Reward system dysfunction in autism spectrum disorders

Kohls, Gregor; Schulte‐Rüther, Martin; Nehrkorn, Barbara; Müller, Kristin; Fink, Gereon R.; Kamp‐Becker, Inge; Herpertz‐Dahlmann, Beate; Schultz, Robert T.; Konrad, Kerstin

doi:10.1093/scan/nss033

Cited by 228 publications

(251 citation statements)

References 39 publications

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“…Abnormal basal ganglia function has been proposed as a key feature of autism (Di Martino et al, 2011;Kohls et al, 2012). In this study, deficient social behavior and motor clumsiness associated with stereotypic behavior in Oprm1 À / À animals point towards ventral and dorsal striatal dysfunction.…”

Section: Mutant Mice Display Abnormal Striatal Synapses and Modified mentioning

confidence: 61%

Autistic-Like Syndrome in Mu Opioid Receptor Null Mice is Relieved by Facilitated mGluR4 Activity

Becker

Clesse

Spiegelhalter

et al. 2014

Neuropsychopharmacol

106

161

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The etiology of Autism Spectrum Disorders (ASDs) remains largely unknown. Identifying vulnerability genes for autism represents a major challenge in the field and allows the development of animal models for translational research. Mice lacking the mu opioid receptor gene (Oprm1 À / À ) were recently proposed as a monogenic mouse model of autism, based on severe deficits in social behavior and communication skills. We confirm this hypothesis by showing that adult Oprm1 À / À animals recapitulate core and multiple comorbid behavioral symptoms of autism and also display anatomical, neurochemical, and genetic landmarks of the disease. Chronic facilitation of mGluR4 signaling, which we identified as a novel pharmacological target in ASDs in these mice, was more efficient in alleviating behavioral deficits than the reference molecule risperidone. Altogether, our data provide first evidence that disrupted mu opioid receptor signaling is sufficient to trigger a comprehensive autistic syndrome, maybe through blunted social reward processes, and this mouse model opens promising avenues for therapeutic innovation.

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Section: Mutant Mice Display Abnormal Striatal Synapses and Modified mentioning

confidence: 61%

Autistic-Like Syndrome in Mu Opioid Receptor Null Mice is Relieved by Facilitated mGluR4 Activity

Becker

Clesse

Spiegelhalter

et al. 2014

Neuropsychopharmacol

106

161

View full text Add to dashboard Cite

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“…These studies have primarily contrasted social reward stimuli (ie, faces) to monetary reward in individuals with ASD and neurotypical controls. Compared with controls, children, adolescents, and adults with ASD show aberrant activity during monetary reward conditions in the anterior cingulate, frontal cortex, and ventral striatum Kohls et al, 2013;Schmitz et al, 2008;. During positive social reward conditions (ie, smiling faces), ASD participants show reduced striatal activity in comparison with controls (Delmonte et al, 2012;.…”

Section: Reward Processingmentioning

confidence: 98%

Neural Signatures of Autism Spectrum Disorders: Insights into Brain Network Dynamics

Hernandez

Rudie

Green

et al. 2014

Neuropsychopharmacol

115

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Neuroimaging investigations of autism spectrum disorders (ASDs) have advanced our understanding of atypical brain function and structure, and have recently converged on a model of altered network-level connectivity. Traditional task-based functional magnetic resonance imaging (MRI) and volume-based structural MRI studies have identified widespread atypicalities in brain regions involved in social behavior and other core ASD-related behavioral deficits. More recent advances in MR-neuroimaging methods allow for quantification of brain connectivity using diffusion tensor imaging, functional connectivity, and graph theoretic methods. These newer techniques have moved the field toward a systems-level understanding of ASD etiology, integrating functional and structural measures across distal brain regions. Neuroimaging findings in ASD as a whole have been mixed and at times contradictory, likely due to the vast genetic and phenotypic heterogeneity characteristic of the disorder. Future longitudinal studies of brain development will be crucial to yield insights into mechanisms of disease etiology in ASD sub-populations. Advances in neuroimaging methods and large-scale collaborations will also allow for an integrated approach linking neuroimaging, genetics, and phenotypic data.

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“…An early study using a continuous performance task found no behavioral evidence for group differences in trials with monetary rewards versus nonrewards [78]. Similarly, comparable behavioral performance in a reward-processing task using a variant of the go-no-go task was found in children and adults with and without ASD [79,80]. In contrast, using a similar task, DeMurie et al [81] demonstrated that children with ASD were slower in responding to social rewards than monetary rewards, but this was not specific to ASD.…”

Section: Autism and Reward Systemmentioning

confidence: 99%

Endocannabinoid Signaling in Autism

et al. 2015

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Autism spectrum disorder (ASD) is a complex behavioral condition with onset during early childhood and a lifelong course in the vast majority of cases. To date, no behavioral, genetic, brain imaging, or electrophysiological test can specifically validate a clinical diagnosis of ASD. However, these medical procedures are often implemented in order to screen for syndromic forms of the disorder (i.e., autism comorbid with known medical conditions). In the last 25 years a good deal of information has been accumulated on the main components of the Bendocannabinoid (eCB) system^, a rather complex ensemble of lipid signals (Bendocannabinoids^), their target receptors, purported transporters, and metabolic enzymes. It has been clearly documented that eCB signaling plays a key role in many human health and disease conditions of the central nervous system, thus opening the avenue to the therapeutic exploitation of eCB-oriented drugs for the treatment of psychiatric, neurodegenerative, and neuroinflammatory disorders. Here we present a modern view of the eCB system, and alterations of its main components in human patients and animal models relevant to ASD. This review will thus provide a critical perspective necessary to explore the potential exploitation of distinct elements of eCB system as targets of innovative therapeutics against ASD.Key Words Autism spectrum disorder . endocannabinoid system . fragile X syndrome . metabolic regulation . reward system The Endocannabinoid SystemTwenty-five years after the cloning and expression of a complementary DNA that encoded a G protein-coupled receptor, named type-1 cannabinoid (CB 1 ) receptor [1], there is a good deal of information on the main components of the so-called Bendocannabinoid (eCB) system^, as well as on its role in controlling cannabinergic signaling in human health and disease [2][3][4]. Anandamide (AEA) and 2-arachidonoylglycerol (2-AG) are the most active eCBs as yet identified, although this family of bioactive lipids includes other arachidonic acid (AA) derivatives with cannabimimetic properties (i.e., noladin ether, virodhamine, N-arachidonoyldopamine, to name but a few). The classical dogma that eCBs are synthesized and released Bon demand^upon (patho)physiological stimuli has been recently revisited on the basis of unexpected evidence for intracellular reservoirs and transporters of eCBs. These new entities have been shown to drive intracellular trafficking of eCBs, adding a new dimension to the regulation of their biological activity [5]. To date, several metabolic routes have B. Chakrabarti, A. Persico and N. Battista are equal first authors.

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Reward system dysfunction in autism spectrum disorders

Cited by 228 publications

References 39 publications

Autistic-Like Syndrome in Mu Opioid Receptor Null Mice is Relieved by Facilitated mGluR4 Activity

Autistic-Like Syndrome in Mu Opioid Receptor Null Mice is Relieved by Facilitated mGluR4 Activity

Neural Signatures of Autism Spectrum Disorders: Insights into Brain Network Dynamics

Endocannabinoid Signaling in Autism

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