolescent patients.
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2018 (English)In: International Journal of Eating Disorders, ISSN 0276-3478, E-ISSN 1098-108X, Vol. 51, no 1, p. 39-45Article in journal (Refereed) Published
Abstract [en]

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.

Keywords
MRI, OSFED, VBM, adolescent, anorexia, eating disorders, imaging
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-336179 (URN)10.1002/eat.22805 (DOI)000418270800005 ()29215777 (PubMedID)
Funder
Swedish Research Council FormasSwedish Research CouncilThe Swedish Brain Foundation
Available from: 2017-12-12 Created: 2017-12-12 Last updated: 2019-07-30Bibliographically approved
2. Preserved white matter microstructure in adolescent patients with atypical anorexia nervosa
Open this publication in new window or tab >>Preserved white matter microstructure in adolescent patients with atypical anorexia nervosa
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2019 (English)In: International Journal of Eating Disorders, ISSN 0276-3478, E-ISSN 1098-108X, Vol. 52, no 2, p. 166-174Article in journal (Refereed) Published
Abstract [en]

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-naive 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-angstrom sberg 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.

Keywords
adolescent, anorexia nervosa, brain, cognitive neuroscience, diffusion tensor imaging, feeding and eating disorders, neuroimaging
National Category
Psychiatry
Identifiers
urn:nbn:se:uu:diva-378685 (URN)10.1002/eat.23012 (DOI)000458301700008 ()30676658 (PubMedID)
Funder
Swedish Research CouncilThe Swedish Brain Foundation
Available from: 2019-03-12 Created: 2019-03-12 Last updated: 2019-07-30Bibliographically approved
3. Reduced resting-state connectivity in areas involved in processing of face-related social cues in female adolescents with atypical anorexia nervosa
Open this publication in new window or tab >>Reduced resting-state connectivity in areas involved in processing of face-related social cues in female adolescents with atypical anorexia nervosa
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2018 (English)In: Translational Psychiatry, ISSN 2158-3188, E-ISSN 2158-3188, Vol. 8, article id 275Article in journal (Refereed) Published
Abstract [en]

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-naive 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-Asberg 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.

National Category
Psychiatry
Identifiers
urn:nbn:se:uu:diva-373370 (URN)10.1038/s41398-018-0333-1 (DOI)000454240100002 ()30546060 (PubMedID)
Funder
Swedish Research Council FormasSwedish Research CouncilThe Swedish Brain Foundation
Available from: 2019-01-15 Created: 2019-01-15 Last updated: 2019-07-30Bibliographically approved
4. Functional connectivity underlying hedonic response to food in female adolescents with atypical AN: The role of somatosensory and salience networks
Open this publication in new window or tab >>Functional connectivity underlying hedonic response to food in female adolescents with atypical AN: The role of somatosensory and salience networks
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

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 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 behaviour in atypical AN might help designing specific treatment strategies.

National Category
Psychiatry
Identifiers
urn:nbn:se:uu:diva-385193 (URN)
Available from: 2019-06-12 Created: 2019-06-12 Last updated: 2019-07-30

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