1. Athnaiel O, Job GA, Ocampo R, Teneqexhi P, Messer WS, Ragozzino ME. Effects of the Partial M1 Muscarinic Cholinergic Receptor Agonist CDD-0102A on Stereotyped Motor Behaviors and Reversal Learning in the BTBR Mouse Model of Autism. The international journal of neuropsychopharmacology. 2022; 25(1): 64-74.

BACKGROUND: Autism spectrum disorders (ASD) are a set of neurodevelopmental disorders marked by a lack of social interaction, restrictive interests, and repetitive behaviors. There is a paucity of pharmacological treatments to reduce core ASD symptoms. Various lines of evidence indicate that reduced brain muscarinic cholinergic receptor activity may contribute to an ASD phenotype. METHODS: The present experiments examined whether the partial M1 muscarinic receptor agonist, 5-(3-ethyl-1,2,4-oxadiazol-5-yl)-1,4,5,6-tetrahydropyrimidine hydrochloride (CDD-0102A), alleviates behavioral flexibility deficits and/or stereotyped motor behaviors in the BTBR mouse model of autism. Behavioral flexibility was tested using a reversal learning test. Stereotyped motor behaviors were measured by eliciting digging behavior after removal of nesting material in a home cage and by measuring repetitive grooming. RESULTS: CDD-0102A (0.2 and 0.6 mg/kg but not 1.2 mg/kg) injected prior to reversal learning attenuated a deficit in BTBR mice but did not affect performance in B6 mice. Acute CDD-0102A treatment (1.2 and 3 mg/kg) reduced self-grooming in BTBR mice and reduced digging behavior in B6 and BTBR mice. The M1 muscarinic receptor antagonist VU0255035 (3 mg/kg) blocked the effect of CDD-0102A on grooming behavior. Chronic treatment with CDD-0102A (1.2 mg/kg) attenuated self-grooming and digging behavior in BTBR mice. Direct CDD-0102A infusions (1 µg) into the dorsal striatum reduced elevated digging behavior in BTBR mice. In contrast, CDD-0102A injections in the frontal cortex were not effective. CONCLUSIONS: The results suggest that treatment with a partial M1 muscarinic receptor agonist may reduce repetitive behaviors and restricted interests in autism in part by stimulating striatal M1 muscarinic receptors.

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2. Ding H, Yi X, Zhang X, Wang H, Liu H, Mou WW. Imbalance in the Gut Microbiota of Children With Autism Spectrum Disorders. Frontiers in cellular and infection microbiology. 2021; 11: 572752.

BACKGROUND: Autism spectrum disorder (ASD) are complex behavioral changes manifesting early in childhood, which impacts how an individual perceives and socializes with others. The study aims to assess the disparities in gut microbiota (GM) amongst healthy controls and children with ASD. METHODS: The study was performed on 25 children with ASD and 20 healthy children. Autistic symptoms were diagnosed and assessed with the Diagnostic and Statistical Manual for Mental Disorders and the Autism Treatment Evaluation Checklist (ATEC). Gastrointestinal (GI) symptoms were assessed with a GI Severity Index (GSI) questionnaire. The fecal bacteria composition was investigated by the high-throughput sequencing of the V3-V4 region of the 16S rRNA gene. The alpha diversity was estimated using the Shannon, Chao, and ACE indexes. The unweighted UniFrac analysis and the PCA plots were used to represent the beta diversity. LDA and LEfSe were used to assess the effect sizes of each abundant differential taxon. RESULTS: Children with high GSI scores had much higher ATEC Total scores than those with lower GSI-scores. GI symptoms were strongly associated with symptoms of ASD. There was no difference in Chao, ACE, and Shannon indexes between ASD patients and healthy controls. Both groups showed a significant microbiota structure clustering in the plotted PCAs and significant differences in its composition at the family, order, genus, and phyla levels. There were also noteworthy overall relative differences in Actinobacteria and Firmicutes between both groups. CONCLUSIONS: This study shows the relationship between the clinical manifestations of Autistic symptoms and GI symptoms. ASD patients have dysbiosis of gut microbiota, which may be related to the onset of ASD. These findings may be beneficial for developing ASD symptoms by changing gut microbiota.

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3. Ding Q, Wu X, Li X, Wang H. Vorinostat Corrects Cognitive and Non-Cognitive Symptoms in a Mouse Model of Fragile X Syndrome. The international journal of neuropsychopharmacology. 2022; 25(2): 147-59.

BACKGROUND: Fragile X syndrome (FXS) is caused by mutations in the FMR1 gene. It is a form of heritable intellectual disability and autism. Despite recent advance in elucidating disease mechanisms, there is no efficacious medication. Because de novo drug development is a lengthy process, repurposing the existing FDA-approved drugs offers an opportunity to advance clinical intervention for FXS. Our previous study with transcriptome analysis predicts potential therapeutic effects of vorinostat on FXS. METHODS: We analyzed the vorinostat-induced transcriptome changes and confirmed its similarity to that induced by trifluoperazine, which was previously shown to correct pathological outcomes associated with FXS. To validate the therapeutic efficacy, we examined vorinostat’s effect on correcting the key behavioral and cellular symptoms in a mouse model of FXS. RESULTS: We found that vorinostat restores object location memory and passive avoidance memory in the Fmr1 knockout mice. For the non-cognitive behavioral symptoms, vorinostat corrected the autism-associated alterations, including repetitive behavior and social interaction deficits. In the open field test, vorinostat dampened hyperactivity in the center area of the arena. Surprisingly, vorinostat did not correct the abnormally elevated protein synthesis in cultured Fmr1 knockout hippocampal neurons, suggesting that different aspects of pathological outcomes may respond differently to a specific therapeutic intervention. CONCLUSIONS: We used the drug-induced transcriptome signature to predict new application of existing drugs. Our data reveal the therapeutic effects of the FDA-approved drug vorinostat in a mouse model of FXS.

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4. Gigliucci V, Teutsch J, Woodbury-Smith M, Luoni M, Busnelli M, Chini B, Banerjee A. Region-Specific KCC2 Rescue by rhIGF-1 and Oxytocin in a Mouse Model of Rett Syndrome. Cerebral cortex (New York, NY : 1991). 2021.

Rett syndrome (RTT) is characterized by dysfunction in neuronal excitation/inhibition (E/I) balance, potentially impacting seizure susceptibility via deficits in K+/Cl- cotransporter 2 (KCC2) function. Mice lacking the Methyl-CpG binding protein 2 (MeCP2) recapitulate many symptoms of RTT, and recombinant human insulin-like growth factor-1 (rhIGF-1) restores KCC2 expression and E/I balance in MeCP2 KO mice. However, clinical trial outcomes of rhIGF-1 in RTT have been variable, and increasing its therapeutic efficacy is highly desirable. To this end, the neuropeptide oxytocin (OXT) is promising, as it also critically modulates KCC2 function during early postnatal development. We measured basal KCC2 expression levels in MeCP2 KO mice and identified 3 key frontal brain regions showing KCC2 alterations in young adult mice, but not in postnatal P10 animals. We hypothesized that deficits in an IGF-1/OXT signaling crosstalk modulating KCC2 may occur in RTT during postnatal development. Consistently, we detected alterations of IGF-1 receptor and OXT receptor levels in those brain areas. rhIGF-1 and OXT treatments in KO mice rescued KCC2 expression in a region-specific and complementary manner. These results suggest that region-selective combinatorial pharmacotherapeutic strategies could be most effective at normalizing E/I balance in key brain regions subtending the RTT pathophysiology.

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5. Li W, Rohde H, Corley M. Veritable Untruths: Autistic Traits and the Processing of Deception. Journal of autism and developmental disorders. 2021.

How do we decide whether a statement is literally true? Here, we contrast participants’ eventual evaluations of a speaker’s meaning with the real-time processes of comprehension. We record participants’ eye movements as they respond to potentially misleading instructions to click on one of two objects which might be concealing treasure (the treasure is behind thee, uh, hat). Participants are less likely to click on the named object when the instructions are disfluent. However, when hearing disfluent utterances, a tendency to fixate the named object early increases with participants’ autism quotient scores. This suggests that, even where utterances are equivalently understood, the processes by which interpretations are achieved vary across individuals.

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6. Liu Y, Yang Z, Du Y, Shi S, Cheng Y. Antioxidant interventions in autism spectrum disorders: A meta-analysis. Progress in neuro-psychopharmacology & biological psychiatry. 2022; 113: 110476.

BACKGROUND: Autism spectrum disorder (ASD) might be associated with oxidative stress, and antioxidants are commonly used in the treatment of young people with ASD. However, the evidence about the effectiveness of these interventions remains debatable. We performed a meta-analysis to evaluate the effect of antioxidants on the symptoms of patients with autism. METHODS: Data sources: PubMed and Web of Science databases. STUDY SELECTION: We selected placebo-controlled, double-blind, randomized clinical trials published until February 2021 to evaluate the efficacy of antioxidant interventions on ASD. DATA ANALYSIS: Aberrant Behavior Checklist (ABC), Repetitive Behavior Scale-Revised (RBS), Social Responsiveness Scale (SRS), Developmental Behavior Checklist (DBC) and Clinical Global Impressions Severity scale (CGIS) were used to evaluate the 22 different symptom outcomes. The Hedges-adjusted g value was used to estimate the effect of each dietary intervention relative to the placebo. RESULTS: In this meta-analysis, we examined 13 double-blind randomized clinical trials, comprising a total of 570 patients with ASD: 293 in the intervention group and 277 in the placebo group. Antioxidants (N-acetylcysteine (NAC), other antioxidants) are more effective than placebos in improving the irritability among symptoms in the ABC and communication disturbance symptoms in the DBC. There was a good trend of improvement in the stereotypic behavior symptoms in the ABC. Treatment with NAC antioxidants showed a good trend of improvement in irritability in the ABC and symptoms of hyperactivity. The effect size was small, and there was a low risk of statistical heterogeneity and publication bias. LIMITATIONS: The number of studies in this meta-analysis was small and the sample size was small. CONCLUSION: This meta-analysis suggests that antioxidant intervention has a potential role in the management of some symptoms in patients with ASD, and indicates the feasibility of using antioxidants to treat autism in the future.

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7. Loth E, Ahmad J, Chatham C, López B, Carter B, Crawley D, Oakley B, Hayward H, Cooke J, San José Cáceres A, Bzdok D, Jones E, Charman T, Beckmann C, Bourgeron T, Toro R, Buitelaar J, Murphy D, Dumas G. The meaning of significant mean group differences for biomarker discovery. PLoS computational biology. 2021; 17(11): e1009477.

Over the past decade, biomarker discovery has become a key goal in psychiatry to aid in the more reliable diagnosis and prognosis of heterogeneous psychiatric conditions and the development of tailored therapies. Nevertheless, the prevailing statistical approach is still the mean group comparison between « cases » and « controls, » which tends to ignore within-group variability. In this educational article, we used empirical data simulations to investigate how effect size, sample size, and the shape of distributions impact the interpretation of mean group differences for biomarker discovery. We then applied these statistical criteria to evaluate biomarker discovery in one area of psychiatric research-autism research. Across the most influential areas of autism research, effect size estimates ranged from small (d = 0.21, anatomical structure) to medium (d = 0.36 electrophysiology, d = 0.5, eye-tracking) to large (d = 1.1 theory of mind). We show that in normal distributions, this translates to approximately 45% to 63% of cases performing within 1 standard deviation (SD) of the typical range, i.e., they do not have a deficit/atypicality in a statistical sense. For a measure to have diagnostic utility as defined by 80% sensitivity and 80% specificity, Cohen’s d of 1.66 is required, with still 40% of cases falling within 1 SD. However, in both normal and nonnormal distributions, 1 (skewness) or 2 (platykurtic, bimodal) biologically plausible subgroups may exist despite small or even nonsignificant mean group differences. This conclusion drastically contrasts the way mean group differences are frequently reported. Over 95% of studies omitted the « on average » when summarising their findings in their abstracts (« autistic people have deficits in X »), which can be misleading as it implies that the group-level difference applies to all individuals in that group. We outline practical approaches and steps for researchers to explore mean group comparisons for the discovery of stratification biomarkers.

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8. Manoharan TA, Radhakrishnan M. Region-Wise Brain Response Classification of ASD Children Using EEG and BiLSTM RNN. Clinical EEG and neuroscience. 2021: 15500594211054990.

AbstractAutism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairment in sensory modulation. These sensory modulation deficits would ultimately lead them to difficulties in adaptive behavior and intellectual functioning. The purpose of this study was to observe changes in the nervous system with responses to auditory/visual and only audio stimuli in children with autism and typically developing (TD) through electroencephalography (EEG). In this study, 20 children with ASD and 20 children with TD were considered to investigate the difference in the neural dynamics. The neural dynamics could be understood by non-linear analysis of the EEG signal. In this research to reveal the underlying nonlinear EEG dynamics, recurrence quantification analysis (RQA) is applied. RQA measures were analyzed using various parameter changes in RQA computations. In this research, the cosine distance metric was considered due to its capability of information retrieval and the other distance metrics parameters are compared for identifying the best biomarker. Each computational combination of the RQA measure and the responding channel was analyzed and discussed. To classify ASD and TD, the resulting features from RQA were fed to the designed BiLSTM (bi-long short-term memory) network. The classification accuracy was tested channel-wise for each combination. T3 and T5 channels with neighborhood selection as FAN (fixed amount of nearest neighbors) and distance metric as cosine is considered as the best-suited combination to discriminate between ASD and TD with the classification accuracy of 91.86%, respectively.

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9. Saha S, Saha T, Rajamma U, Sinha S, Mukhopadhyay K. Analysis of association between components of the folate metabolic pathway and autism spectrum disorder in eastern Indian subjects. Molecular biology reports. 2022; 49(2): 1281-93.

BACKGROUND: Folate has a pivotal role in maintaining different cellular processes including DNA integrity and neurotransmitter levels. Further, folate deficiency was reported in subjects with neuropsychiatric disorders including autism spectrum disorder (ASD). METHODS AND RESULTS: We recruited ASD probands following the Diagnostic and Statistical Manual of Mental Disorder-IV/-5. Severity was assessed by the Childhood Autism Rating Scale2-Standard Test (CARS2-ST). Functional SNPs in reduced folate carrier1 (rs1051266), methylenetetrahydrofolate dehydrogenase (rs2236225), methylenetetrahydrofolate methyltransferase (rs1805087), methylenetetrahydrofolate reductase (rs1801133 and rs1801131), cystathionine-beta- synthase (rs5742905), and serine hydroxymethyltransferase (rs1979277) genes were analyzed in the ASD probands (N = 203), their parents and controls (N = 250) by PCR/TaqMan based methods. Plasma homocysteine and vitamin B12 levels were examined by Enzyme-Linked ImmunoSorbent Assay. Statistical analysis revealed higher frequencies of rs1051266 and rs1805087 « A » alleles (P = 8.233e-005 and P = 0.010 respectively) and rs1051266 « AA » genotype (P = 0.02) in the ASD probands. Gender based stratified analysis revealed higher frequency of rs1051266 « AA » in the male probands (P = 0.001) while frequencies of rs1805087 « A » (P = 0.001) and « AA » (P < 0.05), and rs2236225 "CC" (P = 0.03) were higher in the females. The case-control analysis also exhibited a significant difference in the occurrence of biallelic and triallelic haplotypes. rs1051266 "A", rs1979277 "T" and rs5742905 "C" alleles showed biased parental transmission (P = 0.02). CARS2-ST scores were higher in the presence of rs5742905 "T" while scores were lower in the presence of rs1979277 "T" and rs1051266 "A". ASD probands showed vitamin B12 deficiency. CONCLUSION: Based on these observations, we infer that components needed for proper folate metabolism may influence ASD severity in this population.

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10. Seif A, Shea C, Schmid S, Stevenson RA. A Systematic Review of Brainstem Contributions to Autism Spectrum Disorder. Frontiers in integrative neuroscience. 2021; 15: 760116.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that affects one in 66 children in Canada. The contributions of changes in the cortex and cerebellum to autism have been studied for decades. However, our understanding of brainstem contributions has only started to emerge more recently. Disruptions of sensory processing, startle response, sensory filtering, sensorimotor gating, multisensory integration and sleep are all features of ASD and are processes in which the brainstem is involved. In addition, preliminary research into brainstem contribution emphasizes the importance of the developmental timeline rather than just the mature brainstem. Therefore, the purpose of this systematic review is to compile histological, behavioral, neuroimaging, and electrophysiological evidence from human and animal studies about brainstem contributions and their functional implications in autism. Moreover, due to the developmental nature of autism, the review pays attention to the atypical brainstem development and compares findings based on age. Overall, there is evidence of an important role of brainstem disruptions in ASD, but there is still the need to examine the brainstem across the life span, from infancy to adulthood which could lead the way for early diagnosis and possibly treatment of ASD.

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11. Shao L, Fu C, You Y, Fu D. Classification of ASD based on fMRI data with deep learning. Cognitive neurodynamics. 2021; 15(6): 961-74.

Autism spectrum disorder (ASD) is a neuro-developmental disorder that affects the social abilities of patients. Studies have shown that a small number of abnormal functional connections (FCs) exist in the cerebral hemisphere of ASD patients. The identification of these abnormal FCs provides a biological ground for the diagnosis of ASD. In this paper, we propose a combined deep feature selection (DFS) and graph convolutional network method to classify ASD. Firstly, in the DFS process, a sparse one-to-one layer is added between the input and the first hidden layer of a multilayer perceptron, thus each functional connection (FC) feature can be weighted and a subset of FC features can be selected accordingly. Then based on the selected FCs and the phenotypic information of subjects, a graph convolutional network is constructed to classify ASD and typically developed controls. Finally, we test our proposed method on the ABIDE database and compare it with some other methods in the literature. Experimental results indicate that the DFS can effectively select critical FC features for classification according to the weights of input FC features. With DFS, the performance of GCN classifier can be improved dramatically. The proposed method achieves state-of-the-art performance with an accuracy of 79.5% and an area under the receiver operating characteristic curve (AUC) of 0.85 on the preprocessed ABIDE dataset; it is superior to the other methods. Further studies on the top-ranked thirty FCs obtained by DFS show that these FCs are widespread over the cerebral hemisphere, and the ASD group appears a significantly higher number of weak connections compared to the typically developed group.

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12. Shtayermman O, Zhang Y. Attachment Style and Mental Health Profiles of Parents Caring for a Child with Autism: Suicidal Ideation, Depression and Anxiety. Journal of autism and developmental disorders. 2021.

The study investigated association between attachment style of parents with a child diagnosed with Autism and mental health. A cross-sectional web-based survey collected data from 184 parents of individuals with autism. Findings from the study indicated association between an avoidant and anxious attachment style and mental health. Mainly, a link between avoidant attachment style and parents’ levels of suicidal ideation and depression, an association between anxious attachment style and the parent’s level of suicidal ideation, depression and anxiety. Several sociodemographic variables were associated with suicidal ideation and mental health. Specifically, we identified impacts of child’s race on suicidal ideation, marital status on depression as well as impact of education on anxiety. Implication for future research, assessment and treatment are presented.

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13. Siddiqui S, Gunaseelan L, Shaikh R, Khan A, Mankad D, Hamid MA. Food for Thought: Machine Learning in Autism Spectrum Disorder Screening of Infants. Cureus. 2021; 13(10): e18721.

Diagnoses of autism spectrum disorders (ASD) are typically made after toddlerhood by examining behavioural patterns. Earlier identification of ASD enables earlier intervention and better outcomes. Machine learning provides a data-driven approach of diagnosing autism at an earlier age. This review aims to summarize recent studies and technologies utilizing machine learning based strategies to screen infants and children under the age of 18 months for ASD, and identify gaps that can be addressed in the future. We reviewed nine studies based on our search criteria, which includes primary studies and technologies conducted within the last 10 years that examine children with ASD or at high risk of ASD with a mean age of less than 18 months old. The studies must use machine learning analysis of behavioural features of ASD as major methodology. A total of nine studies were reviewed, of which the sensitivity ranges from 60.7% to 95.6%, the specificity ranges from 50% to 100%, and the accuracy ranges from 60.9% to 97.7%. Factors that contribute to the inconsistent findings include the varied presentation of ASD among patients and study design differences. Previous studies have shown moderate accuracy, sensitivity and specificity in the differentiation of ASD and non-ASD individuals under the age of 18 months. The application of machine learning and artificial intelligence in the screening of ASD in infants is still in its infancy, as observed by the granularity of data available for review. As such, much work needs to be done before the aforementioned technologies can be applied into clinical practice to facilitate early screening of ASD.

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14. Spiteri S, Crewther D. Neural Mechanisms of Visual Motion Anomalies in Autism: A Two-Decade Update and Novel Aetiology. Frontiers in neuroscience. 2021; 15: 756841.

The 21st century has seen dramatic changes in our understanding of the visual physio-perceptual anomalies of autism and also in the structure and development of the primate visual system. This review covers the past 20 years of research into motion perceptual/dorsal stream anomalies in autism, as well as new understanding of the development of primate vision. The convergence of this literature allows a novel developmental hypothesis to explain the physiological and perceptual differences of the broad autistic spectrum. Central to these observations is the development of motion areas MT+, the seat of the dorsal cortical stream, central area of pre-attentional processing as well as being an anchor of binocular vision for 3D action. Such development normally occurs via a transfer of thalamic drive from the inferior pulvinar → MT to the anatomically stronger but later-developing LGN → V1 → MT connection. We propose that autistic variation arises from a slowing in the normal developmental attenuation of the pulvinar → MT pathway. We suggest that this is caused by a hyperactive amygdala → thalamic reticular nucleus circuit increasing activity in the PIm → MT via response gain modulation of the pulvinar and hence altering synaptic competition in area MT. We explore the probable timing of transfer in dominance of human MT from pulvinar to LGN/V1 driving circuitry and discuss the implications of the main hypothesis.

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15. Thomas S, Fayet OM, Truffault F, Fadel E, Provost B, Hamza A, Berrih-Aknin S, Bonnefont JP, Le Panse R. Altered expression of fragile X mental retardation-1 (FMR1) in the thymus in autoimmune myasthenia gravis. Journal of neuroinflammation. 2021; 18(1): 270.

Predisposition to autoimmunity and inflammatory disorders is observed in patients with fragile X-associated syndromes. These patients have increased numbers of CGG triplets in the 5′ UTR region of FMR1 (Fragile X Mental Retardation 1) gene, that affects its expression. FMR1 is decreased in the thymus of myasthenia gravis (MG) patients, a prototypical autoimmune disease. We thus analyzed the number of CGG triplets in FMR1 in MG, and explored the regulatory mechanisms affecting thymic FMR1 expression. We measured the number of CGGs using thymic DNA from MG and controls, but no abnormalities in CGGs were found in MG that could explain thymic decrease of FMR1. We next analyzed by RT-PCR the expression of FMR1 and its transcription factors in thymic samples, and in thymic epithelial cell cultures in response to inflammatory stimuli. In control thymuses, FMR1 expression was higher in males than females, and correlated with CTCF (CCCTC-binding factor) expression. In MG thymuses, decreased expression of FMR1 was correlated with both CTCF and MAX (Myc-associated factor X) expression. Changes in FMR1 expression were supported by western blot analyses for FMRP. In addition, we demonstrated that FMR1, CTCF and MAX expression in thymic epithelial cells was also sensitive to inflammatory signals. Our results suggest that FMR1 could play a central role in the thymus and autoimmunity. First, in relation with the higher susceptibility of females to autoimmune diseases. Second, due to the modulation of its expression by inflammatory signals that are known to be altered in MG thymuses.

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16. Wiwe Lipsker C, Hirvikoski T, Balter LJT, Bölte S, Lekander M, Holmström L, Wicksell RK. Autistic Traits and Attention-Deficit Hyperactivity Disorder Symptoms Associated With Greater Pain Interference and Depression, and Reduced Health-Related Quality of Life in Children With Chronic Pain. Frontiers in neuroscience. 2021; 15: 716887.

Previous research indicates elevated levels of clinically significant traits and symptoms of autism spectrum disorder and attention-deficit hyperactivity disorder (ADHD) in children with chronic pain, but associations with functioning and depression are yet unclear. The current study examined the relationships of autistic traits and ADHD symptoms with pain interference, depression, and health-related quality of life, as well as the mediating roles of insomnia and psychological inflexibility, in children with chronic pain (n = 146, 8-17 years, 102 girls) presenting at a tertiary pain clinic. Children completed measures of pain intensity, depression, pain interference, health-related quality of life, insomnia, and psychological inflexibility. Parents (n = 146, 111 mothers) completed measures to assess autistic traits and ADHD symptoms in their children. Children with clinically significant autistic traits and ADHD symptoms presented with significantly higher levels of depressive symptoms and pain interference, and significantly lower health-related quality of life, than did the other children. Autistic traits and ADHD symptoms contributed significantly to the prediction of pain interference and depressive symptoms, as well as health-related quality of life. Psychological inflexibility mediated the relationships between ADHD symptoms and autistic traits on the one hand and depression, pain interference, and health-related quality of life on the other, while insomnia mediated the relationships between ADHD symptoms and depression, pain interference, and health-related quality of life. All analyses were adjusted for demographics and pain intensity. Results suggest the utility of screening for neurodevelopmental disorders in children with chronic pain. Furthermore, the findings may indicate insomnia and skills related to psychological flexibility as potential treatment targets in interventions aiming at improving functioning and health-related quality of life in children with chronic pain and co-occurring symptoms of neurodevelopmental disorders.

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17. Xu J, Zhou L, Liu F, Xue C, Jiang J, Jiang C. The autistic brain can process local but not global emotion regularities in facial and musical sequences. Autism research : official journal of the International Society for Autism Research. 2022; 15(2): 222-40.

Whether autism spectrum disorder (ASD) is associated with a global processing deficit remains controversial. Global integration requires extraction of regularity across various timescales, yet little is known about how individuals with ASD process regularity at local (short timescale) versus global (long timescale) levels. To this end, we used event-related potentials to investigate whether individuals with ASD would show different neural responses to local (within trial) versus global (across trials) emotion regularities extracted from sequential facial expressions; and if so, whether this visual abnormality would generalize to the music (auditory) domain. Twenty individuals with ASD and 21 age- and IQ-matched individuals with typical development participated in this study. At an early processing stage, ASD participants exhibited preserved neural responses to violations of local emotion regularity for both faces and music. At a later stage, however, there was an absence of neural responses in ASD to violations of global emotion regularity for both faces and music. These findings suggest that the autistic brain responses to emotion regularity are modulated by the timescale of sequential stimuli, and provide insight into the neural mechanisms underlying emotional processing in ASD.

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18. Zaharia A, Noir-Kahlo K, Bressoud N, Sander D, Dukes D, Samson AC. Proof of Concept: A Brief Psycho-Educational Training Program to Increase the Use of Positive Emotion Regulation Strategies in Individuals With Autism Spectrum Disorder. Frontiers in psychology. 2021; 12: 705937.

Attenuated positive emotions and difficulties in regulating emotions are frequently observed in individuals with autism spectrum disorders (ASD) and are linked to increased risk of affective disorders, problematic behaviors, and impaired socio-emotional functioning. As such, interventions specifically focused on positive emotion regulation (ER) skills could be very valuable for individuals with ASD, their caregivers, and therapists. However, the field of positive ER in ASD is under-researched. The present study aimed at testing the practical potential and the preliminary effects of a brief novel psycho-educational training program on positive ER for individuals with ASD. Thirty male participants with ASD (aged 10-35years; N (training)=14, N (waitlist)=16) underwent a three-session program on the use of adaptive positive ER strategies (i.e., attentional deployment, cognitive change, and response modulation). Participants rated the program as easy to understand, interesting, pleasant, and likable. No dropouts or adverse effects were observed. The training group showed a significant increase in the self-reported use of the ER strategies compared to the waitlist group. The increase in the use of ER strategies maintained up to 7 weeks in the overall sample. Having reached high satisfaction rates and the intended effects in this proof of concept study, this novel program represents a promising tool to support ER. Future research should next investigate the efficacy of the intervention on day-to-day emotional experience and wellbeing. Clinical Trial Registration: ClinicalTrials.gov # NCT02898298.

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