Exaggerated 5-HT1A but Normal 5-HT2A Receptor Activity in Individuals Ill with Anorexia Nervosa

Department of Psychiatry, Western Psychiatric Institute and Clinic, School of Medicine, Pittsburgh, University of Pittsburgh, Pennsylvania 15213, USA.
Biological Psychiatry (Impact Factor: 10.26). 06/2007; 61(9):1090-9. DOI: 10.1016/j.biopsych.2006.07.018
Source: PubMed


Many studies have found disturbances of serotonin (5-HT) activity in anorexia nervosa (AN). Because little is known about 5-HT receptor function in AN, positron emission tomography (PET) imaging with 5-HT receptor-specific radioligands was used to characterize 5-HT1A and 5-HT2A receptors.
Fifteen women ill with AN (ILL AN) were compared with 29 healthy control women (CW); PET and [11C]WAY100635 were used to assess binding potential (BP) of the 5-HT1A receptor, and [18F]altanserin was used to assess postsynaptic 5-HT2A receptor BP. [15O] water and PET were used to assess cerebral blood flow.
The ILL AN women had a highly significant (30%-70%) increase in [11C]WAY100635 BP in prefrontal and lateral orbital frontal regions, mesial and lateral temporal lobes, parietal cortex, and dorsal raphe nuclei compared with CW. The [18F]altanserin BP was normal in ILL AN but was positively and significantly related to harm avoidance in suprapragenual cingulate, frontal, and parietal regions. Cerebral blood flow was normal in ILL AN women.
Increased activity of 5-HT1A receptor activity may help explain poor response to 5-HT medication in ILL AN. This study extends data suggesting that 5-HT function, and, specifically, the 5-HT2A receptor, is related to anxiety in AN.

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Available from: Walter H Kaye, Oct 06, 2015
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    • "(Dourish et al., 1985; Gilbert and Dourish, 1987; Fletcher and Davies, 1990; Ebenezer, 1992; Ebenezer and Tite, 1994; Ebenezer and Surujbally, 2007). Furthermore, imaging studies have shown that 5-HT 1A receptor expression increased significantly in recovered AN patients' brains compared to the ill AN patients' brains, while 5-HT 2A receptor expression is unchanged (Audenaert et al., 2003; Bailer et al., 2007; Galusca et al., 2008). As such, the perturbation of 5-HT 1A receptor activity is important in eating disorders. "
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    ABSTRACT: Both common eating disorders anorexia nervosa and bulimia nervosa are characteristically diseases of women. To characterize the role of the 5-HT1A receptor (5-HT1A-R) in these eating disorders in females, we investigated the effect of saline or 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) treatment on feeding behavior and body weight in adult WT female mice and in adult 5-HT1A-R knockout (KO) female mice. Our results showed that KO female mice have lower food intake and body weight than WT female mice. Administration of 8-OH-DPAT decreased food intake but not body weight in WT female mice. Furthermore, qRT-PCR was employed to analyze the expression levels of neuropeptides, γ-aminobutyric acid A receptor subunit β (GABAA β subunits) and glutamic acid decarboxylase in the hypothalamic area. The results showed the difference in food intake between WT and KO mice was accompanied by differential expression of POMC, CART and GABAA β2, and the difference in body weight between WT and KO mice was associated with significantly different expression levels of CART and GABAA β2. As such, our data provide new insight into the role of 5-HT1A-R in both feeding behavior and the associated expression of neuropeptides and the GABAA receptor.
    Neuropeptides 10/2014; 48(5). DOI:10.1016/j.npep.2014.07.003 · 2.64 Impact Factor
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    • "The 5-HT system has been extensively studied in AN, with much evidence of dysfunction in this system (for a recent review see Kaye et al., 2013b). Imaging studies have consistently shown increased 5HT-1A and decreased 2A receptor binding potential in individuals both currently ill and recovered from AN (Kaye et al., 2005a,b; Bailer et al., 2007), suggesting a trait and not state related alteration. Interaction between 5HT-1A and 2A receptors in the medial prefrontal cortex (mPFC) have been suggested to modulate impulsivity and compulsivity (Carli et al., 2006), although there is yet to be evidence of this mechanism in the development of compulsive behavior in AN. "
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    ABSTRACT: The compulsive nature of weight loss behaviors central to anorexia nervosa (AN), such as relentless self-starvation and over-exercise, has led to the suggestion of parallels between AN and other compulsive disorders such as obsessive-compulsive disorder (OCD) and addictions. There is a huge unmet need for effective treatments in AN, which has high rates of morbidity and the highest mortality rate of any psychiatric disorder, yet a grave paucity of effective treatments. Viewing compulsivity as a transdiagnostic concept, seen in various manifestations across disorders, may help delineate the mechanisms responsible for the persistence of AN, and aid treatment development. We explore models of compulsivity that suggest dysfunction in cortico-striatal circuitry underpins compulsive behavior, and consider evidence of aberrancies in this circuitry across disorders. Excessive habit formation is considered as a mechanism by which initially rewarding weight loss behavior in AN may become compulsive over time, and the complex balance between positive and negative reinforcement in this process is considered. The physiological effects of starvation in promoting compulsivity, positive reinforcement, and habit formation are also discussed. Further research in AN may benefit from a focus on processes potentially underlying the development of compulsivity, such as aberrant reward processing and habit formation. We discuss the implications of a transdiagnostic perspective on compulsivity, and how it may contribute to the development of novel treatments for AN.
    Frontiers in Psychology 07/2014; 5:778. DOI:10.3389/fpsyg.2014.00778 · 2.80 Impact Factor
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    • "by Bailer and colleagues ( 2007b ) , the investigators reported that ill AN individuals had increased 5 - HT 1A binding in the subgenual , mesial temporal , orbital frontal and raphae brain regions , and the prefrontal , lateral temporal , ACC and pari - etal regions . Similar findings have been reported for 5 - HT 1A binding in ill participants ( Bailer et al . , 2007b ; Galusca et al . , 2008 ) , whereas recovered AN sufferers 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 corti"
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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.
    Australian and New Zealand Journal of Psychiatry 11/2013; 48(2). DOI:10.1177/0004867413509693 · 3.41 Impact Factor
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