Review
Towards a neurocircuitry in anorexia nervosa: Evidence from functional neuroimaging studies

https://doi.org/10.1016/j.jpsychires.2009.04.005Get rights and content

Abstract

Functional neuroimaging is widely used to unravel changes in brain functioning in psychiatric disorders. In the current study, we review single-photon emission tomography (SPECT), positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) studies in anorexia nervosa (AN), a difficult-to-treat eating disorder with the highest mortality rate among psychiatric disorders. We discuss the role of the parietal cortex, anterior and subgenual cingulate cortex, frontal cortex and temporal lobe in light of the cardinal symptoms of AN. The insights of the current review may ultimately lead to the development of new treatments.

Introduction

Anorexia nervosa (AN) is characterized by a relentless pursuit of thinness and a refusal to maintain body weight at 85% of the expected standard for age and height combined with an intense fear of gaining weight or becoming fat (American Psychiatric Association, 2000). Furthermore, individuals with AN place undue value on weight and typically exhibit disturbed perceptions of their own body shape and size. Lastly, post-menarchal females with the disorder show amenorrhea. DSM-IV-TR recognizes two clinical subtypes: the restricting (AN-R) and the bingeing/purging (AN-P) type. While individuals with the former accomplish weight loss primarily through fasting or excessive exercise, subjects with the latter have times when they loose control over eating and/or attempt to reduce weight through such behaviors as self-induced vomiting or laxative abuse.

The prevalence of strictly defined AN is up to 0.9% with the average of the European studies using DSM-IV-TR criteria being 0.29% among young females. Females are more frequently affected than males, the female-to-male ratio being higher than 10:1. The 15–19 age group represents the highest incidence rate, constituting approximately 40% of all identified cases (Hoek and van Hoeken, 2003).

The course and outcome of AN are heterogeneous and the disorder elicits important physical and psychosocial morbidity and mortality in adolescent girls and young adult women. Less than half of the patients make a full recovery and a third of them experiences only partial remission and continues to evidence at least some eating disorder related symptomatology (Steinhausen, 2002, Steinhausen et al., 2000, Strober et al., 1997, Sullivan, 1995, Walsh and Klein, 2003).

There is substantial scientific evidence for changes in central nervous system function in AN patients compared to healthy controls (Frank et al., 2004, Stamatakis and Hetherington, 2003). While earlier studies investigated metabolic network differences, more recent imaging studies have concentrated specifically on cognitive paradigms using fMRI and neurochemical changes in transmitter systems such as serotonin and dopamine (Frank et al., 2005a, Frank and Kaye, 2005b; Kaye et al., 2005a, Kaye et al., 2005b, Kaye et al., 2005c). The main goals of the current review are to (1) provide an overview of functional neuroimaging techniques in AN; (2) discuss issues on functional neuroimaging, related to AN; (3) provide an updated overview of changes in regional brain metabolism in AN; (4) discuss the main findings.

Section snippets

SPECT, PET and fMRI

Functional neuroimaging covers a broad range of techniques used to visualize cerebral activity. These techniques differ in the underlying physiological approaches and in spatial and time resolution. For the current review, we have addressed original studies describing the results of single-photon emission computed tomography (SPECT), positron emission tomography (PET), and functional magnetic resonance imaging (fMRI). Electrophysiological techniques (such as quantitative electroencephalography

Cachexia

Several functional neuroimaging techniques, like FDG-PET, determine regional brain activity by (indirectly) estimating glucose metabolism. Ketones and lactate can be used as additional resources for the brain (Pellerin and Magistretti, 2004) and there is evidence that the proportional use of glucose relative to the other energy resources is altered in AN. The prolonged deficient energy intake in AN results in a decrease in plasma glucose and an increase in plasma ketones and plasma free fatty

Early SPECT and PET studies

The number of AN patients in early PET studies was low (5–7 patients; Herholz et al., 1987, Krieg et al., 1986, Krieg et al., 1991) and control groups often consisted of considerably older, male subjects (Herholz et al., 1987, Krieg, 1991, Krieg et al., 1986, Krieg et al., 1989). The latter was due to the albeit small genotoxic risk associated with radiation for reproductive young female healthy volunteers. The main findings were an increased metabolism bilaterally in the caudate nuclei in AN

Correlations

The aim of correlation analysis in functional neuroimaging studies in patients is to relate changes in local brain metabolism to specific symptoms or character traits, to allow deduction of more robust and possibly causal relationships.

In patients with AN, some psychological measures have already been correlated to changes in receptor binding. Interoceptive awareness, or the ability to recognize and label one’s own internal emotional state, is affected in patients with AN and is at the core of

The restricting (AN-R) versus the binge-purging subtype (AN-P): a continuum or distinct disorders?

The American Psychiatric Association recognizes in the DSM-IV two clinical subtypes of AN: the restricting (AN-R) and the bingeing/purging (AN-P) type (see introduction). It still a matter of debate whether these subtypes differ in personality and prevalence of co-morbid psychiatric disorders (Blinder et al., 2006, Diaz-Marsa et al., 2000, Sansone et al., 2005, Speranza et al., 2001). Only a few functional neuroimaging studies have directly compared patients of the AN-R and AN-P subtype.

Variability

The current review reveals a large variability in patient characteristics and methodology within functional neuroimaging studies in AN, as demonstrated by differences in demographic variables (age, BMI, etc.), phase in the recovery process (currently-ill, treatment or recovered), imaging condition (rest or provocation), techniques (SPECT, PET and fMRI) and statistical analysis (ROI, VOI and SPM). This variability in combination with the relatively small number of studies hampers a direct

Role of funding source

None of the funding institutes (see acknowledgements) had a role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.

Conflict of interest statement

There was no conflict of interest for any of the authors.

Acknowledgements

We acknowledge the financial support of the Research Fund K.U.Leuven (project VIS/02/007 and OT/03/57 and OT/05/58), the Institute for the Promotion of Innovation by Science and Technology in Flanders (SBO50151) and the Fonds voor Wetenschappelijk Onderzoek – Vlaanderen (G.0598.06).

References (134)

  • V. Delvenne et al.

    Brain hypometabolism of glucose in anorexia nervosa: a PET scan study

    Biological Psychiatry

    (1995)
  • C. Devue et al.

    Here I am: the cortical correlates of visual self-recognition

    Brain Research

    (2007)
  • Z. Ellison et al.

    Functional anatomy of calorie fear in anorexia nervosa

    Lancet

    (1998)
  • K.D. Fitzgerald et al.

    Error-related hyperactivity of the anterior cingulate cortex in obsessive-compulsive disorder

    Biological Psychiatry

    (2005)
  • G.K. Frank et al.

    Positron emission tomography studies in eating disorders: multireceptor brain imaging, correlates with behavior and implications for pharmacotherapy

    Nuclear Medicine and Biology

    (2005)
  • G.K. Frank et al.

    Reduced 5-HT2A receptor binding after recovery from anorexia nervosa

    Biological Psychiatry

    (2002)
  • B. Galusca et al.

    Organic background of restrictive-type anorexia nervosa suggested by increased serotonin 1A receptor binding in right frontotemporal cortex of both lean and recovered patients: [18F]MPPF PET scan study

    Biological Psychiatry

    (2008)
  • C.D. Good et al.

    Cerebral asymmetry and the effects of sex and handedness on brain structure: a voxel-based morphometric analysis of 465 normal adult human brains

    Neuroimage

    (2001)
  • C.M. Gordon et al.

    Neural substrates of anorexia nervosa: a behavioral challenge study with positron emission tomography

    The Journal of Pediatrics

    (2001)
  • J.P. Herman et al.

    Central mechanisms of stress integration: hierarchical circuitry controlling hypothalamo-pituitary-adrenocortical responsiveness

    Frontiers in Neuroendocrinology

    (2003)
  • W.H. Kaye et al.

    Serotonin alterations in anorexia and bulimia nervosa: new insights from imaging studies

    Physiology and Behavior

    (2005)
  • T.W. Kjaer et al.

    Reflective self-awareness and conscious states: PET evidence for a common midline parietofrontal core

    Neuroimage

    (2002)
  • S. Kojima et al.

    Comparison of regional cerebral blood flow in patients with anorexia nervosa before and after weight gain

    Psychiatry Research 140, 251-258

    (2005)
  • J.C. Krieg et al.

    Brain morphology and regional cerebral blood flow in anorexia nervosa

    Biological Psychiatry

    (1989)
  • M.L. Kringelbach et al.

    The functional neuroanatomy of the human orbitofrontal cortex: evidence from neuroimaging and neuropsychology

    Progress in Neurobiology

    (2004)
  • R. Matsumoto et al.

    Regional cerebral blood flow changes associated with interoceptive awareness in the recovery process of anorexia nervosa

    Progress in Neuropsychopharmacol and Biological Psychiatry

    (2006)
  • H.S. Mayberg et al.

    Deep brain stimulation for treatment-resistant depression

    Neuron

    (2005)
  • K.K. Miller et al.

    Testosterone administration attenuates regional brain hypometabolism in women with anorexia nervosa

    Psychiatry Research

    (2004)
  • T. Nakao et al.

    Brain activation of patients with obsessive-compulsive disorder during neuropsychological and symptom provocation tasks before and after symptom improvement: a functional magnetic resonance imaging study

    Biological Psychiatry

    (2005)
  • P. Nopoulos et al.

    Sexual dimorphism in the human brain: evaluation of tissue volume, tissue composition and surface anatomy using magnetic resonance imaging

    Psychiatry Research

    (2000)
  • S. Nozoe et al.

    Changes in regional cerebral blood flow in patients with anorexia nervosa detected through single photon emission tomography imaging

    Biological Psychiatry

    (1993)
  • S. Nozoe et al.

    Comparison of regional cerebral blood flow in patients with eating disorders

    Brain Research Bulletin

    (1995)
  • K.M. O’Brien et al.

    Psychiatric comorbidity in anorexia and bulimia nervosa: nature, prevalence, and causal relationships

    Clinical Psychology Review

    (2003)
  • P. Sachdev et al.

    Brains of anorexia nervosa patients process self-images differently from non-self-images: an fMRI study

    Neuropsychologia

    (2008)
  • S. Santel et al.

    Hunger and satiety in anorexia nervosa: fMRI during cognitive processing of food pictures

    Brain Research

    (2006)
  • P.D. Acton et al.

    Statistical parametric mapping in functional neuroimaging: beyond PET and fMRI activation studies

    European Journal of Nuclear Medicine

    (1998)
  • J.S. Allen et al.

    Normal neuroanatomical variation in the human brain: an MRI-volumetric study

    American Journal of Physical Anthropology

    (2002)
  • L.S. Allen et al.

    Sex difference in the bed nucleus of the stria terminalis of the human brain

    Journal of Comparative Neurology

    (1990)
  • D.G. Amaral et al.

    Amygdalo-cortical projections in the monkey (Macaca fascicularis)

    Journal of Comparative Neurology

    (1984)
  • American Psychiatric Association. (2000). Diagnostic and Statistic Manual of Mental Disorders - Fourth Edition - Text...
  • R.A. Andersen et al.

    Corticocortical connections of anatomically and physiologically defined subdivisions within the inferior parietal lobule

    Journal of Comparative Neurology

    (1990)
  • K. Audenaert et al.

    Decreased 5-HT2a receptor binding in patients with anorexia nervosa

    Journal of Nuclear Medicine

    (2003)
  • U.F. Bailer et al.

    Serotonin transporter binding after recovery from eating disorders

    Psychopharmacology (Berlin)

    (2007)
  • U.F. Bailer et al.

    Altered Brain Serotonin 5-HT1A Receptor Binding After Recovery From Anorexia Nervosa Measured by Positron Emission Tomography and [Carbonyl11C]WAY-100635

    Archives of General Psychiatry

    (2005)
  • U.F. Bailer et al.

    Altered 5-HT(2A) receptor binding after recovery from bulimia-type anorexia nervosa: relationships to harm avoidance and drive for thinness

    Neuropsychopharmacology

    (2004)
  • S.E. Best et al.

    Striatal dopamine transporter availability with [123I]beta-CIT SPECT is unrelated to gender or menstrual cycle

    Psychopharmacology (Berlin)

    (2005)
  • B.J. Blinder et al.

    Psychiatric comorbidities of female inpatients with eating disorders

    Psychosomatic Medicine

    (2006)
  • E. Bonda et al.

    Neural correlates of mental transformations of the body-in-space

    Proceedings of the National Academy of Sciences of the United States of America

    (1995)
  • H.D. Burns et al.

    [18F]MK-9470, a positron emission tomography (PET) tracer for in vivo human PET brain imaging of the cannabinoid-1 receptor

    Proceedings of the National Academy of Sciences of the United States of America

    (2007)
  • R.C. Casper

    Behavioral activation and lack of concern, core symptoms of anorexia nervosa?

    The International Journal of Eating Disorders

    (1998)
  • Cited by (0)

    View full text