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Dynamic changes of the structural and functional brain connectome in anorexia nervosa (revision)

Subject Area Clinical Psychiatry, Psychotherapy, Child and Adolescent Psychiatry
Biological Psychiatry
Term from 2017 to 2023
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 320247098
 
Final Report Year 2024

Final Report Abstract

This research project focused on examining the structural and functional changes in the brains of individuals with Anorexia Nervosa (AN) before, during and after weight normalization. Using state-of-the-art neuroimaging techniques and an extensive cohort of patients and healthy controls, the study aimed to characterize changes in the A) Structural brain network, B) Functional brain network, and C) Mechanisms behind the changes. The results revealed profound alterations in cortical thickness, volumes of gray matter, including a range of substructures. The magnitude of these changes is tha largest in psychiatry. A decrease in cortical thickness was observed, particularly in regions described as energetically demanding. Changes in the "integrity" of white matter showed a similar pattern, though with smaller effect sizes than in gray matter. Furthermore, the results indicated alterations in the (dynamic) functional network architecture, especially at a global level in acute AN and former (now recovered) patients. These changes were particularly evident in networks with attributed relevance to AN, including networks associated with cognitive control, habit formation, and reward experience. The reversibility of structural changes and the normalization of network features during weight gain were observed for many structural but not all functional domains. Some straightforward explanations for structural changes in the state of acute underweight, such as dehydration or apoptosis and neurogenesis, were largely ruled out based on biochemical parameters and temporal patterns. Instead, structural changes were often associated with biomarkers such as the appetite-regulating hormone leptin and markers of neuronal integrity - Neurofilament Light (NFL), or N-acetyl-aspartate (NAA), or even mediated by them (mediation). Changes in the (dynamic) functional network architecture may be driven by alterations in voxellevel signal characteristics, which in turn are related to structural brain changes in the acute state of the illness. Despite the extensive normalization of structural changes, machine learning identified subtly persistent changes in patients in early remission, which, in turn, proved predictive of a later poorer outcome. This project contributes to understanding the neurobiological foundations of AN and, possibly, developing personalized intervention approaches.

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