The investigation of functional magnetic resonance imaging (fMRI) data with traditional machine learning (ML) and deep learning (DL) classifiers has been widely used to study autism spectrum disorders (ASDs).  This condition is characterized by symptoms that affect the individual’s behavioral aspects and social relationships.  Early diagnosis is crucial for intervention, but the complexity of ASD poses challenges for the development of effective treatments.  This study compares traditional ML and DL classifiers in the analysis of tabular data, in particular, functional connectivity measures obtained from the time series of a public multicenter dataset, and evaluates whether the features that contribute most to the classification task vary depending on the classifier used.  Specifically, Support Vector Machine (SVM) classifiers, with both linear and radial basis function (RBF) kernels, and Extreme Gradient Boosting (XGBoost) classifiers are compared against the TabNet classifier (a DL architecture customized for tabular data analysis) and a Multi Layer Perceptron (MLP).  The findings suggest that DL classifiers may not be optimal for the type of data analyzed, as their performance trails behind that of standard classifiers.  Among the latter, SVMs outperform the other classifiers with an AUC of around 75%, whereas the best performances of TabNet and MLP reach 65% and 71% at most, respectively.  Furthermore, the analysis of the feature importance showed that the brain regions that contribute the most to the classification task are those primarily responsible for sensory and spatial perception, as well as attention modulation, which is known to be altered in ASDs.

Researchers studying autism spectrum disorder (ASD) lack a comprehensive map of the functional network topography in the ASD brain. We used high-quality resting state functional MRI (rs-fMRI) connectivity data and a robust parcellation routine to provide a whole-brain map of functional networks in a group of seventy high-functioning individuals with ASD and a group of seventy typically developing (TD) individuals. The rs-fMRI data were collected using an imaging sequence optimized to achieve high temporal signal-to-noise ratio (tSNR) across the whole-brain. We identified functional networks using a parcellation routine that intrinsically incorporates internal consistency and repeatability of the networks by keeping only network distinctions that agree across halves of the data over multiple random iterations in each group. The groups were tightly matched on tSNR, in-scanner motion, age, and IQ. We compared the maps from each group and found that functional networks in the ASD group are atypical in three seemingly related ways: (1) whole-brain connectivity patterns are less stable across voxels within multiple functional networks, (2) the cerebellum, subcortex, and hippocampus show weaker differentiation of functional subnetworks, and (3) subcortical structures and the hippocampus are atypically integrated with the neocortex. These results were statistically robust and suggest that patterns of network connectivity between the neocortex and the cerebellum, subcortical structures, and hippocampus are atypical in ASD individuals.

Autism spectrum disorders (ASD) are neurodevelopmental disorders characterized by varying degrees of dysfunctional communication and social interactions, repetitive and stereotypic behaviors, as well as learning and sensory deficits.  Despite the impressive rise in the prevalence of autism during the last two decades, there are few if any clues for its pathogenesis, early detection or treatment.  Increasing evidence indicates high brain expression of pro-inflammatory cytokines and the presence of circulating antibodies against brain proteins.  A number of papers, mostly based on parental reporting on their children's health problems, suggest that ASD children may present with “allergic-like” problems in the absence of elevated serum IgE and chronic urticaria.  These findings suggest non-allergic mast cell activation, probably in response to environmental and stress triggers that could contribute to inflammation. In utero inflammation can lead to preterm labor and has itself been strongly associated with adverse neurodevelopmental outcomes.  Premature babies have about four times higher risk of developing ASD and are also more vulnerable to infections, while delayed development of their gut–blood–brain barriers makes exposure to potential neurotoxins likely.  Perinatal mast cell activation by infectious, stress-related, environmental or allergic triggers can lead to release of pro-inflammatory and neurotoxic molecules, thus contributing to brain inflammation and ASD pathogenesis, at least in a subgroup of ASD patients.  This article is part of a Special Issue entitled: Mast cells in inflammation.

Objective:  Symptoms of ADHD are expected to be more difficult to treat in patients with a combination of ADHD and autism spectrum disorder (ASD) as opposed to only ADHD.  Little evidence is available on the influence of ASD on the effects of pharmacotherapy in adults with ADHD.  This study addresses this gap.  Method:  60 adults with ADHD and comorbid ASD were selected from an outpatient clinic and compared with 226 adults from the same clinic with only ADHD.  Similar treatment regimens were received.  Results:  Significant decreases in symptoms of ADHD were found in both groups.  A diagnosis of ASD did not affect the reduction in symptoms of ADHD.  No significant group differences in side effects or vital signs were found.  Conclusion:  Results show that medication for ADHD can effectively and safely be prescribed to patients with ADHD and comorbid ASD.  Suggestions for future research are discussed.

Autism is a highly heritable, heterogeneous, neurodevelopmental condition. Large-scale genetic studies, predominantly focussing on simplex families and clinical diagnoses of autism have identified hundreds of genes associated with autism. Yet, the contribution of these classes of genes to multiplex families and autistic traits still warrants investigation. Here, we conducted whole-genome sequencing of 21 highly multiplex autism families, with at least three autistic individuals in each family, to prioritise genes associated with autism. Using a combination of both autistic traits and clinical diagnosis of autism, we identify rare variants in genes associated with autism, and related neurodevelopmental conditions in multiple families. We identify a modest excess of these variants in autistic individuals compared to individuals without an autism diagnosis. Finally, we identify a convergence of the genes identified in molecular pathways related to development and neurogenesis. In sum, our analysis provides initial evidence to demonstrate the value of integrating autism diagnosis and autistic traits to prioritise genes.

Increasingly adults over the age of 50 are receiving a diagnosis of autism spectrum condition. Growing up in a time when autism was poorly recognised, these adults have lived unknowingly with the condition and face readjustment. This paper reports the first study to investigate this population.  Nine adults over the age of 50, who had recently been diagnosed with ASC, were interviewed, and thematic analysis was used to analyse the transcripts. Results showed that the participants had received treatment for anxiety and depression. They reported ASC behaviours in their childhood and growing up they felt isolated and alien. Receiving a diagnosis was seen as a positive step and allowed for a reconfiguration of self and an appreciation of individual needs. Given the positive aspects of receiving a late diagnosis, more work is needed to identify older adults with undiagnosed ASC.

Individuals with autism spectrum disorder (ASD) are thought to lack self-awareness and to experience difficulty empathizing with others.  Although these deficits have been demonstrated in previous studies, most of the target stimuli were constructed for typically developing (TD) individuals. We employed judgment tasks capable of indexing self-relevant processing in individuals with and without ASD.  Fourteen Japanese men and 1 Japanese women with high-functioning ASD (17–41 years of age) and 13 Japanese men and 2 TD Japanese women (22–40 years of age), all of whom were matched for age and full and verbal intelligence quotient scores with the ASD participants, were enrolled in this study.  The results demonstrated that the ventromedial prefrontal cortex was significantly activated in individuals with ASD in response to autistic characters and in TD individuals in response to non-autistic characters.  Although the frontal–posterior network between the ventromedial prefrontal cortex and superior temporal gyrus participated in the processing of non-autistic characters in TD individuals, an alternative network was involved when individuals with ASD processed autistic characters.  This suggests an atypical form of empathy in individuals with ASD toward others with ASD.

Autism is a neurodevelopmental condition involving atypical sensory-perceptual functions together with language and socio-cognitive deficits. Previous work has reported subtle alterations in the asymmetry of brain structure and reduced laterality of functional activation in individuals with autism relative to non-autistic individuals (NAI). However, whether functional asymmetries show altered intrinsic systematic organization in autism remains unclear. Here, we examined inter- and intra-hemispheric asymmetry of intrinsic functional gradients capturing connectome organization along three axes, stretching between sensory-default, somatomotor-visual, and default-multiple demand networks, to study system-level hemispheric imbalances in autism. We observed decreased leftward functional asymmetry of language network organization in individuals with autism, relative to NAI. Whereas language network asymmetry varied across age groups in NAI, this was not the case in autism, suggesting atypical functional laterality in autism may result from altered developmental trajectories. Finally, we observed that intra- but not inter-hemispheric features were predictive of the severity of autistic traits. Our findings illustrate how regional and patterned functional lateralization is altered in autism at the system level. Such differences may be rooted in atypical developmental trajectories of functional organization asymmetry in autism.

Normal brain functioning relies on high aerobic energy production provided by mitochondria. Failure to supply a sufficient amount of energy, seen in different brain disorders, including autism spectrum disorder (ASD), may have a significant negative impact on brain development and support of different brain functions. Mitochondrial dysfunction, manifested in the abnormal activities of the electron transport chain and impaired energy metabolism, greatly contributes to ASD. The aberrant functioning of this organelle is of such high importance that ASD has been proposed as a mitochondrial disease. It should be noted that aerobic energy production is not the only function of the mitochondria. In particular, these organelles are involved in the regulation of Ca2+ homeostasis, different mechanisms of programmed cell death, autophagy, and reactive oxygen and nitrogen species (ROS and RNS) production. Several syndromes originated from mitochondria-related mutations display ASD phenotype. Abnormalities in Ca2+ handling and ATP production in the brain mitochondria affect synaptic transmission, plasticity, and synaptic development, contributing to ASD. ROS and Ca2+ regulate the activity of the mitochondrial permeability transition pore (mPTP). The prolonged opening of this pore affects the redox state of the mitochondria, impairs oxidative phosphorylation, and activates apoptosis, ultimately leading to cell death. A dysregulation between the enhanced mitochondria-related processes of apoptosis and the inhibited autophagy leads to the accumulation of toxic products in the brains of individuals with ASD. Although many mitochondria-related mechanisms still have to be investigated, and whether they are the cause or consequence of this disorder is still unknown, the accumulating data show that the breakdown of any of the mitochondrial functions may contribute to abnormal brain development leading to ASD. In this review, we discuss the multifaceted role of mitochondria in ASD from the various aspects of neuroscience.

Rationale  Standard therapeutic approaches to reduce social anxiety in autistic adults have limited effectiveness. Since 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy shows promise as a treatment for other anxiety disorders, a blinded, placebo-controlled pilot study was conducted. Objectives  To explore feasibility and safety of MDMA-assisted psychotherapy for reduction of social fear and avoidance that are common in the autistic population. Methods  Autistic adults with marked to very severe social anxiety were randomized to receive MDMA (75 to 125 mg, n = 8) or inactive placebo (0 mg, n = 4) during two 8-h psychotherapy sessions (experimental sessions) in a controlled clinical setting. Double-blinded experimental sessions were spaced approximately 1 month apart with 3 non-drug psychotherapy sessions following each.  The primary outcome was change in Leibowitz Social Anxiety Scale (LSAS) Total scores from Baseline to one month after the second experimental session.  Outcomes were measured again six months after the last experimental session.   Results  Improvement in LSAS scores from baseline to the primary endpoint was significantly greater for MDMA group compared to the placebo group (P = 0.037), and placebo-subtracted Cohen’s d effect size was very large (d = 1.4, CI − 0.074, 2.874).  Change in LSAS scores from baseline to 6-month follow-up showed similar positive results (P = 0.036), with a Cohen’s d effect size of 1.1 (CI − 0.307, 2.527).  Social anxiety remained the same or continued to improve slightly for most participants in the MDMA group after completing the active treatment phase. Conclusions  This pilot trial demonstrated rapid and durable improvement in social anxiety symptoms in autistic adults following MDMA-assisted psychotherapy.  Initial safety and efficacy outcomes support expansion of research into larger samples to further investigate this novel treatment for social anxiety.

Autism spectrum conditions were once seen as a predominantly male condition. This has caused a paucity of information on common events in the lives of women, such as menstruation and menopause. Some smaller studies indicate that autistic women might suffer from increased difficulties surrounding these events. This study aims to investigate whether autistic women experience more frequent premenstrual dysphoric disorder, and increased complaints surrounding menopause. In partly overlapping samples (premenstrual dysphoric disorder, n = 70, nASC = 28, ncomparisons = 42; menopause, n = 65, nASC = 30, ncomparisons = 35), we investigated premenstrual dysphoric disorder prevalence and menopausal complaints. In 70 individuals, we did not find an increased prevalence of premenstrual dysphoric disorder in autistic women (14.3%) compared with non-autistic women (9.5%). In 65 women aged 40 years and above, we found that autistic women did experience higher levels of menopausal complaints. In autistic women, higher menopausal complaints were associated with higher levels of depression and autistic traits. In non-autistic women, menopausal complaints were associated with increased inattention, hyperactivity/impulsivity (i.e. attention deficit hyperactivity disorder traits), and depression. With this work, we show the important role that major reproductive milestones can have in an autistic woman’s life.

Influential theories suggest emotional feeling states arise from physiological changes from within the body. Interoception describes the afferent signalling, central processing, and neural and mental representation of internal bodily signals. Recent progress is made in conceptualizing interoception and its neural underpinnings. These developments are supported by empirical data concerning interoceptive mechanisms and their contribution to emotion. Fresh insights include description of short-term interoceptive effects on neural and mental processes (including fear-specific cardiac effects), the recognition of dissociable psychological dimensions of interoception, and models of interoceptive predictive coding that explain emotions and selfhood (reinforced by structural anatomical models and brain and experimental findings). This growing grasp of interoception is enriching our understanding of emotion and its disorders.