Publications by authors named "Matthew J Hollocks"

27 Publications

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The association of adverse life events and parental mental health with emotional and behavioral outcomes in young adults with autism spectrum disorder.

Autism Res 2021 Aug 2;14(8):1724-1735. Epub 2021 Jun 2.

Department of Child and Adolescent Psychiatry, King's College London, Institute of Psychiatry, Psychology & Neuroscience, and South London and Maudsley Foundation Trust, London, UK.

People with autism spectrum disorder (ASD) are at increased risk of developing co-occurring mental health difficulties across the lifespan. Exposure to adverse life events and parental mental health difficulties are known risk factors for developing a range of mental health difficulties. This study investigates the association of adverse life events, parental stress and mental health with emotional and behavioral problems in young adults with ASD. One hundred and fifteen young adults with ASD derived from a population-based longitudinal study were assessed at three time-points (12-, 16-, and 23-year) on questionnaire measures of emotional and behavioral problems. Parent-reported exposure to adverse life events and parental stress/mental health were measured at age 23. We used structural equation modeling to investigate the stability of emotional and behavioral problems over time, and the association between adverse life events and parental stress and mental health and emotional and behavioral outcomes at 23-year. Our results indicate that exposure to adverse life events was significantly associated with increased emotional and behavioral problems in young adults with ASD, while controlling for symptoms in childhood and adolescence. Higher reported parental stress and mental health difficulties were associated with a higher frequency of behavioral, but not emotional problems, and did not mediate the impact of adverse life events. These results suggest that child and adolescent emotional and behavioral problems, exposure to life events and parent stress and mental health are independently associated, to differing degrees, with emotional or behavioral outcomes in early adulthood. LAY SUMMARY: People with autism experience high rates of mental health difficulties throughout childhood and into adult life. Adverse life events and parental stress and mental health may contribute to poor mental health in adulthood. We used data at three time points (12-, 16-, and 23-year) to understand how these factors relate to symptoms at 23-year. We found that emotional and behavioral problems in childhood, adverse life events and parent mental health were all associated with increased emotional and behavioral problems in adulthood.
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http://dx.doi.org/10.1002/aur.2548DOI Listing
August 2021

Inspecting the Glass Half-Full Identifies Strengths in the Development of Children With Autism Spectrum Disorder.

JAMA Netw Open 2021 03 1;4(3):e213155. Epub 2021 Mar 1.

Department of Child and Adolescent Psychiatry, King's College London, Institute of Psychiatry, Psychology, and Neuroscience and Maudsley Biomedical Research Centre for Mental Health, London, United Kingdom.

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http://dx.doi.org/10.1001/jamanetworkopen.2021.3155DOI Listing
March 2021

Is cognitive inflexibility a missing link? The role of cognitive inflexibility, alexithymia and intolerance of uncertainty in externalising and internalising behaviours in young people with autism spectrum disorder.

J Child Psychol Psychiatry 2021 Jun 21;62(6):715-724. Epub 2020 Aug 21.

Newcomen Centre, Evelina London Children's Hospital, Guy's & St Thomas' NHS Foundation Trust, London, UK.

Background: Internalising (anxiety and low mood) and externalising (aggressive or outburst behaviours, and irritability) difficulties are very common in autism spectrum disorder (ASD) across the life span, relatively stable over time and often associated with poorer quality of life. Understanding the cognitive mechanisms underlying internalising and externalising difficulties in ASD is essential for developing targeted supports and interventions. In the present study, we investigated established and less-researched cognitive factors hypothesised to contribute to internalising and/or externalising difficulties in ASD, namely cognitive inflexibility (CI), intolerance of uncertainty (IU) and alexithymia. Based on previous models and clinical experience, we hypothesised that IU would lead to internalising symptoms, with alexithymia contributing to this pathway, and that CI would have a direct effect on externalising behaviours and may indirectly contribute to internalising symptoms via increasing IU.

Methods: Our sample consisted of 95 5- to 18-year-olds presenting to a specialist neurodevelopmental clinic and receiving a diagnosis of ASD. Parents/caregivers completed questionnaires assessing ASD symptomatology, internalising and externalising difficulties, CI, IU and alexithymia. Structural equation modelling was used to examine the hypothesised pathways and relationships between the main variables of interest.

Results: Cognitive Inflexibility played a significant direct role in the pathway from ASD symptoms to externalising symptoms in ASD, and indirect role via IU in the pathway to internalising problems. Relationships between alexithymia and both internalising and externalising symptoms were weaker, with alexithymia predicting internalising difficulties via IU only.

Conclusions: The finding of a direct pathway from CI to externalising behaviours is novel, as is the indirect role of CI in internalising symptomatology. Of the three cognitive mechanisms examined, only CI significantly predicted externalising symptoms. Possible implications for interventions and supports targeting these cognitive processes in ASD are discussed.
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http://dx.doi.org/10.1111/jcpp.13295DOI Listing
June 2021

Network neuroscience of apathy in cerebrovascular disease.

Prog Neurobiol 2020 05 6;188:101785. Epub 2020 Mar 6.

Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.

Apathy is a reduction in motivated goal-directed behavior (GDB) that is prevalent in cerebrovascular disease, providing an important opportunity to study the mechanistic underpinnings of motivation in humans. Focal lesions, such as those seen in stroke, have been crucial in developing models of brain regions underlying motivated behavior, while studies of cerebral small vessel disease (SVD) have helped define the connections between brain regions supporting such behavior. However, current lesion-based models cannot fully explain the neurobiology of apathy in stroke and SVD. To address this, we propose a network-based model which conceptualizes apathy as the result of damage to GDB-related networks. A review of the current evidence suggests that cerebrovascular disease-related pathology can lead to network changes outside of initially damaged territories, which may propagate to regions that share structural or functional connections. The presentation and longitudinal trajectory of apathy in stroke and SVD may be the result of these network changes. Distinct subnetworks might support cognitive components of GDB, the disruption of which results in specific symptoms of apathy. This network-based model of apathy may open new approaches for investigating its underlying neurobiology, and presents novel opportunities for its diagnosis and treatment.
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http://dx.doi.org/10.1016/j.pneurobio.2020.101785DOI Listing
May 2020

Anxiety in young people with autism spectrum disorder: Common and autism-related anxiety experiences and their associations with individual characteristics.

Autism 2020 07 19;24(5):1111-1126. Epub 2019 Dec 19.

National University of Singapore, Singapore.

Anxiety is common in autism spectrum disorder. Many anxiety symptoms in autism spectrum disorder are consistent with (5th ed.) anxiety disorders (termed "common" anxieties), but others may be qualitatively different, likely relating to autism spectrum disorder traits (herein termed "autism-related" anxieties). To date, few studies have examined both "common" and "autism-related" anxiety experiences in autism spectrum disorder. We explored caregiver-reported Spence Children's Anxiety Scale-Parent version data from a multi-site (United Kingdom, Singapore, and United States) pooled database of 870 6- to 18-year-old participants with autism spectrum disorder, of whom 287 provided at least one written response to the optional open-ended Spence Children's Anxiety Scale-Parent item 39 ("?"). Responses were thematically coded to explore (a) common and autism-related anxiety presentations and (b) their relationship with young people's characteristics. Nearly half of the responses were autism-related anxieties (mostly sensory, uncommon, or idiosyncratic specific phobias and worries about change and unpredictability). The other half described additional common anxieties not covered in the original measure (mostly social, weather and environmental disasters, and animals). Caregivers of participants who were more severely affected by autism spectrum disorder symptoms reported more autism-related, as compared to common, additional anxieties. Implications for the assessment and understanding of anxiety in autism are discussed.
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http://dx.doi.org/10.1177/1362361319886246DOI Listing
July 2020

Brief Report: An Evaluation of the Social Communication Questionnaire as a Screening Tool for Autism Spectrum Disorder in Young People Referred to Child & Adolescent Mental Health Services.

J Autism Dev Disord 2019 Jun;49(6):2618-2623

Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, UK.

The SCQ is a widely used screening measure for the assessment of autism spectrum disorder (ASD). However, its sensitivity and specificity when used with older children in the context of community Child & Adolescent Mental Health services is unclear. Seventy-seven (Mean age = 12.8 years) young people with suspected ASD were screened using parent- and teacher-reported SCQ's before completing a comprehensive diagnostic assessment. Of the 77 young people included, 44 (57%) met criteria for an ASD diagnosis. Our results indicated that regardless of informant, SCQ scores did not significantly predict the outcome of the diagnostic assessment. Based on the published cut-off score for the SCQ, Receiver Operating Characteristic curve analyses revealed a lower than expected sensitivity and specificity. This suggests that the SCQ is not an effective screening tool when used in the context of community Child & Adolescent Mental Health services.
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http://dx.doi.org/10.1007/s10803-019-03982-6DOI Listing
June 2019

Apathy is associated with large-scale white matter network disruption in small vessel disease.

Neurology 2019 03 8;92(11):e1157-e1167. Epub 2019 Feb 8.

From the Department of Clinical Neurosciences (J.T., M.J.H., R.L.B., D.J.T., H.S.M.), University of Cambridge, UK; Department of Neurology (A.M.T., F.-E.d.L.), Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands; Neuroscience Research Centre (T.R.B.), Molecular and Clinical Sciences Research Institute, St. George's University of London; and Nuffield Department of Clinical Neurosciences (M.H.), University of Oxford, UK.

Objective: To investigate whether white matter network disruption underlies the pathogenesis of apathy, but not depression, in cerebral small vessel disease (SVD).

Methods: Three hundred thirty-one patients with SVD from the Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Cohort (RUN DMC) study completed measures of apathy and depression and underwent structural MRI. Streamlines reflecting underlying white matter fibers were reconstructed with diffusion tensor tractography. First, path analysis was used to determine whether network measures mediated associations between apathy and radiologic markers of SVD. Next, we examined differences in whole-brain network measures between participants with only apathy, only depression, and comorbid apathy and depression and a control group free of neuropsychiatric symptoms. Finally, we examined regional network differences associated with apathy.

Results: Path analysis demonstrated that network disruption mediated the relationship between apathy and SVD markers. Patients with apathy, compared to all other groups, were impaired on whole-brain measures of network density and efficiency. Regional network analyses in both the apathy subgroup and the entire sample revealed that apathy was associated with impaired connectivity in premotor and cingulate regions.

Conclusions: Our results suggest that apathy, but not depression, is associated with white matter tract disconnection in SVD. The subnetworks delineated suggest that apathy may be driven by damage to white matter networks underlying action initiation and effort-based decision making.
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http://dx.doi.org/10.1212/WNL.0000000000007095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6511108PMC
March 2019

Brief Report: Testing the Psychometric Properties of the Spence Children's Anxiety Scale (SCAS) and the Screen for Child Anxiety Related Emotional Disorders (SCARED) in Autism Spectrum Disorder.

J Autism Dev Disord 2020 Jul;50(7):2625-2632

Institute of Psychology, Psychiatry, and Neuroscience, Department of Child & Adolescent Psychiatry, King's College London, 16 De Crespigny Park, Denmark Hill, London, SE5 8AF, UK.

Anxiety is a prevalent and impairing co-morbidity among individuals with autism spectrum disorder (ASD), yet assessment measures, including screening tools, are seldom validated with autism samples. We explored the psychometric properties of the child and parent reports of the Spence Children's Anxiety Scale (SCAS) and the Screen for Anxiety Related Disorder-71 (SCARED-71) with 49 males with ASD (10-16 years, 63% co-occurring anxiety). Both measures had excellent internal consistency and fair-good parent-child agreement. The SCAS has a higher proportion of items evaluating observable behaviors. Predictive power of the measures did not differ. Higher cut-points in the parent reports (SCARED only) and lower cut-points in the child reports may enhance prediction in this sample. Choice of measure and cut-points should be considered alongside intended purpose.
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http://dx.doi.org/10.1007/s10803-018-3774-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7308247PMC
July 2020

Anxiety and depression in adults with autism spectrum disorder: a systematic review and meta-analysis.

Psychol Med 2019 03 4;49(4):559-572. Epub 2018 Sep 4.

Department of Health Sciences,University of Leicester,Leicester,UK.

Adults with autism spectrum disorder (ASD) are thought to be at disproportionate risk of developing mental health comorbidities, with anxiety and depression being considered most prominent amongst these. Yet, no systematic review has been carried out to date to examine rates of both anxiety and depression focusing specifically on adults with ASD. This systematic review and meta-analysis examined the rates of anxiety and depression in adults with ASD and the impact of factors such as assessment methods and presence of comorbid intellectual disability (ID) diagnosis on estimated prevalence rates. Electronic database searches for studies published between January 2000 and September 2017 identified a total of 35 studies, including 30 studies measuring anxiety (n = 26 070; mean age = 30.9, s.d. = 6.2 years) and 29 studies measuring depression (n = 26 117; mean age = 31.1, s.d. = 6.8 years). The pooled estimation of current and lifetime prevalence for adults with ASD were 27% and 42% for any anxiety disorder, and 23% and 37% for depressive disorder. Further analyses revealed that the use of questionnaire measures and the presence of ID may significantly influence estimates of prevalence. The current literature suffers from a high degree of heterogeneity in study method and an overreliance on clinical samples. These results highlight the importance of community-based studies and the identification and inclusion of well-characterized samples to reduce heterogeneity and bias in estimates of prevalence for comorbidity in adults with ASD and other populations with complex psychiatric presentations.
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http://dx.doi.org/10.1017/S0033291718002283DOI Listing
March 2019

Framingham vascular age is associated with worse cognitive performance in the middle-aged and elderly.

Neuropsychol Dev Cogn B Aging Neuropsychol Cogn 2019 07 27;26(4):531-540. Epub 2018 Jul 27.

b Department of Clinical Neurosciences , University of Cambridge, Addenbrookes Biomedical Campus , Cambridge , UK.

"Normal" age-related cognitive decline has been associated with cardiovascular risk factors. Framingham Vascular Age is age-normed cardiovascular risk which may help communicate risk to patients and identify those at relatively higher risk. We aim to assess the association between Framingham Vascular Age and cognition. 346 "healthy" participants (57±10 years) without neuropsychiatric disorders or clinical manifestations of cardiovascular disease were studied. Cognition was evaluated using the Brief Memory and Executive Test and Framingham Vascular Age was calculated. The association between Framingham Vascular Age and cognitive performance was determined through General Linear Models to control for covariates. Framingham Vascular age was associated with poorer Memory and Executive Function/Processing Speed indices (p= 0.019 and p<0.001, respectively). We conclude Framingham Vascular Age is associated with worse Executive Function/Processing Speed and Memory. Vascular Age may help identify patients at higher risk of age-related cognitive decline with implications for communicating the morbidity associated with cardiovascular risk.
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http://dx.doi.org/10.1080/13825585.2018.1499866DOI Listing
July 2019

The Brief Memory and Executive Test (BMET): A cognitive screening tool to detect and differentiate vascular cognitive impairment and Alzheimer's disease.

Int J Geriatr Psychiatry 2018 02 7;33(2):e273-e279. Epub 2017 Sep 7.

Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.

Objective: While there are several cognitive screening tests available for the detection of cortical dementias such as Alzheimer's disease (AD), these are rarely designed to be sensitive to vascular cognitive impairment (VCI). The Brief Memory and Executive Test (BMET) is a screening measure designed to be sensitive to the cognitive profile of both VCI and AD. This study investigated the ability of the BMET to detect AD, and to differentiate between VCI and AD.

Methods: This study included 150 patients, with either SVD, both with (n = 48) and without VCI (n = 51), or AD (N = 51) and 51 healthy controls. Participants were aged between 40 and 90 years of age and completed both the BMET and the MMSE.

Results: Receiver operator characteristic (ROC) curve analysis showed as before the BMET is a good predictor SVD. Additionally, the BMET was a good predictor of AD (AUC = 0.96) and performed at least as well as the MMSE (AUC = 0.92) when differentiating AD patients from healthy controls. The BMET had a sensitivity of 86% and specificity of 100% for detecting AD patients from control subjects. Using the difference in cognitive profile between the AD and VCI group, we developed an index score which correctly classified 76% of patients as either having VCI or AD.

Conclusion: The BMET is a brief and sensitive tool for the detection of cognitive impairment due to both SVD and AD and can be used to aid in the differentiation of the 2 diseases.
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http://dx.doi.org/10.1002/gps.4787DOI Listing
February 2018

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.

Autism Res 2017 Oct 2;10(10):1629-1652. Epub 2017 Jun 2.

Wales Autism Research Centre, School of Psychology, Cardiff University, Cardiff, CF10 3AT, UK.

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 Children's 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 study's 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. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/aur.1809DOI Listing
October 2017

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

PLoS One 2017 11;12(5):e0176943. Epub 2017 May 11.

Stroke Research Group, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom.

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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0176943PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5426624PMC
September 2017

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

Stroke 2016 10 13;47(10):2482-7. Epub 2016 Sep 13.

From the Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Biomedical Campus, United Kingdom (R.L.B., M.J.H., R.Y.Y.T., H.S.M.); and Department of Psychology, Psychology and Neurosciences, Institute of Psychiatry, King's College London, London, United Kingdom (R.G.M.).

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.
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http://dx.doi.org/10.1161/STROKEAHA.116.013761DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5049939PMC
October 2016

Dual Cognitive and Biological Correlates of Anxiety in Autism Spectrum Disorders.

J Autism Dev Disord 2016 Oct;46(10):3295-307

Department of Child and Adolescent Psychiatry and Biomedical Research Centre for Mental Health, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.

Young people with autism spectrum disorder (ASD) have a high prevalence (~40 %) of anxiety disorders compared to their non-ASD peers. It is unclear whether cognitive and biological processes associated with anxiety in ASD are analogous to anxiety in typically developing (TD) populations. In this study 55 boys with ASD (34 with a co-occurring anxiety disorder, 21 without) and 28 male controls, aged 10-16 years and with a full-scale IQ ≥ 70, completed a series of clinical, cognitive (attention bias/interpretation bias) and biological measures (salivary cortisol/HR response to social stress) associated with anxiety in TD populations. Structural equation modelling was used to reveal that that both attentional biases and physiological responsiveness were significant, but unrelated, predictors of anxiety in ASD.
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http://dx.doi.org/10.1007/s10803-016-2878-2DOI Listing
October 2016

Anxious Imagery in Children With and Without Autism Spectrum Disorder: An Investigation into Occurrence, Content, Features and Implications for Therapy.

J Autism Dev Disord 2017 Dec;47(12):3822-3832

MRC Cognition and Brain Sciences Unit, Cambridge, UK.

Mental imagery has been implicated in anxiety disorders in adults, but has not been investigated in child and adolescent populations. Anxiety is highly prevalent in autism spectrum disorder (ASD), and as people with ASD are often thought of as 'visual thinkers', the potential role of distressing imagery in children with ASD merits exploration. Participants aged 8-16 years were grouped as follows: ASD/high anxiety, ASD/low anxiety, non-ASD/high anxiety and non-ASD/low anxiety. Imagery and associated features were assessed using an interview. Group differences were found in number and frequency of images experienced. There were few differences between the groups in the characteristics of the spontaneous images, which included emotional valence, vividness, controllability and realism. Implications for treatment are discussed.
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http://dx.doi.org/10.1007/s10803-016-2840-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5676832PMC
December 2017

Associations between the Brief Memory and Executive Test (BMET), Activities of Daily Living, and Quality of Life in Patients with Cerebral Small Vessel Disease.

J Int Neuropsychol Soc 2016 May 6;22(5):561-9. Epub 2016 Apr 6.

1University of Cambridge,Department of Clinical Neurosciences,R3,Box 183,Addenbrookes Biomedical Campus,Cambridge,CB2 0QQ,United Kingdom.

Objectives: In addition to neuropsychological difficulties, patients with cerebral small vessel disease (SVD) can have reduced activities of daily living and a poorer quality of life compared to healthy adults. The Brief Memory and Executive Test (BMET), is a cognitive screening tool designed to be sensitive to the neuropsychological profile of patients with SVD. While the BMET is sensitive to the cognitive consequences of SVD, it is unclear how well scores on this measure relate to functional outcomes. The aims of this study are to investigate the relationship between scores on the BMET and functional outcomes (activities of daily living and quality of life) in SVD, and to compare this with other commonly used cognitive screening tools.

Methods: This study included 184 participants with SVD (mean age=63.2; SD=9.9) and 299 healthy controls (mean age=62.4; SD=13.8) who were tested using the BMET, Montreal Cognitive Assessment (MoCA), Mini-Mental State Examination (MMSE), Stroke Specific - Quality of Life Scale (SS-QoL), Geriatric Depression Scale (GDS), and measures of both instrumental activities of daily living (IADL) and basic activities of daily living (BADL).

Results: After controlling for covariates the scores on the BMET, but not the MoCA or MMSE, were significantly related to poorer IADL and quality of life in the SVD group. In addition to the BMET scores, symptoms of depression were found to be significant associated with functional outcome.

Conclusion: These results support the clinical utility of using of the BMET, in combination with a standardized depression questionnaire, during the early assessment of patients with SVD.
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http://dx.doi.org/10.1017/S1355617716000187DOI Listing
May 2016

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

Brain 2015 Dec 21;138(Pt 12):3803-15. Epub 2015 Oct 21.

1 Stroke Research Group, University of Cambridge, Department of Clinical Neurosciences, R3, Box 183, Addenbrooke's Biomedical Campus, Cambridge, CB2 0QQ, UK.

Small vessel disease is a stroke subtype characterized by pathology of the small perforating arteries, which supply the sub-cortical structures of the brain. Small vessel disease is associated with high rates of apathy and depression, thought to be caused by a disruption of white matter cortical-subcortical pathways important for emotion regulation. It provides an important biological model to investigate mechanisms underlying these key neuropsychiatric disorders. This study investigated whether apathy and depression can be distinguished in small vessel disease both in terms of their relative relationship with white matter microstructure, and secondly whether they can independently predict functional outcomes. Participants with small vessel disease (n = 118; mean age = 68.9 years; 65% male) defined as a clinical and magnetic resonance imaging confirmed lacunar stroke with radiological leukoaraiosis were recruited and completed cognitive testing, measures of apathy, depression, quality of life and diffusion tensor imaging. Healthy controls (n = 398; mean age = 64.3 years; 52% male) were also studied in order to interpret the degree of apathy and depression found within the small vessel disease group. Firstly, a multilevel structural equation modelling approach was used to identify: (i) the relationships between median fractional anisotropy and apathy, depression and cognitive impairment; and (ii) if apathy and depression make independent contributions to quality of life in patients with small vessel disease. Secondly, we applied a whole-brain voxel-based analysis to investigate which regions of white matter were associated with apathy and depression, controlling for age, gender and cognitive functioning. Structural equation modelling results indicated both apathy (r = -0.23, P ≤ 0.001) and depression (r = -0.41, P ≤ 0.001) were independent predictors of quality of life. A reduced median fractional anisotropy was significantly associated with apathy (r = -0.38, P ≤ 0.001), but not depression (r = -0.16, P = 0.09). On voxel-based analysis, apathy was associated with widespread reduction in white matter integrity, with the strongest effects in limbic association tracts such as the anterior cingulum, fornix and uncinate fasciculus. In contrast, when controlling for apathy, we found no significant relationship between our white matter parameters and symptoms of depression. In conclusion, white matter microstructural changes in small vessel disease are associated with apathy but not directly with depressive symptoms. These results suggest that apathy, but not depression, in small vessel disease is related to damage to cortical-subcortical networks associated with emotion regulation, reward and goal-directed behaviour.
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http://dx.doi.org/10.1093/brain/awv304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4655344PMC
December 2015

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

Stroke 2015 Jul 12;46(7):1793-9. Epub 2015 May 12.

From the Developmental Imaging and Biophysics Section (J.M.K., J.D.C., C.A.C.), Clinical Neurosciences Section (F.J.K.), and Cognitive Neuroscience and Neuropsychiatry Section (E.L.S., R.E.), UCL Institute of Child Health, London, United Kingdom; Department of Clinical Neuroscience, University of Cambridge, Cambridge, United Kingdom (M.J.H.); Department of Paediatric Haematology, Barts and The London Hospital NHS Trust, London, United Kingdom (P.T.); Department of Paediatrics, Whittington Hospital NHS Trust, London, United Kingdom (A.R.); Department of Paediatrics, North Middlesex University Hospital NHS Trust, London, United Kingdom (O.W.); Wessex Neurological Centre (S.B.), and Department of Child Health (F.J.K.), Southampton University Hospitals NHS Trust, Southampton, United Kingdom (S.B.); and Department of Radiology, Great Ormond Street Hospital, London, United Kingdom (T.C.S.C.).

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.
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http://dx.doi.org/10.1161/STROKEAHA.115.008721DOI Listing
July 2015

The Brief Memory and Executive Test (BMET) for detecting vascular cognitive impairment in small vessel disease: a validation study.

BMC Med 2015 Mar 11;13:51. Epub 2015 Mar 11.

Background: Cognitive impairment is common in patients with cerebral small vessel disease, but is not well detected using common cognitive screening tests which have been primarily devised for cortical dementias. We developed the Brief Memory and Executive Test (BMET); a rapid screening measure sensitive to the impaired executive function and processing speed characteristic of small vessel disease (SVD). To assess the BMET's validity for general use, we evaluated it when administered by non-psychologists in a multicentre study and collected control data to derive normative scores.

Methods: Two-hundred participants with SVD, defined as a clinical lacunar stroke and a corresponding lacunar infarct on MRI, and 303 healthy controls aged between 40-90 years old were recruited. The BMET, as well as the Montreal Cognitive Assessment (MoCA) and Mini Mental State Examination (MMSE), were performed. Overall, 55 SVD participants underwent repeat testing at 3 months to assess the BMET test-retest reliability.

Results: Administering the BMET took a mean (SD) of 12.9 (4.7) in cases and 9.5 (2.6) minutes in controls. Receiver Operator Curve analysis showed the BMET was a good predictor of cognitive impairment in SVD (AUC = 0.94) and performed significantly better than both the MoCA (AUC = 0.77) and the MMSE (AUC = 0.70). Using a cut-off score of 13, the BMET had a sensitivity of 93% and specificity of 76% for detecting cognitive impairment in SVD.

Conclusions: The BMET is a brief and sensitive tool for the detection of cognitive impairment in patients with SVD.
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http://dx.doi.org/10.1186/s12916-015-0290-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4372040PMC
March 2015

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

J Child Psychol Psychiatry 2015 Oct 28;56(10):1118-26. Epub 2015 Jan 28.

Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.

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.
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http://dx.doi.org/10.1111/jcpp.12382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4737220PMC
October 2015

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

Psychoneuroendocrinology 2014 Aug 18;46:32-45. Epub 2014 Apr 18.

King's College London, Institute of Psychiatry, Department of Child & Adolescent Psychiatry and Biomedical Research Centre for Mental Health, London SE5 8AF, United Kingdom.

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.
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http://dx.doi.org/10.1016/j.psyneuen.2014.04.004DOI Listing
August 2014

The association between social cognition and executive functioning and symptoms of anxiety and depression in adolescents with autism spectrum disorders.

Autism Res 2014 Apr 12;7(2):216-28. Epub 2014 Mar 12.

Department of Child & Adolescent Psychiatry, Institute of Psychiatry, King's College London, London, United Kingdom.

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.
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http://dx.doi.org/10.1002/aur.1361DOI Listing
April 2014

Brief report: The use of self-report measures in young people with autism spectrum disorder to access symptoms of anxiety, depression and negative thoughts.

J Autism Dev Disord 2014 Apr;44(4):969-74

Children's Neurosciences Department, Newcomen at St Thomas', St Thomas' Hospital, Staircase D, South Wing, Westminster Bridge Road, London, SE1 7EH, UK,

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.
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http://dx.doi.org/10.1007/s10803-013-1937-1DOI Listing
April 2014

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

Autism Res 2013 Aug 21;6(4):237-47. Epub 2013 Mar 21.

Department of Child & Adolescent Psychiatry, Institute of Psychiatry, King's College, London, London, UK.

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.
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http://dx.doi.org/10.1002/aur.1285DOI Listing
August 2013

Nocturnal oxygen desaturation and disordered sleep as a potential factor in executive dysfunction in sickle cell anemia.

J Int Neuropsychol Soc 2012 Jan 24;18(1):168-73. Epub 2011 Nov 24.

Neurosciences & Mental Health, Institute of Child Health, University College London, United Kingdom.

Previous research has identified cognitive impairment in children with sickle cell anemia (SCA, Hemoglobin SS) compared with controls, partly accounted for by overt neuropathology after clinical stroke, "covert" ("silent") infarction, and severity of anemia. However, cognitive deficits have also been identified in children with SCA with no history of stroke and a normal T2-weighted magnetic resonance imaging (MRI) scan. Our aim was to investigate whether nocturnal hemoglobin oxygen desaturation and sleep fragmentation could be associated with cognitive impairment in children with SCA. We assessed 10 children with SCA (9 with normal MRI) using neuropsychological measures of executive function. Cognitive assessment was immediately followed by overnight polysomnography to record nocturnal hemoglobin oxygen saturation and sleep arousals. Decreases in hemoglobin oxygen saturation and/or increased sleep arousals were associated with reduced performance on cognitive assessment. Nocturnal hemoglobin oxygen desaturation and sleep fragmentation may be a contributing factor to executive dysfunction in SCA.
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http://dx.doi.org/10.1017/S1355617711001469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3729265PMC
January 2012
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