Exaggerated 5-HT1A but normal 5-HT2A receptor activity in individuals ill with anorexia nervosa. Biol Psychiatry 61: 1090-1099

Department of Psychiatry, Western Psychiatric Institute and Clinic, School of Medicine, Pittsburgh, University of Pittsburgh, Pennsylvania 15213, USA.
Biological Psychiatry (Impact Factor: 9.47). 06/2007; 61(9):1090-9. DOI: 10.1016/j.biopsych.2006.07.018
Source: PubMed

ABSTRACT 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.

Download full-text


Available from: Walter H Kaye, Jul 06, 2015
  • Source
    [Show abstract] [Hide abstract]
    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; DOI:10.1016/j.npep.2014.07.003 · 2.55 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    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; DOI:10.1177/0004867413509693 · 3.77 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Anorexia nervosa (AN) is a severe psychiatric disorder associated with food avoidance and malnutrition. In this study, we wanted to test whether we would find brain reward alterations in AN, compared with individuals with normal or increased body weight. We studied 21 underweight, restricting-type AN (age M 22.5, SD 5.8 years), 19 obese (age M 27.1, SD 6.7 years), and 23 healthy control women (age M 24.8, SD 5.6 years), using blood oxygen level-dependent functional magnetic resonance brain imaging together with a reward-conditioning task. This paradigm involves learning the association between conditioned visual stimuli and unconditioned taste stimuli, as well as the unexpected violation of those learned associations. The task has been associated with activation of brain dopamine reward circuits, and it allows the comparison of actual brain response with expected brain activation based on established neuronal models. A group-by-task condition analysis (family-wise-error-corrected P<0.05) indicated that the orbitofrontal cortex differentiated all three groups. The dopamine model reward-learning signal distinguished groups in the anteroventral striatum, insula, and prefrontal cortex (P<0.001, 25 voxel cluster threshold), with brain responses that were greater in the AN group, but lesser in the obese group, compared with controls. These results suggest that brain reward circuits are more responsive to food stimuli in AN, but less responsive in obese women. The mechanism for this association is uncertain, but these brain reward response patterns could be biomarkers for the respective weight state.
    Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 05/2012; 37(9):2031-46. DOI:10.1038/npp.2012.51 · 7.83 Impact Factor