Ashley J. Harrison

Attentional Biases in Currently Depressed Children: An Eye-Tracking Study of Biases in Sustained Attention to Emotional Stimuli

Cognitive theories state attentional biases contribute to the development and maintenance of depression. Like depressed adults, there is growing evidence for the presence of attentional biases to sad stimuli in depressed youth. Although the direction of this bias among children remains unclear, preliminary evidence indicates attentional avoidance of sad stimuli in children. This is the first known sudy to use eye-tracking to investigate the exact nature of attention biases among depressed children. To assess sustained attention, the current study used eye-tracking and a passive viewing task in which children viewed a series of four facial expressions (angry, happy, sad, neutral) presented simultatiously for 20 s on a computer screen. The current study compared the attentional allocation of currently depressed children (n = 19; M age = 11.21) to a group of never depressed children (n = 22; M age = 10.82). Consitent with earlier research with children, we found that children with current major or minor depression, compared to children with no history of depression, exhibited attentional avoidance of sad facial stimuil as well as some evidence for preferential attention to happy faces. This study provides additional evidence that although depressed children demonstrate mood congruent attentional biases like that observed depressed adults, the nature of these biases may reflect attentional avoidance of sad stimuli, rather than preferential attention.

Expansion of the clinical phenotype associated with mutations in activity-dependent neuroprotective protein

Activity-dependent neuroprotective protein (ADNP) is a highly conserved transcription factor comprised of nine-zinc finger domains and a homeobox domain.1 ,2 It is highly expressed prenatally during critical stages of embryonic brain development.3 Knockout (KO) mouse embryos demonstrate severe neurodevelopmental morphological profiles.4 Although the ADNP KO is lethal, heterozygous embryos demonstrate typical embryogenesis yet display a neurodevelopmental delay phenotype including decreased neuronal survival.3 ,5 Exome sequencing in the Simons Simplex Collection autism dataset identified ADNP mutations as a putative autism gene candidate.6 ,7 Helsmoortel et al 8 recently reported 10 individuals with autism spectrum disorder (ASD) and mutations in exon 5 of the ADNP gene, nine of which were confirmed de novo. These patients also exhibited intellectual disability (ID) and dysmorphic features such as a prominent forehead. Mutations in the ADNP gene are estimated to be present in at least 0.17% of ASD cases. The current report further expands the ADNP phenotype to include abnormalities in the developing visual system (such as eye movement abnormalities and cortical visual impairment). We advise appropriate screening of eye movement and visual symptoms by clinicians in patients who have mutations in ADNP . The 6-year-old patient was the first child born to healthy non-consanguineous parents. Pregnancy was notable for placenta previa and early dilation and effacement of the cervix 3 weeks prior to delivery. The patient was born at 40 weeks via C-section secondary to failure to progress and maternal (i.e. maternal hypertension) hypertension weighing 6 pounds 14 ounces. She had a short stay in the neonatal intensive care unit (NICU) for breathe holding and feeding problems. She was also hospitalised at 6 weeks for an acute life-threatening event of multiple cyanotic episodes thought to be due to breath holding. Our patient has been diagnosed with hypotonia and mixed developmental …

Executive Function in Probands With Autism With Average IQ and Their Unaffected First-Degree Relatives

OBJECTIVE This study aimed to characterize executive function (EF) in pedigrees of children with autism spectrum disorder (ASD) and average IQ. The authors examined the hypothesis that deficits in EF relate to lower levels of adaptive functioning, and they assessed evidence for a cognitive extended phenotype in unaffected relatives in a large, well-characterized sample. METHOD Proband EF was assessed by parent-report questionnaires (Behavior Rating Inventory of Executive Functioning [BRIEF], n = 109) and child neuropsychological tests (Delis-Kaplan Executive Functioning System [D-KEFS], n = 35). EF also was examined in parents (D-KEFS, n = 335) and unaffected siblings (BRIEF, n = 114; D-KEFS, n = 57). Adaptive functioning was assessed by the Vineland Adaptive Behavior Scales-II (n = 155). All data were obtained from the Autism Consortium Clinical Genetics Database. RESULTS Individuals with ASD showed important EF weaknesses. Multiple regression analyses showed that parent-reported EF deficits were related to profound decreases in adaptive functioning even after controlling for age, IQ, and severity of ASD symptoms. Parent-reported EF also was related to adaptive skills in preschoolers. First-degree unaffected relatives did not demonstrate difficulties with EF compared with normative data. CONCLUSION In this study, EF impairments do not appear to relate to broad familial risk factors for ASD but may be associated with factors relevant to the expression of ASD in probands. Results support the benefits of EF assessment as a way to identify potential therapeutic targets that could lead to improved adaptive behavior in children with ASD and average IQ.

An international review of autism knowledge assessment measures

Autism spectrum disorder-specific knowledge deficits contribute to current disparities in the timing and quality of autism spectrum disorder services throughout the United States and globally. This study conducted a systematic review of Western and International literature to examine measures used to assess autism spectrum disorder knowledge. This review identified 44 unique autism spectrum disorder knowledge measures across 67 studies conducted in 21 countries. Measures used in each study were evaluated in terms of psychometric strength. Of the 67 studies reviewed, only 7% were rated as using a measure with strong psychometric support compared to 45% that were rated as using a measure with no reported psychometric support. Additionally, we examined content overlap and subdomains of autism spectrum disorder knowledge assessed (e.g. etiology, symptoms) and cross-cultural adaptation procedures utilized in the field. Based on these findings, the need for a cross-culturally valid and psychometrically sound measure of autism spectrum disorder knowledge is discussed and recommendations for improving current assessment methods are presented, including suggestions for measure subdomains.

Genetic Variation in the Oxytocin Receptor Gene is Associated With a Social Phenotype in Autism Spectrum Disorders

Oxytocin regulates social behavior in animal models. Research supports an association between genetic variation in the oxytocin receptor gene (OXTR) and autism spectrum disorders (ASD). In this study, we examine the association between the OXTR gene and a specific social phenotype within ASD. This genotype–phenotype investigation may provide insight into how OXTR conveys risk for social impairment. The current study investigated 10 SNPS in the OXTR gene that have been previously shown to be associated with ASD. We examine the association of these SNPs with both a social phenotype and a repetitive behavior phenotype comprised of behaviors commonly impaired in ASD in the Simons simplex collection (SSC). Using a large sample to examine the association between OXTR and ASD (n = range: 485–1002), we find evidence to support a relation between two OXTR SNPs and the examined social phenotype among children diagnosed with ASD. Greater impairment on the social responsiveness scale standardized total score and on several subdomains was observed among individuals with one or more copies of the minor frequency allele in both rs7632287 and rs237884. Linkage disequilibrium (LD) mapping suggests that these two SNPs are in LD within and overlapping the 3′ untranslated region (3′‐UTR) of the OXTR gene. These two SNPs were also associated with greater impairment on the repetitive behavior scale. Results of this study indicate that social impairment and repetitive behaviors in ASD are associated with genomic variation in the 3′UTR of the OXTR gene. These variants may be linked to an allele that alters stability of the mRNA message although further work is necessary to test this hypothesis.

Eye tracking indices of attentional bias in children of depressed mothers: Polygenic influences help to clarify previous mixed findings

Information-processing biases may contribute to the intergenerational transmission of depression. There is growing evidence that children of depressed mothers exhibit attentional biases for sad faces. However, findings are mixed as to whether this bias reflects preferential attention toward, versus attentional avoidance of, sad faces, suggesting the presence of unmeasured moderators. To address these mixed findings, we focused on the potential moderating role of genes associated with hypothalamic-pituitary-adrenal axis reactivity. Participants included children (8-14 years old) of mothers with (n = 81) and without (n = 81) a history of depression. Eye movements were recorded while children passively viewed arrays of angry, happy, sad, and neutral faces. DNA was obtained from buccal cells. Children of depressed mothers exhibited more sustained attention to sad faces than did children of nondepressed mothers. However, it is important that this relation was moderated by childrens genotype. Specifically, children of depressed mothers who carried reactive genotypes across the corticotropin-releasing hormone type 1 receptor (CHRH1) TAT haplotype and FK506 binding protein 5 (FKBP5) rs1360780 (but not the solute carrier family C6 member 4 [SLC6A4] of the serotonin transporter linked polymorphic region [5-HTTLPR]) exhibited less sustained attention to sad faces and more sustained attention to happy faces. These findings highlight the role played by specific genetic influences and suggest that previous mixed findings may have been due to genetic heterogeneity across the samples.

Observation-centered approach to ASD assessment in Tanzania.

Abstract In many lower-income countries, there is a paucity of assessment services for autism spectrum disorders (ASD)., Guidelines will be provided for conducting cross-cultural assessments in the context of limited validated resources in Tanzania. By examining behavioral, social, and adaptive differences we were able to provide differential diagnostic evaluations aligning with best practice standards for 41 children in Tanzania age 2-21 years. We describe the utility of a flexible, behavioral observation instrument, the Childhood Autism Rating Scales, Second Edition (CARS2), to gather diagnostic information in a culturally sensitive manner. We observed that the ASD group was characterized by significantly higher scores on the CARS2, F  =  21.09, p < .001, η(2)  =  .37, than the general delay comparison group. Additional recommendations are provided for making cultural adaptations to current assessment instruments for use in a country without normed instruments, such as Tanzania.

Development of a Brief Intervention to Improve Knowledge of Autism and Behavioral Strategies Among Parents in Tanzania.

Despite the global presence of autism spectrum disorder (ASD), a paucity of treatment services exists in Tanzania and other low- and middle-income countries. The effect of delayed or low-quality treatments is enduring and contributes to lifelong variability in ASD-related functional impairments. Service disparities in Tanzania derive in part from a widespread lack of national ASD knowledge. Historically, in Western countries, parents have played a major role in increasing ASD awareness, advancing research, and encouraging empirically supported treatments. In the absence of established treatment services, parents of children with ASD have also learned to implement behavioral interventions to reduce the widening skills gaps. This article describes the development of an intervention designed to inform parents in Tanzania about ASD and empirically supported behavioral strategies. Preliminary data, collected from a clinical implementation with 29 Tanzanian families of children diagnosed with ASD or general developmental delays, support the initial feasibility and acceptability of this intervention. This brief intervention may help to ameliorate treatment disparities due to insufficient regional knowledge, language barriers, or limited service availability and may help improve functional outcomes among Tanzanian children with ASD.

Examining the Role of Race, Ethnicity, and Gender on Social and Behavioral Ratings within the Autism Diagnostic Observation Schedule.

The Autism Diagnostic Observation Schedule (ADOS) is widely used to assess symptoms of autism spectrum disorder (ASD). Given well-documented differences in social behaviors across cultures, this study examined whether item-level biases exist in ADOS scores across sociodemographic groups (race, ethnicity, and gender). We examined a subset of ten ADOS items among participants (N = 2458). Holding level of overall ADOS behavioral symptoms constant, we found significant item level bias (measurement noninvariance) for race and ethnicity on three ADOS items. Item-level bias was not apparent across gender. Although the magnitude of bias was small, our findings highlight the need to reevaluate norms and operational definitions used in assessments to increase ASD diagnostic accuracy among culturally-diverse groups.

Cognitive and adaptive correlates of an ADOS-derived joint attention composite

Joint attention skills have been shown to predict language outcomes in children with autism spectrum disorder (ASD). Less is known about the relationship between joint attention (JA) abilities in children with ASD and cognitive and adaptive abilities. In the current study, a subset of items from the Autism Diagnostic Observation Schedule (ADOS), designed to quantify JA abilities, were used to investigate social attention among an unusually large cross-sectional sample of children with ASD (n = 1061). An examination of the association between JA and a range of functional correlates (cognitive and adaptive) revealed JA was significantly related to verbal (VIQ) and non-verbal (NVIQ) cognitive ability as well as all domains of adaptive functioning (socialization, communication, and daily living skills). Additional analyses examined the degree to which the relation between adaptive abilities (socialization, communication, and daily living skills) and JA was maintained after taking into account the potentially mediating role of verbal and nonverbal cognitive ability. Results revealed that VIQ fully mediated the relation between JA and adaptive functioning, whereas the relation between these adaptive variables and JA was only partially mediated by NVIQ. Moderation analyses were also conducted to examine how verbal and non-verbal cognitive ability and gender impacted the relation between JA and adaptive functioning. In line with research showing a relation between language and JA, this indicates that while JA is significantly related to functional outcomes, this appears to be mediated specifically through a verbal cognitive pathway.