1. Asghari SZ, Farashi S, Bashirian S, Jenabi E. Distinctive prosodic features of people with autism spectrum disorder: a systematic review and meta-analysis study. Scientific reports. 2021; 11(1): 23093.

In this systematic review, we analyzed and evaluated the findings of studies on prosodic features of vocal productions of people with autism spectrum disorder (ASD) in order to recognize the statistically significant, most confirmed and reliable prosodic differences distinguishing people with ASD from typically developing individuals. Using suitable keywords, three major databases including Web of Science, PubMed and Scopus, were searched. The results for prosodic features such as mean pitch, pitch range and variability, speech rate, intensity and voice duration were extracted from eligible studies. The pooled standard mean difference between ASD and control groups was extracted or calculated. Using I(2) statistic and Cochrane Q-test, between-study heterogeneity was evaluated. Furthermore, publication bias was assessed using funnel plot and its significance was evaluated using Egger’s and Begg’s tests. Thirty-nine eligible studies were retrieved (including 910 and 850 participants for ASD and control groups, respectively). This systematic review and meta-analysis showed that ASD group members had a significantly larger mean pitch (SMD =  - 0.4, 95% CI [- 0.70, - 0.10]), larger pitch range (SMD =  - 0.78, 95% CI [- 1.34, - 0.21]), longer voice duration (SMD =  - 0.43, 95% CI [- 0.72, - 0.15]), and larger pitch variability (SMD = - 0.46, 95% CI [- 0.84, - 0.08]), compared with typically developing control group. However, no significant differences in pitch standard deviation, voice intensity and speech rate were found between groups. Chronological age of participants and voice elicitation tasks were two sources of between-study heterogeneity. Furthermore, no publication bias was observed during analyses (p > 0.05). Mean pitch, pitch range, pitch variability and voice duration were recognized as the prosodic features reliably distinguishing people with ASD from TD individuals.

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2. Dilmore AH, McDonald D, Nguyen TT, Adams JB, Krajmalnik-Brown R, Elijah E, Dorrestein PC, Knight R. The Fecal Microbiome and Metabolome of Pitt Hopkins Syndrome, a Severe Autism Spectrum Disorder. mSystems. 2021; 6(6): e0100621.

Alterations to the gut microbiome have been reported between children with autism spectrum disorders (ASDs) and typically developing (TD) children. Characterizing these differences has led to the proposal of new treatments for ASD, such as probiotic interventions and fecal matter transplants. However, no study to date has characterized the gut microbiome or metabolome in Pitt Hopkins syndrome (PTHS), a severe ASD with a high incidence of gastrointestinal (GI) disturbances such as constipation. Here, we surveyed the gut microbiome and metabolome in a cohort of PTHS individuals and their unaffected parents. We focused our analysis on Clostridium bolteae, a microbe previously associated with ASD known to chemically modify bile acids in the gut. PTHS individuals carry a higher load of C. bolteae than their parents as well as both ASD and non-ASD individuals from the American Gut Project cohort. Specific metabolites were associated with PTHS, including bile acids and sphingosines. With a metadata reanalysis tool, we found that PTHS-associated metabolites have previously been identified in inflammatory bowel disease and obesity patients. These results suggest microbial involvement in PTHS, but further research must be performed to clarify the exact mechanisms through which microbes may act. Furthermore, new associations between PTHS-specific metabolites and other conditions may lead to additional therapeutic options for PTHS individuals. IMPORTANCE GI disturbances in ASD such as severe constipation can be medically significant and often require medication. This is especially true for individuals with PTHS, suggesting that the gut microbiome may be involved in PTHS’s pathology. Revealing associations between specific gut microbes and PTHS may allow the development of new therapeutics or the application of existing therapeutics to ease day-to-day challenges encountered by PTHS individuals. In this study, we characterized an association between C. bolteae and PTHS, in addition to metabolites linked to both PTHS and C. bolteae. We also identified other microbiome-involved medical conditions where PTHS-associated metabolites have been isolated. Utilizing common metabolites to identify conditions with similar phenotypes may suggest new therapeutic options for GI-related symptoms.

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3. Keating CT, Sowden S, Cook JL. Comparing internal representations of facial expression kinematics between autistic and non-autistic adults. Autism research : official journal of the International Society for Autism Research. 2022; 15(3): 493-506.

Recent developments suggest that autistic individuals require dynamic angry expressions to have a higher speed in order for them to be successfully identified. Therefore, it is plausible that autistic individuals do not have a ‘deficit’ in angry expression recognition, but rather their internal representation of these expressions is characterised by very high-speed movement. In this study, matched groups of autistic and non-autistic adults completed a novel emotion-based task which employed dynamic displays of happy, angry and sad point light facial (PLF) expressions. On each trial, participants moved a slider to manipulate the speed of a PLF stimulus until it moved at a speed that, in their ‘mind’s eye’, was typical of happy, angry or sad expressions. Participants were shown three different types of PLFs-those showing the full-face, only the eye region, and only the mouth region, wherein the latter two were included to test whether differences in facial information sampling underpinned any dissimilarities in speed attributions. Across both groups, participants attributed the highest speeds to angry, then happy, then sad, facial motion. Participants increased the speed of angry and happy expressions by 41% and 27% respectively and decreased the speed of sad expressions by 18%. This suggests that participants have ‘caricatured’ internal representations of emotion, wherein emotion-related kinematic cues are over-emphasised. There were no differences between autistic and non-autistic individuals in the speeds attributed to full-face and partial-face angry, happy and sad expressions respectively. Consequently, we find no evidence that autistic adults possess atypically fast internal representations of anger.

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4. Kerr-Gaffney J, Jones E, Mason L, Hayward H, Murphy D, Loth E, Tchanturia K. Social attention in anorexia nervosa and autism spectrum disorder: Role of social motivation. Autism : the international journal of research and practice. 2021: 13623613211060593.

Research suggests a relationship between autism and anorexia nervosa. For example, rigid and inflexible behaviour, a preference for routine and social difficulties are seen in both conditions. In this study, we examined whether people with anorexia and people with autism show similarities in social attention (where they look while engaging in social interactions or watching a scene with people interacting). This could help us understand why people with anorexia and autism experience difficulties in social situations. Participants with either anorexia or autism, as well as participants with no mental health problems watched a video of a social scene while we recorded which parts of the scene they looked at with an eye-tracker. Participants also completed questionnaires to assess characteristics of autism. We found that autistic participants looked at faces less than typically developing participants. However, participants with anorexia did not show a similar reduction in attention to faces, contrary to our predictions. Autistic features were not related to attention in either group. The results suggest that autistic people may miss important social cues (like facial expressions), potentially contributing to social difficulties. However, this mechanism does not appear explain social difficulties in people with anorexia.

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5. Lannom MC, Nielsen J, Nawaz A, Shilikbay T, Ceman S. FMRP and MOV10 regulate Dicer1 expression and dendrite development. PloS one. 2021; 16(11): e0260005.

Fragile X syndrome results from the loss of expression of the Fragile X Mental Retardation Protein (FMRP). FMRP and RNA helicase Moloney Leukemia virus 10 (MOV10) are important Argonaute (AGO) cofactors for miRNA-mediated translation regulation. We previously showed that MOV10 functionally associates with FMRP. Here we quantify the effect of reduced MOV10 and FMRP expression on dendritic morphology. Murine neurons with reduced MOV10 and FMRP phenocopied Dicer1 KO neurons which exhibit impaired dendritic maturation Hong J (2013), leading us to hypothesize that MOV10 and FMRP regulate DICER expression. In cells and tissues expressing reduced MOV10 or no FMRP, DICER expression was significantly reduced. Moreover, the Dicer1 mRNA is a Cross-Linking Immunoprecipitation (CLIP) target of FMRP Darnell JC (2011), MOV10 Skariah G (2017) and AGO2 Kenny PJ (2020). MOV10 and FMRP modulate expression of DICER1 mRNA through its 3’untranslated region (UTR) and introduction of a DICER1 transgene restores normal neurite outgrowth in the Mov10 KO neuroblastoma Neuro2A cell line and branching in MOV10 heterozygote neurons. Moreover, we observe a global reduction in AGO2-associated microRNAs isolated from Fmr1 KO brain. We conclude that the MOV10-FMRP-AGO2 complex regulates DICER expression, revealing a novel mechanism for regulation of miRNA production required for normal neuronal morphology.

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6. Muellerleile J, Vnencak M, Ippolito A, Krueger-Burg D, Jungenitz T, Schwarzacher SW, Jedlicka P. Neuroligin-3 Regulates Excitatory Synaptic Transmission and EPSP-Spike Coupling in the Dentate Gyrus In Vivo. Molecular neurobiology. 2022; 59(2): 1098-111.

Neuroligin-3 (Nlgn3), a neuronal adhesion protein implicated in autism spectrum disorder (ASD), is expressed at excitatory and inhibitory postsynapses and hence may regulate neuronal excitation/inhibition balance. To test this hypothesis, we recorded field excitatory postsynaptic potentials (fEPSPs) in the dentate gyrus of Nlgn3 knockout (KO) and wild-type mice. Synaptic transmission evoked by perforant path stimulation was reduced in KO mice, but coupling of the fEPSP to the population spike was increased, suggesting a compensatory change in granule cell excitability. These findings closely resemble those in neuroligin-1 (Nlgn1) KO mice and could be partially explained by the reduction in Nlgn1 levels we observed in hippocampal synaptosomes from Nlgn3 KO mice. However, unlike Nlgn1, Nlgn3 is not necessary for long-term potentiation. We conclude that while Nlgn1 and Nlgn3 have distinct functions, both are required for intact synaptic transmission in the mouse dentate gyrus. Our results indicate that interactions between neuroligins may play an important role in regulating synaptic transmission and that ASD-related neuroligin mutations may also affect the synaptic availability of other neuroligins.

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7. Park SS, Kim CJ, Kim SH, Kim TW, Lee SJ. Maternal Swimming Exercise During Pregnancy Improves Memory Through Enhancing Neurogenesis and Suppressing Apoptosis via Wnt/β-Catenin Pathway in Autistic Mice. International neurourology journal. 2021; 25(Suppl 2): S63-71.

PURPOSE: Wnt pathway is closely related to neurodevelopmental process associated with cognitive function. After administration of valproic acid to the pregnant mice, the effect of swimming exercise of pregnant mice on the memory, neuronal production, and apoptosis of pups was studied in relation with Wnt/β-catenin signaling pathway. METHODS: On day 12 of pregnancy, mice were injected subcutaneously with 400-mg/kg valproic acid. The pregnant mice in the control with swimming exercise group and in the valproic acid injection with swimming exercise group were allowed for swimming for 30 minutes one time per a day, repeated 5 days per a week, during 3 weeks. Step-through avoidance task and Morris water maze task for memory function, immunohistochemistry for 5-bromo-2′-deoxyuridine (BrdU)-positive cells and western blot for brain-derived neurotrophic factor (BDNF), Wnt, β-catenin, Bcl-2 related X protein (Bax), B-cell lymphoma 2 (Bcl-2), cleaved caspase-3 were carried out. RESULTS: Maternal swimming exercise during pregnancy improved memory function, increased BDNF expression, and neuronal proliferation in the valproic acid injected pups. Maternal swimming exercise during pregnancy suppressed Wnt expression and phosphorylation of β-catenin in the valproic acid injected pups. Maternal swimming exercise inhibited Bax and cleaved caspase-3 expression and increased Bcl-2 expression in the valproic acid injected pups. CONCLUSION: Maternal swimming exercise during pregnancy improved memory function by increasing cell proliferation and inhibiting apoptosis through Wnt/β-catenin signaling cascade activation in the valproic acid injected pups. Maternal swimming exercise during pregnancy may have a protective effect on factors that induce autism in the fetus.

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8. Putnam-Hornstein E, Ahn E, Prindle J, Webster D. Contact with the child protection system is pervasive, but are recent estimates correct?. Proceedings of the National Academy of Sciences of the United States of America. 2021; 118(49).

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9. Saha S, Chatterjee M, Shom S, Sinha S, Mukhopadhyay K. Functional SLC6A3 polymorphisms differentially affect autism spectrum disorder severity: a study on Indian subjects. Metabolic brain disease. 2022; 37(2): 397-410.

Imbalance in dopamine (DA) signaling is proposed to play a potential role in the etiology of Autism spectrum disorder (ASD) since, as a neuromodulator, DA regulates executive function, motor activity, social peering, attention as well as perception and subjects with ASD often exhibit deficit in these traits. Level of DA in the synaptic cleft is maintained by dopamine transporter (DAT) and hence, to identify the role of DAT in ASD, we have analyzed four functional genetic variants, rs28363170, rs3836790, rs2652511, rs27072, in nuclear families with ASD probands. Subjects were diagnosed based on Diagnostic and Statistical Manual for Mental Disorders and trait severity was assessed by Childhood Autism Rating Scale 2-Standard test. Informed written consent was obtained from the parents/care givers before recruitment followed by collection of peripheral blood for genomic DNA isolation. Target sites were investigated by PCR-based methods and data obtained was analyzed by population- as well as family-based statistical methods. Case-control analysis revealed significant higher frequencies of 9 repeat (9R) and 5 repeat (5R) alleles of rs28363170 and rs3836790 respectively in the ASD probands. Family-based analysis showed statistically significant higher paternal transmission of rs28363170 9R and rs2652511 T alleles. In the presence of rs28363170 9R, rs27072 C, rs3836790 6R6R, and rs2652511 CC variants, trait scores were higher. Studied variants showed independent as well as interactive effects, which varied based on gender of the probands. We infer that altered DA availability mediated through DAT may affect autistic traits warranting further in depth investigation in the field.

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