Autism severity as a predictor of inattention and impulsivity in toddlers

Tureck, Kim; Matson, Johnny L.; Cervantes, Paige E.; Turygin, Nicole

doi:10.3109/17518423.2013.807884

Cited by 16 publications

(7 citation statements)

References 56 publications

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“…Work in atypically developing toddlers aged 18–37 months suggested ASD symptom severity was positively and significantly associated with inattention/impulsivity (Tureck et al 2013). Follow-up studies of educational attainment for children with combined ASD and ADHD symptoms are needed to determine the impact of such symptoms on academic achievement and other crucial outcomes.…”

Section: Discussionmentioning

confidence: 99%

Inattention and hyperactivity in association with autism spectrum disorders in the CHARGE study

Lyall

Schweitzer

Schmidt

et al. 2017

Research in Autism Spectrum Disorders

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Background Attention deficits in young children with autism spectrum disorder (ASD) are not well understood. This study sought to determine: 1) the prevalence of ADHD symptoms in young children with ASD, typical development (TD), and developmental delay (DD) and 2) the association between ADHD symptoms and cognitive and behavioral functioning in children with ASD. Method ADHD symptoms, defined according to Aberrant Behavior Checklist (ABC) hyperactivity subscale scores, were compared across children aged 2–5 from a large case-control study with ASD (n=548), TD (n=423), and DD (n=180). Inattention and hyperactivity items within this subscale were also explored. Within the ASD group, linear and logistic regression were used to examine how ADHD symptoms were associated with cognition as assessed by the Mullen Scales of Early Learning and adaptive functioning as assessed by the Vineland Adaptive Behavior Scales. Results Mean hyperactivity subscale scores were lowest in children with TD (mean=3.19), higher in children with DD (12.3), and highest in children with ASD (18.2; between-group p<0.001). Among children with ASD, significant associations were observed with higher ADHD symptoms and poorer adaptive and cognitive functioning (adjusted beta for hyperactivity score in association with: Vineland composite = −5.63, p=0.0005; Mullen visual reception scale = −2.94, p=0.02; for the highest vs. lowest quartile of hyperactivity score, odds of lowest quintile of these scores was approximately doubled). Exploratory analyses highlighted associations with inattention-related items specifically. Conclusion These results suggest ADHD symptoms may play a key role in the functioning of young children with ASD.

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Section: Discussionmentioning

confidence: 99%

Inattention and hyperactivity in association with autism spectrum disorders in the CHARGE study

Lyall

Schweitzer

Schmidt

et al. 2017

Research in Autism Spectrum Disorders

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“… 25 Consistently, a study by Gordon et al 26 demonstrated that genetic variation in the dopamine transporter (DAT) impacts cross-network connectivity that correlates with measures of impulsivity and inattention, two features of both ASD and ADHD. 27 These data underscore the significance of determining the molecular mechanisms underlying impairments within the dopaminergic system associated with ASD and related disorders with the intent to further define the etiology of this devastating disease.…”

Section: Introductionmentioning

confidence: 95%

SLC6A3 coding variant Ala559Val found in two autism probands alters dopamine transporter function and trafficking

et al. 2014

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Emerging evidence associates dysfunction in the dopamine (DA) transporter (DAT) with the pathophysiology of autism spectrum disorder (ASD). The human DAT (hDAT; SLC6A3) rare variant with an Ala to Val substitution at amino acid 559 (hDAT A559V) was previously reported in individuals with bipolar disorder or attention-deficit hyperactivity disorder (ADHD). We have demonstrated that this variant is hyper-phosphorylated at the amino (N)-terminal serine (Ser) residues and promotes an anomalous DA efflux phenotype. Here, we report the novel identification of hDAT A559V in two unrelated ASD subjects and provide the first mechanistic description of its impaired trafficking phenotype. DAT surface expression is dynamically regulated by DAT substrates including the psychostimulant amphetamine (AMPH), which causes hDAT trafficking away from the plasma membrane. The integrity of DAT trafficking directly impacts DA transport capacity and therefore dopaminergic neurotransmission. Here, we show that hDAT A559V is resistant to AMPH-induced cell surface redistribution. This unique trafficking phenotype is conferred by altered protein kinase C β (PKCβ) activity. Cells expressing hDAT A559V exhibit constitutively elevated PKCβ activity, inhibition of which restores the AMPH-induced hDAT A559V membrane redistribution. Mechanistically, we link the inability of hDAT A559V to traffic in response to AMPH to the phosphorylation of the five most distal DAT N-terminal Ser. Mutation of these N-terminal Ser to Ala restores AMPH-induced trafficking. Furthermore, hDAT A559V has a diminished ability to transport AMPH, and therefore lacks AMPH-induced DA efflux. Pharmacological inhibition of PKCβ or Ser to Ala substitution in the hDAT A559V background restores AMPH-induced DA efflux while promoting intracellular AMPH accumulation. Although hDAT A559V is a rare variant, it has been found in multiple probands with neuropsychiatric disorders associated with imbalances in DA neurotransmission, including ADHD, bipolar disorder, and now ASD. These findings provide valuable insight into a new cellular phenotype (altered hDAT trafficking) supporting dysregulated DA function in these disorders. They also provide a novel potential target (PKCβ) for therapeutic interventions in individuals with ASD.

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“…Level of infant autism features was positively correlated with internalizing symptoms, but unrelated to externalizing symptoms. The latter nonsignificant association might be due to the young age and limited behavioral repertoire of our sample, as a positive correlation between autism and externalizing symptoms been reported among autistic preschoolers [Tureck, Matson, Cervantes, & Turygin, 2015]. Furthermore, level of autism features was negatively correlated with temperamental surgency but unrelated to orienting/ regulation and negative affectivity; consequently, the nonsignificant interaction of AOSI Total and negative affectivity in the mediation models was not all that surprising.…”

Section: Discussionmentioning

confidence: 55%

The Role of Negative Affectivity in Concurrent Relations Between Caregiver Psychological Distress and Social‐Emotional Difficulties in Infants With Early Signs of Autism

et al. 2020

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Recent evidence suggests the link between caregiver psychological distress and offspring social‐emotional difficulties may be accounted for by offspring temperament characteristics. However, existing studies have only focused on neurotypical children; thus, the current study sought to provide an initial examination of this process among children with varying levels of early autism features. Participants included 103 infants aged 9–16 months (M = 12.39, SD = 1.97; 68% male) and their primary caregiver (96% mothers) referred to a larger study by community healthcare professionals. We utilized caregiver‐reported measures of psychological distress (Depression Anxiety Stress Scales), infant temperament (Infant Behavior Questionnaire‐Revised) and internalizing and externalizing symptoms (Infant‐Toddler Social and Emotional Assessment) and administered the Autism Observation Schedule for Infants (AOSI) at an assessment visit to quantify autism features. Infant negative affectivity was found to mediate positive concurrent relations between caregiver psychological distress and infant internalizing and externalizing symptoms, irrespective of the infants' AOSI score. While preliminary and cross‐sectional, these results replicate and extend previous findings suggesting that the pathway from caregiver psychological distress to negative affectivity to social‐emotional difficulties might also be apparent among infants with varying levels of autism features. More rigorous tests of causal effects await future longitudinal investigation. Lay Summary Offspring of caregivers experiencing psychological distress (i.e., symptoms of depression, anxiety, and/or stress) may themselves be at increased risk of poor mental health outcomes. Several previous studies conducted with neurotypical children suggest that this link from caregiver‐to‐child may be facilitated by children's temperament qualities. This study was a preliminary cross‐sectional exploration of these relationships in infants with features of autism. We found that infants' elevated negative emotions were involved in the relation between caregiver heightened psychological distress and children's mental health difficulties, consistent with neurotypical development. Autism Res 2020, 13: 1349–1357. © 2020 International Society for Autism Research, Wiley Periodicals, Inc.

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Autism severity as a predictor of inattention and impulsivity in toddlers

Abstract: ASD symptom severity predicts rates of ADHD symptoms in atypically developing toddlers. The implications of these findings are discussed in the context of other research.

Cited by 16 publications

References 56 publications

Inattention and hyperactivity in association with autism spectrum disorders in the CHARGE study

Inattention and hyperactivity in association with autism spectrum disorders in the CHARGE study

SLC6A3 coding variant Ala559Val found in two autism probands alters dopamine transporter function and trafficking

The Role of Negative Affectivity in Concurrent Relations Between Caregiver Psychological Distress and Social‐Emotional Difficulties in Infants With Early Signs of Autism

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