1. Akbari M, Eghtedarian R, Hussen BM, Eslami S, Taheri M, Neishabouri SM, Ghafouri-Fard S. Assessment of Expression of Regulatory T Cell Differentiation Genes in Autism Spectrum Disorder. Front Mol Neurosci;2022;15:939224.

Dysfunction of regulatory T cells (Tregs) has been shown to affect the etiology of autism spectrum disorder (ASD). Differentiation of this group of T cells has been found to be regulated by a group of long non-coding RNAs (lncRNAs). In this study, we have examined the expression of five lncRNAs that regulate this process in the blood samples of ASD cases compared with controls. These lncRNAs were FOXP3 regulating long intergenic non-coding RNA (FLICR), MAF transcriptional regulator RNA (MAFTRR), NEST (IFNG-AS1), RNA component of mitochondrial RNA processing endoribonuclease (RMRP), and Th2 cytokine locus control region (TH2-LCR). Expression of RMRP was significantly lower in total ASD cases compared to controls [expression ratio (95% CI) = 0.11 (0.08-0.18), adjusted P-value < 0.0001]. This pattern was also detected in both men and women cases compared with corresponding controls [expression ratio (95% CI) = 0.15 (0.08-0.29) and 0.08 (0.03-0.2), respectively]. Likewise, expression of NEST was reduced in total cases and cases among men and women compared with corresponding controls [expression ratio (95% CI) = 0.2 (0.14-0.28); 0.22 (0.12-0.37); and 0.19 (0.09-0.43), respectively; adjusted P-value < 0.0001]. Lastly, FLICR was downregulated in total cases and cases among both boys and girls compared with matched controls [expression ratio (95% CI) = 0.1 (0.06-0.19); 0.19 (0.08-0.46); and 0.06 (0.01-0.21), respectively; adjusted P-value < 0.0001]. These three lncRNAs had appropriate diagnostic power for differentiation of ASD cases from controls. Cumulatively, our study supports dysregulation of Treg-related lncRNAs in patients with ASD and suggests these lncRNAs as proper peripheral markers for ASD.

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2. AlOlaby RR, Zafarullah M, Barboza M, Peng G, Varian BJ, Erdman SE, Lebrilla C, Tassone F. Differential Methylation Profile in Fragile X Syndrome-Prone Offspring Mice after in Utero Exposure to Lactobacillus Reuteri. Genes (Basel);2022 (Jul 22);13(8)

Environmental factors such as diet, gut microbiota, and infections have proven to have a significant role in epigenetic modifications. It is known that epigenetic modifications may cause behavioral and neuronal changes observed in neurodevelopmental disabilities, including fragile X syndrome (FXS) and autism (ASD). Probiotics are live microorganisms that provide health benefits when consumed, and in some cases are shown to decrease the chance of developing neurological disorders. Here, we examined the epigenetic outcomes in offspring mice after feeding of a probiotic organism, Lactobacillus reuteri (L. reuteri), to pregnant mother animals. In this study, we tested a cohort of Western diet-fed descendant mice exhibiting a high frequency of behavioral features and lower FMRP protein expression similar to what is observed in FXS in humans (described in a companion manuscript in this same GENES special topic issue). By investigating 17,735 CpG sites spanning the whole mouse genome, we characterized the epigenetic profile in two cohorts of mice descended from mothers treated and non-treated with L. reuteri to determine the effect of prenatal probiotic exposure on the prevention of FXS-like symptoms. We found several genes involved in different neurological pathways being differentially methylated (p ≤ 0.05) between the cohorts. Among the key functions, synaptogenesis, neurogenesis, synaptic modulation, synaptic transmission, reelin signaling pathway, promotion of specification and maturation of neurons, and long-term potentiation were observed. The results of this study are relevant as they could lead to a better understanding of the pathways involved in these disorders, to novel therapeutics approaches, and to the identification of potential biomarkers for early detection of these conditions.

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3. Calabrò RS, Pioggia G, Contrada M, Cerasa A. Sexual Coach in High-Functioning Autism: A Growing Need. Brain Sci;2022 (Jul 22);12(8)

When individuals with autism spectrum disorders (ASD) reach adulthood, they may experience a set of challenges related to sexual health, dating and romantic relationships […].

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4. Caudill A, Hladik L, Gray M, Dulaney N, Barton K, Rogers J, Noblet N, Ausderau KK. Health Narratives as a Therapeutic Tool for Health Care Access for People with Intellectual and Developmental Disabilities. Occup Ther Health Care;2022 (Jul 22):1-18.

Individuals with intellectual and developmental disabilities (IDD) have unique and complex health care needs that require health care access. Barriers, such as decreased health literacy and a lack of experienced physicians working with this population, make access to inclusive health care increasingly difficult. Therefore, it is important for occupational therapists to intentionally create opportunities to improve healthcare access and utilization for this population. This paper describes the collaborative health narrative development process as well as the inclusion of three examples created by co-authors with intellectual or developmental disability.

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5. Das DK, Udani V. Coexistence of Rett & Angelman syndrome: A rare clinical presentation. Indian J Med Res;2022 (Jan);155(1):79-80.

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6. Hernando-Davalillo C, Martín AAS, Borregan Prats M, Ortigoza-Escobar JD. De novo 4q35.2 duplication containing FAT1 is associated with autism spectrum disorder. Clin Genet;2022 (Jul 21)

Genetic studies have established a connection between FAT1 (FAT atypical cadherin 1) deletion and variants and autism spectrum disorder (ASD). Here, we describe a 7-year-old girl who sought a neurology consultation in order to be evaluated for ASD and was found to have a de novo 4q35.2 duplication containing the FAT1 gene. Similar to other reported cases of FAT1 variants or deletion, this patient exhibits non-syndromic ASD without facial dysmorphism or brain MRI abnormalities. We suggest also considering FAT1 duplication as a potential ASD cause. This article is protected by copyright. All rights reserved.

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7. Kummer S, Rinné S, Seemann G, Bachmann N, Timothy K, Thornton PS, Pillekamp F, Mayatepek E, Bergmann C, Meissner T, Decher N. Hyperinsulinemic Hypoglycemia Associated with a Ca(V)1.2 Variant with Mixed Gain- and Loss-of-Function Effects. Int J Mol Sci;2022 (Jul 22);23(15)

The voltage-dependent L-type calcium channel isoform Ca(V)1.2 is critically involved in many physiological processes, e.g., in cardiac action potential formation, electromechanical coupling and regulation of insulin secretion by beta cells. Gain-of-function mutations in the calcium voltage-gated channel subunit alpha 1 C (CACNA1C) gene, encoding the Ca(V)1.2 α(1)-subunit, cause Timothy syndrome (TS), a multisystemic disorder that includes autism spectrum disorders and long QT (LQT) syndrome. Strikingly, TS patients frequently suffer from hypoglycemia of yet unproven origin. Using next-generation sequencing, we identified a novel heterozygous CACNA1C mutation in a patient with congenital hyperinsulinism (CHI) and associated hypoglycemic episodes. We characterized the electrophysiological phenotype of the mutated channel using voltage-clamp recordings and in silico action potential modeling experiments. The identified Ca(V)1.2(L566P) mutation causes a mixed electrophysiological phenotype of gain- and loss-of-function effects. In silico action potential modeling supports that this mixed electrophysiological phenotype leads to a tissue-specific impact on beta cells compared to cardiomyocytes. Thus, CACNA1C variants may be associated with non-syndromic hyperinsulinemic hypoglycemia without long-QT syndrome, explained by very specific electrophysiological properties of the mutated channel. We discuss different biochemical characteristics and clinical impacts of hypoglycemia in the context of CACNA1C variants and show that these may be associated with significant morbidity for Timothy Syndrome patients. Our findings underline that the potential of hypoglycemia warrants careful attention in patients with CACNA1C variants, and such variants should be included in the differential diagnosis of non-syndromic congenital hyperinsulinism.

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8. Leadbitter K, Smallman R, James K, Shields G, Ellis C, Langhorne S, Harrison L, Hackett L, Dunkerley A, Kroll L, Davies L, Emsley R, Bee P, Green J. REACH-ASD: a UK randomised controlled trial of a new post-diagnostic psycho-education and acceptance and commitment therapy programme against treatment-as-usual for improving the mental health and adjustment of caregivers of children recently diagnosed with autism spectrum disorder. Trials;2022 (Jul 22);23(1):585.

BACKGROUND: Autism is a neurodevelopmental disability affecting over 1% of UK children. The period following a child’s autism diagnosis can present real challenges in adaptation for families. Twenty to 50% of caregivers show clinically significant levels of mental health need within the post-diagnostic period and on an ongoing basis. Best practice guidelines recommend timely post-diagnostic family support. Current provision is patchy, largely unevidenced, and a source of dissatisfaction for both families and professionals. There is a pressing need for an evidenced programme of post-diagnostic support focusing on caregiver mental health and adjustment, alongside autism psycho-education. This trial tests the clinical and cost-effectiveness of a new brief manualised psychosocial intervention designed to address this gap. METHODS: This is a multi-centre two-parallel-group single (researcher)-blinded randomised controlled trial of the Empower-Autism programme plus treatment-as-usual versus usual local post-diagnostic offer plus treatment-as-usual. Caregivers of children aged 2-15 years with a recent autism diagnosis will be recruited from North West England NHS or local authority centres. Randomisation is individually by child, with one « index » caregiver per child, stratified by centre, using 2:1 randomisation ratio to assist recruitment and timely intervention. Empower-Autism is a group-based, manualised, post-diagnostic programme that combines autism psycho-education and psychotherapeutic components based on Acceptance and Commitment Therapy to support caregiver mental health, stress management and adjustment to their child’s diagnosis. The comparator is any usual local group-based post-diagnostic psycho-education offer. Receipt of services will be specified through health economic data. PRIMARY OUTCOME: caregiver mental health (General Health Questionnaire-30) at 52-week follow-up. SECONDARY OUTCOMES: key caregiver measures (wellbeing, self-efficacy, adjustment, autism knowledge) at 12-, 26- and 52-week follow-up and family and child outcomes (wellbeing and functioning) at 52-week endpoint. SAMPLE: N=380 (approximately 253 intervention/127 treatment-as-usual). Primary analysis will follow intention-to-treat principles using linear mixed models with random intercepts for group membership and repeated measures. Cost-effectiveness acceptability analyses will be over 52 weeks, with decision modelling to extrapolate to longer time periods. DISCUSSION: If effective, this new approach will fill a key gap in the provision of evidence-based care pathways for autistic children and their families. TRIAL REGISTRATION: ISRCTN 45412843 . Prospectively registered on 11 September 2019.

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9. Malhi P, Shetty AR, Bharti B, Saini L. Parenting a child with autism spectrum disorder: A qualitative study. Indian J Public Health;2022 (Apr-Jun);66(2):121-127.

BACKGROUND: Research in India has seldom studied caregivers’ perceptions, experiences, and needs for information and personal support after an autism spectrum disorder (ASD) diagnosis. OBJECTIVES: The objectives of the study were to understand the perceived barriers for obtaining a diagnosis and the perspectives and experiences of parents of children with autism. MATERIALS AND METHODS: Parents with a diagnosed ASD child (within a year of diagnosis) in the 3-8 years range were recruited from the Pediatric Psychology and Neurodevelopmental Clinic from a tertiary care teaching hospital in North India. An interview guide elicited information about experiences regarding obtaining an ASD diagnosis, perceived barriers and facilitators, reactions to diagnosis, postdiagnostic family and community experiences, and stress experienced by parents. Qualitative responses were analyzed using thematic analysis. Participants were recruited till there was a saturation of themes. The ethics clearance was provided by the institutional review board. RESULTS: Twenty-eight caregivers of children with ASD were recruited for the study. Overall, nine themes were identified from the qualitative analysis of the interviews: two before diagnosis (delayed help-seeking and experiences with healthcare), one at the time of diagnosis disclosure (heightened emotional response to diagnosis), and six themes after the diagnosis (increased stress, behavioral challenges, deterioration in family relationships, negative attitudes of the family, seeking support, and moving forward with hope for the future). CONCLUSIONS: There are several barriers and gaps in the autism-related available services in the country, and there is a need to provide inclusive, supportive, culturally sensitive, and family-centered model of care for parents raising children with ASD.

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10. Morrill NK, Joly-Amado A, Li Q, Prabhudeva S, Weeber EJ, Nash KR. Reelin central fragment supplementation improves cognitive deficits in a mouse model of Fragile X Syndrome. Exp Neurol;2022 (Jul 19);357:114170.

Fragile X Syndrome (FXS) is the most common form of inherited intellectual disability and is characterized by autistic behaviors, childhood seizures, and deficits in learning and memory. FXS has a loss of function of the FMR1 gene that leads to a lack of Fragile X Mental Retardation Protein (FMRP) expression. FMRP is critical for synaptic plasticity, spatial learning, and memory. Reelin is a large extracellular glycoprotein essential for synaptic plasticity and numerous neurodevelopmental processes. Reduction in Reelin signaling is implicated as a contributing factor in disease etiology in several neurological disorders, including schizophrenia, and autism. However, the role of Reelin in FXS is poorly understood. We demonstrate a reduction in Reelin in Fmr1 knock-out (KO) mice, suggesting that a loss of Reelin activity may contribute to FXS. We demonstrate here that Reelin signaling enhancement via a single intracerebroventricular injection of the Reelin central fragment into Fmr1 KO mice can profoundly rescue cognitive deficits in hidden platform water maze and fear conditioning, as well as hyperactivity during the open field. Improvements in behavior were associated with rescued levels of post synaptic marker in Fmr1 KO mice when compared to controls. These data suggest that increasing Reelin signaling in FXS could offer a novel therapeutic for improving cognition in FXS.

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11. Prahbhjot M, Singhi P. Age at diagnosis for autism spectrum disorders: Does it differ by place of residence?. Indian J Public Health;2022 (Apr-Jun);66(2):166-170.

BACKGROUND: Despite steady decline in the age of diagnosis (AOD) at the global level, it has not declined uniformly, and marked disparities are documented by income, education, race, and access to health care. OBJECTIVES: The objectives of the study are to examine the urban/rural disparities in the initial age of autism diagnosis and to understand the interplay of the underlying demographic and social factors. METHODS: A retrospective case record review of all children who received their initial diagnosis of autism at the Pediatric Psychology Clinic (1997-2018) of a tertiary advanced pediatric center at Chandigarh was conducted. A structured abstraction data form was used to extract demographic, socioeconomic, and clinical information from the files maintained at the clinic. RESULTS: A total of 1321 case records were examined. The mean AOD was 4.62 years (standard deviation = 2.38) and children from rural communities were diagnosed at 4.87 years, nearly 0.35 years later than urban children (t = 2.47, P = 0.013). Results indicated that 31.1% of the variance in the AOD for children from rural areas was predicted by two variables, namely the number of children in the family and total Childhood Autism Rating Scale (CARS) score (F = 13.62, P = 0.001). For the urban sample, three variables emerged as significant predictors including the number of children in the family, total CARS score, and maternal education and these together explained 20.2% of the variance in the AOD (F = 19.60, P = 0.001). CONCLUSION: The public health system must be sensitized to the unmet needs of the marginalized socioeconomic groups to access diagnostic and management services in a timely manner.

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12. Pridmore C, D’Arco F, Siyani V, Bull L, Richardson H. Hypothalamic hamartoma: epilepsy and neurodevelopmental profiles in a clinical cohort. Epileptic Disord;2022 (Oct 1);24(5):1-10.

OBJECTIVE: We aimed to determine the prevalence of epilepsy and neurodevelopmental disorders, including autism spectrum disorder, in children and adolescents with hypothalamic hamartoma (HH). We also sought to explore the relationship between these neurodevelopmental comorbidities and epilepsy and to establish the predictive value of structural characteristics of the hamartoma itself. METHODS: We retrospectively studied a cohort of 62 children with HH, with neuroimaging reviewed at Great Ormond Street Hospital (GOSH) between 2008 and 2018. Clinical records were reviewed, cognitive and language data analysed, and MRI scans studied. RESULTS: We confirmed a high burden of epilepsy (56%), autism (19%) and other neurodevelopmental disorders. Although rates of some neurodevelopmental disorders were significantly higher in those with epilepsy, autistic features and/or early developmental concerns often predated the onset of seizures, in particular generalized seizures, or occurred independently of seizures. We found a significant correlation between certain structural characteristics of the hamartoma itself and both epilepsy and certain neurodevelopmental comorbidities. SIGNIFICANCE: These findings suggest that although seizure burden clearly contributes to the cognitive and behavioural phenotypes seen, the hamartoma itself, and particular characteristics of it, are likely to be primary determinants of both the epilepsy and neurodevelopmental profiles. It is also probable that the underlying aetiology, likely genetic, directly contributes to the clinical profile, with epilepsy, neurodevelopmental impairment and the hamartoma itself representing markers of this aetiology. We propose that atypical neurodevelopmental profiles in HH could best be conceptualized as a developmental and epileptic encephalopathy. These findings have implications for counselling, monitoring and treatment.

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13. Qin B, Wang L, Cai J, Li T, Zhang Y. Functional Brain Networks in Preschool Children With Autism Spectrum Disorders. Front Psychiatry;2022;13:896388.

OBJECTIVE: The present study aims to investigate the functional brain network characteristics of preschool children with autism spectrum disorder (ASD) through functional connectivity (FC) calculations using resting-state functional MRI (rs-fMRI) and graph theory analysis to better understand the pathogenesis of ASD and provide imaging evidence for the early assessment of this condition. METHODS: A prospective study of preschool children including 32 with ASD (ASD group) and 22 healthy controls (HC)group was conducted in which all subjects underwent rs-fMRI scans, and then the differences in FC between the two groups was calculated, followed by graph-theoretic analysis to obtain the FC properties of the network. RESULTS: In the calculation of FC, compared with the children in the HC group, significant increases or decreases in subnetwork connectivity was found in the ASD group. There were 25 groups of subnetworks with enhanced FC, of which the medial prefrontal and posterior cingulate gyrus and angular gyrus were all important components of the default mode network (DMN). There were 11 groups of subnetworks with weakened FC, including the hippocampus, parahippocampal gyrus, superior frontal gyrus, inferior temporal gyrus, precuneus, amygdala, and perirhinal cortex, with the hippocampus and parahippocampal gyrus predominating. In the network properties determined by graph theory, the clustering coefficient and local efficiency of the functional network was increased in the ASD group; specifically, compared with those in the HC group, nodes in the left subinsular frontal gyrus and the right middle temporal gyrus had increased efficiency, and nodes in the left perisylvian cortex, the left lingual gyrus, and the right hippocampus had decreased efficiency. CONCLUSION: Alterations in functional brain networks are evident in preschool children with ASD and can be detected with sleep rs-fMRI, which is important for understanding the pathogenesis of ASD and assessing this condition early.

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14. Shanok NA, Sotelo M. A pilot tennis program for training fitness and social behaviors in individuals with autism spectrum disorder. J Sports Med Phys Fitness;2022 (Aug);62(8):1118-1126.

BACKGROUND: The aim of this pilot study was to determine the effectiveness of a tennis-training program for individuals with autism spectrum disorder. METHODS: The program consisted of 12 lessons delivered over a 6-week time frame that incorporated tennis-specific abilities (i.e. forehand, backhand, rallying) with targeted autism skills (social skills, reception skills). RESULTS: In this study, (N-=15) participants showed significant improvements in a variety of tennis-related skills including ready position, side-shuffle, forehand, backhand, volleys, and rallying. Additional advancements were observed on hand-eye coordination (catching balls with one-hand) and leg strength (long-jump) using a structured fitness assessment. Lastly, participants demonstrated improvements in social skills, receptive communication skills, and reception skills from pre-training to -post. CONCLUSIONS: The results of this study highlight the potential of tennis training as a valuable element of autism therapeutic programs, enabling participants to train motor and social skills in a fun, recreational setting.

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15. Stark I, Rai D, Lundberg M, Culpin I, Nordström SI, Ohlis A, Magnusson C. Autism and self-harm: a population-based and discordant sibling study of young individuals. Acta Psychiatr Scand;2022 (Jul 22)

OBJECTIVE: Self-harm among young autistic individuals is a clinical challenge, and the risk of premature death by suicide is strongly increased in this group. Using the advantage of total-population and family-based data we investigated whether autism per se is a risk factor for self-harm independently of psychiatric comorbidities and how it differs from self-harm in non-autistic individuals. METHODS: We used The Stockholm Youth Cohort, a total-population register study, including all residents in Stockholm County aged 0-17 years between 2001-2011.Study participants were followed from age 10 to 27 for hospital admissions due to self -harm. We used modified Poisson regression to calculate relative risks (RR) using robust standard error to derive 95 % confidence intervals (CI). RESULTS: In all, 410,732 individuals were included in the cohort (9,070 with a diagnosis of autism). Autistic individuals had a fivefold increased adjusted relative risk of self-harm (RR 5.0 [95 % CI 4.4-5.6]). The risk increase was more pronounced for autism without intellectual disability and particularly high for self-cutting 10.2 [7.1-14.7] and more violent methods 8.9, [5.2-15.4]. The association between autism and self-harm was independent of, but clearly exacerbated by comorbid psychiatric conditions. It was of similar magnitude as risks linked to these conditions per se, and not explained by shared familial factors. CONCLUSION: Self-harm severe enough to present to medical services is as common in autistic youth as in those with depression or ADHD. Potentially more lethal methods are more likely to be used of autistic self-harmers.

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16. Tso RV, Chui CO, Hsiao JH. How does face mask in COVID-19 pandemic disrupt face learning and recognition in adults with autism spectrum disorder?. Cogn Res Princ Implic;2022 (Jul 22);7(1):64.

Use of face masks is one of the measures adopted by the general community to stop the transmission of disease during this ongoing COVID-19 pandemic. This wide use of face masks has indeed been shown to disrupt day-to-day face recognition. People with autism spectrum disorder (ASD) often have predisposed impairment in face recognition and are expected to be more vulnerable to this disruption in face recognition. Here, we recruited typically developing adult participants and those with ASD, and we measured their non-verbal intelligence, autism spectrum quotient, empathy quotient, and recognition performances of faces with and without a face mask covering the lower halves of the face. When faces were initially learned unobstructed, we showed that participants had a general reduced face recognition performance for masked faces. In contrast, when masked faces were first learned, typically developing adults benefit with an overall advantage in recognizing both masked and unmasked faces; while adults with ASD recognized unmasked faces with a significantly more reduced level of performance than masked faces-this face recognition discrepancy is predicted by a higher level of autistic traits. This paper also discusses how autistic traits influence processing of faces with and without face masks.

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17. Xiang L, Wu Q, Sun H, Miao X, Lv Z, Liu H, Chen L, Gu Y, Chen J, Zhou S, Jiang H, Du S, Zhou Y, Dong H, Fan Y, Miao S, Lu Q, Chang L, Wang H, Lu Y, Xu X, Wang W, Huang Z. SARM1 deletion in parvalbumin neurons is associated with autism-like behaviors in mice. Cell Death Dis;2022 (Jul 22);13(7):638.

Autism spectrum disorder (ASD), a group of neurodevelopmental disorder diseases, is characterized by social deficits, communication difficulties, and repetitive behaviors. Sterile alpha and TIR motif-containing 1 protein (SARM1) is known as an autism-associated protein and is enriched in brain tissue. Moreover, SARM1 knockdown mice exhibit autism-like behaviors. However, its specific mechanism in ASD pathogenesis remains unclear. Here we generated parvalbumin-positive interneurons (PVI)-specific conditional SARM1 knockout (SARM1(PV)-CKO) mice. SARM1(PV)-CKO male mice showed autism-like behaviors, such as mild social interaction deficits and repetitive behaviors. Moreover, we found that the expression level of parvalbumin was reduced in SARM1(PV)-CKO male mice, together with upregulated apoptosis-related proteins and more cleaved-caspase-3-positive PVIs, suggesting that knocking out SARM1 may cause a reduction in the number of PVIs due to apoptosis. Furthermore, the expression of c-fos was shown to increase in SARM1(PV)-CKO male mice, in combination with upregulation of excitatory postsynaptic proteins such as PSD-95 or neuroligin-1, indicating enhanced excitatory synaptic input in mutant mice. This notion was further supported by the partial rescue of autism-like behavior deficits by the administration of GABA receptor agonists in SARM1(PV)-CKO male mice. In conclusion, our findings suggest that SARM1 deficiency in PVIs may be involved in the pathogenesis of ASD.

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18. Zhang F, Wei Y, Liu J, Wang Y, Xi W, Pan Y. Identification of Autism spectrum disorder based on a novel feature selection method and Variational Autoencoder. Comput Biol Med;2022 (Jul 15);148:105854.

The development of noninvasive brain imaging such as resting-state functional magnetic resonance imaging (rs-fMRI) and its combination with AI algorithm provides a promising solution for the early diagnosis of Autism spectrum disorder (ASD). However, the performance of the current ASD classification based on rs-fMRI still needs to be improved. This paper introduces a classification framework to aid ASD diagnosis based on rs-fMRI. In the framework, we proposed a novel filter feature selection method based on the difference between step distribution curves (DSDC) to select remarkable functional connectivities (FCs) and utilized a multilayer perceptron (MLP) which was pretrained by a simplified Variational Autoencoder (VAE) for classification. We also designed a pipeline consisting of a normalization procedure and a modified hyperbolic tangent (tanh) activation function to replace the classical tanh function, further improving the model accuracy. Our model was evaluated by 10 times 10-fold cross-validation and achieved an average accuracy of 78.12%, outperforming the state-of-the-art methods reported on the same dataset. Given the importance of sensitivity and specificity in disease diagnosis, two constraints were designed in our model which can improve the model’s sensitivity and specificity by up to 9.32% and 10.21%, respectively. The added constraints allow our model to handle different application scenarios and can be used broadly.

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