A generalizable connectome-based marker of in-scan sustained attention in neurodiverse youth.

Difficulty with attention is an important symptom in many conditions in psychiatry, including neurodiverse conditions such as autism. There is a need to better understand the neurobiological correlates of attention and leverage these findings in healthcare settings. Nevertheless, it remains unclear if it is possible to build dimensional predictive models of attentional state in a sample that includes participants with neurodiverse conditions. Here, we use 5 datasets to identify and validate functional connectome-based markers of attention. In dataset 1, we use connectome-based predictive modeling and observe successful prediction of performance on an in-scan sustained attention task in a sample of youth, including participants with a neurodiverse condition. The predictions are not driven by confounds, such as head motion. In dataset 2, we find that the attention network model defined in dataset 1 generalizes to predict in-scan attention in a separate sample of neurotypical participants performing the same attention task. In datasets 3-5, we use connectome-based identification and longitudinal scans to probe the stability of the attention network across months to years in individual participants. Our results help elucidate the brain correlates of attentional state in youth and support the further development of predictive dimensional models of other clinically relevant phenotypes.

Seeing the forest and the trees: Disentangling autism phenotypes in the age of DSM-5.

This paper, written in honor of Professor Ed Zigler, focuses on some of the themes in developmental disabilities research that were so central to his work. It has now been nearly 80 years since Leo Kanner first identified the prototypic form - early infantile autism - of what is now autism spectrum disorder. In this article we summarize the development of the concept and the important accumulation of knowledge over time that has now led us to the recognition of a broader autism phenotype just as, at the same time, the current official diagnostic system in the USA has narrowed the concept. We also address current controversies regarding autism as the diagnosis is impacted by age and developmental factors, gender, and cultural issues. In parallel to the work on intellectual deficiency and development pioneered by Zigler and his colleagues, we summarize some of the challenges for the years ahead.

Assessing Binary Diagnoses of Bio-behavioral Disorders: The Clinical Relevance of Cohen's Kappa.

Cohen's (Educ Psychol Meth. 1960;23:37-40) kappa statistic has been criticized recently for providing low chance-corrected coefficients (<0.40) despite high levels of examiner agreement (e.g., ≥85%). The AC1 statistic (Series. 2002;2:1-9; BMC Med Res Methodol. 2013;13:61), the alpha statistic (J Clin Epidemiol. 1996;49:775-782), the B statistic (BMC Med Res Methodol. 2013;13:97), and the delta statistic (Commun Statist Theory Meth. 2008;37:760-772) were developed to "correct" this "problem." Each of these statistics produces inaccurate results because they either derive from levels of chance agreement that are incorrect (Gwet's AC1 statistic) or fail to correct for chance levels of agreement (the alpha, B, and delta approaches). Implications for diagnoses of psychiatric disorders are critically discussed. The importance of kappa is demonstrated in a number of clinical scenarios.

White Matter Abnormalities in Autism and Unaffected Siblings.

This study was conducted to identify a potential neuroendophenotype for autism using diffusion tensor imaging. Whole-brain, voxel-based analysis of fractional anisotropy was conducted in 50 children: 19 with autism, 20 unaffected siblings, and 11 controls. Relative to controls, participants with autism exhibited bilateral reductions in fractional anisotropy across association, commissure, and projection fibers. The most severely affected tracts included the uncinate fasciculus, forceps minor, and inferior fronto-occipital fasciculus. Unaffected siblings also exhibited reductions in fractional anisotropy, albeit less severe with fewer affected tracts, sparing the uncinate fasciculus and forceps minor. These results suggest the presence of a neuroendophenotype for autism.

Gender identity and autism spectrum disorders.

In this review, we briefly summarize much of the existing literature on gender-related concerns and autism spectrum disorders (ASD), drawing attention to critical shortcomings in our current understanding and potential clinical implications. Some authors have concluded that gender identity disorder (GID), or gender dysphoria (GD), is more common in individuals with ASD, providing a range of potential explanations. However, existing literature is quantitatively limited, and our capacity to draw conclusions is further complicated by conceptual challenges regarding how gender identity is best understood. Discourses that emphasize gender as a component of identity formation are gaining prominence and seem particularly salient when applied to ASD. Individuals with ASD should enjoy equal rights with regard to treatment for gender dysphoria. Clinicians may be able to assist individuals in understanding this aspect of their identity by broadening the social frame and facilitating an exploration of gender roles.

Sensory features as diagnostic criteria for autism: sensory features in autism.

In this study, we examined the frequency of sensory-related issues as reported by parents in a large sample of school-age adolescents and adults with autism/autism spectrum disorder (ASD) [1] as compared to a group of individuals receiving similar clinical evaluations for developmental/behavioral difficulties but whose final diagnoses were not on the autism spectrum. In no comparison were the features examined predictive of autism or autism spectrum in comparison to the non-ASD sample. Only failure to respond to noises had sensitivity above .75 in the comparison of the broader autism spectrum group, but specificity was poor. While sensory issues are relatively common in autism/ASD, they are also frequent in other disorders. These results question the rationale for including sensory items as a diagnostic criterion for autism.

Autism Spectrum Disorders: In Theory and Practice.

Autism is a prevalent and strongly genetic brain-based disorder. Early focus in the field on the relevance of psychogenic factors led to the blaming of parents for the occurrence of the disorder, and as a result mainstream research on psychotherapeutic approaches has until recently been limited. Although psychoanalytic approaches continue to be considered of limited relevance for these individuals, dynamic theory is both informative and informed by conceptual approaches to the understanding of autism. Theory of mind in particular is a prominent model for understanding the core deficits of autism and bears strong resemblance to the concept of mentalization. Although cognitive-behavioral and social skills interventions may form the cornerstone of psychotherapy for individuals with autism, the formation of a treatment alliance remains crucial and may require a particular willingness for flexibility on the part of the therapist.

From Kanner to DSM-5: autism as an evolving diagnostic concept.

Seven decades have elapsed since Leo Kanner described the syndrome he termed early infantile autism. Over this time, and particularly over the past two decades, noteworthy changes have occurred in how the condition is conceptualized. Here we provide an overview of these changes, beginning with a brief discussion of the significance of classification in general before discussing Kanner's original paper and subsequent changes. We touch on relevant issues, such as comorbidity, dimensional aspects of diagnosis and screening, and the complex issue of diagnosis relative to eligibility for services. Approaches to diagnosis have tended to swing from emphasizing overarching groups (lumping) to focusing on potentially distinct subgroups (splitting). Autism raises particular problems given the broad range of syndrome expression over age and developmental level. The most recent revision of the American Psychiatric Association's diagnostic taxonomy marks a significant departure from its predecessor and has been the focus of much debate. It remains unclear which of the currently existing categorical approaches will ultimately be most widely applied. We hope to convey a sense of areas in which consensus has been achieved and areas of continued controversy.

Vulnerability to Ideologically-Motivated Violence Among Individuals With Autism Spectrum Disorder.

People with autism spectrum disorder (ASD) are represented among those who espouse extremist thought and have committed violent acts associated with their beliefs. Media often highlight a perpetrator's psychiatric diagnosis following acts of mass violence, which in some instances has included ASD. ASD may itself not provide useful information for understanding motivations. Instead, understanding specific traits and neuropsychological and other vulnerabilities may offer an opportunity to make sense of these very complex events.

What are we optimizing for in autism screening? Examination of algorithmic changes in the M-CHAT.

The present study objectives were to examine the performance of the new M-CHAT-R algorithm to the original M-CHAT algorithm. The main purpose was to examine if the algorithmic changes increase identification of children later diagnosed with ASD, and to examine if there is a trade-off when changing algorithms. We included 54,463 screened cases from the Norwegian Mother and Child Cohort Study. Children were screened using the 23 items of the M-CHAT at 18 months. Further, the performance of the M-CHAT-R algorithm was compared to the M-CHAT algorithm on the 23-items. In total, 337 individuals were later diagnosed with ASD. Using M-CHAT-R algorithm decreased the number of correctly identified ASD children by 12 compared to M-CHAT, with no children with ASD screening negative on the M-CHAT criteria subsequently screening positive utilizing the M-CHAT-R algorithm. A nonparametric McNemar's test determined a statistically significant difference in identifying ASD utilizing the M-CHAT-R algorithm. The present study examined the application of 20-item MCHAT-R scoring criterion to the 23-item MCHAT. We found that this resulted in decreased sensitivity and increased specificity for identifying children with ASD, which is a trade-off that needs further investigation in terms of cost-effectiveness. However, further research is needed to optimize screening for ASD in the early developmental period to increase identification of false negatives.

Diffusion tensor imaging in autism spectrum disorders: preliminary evidence of abnormal neural connectivity.

OBJECTIVE: This study indirectly tested the hypothesis that individuals with autism spectrum disorders (ASDs) have impaired neural connections between the amygdala, fusiform face area, and superior temporal sulcus, key processing nodes of the 'social brain'. This would be evidenced by abnormalities in the major fibre tracts known to connect these structures, including the inferior longitudinal fasciculus and inferior fronto-occipital fasciculus. METHOD: Magnetic resonance diffusion tensor imaging was performed on 20 right-handed males (ASD = 10, controls = 10) with a mean age 13.5 ± 4.0 years. Subjects were group-matched according to age, full-scale IQ, handedness, and ethnicity. Fractional anisotropy was used to assess structural integrity of major fibre tracts. Voxel-wise comparison of white matter fractional anisotropy was conducted between groups using ANCOVA adjusting for age, full-scale IQ, and brain volume. Volumes of interest were identified using predetermined probability and cluster thresholds. Follow-up tractography was performed to confirm the anatomic location of all volumes of interest which were observed primarily in peri-callosal regions and the temporal lobes. RESULTS: The regions of lower fractional anisotropy, as confirmed by tractography, involved the inferior longitudinal fasciculus/inferior fronto-occipital fasciculus, superior longitudinal fasciculus, and corpus callosum/cingulum. Notably, some volumes of interest were adjacent to the fusiform face area, bilaterally, corresponding to involvement of the inferior longitudinal fasciculus. The largest effect sizes were noted for volumes of interest in the right anterior radiation of the corpus callosum/cingulum and right fusiform face area (inferior longitudinal fasciculus). CONCLUSIONS: This study provides preliminary evidence of impaired neural connectivity in the corpus callosum/cingulum and temporal lobes involving the inferior longitudinal fasciculus/inferior fronto-occipital fasciculus and superior longitudinal fasciculus in ASDs. These findings provide preliminary support for aberrant neural connectivity between the amygdala, fusiform face area, and superior temporal sulcus-temporal lobe structures critical for normal social perception and cognition.

Understanding the social brain in autism.

Autism is an early onset neurodevelopmental disorder characterized by disruption of early social interaction. Although the social disability of autism remains the central defining feature of the condition, mechanisms that might account for this disability remain poorly understood. This paper briefly reviews some aspects of the social deficit in autism focusing on new approaches to characterizing social information processing problems, potential brain mechanisms, and theoretical models of the disorder. It will touch on aspects of specific social processes that appear to develop in unusual ways in autism including facial perception, joint attention, and social information processing. The importance of adopting more ecologically valid methods and for integrating the various approaches in deriving new models for social deficits in autism will be highlighted. Future research should build on the emerging synergy of different aspects of social neuroscience.

Celebrating 40 years since DSM-III.

This special section celebrates the first official recognition of Autism as a diagnostic concept in 1980 in the third edition of the American Psychiatric Association's Diagnostic and Statistical Manual. The articles in this special section note the many areas of significant progress made as well as areas that remain important topics for continued and future research. The official recognition of autism as a diagnostic concept has significantly advanced both clinical work and research.

The Diagnosis of Autism: From Kanner to DSM-III to DSM-5 and Beyond.

In this paper we review the impact of DSM-III and its successors on the field of autism-both in terms of clinical work and research. We summarize the events leading up to the inclusion of autism as a "new" official diagnostic category in DSM-III, the subsequent revisions of the DSM, and the impact of the official recognition of autism on research. We discuss the uses of categorical vs. dimensional approaches and the continuing tensions around broad vs. narrow views of autism. We also note some areas of current controversy and directions for the future.

Low-motion fMRI data can be obtained in pediatric participants undergoing a 60-minute scan protocol.

Performing functional magnetic resonance imaging (fMRI) scans of children can be a difficult task, as participants tend to move while being scanned. Head motion represents a significant confound in fMRI connectivity analyses. One approach to limit motion has been to use shorter MRI protocols, though this reduces the reliability of results. Hence, there is a need to implement methods to achieve high-quality, low-motion data while not sacrificing data quantity. Here we show that by using a mock scan protocol prior to a scan, in conjunction with other in-scan steps (weighted blanket and incentive system), it is possible to achieve low-motion fMRI data in pediatric participants (age range: 7-17 years old) undergoing a 60 min MRI session. We also observe that motion is low during the MRI protocol in a separate replication group of participants, including some with autism spectrum disorder. Collectively, the results indicate it is possible to conduct long scan protocols in difficult-to-scan populations and still achieve high-quality data, thus potentially allowing more reliable fMRI findings.

Autism and autism spectrum disorders: diagnostic issues for the coming decade.

A decade and a half have elapsed since DSM-IV and ICD-10 appeared. During this time the convergent definitions of autism and related disorders in these two diagnostic systems have stimulated tremendous research. In this brief review we summarize areas of progress and continuing controversy, including approaches to diagnosis in more cognitively able individuals on the autism spectrum, diagnosis in very young infants, the issue of subtypes, and the potential contribution of genetic research. The use of dimensional assessments has some advantages as do the insights from prospective studies. At this point it will be important to study not only causative factors but developmental processes disrupted in these disorders.

Asperger syndrome.

Asperger syndrome (AS) is a chronic neurodevelopmental disorder of social interaction, communication, and a restricted range of behaviors or interests. Although not generally associated with intellectual disability, the severe social disability and, in many cases, associated mental health and other medical problems, result in disability throughout life. The diagnosis is often delayed, sometimes into adulthood, which is unfortunate because there are now a range of interventions available, and the current evidence supports intervention starting as early in childhood as possible. The aim of this review is to present a description of AS, an up to date synopsis of the literature pertaining to its etiology, co-morbidity and intervention options, and a discussion of current nosological controversies.

Development of the evaluative method for evaluating and determining evidence-based practices in autism.

Although research in autism has grown more sophisticated, the gap between research knowledge and applicability of research in real world settings has grown. There have been a number of different reviews of evidence-based practices of treatments for young children with autism. Reviews which have critically evaluated the empirical evidence have not found any treatments that can be considered evidence-based. Reasons for this shortcoming are explored, and a new method for the evaluation of empirical evidence is provided. Future uses of this evaluative method are provided as well as a discussion of how this tool might aid in narrowing the research to practice gap.

Reliability of the ADI-R: multiple examiners evaluate a single case.

The authors assessed the reliability of the Autism Diagnostic Interview (ADI-R). Seven Clinical Examiners evaluated a three and one half year old female toddler suspected of being on the Autism Spectrum. Examiners showed agreement levels of 94-96% across all items, with weighted kappa (K(w)) between .80 and .88. They were in 100% agreement on 74% of the items; in excellent agreement on 6% of the items (93-96%, with K(w) between .78 and .85); in good agreement on 7% (89-90%, with K(w) between .62 and 0.68); and in fair agreement on 3% (82 - 84%, with K(w) between .40 and .47). For the remaining 10% of ADI-R items, examiners showed poor agreement (50-81% with K(w )between -.67 and .37).

Brief Report: Bullying and Anxiety in High-Functioning Adolescents with ASD.

Youth with ASD are more likely to experience bullying than their typically developing peers. This risk has not been studied in youth with ASD transitioning to college. We examined the occurrence of bullying in 35 high functioning youth with ASD who were preparing to attend college. We also examined youth anxiety and ASD symptoms. Fifty-one percent of the sample reported being recent victims of bullying; 31% of parents reported their child was a victim of bullying. Parent report of bullying correlated significantly with ratings of youth social anxiety symptoms. These findings suggest that bullying is an issue of concern for higher functioning, older adolescents with ASD, and that their own reports may be particularly important in identifying its occurrence.