1. Guo QY, Ebihara K, Shimodaira T, Fujiwara H, Toume K, Dibwe DF, Awale S, Araki R, Yabe T, Matsumoto K. {{Kami-shoyo-san improves ASD-like behaviors caused by decreasing allopregnanolone biosynthesis in an SKF mouse model of autism}}. {PLoS One}. 2019; 14(1): e0211266.
Dysfunctions in the GABAergic system are associated with the pathogenesis of autism spectrum disorder (ASD). However, the mechanisms by which GABAergic system dysfunctions induce the pathophysiology of ASD remain unclear. We previously demonstrated that a selective type I 5alpha-reductase inhibitor SKF105111 (SKF) induced ASD-like behaviors, such as impaired sociability-related performance and repetitive grooming behaviors, in male mice. Moreover, the effects of SKF were caused by a decrease in the endogenous levels of allopregnanolone (ALLO), a positive allosteric modulator of the GABAA receptor. In this study, we used SKF-treated male mice as a putative animal model of ASD and examined the effects of Kami-shoyo-san (KSS) as an experimental therapeutic strategy for ASD. KSS is a traditional Kampo formula consisting of 10 different crude drugs and has been used for the treatment of neuropsychiatric symptoms. KSS dose-dependently attenuated sociability deficits and suppressed an increase in grooming behaviors in SKF-treated mice without affecting ALLO content in the prefrontal cortex. The systemic administration of the dopamine D1 receptor antagonist SCH23390 reversed the ameliorative effects of KSS. On the other hand, the dopamine D2 receptor antagonist sulpiride and GABAA receptor antagonist bicuculline only attenuated the ameliorative effect of KSS on repetitive self-grooming behaviors. The present results indicate that KSS improves SKF-induced ASD-like behaviors by facilitating dopamine receptor-mediated mechanisms and partly by neurosteroid-independent GABAA receptor-mediated neurotransmission. Therefore, KSS is a potential candidate for the treatment of ASD.
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2. Jasmin K, Gotts SJ, Xu Y, Liu S, Riddell CD, Ingeholm JE, Kenworthy L, Wallace GL, Braun AR, Martin A. {{Overt social interaction and resting state in young adult males with autism: core and contextual neural features}}. {Brain}. 2019.
Conversation is an important and ubiquitous social behaviour. Individuals with autism spectrum disorder (autism) without intellectual disability often have normal structural language abilities but deficits in social aspects of communication like pragmatics, prosody, and eye contact. Previous studies of resting state activity suggest that intrinsic connections among neural circuits involved with social processing are disrupted in autism, but to date no neuroimaging study has examined neural activity during the most commonplace yet challenging social task: spontaneous conversation. Here we used functional MRI to scan autistic males (n = 19) without intellectual disability and age- and IQ-matched typically developing control subjects (n = 20) while they engaged in a total of 193 face-to-face interactions. Participants completed two kinds of tasks: conversation, which had high social demand, and repetition, which had low social demand. Autistic individuals showed abnormally increased task-driven interregional temporal correlation relative to controls, especially among social processing regions and during high social demand. Furthermore, these increased correlations were associated with parent ratings of participants’ social impairments. These results were then compared with previously-acquired resting state data (56 autism, 62 control subjects). While some interregional correlation levels varied by task or rest context, others were strikingly similar across both task and rest, namely increased correlation among the thalamus, dorsal and ventral striatum, somatomotor, temporal and prefrontal cortex in the autistic individuals, relative to the control groups. These results suggest a basic distinction. Autistic cortico-cortical interactions vary by context, tending to increase relative to controls during task and decrease during test. In contrast, striato- and thalamocortical relationships with socially engaged brain regions are increased in both task and rest, and may be core to the condition of autism.
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3. Liu F, Li J, Wu F, Zheng H, Peng Q, Zhou H. {{Altered composition and function of intestinal microbiota in autism spectrum disorders: a systematic review}}. {Translational psychiatry}. 2019; 9(1): 43.
At present, the pathophysiology of autism spectrum disorder (ASD) remains unclear. Increasing evidence suggested that gut microbiota plays a critical role in gastrointestinal symptoms and behavioral impairment in ASD patients. The primary aim of this systematic review is to investigate potential evidence for the characteristic dysbiosis of gut microbiota in ASD patients compared with healthy controls (HCs). The MEDLINE, EMBASE, Web of Science and Scopus were systematically searched before March 2018. Human studies that compared the composition of gut microbiota in ASD patients and HCs using culture-independent techniques were included. Independent data extraction and quality assessment of studies were conducted according to PRISMA statement and Newcastle-Ottawa Scale. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) was used to infer biological functional changes of the shifted microbiota with the available data in four studies. Sixteen studies with a total sample size of 381 ASD patients and 283 HCs were included in this systematic review. The quality of the studies was evaluated as medium to high. The overall changing of gut bacterial community in terms of beta-diversity was consistently observed in ASD patients compared with HCs. Furthermore, Bifidobacterium, Blautia, Dialister, Prevotella, Veillonella, and Turicibacter were consistently decreased, while Lactobacillus, Bacteroides, Desulfovibrio, and Clostridium were increased in patients with ASD relative to HCs in certain studies. This systematic review demonstrated significant alterations of gut microbiota in ASD patients compared with HCs, strengthen the evidence that dysbiosis of gut microbiota may correlate with behavioral abnormality in ASD patients. However, results of inconsistent changing also existed and further big-sampled well-designed studies are needed. Generally, as a potential mediator of risk factors, the gut microbiota could be a novel target for ASD patients in the future.
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4. Mukaetova-Ladinska EB, Simashkova NV, Mukaetova MS, Ivanov MV, Boksha IS. {{[Autism spectrum disorders in children and adults: the experience of reserches from different countries]}}. {Zh Nevrol Psikhiatr Im S S Korsakova}. 2018; 118(12): 92-9.
Current studies on the development autism spectrum disorders (ASD) at different ages are reviewed. The review highlights the increasing interest to this problem and converging positions of researchers from different countries, encouraged by the development of international and other classifications of mental diseases, on the terminology, classification and prevalence of ASD in children. An important feature of the present stage is to draw attention to an understudied problem of ASD in adults, including elderly, and provision of medical and social care to these patients.
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5. Paynter J, Luskin-Saxby S, Keen D, Fordyce K, Frost G, Imms C, Miller S, Trembath D, Tucker M, Ecker U. {{Evaluation of a template for countering misinformation-Real-world Autism treatment myth debunking}}. {PLoS One}. 2019; 14(1): e0210746.
Misinformation poses significant challenges to evidence-based practice. In the public health domain specifically, treatment misinformation can lead to opportunity costs or direct harm. Alas, attempts to debunk misinformation have proven sub-optimal, and have even been shown to « backfire », including increasing misperceptions. Thus, optimized debunking strategies have been developed to more effectively combat misinformation. The aim of this study was to test these strategies in a real-world setting, targeting misinformation about autism interventions. In the context of professional development training, we randomly assigned participants to an « optimized-debunking » or a « treatment-as-usual » training condition and compared support for non-empirically-supported treatments before, after, and six weeks following completion of online training. Results demonstrated greater benefits of optimized debunking immediately after training; thus, the implemented strategies can serve as a general and flexible debunking template. However, the effect was not sustained at follow-up, highlighting the need for further research into strategies for sustained change.
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6. Pereverzeva DS, Gorbachevskaya NL. {{[Neurobiological Markers of Autism Spectrum Disorders in Infancy]}}. {Zhurnal vysshei nervnoi deiatelnosti imeni I P Pavlova}. 2016; 66(3): 289-301.
The article aims to systematically review recent studies on early symptoms of autism developmental dis- orders. Autism spectrum disorders is a group of neurodevelopmental disorders that is characterized by impairment of communication and social interaction. Nevertheless, the earliest detected features of ASD are impairments of attention disengagement and orientation to novel stimulus, perception abnor- malities of stimuli of magnocellular visual pathway and executive control deficit. The role of attention impairment for manifestation of other symptom of ASD including social deficit is discussed. Early ex- ecutive control deficit may in its turn be associated with symptoms of hyperactivity.
7. Ramos TC, Balardin JB, Sato JR, Fujita A. {{Abnormal Cortico-Cerebellar Functional Connectivity in Autism Spectrum Disorder}}. {Frontiers in systems neuroscience}. 2018; 12: 74.
The cerebral cortex and the cerebellum are spatially remote areas that are connected by complex circuits that link both primary and associative areas. Previous studies have revealed abnormalities in autism spectrum disorder (ASD); however, it is not clear whether cortico-cerebellar connectivity is differentially manifested in the disorder. To explore this issue, we investigated differences in intrinsic cortico-cerebellar functional connectivity between individuals with typical development (TD) and those with ASD. To this end, we used functional magnetic resonance imaging (fMRI) of 708 subjects under a resting state protocol provided by the ABIDE I Consortium. We found that people with ASD had diminished functional connectivity between the cerebellum and the following cortical regions: (i) right fusiform gyrus, (ii) right postcentral gyrus, (iii) right superior temporal gyrus, (iv) right middle temporal gyrus, and (v) left middle temporal gyrus. All of these regions are involved in many cognitive systems that contribute to commonly affected functions in ASD. For right fusiform gyrus, right superior temporal gyrus, and left middle temporal gyrus, we reproduced the results in an independent cohort composed of 585 subjects of the ABIDE II Consortium. Our results points toward a consistent atypical cortico-cerebellar connectivity in ASD.
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8. Soda T, Mapelli L, Locatelli F, Botta L, Goldfarb M, Prestori F, D’Angelo E. {{Hyper-excitability and hyper-plasticity disrupt cerebellar signal transfer in the IB2 KO mouse model of autism}}. {J Neurosci}. 2019.
Autism spectrum disorders (ASD) are pervasive neurodevelopmental conditions that often involve mutations affecting synaptic mechanisms. Recently, the involvement of cerebellum in ASD has been suggested but the underlying functional alterations remained obscure. We investigated single-neuron and microcircuit properties in IB2 KO mice of either sex. The IB2 gene (chr22q13.3 terminal region) deletion occurs in virtually all cases of Phelan-McDermid syndrome, causing autistic symptoms and a severe delay in motor skill acquisition. IB2 KO granule cells showed a larger NMDA receptor-mediated current and enhanced intrinsic excitability raising the excitatory/inhibitory balance. Furthermore, the spatial organization of granular layer responses to mossy fibers shifted from a Mexican hat to stovepipe hat profile, with stronger excitation in the core and weaker inhibition in the surround. Finally, the size and extension of long-term synaptic plasticity was remarkably increased. These results show for the first time that hyper-excitability and hyper-plasticity disrupt signal transfer in the granular layer of IB2 KO mice supporting cerebellar involvement in the pathogenesis of ASD.SIGNIFICANCE STATEMENTThis paper shows for the first time a complex set of alterations in the cerebellum granular layer of a mouse model (IB2 KO) of autism spectrum disorders. The IB2 KO in mice mimics the deletion of the corresponding gene in the Phelan McDermid syndrome in humans. The changes reported here are centered on NMDA receptor hyper-activity, hyper -plasticity and hyper-excitability. These, in turn, increase the excitatory/inhibitory balance and alter the shape of center/surround structures that emerge in the granular layer in response to mossy fiber activity. These results supports recent theories suggesting the involvement of cerebellum in autism spectrum disorders.
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9. Zheng R, Naiman ID, Skultety J, Passmore SR, Lyons J, Glazebrook CM. {{The Impact of Different Movement Types on Motor Planning and Execution in Individuals With Autism Spectrum Disorder}}. {Motor control}. 2019: 1-20.
Although there are consistent reports that motor skills are affected in individuals with autism, the details are still debated; specifically, why individuals spend more time preparing movements and whether or not movement execution takes longer. The present study investigated if the conflicting reports were related to: (a) differences in movement type and (b) if longer reaction times were related to the time for motor planning or for force-generation processes. Participants performed three different movement types. People with autism had longer premotor reaction times and movement times for the three-dimensional movements only. We suggest individuals with autism have difficulty planning and executing unconstrained reaching movements specifically. The present results are consistent with evidence that autistic individuals have more difficulty effectively using visual feedback but can use tactile feedback to execute reaching movements efficiently and accurately.
