Neurobiology of Anorexia Nervosa: Serotonin Dysfunctions Link Self-Starvation with Body Image Disturbances through an Impaired Body Memory

Abstract

The etiology of anorexia nervosa (AN) is still unclear, despite that it is a critical and potentially mortal illness. A recent neurobiological model considers AN as the outcome of dysfunctions in the neuronal processes related to appetite and emotionality (Kaye et al., 2009, 2013). However, this model still is not able to answer a critical question: What is behind body image disturbances (BIDs) in AN? The article starts its analysis from reviewing some of the studies exploring the effects of the serotonin systems in memory (episodic, working, and spatial) and its dysfunctions. The review suggests that serotonin disturbances may: (a) facilitate the encoding of third person (allocentric) episodic memories; (b) facilitate the consolidation of emotional episodic memories (e.g., teasing), if preceded by repeated stress; (c) reduce voluntary inhibition of mnestic contents; (d) impair allocentric spatial memory. If we discuss these results within the interpretative frame suggested by the “Allocentric Lock Hypothesis” (Riva, 2012, 2014), we can hypothesize that altered serotoninergic activity in AN patients: (i) improves their ability to store and consolidate negative autobiographical memories, including those of their body, in allocentric perspective; (ii) impairs their ability to trigger voluntary inhibition of the previously stored negative memory of the body; (iii) impairs their capacity to retrieve/update allocentric information. Taken together, these points suggest a possible link between serotonin dysfunctions, memory impairments and BIDs: the impossibility of updating a disturbed body memory using real time experiential data—I'm locked to a wrong body stored in long term memory—pushes AN patients to control body weight and shape even when underweight.

Altered Processing and Integration of Multisensory Bodily Representations and Signals in Eating Disorders: A Possible Path Toward the Understanding of Their Underlying Causes

“…However, as we have just seen, these different sources are all shaped by the process of predictive multisensory integration. More, we know that different processes (i.e., working memory), neurotransmitters (i.e., serotonin) and brain areas related to multisensory integration (i.e., frontal and parietal lobes) are impaired in individuals with EDs (Gaudio et al, 2016 ; Riva, 2016 ; Brooks et al, 2017 ).…”

New Treatment Perspectives in Adolescents With Anorexia Nervosa: The Efficacy of Non-invasive Brain-Directed Treatment

“…A perturbations in the dopaminergic reward pathways has been hypothesized to play a role in the AN pathogenesis (Casper, 2006 ; Alcaro et al, 2007 ). Those alteration included reduced Cerebro Spinal Fluid levels of DA metabolites (Kontis and Theochari, 2012 ), functional DA D2 receptor gene polymorphisms (Bergen et al, 2005 ), and increased D2/D3 receptor binding in the striatum (Kaye et al, 2013 ; Riva, 2016 ), indicating an increased D2/D3 densities and a decreased extracellular DA in this region. Moreover, the evidence of a DA imbalance in the ventral striatum in patients with AN, is considered to contribute to anhedonia of feeding behavior, ascetic and anhedonic temperament (Frank et al, 2017 ), as well as dysphoric mood and anxiety (Kaye et al, 2009 ).…”

“…Altered activity in the insula (Kaye et al, 2010 ; Mohr et al, 2010 ; Bär et al, 2013 ; Oberndorfer et al, 2013 ; Strigo et al, 2013 ), abnormalities in the processing of rewards (Bohon and Stice, 2011 ; Avena and Bocarsly, 2012 ; Ritschel et al, 2017 ) and alterations in frontal regions have been reported (Brooks et al, 2011 ; Celone et al, 2011 ; Strigo et al, 2013 ; Kullmann et al, 2014 ). Subsequently, neural models of ED have been developed (Steinglass and Walsh, 2006 ; Brooks et al, 2011 ; Friederich and Herzog, 2011 ; Riva, 2016 ; Steinglass et al, 2017 ).…”

“…In AN, some studies considered abnormalities in dorsolateral prefrontal cortex (DLPFC) (Kaye et al, 2009 ; Van Kuyck et al, 2009 ; Brooks et al, 2011 ; Ehrlich et al, 2015 ; Hestad et al, 2016 ). Furthermore, fMRI studies, EEG measurements and PET scan in individuals with AN showed a hyperactivity of right hemisphere (Grunwald et al, 2004 ; Brooks et al, 2011 ; Bär et al, 2013 ; Phillipou et al, 2015 ) and clusters' increase of serotonergic and dopaminergic bindings (e.g., Kontis and Theochari, 2012 ; Kaye et al, 2013 ; Riva, 2016 ), particularly in right frontal-temporal regions (Bailer et al, 2007 ; Galusca et al, 2008 ).…”

The neuropharmacology of sleep paralysis hallucinations: serotonin 2A activation and a novel therapeutic drug

“…The serotonin receptors activated by serotonin—mediating both excitatory and inhibitory neurotransmission—include seven major subtypes, namely 5-HT 1–7 . Moreover, 5-HT 1 receptors include 5-HT 1A , 5-HT 1B , and 5-HT 1D ; also, 5-HT 2 receptors include 5-HT 2A , 5-HT 2B , and 5-HT 2C subtypes (e.g., Riva 2016 ; for a review, see Saulin et al 2012 ).…”