Exaggerated 5-HT1A but normal 5-HT2A receptor activity in individuals ill with anorexia nervosa.
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.
SourceAvailable from: Rebecca Jane Park[Show abstract] [Hide abstract]
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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ABSTRACT: Psychiatric disorders are often associated with metabolic and hormonal alterations, including obesity, diabetes, metabolic syndrome as well as modifications in several biological rhythms including appetite, stress, sleep-wake cycles, and secretion of their corresponding endocrine regulators. Among the gastrointestinal hormones that regulate appetite and adapt the metabolism in response to nutritional, hedonic, and emotional dysfunctions, at the interface between endocrine, metabolic, and psychiatric disorders, ghrelin plays a unique role as the only one increasing appetite. The secretion of ghrelin is altered in several psychiatric disorders (anorexia, schizophrenia) as well as in metabolic disorders (obesity) and in animal models in response to emotional triggers (psychological stress …) but the relationship between these modifications and the physiopathology of psychiatric disorders remains unclear. Recently, a large literature showed that this key metabolic/endocrine regulator is involved in stress and reward-oriented behaviors and regulates anxiety and mood. In addition, preproghrelin is a complex prohormone but the roles of the other ghrelin-derived peptides, thought to act as functional ghrelin antagonists, are largely unknown. Altered ghrelin secretion and/or signaling in psychiatric diseases are thought to participate in altered appetite, hedonic response and reward. Whether this can contribute to the mechanism responsible for the development of the disease or can help to minimize some symptoms associated with these psychiatric disorders is discussed in the present review. We will thus describe (1) the biological actions of ghrelin and ghrelin-derived peptides on food and drugs reward, anxiety and depression, and the physiological consequences of ghrelin invalidation on these parameters, (2) how ghrelin and ghrelin-derived peptides are regulated in animal models of psychiatric diseases and in human psychiatric disorders in relation with the GH axis.Frontiers in Endocrinology 10/2014; 5:163. DOI:10.3389/fendo.2014.00163
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ABSTRACT: Objective To provide a neurobiological basis of eating disorders for clinicians and to enlighten how comparing neurobiology and eating disorders with neurobiology of other psychiatric illnesses can improve treatment protocols.MethodA selective review on the neurobiology of eating disorders. The article focuses on clinical research on humans with consideration of the anatomical, neural, and molecular basis of eating disorders.ResultsThe neurobiology of people with eating disorders is altered. Many of the neurobiological regions, receptors, and chemical substrates that are affected in other mental illnesses also play an important role in eating disorders. More knowledge about the neurobiological overlap between eating disorders and other psychiatric populations will help when developing treatment protocols not the least regarding that comorbidity is common in patients with EDs.Conclusion Knowledge about the underlying neurobiology of eating disorders will improve treatment intervention and will benefit from comparisons with other mental illnesses and their treatments.Acta Psychiatrica Scandinavica 09/2014; 131(4). DOI:10.1111/acps.12335 · 5.55 Impact Factor