<i>PAC1R</i> Genotype to Phenotype Correlations in Autism Spectrum Disorder

Goodrich, Meredith; Armour, Anna Chelsea; Panchapakesan, Karuna; You, Xiaozhen; Devaney, Joseph; Knoblach, Susan M.; Sullivan, Catherine; Herrero, María Jesús Presentación; Gupta, Abha R.; Vaidya, Chandan J.; Kenworthy, Lauren; Corbin, Joshua G.

doi:10.1002/aur.2051

Cited by 4 publications

(5 citation statements)

References 54 publications

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“…Consistent with this critical role in information processing, the amygdala has emerged as a key site of dysfunction in ASD as evidenced by cellular, structural, and functional imaging studies [22,23,[41][42][43][44]. For example, fMRI studies reveal altered amygdala activation in face recognition and/or in response to social or emotional cues in individuals with ASD [45][46][47][48]. Thus, the amygdala is one of a likely handful of brain regions that define the "where" in ASD.…”

Section: Discussionmentioning

confidence: 97%

“…Our finding of the majority of dysregulated genes to be in excitatory neurons is particularly intriguing. Excitatory/inhibitory imbalance in neuronal communication in ASD is well supported by studies in animal [48][49][50] and in vitro models derived from human tissue [55]. Though whether this imbalance is causal or compensatory remains to be resolved.…”

Section: Discussionmentioning

confidence: 97%

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Identification of amygdala-expressed genes associated with autism spectrum disorder

et al. 2020

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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 amygdalaexpressed 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.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 97%

Identification of amygdala-expressed genes associated with autism spectrum disorder

et al. 2020

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“…Some MIA associations with genes detected in the present study were also established at the DNA variant level. For example, single nucleotide polymorphism in or near ADCYAP receptor type I (ADCYAP1R1), NPS receptor (NPSR1), estrogen receptor 1 (ESR1), SRSF protein kinase 2 (SRPK2) genes have been associated with autism spectrum disorders, Alzheimer's disease behavioral traits, anxiety, impulsivity and attention deficit-related traits [21,[54][55][56][57][58][59].…”

Section: Transcript Isoform Characterization Of Maternal Immune Activation Effectsmentioning

confidence: 99%

“…The amygdala and hippocampus brain regions are part of the limbic system and modulate behavior, emotion and memory. Amygdala and hippocampus processes have been associated with social behavior [18,19], and disruption of the amygdala has been proposed to underlie autism spectrum dis-orders [20,21]. Despite the established association between behavior disorders and MIA and between behavior disorders and neuropeptide systems, disruptions of the neuropeptide systems associated by MIA in the hippocampus and amygdala are only partially understood.…”

Section: Introductionmentioning

confidence: 99%

Effects of maternal immune activation in porcine transcript isoforms of neuropeptide and receptor genes

Southey¹,

Zhang²,

Keever³

et al. 2021

J. Integr. Neurosci.

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The prolonged effects of maternal immune activation in response stressors during gestation on the offspring’s molecular pathways after birth are beginning to be understood. An association between maternal immune activation and neurodevelopmental and behavior disorders such as autism and schizophrenia spectrum disorders has been detected in long-term gene dysregulation. The incidence of alternative splicing among neuropeptides and neuropeptide receptor genes, critical cell-cell signaling molecules, associated with behavior may compromise the replicability of reported maternal immune activation effects at the gene level. This study aims to advance the understanding of the effect of maternal immune activation on transcript isoforms of the neuropeptide system (including neuropeptide, receptor and connecting pathway genes) underlying behavior disorders later in life. Recognizing the wide range of bioactive peptides and functional receptors stemming from alternative splicing, we studied the effects of maternal immune activation at the transcript isoform level on the hippocampus and amygdala of three-week-old pigs exposed to maternal immune activation due to viral infection during gestation. In the hippocampus and amygdala, 29 and 9 transcript isoforms, respectively, had maternal immune activation effects (P-value < 0.01). We demonstrated that the study of the effect of maternal immune activation on neuropeptide systems at the isoform level is necessary to expose opposite effects among transcript isoforms from the same gene. Genes were maternal immune activation effects have also been associated with neurodevelopmental and behavior disorders. The characterization of maternal immune activation effects at the transcript isoform level advances the understanding of neurodevelopmental disorders and identifies precise therapeutic targets.

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“…There are several scientific studies that contributed to the autism research reveal the relationship between theories of emotion and emotional reciprocity state of the individual with ASD. [70][71][72][73] In this category, we critically analyzed the famous theories such as James-Lange theory, Cannon-Bard theory, Schachter-Singer theory, cognitive appraisal theory, and facial feedback hypothesis and how it is not connected to the emotional regulation of individual with ASD.…”

Section: Autism and Theories Of Emotionsmentioning

confidence: 99%

Autism and Emotion: A Narrative Review

Kanagaraj

Devishrree²,

Swetha³

et al. 2021

Journal of Health and Allied Sciences NU

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Autism spectrum disorder (ASD) includes a variety of childhood-onset and lifelong neurodevelopmental condition with an enduring impact on multiple domains of functioning characterized by persistent deficits in social communication, restricted and repetitive behavior interest, and activities. They often find it hard to recognize and control emotions but their emotional expression can be improved by various intervention techniques that in turn can help them understand and respond more appropriately to other people. Problems in the area on emotional reciprocity among individual with ASD involve recognizing, understanding, expressing, and regulating emotions. Their ability in emotional reciprocity is often improved with a comprehensive treatment approach, especially by focused emotional enhancement intervention. In this review, we followed the standard IMRAD (Introduction, Methods, Results, and Discussion) structure to critically examine the condition of autism and its relation with genetic mechanism, and how theories of emotion and theory of mind associated with persons with ASD, some of the widely used assessment tools and future research direction in the emotional development of individuals diagnosed with ASD by using the narrative review method. Records collected through research databases such as Scopus, PubMed, Web of Science, Medline, EBSCO and published books with ISBN (International Standard Book Number), and published test manuals were evaluated in-depth and summarized based on the subtopic of the proposed title. A critical theoretical analysis of the genetic mechanism of emotions, theories of emotions, and theory of mind was explained in connection with ASD.

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PAC1R Genotype to Phenotype Correlations in Autism Spectrum Disorder

Cited by 4 publications

References 54 publications

Identification of amygdala-expressed genes associated with autism spectrum disorder

Identification of amygdala-expressed genes associated with autism spectrum disorder

Effects of maternal immune activation in porcine transcript isoforms of neuropeptide and receptor genes

Autism and Emotion: A Narrative Review

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