Not to Be Overshadowed or Overlooked: Functional Impairments Associated With Comorbid Anxiety Disorders in Youth With ASD

Kerns, Connor M.; Kendall, Philip C.; Zickgraf, Hana F.; Franklin, Martin E.; Miller, Judith S.; Herrington, John D.

doi:10.1016/j.beth.2014.03.005

Cited by 161 publications

(114 citation statements)

References 65 publications

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“…To study this "three hit" hypothesis of autism (16), we used the Cntnap2 mouse model (17) in which we induced MIA in half of the subjects and tested Cntnap2 −/− and Cntnap2 +/+ male and female littermates on social behavior [ultrasonic vocalizations (USVs) during a maternal separation paradigm and social recognition in adulthood], one of the hallmarks of ASD. Additionally, we investigated motor activity and anxiety-like behavior, as hyperactivity and anxiety are common comorbidities in individuals diagnosed with an ASD (18,19).In the same animals, we measured mRNAs related to the stress response-regulating neuropeptide corticotropin-releasing hormone (20, 21) (CRH). At least in primates, stress-induced maternal hypothalamic-pituitary-adrenal (HPA)-axis activation increases CRH levels in the placenta, which leads to increased circulating CRH in the fetus, which can affect the developing Significance Autism spectrum disorders (ASDs) comprise a heterogeneous set of neurodevelopmental disorders.…”

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confidence: 99%

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confidence: 99%

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Sex-specific gene–environment interactions underlying ASD-like behaviors

Schaafsma

Gagnidze

Reyes

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

102

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The male bias in the incidence of autism spectrum disorders (ASDs) is one of the most notable characteristics of this group of neurodevelopmental disorders. The etiology of this sex bias is far from known, but pivotal for understanding the etiology of ASDs in general. Here we investigate whether a "three-hit" (genetic load × environmental factor × sex) theory of autism may help explain the male predominance. We found that LPS-induced maternal immune activation caused male-specific deficits in certain social responses in the contactin-associated protein-like 2 (Cntnap2) mouse model for ASD. The three "hits" had cumulative effects on ultrasonic vocalizations at postnatal day 3. Hits synergistically affected social recognition in adulthood: only mice exposed to all three hits showed deficits in this aspect of social behavior. In brains of the same mice we found a significant three-way interaction on corticotropin-releasing hormone receptor-1 (Crhr1) gene expression, in the left hippocampus specifically, which co-occurred with epigenetic alterations in histone H3 N-terminal lysine 4 trimethylation (H3K4me3) over the Crhr1 promoter. Although it is highly likely that multiple (synergistic) interactions may be at work, change in the expression of genes in the hypothalamic-pituitary-adrenal/ stress system (e.g., Crhr1) is one of them. The data provide proof-of-principle that genetic and environmental factors interact to cause sex-specific effects that may help explain the male bias in ASD incidence.maternal immune activation | prenatal stress | sex differences | Cntnap2 | autism A utism spectrum disorders (ASDs) comprise a heterogeneous group of neurodevelopmental disorders. The core symptoms of ASD are deficits in social communication and social interactions (Diagnostic and Statistical Manual of Mental Disorders V) and one of the most noticeable biological constants in this group of disorders is the sex difference: ∼80% of the children diagnosed with an ASD are boys (1). Many genes have been implicated in the etiologies underlying ASD in humans and ASD-like behavior in animal models. Some of these genes are located on the sex chromosomes and many of these genes may be able to affect other sex-chromosomal genes or may otherwise indirectly lead to sex-specific effects (reviewed in ref.2). However, it seems unlikely that these genes can account for the full sex bias in incidence and it is becoming increasingly clear that environmental factors play a very important role as well (3), and that these factors can interact with one another (2, 4). Moreover, prenatal testosterone (an indirect genetic factor) affects human behavior (5, 6) and may increase the risk to develop an ASD (7).Although today it is commonly proposed that many neurodevelopmental disorders result from interactions between "nature" and "nurture," studies investigating the gene-environment interaction in the development of ASD are scarce.In this study we tested whether an interaction between an ASD-related genetic mutation and an environmental factor may be a...

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confidence: 99%

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confidence: 99%

Sex-specific gene–environment interactions underlying ASD-like behaviors

Schaafsma

Gagnidze

Reyes

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

102

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“…[1][2][3] A recent meta-analysis indicated that 39.6% of youth with ASD have at least 1 anxiety disorder. 4 Despite this burden, youth with ASD face barriers in accessing timely and appropriate mental health treatment, which places increasing demands on primary care providers to manage anxiety in these children.…”

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confidence: 99%

Assessment and Treatment of Anxiety in Youth With Autism Spectrum Disorders

et al. 2016

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OBJECTIVES: Anxiety is one of the most prevalent co-occurring symptoms in youth with autism spectrum disorder (ASD). The assessment and treatment recommendations proposed here are intended to help primary care providers with the assessment and treatment of anxiety in ASD. METHODS: The Autism Speaks Autism Treatment Network/Autism Intervention Research on Physical Health Anxiety Workgroup, a multidisciplinary team of clinicians and researchers with expertise in ASD, developed the clinical recommendations. The recommendations were based on available scientific evidence regarding anxiety treatments, both in youth with ASD and typically developing youth, and clinical consensus of the workgroup where data were lacking. RESULTS: Assessment of anxiety requires a systematic approach to evaluating symptoms and potential contributing factors across various developmental levels. Treatment recommendations include psychoeducation, coordination of care, and modified cognitive-behavioral therapy, particularly for children and adolescents with high-functioning ASD. Due to the limited evidence base in ASD, medications for anxiety should be prescribed cautiously with close monitoring of potential benefits and side effects. CONCLUSIONS: Assessment and treatment of clinical anxiety in youth with ASD require a standardized approach to improve outcomes for youth with ASD. Although this approach provides a framework for clinicians, clinical judgment is recommended when making decisions about individual patients.

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“…Research has shown that communication deficits and level of intellectual functioning can influence the expression of anxiety behaviors in those with ASD (Grondhuis & Aman, 2012). Additionally, individuals with comorbid ASD and an anxiety disorder display more self-injurious behaviors and depressive symptoms (Kerns et al, 2015). While there is no universal profile of this comorbid combination, much of the literature suggests that there are notable qualitative differences between the social and communicative impairments of the two disorders as well as the function the symptom serves.…”

Section: Statistical Manual Of Mental Disorders Fourth Edition Textmentioning

confidence: 92%

“…Anxiety disorders and ASD are arguably the most commonly co-occurring disorders, especially among those with higher functioning ASD (Kerns, Kendall, Zickgraf, Franklin, Miller, & Herrington, 2015). Research has shown that communication deficits and level of intellectual functioning can influence the expression of anxiety behaviors in those with ASD (Grondhuis & Aman, 2012).…”

Section: Statistical Manual Of Mental Disorders Fourth Edition Textmentioning

confidence: 99%

An Evaluation of Measures Associated with the Differential Diagnosis of Autism Spectrum Disorder Within a University-Based Clinic Sample

Torigoe-Lai¹

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Not to Be Overshadowed or Overlooked: Functional Impairments Associated With Comorbid Anxiety Disorders in Youth With ASD

Cited by 161 publications

References 65 publications

Sex-specific gene–environment interactions underlying ASD-like behaviors

Sex-specific gene–environment interactions underlying ASD-like behaviors

Assessment and Treatment of Anxiety in Youth With Autism Spectrum Disorders

An Evaluation of Measures Associated with the Differential Diagnosis of Autism Spectrum Disorder Within a University-Based Clinic Sample

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