Matthew J. Hollocks

Brief Report: The Use of Self-Report Measures in Young People with Autism Spectrum Disorder to Access Symptoms of Anxiety, Depression and Negative Thoughts

The aims of this study were two-fold; firstly, to investigate whether self-report measures are useful and reflect parent-reported psychiatric symptoms in children with autism spectrum disorder (ASD), and secondly, to investigate whether children with ASD are able to access and report their cognitions, a prerequisite skill for cognitive behavior therapies. Thirty children with ASD and 21 comparison children without ASD completed the Spence Children’s Anxiety Scale and the Children’s Depression Inventory, with parents completing the parent version of both questionnaires. Intraclass correlations revealed that there was good agreement between ASD children and their parents on both measures, but only on the depression measure in non-ASD children. The children in both groups also completed the Children’s Automatic Thoughts Questionnaires; multiple regression analyses indicated that within the ASD group, child-rated scores on the CATS questionnaire were positively related to increased self-reported symptoms of anxiety and depression, but not in the comparison group, suggesting that children with ASD are able to accurately report their anxious and depressed cognitions. The implications of these results for both the practice and theory of CBT for children with ASD are discussed.

Differential relationships between apathy and depression with white matter microstructural changes and functional outcomes

Small vessel disease pathways disrupts subcortical pathways that are important for emotion regulation. Hollocks et al. use brain imaging and statistical modelling to show that white-matter damage is associated with apathy, but not depression, although the latter still has a significant impact on quality of life.

Differences in HPA-axis and heart rate responsiveness to psychosocial stress in children with autism spectrum disorders with and without co-morbid anxiety

Children and adolescents with autism spectrum disorder (ASD) have much higher rates of anxiety disorders relative to their typically developing peers. However, there have been few attempts to investigate what physiological parameters may be associated with this elevated rate of anxiety. Therefore, this study investigated the physiological correlates of anxiety in ASD, with a focus on whether measures of heart rate and cortisol responsiveness to psychosocial stress differentiate those participants with ASD with and without a co-occurring anxiety disorder. A total of 75 male participants aged 10-16 years with normal intellectual ability underwent a psychosocial stress test. The participants included healthy controls (n=23), ASD only (ASD; n=20) and ASD with a comorbid anxiety disorder (ASDanx; n=32). Heart rate, heart rate variability and salivary cortisol were compared by fitting a piecewise regression model to examine baseline levels and change over time within and between the rest, stress and recovery phases of the stress test. The ASDanx group had different response patterns from both the ASD and control groups. The ASDanx group was characterized by a blunted cortisol and heart rate response to psychosocial stress. Furthermore, in the ASDanx group, reduced heart rate and cortisol responsiveness were significantly related to increased anxiety symptoms. This is the first study to report a possible physiological basis for co-occurring anxiety disorders in children and adolescents with ASD. It is possible that a non-adaptive physiological response to psychosocial stress may be related to the high prevalence of co-occurring anxiety disorders in people with ASD.

The Association Between Social Cognition and Executive Functioning and Symptoms of Anxiety and Depression in Adolescents With Autism Spectrum Disorders

While high levels of anxiety and depression are now recognized as major co‐occurring problems in children and young people with an autism spectrum disorder (ASD), research examining possible associations with individual differences in neurocognitive functioning has been limited. This study included 90 adolescents with an ASD aged 14–16 years with a full‐scale IQ > 50. Using structural equation modeling, we examined the independent relationships between multiple measures of executive functioning and social cognition on severity of anxiety or depressive symptoms. Results indicated a significant association between poorer executive functioning and higher levels of anxiety, but not depression. In contrast, social cognition ability was not associated with either anxiety or depression. This study is the first to report significant associations between executive functions and anxiety in ASD. This may suggest that poor executive functioning is one factor associated with the high prevalence of anxiety disorder in children and adolescents with ASD. Autism Res 2014, 7: 216–228.

The relationship between attentional bias and anxiety in children and adolescents with autism spectrum disorders

Young people with an autism spectrum disorder (ASD) are more likely to have heightened levels of anxiety compared with their typically developing (non‐ASD) peers. The reasons for this are poorly understood, and there has been little research investigating the cognitive correlates of anxiety in individuals with ASD. Typically developing youth with anxiety disorders have frequently been found to show an attentional bias toward threatening information. In this study, we examined whether such a bias was also found in young people with ASD and anxiety symptoms. The protocol utilized two versions of the dot‐probe paradigm, the first with emotional faces and the second with emotional words. Participants comprised 38 boys with an ASD and 41 typically developing controls aged 10–16 years of age. Those with an ASD displayed higher levels of parent‐ and child‐rated anxiety (both P < 0.001) and depression (P < 0.001) compared with controls. However, there were no significant group differences in attentional bias scores and no significant relationship between anxiety and attentional bias in either the face or word tasks, for either group. Our findings suggest that, for young people with ASD, unlike non‐ASD individuals with an anxiety disorder, high levels of anxiety may not be associated with attentional bias to threat. This may indicate that anxiety in ASD has different cognitive correlates from anxiety in the typically developing population. Further conclusions, study limitations, and future directions are discussed. Autism Res 2013, ●●: ●●–●●.

Irritability in boys with autism spectrum disorders: an investigation of physiological reactivity.

Background Irritability in people with autism spectrum disorders (ASD) is common and impairing, yet its mechanisms remain understudied. We investigated symptom reporting and mechanisms of irritability in ASD, focusing on the relation between irritability and physiological stress responses. Methods Forty‐seven unmedicated boys with high‐functioning ASD (hfASD) and 23 typically developing boys aged 10–16 years completed a psychosocial stress test. Changes in cortisol, heart rate and heart rate variability throughout the test were recorded. Self‐ and parent‐reported measures of irritability were obtained. Irritability symptom reporting in the hfASD group was compared to two groups of boys without ASD: highly irritable boys (severe mood dysregulation, SMD; n = 40) and healthy‐control boys (HC; n = 30). Results Boys with hfASD scored significantly higher on irritability than HC boys, and they reported a pattern of irritability symptoms closely resembling that of boys with SMD. The internal consistency of irritability in hfASD was high by parent‐ and self‐report. Although boys with hfASD showed significant stress‐induced changes in cortisol and heart rate, those who rated themselves as highly irritable had lower cortisol levels throughout the test compared to those low on irritability. Participants rated as highly irritable by their parents showed blunted cortisol and heart rate responses to stress. The effects of irritability on heart rate, but not cortisol, were accounted for by trait anxiety. Conclusions Irritability can be measured reliably in hfASD and is associated with distinct biological responses to stress.

White Matter Damage Relates to Oxygen Saturation in Children With Sickle Cell Anemia Without Silent Cerebral Infarcts

Background and Purpose— Sickle cell anemia is associated with compromised oxygen-carrying capability of hemoglobin and a high incidence of overt and silent stroke. However, in children with no evidence of cerebral infarction, there are changes in brain morphometry relative to healthy controls, which may be related to chronic anemia and oxygen desaturation. Methods— A whole-brain tract-based spatial statistics analysis was carried out in 25 children with sickle cell anemia with no evidence of abnormality on T2-weighted magnetic resonance imaging (13 male, age range: 8–18 years) and 14 age- and race-matched controls (7 male, age range: 10–19 years) to determine the extent of white matter injury. The hypotheses that white matter damage is related to daytime peripheral oxygen saturation and steady-state hemoglobin were tested. Results— Fractional anisotropy was found to be significantly lower in patients in the subcortical white matter (corticospinal tract and cerebellum), whereas mean diffusivity and radial diffusivity were higher in patients in widespread areas. There was a significant negative relationship between radial diffusivity and oxygen saturation (P<0.05) in the anterior corpus callosum and a trend-level negative relationship between radial diffusivity and hemoglobin (P<0.1) in the midbody of the corpus callosum. Conclusions— These data show widespread white matter abnormalities in a sample of asymptomatic children with sickle cell anemia, and provides for the first time direct evidence of a relationship between brain microstructure and markers of disease severity (eg, peripheral oxygen saturation and steady-state hemoglobin). This study suggests that diffusion tensor imaging metrics may serve as a biomarker for future trials of reducing hypoxic exposure.

The measurement properties of the spence children's anxiety scale-parent version in a large international pooled sample of young people with autism spectrum disorder

Anxiety‐related difficulties are common in ASD, but measuring anxiety reliably and validly is challenging. Despite an increasing number of studies, there is no clear agreement on which existing anxiety measure is more psychometrically sound and what is the factor structure of anxiety in ASD. The present study examined the internal consistency, convergent, divergent, and discriminant validity, as well as the factor structure of the Spence Childrens Anxiety Scale‐Parent Version (SCAS‐P), in a large international pooled sample of 870 caregivers of youth with ASD from 12 studies in the United Kingdom, United States, and Singapore who completed the SCAS‐P. Most were community recruited, while the majority had at least one measure of ASD symptomatology and either cognitive or adaptive functioning measures completed. Existing SCAS‐P total scale and subscales had excellent internal consistency and good convergent, divergent and discriminant validity similar to or better than SCAS‐P properties reported in typically developing children, except for the poorer internal consistency of the physical injury subscale. Confirmatory Factor Analysis (CFA) of the existing SCAS‐P six‐correlated factor structure was a poor fit for this pooled database. Principal component analysis using half of the pooled sample identified a 30‐item five correlated factor structure, but a CFA of this PCA‐derived structure in the second half of this pooled sample revealed a poor fit, although the PCA‐derived SCAS‐P scale and subscales had stronger validity and better internal consistency than the original SCAS‐P. The studys limitations, the use of the SCAS‐P to screen for DSM‐derived anxiety problems in ASD and future research directions are discussed. Autism Res 2017, 10: 1629–1652.

Apathy, but not depression, is associated with executive dysfunction in cerebral small vessel disease

Objective To determine the prevalence of apathy and depression in cerebral small vessel disease (SVD), and the relationships between both apathy and depression with cognition. To examine whether apathy is specifically related to impairment in executive functioning and processing speed. Methods 196 patients with a clinical lacunar stroke and an anatomically corresponding lacunar infarct on MRI were compared to 300 stroke-free controls. Apathy and depression were measured using the Geriatric Depression Scale, and cognitive functioning was assessed using an SVD cognitive screening tool, the Brief Memory and Executive Test, which measures executive functioning/processing speed and memory/orientation. Path analysis and binary logistic regression were used to assess the relation between apathy, depression and cognitive impairment. Results 31 participants with SVD (15.8%) met criteria for apathy only, 23 (11.8%) for both apathy and depression, and 2 (1.0%) for depression only. In the SVD group the presence of apathy was related to global cognition, and specifically to impaired executive functioning/processing speed, but not memory/orientation. The presence of depression was not related to global cognition, impaired executive functioning/processing speed or memory/orientation. Conclusions Apathy is a common feature of SVD and is associated with impaired executive functioning/processing speed suggesting the two may share biological mechanisms. Screening for apathy should be considered in SVD, and further work is required to develop and evaluate effective apathy treatment or management in SVD.

Brief Screening of Vascular Cognitive Impairment in Patients With Cerebral Autosomal-Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy Without Dementia

Background and Purpose— Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a monogenic form of cerebral small vessel disease leading to early-onset stroke and dementia, with younger patients frequently showing subclinical deficits in cognition. At present, there are no targeted cognitive screening measures for this population. However, the Brief Memory and Executive Test (BMET) and the Montreal Cognitive Assessment (MoCA) have shown utility in detecting cognitive impairment in sporadic small vessel disease. This study assesses the BMET and the MoCA as clinical tools for detecting mild cognitive deficits in CADASIL. Methods— Sixty-six prospectively recruited patients with CADASIL, and 66 matched controls completed the BMET, with a subset of these also completing the MoCA. Receiver operating characteristic curves were calculated to examine the sensitivity and specificity of clinical cutoffs for the detection of vascular cognitive impairment and reduced activities of daily living. Results— Patients with CADASIL showed more cognitive impairment overall and were poorer on both executive/processing and memory indices of the BMET relative to controls. The BMET showed good accuracy in predicting vascular cognitive impairment (85% sensitivity and 84% specificity) and impaired instrumental activities of daily living (92% sensitivity and 77% specificity). The MoCA also showed good predictive validity for vascular cognitive impairment (80% sensitivity and 78% specificity) and instrumental activities of daily living (75% sensitivity and 76% specificity). The most important background predictor of vascular cognitive impairment was a history of stroke. Conclusions— The results indicate that the BMET and the MoCA are clinically useful and sensitive screening measures for early cognitive impairment in patients with CADASIL.