Autism Spectrum Disorder Adults Research Articles

Oxytocin receptor gene variations predict neural and behavioral response to oxytocin in autism.

Oxytocin appears beneficial for autism spectrum disorder (ASD), and more than 20 single-nucleotide polymorphisms (SNPs) in oxytocin receptor (OXTR) are relevant to ASD. However, neither biological functions of OXTR SNPs in ASD nor critical OXTR SNPs that determine oxytocin’s effects on ASD remains known. Here, using a machine-learning algorithm that was designed to evaluate collective effects of multiple SNPs and automatically identify most informative SNPs, we examined relationships between 27 representative OXTR SNPs and six types of behavioral/neural response to oxytocin in ASD individuals. The oxytocin effects were extracted from our previous placebo-controlled within-participant clinical trial administering single-dose intranasal oxytocin to 38 high-functioning adult Japanese ASD males. Consequently, we identified six different SNP sets that could accurately predict the six different oxytocin efficacies, and confirmed the robustness of these SNP selections against variations of the datasets and analysis parameters. Moreover, major alleles of several prominent OXTR SNPs—including rs53576 and rs2254298—were found to have dissociable effects on the oxytocin efficacies. These findings suggest biological functions of the OXTR SNP variants on autistic oxytocin responses, and implied that clinical oxytocin efficacy may be genetically predicted before its actual administration, which would contribute to establishment of future precision medicines for ASD.

Difficulty with selective listening in Autism spectrum disorder

Individuals with autism spectrum disorder (ASD) often experience difficulty with selective listening in the presence of multiple sounds despite their normal puretone thresholds. We have been conducting a series of studies to uncover neural bases for such difficulty in ASD adults without intellectual disability. First, we compared basic auditory functions between ASD and neurotypical (NT) groups, and found that (1) sensitivities to interaural time and level differences were lower in ASD than NT, and (2) a sub-group of ASD showed low sensitivity to temporal fine structure of acoustic waveforms. These findings suggest deficits in auditory processing in the brainstem of ASD. Second, we compared target detection thresholds between the two groups in the presence of distractors having little energetic masking on the target. Detection performance was dependent on the spectrotemporal coherence of target and distractor components in NT, whereas no such difference was observed in ASD, suggesting that ASD may lack automatic grouping across frequency channels. Additionally, we have observed significant differences between the two groups in behavioral, perceptual, autonomic, and brain responses to speech and/or non-speech stimuli. Taken together, difficulty with selective listening in ASD may involve several different mechanisms in both cortical and sub-cortical neural sites.

Interaction takes two: Typical adults exhibit mind-blindness towards those with autism spectrum disorder.

Recent work suggests that we are better at interpreting the movements of others who move like us, and that individuals with Autism Spectrum Disorder (ASD) move in a quantifiably different way from typical individuals. Therefore, "social impairments" exhibited by individuals with ASD may, at least in part, represent a failure by typical individuals to infer the correct mental states from the movements of those with ASD. To examine this possibility, individuals with ASD and typical adults manually directed 2 triangles to generate animations depicting mental state interactions. Kinematic analysis of the generated animations demonstrated that the participants with ASD moved atypically, specifically with increased jerk compared to the typical participants. In confirmation of our primary hypothesis, typical individuals were better able to identify the mental state portrayed in the animations produced by typical, relative to autistic, individuals. The participants with ASD did not show this "same group" advantage, demonstrating comparable performance for the 2 sets of animations. These findings have significant implications for clinical assessment and intervention in ASD, and potentially other populations with atypical movement. (PsycINFO Database Record

Unusual auditory/speech processing in autism spectrum disorder revealed by verbal transformation effects

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by an impaired ability to communicate and restricted and repetitive patterns of behavior. Sensory abnormality, a trait included in restricted patterns of behavior, is often observed in individuals with ASD. This study used an auditory illusion called “verbal transformation (VT)” to examine abnormal auditory/speech processing in ASD. In VT, a series of subjective perceptual changes occurs when subjects listen to a repeating word without a pause. The characteristic of VT is that, physically, the stimulus is the same repeated word but the perceptual change differs for each person. In this point, VT could be useful for demonstrating certain ASD traits such as favoring repetition. Twenty-four ASD adults and 24 neurotypical controls listened to three samples of repeated Japanese words for five minutes, and reported their percepts verbally whenever they experienced perceptual changes. As for the number of perceptual changes and that of reported forms, we found no significant difference between the ASD group and controls. However, the phonetic variations of form changes were different, and ASD group showed more phonetic variation than controls. We interpret the results from the viewpoint of unusual adaptation in auditory and/or phonetic processing.

White Matter Diffusion of Major Fiber Tracts Implicated in Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder found to have widespread alterations in the function and synchrony of brain regions. These differences may underlie alterations in microstructural organization, such as in white matter pathways. To investigate the diffusion of major white matter tracts, the current study examined multiple indices of white matter diffusion in 42 children and adults with ASD and 44 typically developing (TD) age- and IQ-matched peers using diffusion tensor imaging. Diffusivity measures were compared between groups for the following tracts: bilateral cingulum bundle, corpus callosum, inferior longitudinal fasciculus, superior longitudinal fasciculus, and uncinate fasciculus. Results indicate a significant reduction in fractional anisotropy (FA) for the left superior longitudinal fasciculus (LSLF) in ASD children and adults compared with TD peers. A significant increase in radial diffusivity for ASD participants was also found in the same cluster along the LSLF. In addition, a significant positive correlation emerged for all subjects between FA for the LSLF and age, with FA increasing with age. These findings point to a significant alteration in long-distance white matter connectivity in children and adults with ASD, potentially underscoring the relationship between alterations in white matter diffusion and the ASD phenotype. These results also suggest that the white matter alterations in autism may be subtle and related to the developmental trajectory.

Social anxiety in adult males with autism spectrum disorders

BackgroundPsychiatric conditions, notably anxiety, commonly co-occur with autism spectrum disorders (ASD). MethodThis study investigated self-reported behavioural, cognitive and affective symptoms of social anxiety (SA) in 50 adult males with ASD. Associations between SA, core ASD symptoms and facets of neuropsychological functioning were also examined. ResultsTwenty-six participants (52%) endorsed levels of SA that exceeded the suggested caseness threshold for social anxiety disorder. Categorical and dimensional data analyses indicated that there were no relationships between SA symptoms, present-state or childhood ASD symptom-severity, or measures of socio-emotional processing in this sample. ConclusionsStudy findings suggest that severity of SA is not merely a reflection of ASD symptom-severity. Further research is needed to ascertain the prevalence of SA in adult ASD epidemiological samples, and identify causal and maintaining mechanisms for these co-morbid symptoms.

Why are they waiting? Exploring professional perspectives and developing solutions to delayed diagnosis of autism spectrum disorder in adults and children

BackgroundThis paper reports on the development of child and adult Action Plans for Autism Spectrum Disorder to address the problem of delayed diagnosis and lengthy waiting times. Evidence used in the development of action plans was gathered from a sequential mixed methods study to further understand the reasons for the long waiting time and potential solutions. This is the first published investigation, from the perspective of diagnosing professional teams, of the reasons for delays, which also generates solutions. MethodsNinety five clinicians from 8 child and 8 adult services attended 16 focus groups to explore clinicians’ views on a) reducing the wait for diagnosis and b) providing a good quality diagnostic process with good adherence to clinical guidelines. During focus groups, quantitative data were fed back, used to frame discussions and facilitate solution focused action planning with each service. Sixteen local action plans were synthesised to create an ASD Action Plan for children and an ASD Action Plan for adults. ResultsKey solutions are proposed to support the reduction of the wait for diagnostic assessment, through reducing non-attendance rates, reducing inappropriate referrals, developing efficient working and communication and improving the effectiveness of care pathways. These are presented in actions plans for use by clinical teams. ConclusionThe first step in addressing the clinical challenge of increased wait for diagnostic assessment of ASD is understanding the complex and multi-factorial reasons for delays. The action plans developed here through systematic enquiry and synthesis may provide clinical diagnostic teams with evidence based guidance on common challenges and solutions to guide future quality improvement programmes. Future research to evaluate whether using Action Plans leads to a reduction in waiting times would be of value.

Anatomical imbalance between cortical networks in autism.

Influential psychological models of autism spectrum disorder (ASD) have proposed that this prevalent developmental disorder results from impairment of global (integrative) information processing and overload of local (sensory) information. However, little neuroanatomical evidence consistent with this account has been reported. Here, we examined relative grey matter volumes (rGMVs) between three cortical networks, how they changed with age, and their relationship with core symptomatology. Using public neuroimaging data of high-functioning ASD males and age-/sex-/IQ-matched controls, we first identified age-associated atypical increases in rGMVs of the regions of two sensory systems (auditory and visual networks), and an age-related aberrant decrease in rGMV of a task-control system (fronto-parietal network, FPN) in ASD children. While the enlarged rGMV of the auditory network in ASD adults was associated with the severity of autistic socio-communicational core symptom, that of the visual network was instead correlated with the severity of restricted and repetitive behaviours in ASD. Notably, the atypically decreased rGMV of FPN predicted both of the two core symptoms. These findings suggest that disproportionate undergrowth of a task-control system (FPN) may be a common anatomical basis for the two ASD core symptoms, and relative overgrowth of the two different sensory systems selectively compounds the distinct symptoms.

Does sex influence the diagnostic evaluation of autism spectrum disorder in adults?

It is unknown whether sex influences the diagnostic evaluation of autism spectrum disorder, or whether male and female adults within the spectrum have different symptom profiles. This study reports sex differences in clinical outcomes for 1244 adults (935 males and 309 females) referred for autism spectrum disorder assessment. Significantly, more males (72%) than females (66%) were diagnosed with an autism spectrum disorder of any subtype (x2 = 4.09; p = 0.04). In high-functioning autism spectrum disorder adults (IQ > 70; N = 827), there were no significant sex differences in severity of socio-communicative domain symptoms. Males had significantly more repetitive behaviours/restricted interests than females (p = 0.001, d = 0.3). A multivariate analysis of variance indicated a significant interaction between autism spectrum disorder subtype (full-autism spectrum disorder/partial-autism spectrum disorder) and sex: in full-autism spectrum disorder, males had more severe socio-communicative symptoms than females; for partial-autism spectrum disorder, the reverse was true. There were no sex differences in prevalence of co-morbid psychopathologies. Sex influenced diagnostic evaluation in a clinical sample of adults with suspected autism spectrum disorder. The sexes may present with different manifestations of the autism spectrum disorder phenotype and differences vary by diagnostic subtype. Understanding and awareness of adult female repetitive behaviours/restricted interests warrant attention and sex-specific diagnostic assessment tools may need to be considered.

Autism spectrum disorder in adults: diagnosis, management, and health services development.

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder characterized by pervasive difficulties since early childhood across reciprocal social communication and restricted, repetitive interests and behaviors. Although early ASD research focused primarily on children, there is increasing recognition that ASD is a lifelong neurodevelopmental disorder. However, although health and education services for children with ASD are relatively well established, service provision for adults with ASD is in its infancy. There is a lack of health services research for adults with ASD, including identification of comorbid health difficulties, rigorous treatment trials (pharmacological and psychological), development of new pharmacotherapies, investigation of transition and aging across the lifespan, and consideration of sex differences and the views of people with ASD. This article reviews available evidence regarding the etiology, legislation, diagnosis, management, and service provision for adults with ASD and considers what is needed to support adults with ASD as they age. We conclude that health services research for adults with ASD is urgently warranted. In particular, research is required to better understand the needs of adults with ASD, including health, aging, service development, transition, treatment options across the lifespan, sex, and the views of people with ASD. Additionally, the outcomes of recent international legislative efforts to raise awareness of ASD and service provision for adults with ASD are to be determined. Future research is required to identify high-quality, evidence-based, and cost-effective models of care. Furthermore, future health services research is also required at the beginning and end of adulthood, including improved transition from youth to adult health care and increased understanding of aging and health in older adults with ASD.

Predicting the diagnosis of autism in adults using the Autism-Spectrum Quotient (AQ) questionnaire.

Many adults with autism spectrum disorder (ASD) remain undiagnosed. Specialist assessment clinics enable the detection of these cases, but such services are often overstretched. It has been proposed that unnecessary referrals to these services could be reduced by prioritizing individuals who score highly on the Autism-Spectrum Quotient (AQ), a self-report questionnaire measure of autistic traits. However, the ability of the AQ to predict who will go on to receive a diagnosis of ASD in adults is unclear. We studied 476 adults, seen consecutively at a national ASD diagnostic referral service for suspected ASD. We tested AQ scores as predictors of ASD diagnosis made by expert clinicians according to International Classification of Diseases (ICD)-10 criteria, informed by the Autism Diagnostic Observation Schedule-Generic (ADOS-G) and Autism Diagnostic Interview-Revised (ADI-R) assessments. Of the participants, 73% received a clinical diagnosis of ASD. Self-report AQ scores did not significantly predict receipt of a diagnosis. While AQ scores provided high sensitivity of 0.77 [95% confidence interval (CI) 0.72-0.82] and positive predictive value of 0.76 (95% CI 0.70-0.80), the specificity of 0.29 (95% CI 0.20-0.38) and negative predictive value of 0.36 (95% CI 0.22-0.40) were low. Thus, 64% of those who scored below the AQ cut-off were 'false negatives' who did in fact have ASD. Co-morbidity data revealed that generalized anxiety disorder may 'mimic' ASD and inflate AQ scores, leading to false positives. The AQ's utility for screening referrals was limited in this sample. Recommendations supporting the AQ's role in the assessment of adult ASD, e.g. UK NICE guidelines, may need to be reconsidered.

The incremental validity of a computerised assessment added to clinical rating scales to differentiate adult ADHD from autism spectrum disorder

There is a clinical need for objective evidence-based measures that are sensitive and specific to ADHD when compared with other neurodevelopmental disorders. This study evaluated the incremental validity of adding an objective measure of activity and computerised cognitive assessment to clinical rating scales to differentiate adult ADHD from Autism spectrum disorders (ASD).Adults with ADHD (n=33) or ASD (n=25) performed the QbTest, comprising a Continuous Performance Test with motion-tracker to record physical activity. QbTest parameters measuring inattention, impulsivity and hyperactivity were combined to provide a summary score (‘QbTotal’). Binary stepwise logistic regression measured the probability of assignment to the ADHD or ASD group based on scores on the Conners Adult ADHD Rating Scale–subscale E (CAARS-E) and Autism Quotient (AQ10) in the first step and then QbTotal added in the second step. The model fit was significant at step 1 (CAARS-E, AQ10) with good group classification accuracy. These predictors were retained and QbTotal was added, resulting in a significant improvement in model fit and group classification accuracy. All predictors were significant. ROC curves indicated superior specificity of QbTotal. The findings present preliminary evidence that adding QbTest to clinical rating scales may improve the differentiation of ADHD and ASD in adults.

Multidisciplinary Treatment for Adults with Autism Spectrum Disorder and Co-Occurring Mental Health Disorders: Adapting Clinical Research Tools to Everyday Clinical Practice

ABSTRACTIn California, individuals with autism and co-occurring mental disorders, and their families, face two serious barriers when attempting to access the mental health services they need. The first is that the State Mental Health Specialty Service guidelines specifically exclude autism as a qualifying primary diagnosis for eligibility for mental health treatment and funding. The second is the lack of understanding and awareness regarding the challenges faced by individuals with classic autism and co-occurring mental disorders and their families. These two barriers, combined with the absence of a clear protocol for referral and assessment, have made access to services for clients and their families difficult. The Adult Autism Spectrum Disorder and Co-Occurring Mental Health Disorders project was an opportunity to study potential assessment tools and referral guidelines. We evaluated the use in a clinical setting of the Schedule for the Assessment of Psychiatric Problems Associated with Autism—a research instrument designed specifically for the psychiatric evaluation of patients with autism—to assist in diagnosing co-occurring mental health disorders. The experience gained in this study helped identify effective treatment options as well. After the assessment, clients were offered choices among several possible treatments fitting their specific needs. Our experience indicates that while adapting a research tool to everyday clinical service may encourage a more rigorous standardized approach to clinical assessment and evaluation, it may be difficult to employ such a tool in a clinical setting because of service needs and managed care constraints of serving a large and diverse population.

Characterization of immune cell phenotypes in adults with autism spectrum disorders

Autism spectrum disorders (ASDs) are neurodevelopmental disorders characterized by impairments in verbal and non-verbal communication, impaired social interactions and repetitive behaviors. There is evidence of a link between ASD symptoms...

Fast response to human voices in autism.

Individuals with autism spectrum disorders (ASD) are reported to allocate less spontaneous attention to voices. Here, we investigated how vocal sounds are processed in ASD adults, when those sounds are attended. Participants were asked to react as fast as possible to target stimuli (either voices or strings) while ignoring distracting stimuli. Response times (RTs) were measured. Results showed that, similar to neurotypical (NT) adults, ASD adults were faster to recognize voices compared to strings. Surprisingly, ASD adults had even shorter RTs for voices than the NT adults, suggesting a faster voice recognition process. To investigate the acoustic underpinnings of this effect, we created auditory chimeras that retained only the temporal or the spectral features of voices. For the NT group, no RT advantage was found for the chimeras compared to strings: both sets of features had to be present to observe an RT advantage. However, for the ASD group, shorter RTs were observed for both chimeras. These observations indicate that the previously observed attentional deficit to voices in ASD individuals could be due to a failure to combine acoustic features, even though such features may be well represented at a sensory level.

The intersection of autism spectrum disorder and intellectual disability

The intersection of autism spectrum disorder and intellectual disability

Screening for ASD in adults with ID-moving toward a standard using the DiBAS-R and the ACL.

Identification of Autism Spectrum Disorder (ASD) in persons with intellectual disability (ID) is challenging but essential to allow adequate treatment to be given. This study examines whether the combination of two ASD screening instruments specifically developed for persons with ID, namely, the Diagnostic Behavioral Assessment for ASD-Revised (DiBAS-R) and the Autism Checklist (ACL), improves diagnostic accuracy when used in combination compared to the application of the single instrument. A clinical sample of adults with ID who are suspected of having ASD (N =148) was assessed using two ID specific screening scales (DiBAS-R and ACL). The diagnostic validity of the single instruments and of their combination was assessed. While both instruments showed acceptable diagnostic validity when applied alone (DiBAS-R/ACL: sensitivity: 75%/91%; specificity: 75%/75%; overall agreement: 75%/83%), specificity increased when two positive screening results were used (88%), and sensitivity increased (95%) when at least one positive screening result was used. Different combinations of the ASD screening instruments DiBAS-R and ACL lead to improvements in sensitivity and specificity. The complementary use of the ACL in addition to the sole use of the DiBAS-R improves overall accuracy.

A small number of abnormal brain connections predicts adult autism spectrum disorder.

Although autism spectrum disorder (ASD) is a serious lifelong condition, its underlying neural mechanism remains unclear. Recently, neuroimaging-based classifiers for ASD and typically developed (TD) individuals were developed to identify the abnormality of functional connections (FCs). Due to over-fitting and interferential effects of varying measurement conditions and demographic distributions, no classifiers have been strictly validated for independent cohorts. Here we overcome these difficulties by developing a novel machine-learning algorithm that identifies a small number of FCs that separates ASD versus TD. The classifier achieves high accuracy for a Japanese discovery cohort and demonstrates a remarkable degree of generalization for two independent validation cohorts in the USA and Japan. The developed ASD classifier does not distinguish individuals with major depressive disorder and attention-deficit hyperactivity disorder from their controls but moderately distinguishes patients with schizophrenia from their controls. The results leave open the viable possibility of exploring neuroimaging-based dimensions quantifying the multiple-disorder spectrum.

Microduplications at the pseudoautosomal SHOX locus in autism spectrum disorders and related neurodevelopmental conditions

BackgroundThe pseudoautosomal short stature homeobox-containing (SHOX) gene encodes a homeodomain transcription factor involved in cell-cycle and growth regulation. SHOX/SHOX enhancers deletions cause short stature and skeletal abnormalities in a female-dominant...

Exploring the Experience of Self-Diagnosis of Autism Spectrum Disorder in Adults

One in 68 Americans has autism spectrum disorder (ASD), and diagnosis is often delayed into adulthood in individuals without comorbid intellectual disability. Many undiagnosed adults resort to self-diagnosis. The purpose of this descriptive phenomenology was to explore the experience of realizing a self-diagnosis of ASD among 37 individuals who were not formally diagnosed. Results revealed five themes: feeling “othered,” managing self doubt, sense of belonging, understanding myself, and questioning the need for formal diagnosis. Healthcare professionals must have an understanding of self-diagnosis to help individuals transition to formal diagnosis and to adequately educate, support, and screen this population for comorbidities.