Article

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

Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
Archives of General Psychiatry (Impact Factor: 14.48). 10/2005; 62(9):1032-41. DOI: 10.1001/archpsyc.62.9.1032
Source: PubMed

ABSTRACT

Previous studies have shown that women with anorexia nervosa (AN), when ill and after recovery, have alterations of serotonin (5-HT) neuronal activity and core eating disorder symptoms, such as anxiety.
To further characterize the 5-HT system in AN, we investigated 5-HT1A receptor activity using positron emission tomography imaging because this receptor is implicated in anxiety and feeding behavior.
To avoid the confounding effects of malnutrition, we studied 13 women who had recovered from restricting-type AN (mean age, 23.3 +/- 5.2 years) and 12 women who had recovered from bulimia-type AN (mean age, 28.6 +/- 7.3 years) (>1 year normal weight, regular menstrual cycles, no bingeing or purging). These subjects were compared with 18 healthy control women (mean age, 25.1 +/- 5.8 years). Intervention The 5-HT1A receptor binding was measured using positron emission tomography imaging and a specific 5-HT1A receptor antagonist, [carbonyl-11C]WAY-100635.
Specific 5-HT1A receptor binding was assessed using the binding potential measure. Binding potential values were derived using both the Logan graphical method and compartmental modeling. The binding potential in a region of interest was calculated with the formula: binding potential = distribution volume of the region of interest minus distribution volume of the cerebellum.
Women recovered from bulimia-type AN had significantly (P<.05) increased [11C]WAY-100635 binding potential in cingulate, lateral and mesial temporal, lateral and medial orbital frontal, parietal, and prefrontal cortical regions and in the dorsal raphe compared with control women. No differences were found for women recovered from restricting-type AN relative to controls. For women recovered from restricting-type AN, the 5-HT1A postsynaptic receptor binding in mesial temporal and subgenual cingulate regions was positively correlated with harm avoidance.
We observed increased 5-HT1A receptor binding in women who had recovered from bulimia-type AN but not restricting-type AN. However, 5-HT1A receptor binding was associated with a measure of anxiety in women recovered from restricting-type AN. These data add to a growing body of evidence showing that altered serotonergic function and anxiety symptoms persist after recovery from AN. These psychobiological alterations may be trait related and may contribute to the pathogenesis of AN.

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    • "This model hypothesizes that patients with anorexia nervosa are extremely prone to fear conditioning , which may underlie the phobia of weight gain, which is encapsulated from cognitive control leading to an irrational resistance to the extinction of this fear (Strober, 2004). In line with these assumptions, recent research has shown altered binding of serotonin receptors in the amygdala, hippocampus and cingulate in women with anorexia nervosa, suggesting aberrations in neuronal circuitry known to be involved in regulating fear conditioning (Bailer et al., 2005;Frank et al., 2002). A shared genetic susceptibility of anorexia nervosa and anxiety disorder has been suggested by twin studies (Keel, Klump, Miller, McGue, &amp; Iacono, 2005;Silberg &amp; Bulik, 2005). "
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    • "Biological marker Age PET effect Brain region Recovered ED (sample size, n's) Serotonin system 5-HT1a receptor Bailer et al., 2005 "
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    • "rers have been reported to have diminished binding potential for 5 - HT 2A and increased binding potential of 5 - HT 1A . Audenaert et al . ( 2003 ) reported significantly reduced 5 - HT 2A binding in the left frontal cortex as well as the left and right parietal and occipital cortices of individuals with AN in comparison to control participants . Bailer et al . ( 2005 ) , on the other hand , reported increased 5 - HT 1A binding potential of the dorsal raphe , and the cingulate , lateral and medial tempo - ral , lateral and medial orbitofrontal , parietal and prefrontal cortices in weight - recovered AN . Studies investigating the specific subtypes of AN found that weight - restored restrict - ing sub"
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