Individuals with Autism Spectrum Disorder (ASD) exhibit difficulties in social communication and relating, as well as restricted and repetitive patterns of behaviour and atypicalities in sensory modulation (DSM-5; American Psychological Association 2013). There is a 1% prevalence rate of ASD in the general population (Baird et al. 2006
; Christensen et al. 2016
), while recurrence rates in younger siblings of children with ASD are ~10% (Constantino et al. 2010
). Prospective high-risk studies have reported that up to 20% of siblings actually meet diagnostic criteria for ASD and that there is increased ASD symptomatology among those that do not have the condition (Messinger et al. 2013
; Ozonoff et al. 2011
). Taken together, these findings suggest that there is high familial risk for ASD.
In addition to the core symptoms, individuals with ASD frequently experience co-occurring mental health difficulties, notably anxiety disorders (Simonoff et al. 2008
). Up to 80% of individuals with ASD report anxiety symptoms, which are often impairing (White et al. 2009
). Increased prevalence of anxiety is also reported in first-degree relatives of individuals with ASD (Lainhart 2009
), including young children at increased familial risk as siblings of probands with a diagnosis (Schwichtenberg et al. 2013
). Hallett et al. (2013b
) directly compared anxiety symptoms in probands with ASD and their twins, who were either typically developing (TD) or manifested aspects of the Broader Autism Phenotype (BAP), sub-clinical traits of autism in family members (Bolton et al. 1994
). The findings suggested that anxiety was most highly elevated among the ASD probands and twins with BAP.
While elevated rates of anxiety have been observed in individuals with ASD and their siblings, there is a scarcity of research examining the shared underlying neurocognitive mechanisms of the two conditions. Wood and Gadow (2010
) suggest that such investigation is highly relevant, as it is presently unclear whether the co-occurrence of ASD and anxiety represents a true comorbidity, the manifestation of two separate conditions in the same individual, or if it results from an overlap in symptom presentation and difficulties with self- and caregiver-report. One way to better understand the manifestation of anxiety within ASD is to examine whether the neurocognitive mechanisms that are associated with anxiety in non-ASD populations, such as increased attentional allocation to threat, are also present and relate to anxiety symptoms in children with ASD and their siblings.
The present study addresses the association between anxiety symptoms and attentional allocation to threat within the context of a prospective longitudinal study of children at high familial risk for ASD (due to having an older sibling with the condition). This design provides a unique opportunity to examine the cognitive correlates of anxiety in high-risk siblings who themselves meet diagnostic criteria for ASD and those who do not. This allows for the comparison of siblings with ASD and those who go on to have typical development, as well as the examination of the relationship between anxiety, attention to threat and sub-clinical traits of ASD.
Attentional Bias to Threat and Anxiety
Cognitive theories of anxiety disorders posit that highly anxious individuals may be particularly sensitive to threat-relevant information in the environment (Bar-Haim et al. 2007
). Biased processing of threat is thought to contribute to both the development and maintenance of anxiety disorders (Beck and Clark 1997
; Eysenck 1992
). This cognitive style has been demonstrated experimentally using a number of tasks that compare reaction times (RTs) to threatening and non-threatening stimuli (for review see Bar-Haim et al. 2007
). Studies using the dot-probe paradigm, one of the most widely used measures of attentional bias (Macleod et al. 1986
), report that individuals with heightened anxiety are faster to detect a probe that has previously been paired with a threatening (compared to a neutral) stimulus, suggesting that they are hypervigilant for threat-relevant information (Macleod et al. 1986
; Mogg and Bradley 1999
However, the dot-probe paradigm has received criticism for not differentiating between different components of attention. Fox et al. (2001
) argue that faster RTs to threatening stimuli may be a consequence of delayed disengagement from, rather than faster orienting to, threatening stimuli. Studies using paradigms that disentangle different facets of attention corroborate the postulation that anxiety is specifically associated with delayed disengagement from threatening stimuli, but not faster orienting towards it (Yiend and Mathews 2001
; Salemink et al. 2007
). This may be particularly relevant for individuals with ASD, who exhibit difficulties in flexibly shifting attention (Elsabbagh et al. 2013
; Landry and Bryson 2004
). Perhaps this cognitive style also contributes to cognitive processing in anxiety among individuals with ASD, resulting in more difficulty in shifting attention away from threat.
Given that most anxiety disorders first manifest in childhood (Beesdo et al. 2009
), assessing threat bias among school-aged children at-risk for ASD may be particularly relevant in describing the early processes associated with the development of anxiety in this population. The association between threat bias and anxiety has been reported in both adults and children, but Dudeney et al. (2015
) suggest that the strength of this association increases with age from early childhood to adolescence. Nevertheless, several studies using RT paradigms have reported that children as young as preschool-age with heightened anxiety exhibit both faster detection of and slower disengagement from threatening stimuli (Mian et al. 2015
; Briggs-Gowan et al. 2015
; Bar-Haim et al. 2011
While threat bias has been studied very extensively among individuals with anxiety disorders, there is a dearth in research investigating this among ASD populations and studies to date have yielded equivocal results. Two studies examined attentional bias to angry faces and found that young people with ASD and elevated anxiety did not exhibit enhanced engagement to or delayed disengagement from threat, compared to participants with ASD who did not have heightened anxiety or TD controls (Hollocks et al. 2013
; May et al. 2015
). On the other hand, using an eye-tracking paradigm, White et al. (2015
) found that prolonged fixation to threatening faces, depicting expressions of disgust and anger, was associated with fear of negative social evaluation (a construct linked to social phobia) in adolescents with ASD. In contrast to these studies, Isomura et al. (2015
) found that children with ASD, who did not have clinical-level anxiety symptoms, exhibited prolonged disengagement from threatening (snakes) compared with non-threatening (flowers) stimuli. While it is not unusual to find a general bias to threat in children and adults (Lobue and Deloache 2008
), participants with ASD had longer disengagement from the threatening stimuli than TD controls. It is important to note that, although participants in this study did not have clinical diagnoses of anxiety, subclinical symptoms or traits were not measured. Given that delayed disengagement is frequently observed among individuals with ASD and anxiety symptoms were not measured, it is unclear whether the attentional bias to threat reported in this study is a consequence of ASD symptoms, anxiety, or an interplay of both.
Social and Non-Social Threat Stimuli
One of the limitations of previous studies examining threat bias in ASD is the use of human facial expressions as stimuli. There is a broad literature suggesting atypical face processing and emotion recognition among individuals with ASD (e.g. Harms et al. 2010
). A recent meta-analysis suggests that individuals with ASD exhibit reduced performance on tasks that measure emotion recognition, particularly for negative emotions such as anger and fear (Uljarević and Hamilton 2013
). Multiple studies also report both reduced accuracy in emotion labelling and attenuated neural activity when viewing emotional faces among first-degree relatives of individuals with ASD (Sucksmith et al. 2013
; Spencer et al. 2011
; Oerlemans et al. 2014
). In the context of this evidence, the use of threatening facial expressions as stimuli may not be salient enough to detect an association between anxiety and attentional bias among ASD populations. On the contrary, individuals with ASD have exhibited heightened neural responses to unpleasant non-social stimuli, comparable to neural activity observed in TD controls (Silani et al. 2008
), which is perhaps why bias to images of snakes compared to flowers was observed in children with ASD (Isomura et al. 2015
). An additional challenge exists in selecting appropriate non-threatening comparison stimuli. Children with ASD often exhibit fears and phobias of unusual or commonplace objects (Mayes et al. 2013
; Kerns et al. 2014
). As a consequence, the traditional use of neutral stimuli may not be as clearly non-threatening to children with ASD. Perhaps more clearly positively valenced stimuli may be more effective in detecting differences in attentional allocation to threatening and non-threatening information.
The Present Study
The present study sought to extend current understanding of anxiety in ASD by examining the association between parent-reported anxiety and threat bias, in a cohort of children at high familial risk for ASD (HR), some of whom met diagnostic criteria for ASD (HR-ASD) and others who did not (HR-non ASD), compared to low-risk (LR) controls. Importantly, we aim to address limitations in previous work by examining bias to non-social threatening stimuli, which may be more salient among children with ASD. In our recent work with this cohort, we found that anxiety was substantially elevated in the HR children, most highly among those who were HR-ASD and to a slightly lesser degree among HR-non ASD children (Shephard et al. 2016
). The present study focuses primarily on parent-reported anxiety both due to the young age of our participants and previous reports that children with ASD may have difficulty reflecting on their internal states and under-report symptoms of anxiety (e.g. Mazefsky et al. 2011
Given the present literature, this study aims to address the following hypotheses:
Children at HR for ASD will show evidence of attentional threat bias. In light of the literature suggesting that anxiety may be associated with prolonged disengagement from threat (Fox et al. 2001
) and reports that children with ASD have difficulty in flexibly shifting attention (Elsabbagh et al. 2013
; Landry and Bryson 2004
), we predict that threat bias will be observed through delayed disengagement from, rather than faster orienting to, threatening stimuli.
Previous findings suggest that anxiety is highly elevated among siblings who themselves have ASD, and also (albeit to a lesser degree) among those who do not have ASD (Hallett et al. 2013b
; Shephard et al. 2016
). Therefore, we predict that threat bias will also be highest among children in the HR-ASD group, followed by those who are HR-non ASD, and lowest in LR controls.
Since children with ASD report heightened fear of atypical or commonplace objects (Mayes et al. 2013
; Kerns et al. 2014
), threat bias will be more readily observed when comparing threatening with positive, rather than threatening with neutral, stimuli within the HR sample.
Finally, there will be an association between anxiety symptom severity and attentional threat bias, regardless of ASD severity.