1. Bin-Khattaf RM, Al-Dbass AM, Alonazi M, Bhat RS, Al-Daihan S, El-Ansary AK. In a rodent model of autism, probiotics decrease gut leakiness in relation to gene expression of GABA receptors: Emphasize how crucial the gut-brain axis. Transl Neurosci. 2024; 15(1): 20220354.

OBJECTIVE: Rodent models may help investigations on the possible link between autism spectrum disorder and increased permeability of the gastrointestinal (GI) tract since autistic patients frequently manifested GI troubles as comorbidities. METHODS: Forty young male western Albino rats, weighing approximately 60-70 g and aged 3-4 weeks, were used. In each of the six experimental groups, eight animals were treated as follows. The mice in the control group (I) received phosphate-buffered saline orally. For 3 days, the animals in the propionic acid (PPA)-treated groups (II and III) were given an oral neurotoxic dose of PPA (250 mg/kg body weight each day). Group II was euthanized after 3 days; however, Group III was left alive to be euthanized alongside the other groups. The animals were kept at 22 ± 1°C and allowed to access water and normal food as needed. Identical dosages of PPA were given to the rats in the three treatment groups (IV, V, and VI), and for 3 weeks, they were given the following treatments: 0.2 g/kg body weight of pure Bifidobacterium infantis, a probiotic mixture of PROTEXIN®, Somerset, UK and pure Lactobacillus bulgaricus, respectively. The six groups underwent measurements of serum zonulin and occludin as variables associated with leaky gut, glutathione, malondialdehyde, and catalase as oxidative stress-related variables, with gamma-aminobutyric acid (GABA) receptor gene expression. RESULTS: This study demonstrated the potential effects of pure or mixed probiotics in lowering zonulin and occludin as markers of increased intestinal permeability, enhancing GABA receptor expression, and reducing oxidative stress as neurotoxic effects of PPA. CONCLUSIONS: This study demonstrates that various probiotics protect gut barrier function and could be used to alleviate increased intestinal permeability caused by oxidative stress and impaired GABA signaling as a result of PPA neurotoxicity, addressing the clinical implications of probiotic supplements.

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2. Brown K. Navigating surgery with ADHD and autism. Bmj. 2024; 387: q1834.

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3. Moerman F, Warreyn P, Noens I, Steyaert J, van Esch L, de Vries L, Madarevic M, Segers J, Van Lierde T, Roeyers H. Exploring cascading effects of sensory processing on language skills and social-communicative difficulties through play in young children at elevated likelihood for autism. Infancy. 2024.

This study investigated the association between Sensory processing (SP) (i.e., hyporesponsiveness, Sensory Seeking (SS) and hyperresponsiveness) at 10 months (M) and language/social-communicative difficulties at 24M, mediated through object play at 14M in young children at elevated likelihood for autism (EL). Parent-report instruments were used to measure all variables in younger siblings of children with autism (siblings, n = 74) and children born before 30 gestational weeks (preterms, n = 38). Higher scores of object play fully mediated the association between more SS and better language/less social-communicative difficulties. Hypo- and hyperresponsiveness at 10M did not seem to predict language heterogeneity at 24M, but more hypo- and less hyperresponsiveness at 10M were associated with more social-communicative difficulties at 24M. The explained variance in social-communicative difficulties and language was limited (15.25%-16.39%). Similar associations were found for siblings and preterms. This highlights that high frequency of SP behaviors does not necessarily negatively affect communication in young EL-children as is commonly assumed. Early object play skills play a role in the association between early SS and later language/social communicative difficulties. This implies that some criteria of the two core domains of characteristics of autism are interrelated in EL-children, and this may have implications for early intervention programs.

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4. Moreno RJ, Amara R, Ashwood P. Toward a better understanding of T cell dysregulation in autism: An integrative review. Brain Behav Immun. 2024.

Autism spectrum disorder (ASD) is a highly heterogeneous disorder characterized by impairments in social, communicative, and restrictive behaviors. Over the past 20 years, research has highlighted the role of the immune system in regulating neurodevelopment and behavior. In ASD, immune abnormalities are frequently observed, such as elevations in pro-inflammatory cytokines, alterations in immune cell frequencies, and dysregulated mechanisms of immune suppression. The adaptive immune system – the branch of the immune system conferring cellular immunity – may be involved in the etiology of ASD. Specifically, dysregulated T cell activity, characterized by altered cellular function and increased cytokine release, presence of inflammatory phenotypes and altered cellular signaling, has been consistently observed in several studies across multiple laboratories and geographic regions. Similarly, mechanisms regulating their activation are also disrupted. T cells at homeostasis coordinate the healthy development of the central nervous system (CNS) during early prenatal and postnatal development, and aid in CNS maintenance into adulthood. Thus, T cell dysregulation may play a role in neurodevelopment and the behavioral and cognitive manifestations observed in ASD. Outside of the CNS, aberrant T cell activity may also be responsible for the increased frequency of immune based conditions in the ASD population, such as allergies, gut inflammation and autoimmunity. In this review, we will discuss the current understanding of T cell biology in ASD and speculate on mechanisms behind their dysregulation. This review also evaluates how aberrant T cell biology affects gastrointestinal issues and behavior in the context of ASD.

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5. Mournet AM, Kellerman JK, Garner RC, Kleiman EM. Suicidal Thoughts and Behaviors Among Autistic Transgender or Gender-Nonconforming US College Students. JAMA Netw Open. 2024; 7(10): e2438345.

IMPORTANCE: Suicide risk is a global public health crisis, with suicide ranking as a consistent leading cause of death among adults in the US. Autistic individuals and transgender or gender-nonconforming (TGNC) individuals represent populations with notably elevated rates of suicidal thoughts and behaviors (STBs). OBJECTIVE: To characterize suicidal thoughts and behaviors among TGNC and autistic individuals, using a large, nationally representative sample. DESIGN, SETTING, AND PARTICIPANTS: This study is a secondary analysis of cross-sectional data from students at colleges and universities throughout the US who participated in the American College Health Association National College Health Assessment from 2019 to 2023. EXPOSURES: Autistic and TGNC identities were self-reported by participants. MAIN OUTCOMES AND MEASURES: The frequency of intersectionality of autism and TGNC identities and whether those who had intersectional marginalized identities had increased likelihood of STBs were examined. STBs were self-reported by participants. A series of moderated regression analyses were performed to examine how the interaction between autism and possessing a marginalized gender identity (ie, TGNC status) was associated with STBs. RESULTS: The sample included 41 507 college students with a mean (SD) age of 23.35 (6.83) years. A total of 2410 participants (5.81%) identified as being TGNC. Overall, 326 TGNC participants (13.53%) also identified as autistic, whereas 625 of those who identified as cisgender (1.58%) also identified as autistic. Gender identity and autism were associated with greater odds of STBs. For suicidal ideation, gender identity had an odds ratio (OR) of 3.34 (95% CI, 2.99-3.73), and autism had an OR of 2.06 (95% CI, 1.76-2.42). For suicide attempts, gender identity had an OR of 2.74 (95% CI, 2.13-3.52), and autism had an OR of 2.39 (95% CI, 1.62-3.52). A significant interaction existed for attempts (OR, 0.51; 95% CI, 0.27-0.97); nonautistic cisgender individuals had the lowest attempt rate. CONCLUSIONS AND RELEVANCE: This cross-sectional study addresses the dearth of information on how intersectionality in gender and autism status impacts the risk of STBs, and the results confirm the elevated risk of STBs among TGNC and autistic populations. Interventions are needed to support college students with these identities.

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6. Nenadić I, Schröder Y, Hoffmann J, Evermann U, Pfarr JK, Bergmann A, Hohmann DM, Keil B, Abu-Akel A, Stroth S, Kamp-Becker I, Jansen A, Grezellschak S, Meller T. Superior temporal sulcus folding, functional network connectivity, and autistic-like traits in a non-clinical population. Mol Autism. 2024; 15(1): 44.

BACKGROUND: Autistic-like traits (ALT) are prevalent across the general population and might be linked to some facets of a broader autism spectrum disorder (ASD) phenotype. Recent studies suggest an association of these traits with both genetic and brain structural markers in non-autistic individuals, showing similar spatial location of findings observed in ASD and thus suggesting a potential neurobiological continuum. METHODS: In this study, we first tested an association of ALTs (assessed with the AQ questionnaire) with cortical complexity, a cortical surface marker of early neurodevelopment, and then the association with disrupted functional connectivity. We analysed structural T1-weighted and resting-state functional MRI scans in 250 psychiatrically healthy individuals without a history of early developmental disorders, in a first step using the CAT12 toolbox for cortical complexity analysis and in a second step we used regional cortical complexity findings to apply the CONN toolbox for seed-based functional connectivity analysis. RESULTS: Our findings show a significant negative correlation of both AQ total and AQ attention switching subscores with left superior temporal sulcus (STS) cortical folding complexity, with the former being significantly correlated with STS to left lateral occipital cortex connectivity, while the latter showed significant positive correlation of STS to left inferior/middle frontal gyrus connectivity (n = 233; all p < 0.05, FWE cluster-level corrected). Additional analyses also revealed a significant correlation of AQ attention to detail subscores with STS to left lateral occipital cortex connectivity. LIMITATIONS: Phenotyping might affect association results (e.g. choice of inventories); in addition, our study was limited to subclinical expressions of autistic-like traits. CONCLUSIONS: Our findings provide further evidence for biological correlates of ALT even in the absence of clinical ASD, while establishing a link between structural variation of early developmental origin and functional connectivity.

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7. Purba CAP, Febriyana N, Setiawati Y. Managing Aggressive Behavior in Adolescents With Autism Spectrum Disorder: Pharmacological and Non-Pharmacological Approaches. Soa Chongsonyon Chongsin Uihak. 2024; 35(4): 223-9.

Adolescents diagnosed with autism spectrum disorder (ASD) often encounter significant challenges, particularly aggressive behaviors that persist into adulthood and profoundly affect their daily functioning and quality of life. These behaviors not only pose hurdles for affected individuals but also present considerable challenges for caregivers and families. Managing aggression in adolescents with ASD requires comprehensive treatment approaches encompassing both non-pharmacological and pharmacological interventions. This paper reviews current interventions that have proven to be effective through empirical studies in managing aggression among adolescents with ASD. By synthesizing evidence-based practices, this study underscores the importance of a multidisciplinary approach involving medical, psychological, and educational interventions to effectively manage aggression among adolescents with ASD. It aimed to inform clinicians, educators, and caregivers of practical strategies and evidence-based interventions to address aggression in this population.

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8. Rajabi P, Noori AS, Sargolzaei J. Autism spectrum disorder and various mechanisms behind it. Pharmacol Biochem Behav. 2024: 173887.

Autism Spectrum Disorder (ASD) is a complex and heterogeneous neurodevelopmental condition characterized by a range of social, communicative, and behavioral challenges. This comprehensive review delves into key aspects of ASD. Clinical Overview and genetic features provide a foundational understanding of ASD, highlighting the clinical presentation and genetic underpinnings that contribute to its complexity. We explore the intricate neurobiological mechanisms at play in ASD, including structural and functional differences that may underlie the condition’s hallmark traits. Emerging research has shed light on the role of the immune system and neuroinflammation in ASD. This section investigates the potential links between immunological factors and ASD, offering insights into the condition’s pathophysiology. We examine how atypical functional connectivity and alterations in neurotransmitter systems may contribute to the unique cognitive and behavioral features of ASD. In the pursuit of effective interventions, this section reviews current therapeutic strategies, ranging from behavioral and educational interventions to pharmacological approaches, providing a glimpse into the diverse and evolving landscape of ASD treatment. This holistic exploration of mechanisms in ASD aims to contribute to our evolving understanding of the condition and to guide the development of more targeted and personalized interventions for individuals living with ASD.

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9. Wang Z, Zheng L, Yang L, Yin S, Yu S, Chen K, Zhang T, Wang H, Zhang T, Zhang Y. Structural and functional whole brain changes in autism spectrum disorder at different age stages. Eur Child Adolesc Psychiatry. 2024.

Autism spectrum disorder (ASD) is a developmental disorder involving regional changes and local neural disturbances. However, few studies have investigated the dysfunctional phenomenon across different age stages. This study explores the structural and functional brain changes across different developmental stages in individuals with ASD, focusing on childhood (6-12 years), adolescence (12-18 years), and adulthood (18 + years). Using a comprehensive set of neuroimaging metrics, including modulated and non-modulated voxel-based morphometry (VBM), regional homogeneity (ReHo), amplitude of low-frequency fluctuation (ALFF), and fractional ALFF (fALFF), we identified significant stage-specific alterations in both VBM and functional measurements. Our results reveal that ASD is associated with progressive and stage-specific abnormalities in brain structure and function, with distinct patterns emerging at each developmental stage. Specifically, we observed significant modulated VBM reductions in the precuneus, lentiform nucleus, and inferior parietal lobule, accompanied by increases in the midbrain and sub-gyral regions. Moreover, we observed unmodulated VBM increment in regions including lentiform nucleus and thalamus. Functionally, ReHo analyses demonstrated disrupted local synchronization in the medial frontal gyrus, while ALFF and fALFF metrics highlighted altered spontaneous brain activity in the sub-gyral and sub-lobar. Finally, correlation analyses revealed that stage-specific findings are closely linked to clinical social- and behavior-related scores, with VBM in the inferior parietal lobule and putamen as well as ReHo in supplemental motor area being significantly associated with restrictive repetitive behaviors in childhood. These findings underscore the importance of considering age-specific brain changes when studying ASD and suggest that targeted interventions may be necessary at different developmental stages.

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