The clinical pathway in ADMiRE, Ireland's first public specialist service for children and adolescents with attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) is a highly prevalent neurodevelopmental disorder occurring in approximately one in twenty young people in Ireland, and in one-third of those attending Irish Child and Adolescent Mental Health Services (CAMHS). It is important to treat ADHD, as un/poorly treated ADHD is associated with a raft of negative health and socio-economic outcomes. Effective interventions for ADHD are available, and the use of standardised, evidence-based pathways for assessment and management of ADHD optimises outcomes. Despite this, there is no national standardised clinical pathway for assessment and treatment of ADHD in Ireland. ADMiRE, the first public healthcare specialist service for children and adolescents in Ireland, has developed a strongly evidence-based, efficient, effective and safe clinical pathway for assessment and management of ADHD. This paper describes the ADMiRE Clinical Pathway and references ADMiRE resources that are available to other services.

Associations between sleep problems in children with ADHD and parental insomnia and ADHD symptoms.

Sleep problems are common in children with attention deficit hyperactivity disorder (ADHD). Children's sleep problem may influence, and be influenced by, parents' sleep problems as well as parents' ADHD symptoms. In the current study we examined the associations of parent-rated sleep quality and sleep timing of pre-adolescent children with parental insomnia symptoms, parental ADHD symptoms and dysfunctional attitudes and beliefs about sleep in a convenience sample recruited by advertisement (N = 120). Childhood sleep problems were common in the sample, with 82% of children exceeding the threshold for the presence of a paediatric sleep disorder. Children's sleep quality showed minimal association with their sleep timing and chronotype. Parental insomnia symptoms, ADHD symptoms and dysfunctional beliefs and attitudes about sleep all associated with their children's sleep quality, and with the sleep subdomains of sleep anxiety and parasomnias. In multiple regression analysis only parental insomnia score was a significant predictor of children's sleep quality. Children's bedtimes, wake times, sleep duration, chronotype or social jetlag did not associate with parents' ADHD or insomnia symptoms. Sleep quality was significantly poorer in children whose parents scored as both consistent for adult ADHD and probable for insomnia disorder compared to parents who scored as either ADHD consistent or insomnia probable, or those who parents scored as neither. We discuss the putative nature of the relationships between sleep quality of children with ADHD and parental ADHD and insomnia symptoms, and suggest that clinicians consider parental sleep when attending to children with ADHD.

A robust brain network for sustained attention from adolescence to adulthood that predicts later substance use.

Substance use, including cigarettes and cannabis, is associated with poorer sustained attention in late adolescence and early adulthood. Previous studies were predominantly cross-sectional or under-powered and could not indicate if impairment in sustained attention was a consequence of substance-use or a marker of the inclination to engage in such behaviour. This study explored the relationship between sustained attention and substance use across a longitudinal span from ages 14 to 23 in over 1,000 participants. Behaviours and brain connectivity associated with diminished sustained attention at age 14 predicted subsequent increases in cannabis and cigarette smoking, establishing sustained attention as a robust biomarker for vulnerability to substance use. Individual differences in network strength relevant to sustained attention were preserved across developmental stages and sustained attention networks generalized to participants in an external dataset. In summary, brain networks of sustained attention are robust, consistent, and able to predict aspects of later substance use.

The Limbic System in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder: A Longitudinal Structural Magnetic Resonance Imaging Analysis.

Background: During childhood and adolescence, attention-deficit/hyperactivity disorder (ADHD) is associated with changes in symptoms and brain structures, but the link between brain structure and function remains unclear. The limbic system, often termed the "emotional network," plays an important role in a number of neurodevelopmental disorders, yet this brain network remains largely unexplored in ADHD. Investigating the developmental trajectories of key limbic system structures during childhood and adolescence will provide novel insights into the neurobiological underpinnings of ADHD. Methods: Structural magnetic resonance imaging data (380 scans), emotional regulation (Affective Reactivity Index), and ADHD symptom severity (Conners 3 ADHD Index) were measured at up to 3 time points between 9 and 14 years of age in a sample of children and adolescents with ADHD (n = 57) and control children (n = 109). Results: Compared with the control group, the ADHD group had lower volume of the amygdala (left: ß standardized [ß_std] = -0.38; right: ß_std = -0.34), hippocampus (left: ß_std = -0.44; right: ß_std = -0.34), cingulate gyrus (left: ß_std = -0.42; right: ß_std = -0.32), and orbitofrontal cortex (right: ß_std = -0.33) across development (9-14 years). There were no significant group-by-age interactions in any of the limbic system structures. Exploratory analysis found a significant Conners 3 ADHD Index-by-age interaction effect on the volume of the left mammillary body (ß_std = 0.17) in the ADHD group across the 3 study time points. Conclusions: Children and adolescents with ADHD displayed lower volume and atypical development in limbic system structures. Furthermore, atypical limbic system development was associated with increased symptom severity, highlighting a potential neurobiological correlate of ADHD severity.

"Tell Me More About Your Child's Sleep": A Qualitative Investigation Of Sleep Problems In Children With ADHD.

OBJECTIVE: To investigate parental experiences and perceptions of sleep problems in their children with Attention Deficit Hyperactivity Disorder (ADHD), the perceived impacts of sleep problems and coping strategies deployed by parents. METHODS: Semi-structured interviews with twenty-six parents of pre-adolescent children with a diagnosis of ADHD, followed by thematic analysis of the interview transcripts. RESULTS: Three themes were generated from the data: Children's Sleep Difficulties; Impacts of Children's Sleep; and Improving Children's Sleep. Sleep initiation problems in children with ADHD were commonly reported by parents, were perceived to be linked in a bidirectional manner with executive and emotional problems, and were reported as being disruptive to parental sleep. Some parents reported that their children's sleep problems were the initial prompt that lead to a diagnosis of ADHD. Parents reported utilizing a range of coping strategies to mitigate sleep problems, such as controlling the bedroom sensory environment and using emotional "wind down" as part of the bedtime routine. Some parents endorsed a beneficial effect of melatonin on their children's sleep. CONCLUSIONS: Sleep problems in children with ADHD were perceived as important issues by parents. Equipping parents with evidence-based strategies for the management of their children's sleep may lead to benefits for the children, parents and wider household.

CRISIS AFAR: an international collaborative study of the impact of the COVID-19 pandemic on mental health and service access in youth with autism and neurodevelopmental conditions.

BACKGROUND: Heterogeneous mental health outcomes during the COVID-19 pandemic are documented in the general population. Such heterogeneity has not been systematically assessed in youth with autism spectrum disorder (ASD) and related neurodevelopmental disorders (NDD). To identify distinct patterns of the pandemic impact and their predictors in ASD/NDD youth, we focused on pandemic-related changes in symptoms and access to services. METHODS: Using a naturalistic observational design, we assessed parent responses on the Coronavirus Health and Impact Survey Initiative (CRISIS) Adapted For Autism and Related neurodevelopmental conditions (AFAR). Cross-sectional AFAR data were aggregated across 14 European and North American sites yielding a clinically well-characterized sample of N = 1275 individuals with ASD/NDD (age = 11.0 ± 3.6 years; n females = 277). To identify subgroups with differential outcomes, we applied hierarchical clustering across eleven variables measuring changes in symptoms and access to services. Then, random forest classification assessed the importance of socio-demographics, pre-pandemic service rates, clinical severity of ASD-associated symptoms, and COVID-19 pandemic experiences/environments in predicting the outcome subgroups. RESULTS: Clustering revealed four subgroups. One subgroup-broad symptom worsening only (20%)-included youth with worsening across a range of symptoms but with service disruptions similar to the average of the aggregate sample. The other three subgroups were, relatively, clinically stable but differed in service access: primarily modified services (23%), primarily lost services (6%), and average services/symptom changes (53%). Distinct combinations of a set of pre-pandemic services, pandemic environment (e.g., COVID-19 new cases, restrictions), experiences (e.g., COVID-19 Worries), and age predicted each outcome subgroup. LIMITATIONS: Notable limitations of the study are its cross-sectional nature and focus on the first six months of the pandemic. CONCLUSIONS: Concomitantly assessing variation in changes of symptoms and service access during the first phase of the pandemic revealed differential outcome profiles in ASD/NDD youth. Subgroups were characterized by distinct prediction patterns across a set of pre- and pandemic-related experiences/contexts. Results may inform recovery efforts and preparedness in future crises; they also underscore the critical value of international data-sharing and collaborations to address the needs of those most vulnerable in times of crisis.

Service user satisfaction with care in a specialist service for young people with attention deficit hyperactivity disorder.

OBJECTIVES: Consumer satisfaction is considered one of the most important measures of service quality in child mental health; however, there is limited understanding of factors that influence satisfaction. The objective of this study was to investigate key factors influencing satisfaction with care (SWC) in ADMiRE, a specialist service for young people (YP) with attention deficit hyperactivity disorder (ADHD). METHODS: Parents/carers (n = 67) and YP > 9 years (n = 44) attending ADMiRE completed an anonymous Experience of Service Questionnaire (ESQ), a quantitative/qualitative measure of service user satisfaction. Parents/carers also completed symptom severity rating scales. Data were analysed to determine (i) overall SWC, (ii) the relationship between parent- and youth-reported SWC and (iii) the impact of symptom severity on SWC. Thematic analysis of qualitative ESQ data was completed. RESULTS: Parents/carers were significantly more satisfied than YP (p = 0.028). Symptom severity did not impact significantly on parent/carer satisfaction. YP with severe hyperactive/impulsive and inattentive ADHD symptoms were significantly less satisfied with care than those with less severe ADHD symptoms (p = 0.022 and p = 0.017 respectively). Factors related to the therapeutic alliance were identified as being particularly important to both parents/carers and YP. CONCLUSIONS: This is the first Irish study that has investigated the impact of symptom severity on service user satisfaction in a child mental health service. The results highlight the different perspectives of YP and parents and provide novel insights into the impact of symptom severity on service user satisfaction. The importance of the therapeutic alliance should not be underestimated in future development of services.

White matter microstructure in children and adolescents with ADHD.

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. Advances in diffusion magnetic resonance imaging (MRI) acquisition sequences and analytic techniques have led to growing body of evidence that abnormal white matter microstructure is a core pathophysiological feature of ADHD. This systematic review provides a qualitative assessment of research investigating microstructural organisation of white matter amongst children and adolescents with ADHD. This review included 46 studies in total, encompassing multiple diffusion MRI imaging techniques and analytic approaches, including whole-brain, region of interest and connectomic analyses. Whole-brain and region of interest analyses described atypical organisation of white matter microstructure in several white matter tracts: most notably in frontostriatal tracts, corpus callosum, superior longitudinal fasciculus, cingulum bundle, thalamic radiations, internal capsule and corona radiata. Connectomic analyses, including graph theory approaches, demonstrated global underconnectivity in connections between functionally specialised networks. Although some studies reported significant correlations between atypical white matter microstructure and ADHD symptoms or other behavioural measures there was no clear pattern of results. Interestingly however, many of the findings of disrupted white matter microstructure were in neural networks associated with key neuropsychological functions that are atypical in ADHD. Limitations to the extant research are outlined in this review and future studies in this area should carefully consider factors such as sample size, sex balance, head motion and medication status.

Subtly altered topological asymmetry of brain structural covariance networks in autism spectrum disorder across 43 datasets from the ENIGMA consortium.

Small average differences in the left-right asymmetry of cerebral cortical thickness have been reported in individuals with autism spectrum disorder (ASD) compared to typically developing controls, affecting widespread cortical regions. The possible impacts of these regional alterations in terms of structural network effects have not previously been characterized. Inter-regional morphological covariance analysis can capture network connectivity between different cortical areas at the macroscale level. Here, we used cortical thickness data from 1455 individuals with ASD and 1560 controls, across 43 independent datasets of the ENIGMA consortium's ASD Working Group, to assess hemispheric asymmetries of intra-individual structural covariance networks, using graph theory-based topological metrics. Compared with typical features of small-world architecture in controls, the ASD sample showed significantly altered average asymmetry of networks involving the fusiform, rostral middle frontal, and medial orbitofrontal cortex, involving higher randomization of the corresponding right-hemispheric networks in ASD. A network involving the superior frontal cortex showed decreased right-hemisphere randomization. Based on comparisons with meta-analyzed functional neuroimaging data, the altered connectivity asymmetry particularly affected networks that subserve executive functions, language-related and sensorimotor processes. These findings provide a network-level characterization of altered left-right brain asymmetry in ASD, based on a large combined sample. Altered asymmetrical brain development in ASD may be partly propagated among spatially distant regions through structural connectivity.

Shared and Supported Decision Making in Medication in a Mental Health Setting: How Far Have We Come?

Personalised care involves shared decision making (SDM) across all levels including choice in medication. However, there are a number of barriers which prevent its effective implementation in routine mental health settings. Therefore, we undertook a study to benchmark current practice across clinical services of a large urban mental health provider. The study formed part of the trust-wide 'Supported Decision Making in Medication' Co-Production Project and aims to inform future recommendations in delivering against contemporary best practice, guidance and policy. A survey exploring the views and experiences of service users and prescribers on shared and supported decision-making in medication was carried out in West London NHS Trust. Questionnaires were fully co-designed and co-delivered by a group of health professionals and individuals with lived experience. There were 100 responses from service users and 35 from prescribers. There was some good practice where both parties reported good quality conversations concerning dialogic styles, collaborative process, information provided and range of choice offered. However, prescriber's perception of their practice was not always mirrored by service user feedback whose experiences often depended upon the prescriber, the time available or the part of the service. Generally, service user experience fell short of the good practice cited by clinicians though there was noticeable variability. Commitment from organizations and increasing understanding from practitioners are vital in transforming SDM from rhetoric into reality. From our findings a further challenge is to ensure that prescribers and service users have the time, information and tools to implement it consistently.

Correction to: The child and adolescent psychiatry: study of training in Europe (CAP­STATE).

The original article has been corrected.

The child and adolescent psychiatry: study of training in Europe (CAP-STATE).

There is great cultural diversity across Europe. This is reflected in the organisation of child and adolescent mental health (CAMH) services and the training of the respective professionals in different countries in Europe. Patients and their parents will want a high quality, knowledgeable, and skillful service from child and adolescent psychiatrists (CAPs) wherever they see them in Europe. A European comparison of training programs allows all stakeholders in different European countries to assess the diversity and to initiate discussions as to the introduction of improvements within national training programs. Major issues to be addressed in comparing child and adolescent psychiatric training programs across Europe include: (1) formal organisation and content of training programs and the relationship to adult psychiatry and paediatrics; (2) flexibility of training, given different trainee interests and that many trainees will have young families; (3) quality of governance of training systems; (4) access to research; and (5) networking. The Child and Adolescent Psychiatry-Study of Training in Europe (CAP-State) is a survey of training for child and adolescent psychiatrists (CAPs) across European countries. It aims to revisit and extend the survey carried out in 2006 by Karabekiroglu and colleagues. The current article is embedded in a special issue of European Child + Adolescent Psychiatry attempting to for the first time address training in CAP at the European and global levels. Structured information was sought from each of 38 European and neighboring countries (subsequently loosely referred to as Europe) and obtained from 31. The information was provided by a senior trainee or recently qualified specialist and their information was checked and supplemented by information from a senior child and adolescent psychiatry trainer. Results showed that there is a very wide range of provision of training in child and adolescent psychiatry in different countries in Europe. There remains very substantial diversity in training across Europe and in the degree to which it is subject to national oversight and governance. Some possible reasons for this variation are discussed and some recommendations made.

Altered structural brain asymmetry in autism spectrum disorder in a study of 54 datasets.

Altered structural brain asymmetry in autism spectrum disorder (ASD) has been reported. However, findings have been inconsistent, likely due to limited sample sizes. Here we investigated 1,774 individuals with ASD and 1,809 controls, from 54 independent data sets of the ENIGMA consortium. ASD was significantly associated with alterations of cortical thickness asymmetry in mostly medial frontal, orbitofrontal, cingulate and inferior temporal areas, and also with asymmetry of orbitofrontal surface area. These differences generally involved reduced asymmetry in individuals with ASD compared to controls. Furthermore, putamen volume asymmetry was significantly increased in ASD. The largest case-control effect size was Cohen's d = -0.13, for asymmetry of superior frontal cortical thickness. Most effects did not depend on age, sex, IQ, severity or medication use. Altered lateralized neurodevelopment may therefore be a feature of ASD, affecting widespread brain regions with diverse functions. Large-scale analysis was necessary to quantify subtle alterations of brain structural asymmetry in ASD.

Exploring, measuring and enhancing the coproduction of health and well-being at the national, regional and local levels through comparative case studies in Sweden and England: the 'Samskapa' research programme protocol.

INTRODUCTION: Cocreation, coproduction and codesign are advocated as effective ways of involving citizens in the design, management, provision and evaluation of health and social care services. Although numerous case studies describe the nature and level of coproduction in individual projects, there remain three significant gaps in the evidence base: (1) measures of coproduction processes and their outcomes, (2) mechanisms that enable inclusivity and reciprocity and (3) management systems and styles. By focusing on these issues, we aim to explore, enhance and measure the value of coproduction for improving the health and well-being of citizens. METHODS AND ANALYSIS: Nine ongoing coproduction projects form the core of an interactive research programme ('Samskapa') during a 6-year period (2019-2024). Six of these will take place in Sweden and three will be undertaken in England to enable knowledge exchange and cross-cultural comparison. The programme has a longitudinal case study design using both qualitative and quantitative methods. Cross-case analysis and a sensemaking process will generate relevant lessons both for those participating in the projects and researchers. Based on the findings, we will develop explanatory models and other outputs to increase the sustained value (and values) of future coproduction initiatives in these sectors. ETHICS AND DISSEMINATION: All necessary ethical approvals will be obtained from the regional Ethical Board in Sweden and from relevant authorities in England. All data and personal data will be handled in accordance with General Data Protection Regulations. Given the interactive nature of the research programme, knowledge dissemination to participants and stakeholders in the nine projects will be ongoing throughout the 6 years. External workshops-facilitated in collaboration with participating case studies and citizens-both during and at the end of the programme will provide an additional dissemination mechanism and involve health and social care practitioners, policymakers and third-sector organisations.

Widespread Disrupted White Matter Microstructure in Autism Spectrum Disorders.

Autism Spectrum Disorders (ASDs) are characterised by impaired social communication and restricted repetitive behaviours. Researchers posit that these core features may be underpinned by disrupted structural connectivity. A tract based spatial statistical analysis of diffusion MRI data was performed to investigate white matter organisation (an indication of structural connectivity) in a well-defined cohort of 45 ASD and 45 age and IQ matched control participants. Aberrant structural connectivity characterised by reduced fractional anisotropy was observed in several fiber pathways in ASD relative to controls. Disrupted white matter organisation was associated with social deficits and restricted repetitive behaviours in ASD. Abnormal structural connectivity is apparent in ASD and may be linked to the core behavioural features of the disorder.

Abnormal fronto-parietal white matter organisation in the superior longitudinal fasciculus branches in autism spectrum disorders.

Core features of autism spectrum disorder (ASD) may be underpinned by disrupted functional and structural neural connectivity. Abnormal fronto-parietal functional connectivity has been widely reported in the literature; this may be underpinned by disrupted microstructural organisation of white matter. The superior longitudinal fasciculus (SLF) is a major fronto-parietal white matter tract, the structure of which has been little studied in ASD. The fronto-parietal projections of this tract (SLF I, II and III) are thought to play an important role in a number of cognitive functions including attention and visuospatial processing. To date, the isolation of the fronto-parietal branches of the SLF has been hampered by limitations of traditional tractography approaches. Constrained spherical deconvolution (CSD)-based tractography is an advanced approach that allows valid isolation of the fronto-parietal branches of the SLF. Diffusion MRI data were acquired from 45 participants with ASD and 45 age- and IQ-matched controls. The SLF I, II and III branches were isolated using CSD-based tractography in ExploreDTI. Significantly greater fractional anisotropy (FA) was observed in the right SLF II relative to controls. The ASD group also showed greater linear diffusion coefficient in the left SLF I and the right SLF II. In the SLF II, the ASD group had significantly greater right lateralisation of FA in comparison with the control group. The clinical and functional implications of increased FA in white matter are poorly understood; however, it is possible that this increased white matter organisation in the SLF in ASD may contribute to relative processing advantages in the condition.

Cortical and Subcortical Brain Morphometry Differences Between Patients With Autism Spectrum Disorder and Healthy Individuals Across the Lifespan: Results From the ENIGMA ASD Working Group.

OBJECTIVE: Neuroimaging studies show structural differences in both cortical and subcortical brain regions in children and adults with autism spectrum disorder (ASD) compared with healthy subjects. Findings are inconsistent, however, and it is unclear how differences develop across the lifespan. The authors investigated brain morphometry differences between individuals with ASD and healthy subjects, cross-sectionally across the lifespan, in a large multinational sample from the Enhancing Neuroimaging Genetics Through Meta-Analysis (ENIGMA) ASD working group. METHOD: The sample comprised 1,571 patients with ASD and 1,651 healthy control subjects (age range, 2-64 years) from 49 participating sites. MRI scans were preprocessed at individual sites with a harmonized protocol based on a validated automated-segmentation software program. Mega-analyses were used to test for case-control differences in subcortical volumes, cortical thickness, and surface area. Development of brain morphometry over the lifespan was modeled using a fractional polynomial approach. RESULTS: The case-control mega-analysis demonstrated that ASD was associated with smaller subcortical volumes of the pallidum, putamen, amygdala, and nucleus accumbens (effect sizes [Cohen's d], 0.13 to -0.13), as well as increased cortical thickness in the frontal cortex and decreased thickness in the temporal cortex (effect sizes, -0.21 to 0.20). Analyses of age effects indicate that the development of cortical thickness is altered in ASD, with the largest differences occurring around adolescence. No age-by-ASD interactions were observed in the subcortical partitions. CONCLUSIONS: The ENIGMA ASD working group provides the largest study of brain morphometry differences in ASD to date, using a well-established, validated, publicly available analysis pipeline. ASD patients showed altered morphometry in the cognitive and affective parts of the striatum, frontal cortex, and temporal cortex. Complex developmental trajectories were observed for the different regions, with a developmental peak around adolescence. These findings suggest an interplay in the abnormal development of the striatal, frontal, and temporal regions in ASD across the lifespan.

Measuring Unmet Needs for Anticipatory Guidance Among Adolescents at School-Based Health Centers.

PURPOSE: Our previously validated Youth Engagement with Health Services survey measures adolescent health care quality. The survey response format allows adolescents to indicate whether their needs for anticipatory guidance were met. Here, we describe the unmet needs for anticipatory guidance reported by adolescents and identify adolescent characteristics related to unmet needs for guidance. METHODS: We administered the survey in 2013-2014 to 540 adolescents who used school-based health centers in Colorado and New Mexico. A participant was considered to have unmet needs for anticipatory guidance if they indicated that guidance was needed on a given topic but not received or guidance was received that did not meet their needs. We calculated proportions of students with unmet needs for guidance and examined associations between unmet needs for guidance and participant characteristics using the chi-square test and logistic regression. RESULTS: Among participants, 47.4% reported at least one unmet need for guidance from a health care provider in the past year. Topics with the highest proportions of adolescents reporting unmet needs included healthy diet (19.5%), stress (18.0%), and body image (17.0%). In logistic regression modeling, adolescents at risk for depression and those with minority or immigrant status had increased unmet needs for guidance. Adolescents reporting receipt of patient-centered care were less likely to report unmet needs for guidance. CONCLUSIONS: The Youth Engagement with Health Services survey provides needs-based measurement of anticipatory guidance received that may support targeted improvements in the delivery of adolescent preventive counseling. Interventions to improve patient-centered care and preventive counseling for vulnerable youth populations may be warranted.

Multimodal MRI reveals structural connectivity differences in 22q11 deletion syndrome related to impaired spatial working memory.

INTRODUCTION: Impaired spatial working memory is a core cognitive deficit observed in people with 22q11 Deletion syndrome (22q11DS) and has been suggested as a candidate endophenotype for schizophrenia. However, to date, the neuroanatomical mechanisms describing its structural and functional underpinnings in 22q11DS remain unclear. We quantitatively investigate the cognitive processes and associated neuroanatomy of spatial working memory in people with 22q11DS compared to matched controls. We examine whether there are significant between-group differences in spatial working memory using task related fMRI, Voxel based morphometry and white matter fiber tractography. MATERIALS AND METHODS: Multimodal magnetic resonance imaging employing functional, diffusion and volumetric techniques were used to quantitatively assess the cognitive and neuroanatomical features of spatial working memory processes in 22q11DS. Twenty-six participants with genetically confirmed 22q11DS aged between 9 and 52 years and 26 controls aged between 8 and 46 years, matched for age, gender, and handedness were recruited. RESULTS: People with 22q11DS have significant differences in spatial working memory functioning accompanied by a gray matter volume reduction in the right precuneus. Gray matter volume was significantly correlated with task performance scores in these areas. Tractography revealed extensive differences along fibers between task-related cortical activations with pronounced differences localized to interhemispheric commissural fibers within the parietal section of the corpus callosum. CONCLUSIONS: Abnormal spatial working memory in 22q11DS is associated with aberrant functional activity in conjunction with gray and white matter structural abnormalities. These anomalies in discrete brain regions may increase susceptibility to the development of psychiatric disorders such as schizophrenia. Hum Brain Mapp 37:4689-4705, 2016. © 2016 Wiley Periodicals, Inc.