1. Baribeau D, Vorstman J, Anagnostou E. Novel treatments in autism spectrum disorder. Current opinion in psychiatry. 2022; 35(2): 101-10.

PURPOSE OF REVIEW: There are currently no approved medications for the core symptoms of autism spectrum disorder (ASD), and only limited data on the management of co-occurring mental health and behavioural symptoms. The purpose of this review is to synthesize recent trials on novel treatments in ASD, with a focus on research trends in the past 2 years. RECENT FINDINGS: No new pharmacologic agents received regulatory approval for use in ASD. Several large randomized controlled trials (RCTs) had negative or ambiguous results (e.g. fluoxetine, oxytocin). A cross-over RCT of an oral cannabinoid suggested possible benefits for disruptive behaviours. Two large-scale multicentre trials of bumetanide were terminated early for lack of efficacy. Multicenter trials using repetitive transcranial magnetic stimulation are underway. Recent meta-analyses indicate that specific behavioural and psychological interventions can support social communication and treat anxiety. Numerous novel treatment targets informed by biological mechanisms are under investigation. SUMMARY: Recent data support the use of behavioural and psychological interventions for social communication and anxiety in ASD; data are more limited regarding pharmacotherapy for core and associated symptoms. Next steps include replication of early findings, trials of new molecular targets, and the identification of novel biomarkers, including genetic predictors, of treatment response.

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2. Borsani E, Bonomini F, Bonini SA, Premoli M, Maccarinelli G, Giugno L, Mastinu A, Aria F, Memo M, Rezzani R. Role of melatonin in autism spectrum disorders in a male murine transgenic model: Study in the prefrontal cortex. Journal of neuroscience research. 2022; 100(3): 780-97.

Autism spectrum disorders (ASDs) are a group of clinically heterogeneous neurodevelopmental disorders sharing common features related to impaired social and communication abilities in addition to stereotyped behaviors. ASD patients present encephalic morphological, physiological, and biomolecular alterations with low levels of melatonin due to alterations in its pathways. Therefore, even if ASDs have traditionally been framed as behavioral disorders, several lines of evidence are accumulating that ASDs are characterized by certain anatomical and physiological abnormalities, including oxidative stress and inflammation in peripheral biomarkers, but likewise present in human brain tissue also characterized by alterations in synaptic remodeling and neuromodulation. Melatonin has also protective and antioxidant properties, so we can therefore hypothesize that alterations in melatonin’s pathways may be one of the causes of the symptomatology of autism. The aim of the present study was to analyze the beneficial effect induced by melatonin administration and its possible mechanism of action in a transgenic mouse model of autism, immediately after weaning. The male mice were daily treated per os with melatonin (10 mg/Kg/day) or vehicle for 8 weeks starting from the sixth week of life. The antioxidant modulation, the GABAergic/glutamatergic impairment, and the synaptic remodeling in the prefrontal cortex have been evaluated. Social and repetitive behaviors were also evaluated. The behavioral results showed no statistical evidences, instead the immunohistochemical results indicated the ability of melatonin to promote the activity of antioxidant system, the GABAergic/glutamatergic equilibrium, and the synaptic remodeling. The results show that melatonin may be a possible adjuvant therapeutic strategy in ASDs.

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3. Calderoni S. Sex/gender differences in children with autism spectrum disorder: A brief overview on epidemiology, symptom profile, and neuroanatomy. Journal of neuroscience research. 2022.

Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental conditions whose shared core features are impairments in social interaction and communication as well as restricted patterns of behavior, interests, and activities. The significant and consistent male preponderance in ASD prevalence has historically affected the scientific knowledge of autism in females as regards, inter alia, the clinical presentation, the genetic architecture, and the structural brain underpinnings. Indeed, females with ASD are under-investigated as samples recruited for clinical research typically reflect the strong male bias of the disorder. In the last years, the study of the various aspects of sex/gender (s/g) differences in ASD is gaining increased clinical and research interest resulting in a growing number of investigations on this topic. Here, I review and discuss evidence emerged from epidemiological, clinical, and neuroimaging studies in the last decade focusing on s/g differences in children with ASD. These studies are the prerequisites for the development of assessment and treatment practices which take into consideration s/g differences in ASD. Ultimately, a better understanding of s/g differences aims at improving healthcare for both ASD males and females.

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4. Denney KE, Anderson KL, Watson JM. Exploring the communication needs and challenges of adults with autism spectrum disorders: Communication partners’ perspectives. International journal of speech-language pathology. 2022: 1-9.

Purpose: Individuals with autism spectrum disorders (ASD) and Complex Communication Needs (CCN) require additional support from communication partners in order to communicate effectively. This study aimed to address a current gap in the literature by exploring communication partners’ perspectives of their role. Method: A qualitative multiple case study design was used. The sample consisted of four participants who represented a diverse range of relationships with adults with ASD and CCN. Individual, in-depth, semi-structured interviews were conducted. Interview transcripts were analysed using the Framework Method of thematic analysis. Result: Four key themes were identified: (1) respecting the individual (2) flexibility (3) reaching beyond the dyad and (4) underlying beliefs. Due to the diverse range of relationships represented in this study, each case provided a unique perspective and therefore the results of each individual case were contrasted within each theme. Conclusion: The findings of this study highlight the crucial role that communication partners play in enabling interactions with adults who have ASD and CCN. Additionally, these findings provide preliminary evidence to support an expansion of the existing framework of communicative competence for individuals with CCN. Future research should aim to expand on these findings in order to investigate their generalisability.

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5. Muller K, Brady NC, Fleming KK. Alternative receptive language assessment modalities and stimuli for autistic children who are minimally verbal. Autism : the international journal of research and practice. 2022: 13623613211065225.

It is difficult to measure language comprehension abilities in autistic children who have limited expressive language skills. Results from available assessments may underestimate autistic children’s receptive language skills. The primary purpose of this study was to compare alternative modalities and stimuli used to measure receptive vocabulary skills in autistic children who are minimally verbal. This study compared participants’ outcomes on three different receptive vocabulary assessment conditions: an assessment that used a low-tech stimulus book, a touchscreen assessment, and an assessment that used real-object stimuli. Twenty-seven students between the ages of 3 and 12 who had minimal verbal skills and a diagnosis of autism spectrum disorder participated in this study. Results showed that participants’ scores in the real-object assessment condition were significantly higher than in the low-tech condition and marginally higher than scores in the touchscreen condition. These results suggest real-object stimuli may provide a more robust measure of autistic children’s receptive vocabulary skills than traditional low-tech picture stimuli. Although many direct standardized assessments use picture stimuli to measure word understanding, when assessing autistic individuals who have limited expressive language, real objects can be used in replacement of, or in addition to, picture stimuli.

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6. Odom SL, Sam AM, Tomaszewski B. Factors associated with implementation of a school-based comprehensive program for students with autism. Autism : the international journal of research and practice. 2022; 26(3): 703-15.

The purpose of this study was to identify influences on the implementation of a school-based, comprehensive program for autistic students. Influences from the community context, from within the school organization, and from features of the intervention itself were examined. The study took place in 39 elementary schools in a southeastern state in the United States. Transformational leadership style of the building principal, percentage of white students at the school (which was proposed as a broader community socioeconomic variable), and adequacy of coaching were all associated with implementation.

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7. Shanker S, Pradhan B. Effect of Yoga on the Motor Proficiency of Children with Autism Spectrum Disorder and the Feasibility of its Inclusion in Special School Environments. Adapted physical activity quarterly : APAQ. 2022; 39(2): 247-67.

Yoga as a movement-based intervention is increasingly considered to improve the motor skills of children with autism spectrum disorder (ASD). However, there is little evidence of the effect of yoga on their motor skills. The current study aims to explore the effect of group yoga program on motor proficiency of children with ASD and feasibility of its inclusion in special schools. Forty-three children with ASD from four special schools were randomized into yoga (n = 23) and control (n = 20) group. A structured yoga program of 45 min for 12 weeks was delivered by trained yoga teachers who also tracked their daily responses. The Bruininks-Oseretsky Test of Motor Proficiency. Second Edition was used to assess both the groups pre- and postintervention. In conclusion, the study highlighted that yoga appears to have a positive impact on the gross motor rather than fine motor proficiency of children with ASD and is feasible to be delivered as group intervention in special schools.

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8. Thorne BN, Ellenbroek BA, Day DJ. The serotonin reuptake transporter modulates mitochondrial copy number and mitochondrial respiratory complex gene expression in the frontal cortex and cerebellum in a sexually dimorphic manner. Journal of neuroscience research. 2022; 100(3): 869-79.

Neuropsychiatric and neurodevelopmental disorders such as major depressive disorder (MDD) and autism spectrum disorder (ASD) are complex conditions attributed to both genetic and environmental factors. There is a growing body of evidence showing that serotonergic signaling and mitochondrial dysfunction contribute to the pathophysiology of these disorders and are linked as signaling through specific serotonin (5-HT) receptors drives mitochondrial biogenesis. The serotonin transporter (SERT) is important in these disorders as it regulates synaptic serotonin and therapeutically is the target of selective serotonin reuptake inhibitors which are a major class of anti-depressant drug. Human allelic variants of the serotonin transporter-linked polymorphic region (5-HTTLPR) such as the S/S variant, are associated with reduced SERT expression and increased susceptibility for developing neuropsychiatric disorders. Using a rat model that is haploinsufficient for SERT and displays reduced SERT expression similar to the human S/S variant, we demonstrate that reduced SERT expression modulates mitochondrial copy number and expression of respiratory chain electron transfer components in the brain. In the frontal cortex, genotype-related trends were opposing for males and females, such that reduced SERT expression led to increased expression of the Complex I subunit mt-Nd1 in males but reduced expression in females. Our findings suggest that SERT expression and serotonergic signaling have a role in regulating mitochondrial biogenesis and adenosine triphosphate (ATP) production in the brain. We speculate that the sexual dimorphism in mitochondrial abundance and gene expression contributes to the sex bias found in the incidence of neuropsychiatric disorders such as MDD and ASD.

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