Core Symptoms Of Autism Spectrum Disorder Research Articles

Absence of parvalbumin increases mitochondria volume and branching of dendrites in inhibitory Pvalb neurons in vivo: a point of convergence of autism spectrum disorder (ASD) risk gene phenotypes

BackgroundIn fast firing, parvalbumin (PV)-expressing (Pvalb) interneurons, PV acts as an intracellular Ca2+ signal modulator with slow-onset kinetics. In Purkinje cells of PV−/− mice, adaptive/homeostatic mechanisms lead to an increase in mitochondria, organelles equally capable of delayed Ca2+ sequestering/buffering. An inverse regulation of PV and mitochondria likewise operates in cell model systems in vitro including myotubes, epithelial cells, and oligodendrocyte-like cells overexpressing PV. Whether such opposite regulation pertains to all Pvalb neurons is currently unknown. In oligodendrocyte-like cells, PV additionally decreases growth and branching of processes in a cell-autonomous manner.MethodsThe in vivo effects of absence of PV were investigated in inhibitory Pvalb neurons expressing EGFP, present in the somatosensory and medial prefrontal cortex, striatum, thalamic reticular nucleus, hippocampal regions DG, CA3, and CA1 and cerebellum of mice either wild-type or knockout (PV−/−) for the Pvalb gene. Changes in Pvalb neuron morphology and PV concentrations were determined using immunofluorescence, followed by 3D-reconstruction and quantitative image analyses.ResultsPV deficiency led to an increase in mitochondria volume and density in the soma; the magnitude of the effect was positively correlated with the estimated PV concentrations in the various Pvalb neuron subpopulations in wild-type neurons. The increase in dendrite length and branching, as well as thickness of proximal dendrites of selected PV−/− Pvalb neurons is likely the result of the observed increased density and length of mitochondria in these PV−/− Pvalb neuron dendrites. The increased branching and soma size directly linked to the absence of PV is assumed to contribute to the increased volume of the neocortex present in juvenile PV−/− mice. The extended dendritic branching is in line with the hypothesis of local hyperconnectivity in autism spectrum disorder (ASD) and ASD mouse models including PV−/− mice, which display all ASD core symptoms and several comorbidities including cortical macrocephaly at juvenile age.ConclusionPV is involved in most proposed mechanisms implicated in ASD etiology: alterations in Ca2+ signaling affecting E/I balance, changes in mitochondria structure/function, and increased dendritic length and branching, possibly resulting in local hyperconnectivity, all in a likely cell autonomous way.

Sleep Problems in Children with Autism Spectrum Disorder.

Sleep disorders are one of the most frequent comorbidities in children with autism spectrum disorder (ASD). Heterogeneous sleep problems in children with ASD have been reported, and insomnia has a prevalence in children with ASD ranging from 60% to 86%. Poor sleep can cause harmful effects on cognitive functions, fostering the appearance of aggression, irritability, inattention, and hyperactivity in children with ASD. Sleep disorders can also be related to the severity of the core symptoms of ASD, including social cognition and communication, stereotypic behavior, and hypersensitivity to the environment. The etiology of sleep disorders in children with ASD is multifactorial, related to complex interactions between biological factors and psychological, socio-environmental, and family factors. From the therapeutic perspective, interventions should only be considered after any medical conditions potentially contributing to sleep disorders have been carefully evaluated. [Pediatr Ann. 2020;49(6):e278-e282.].

Changes in Developmental Trajectories of Preschool Children with Autism Spectrum Disorder during Parental Based Intensive Intervention.

Background: Research highlights the positive effects of early intensive intervention with parent and school involvement for preschool children with Autism Spectrum Disorder (ASD) on general developmental outcomes and social skills in randomized controlled trials. However, given the inter-individual variability in the response to treatment, it is necessary to investigate intervention effects in terms of mediators and moderators in order to explain variability and to highlight mechanisms of change. Methods: 25 children in the experimental group were exposed to early intensive intervention and 14 children in the control group were subjected to “as usual” intervention. The initial assessment was obtained at the time of diagnosis (T1) and the follow-up assessment was conducted after 15 months of intervention (T2) in both groups. Results: Participants in the experimental group achieved more prominent gains in both cognitive and socio-interactive skills. The role of specific factors able to predict general quotient and language quotient after intervention were investigated, pointing out the contribution of personal–social and performance abilities. Conclusions: The findings support the importance of parental involvement in targeting ASD core symptoms. Further, results informed our understanding of early predictors in order to identify specific elements to be targeted in the individualized intervention design.

Temporal Aspects of Corollary Discharge Functioning in Adults With ASD

Motor and sensory abnormalities are features of autism spectrum disorder (ASD). Recently, we proposed that core symptoms of ASD may result from reduced attenuation of self-generated sensory information. Namely, corollary discharge (CD) signals allowing inhibition of neural responses to self-generated actions may be disturbed in ASD. Despite evidence for temporal processing deficits in ASD, the effects of temporal offset between action and perception are unknown.

Public knowledge and stigma of autism spectrum disorder: Comparing China with the United States.

Autism spectrum disorder in China differs considerably from autism spectrum disorder in the West in terms of prevalence estimates, education opportunities, and life outcomes of autistic people. The lack of autism spectrum disorder awareness could be a key factor underlying the disparities. To date, there has been no evaluation of autism spectrum disorder knowledge among the general public of China. Using the Autism Stigma and Knowledge Questionnaire developed for use in diverse cultural contexts, this study uncovered profoundly different public views about autism spectrum disorder in China compared with the United States. Determined by cognitive diagnosis modeling, 86%-91% of the surveyed U.S. citizens (N = 1127) achieved adequate autism spectrum disorder knowledge in diagnosis/symptoms, etiology, and treatment, whereas for the Chinese citizens (N = 1254) the percentages were only 57%-65%. Moreover, 14% of the participants from the United States were classified to endorse autism spectrum disorder stigma; in comparison, 38% of the Chinese participants endorsed autism spectrum disorder stigma. The Chinese citizens displayed knowledge deficits primarily in the areas of autism spectrum disorder core symptoms, comorbid intellectual impairment, and prognosis. Sociodemographic factors associated with the Chinese citizen's misconceptions included gender, ethnicity, social economic factors, among others. These results have important implications for increasing public awareness and promoting community participation for autistic individuals in China.Lay abstractASD in China differs considerably from ASD in the West in terms of prevalence estimates, education opportunities and life outcomes of autistic people. The lack of ASD awareness could be a key factor underlying these disparities. We asked 1127 U.S. citizens and 1254 Chinese citizens about their autism knowledge using the Autism Stigma and Knowledge Questionnaire (ASK-Q).The results indicated profoundly different public views about ASD in China compared to the U.S. Specifically, only 57%-65% of the Chinese citizens demonstrated adequate ASD knowledge compared to 86%-91% in the U.S. citizens. Fourteen percent of the U.S. citizens were shown to hold stigma beliefs towards ASD; in comparison, 38% of the Chinese citizens indicated ASD stigma. The Chinese citizens displayed misconceptions about ASD related to symptoms, causes, and possible long-term outcomes. In China but not in the U.S., male citizens and citizens with lower social economic status were more likely to have misconceptions about ASD than others were. The findings of this research can help increase public awareness about ASD and create a more inclusive environment for autistic people in China.

Altered gut microbial profile is associated with abnormal metabolism activity of Autism Spectrum Disorder

ABSTRACT Autism Spectrum Disorder (ASD) is a severe neurodevelopmental disorder. To enhance the understanding of the gut microbiota structure in ASD children at different ages as well as the relationship between gut microbiota and fecal metabolites, we first used the 16S rRNA sequencing to evaluate the gut microbial population in a cohort of 143 children aged 2–13 years old. We found that the α-diversity of ASD group showed no significant change with age, while the TD group showed increased α-diversity with age, which indicates that the compositional development of the gut microbiota in ASD varies at different ages in ways that are not consistent with TD group. Recent studies have shown that chronic constipation is one of the most commonly obvious gastrointestinal (GI) symptoms along with ASD core symptoms. To further investigate the potential interaction effects between ASD and GI symptoms, the 30 C-ASD and their aged-matched TD were picked out to perform metagenomics analysis. We observed that C-ASD group displayed decreased diversity, depletion of species of Sutterella, Prevotella, and Bacteroides as well as dysregulation of associated metabolism activities, which may involve in the pathogenesis of C-ASD. Consistent with metagenomic analysis, liquid chromatography-mass spectrometry (LC/MS) revealed some of the differential metabolites between C-ASD and TD group were involved in the metabolic network of neurotransmitters including serotonin, dopamine, histidine, and GABA. Furthermore, we found these differences in metabolites were associated with altered abundance of specific bacteria. The study suggested possible future modalities for ASD intervention through targeting the specific bacteria associated with neurotransmitter metabolism.

Significance of Beta-Band Oscillations in Autism Spectrum Disorders During Motor Response Inhibition Tasks: A MEG Study

In Autism Spectrum Disorders (ASD), impaired response inhibition and lack of adaptation are hypothesized to underlie core ASD symptoms, such as social communication and repetitive, stereotyped behavior. Thus, the aim of the present study was to compare neural correlates of inhibition, post-error adaptation, and reaction time variability in ASD and neuro-typical control (NTC) participants by investigating possible differences in error-related changes of oscillatory MEG activity. Twelve male NTC (mean age 20.3 ± 3.7) and fourteen male patients with ASD (mean age 17.8 ± 2.9) were included in the analysis. Subjects with ASD showed increased error-related reaction time variability. MEG analysis revealed decreased beta power in the ASD group in comparison to the NTC group over the centro-parietal channels in both, the pre-stimulus and post-response interval. In the ASD group, mean centro-parietal beta power negatively correlated with dimensional autism symptoms. In both groups, false alarms were followed by an early increase in temporo-frontal theta to alpha power; and by a later decrease in alpha to beta power at central and posterior sensors. Single trial correlations were additionally studied in the ASD group, who showed a positive correlation of pre-stimulus beta power with post-response theta, alpha, and beta power, particularly after hit trials. On a broader scale, the results deliver important insights into top-down control deficits that may relate to core symptoms observed in ASD.

Differences in Developmental Functioning Profiles Between Male and Female Preschoolers Children With Autism Spectrum Disorder.

This study investigated differences in clinical symptoms and developmental functioning profiles as well as sex-specific correlations of clinical characteristics and communication abilities, motor skills, and maladaptive behaviors in male and female preschoolers with autism spectrum disorder (ASD). Fifty-two females (mean age 4.5 ± 2.16 years old) and 62 males (mean age 4.2 ± 1.17 years old) with ASD were enrolled and assessed by measures including the Autism Diagnostic Observation Schedule-Second Edition (ADOS-2) and Psychoeducational Profile-Third Edition (PEP-3). We found intellectual disability in 91.2% of the children. While preschoolers with ASD showed comparable severity of restricted and repetitive behaviors (P = 0.17), females with ASD were less severely affected than age and intelligence quotient-matched males with ASD in the ADOS-2 social affect domain (P value = 0.001) and calibrated severity scores (P = 0.002). Interestingly, sex-specific linear regressions revealed that fine motor skills were predictive of impaired social affect in males but not in females. Specifically, motor skills might be the core feature for sex differences in ASD. Although preliminary, this finding suggests the need for more sex-specific diagnostic and intervention strategies in order to improve early identification efforts and specific intervention targets. LAY SUMMARY: Little is known about differences in developmental and functional profiles in males and females with autism spectrum disorder (ASD). We found important similarities and differences in the core ASD symptoms between male and female preschoolers. In addition, fine motor skills seem to predict social affect impairment and ASD symptom severity in males with ASD. Autism Res 2020, 13: 1537-1547. © 2020 International Society for Autism Research, Wiley Periodicals, Inc.

Sleep, brain development, and autism spectrum disorders: Insights from animal models.

Sleep is an evolutionarily conserved and powerful drive, although its complete functions are still unknown. One possible function of sleep is that it promotes brain development. The amount of sleep is greatest during ages when the brain is rapidly developing, and sleep has been shown to influence critical period plasticity. This supports a role for sleep in brain development and suggests that abnormal sleep in early life may lead to abnormal development. Autism spectrum disorder (ASD) is the most prevalent neurodevelopmental disorder in the United States. It is estimated that insomnia affects 44%-86% of the ASD population, predicting the severity of ASD core symptoms and associated behavioral problems. Sleep problems impact the quality of life of both ASD individuals and their caregivers, thus it is important to understand why they are so prevalent. In this review, we explore the role of sleep in early life as a causal factor in ASD. First, we review fundamental steps in mammalian sleep ontogeny and regulation and how sleep influences brain development. Next, we summarize current knowledge gained from studying sleep in animal models of ASD. Ultimately, our goal is to highlight the importance of understanding the role of sleep in brain development and the use of animal models to provide mechanistic insight into the origin of sleep problems in ASD.

Rigidity and Sensory Sensitivity: Independent Contributions to Selective Eating in Children, Adolescents, and Young Adults

ABSTRACTObjective: Selective or “picky” eating (SE) refers to rejection of a wide range of familiar and unfamiliar foods based on aversions to their sensory properties. When severe, SE can cause symptoms of avoidant/restrictive food intake disorder (ARFID), including weight loss, nutritional deficiencies, and/or psychosocial impairment. SE is highly prevalent in autism spectrum disorder (ASD) compared to both typical development and other developmental disorders. A possible explanation for the high prevalence of SE in ASD is the effect of core ASD symptoms, repetitive/restrictive behaviors (e.g., rigidity), and sensory sensitivity on feeding behaviors. These traits are found not only in ASD but also in other clinical groups and the general population, albeit often at subclinical levels. Identifying mechanisms of SE across various populations is critical to inform intervention approaches.Methods: In 263 unselected children ages 5–17, 534 unselected college students ages 18–22, 179 children with anxiety/obsessive spectrum disorders ages 5–17, and 185 children with ASD ages 4–17, we explored the unique contributions of sensory (i.e., oral texture and olfactory) sensitivities and rigidity as predictors of self/parent-reported SE.Results: In each sample, rigidity and oral texture sensitivity, controlling for olfactory sensitivity, age, and gender, emerged as significant, independent predictors of SE.Conclusions: This is the first study to highlight the importance of cognitive/behavioral rigidity to SE, and one of the first to illustrate the domain-specificity of the relationship between sensory sensitivity and SE.

Socio-emotional determinants of depressive symptoms in adolescents and adults with autism spectrum disorder: A systematic review.

Many adolescents and adults with autism spectrum disorder experience difficulty with symptoms of depression. These symptoms can contribute to poor quality of life and lack of independence for adolescents and adults. To better understand these symptoms, we conducted a review of articles that examined the presentation of depression specific to autism spectrum disorder. Our goals in conducting this study were (1) to examine whether depression may be associated with symptoms that are common among people with autism spectrum disorder, such as loneliness or poor social motivation; (2) to determine whether people with autism spectrum disorder experience depression in a different way than the general population; and (3) to add to other recent studies that have examined how common depression is in autism spectrum disorder and how it is typically measured. Our study reviewed 48 papers on this topic. Results showed that a substantial proportion of people with autism spectrum disorder experience significant symptoms of depression. We related our results to social factors commonly studied in this field (i.e. social motivation) and proposed a new model for the development of depression in this population.

The effect of dialectical behaviour therapy in autism spectrum patients with suicidality and/ or self-destructive behaviour (DIASS): study protocol for a multicentre randomised controlled trial

BackgroundMany persons with autism spectrum disorder (ASD) are treated in long-term specialised care. In this population, suicidal behaviour troubles patients, families, and specialists in the field because it is difficult to treat. At present, there is no documented effective therapy for suicidal behaviour in ASD (Autism Research 7:507-521, 2014; Crisis 35:301-309, 2014). Dialectical Behaviour Therapy (DBT) is an efficacious treatment programme for chronically suicidal and/or self-harm behaviour in patients with Borderline Personality Disorder (J Psychiatry 166:1365-1374, 2014; Linehan MM. Cognitive behavioural therapy of borderline personality disorder. 1993). This study will evaluate the efficacy of DBT in persons with ASD and suicidal/ self- destructive behaviour in a multicentre randomised controlled clinical trial.MethodOne hundred twenty-eight persons with autism and suicidal and/or self-harming behaviour will be recruited from specialised mental healthcare services and randomised into two conditions: 1) the DBT condition in which the participants have weekly individual cognitive behavioural therapy sessions and a 2.5 h skills training group session twice per week during 6 months, and 2) the treatment as usual condition which consists of weekly individual therapy sessions of 30–45 min with a psychotherapist or social worker. Assessments will take place at baseline, at post-treatment (6 months), and after a follow-up period of 12 months. The mediators will also be assessed at 3 months. The primary outcome is the level of suicidal ideation and behaviour. The secondary outcomes are anxiety and social performance, depression, core symptoms of ASD, quality of life, and cost-utility. Emotion regulation and therapeutic alliance are hypothesised to mediate the effects on the primary outcome.DiscussionThe results from this study will provide an evaluation of the efficacy of DBT treatment in persons with ASD on suicidal and self-harming behaviour. The study is conducted in routine mental health services which enhances the generalisability of the study results to clinical practice.Trial registrationISRCTN96632579. Registered 1 May 2019. Retrospectively registered.

Empirically based developmental and behavioral intervention programs targeting the core symptoms and language development in toddlers and preschool children with autism spectrum disorder

Empirically based developmental and behavioral intervention programs targeting the core symptoms and language development in toddlers and preschool children with autism spectrum disorder Abstract. This systematic review summarizes findings of articles included in the German AWMF-S3 clinical guideline on early intervention in autism spectrum disorders (ASD). We present the current state-of the art of evidence-based interventions for toddlers and preschool-aged children with ASD, specifically targeting the core symptoms and language development. We included studies on manualized developmental and behavioral interventions for children with ASD aged <7 years according to DSM-III(R), DSM-IV(TR), DSM-5, and ICD-10. The publication dates ranged from 1 January 2011 to 31 August 2018 or as included in the NICE-children guidelines. Studies were included by an iterative hierarchy: systematic review > randomized-controlled trial > clinically controlled trial. Outcome measures were core ASD symptoms and precursor abilities, or language abilities. The interventions were collated by (1) frequency and (2) approach. The studies focused on low-intensive interventions targeting parental synchrony, the child's initiations, reciprocity, joint attention, play and imitation skills as well as comprehensive interventions. Improvement of core ASD symptoms regarding social communication was observed for low-intensive training of parental synchrony and child's reciprocity as well as for low-intensive comprehensive developmental interventions implementing natural-learning paradigms. High-frequency discrete trial interventions did not improve social communication. Language abilities improved by comprehensive interventions. In conclusion, intervention recommendations are summarized.

Inflammation (IL-1β) Modifies the Effect of Vitamin D and Omega-3 Long Chain Polyunsaturated Fatty Acids on Core Symptoms of Autism Spectrum Disorder-An Exploratory Pilot Study‡.

Background: The role of vitamin D and omega-3 long chain polyunsaturated fatty acids (omega-3 LCPUFA) in improving core symptoms of autism spectrum disorder (ASD) in children has been investigated by a few randomised controlled trials and the results are mixed and inconclusive. The response to treatment with these nutrients is heterogenous and may be influenced by inflammatory state. As an exploratory analysis, we investigated whether inflammatory state would modulate the effect of these nutrients on core symptoms of ASD. Methods: Seventy-three New Zealand children with ASD (2.5–8.0 years) completed a 12-month randomised, double-blind, placebo-controlled trial of vitamin D (VID, 2000 IU/day), omega-3 LCPUFA; (OM, 722 mg/day docosahexaenoic acid), or both (VIDOM). Non-fasting baseline plasma interleukin-1β (IL-1β) was available for 67 children (VID = 15, OM = 21, VIDOM = 15, placebo = 16). Children were categorised as having undetectable/normal IL-1β (<3.2 pg/ml, n = 15) or elevated IL-1β (≥3.2 pg/mL, n = 52). The Social Responsiveness Scale (SRS) questionnaire was used to assess core symptoms of ASD (baseline, 12-month). Mixed model repeated measure analyses (including all children or only children with elevated IL-1β) were used. Results: We found evidence for an interaction between baseline IL-1β and treatment response for SRS-total, SRS-social communicative functioning, SRS-awareness and SRS-communication (all Pinteraction < 0.10). When all children were included in the analysis, two outcome comparisons (treatments vs. placebo) showed greater improvements: VID, no effect (all P > 0.10); OM and VIDOM (P = 0.01) for SRS-awareness. When only children with elevated IL-1β were included, five outcomes showed greater improvements: OM (P = 0.01) for SRS-total; OM (P = 0.03) for SRS-social communicative functioning; VID (P = 0.01), OM (P = 0.003) and VIDOM (P = 0.01) for SRS-awareness. Conclusion: Inflammatory state may have modulated responses to vitamin D and omega-3 LCPUFA intervention in children with ASD, suggesting children with elevated inflammation may benefit more from daily vitamin D and omega-3 LCPUFA supplementation.

Resveratrol in Autism Spectrum Disorders: Behavioral and Molecular Effects.

Resveratrol (RSV) is a polyphenolic stillbenoid with significant anti-oxidative and anti-inflammatory properties recently tested in animal models of several neurological diseases. Altered immune alteration and oxidative stress have also been found in patients with autism spectrum disorders (ASD), and these alterations could add to the pathophysiology associated with ASD. We reviewed the current evidence about the effects of RSV administration in animal models and in patients with ASD. RSV administration improves the core-symptoms (social impairment and stereotyped activity) in animal models and it also displays beneficial effects in other behavioral abnormalities such as hyperactivity, anxiety and cognitive function. The molecular mechanisms by which RSV restores or improves behavioral abnormalities in animal models encompass both normalization of central and peripheral immune alteration and oxidative stress markers and new molecular mechanisms such as expression of cortical gamma-amino butyric acid neurons, certain type of miRNAs that regulate spine growth. One randomized, placebo-controlled clinical trial (RCT) suggested that RSV add-on risperidone therapy improves comorbid hyperactivity/non-compliance, whereas no effects where seen in core symptoms of ASD No RCTs about the effect of RSV as monotherapy have been performed and the results from preclinical studies encourage its feasibility. Further clinical trials should also identify those ASD patients with immune alterations and/or with increased oxidative stress markers that would likely benefit from RSV administration.

The role of emotion regulation and core autism symptoms in the experience of anxiety in autism.

Many children with autism spectrum disorder have problems with managing their emotions (emotion regulation) and anxiety. In this study, over 1000 parents completed an online survey which showed that emotion regulation and anxiety are closely linked. Although emotion regulation and anxiety are inter-connected, the results also show that autism symptoms play an important role in anxiety in autism spectrum disorder. Emotion regulation problems may be an important target for the treatment of anxiety in autism.

THE EFFECT OF BIOFEEDBACK THERAPY FOR AUTISTIC SPECTRUM DISORDER (ASD)

Biofeedback has been reported to reduce symptoms of autism spectrum disorders (ASD) in several studies. Children affected by autism spectrum disorder (ASD) often have impairment of social interaction and demonstrate difficulty with emotional communication, display of posture and facial expression, with recognized relationships between postural control mechanisms and cognitive functions. Beside standard biomedical interventions and psychopharmacological treatments, there is increasing interest in the use of alternative non-invasive treatments such as biofeedback that could potentially modulate brain activity resulting in behavioral modification.&#x0D; Biofeedback therapy is a form of alternative medicine that involves measuring a patient’s quantifiable bodily functions such as sweat gland activity, skin temperature, blood pressure, heart rate and muscle tension, conveying the information to the patient in real time, this will arise the patient’s awareness and conscious control of their unconscious physiological activities. The purpose of this paper is to assess the effectiveness of biofeedback as a method of treatment of the core symptoms of ASD.&#x0D; Keywords: Biofeedback, Autistic Spectrum Disorder

Actions Speak Louder Than Words: The Role of Action in Self-Referential Advantage in Children With Autism.

Impaired self-processing in children with autism spectrum disorder (ASD) is believed to be closely associated with social-communicative deficits, a core symptom of ASD. In three experiments, we aimed to investigate (a) whether children with ASD exhibited deficient in self-processing, as reflected by their superior memory for self-related items as compared to other-related items, and (b) the role that action played in promoting self-processing in ASD. In Experiment 1, children with ASD, children with intellectual disability (ID), and typically developing children were asked to memorize items on the cards assigned to them or to the experimenter. The results indicated that the TD and ID groups had a self-referential memory advantage, but the ASD group did not. Experiments 2 and 3 examined whether the deficit in self-processing among children with ASDs was ameliorated when participants performed or observed an action to indicate the ownership of the items. We found that when children with ASD performed self-generated actions or observed virtual actions, they displayed a similar self-referential memory advantage as the other two groups. Our findings reveal that action plays an important role in the self-processing in children with ASD, and thereby contribute to a more comprehensive understanding of self-processing deficits in this population. Autism Res 2020, 13: 810-820. © 2020 International Society for Autism Research,Wiley Periodicals, Inc. LAY SUMMARY: We aimed to study whether children with autism spectrum disorder (ASD) exhibited deficient in self-processing and the role of action in promoting self-processing in ASD. We found that the typically developing and intellectual disability groups had a self-referential memory advantage, but the ASD group did not. However, children with ASD showed a significant self-referential advantage when they performed or observed an action to indicate the ownership of items. These findings highlight the vital role that action plays in cognitively enhancing their self-processing.

Symptom improvement in children with autism spectrum disorder following bumetanide administration is associated with decreased GABA/glutamate ratios

Bumetanide has been reported to alter synaptic excitation–inhibition (E-I) balance by potentiating the action of γ-aminobutyric acid (GABA), thereby attenuating the severity of autism spectrum disorder (ASD) in animal models. However, clinical evidence of its efficacy in young patients with ASD is limited. This was investigated in the present clinical trial of 83 patients, randomised to the bumetanide group (bumetanide treatment, 0.5 mg twice daily) or the control group (no bumetanide treatment). Primary [Children Autism Rating Scale (CARS)], secondary [Clinical Global Impressions (CGI)], and exploratory [inhibitory (γ-aminobutyric acid, GABA) and excitatory (glutamate, Glx) neurotransmitter concentrations measured in the insular cortex (IC) and visual cortex (VC) by magnetic resonance spectroscopy (MRS)] outcome measures were evaluated at baseline and at the 3-month follow-up. Side effects were monitored throughout the treatment course. Compared with the control group, the bumetanide group showed significant reduction in symptom severity, as indicated by both total CARS score and number of items assigned a score ≥ 3. The improvement in clinical symptoms was confirmed by CGI. GABA/Glx ratio in both the IC and VC decreased more rapidly over the 3-month period in the bumetanide group than that in the control group. This decrease in the IC was associated with the symptom improvement in the bumetanide group. Our study confirmed the clinical efficacy of bumetanide on alleviating the core symptoms of ASD in young children and it is the first demonstration that the improvement is associated with reduction in GABA/Glx ratios. This study suggests that the GABA/Glx ratio measured by MRS may provide a neuroimaging biomarker for assessing treatment efficacy for bumetanide.

Treatment of Adults with Autism and Major Depressive Disorder Using Transcranial Magnetic Stimulation: An Open Label Pilot Study.

Patients with autism spectrum disorder (ASD) are at high risk for comorbid major depressive disorder (MDD), which can severely impair functioning and quality of life. Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive brain stimulation technique, which is Food and Drug Administration (FDA) cleared for the treatment of MDD in adults. Despite demonstrated efficacy in the treatment of depression, there are limited data on the use of rTMS in patients with ASD and comorbid MDD. We hypothesized that a standard rTMS protocol for MDD would reduce depressive symptoms for adults with ASD and MDD. Secondarily, we investigated whether this treatment would also reduce core ASD symptoms. Participants of 18-65 years old with ASD and MDD without any medication changes in the last month were eligible for this open-label trial. Participants underwent 25 sessions of rTMS (figure-of-eight coil, 100-120% resting motor threshold, 10 Hz, 3,000 pulses per session) applied to the left dorsolateral prefrontal cortex. Thirteen participants enrolled in the study, with two withdrawing due to tolerability, and one excluded from analysis. Overall, side effects were mild and rTMS was well tolerated. The Hamilton rating scale for depression (HAM-D17 ) improved 13.5 points (IQR 5-15), and 40% of participants achieved remission (HAM-D17 ≤ 7) after rTMS treatment. Informant clinical scales of core symptoms of autism also suggested improvement with rTMS, though no change was observed by the participants themselves. Thus, this open-label trial suggests that high-frequency rTMS is well tolerated by adults with autism and MDD, with improvement in depressive symptoms and possible effects on core autism symptoms. Autism Res 2020, 13: 346-351. © 2020 International Society for Autism Research,Wiley Periodicals, Inc. LAY SUMMARY: This study evaluated the safety and effects of repetitive transcranial magnetic stimulation (rTMS) on depression and autism symptoms in individuals with both major depressive disorder and autism spectrum disorder. rTMS was well tolerated by the participants, depression improved with treatment, and family members' assessment of autism symptoms improved as well. This study supports the need for further work to evaluate rTMS in individuals who have both autism and depression.