Dataset Information

RDoC-based categorization of amygdala functions and its implications in autism.

ABSTRACT: Confusion endures as to the exact role of the amygdala in relation to autism. To help resolve this we turned to the NIMH's Research Domain Criteria (RDoC) which provides a classification schema that identifies different categories of behaviors that can turn pathologic in mental health disorders, e.g. autism. While RDoC incorporates all the known neurobiological substrates for each domain, this review will focus primarily on the amygdala. We first consider the amygdala from an anatomical, historical, and developmental perspective. Next, we examine the different domains and constructs of RDoC that the amygdala is involved in: Negative Valence Systems, Positive Valence Systems, Cognitive Systems, Social Processes, and Arousal and Regulatory Systems. Then the evidence for a dysfunctional amygdala in autism is presented with a focus on alterations in development, prenatal valproic acid exposure as a model for ASD, and changes in the oxytocin system therein. Finally, a synthesis of RDoC, the amygdala, and autism is offered, emphasizing the task of disambiguation and suggestions for future research.

SUBMITTER: Hennessey T

PROVIDER: S-EPMC6250055 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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RDoC-based categorization of amygdala functions and its implications in autism.

Hennessey Thomas T Andari Elissar E Rainnie Donald G DG

Neuroscience and biobehavioral reviews 20180413

Confusion endures as to the exact role of the amygdala in relation to autism. To help resolve this we turned to the NIMH's Research Domain Criteria (RDoC) which provides a classification schema that identifies different categories of behaviors that can turn pathologic in mental health disorders, e.g. autism. While RDoC incorporates all the known neurobiological substrates for each domain, this review will focus primarily on the amygdala. We first consider the amygdala from an anatomical, histori ...[more]

PMID: 29660417

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Project description:BACKGROUND:Studies of individuals with autism spectrum disorder (ASD) have revealed a strong multigenic basis with the identification of hundreds of ASD susceptibility genes. ASD is characterized by social deficits and a range of other phenotypes, implicating complex genetics and involvement of a variety of brain regions. However, how mutations and mis-expression of select gene sets are associated with the behavioral components of ASD remains unknown. We reasoned that for genes to be associated with ASD core behaviors they must be: (1) expressed in brain regions relevant to ASD social behaviors and (2) expressed during the ASD susceptible window of brain development. METHODS:Focusing on the amygdala, a brain region whose dysfunction has been highly implicated in the social component of ASD, we mined publicly available gene expression databases to identify ASD-susceptibility genes expressed during human and mouse amygdala development. We found that a large cohort of known ASD susceptibility genes is expressed in the developing human and mouse amygdala. We further performed analysis of single-nucleus RNA-seq (snRNA-seq) data from microdissected amygdala tissue from five ASD and five control human postmortem brains ranging in age from 4 to 20?years to elucidate cell type specificity of amygdala-expressed genes and their dysregulation in ASD. RESULTS:Our analyses revealed that of the high-ranking ASD susceptibility genes, 80 are expressed in both human and mouse amygdala during fetal to early postnatal stages of development. Our human snRNA-seq analyses revealed cohorts of genes with altered expression in the ASD amygdala postnatally, especially within excitatory neurons, with dysregulated expression of seven genes predicted from our datamining pipeline. LIMITATIONS:We were limited by the ages for which we were able to obtain human tissue; therefore, the results from our datamining pipeline approach will require validation, to the extent possible, in human tissue from earlier developmental stages. CONCLUSIONS:Our pipeline narrows down the number of amygdala-expressed genes possibly involved in the social pathophysiology of ASD. Our human single-nucleus gene expression analyses revealed that ASD is characterized by changes in gene expression in specific cell types in the early postnatal amygdala.

Dataset Information

RDoC-based categorization of amygdala functions and its implications in autism.

Publications

RDoC-based categorization of amygdala functions and its implications in autism.

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