Abstract
Background
Anorexia nervosa (AN) is characterized by disturbances in cognition and behavior surrounding
eating and weight. The severity of AN combined with the absence of localized brain
abnormalities suggests distributed, systemic underpinnings that may be identified
using diffusion-weighted magnetic resonance imaging and tractography to reconstruct
white matter pathways.
Methods
Diffusion-weighted magnetic resonance imaging data acquired from female patients with
AN (n = 147) and female healthy control (HC) participants (n = 119), ages 12 to 40 years, were combined across 5 studies. Probabilistic tractography
was completed, and full-cortex connectomes describing streamline counts between 84
brain regions were generated and harmonized. Graph theory methods were used to describe
alterations in network organization in AN. The network-based statistic tested between-group
differences in brain subnetwork connectivity. The metrics strength and efficiency
indexed the connectivity of brain regions (network nodes) and were compared between
groups using multiple linear regression.
Results
Individuals with AN, relative to HC peers, had reduced connectivity in a network comprising
subcortical regions and greater connectivity between frontal cortical regions (p < .05, familywise error corrected). Node-based analyses indicated reduced connectivity
of the left hippocampus in patients relative to HC peers (p < .05, permutation corrected). Severity of illness, assessed by body mass index, was
associated with subcortical connectivity (p < .05, uncorrected).
Conclusions
Analyses identified reduced structural connectivity of subcortical networks and regions,
and stronger cortical network connectivity, among individuals with AN relative to
HC peers. These findings are consistent with alterations in feeding, emotion, and
executive control circuits in AN, and may direct hypothesis-driven research into mechanisms
of persistent restrictive eating behavior.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Biological Psychiatry: Cognitive Neuroscience and NeuroimagingAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Diagnostic and Statistical Manual of Mental Disorders.5th ed. American Psychiatric Press, Washington, DC2013
- Mortality rates in patients with anorexia nervosa and other eating disorders. A meta-analysis of 36 studies.Arch Gen Psychiatry. 2011; 68: 724-731
- Anorexia nervosa - medical complications.J Eat Disord. 2015; 3: 11
- Psychiatric comorbidity in women and men with eating disorders results from a large clinical database.Psychiatry Res. 2015; 230: 294-299
- A systematic review of the health-related quality of life and economic burdens of anorexia nervosa, bulimia nervosa, and binge eating disorder.Eat Weight Disord. 2016; 21: 353-364
- Relapse in anorexia nervosa: A systematic review and meta-analysis.Curr Opin Psychiatry. 2018; 31: 445-455
- Time to make a change: A call for more experimental research on key mechanisms in anorexia nervosa.Eur Eating Disord Rev. 2020; 28: 361-367
- Network structure shapes spontaneous functional connectivity dynamics.J Neurosci. 2015; 35: 5579-5588
- The structural–functional connectome and the default mode network of the human brain.NeuroImage. 2014; 102: 142-151
- MR imaging of intravoxel incoherent motions: Application to diffusion and perfusion in neurologic disorders.Radiology. 1986. 1986; 161: 401-407
- Altered thalamo–cortical and occipital–parietal–temporal–frontal white matter connections in patients with anorexia and bulimia nervosa: A systematic review of diffusion tensor imaging studies.J Psychiatry Neurosci. 2019; 44: 324-339
- Abnormal reward circuitry in anorexia nervosa: A longitudinal, multimodal MRI study.Human Brain Mapp. 2016; 37: 3835-3846
- White matter tracts characteristics in habitual decision-making circuit underlie ritual behaviors in anorexia nervosa.Sci Rep. 2021; 1115980
- Altered white matter connectivity in young acutely underweight patients with anorexia nervosa.J Am Acad Chiuld Adolesc Psychiatry. 2022; 61: 331-340
- MRtrix: Diffusion tractography in crossing fiber regions.Int J Imaging Syst Technol. 2012; 22: 53-66
- White matter fiber tractography: Why we need to move beyond DTI.J Neurosurg. 2013; 118: 1367-1377
- Diffusion tensor imaging and beyond.Magn Reson Med. 2011; 65: 1532-1556
- The human connectome: A structural description of the human brain.PLoS Comput Biol. 2005; 1: e42
- Test–retest reliability of structural brain networks from diffusion MRI.NeuroImage. 2014; 86: 231-243
- Reproducibility and intercorrelation of graph theoretical measures in structural brain connectivity networks.Med Image Anal. 2019; 52: 56-67
- Test–retest reliability of computational network measurements derived from the structural connectome of the human brain.Brain Connect. 2013; 3: 160-176
- Large-scale brain networks and psychopathology: A unifying triple network model.Trends Cogn Sci. 2011; 15: 483-506
- Shift toward randomness in brain networks of patients with anorexia nervosa: The role of malnutrition.Front Neurosci. 2021; 15645139
- Brain connectome modularity in weight-restored anorexia nervosa and body dysmorphic disorder.Psychol Med. 2016; 46: 2785-2797
- Differentiating weight-restored anorexia nervosa and body dysmorphic disorder using neuroimaging and psychometric markers.PLoS One. 2019; 14e0213974
- Neural mechanisms supporting maladaptive food choices in anorexia nervosa.Nat Neurosci. 2015; 18: 1571-1573
- Restrictive eating across a spectrum from healthy to unhealthy: Behavioral and neural mechanisms [published online ahead of print Oct 13].Psychol Med. 2020;
- Resting-state connectivity within and across neural circuits in anorexia nervosa.Brain Behav. 2019; 9e01205
Lloyd EC, Foerde K, Posner JP, Steinglass J. Longitudinal assessment of neural circuits in adolescents with anorexia nervosa: Preliminary behavioral findings. Presented at Eating Disorders Research Society Annual Meeting, Oct 12-16, 2020, Virtual.
- Binge Eating: Nature, Assessment, and Treatment.Guilford Press, New York1993
- The eating disorder assessment for DSM-5 (EDA-5): Development and validation of a structured interview for feeding and eating disorders.Int J Eating Disord. 2015; 48: 452-463
- Structured Clinical Interview for the DSM (SCID).in: The Encyclopedia of Clinical Psychology. Wiley, Hoboken, NJ2014: 1-6
- Schedule for affective disorders and schizophrenia for school-age children-present and lifetime version (K-SADS-PL): Initial reliability and validity data.J Am Acad Chiuld Adolesc Psychiatry. 1997. 1997; 36: 980-988
- FreeSurfer. NeuroImage. 2012; 62: 774-781
- Whole brain segmentation: Automated labeling of neuroanatomical structures in the human brain.Neuron. 2002. 2002; 33: 341-355
- An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest.NeuroImage. 2006. 2006; 31: 968-980
- MRtrix3: A fast, flexible and open software framework for medical image processing and visualisation.NeuroImage. 2019; 202116137
- Robust determination of the fibre orientation distribution in diffusion MRI: Non-negativity constrained super-resolved spherical deconvolution.NeuroImage. 2007. 2007; 35: 1459-1472
- Harmonization of multi-site diffusion tensor imaging data.NeuroImage. 2017; 161: 149-170
- Harmonization of cortical thickness measurements across scanners and sites.NeuroImage. 2018; 167: 104-120
- Is removal of weak connections necessary for graph-theoretical analysis of dense weighted structural connectomes from diffusion MRI?.NeuroImage. 2019; 194: 68-81
- Network-based statistic: Identifying differences in brain networks.NeuroImage. 2010; 53: 1197-1207
- Complex network measures of brain connectivity: Uses and interpretations.NeuroImage. 2010; 52: 1059-1069
- Efficient behavior of small-world networks.Phys Rev Lett. 2001; 87198701
Frossard J, Renaud O. Permuco: Permutation Tests for Regression, (Repeated Measures) ANOVA/ANCOVA and Comparison of Signals. R package version 1.1.0. Available at: https://cran.r-project.org/web/packages/permuco/index.html. Accessed April 10, 2022.
- Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa.Nat Genet. 2019; 51: 1207-1214
- Neuronal circuits for fear and anxiety.Nat Rev Neurosci. 2015; 16: 317-331
- The Paraventricular nucleus of the thalamus as an integrating and relay node in the brain anxiety network.Front Behav Neurosci. 2021; 15: 21
- Associations between mealtime anxiety and food intake in anorexia nervosa.Int J Eating Disord. 2021; 54: 1711-1716
- Comorbidity of anxiety disorders with anorexia and bulimia nervosa.Am J Psychiatry. 2004. 2004; 161: 2215-2221
- New insights into symptoms and neurocircuit function of anorexia nervosa.Nat Rev Neurosci. 2009. 2009; 10: 573-584
- Hungry for reward: How can neuroscience inform the development of treatment for anorexia nervosa?.Behav Res Ther. 2014; 62: 47-59
- The enigmatic persistence of anorexia nervosa.Am J Psychiatry. 2013; 170: 477-484
- Rich-club organization of the human connectome.J Neurosci. 2011; 31: 15775-15786
- Disrupted rich-club network organization and individualized identification of patients with major depressive disorder.Prog Neuropsychopharmacol Biol Psychiatry. 2021; 108110074
- Aberrant rich club organization in patients with obsessive-compulsive disorder and their unaffected first-degree relatives.NeuroImage Clin. 2021; 32102808
- Abnormal rich club organization and functional brain dynamics in schizophrenia.JAMA Psychiatry. 2013; 70: 783-792
- Connectomics-based structural network alterations in obsessive-compulsive disorder.Transl Psychiatry. 2016; 6e882
- White matter structural network disturbances in first-episode, drug-naïve adolescents with generalized anxiety disorder.J Psychiatr Res. 2020; 130: 394-404
- Abnormal structural networks characterize major depressive disorder: A connectome analysis.Biol Psychiatry. 2014; 76: 567-574
- White matter microstructural changes in adolescent anorexia nervosa including an exploratory longitudinal study.NeuroImage Clin. 2016; 11: 614-621
- Localized brain volume and white matter integrity alterations in adolescent anorexia nervosa.J Am Acad Child Adolesc Psychiatry. 2013; 52: 1066-1075.e5
- Fornix under water? Ventricular enlargement biases forniceal diffusion magnetic resonance imaging indices in anorexia nervosa.Biol Psychiatry Cogn Neurosci Neuroimaging. 2017; 2: 430-437
- Dynamic changes in white matter microstructure in anorexia nervosa: Findings from a longitudinal study.Psychol Med. 2019; 49: 1555-1564
- Altered structural and effective connectivity in anorexia and bulimia nervosa in circuits that regulate energy and reward homeostasis.Transl Psychiatry. 2016; 6: e932
- Global cortical thinning in acute anorexia nervosa normalizes following long-term weight restoration.Biol Psychiatry. 2015; 77: 624-632
- Weight restoration therapy rapidly reverses cortical thinning in anorexia nervosa: A longitudinal study.NeuroImage. 2016; 130: 214-222
- White matter tissue quantification at low b-values within constrained spherical deconvolution framework.Front Neurol. 2018; 9: 716
- Psychiatric and medical correlates of DSM-5 eating disorders in a nationally representative sample of adults in the United States.Int J Eating Disord. 2019; 52: 42-50
Article info
Publication history
Published online: June 14, 2022
Accepted:
June 1,
2022
Received in revised form:
May 27,
2022
Received:
February 2,
2022
Publication stage
In Press Journal Pre-ProofFootnotes
JES and JP contributed equally to this work as joint senior authors.
Identification
Copyright
© 2022 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
