Original article[123I] β-CIT and single photon emission computed tomography reveal reduced brain serotonin transporter availability in bulimia nervosa
Introduction
In the past, the etiology of eating disorders had been primarily attributed to psychologic variables; however, several lines of evidence suggest neurobiological alterations and, in particular, a role for the neurotransmitter serotonin (5-HT) in the pathophysiology of eating disorders. Hypothalamic 5-HT transmission has been shown to be involved in the control of eating behavior, meal size, and body weight (Leibowitz and Alexander 1998), and elevated serotonin uptake was found in blood platelets of bulimia nervosa (BN) patients (Goldbloom et al 1990). Antidepressant drugs targeting the 5-HT reuptake transporter (e.g., the selective serotonin reuptake inhibitor [SSRI] fluoxetine) proved to be clinically efficacious in alleviating bulimic symptoms (Wood 1993). Furthermore, there is evidence that decreased central serotonergic transmission in BN may lead to impaired satiety signals, thus contributing to BN symptoms (Jimerson et al 1997), and women with BN seem to be more vulnerable to mood-lowering effects of acute tryptophan depletion, thus suggesting that they may suffer from altered modulation of central serotonin systems (Kaye et al 2000).
Iodine-labeled [123I]-2β-carbomethoxy-3β-(4-iodophenyl)tropane ([123I] β-CIT) and single photon emission computed tomography (SPECT) can be used to visualize serotonin transporters (SERTs) and dopamine transporters (DATs) in the human brain Brucke et al 1993, Innis et al 1991, Kuikka et al 1993. Quantification of [123I] β-CIT binding to hypothalamic and thalamic SERTs as well as to striatal DATs can be achieved by means of a simple ratio of [123I] β-CIT binding in these regions to a reference region—for example, the cerebellum (V3″ = target region − cerebellum/cerebellum = target region/cerebellum − 1). During equilibrium conditions, this ratio can be used as an estimate for the binding potential (Mintun et al 1984), assuming that the reference region is devoid of significant specific binding to SERTs and DATs.
Recently, a reduction in brain stem SERT availability in major depression was shown with [123I] β-CIT and SPECT (Malison et al 1998). Our group was able to replicate this finding in drug-free depressed patients with seasonal affective disorder (Willeit et al 2000). Decreased SERT availability was also reported in alcoholism (Heinz et al 1998). On the other hand, schizophrenia was not associated with alterations of DAT in the striatum or SERT in the brain stem, as measured with [123I] β-CIT and SPECT [Laruelle et al 2000).
There is evidence for impaired serotonin transmission in bulimia nervosa (Jimerson et al 1997). Furthermore, central SERTs are in a key position to regulate serotonin function. As outlined above, there may be some similarities in the pathophysiology of BN and depression, for which reduced SERT availability was described (Malison et al 1998). Accordingly, we investigated [123I] β-CIT binding to SERTs in a brain region comprising the thalamus and, to a smaller extent, the hypothalamus of BN patients in comparison with age- and gender-matched healthy control subjects.
Section snippets
Subjects
We investigated 10 female patients with a BN diagnosis, purging type (DSM-IV 307.51 [American Psychiatric Association 1994]), established by a structured clinical interview for DSM-IV (SCID-1; First et al 1996). They were not allowed any psychotropic medication within 3 months before the SPECT scan. The average duration of illness was 5 years (range 2–10), with a mean age of onset of 19 years (range 13–25). The self-reported binge eating and vomiting frequencies ranged from once a month to five
Results
Single photon emission computed tomography investigations performed approximately 24 hours after injection of [123I] β-CIT revealed that its brain uptake was significantly reduced by 17% in the ROI comprising the thalamus and to a smaller extent, the hypothalamus of bulimic patients, as compared with healthy control subjects (V3″ SERT: 2.4 ± 0.4 vs. 2.9 ± 0.4, p = .026; Figure 2). Additionally, there was a statistically significant difference in striatal V3″ between groups (10.0 ± 1.3 vs. 11.8
Discussion
To our knowledge, this is the first exploratory in vivo investigation of brain serotonin and dopamine transporter availability in BN using [123I] β-CIT and SPECT. The main finding was a significant reduction of diencephalic and striatal [123I] β-CIT binding in 10 bulimic patients compared with 10 healthy control subjects matched for age and gender. The reduced binding in SERT-rich brain regions suggests a reduced hypothalamic and thalamic SERT availability in bulimia, and is in line with a
Acknowledgements
The authors thank Mr. Harald Frassine and Mr. Miladin Rasoljevic, technologists, for their excellent assistance in this study. Furthermore, we express our gratitude to Nicholaas Paul L.G. Verhoeff, M.D., Ph.D., for his most valuable contributions to the manuscript.
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