Autism Spectrum Disorder Adults Research Articles

Altered cytokine levels in the cerebrospinal fluid of adult patients with autism spectrum disorder

BackgroundDespite intensive research, the etiological causes of autism spectrum disorder (ASD) remain elusive. Immunological mechanisms have recently been studied more frequently in the context of maternal autoantibodies and infections, as well as altered cytokine profiles. For the detection of immunological processes in the central nervous system, analyses of cerebrospinal fluid (CSF) are advantageous due to its proximity to the brain. However, cytokine studies in the CSF of ASD patients are sparse. MethodsCSF was collected from a patient sample of 24 adults (m = 16, f = 8, age: 30.3 ± 11.6 years) with ASD and compared to a previously published mentally healthy control sample of 39 neurological patients with idiopathic intracranial hypertension. A magnetic bead multiplexing immunoassay was used to measure multiple cytokines in CSF. ResultsSignificantly decreased interferon-γ-induced protein-10 (p = 0.001) and monocyte chemoattractant protein-1 (p = 0.041) levels as well as significantly higher interleukin-8 levels (p = 0.041) were detected in patients with ASD compared with the control group. ConclusionThe main finding of this study is an altered cytokine profile in adult patients with ASD compared to the control group. This may indicate immune dysregulation in a subgroup of adult ASD patients. Further studies in larger cohorts that examine a broader spectrum of chemokines and cytokines in general are needed to detect possible specific immune signatures in ASD.

Adult autism spectrum disorder: knowledge, attitude and practice of health system professionals

PurposeThe prevalence of children with autism spectrum disorder (ASD) is rising. As children with ASD become adults, the need for appropriate physical and mental health care becomes more evident. Lack of knowledge and inadequate training about adult ASD can lead to discomfort in management and service delivery to this population. This study aims to assess knowledge, attitude and practice of health-care providers for patients with adult ASD and to determine the needs of health-care staff to provide convenient care to adult patients with ASD.Design/methodology/approachThis cross-sectional study was conducted in 2019–2020 among health-care professionals in Iran using an online questionnaire.FindingsIn this study, 182 health-care professionals (67.6% mental health professionals) participated. A minority of participants mentioned having excellent or very good knowledge about autism (10%) or acceptable access to clinical tools and guidelines (27%). Around 67% of professionals believed that patients with ASD are not cooperative. The most preferred training was training on effective communication strategies with ASD patients (64.8%).Practical implicationsThe authors found a gap in knowledge and training of adult ASD diagnosis and management among health-care providers.Originality/valueThis study highlights the significance of empowering professionals with better training to manage adult autism.

The experiencing sensory overload project (ESOP): developing an immersive simulation experience for healthcare professionals.

Atypical sensory processing is described as a difficulty in regulating and managing sensory input in a meaningful, ordered way to make sense of the world and environment in which you find yourself. Sensory processing disorder (SPD) is common in individuals with autism, pervasive development disorders, and neurodivergent conditions [1,2,3]. The National Institute of Clinical Excellence (NICE) [2] suggest sensory processing disorders are often overlooked by education, social, and healthcare professionals, leading to health and social inequalities with individuals less able to access ‘support and services that they need to live independently’ [2 p5]. The Experiencing Sensory Overload Project (ESOP) aims to champion inclusive practice and reduce health inequalities by encouraging and enabling healthcare professionals to reconsider their approach, and their working environments to create sensorily safe spaces for individuals who may experience sensory overload. The authors recognised there was insufficient education on SPD within the current nursing curriculum. To address this theory/practice gap, training was sought externally. This consisted of a short simulation-based activity with training delivered by carers who had experience of sensory overload. This was well evaluated by the student participants; however lecturing staff felt the training did not meet our university teaching and learning standards. The positive student feedback provided the impetus to forge links with digital arts colleagues to co-create a robust, pedagogically sound and immersive learning experience. The collaborative journey of ESOP has been led and facilitated by academics from the School of Nursing and Midwifery and the School of Arts in a cross-school alliance ( Immersive learning experiences that recognise and champion diversity must be integrated into the curricular of all healthcare professionals to promote the highest standards of patient care. Meeting this demand with innovative, immersive technology demands collaborative working. This cross-school alliance has produced a learning experience that can work towards reducing health inequalities, promoting independence, and championing inclusive practice. The experiencing sensory overload project (ESOP) collaborative journey 2019–2022 1. Walbam KM. The relevance of sensory processing disorder to social work practice: An interdisciplinary approach. Child and Adolescent Social Work Journal. 2014;31(1):61–70. 2. National institute Clinical Excellence. Autism spectrum disorder in adults: diagnosis and management. London: NICE; 2012. 1–42. CG142 3. Bolaños C, Gomez MM, Ramos G, Rios del Rio J. Developmental risk signals as a screening tool for early identification of sensory processing disorders. Occupational therapy international. 2016;23(2):154–164.

Neural substrates of theory of mind in adults with autism spectrum disorder: An fMRI study of the social animation task

Although the neural mechanisms of the theory of mind (ToM) in children with autism spectrum disorder (ASD) through fMRI using the social animation task have been investigated, little is known in adults with ASD. Therefore, the present study aimed to explore the neural substrates of ToM in adults with ASD. Moreover, we aimed to elucidate the relationship between brain activation and behavior of social interaction in adults with ASD. Twenty-four healthy controls and 24 adults with the clinical diagnosis of ASD were recruited. Participants were asked to complete the social animation task in functional magnetic resonance imaging. The imaging analyses of within (whole brain analysis) and between (5 regions of interest) group comparisons were conducted to explore the process of ToM. The correlation analyses were further conducted to explore the relationship between neural activations associated with ToM and social interaction abilities assessed by ADI-R. The ASD group showed greater activation in the left precuneus and right superior temporal gyrus (STG) than the control group. For correlation analyses, greater right STG activation was positively correlated with autistic symptoms assessed by the ADI-R in the ASD group. ASD adults might spend a lot of effort on identification processing, thereby influencing social communication skills. Also, the neural deficits of ToM in ASD adults might be associated with their social interaction difficulties.

Effects of data preprocessing on detecting autism in adults using web-based eye-tracking data

ABSTRACT Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder, often associated with social and communication challenges and whose prevalence has increased significantly over the past two decades. The variety of different manifestations of ASD makes the condition difficult to diagnose, especially in the case of highly independent adults. A large body of work is dedicated to developing new and improved diagnostic techniques, emphasising approaches that rely on objective markers. One such paradigm is investigating eye-tracking data as a promising and objective method to capture attention-related differences between people with and without autism. This study builds upon prior work in this area that focussed on developing a machine-learning classifier trained on gaze data from web-related tasks to detect ASD in adults. Using the same data, we show that a new data pre-processing approach, combined with an exploration of the performance of different classification algorithms, leads to an increased classification accuracy compared to prior work. The proposed approach to data pre-processing is stimulus-independent, suggesting that the improvements in performance shown in these experiments can potentially generalise over other studies that use eye-tracking data for predictive purposes.

Treatment Response of Transcranial Magnetic Stimulation in Intellectually Capable Youth and Young Adults with Autism Spectrum Disorder: A Systematic Review and Meta-Analysis.

To examine current clinical research on the use of transcranial magnetic stimulation (TMS) in the treatment of pediatric and young adult autism spectrum disorder in intellectually capable persons (IC-ASD). We searched peer-reviewed international literature to identify clinical trials investigating TMS as a treatment for behavioral and cognitive symptoms of IC-ASD. We identified sixteen studies and were able to conduct a meta-analysis on twelve of these studies. Seven were open-label or used neurotypical controls for baseline cognitive data, and nine were controlled trials. In the latter, waitlist control groups were often used over sham TMS. Only one study conducted a randomized, parallel, double-blind, and sham controlled trial. Favorable safety data was reported in low frequency repetitive TMS, high frequency repetitive TMS, and intermittent theta burst studies. Compared to TMS research of other neuropsychiatric conditions, significantly lower total TMS pulses were delivered in treatment and neuronavigation was not regularly utilized. Quantitatively, our multivariate meta-analysis results report improvement in cognitive outcomes (pooled Hedges' g = 0.735, 95% CI = 0.242, 1.228; p = 0.009) and primarily Criterion B symptomology of IC-ASD (pooled Hedges' g = 0.435, 95% CI = 0.359, 0.511; p < 0.001) with low frequency repetitive TMS to the dorsolateral prefrontal cortex. The results of our systematic review and meta-analysis data indicate that TMS may offer a promising and safe treatment option for pediatric and young adult patients with IC-ASD. However, future work should include use of neuronavigation software, theta burst protocols, targeting of various brain regions, and robust study design before clinical recommendations can be made.

Altered topological properties of white matter structural network in adults with autism spectrum disorder.

Autism spectrum disorder (ASD) is a complex developmental disability and is currently viewed as a disorder of brain connectivity in which white matter abnormalities. However, the majority of the research to date has focused on children with ASD. Understanding the topological organization of the white matter structural network in adults may help uncover the nature of ASD pathology in adulthood. This study investigated the topological properties of white matter structural network using diffusion tensor imaging and graph theory analysis in a sample of 32 adults with ASD compared to 35 matched typically developing (TD) controls. Group differences in global and nodal topological metrics were compared. The relationships between the altered network metrics and the severity of clinical symptoms were calculated. Compared to TD controls, ASD patients exhibited decreased small-worldness and increased global efficiency. In addition, the reduced nodal efficiency and increased nodal degree were found in the frontal (e.g., the inferior frontal gyrus) and parietal (e.g., postcentral gyrus) regions. Furthermore, the altered topological metrics (e.g., increased global efficiency and reduced nodal efficiency) were correlated with the severity of ASD symptoms. These results indicated that the complicatedly topological organization of the white matter structural network was abnormal and may play an essential role in the underlying pathological mechanism of ASD in adults.

Exploratory Data Analysis and Decision Tree Modeling for Autism Spectrum Disorder: Machine Learning Approach

As the early diagnosis of autism spectrum disorder (ASD) is critical the high accuracy machine learning can be applied to achieve technology based diagnosis. In this context, the present study demonstrates machine learning approach for ASD diagnosis using decision tree (DT) modeling. The dataset employed in the present study comprises two classes of ASD adults with a sample size of 704 instances. The DT model entails a recursive partitioning approach implemented in the “rpart” package of R. The optimum model is derived by tuning parameters such as Min split, Min bucket, Max depth, and complexity. The performance of the model is evaluated in terms of the mean square error estimate of the error rate.

Symptomatic generalised joint hypermobility and autism spectrum disorder are associated in adults

IntroductionIntriguingly, autism spectrum disorders (ASD) and symptomatic generalised joint hypermobility (S-GJH) (e.g. hypermobility spectrum disorders and Ehlers Danlos Syndrome) share several clinical manifestations including motor difficulties, sensory hypersensitivity and autonomic dysfunction. Moreover, many syndromic forms of ASD manifest a hypermobile phenotype. Despite the increased interest in the area, few systematic studies are available.ObjectivesThis large cross-sectional comparative study aimed to examine the association between S-GJH and ASD in adults.MethodsWe assessed GJH by physical examination using the Beighton Scoring System (BSS) and collected data on musculoskeletal symptoms and skin abnormalities amongst 156 adult patients with ASD and 413 adult community controls. A proxy for S-GJH was created by combining a positive BSS with at least one additional musculoskeletal symptom or skin abnormality.ResultsThe prevalence of S-GJH was significantly higher amongst patients with ASD than amongst controls (16.7% vs 4.8%, p&lt; .001). A logistic regression model, adjusting for candidate covariates of GJH (age, sex, race), revealed a significant influence of ASD on S-GJH with adjusted odds ratio of 5.4 (95% CI 2.8-10.5, p&lt; .001).ConclusionsASD and S-GJH are associated in adults. If recognised, musculoskeletal complications related to S-GJH can be relieved by physiotherapy. Clinicians should be familiar with that symptoms frequently occurring in GJH such as pain, fatigue and orthostatic intolerance may mimic or aggravate psychiatric symptoms (e.g. depression, anxiety). Knowledge about comorbidities may provide clues to underlying aethiopathological factors. Future research to clarify the mechanisms behind this association and to evaluate how comorbid S-GJH affects ASD outcome is warranted.DisclosureNo significant relationships.

Autism spectrum disorder in older adults: The case study of a 65-year-old man

IntroductionAutism spectrum disorder (ASD) is a neurodevelopmental disorder characterized with ritualized behavior, difficulties in communication/ social interaction, restricted interests, and sensitivity to external stimuli. The ASD has gained attention in recent years, however it’s still difficult in geropsychiatric setting to identify high-functioning ASD, especially when patients’ coping mechanisms are successful. Not to determine high-functioning ASD structure in older age can lead to wrong diagnosis and inappropriate treatment trials.ObjectivesThe aim of this presentation is to emphasize the importance of the evaluation of ASD-structure in old-age-psychiatry through the case study of a 65-years-old man.MethodsOne case report from the inpatient unit of a psychiatric clinic in Lower Saxony, Germany will be presented.ResultsCase: The patient was referred to our acute-psychiatric-ward due to delusional thoughts, depressive symptoms and lorazepam dependency. Delusional disorder was diagnosed in the outpatient-setting since he had interpreted some external stimuli in an eccentric way. During the therapeutic process, some features of high-functioning ASD such as social difficulties, dislike of change and repetitive/restrictive habits were prominent. Developmental history of the patient and the Autism-Spectrum-Quotient-50 also supported the clinical diagnosis of the ASD. Delusional disorder was excluded, and the therapy organized according to the structure characteristics of the high-functioning ASD which yielded to significant amelioration of depressive symptoms and increased perceived life quality of the patient.ConclusionsAlthough coping mechanisms of the patients can be successful, identifying high-functioning ASD-structure even in an old-age can be quite helpful in diagnostic/therapeutic processes. An elaborate discussion of the subject through contemporary literature will be presented.DisclosureNo significant relationships.

Kynurenine pathway and autism spectrum phenotypes: an investigation among adults with autism spectrum disorder and their first-degree relatives.

Increasing literature highlighted alterations of tryptophan (TRP) metabolism and kynurenine (KYN) pathway in children with autism spectrum disorder (ASD). However, no study specifically focused on adult samples. Meanwhile, several authors stressed the relevance of investigating neurobiological correlates of adult forms of ASD and of those subthreshold ASD manifestations frequently found in relatives of ASD probands, known as broad autism phenotype (BAP). This work aimed to evaluate circulating levels of TRP and metabolites of KYN pathway in a sample of ASD adults, their first-degree relatives and controls (CTLs), investigating also the correlations between biochemical variables' levels and ASD symptoms. A sample of ASD adults, together with a group of first-degree relatives (BAP group) and unrelated CTLs were assessed by means of psychometric scales. Circulating levels of TRP, KYN, quinolinic acid (QA), and kynurenic acid (KYNA) were assessed in all subjects. ASD patients reported significantly higher total scores than the other groups on all psychometric scales. BAP subjects scored significantly higher than CTLs. ASD patients reported significantly lower TRP levels than BAP and CTL groups. Moreover, significantly lower levels of KYNA were reported in both ASD and BAP groups than in CTLs. Specific patterns of associations were found between autism symptoms and biochemical variables. Our findings confirm in adult samples the presence of altered TRP metabolism through KYN pathway. The intermediate alterations reported among relatives of ASD patients further stress the presence of a continuum between subthreshold and full-threshold ASD phenotypes also from a biochemical perspective.

Abnormal Dynamic Functional Network Connectivity in Adults with Autism Spectrum Disorder.

This study sought to explore changes of brain dynamic functional network connectivity (dFNC) in adults with autism spectrum disorder (ASD) and investigate their relationship with clinical manifestations. Resting-state functional magnetic resonance imaging (rs-fMRI) data were acquired from 78adult ASD patients from autism brain imaging data exchange datasets, and 65age-matched healthy controls subjects from the local community. Independent component analysis was conducted to evaluate dFNC patterns on the basis of 13independent components (ICs) within 11resting-state networks (RSN), namely, auditory network (AUDN), basal ganglia network (BGN), language network (LN), sensorimotor network (SMN), precuneus network (PUCN), salience network (SN), visuospatial network (VSN), dorsal default mode network (dDMN), high visual network (hVIS), primary visual network (pVIS), ventral default mode network (vDMN). Fraction time, mean dwell time, number of transitions, and RSN connectivity were calculated for group comparisons. Correlation analyses were performed between abnormal metrics and autism diagnostic observation schedule (ADOS) scores. Compared with controls, ASD patients had higher fraction time and mean dwell time in state2 (P = 0.017, P = 0.014). Reduced dFNC was found in the SMN with PUCN, SMN with hVIS, and increased dFNC was observed in the dDMN with SN in state2 in the ASD group. Fraction time and mean dwell time was positively correlated with stereotyped behavior scores of ADOS. The findings demonstrated the importance of evaluating transient alterations in specific neural networks of adult ASD patients. The abnormal metrics and connectivity may be related to symptoms such as stereotyped behavior.

Motor signature of autism spectrum disorder in adults without intellectual impairment

Motor signs such as dyspraxia and abnormal gait are characteristic features of autism spectrum disorder (ASD). However, motor behavior in adults with ASD has scarcely been quantitatively characterized. In this pilot study, we aim to quantitatively examine motor signature of adults with ASD without intellectual impairment using marker-less visual-perceptive motion capture. 82 individuals (37 ASD and 45 healthy controls, HC) with an IQ > 85 and aged 18 to 65 years performed nine movement tasks and were filmed by a 3D-infrared camera. Anatomical models were quantified via custom-made software and resulting kinematic parameters were compared between individuals with ASD and HCs. Furthermore, the association between specific motor behaviour and severity of autistic symptoms (Autism Diagnostic Observation Schedule 2, Autism Spectrum Quotient) was explored. Adults with ASD showed a greater mediolateral deviation while walking, greater sway during normal, tandem and single leg stance, a reduced walking speed and cadence, a greater arrhythmicity during jumping jack tasks and an impaired manual dexterity during finger tapping tasks (p < 0.05 and |D|> 0.48) compared to HC. Furthermore, in the ASD group, some of these parameters correlated moderately to severity of ASD symptoms. Adults with ASD seem to display a specific motor signature in this disorder affecting movement timing and aspects of balance. The data appear to reinforce knowledge about motor signs reported in children and adolescents with ASD. Also, quantitative motor assessment via visual-perceptive computing may be a feasible instrument to detect subtle motor signs in ASD and perhaps suitable in the diagnosis of ASD in the future.

The utility of the autism-spectrum quotient to screen for autism spectrum disorder in adults with attention deficit/hyperactivity disorder

The co-occurrence of attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) has been reported to be highly prevalent in adults. However, very few studies have assessed the usefulness of screening instruments to detect this co-occurrence, particularly when screening for ASD in the context of ADHD. Our study aimed at assessing the utility of the autism-spectrum quotient (AQ) as a screening tool of ASD in a sample of 153 adults referred for ADHD assessment. Our results showed that the AQ is of limited use in this context as its positive predictive value was low (47%). Particularly, the more severe the attentional deficits the more likely individuals with ADHD were to be misclassified as having a co-occurring ASD based on the AQ. However, the “imagination” subscale of the AQ was able to discriminate those who met ASD criteria from those who did not, suggesting that targeting imagination impairments might be useful when assessing for the ADHD+ASD co-occurrence in clinical settings.

Features and Needs of Autistic Older Adults: A Delphi Study of Clinical Experiences

ABSTRACT Objectives In geriatric psychiatry Autism Spectrum Disorders (ASD) are increasingly recognized. This study explores what clinicians know about diagnostic and/or therapeutic aspects of autistic older adults and how aging plays a role in the course of ASD. Methods A Delphi study outlines the point of view of 11 clinical experts in the Netherlands and Belgium (Flanders). Results Regarding diagnostics, age-specific aspects need to be considered. Age-related characteristics (cognitive differences, life events, co-occurring conditions) influence detecting autistic features in older adults. Regarding treatment, counseling methods need to be adapted. Psychoeducation, family therapy, couples therapy, behavioral counseling and psychopharmaca can be helpful in meeting the needs of autistic older adults. There was no consensus on the effects of aging on autistic older adults. Conclusions Diagnosis and treatment of ASD need adaptation for autistic older adults. Further research is needed on the validation of measurement tools, recorded treatment, therapy, psychoeducation, and the effects of aging among people on the autism spectrum. Clinical Implications Available knowledge helps clinicians to detect ASD in older adults and adapt to the specific features and needs of autistic older adults. The effects of aging on the course of ASD are unclear yet.

Motor Cortex Excitation/Inhibition Imbalance in Young Adults With Autism Spectrum Disorder: A MRS-TMS Approach.

Excitatory/inhibitory imbalance has been suggested as a neurobiological substrate of the cognitive symptomatology in Autism Spectrum Disorder (ASD). Studies using magnetic resonance spectroscopy (MRS) attempted to characterize GABA and Glutamate brain levels in ASD. However mixed findings have been reported. Here, we characterize both neurochemical and physiological aspects of GABA system in ASD by implementing a more comprehensive approach combining MRS and transcranial magnetic stimulation (TMS). A group of 16 young ASD adults and a group of 17 controls participated in this study. We employed one MRS session to assess motor cortex GABA+ and Glutamate+Glutamine (Glx) levels using MEGAPRESS and PRESS sequences, respectively. Additionally, a TMS experiment was implemented including paired-pulse (SICI, ICF and LICI), input-output curve and cortical silent period to probe cortical excitability. Our results showed a significantly increased Glx, with unchanged GABA+ levels in the ASD group compared with controls. Single TMS measures did not differ between groups, although exploratory within-group analysis showed impaired inhibition in SICI5ms, in ASD. Importantly, we observed a correlation between GABA levels and measures of the input-output TMS recruitment curve (slope and MEP amplitude) in the control group but not in ASD, as further demonstrated by direct between group comparisons. In this exploratory study, we found evidence of increased Glx levels which may contribute to ASD excitatory/inhibitory imbalance while highlighting the relevance of conducting further larger-scale studies to investigate the GABA system from complementary perspectives, using both MRS and TMS techniques.

Eye-Tracking Studies in Adults with Autism Spectrum Disorder: A Systematic Review and Meta-analysis.

Eye-tracking studies have shown potential in effectively discriminating between autism spectrum disorder (ASD) and non-ASD groups. The main objective of the present study was to conduct a systematic review and meta-analysis of eye-tracking studies in adults with ASD. A total of 22 studies were included for meta-analysis. Eyes and Non-Social regions proved better for discriminating between ASD and non-ASD adults, while fixation duration seems to be the outcome to choose. Active engaged tasks seem to reduce differences between ASD and non-ASD adults, regardless of the emotional content of the stimuli/task. Proportional fixation duration on eyes and non-social areas in non-active tasks (e.g. free viewing) seems to be the best eye-tracking design for increasing the sensitivity and specificity in ASD adults.

Associations among autistic traits, cognitive and affective empathy, and personality traits in adults with autism spectrum disorder and no intellectual disability

Reported empathy deficits in autism spectrum disorder (ASD) could be attributable to other ASD-related features. We evaluated 28 ASD adults with no intellectual disability and 24 age-matched non-ASD control subjects using the Autism-Spectrum Quotient (AQ), Questionnaire of Cognitive and Affective Empathy (QCAE), Interpersonal Reactivity Index (IRI), and NEO Personality Inventory-Revised (NEO). Compared to the controls, ASD participants showed lower scores for perspective taking, online simulation, cognitive empathy, and peripheral responsivity on the QCAE, and lower scores for perspective taking and empathic concern on the IRI. Within the ASD group, the AQ scores showed significant relationships with perspective taking, online simulation and cognitive empathy on the QCAE, and perspective taking on the IRI. The ASD group also showed higher scores for neuroticism and lower scores for extraversion on the NEO compared to the controls. However, there were no relationships between AQ scores and NEO factors within the ASD group. Multiple regression analysis with stepwise linear regression demonstrated that perspective taking score on the QCAE and extraversion score on the NEO were good predictor variables to autistic traits on the AQ. These findings help us to understand empathy and personality traits in ASD adults with no intellectual disability.

Disease-Specific Contribution of Pulvinar Dysfunction to Impaired Emotion Recognition in Schizophrenia.

One important aspect for managing social interactions is the ability to perceive and respond to facial expressions rapidly and accurately. This ability is highly dependent upon intact processing within both cortical and subcortical components of the early visual pathways. Social cognitive deficits, including face emotion recognition (FER) deficits, are characteristic of several neuropsychiatric disorders including schizophrenia (Sz) and autism spectrum disorders (ASD). Here, we investigated potential visual sensory contributions to FER deficits in Sz (n = 28, 8/20 female/male; age 21–54 years) and adult ASD (n = 20, 4/16 female/male; age 19–43 years) participants compared to neurotypical (n = 30, 8/22 female/male; age 19–54 years) controls using task-based fMRI during an implicit static/dynamic FER task. Compared to neurotypical controls, both Sz (d = 1.97) and ASD (d = 1.13) participants had significantly lower FER scores which interrelated with diminished activation of the superior temporal sulcus (STS). In Sz, STS deficits were predicted by reduced activation of early visual regions (d = 0.85, p = 0.002) and of the pulvinar nucleus of the thalamus (d = 0.44, p = 0.042), along with impaired cortico-pulvinar interaction. By contrast, ASD participants showed patterns of increased early visual cortical (d = 1.03, p = 0.001) and pulvinar (d = 0.71, p = 0.015) activation. Large effect-size structural and histological abnormalities of pulvinar have previously been documented in Sz. Moreover, we have recently demonstrated impaired pulvinar activation to simple visual stimuli in Sz. Here, we provide the first demonstration of a disease-specific contribution of impaired pulvinar activation to social cognitive impairment in Sz.

Efficacy and safety of balovaptan for socialisation and communication difficulties in autistic adults in North America and Europe: a phase 3, randomised, placebo-controlled trial

There are no approved pharmacological therapies to support treatment of the core communication and socialisation difficulties associated with autism spectrum disorder in adults. We aimed to assess the efficacy, safety, and pharmacokinetics of balovaptan, a vasopressin 1a receptor antagonist, versus placebo in autistic adults. V1aduct was a phase 3, randomised, placebo-controlled, double-blind trial, conducted at 46 sites across six countries (the USA, the UK, France, Italy, Spain, and Canada). Eligible participants were aged 18 years or older with an intelligence quotient (IQ) of 70 or higher, and met the criteria for moderate-to-severe autism spectrum disorder (DSM-5 and Autism Diagnostic Observation Schedule). Participants were randomly allocated (1:1), with an independent interactive voice or web-based response system, to receive balovaptan (10 mg) or placebo daily for 24 weeks. Randomisation was stratified by an individual's baseline Vineland-II two-domain composite (2DC) score (<60 or ≥60), sex, region (North America or rest of world), and age (<25 years or ≥25 years). Participants, study site personnel, and the sponsor were masked to treatment assignment. The primary endpoint was change from baseline in Vineland-II 2DC score (the mean composite score across the Vineland-II socialisation and communication domains) at week 24. The primary analysis was done with ANCOVA in the intention-to-treat population. The V1aduct study was terminated for futility after around 50% of participants completed the week 24 visit. This trial is registered with ClinicalTrials.gov (NCT03504917). Between Aug 8, 2018, and July 1, 2020, 540 people were screened for eligibility, of whom 322 were allocated to receive balovaptan (164 [51%]) or placebo (158 [49%]). One participant from the balovaptan group was not treated before trial termination and was excluded from the analysis. 60 participants in the balovaptan group and 55 in the placebo group discontinued treatment before week 24. The sample consisted of 64 (20%) women and 257 (80%) men, with 260 (81%) participants from North America and 61 (19%) from Europe. At baseline, mean age was 27·6 years (SD 9·7) and mean IQ score was 104·8 (18·1). Two (1%) participants were American Indian or Alaska Native, eight (2%) were Asian, 15 (5%) were Black or African American, 283 (88%) were White, four (1%) were of multiple races, and nine (3%) were of unknown race. Mean baseline Vineland-II 2DC scores were 67·2 (SD 15·3) in the balovaptan group and 66·2 (17·7) in the placebo group. The interim futility analysis showed no improvement for balovaptan versus placebo in terms of Vineland-II 2DC score at week 24 compared with baseline, with a least-squares mean change of 2·91 (SE 1·52) in the balovaptan group (n=79) and 4·75 (1·60) in the placebo group (n=71; estimated treatment difference -1·84 [95% CI -5·15 to 1·48]). In the final analysis, mean change from baseline in Vineland-II 2DC score at week 24 was 4·56 (SD 10·85) in the balovaptan group (n=111) and 6·83 (12·18) in the placebo group (n=99). Balovaptan was well tolerated, with similar proportions of participants with at least one adverse event in the balovaptan group (98 [60%] of 163) and placebo group (104 [66%] of 158). The most common adverse events were nasopharyngitis (14 [9%] in the balovaptan group and 19 [12%] in the placebo group), diarrhoea (11 [7%] and 14 [9%]), upper respiratory tract infection (ten [6%] and nine [6%]), insomnia (five [3%] and eight [5%]), oropharyngeal pain (five [3%] and eight [5%]), and dizziness (two [1%] and ten [6%]). Serious adverse events were reported for two (1%) participants in the balovaptan group (one each of suicidal ideation and schizoaffective disorder), and five (3%) participants in the placebo group (one each of suicidal ideation, panic disorder, limb abscess, urosepsis, colitis [in the same participant with urosepsis], and death by suicide). No treatment-related deaths occurred. Balovaptan did not improve social communication in autistic adults. This study provides insights into challenges facing autism spectrum disorder trials, including the considerable placebo response and the selection of appropriate outcome measures. F Hoffmann-La Roche.