Metabotropic glutamate receptor 5 in bulimia nervosa

Abstract

Bulimia nervosa (BN) shares central features with substance-related and addictive disorders. The metabotropic glutamate receptor subtype 5 (mGlu5) plays an important role in addiction. Based on similarities between binge eating and substance-related and addictive disorders, we investigated mGlu5 in vivo in 15 female subjects with BN and 15 matched controls. We measured mGlu5 distribution volume ratio (DVR) with positron emission tomography (PET) using [11 C]ABP688. In BN mGlu5 DVR was higher in the anterior cingulate cortex (ACC), subgenual prefrontal cortex, and straight gyrus (p < 0.05). In BN, higher mGlu5 DVR in various brain regions, including ACC, pallidum, putamen, and caudate, positively correlated with "maturity fears" as assessed using the Eating Disorder Inventory-2 (p < 0.05). In BN and controls, smokers had globally decreased mGlu5 DVR. We present the first evidence for increased mGlu5 DVR in BN. Our findings suggest that pharmacological agents inhibiting mGlu5 might have a therapeutic potential in BN.

Dynamic alterations in the central glutamatergic status following food and glucose intake: in vivo multimodal assessments in humans and animal models

“…These diet-related physiological oscillations of tonic neuronal activities could become deteriorated in a diseased condition, as altered mGluR5 availability was shown to emerge in diverse neuropsychiatric disorders. 48 – 52 A murine model of neurodegenerative diseases also exhibited declines of mGluR5 radioligand binding in our recent PET experiments. 52 We therefore postulate that glucose-induced increase and fasting-induced decrease of ( E )-[ 11 C]ABP688 binding can be dysregulated at a prodromal stage of these illnesses, which might offer biological tests to assist the clinical diagnosis.…”

Negative Modulation of the Metabotropic Glutamate Receptor Type 5 as a Potential Therapeutic Strategy in Obesity and Binge-Like Eating Behavior

“…In addition, the role of mGluR5 on eating disorders was assessed by several authors ( Bradbury et al, 2005 ; Bisaga et al, 2008 ; Guardia et al, 2011 ). More recently, interesting work described the part of mGluR5, in vivo , in bulimia nervosa ( Mihov et al, 2020 ). In this study, the authors found higher distribution volume of mGluR5 in areas linked to processing emotional and cognitive information related to self-control, as anterior cingulate cortex and medial orbitofrontal cortex in individuals with bulimia ( Mihov et al, 2020 ).…”

“…More recently, interesting work described the part of mGluR5, in vivo , in bulimia nervosa ( Mihov et al, 2020 ). In this study, the authors found higher distribution volume of mGluR5 in areas linked to processing emotional and cognitive information related to self-control, as anterior cingulate cortex and medial orbitofrontal cortex in individuals with bulimia ( Mihov et al, 2020 ). Overall, our data confirm the role of mGluR5 on eating disorders and paved the way for the development of therapeutic strategies focused in the glutamatergic transmission for the treatment of this condition.…”

A Molecular Framework for Autistic Experiences: Mitochondrial Allostatic Load as A Mediator between Autism and Psychopathology

“…This underlying neuroendocrinological dysregulation is not only associated with core facets of ASC etiology, but also has direct functional implications for stress-related psychopathology. A disruption of glutamatergic and GABAergic signaling contributes to the etiology of anxiety disorders (313)(314)(315)(316), PTSD (317), eating disorders (318)(319)(320), OCD (321) and substance use disorders (SUDs) (322,323). The serotonergic, dopaminergic and noradrenergic systems are implicated in MDD, anxiety and SUDs (324)(325)(326) while serotonin is also associated with mood disorders, stress, aggression and anti-social conduct (327)(328)(329), and dopamine is thought to play a role in eating disorders (330,331), executive dysfunction and behavioral inhibition (332,333).…”