ReviewTowards a neurocircuitry in anorexia nervosa: Evidence from functional neuroimaging studies
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).
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