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


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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    ABSTRACT: Anxiety disorders and anorexia nervosa are frequently acknowledged to be highly comorbid conditions, but still, little is known about the clinical and aetiological cohesion of specific anxiety diagnoses and anorexia nervosa. Using the comprehensive Danish population registers, we aimed to determine the risk of anorexia nervosa in patients with register-detected severe anxiety disorders. We also explored whether parental psychopathology was associated with offspring's anorexia nervosa. Anxiety disorders increased the risk of subsequent anorexia nervosa, with the highest risk observed in obsessive-compulsive disorder. Especially, male anxiety patients were at an increased risk for anorexia nervosa. Furthermore, an increased risk was observed in offspring of fathers with panic disorder. A diagnosis of an anxiety disorder, specifically obsessive-compulsive disorder, constitutes a risk factor for subsequent diagnosis of anorexia nervosa. These observations support the notion that anxiety disorders and anorexia nervosa share etiological mechanisms and/or that anxiety represents one developmental pathway to anorexia nervosa. Copyright © 2015 John Wiley & Sons, Ltd and Eating Disorders Association.
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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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    ABSTRACT: Eating disorders are severe psychiatric disorders with a complex etiology involving transactions among sociocultural, psychological, and biological influences. Most research and reviews, however, focus on only one level of analysis. To address this gap, we provide a qualitative review and summary using an integrative biopsychosocial approach. We selected variables for which there were available data using integrative methodologies (e.g., twin studies, gene-environment interactions) and/or data at the biological and behavioral level (e.g., neuroimaging). Factors that met these inclusion criteria were idealization of thinness, negative emotionality, perfectionism, negative urgency, inhibitory control, cognitive inflexibility, serotonin, dopamine, ovarian hormones. Literature searches were conducted using PubMed. Variables were classified as risk factors or correlates of eating disorder diagnoses and disordered eating symptoms using Kraemer et al.'s (1997) criteria. Sociocultural idealization of thinness variables (media exposure, pressures for thinness, thin-ideal internalization, thinness expectancies) and personality traits (negative emotionality, perfectionism, negative urgency) attained 'risk status' for eating disorders and/or disordered eating symptoms. Other factors were identified as correlates of eating pathology or were not classified given limited data. Effect sizes for risk factors and correlates were generally small-to-moderate in magnitude. Multiple biopsychosocial influences are implicated in eating disorders and/or disordered eating symptoms and several can now be considered established risk factors. Data suggest that psychological and environmental factors interact with and influence the expression of genetic risk to cause eating pathology. Additional studies that examine risk variables across multiple levels of analysis and that consider specific transactional processes amongst variables are needed to further elucidate the intersection of sociocultural, psychological, and biological influences on eating disorders. © 2015 Association for Child and Adolescent Mental Health.
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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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    ABSTRACT: Objective: Recent advances in neuroimaging techniques have enabled a better understanding of the neurobiological underpinnings of anorexia nervosa (AN). The aim of this paper was to summarise our current understanding of the neurobiology of AN. Methods: The literature was searched using the electronic databases PubMed and Google Scholar, and by additional hand searches through reference lists and specialist eating disorders journals. Relevant studies were included if they were written in English, only used human participants, had a specific AN group, used clinical populations of AN, group comparisons were reported for AN compared to healthy controls and not merely AN compared to other eating disorders or other psychiatric groups, and were not case studies. Results: The systematic review summarises a number of structural and functional brain differences which are reported in individuals with AN, including differences in neurotransmitter function, regional cerebral blood flow, glucose metabolism, volumetrics and the blood oxygen level dependent response. Conclusion: Several structural and functional differences have been reported in AN, some of which reverse and others which persist following weight restoration. These findings have important implications for our understanding of the neurobiological underpinnings of AN, and further research in this field may provide new direction for the development of more effective treatments.
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