Abnormal functional global and local brain connectivity in female patients with anorexia nervosa.

BACKGROUND: Previous resting-state functional connectivity studies in patients with anorexia nervosa used independent component analysis or seed-based connectivity analysis to probe specific brain networks. Instead, modelling the entire brain as a complex network allows determination of graph-theoretical metrics, which describe global and local properties of how brain networks are organized and how they interact. METHODS: To determine differences in network properties between female patients with acute anorexia nervosa and pairwise matched healthy controls, we used resting-state fMRI and computed well-established global and local graph metrics across a range of network densities. RESULTS: Our analyses included 35 patients and 35 controls. We found that the global functional network structure in patients with anorexia nervosa is characterized by increases in both characteristic path length (longer average routes between nodes) and assortativity (more nodes with a similar connectedness link together). Accordingly, we found locally decreased connectivity strength and increased path length in the posterior insula and thalamus. LIMITATIONS: The present results may be limited to the methods applied during preprocessing and network construction. CONCLUSION: We demonstrated anorexia nervosa-related changes in the network configuration for, to our knowledge, the first time using resting-state fMRI and graph-theoretical measures. Our findings revealed an altered global brain network architecture accompanied by local degradations indicating wide-scale disturbance in information flow across brain networks in patients with acute anorexia nervosa. Reduced local network efficiency in the thalamus and posterior insula may reflect a mechanism that helps explain the impaired integration of visuospatial and homeostatic signals in patients with this disorder, which is thought to be linked to abnormal representations of body size and hunger.

Global cortical thinning in acute anorexia nervosa normalizes following long-term weight restoration.

BACKGROUND: Anorexia nervosa (AN) is a serious eating disorder characterized by self-starvation, extreme weight loss, and alterations in brain structure. Structural magnetic resonance imaging studies have documented brain volume reductions in acute AN, but it is unclear whether they are 1) regionally specific, or 2) reversible following weight restoration. Here, we measured cortical thickness (CT) for the first time in AN. METHODS: Structural magnetic resonance imaging data were acquired from adolescent and young adult female patients with acute AN (n = 40), recovered patients following long-term weight restoration (n = 34), and an equal number of age-matched healthy control subjects. Group differences in CT were tested with well-validated procedures implemented in FreeSurfer. The mediating role of clinical variables including body mass index and drive for thinness were explored. For completeness, we also used FreeSurfer's subcortical segmentation stream to test group differences in volumes of select gray matter regions of interest. RESULTS: Vertex-wise analyses revealed significant thinning of over 85% of the cortical surface in patients with acute AN and CT normalization in recovered patients following long-term weight restoration, although normal age-related trajectories were absent in the disorder. This pattern of results was largely mirrored in subcortical volumes. We also observed a strong negative correlation between CT and drive for thinness in extrastriate regions involved in body perception. CONCLUSIONS: Structural brain anomalies in AN as expressed in CT and subcortical volume are primarily the consequence of malnutrition and unlikely to reflect premorbid trait markers or permanent scars, but longitudinal data are needed.

Serum brain-derived neurotrophic factor and cognitive functioning in underweight, weight-recovered and partially weight-recovered females with anorexia nervosa.

Several studies support the assumption that the brain-derived neurotrophic factor (BDNF) plays an important role in the pathophysiology of eating disorders. In the present cross-sectional and longitudinal study, we investigated BDNF levels in patients with anorexia nervosa (AN) at different stages of their illness and the association with cognitive functioning. We measured serum BDNF in 72 acutely underweight female AN patients (acAN), 23 female AN patients who successfully recovered from their illness (recAN), and 52 healthy control women (HCW). Longitudinally, 30 acAN patients were reassessed after short-term weight gain. The association between BDNF levels and psychomotor speed was investigated using the Trail Making Test. BDNF serum concentrations were significantly higher in recAN participants if compared to acAN patients and increased with short-term weight gain. In acAN patients, but not HCW, BDNF levels were inversely associated with psychomotor speed. AcAN patients with higher BDNF levels also had lower life time body mass indexes. Taken together, our results indicate that serum BDNF levels in patients with AN vary with the stage of illness. Based on the pleiotropic functions of BDNF, changing levels of this neurotrophin may have different context-dependent effects, one of which may be the modulation of cognitive functioning in acutely underweight patients.