1. Bast N, Gaigg SB, Bowler DM, Roessner V, Freitag CM, Ring M. Arousal-modulated memory encoding and retrieval in adults with autism spectrum disorder. Autism Res;2022 (Jul 30)

Recently, we have shown that pupil dilation during a recognition memory task can serve as an index of memory retrieval difficulties in autism. At the time of publication, we were unaware of specific data-analysis methods that can be used to shed further light on the origins of such memory related pupil dilation. Specifically, by distinguishing « tonic » from « phasic » changes in pupil dilation and considering their temporal progression, it is possible to draw inferences about the functional integrity of a locus coeruleus-norepinephrine system (LC-NE) that is known to play a key role in regulating memory encoding and retrieval processes. We therefore apply these analyses to our previously published eye-tracking data of adults with ASD (N = 24) and neurotypical development (TD, N = 30) during the recognition memory task. In this re-analysis, we related pupil dilation during encoding and retrieval to recognition accuracy in a per-trial analysis of linear mixed models. In ASD, we replicated attenuated recognition accuracy, which was accompanied by attenuated pupil dilation during encoding and retrieval. Group differences in pupil dilation during retrieval occurred late during the trial (after 1.75 s) and indicated an altered top-down processing like attenuated attribution of semantic salience in response to previously encoded stimuli. In addition, only in the ASD group were higher pupil dilation during encoding and lower pupil dilation during retrieval associated with decreased recognition accuracy. This supports altered modulation of memory encoding and retrieval in ASD, with LC-NE phasic activity as promising underlying mechanism. LAY SUMMARY: We investigated the changes of pupil size during memory testing in autism spectrum disorder. Adults with ASD remembered fewer items correctly than neurotypical individuals (TD). This reduced memory was related to increased pupillary responses at study and decreased pupil dilation at test only for adults with ASD indicating a different modulation of memory by the locus coeruleus.

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2. Cai RY, Gibbs V, Love A, Robinson A, Fung L, Brown L. « Self-compassion changed my life »: The self-compassion experiences of autistic and non-autistic adults and its relationship with mental health and psychological wellbeing. J Autism Dev Disord;2022 (Jul 29)

Self-compassion is a gentle way of relating to oneself, linked to a host of mental health benefits in non-autistic people. Although many autistic individuals report high anxiety and depression symptoms, no research to-date has examined the self-compassion experiences of autistic individuals and determined if self-compassion is associated with psychopathology. Therefore, the purpose of the current study was to address this research gap. The participants (153 autistic and 93 non-autistic adults) completed on online survey and 11 autistic participants were also interviewed. Autistic participants reported significantly lower self-compassion than non-autistic adults, and in both groups, those with higher self-compassion reported higher psychological wellbeing and lower depression symptoms. Demographic predictors of self-compassion were identified. These findings have both clinical and research implications.

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3. Davis K, Iosif AM, Nordahl CW, Solomon M, Krug MK. Correction: Video Game Use, Aggression, and Social Impairment in Adolescents with Autism Spectrum Disorder. J Autism Dev Disord;2022 (Jul 29)

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4. Durankuş F, Albayrak Y, Erdoğan F, Albayrak N, Erdoğan MA, Erbaş O. Granulocyte Colony-Stimulating Factor Has a Sex-Dependent Positive Effect in the Maternal Immune Activation-Induced Autism Model. Int J Dev Neurosci;2022 (Jul 29)

OBJECTIVE: The medical intervention for autism spectrum disorder (ASD) is restricted to ameliorating comorbid situations. Granulocyte colony-stimulating factor (G-CSF) is a growth factor that enhances the proliferation, differentiation and survival of hematopoietic progenitor cells. In the present study, we aimed to investigate the effects of G-CSF in a maternal immune activation-induced autism model. METHODS: Sixteen female and 6 male Wistar adult rats were included in the study. After 21 days, forty-eight littermates (8 male controls, 8 female controls, 16 male lipopolysaccharide (LPS)-exposed rats and 16 female LPS-exposed rats) were divided into groups. Sixteen male LPS-exposed and 16 female LPS-exposed rats were divided into saline and G-CSF treatment groups. RESULTS: In male rats, the LPS-exposed group was found to have significantly higher levels of TNF-α, IL-2, and IL-17 than the LPS-exposed G-CSF group. Levels of nerve growth factor, brain PSD-95 and brain GAD67 were higher in the LPS-exposed G-CSF group than in the LPS-exposed group in male rats. In female rats, brain NGF levels were similar between groups. There was no difference between groups in terms of brain GAD 67 levels. Brain PSD-95 levels were higher in the control group than in both the LPS-exposed and LPS-exposed G-CSF groups in female rats. Both neuronal CA1 and neuronal CA2 levels were lower, and the GFAP immunostaining index (CA1) and GFAP immunostaining index (CA3) were higher in the LPS-exposed group than in the LPS-exposed G-CSF group in male rats. However, neuronal count CA1 and Neuronal count CA3 values were found to be similar between groups in female rats. CONCLUSIONS: The present research is the first to demonstrate the beneficial effects of G-CSF on core symptoms of ASD experimentally depending on male sex. G-CSF can be a good candidate for ameliorating the core symptoms of ASD without serious side effects in males.

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5. Gerber AH, Kang E, Nahmias AS, Libsack EJ, Simson C, Lerner MD. Predictors of Treatment Response to a Community-Delivered Group Social Skills Intervention for Youth with ASD. J Autism Dev Disord;2022 (Jul 29)

Group social skills interventions (GSSIs) are among the most commonly used treatments for improving social competence in youth with ASD, however, results remain variable. The current study examined predictors of treatment response to an empirically-supported GSSI for youth with ASD delivered in the community (N(total)=75). Participants completed a computer-based emotion recognition task and their parents completed measures of broad psychopathology, ASD symptomatology, and social skills. We utilized generalized estimating equations in an ANCOVA-of-change framework to account for nesting. Results indicate differential improvements in emotion recognition by sex as well as ADHD-specific improvements in adaptive functioning. Youth with both co-occurring anxiety and ADHD experienced iatrogenic effects, suggesting that SDARI may be most effective for youth with ASD without multiple co-occurring issues. Findings provide important directions for addressing variability in treatment outcomes for youth with ASD.

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6. Hecker L, Wilson M, Tebartz van Elst L, Kornmeier J. Altered EEG variability on different time scales in participants with autism spectrum disorder: an exploratory study. Sci Rep;2022 (Jul 29);12(1):13068.

One of the great challenges in psychiatry is finding reliable biomarkers that may allow for more accurate diagnosis and treatment of patients. Neural variability received increasing attention in recent years as a potential biomarker. In the present explorative study we investigated temporal variability in visually evoked EEG activity in a cohort of 16 adult participants with Asperger Syndrome (AS) and 19 neurotypical (NT) controls. Participants performed a visual oddball task using fine and coarse checkerboard stimuli. We investigated various measures of neural variability and found effects on multiple time scales. (1) As opposed to the previous studies, we found reduced inter-trial variability in the AS group compared to NT. (2) This effect builds up over the entire course of a 5-min experiment and (3) seems to be based on smaller variability of neural background activity in AS compared to NTs. The here reported variability effects come with considerably large effect sizes, making them promising candidates for potentially reliable biomarkers in psychiatric diagnostics. The observed pattern of universality across different time scales and stimulation conditions indicates trait-like effects. Further research with a new and larger set of participants are thus needed to verify or falsify our findings.

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7. Ludlow AK, Osborne C, Keville S. Selective Mutism in Children With and Without an Autism Spectrum Disorder: The Role of Sensory Avoidance in Mediating Symptoms of Social Anxiety. J Autism Dev Disord;2022 (Jul 29)

The present study addressed the different contributors to social anxiety in children with Selective Mutism (SM), with and without co-occurring Autism Spectrum Disorder (ASD) (SM + ASD). Seventy-five parents completed an online composite questionnaire consisting of the symptoms of SM and ASD, anxiety and sensory measures. The results found the SM + ASD group showed significantly higher levels of social anxiety and sensory avoidance compared to the SM only group. However, a simple mediation model revealed sensory avoidance to be a mediator of this relationship between the diagnosis and social anxiety.. Therefore, higher levels of sensory avoidance may help to differentiate social anxiety between the groups and may also be a sign of ASD in children with SM who have and/or are yet to receive an ASD diagnosis.

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8. Pedrazzi JFC, Ferreira FR, Silva-Amaral D, Lima DA, Hallak JEC, Zuardi AW, Del-Bel EA, Guimarães FS, Costa KCM, Campos AC, Crippa ACS, Crippa JAS. Cannabidiol for the treatment of autism spectrum disorder: hope or hype?. Psychopharmacology (Berl);2022 (Jul 29)

RATIONALE: Autism spectrum disorder (ASD) is defined as a group of neurodevelopmental disorders whose symptoms include impaired communication and social interaction, restricted and repetitive patterns of behavior, and varying levels of intellectual disability. ASD is observed in early childhood and is one of the most severe chronic childhood disorders in prevalence, morbidity, and impact on society. It is usually accompanied by attention deficit hyperactivity disorder, anxiety, depression, sleep disorders, and epilepsy. The treatment of ASD has low efficacy, possibly because it has a heterogeneous nature, and its neurobiological basis is not clearly understood. Drugs such as risperidone and aripiprazole are the only two drugs available that are recognized by the Food and Drug Administration, primarily for treating the behavioral symptoms of this disorder. These drugs have limited efficacy and a high potential for inducing undesirable effects, compromising treatment adherence. Therefore, there is great interest in exploring the endocannabinoid system, which modulates the activity of other neurotransmitters, has actions in social behavior and seems to be altered in patients with ASD. Thus, cannabidiol (CBD) emerges as a possible strategy for treating ASD symptoms since it has relevant pharmacological actions on the endocannabinoid system and shows promising results in studies related to disorders in the central nervous system. OBJECTIVES: Review the preclinical and clinical data supporting CBD’s potential as a treatment for the symptoms and comorbidities associated with ASD, as well as discuss and provide information with the purpose of not trivializing the use of this drug.

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9. Yildirim M, Delepine C, Feldman D, Pham VA, Chou S, Ip J, Nott A, Tsai LH, Ming GL, So PTC, Sur M. Label-free three-photon imaging of intact human cerebral organoids for tracking early events in brain development and deficits in Rett syndrome. Elife;2022 (Jul 29);11

Human cerebral organoids are unique in their development of progenitor-rich zones akin to ventricular zones from which neuronal progenitors differentiate and migrate radially. Analyses of cerebral organoids thus far have been performed in sectioned tissue or in superficial layers due to their high scattering properties. Here, we demonstrate label-free three-photon imaging of whole, uncleared intact organoids (~2 mm depth) to assess early events of early human brain development. Optimizing a custom-made three-photon microscope to image intact cerebral organoids generated from Rett Syndrome patients, we show defects in the ventricular zone volumetric structure of mutant organoids compared to isogenic control organoids. Long-term imaging live organoids reveals that shorter migration distances and slower migration speeds of mutant radially migrating neurons are associated with more tortuous trajectories. Our label-free imaging system constitutes a particularly useful platform for tracking normal and abnormal development in individual organoids, as well as for screening therapeutic molecules via intact organoid imaging.

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10. Zarakoviti E, Shafran R, Skuse D, McTague A, Batura N, Palmer T, Dalrymple E, Bennett SD, Reilly C. Factor associated with the occurrence of epilepsy in autism: a systematic review. J Autism Dev Disord;2022 (Jul 29)

This systematic review aimed to identify factors significantly associated with the occurrence of epilepsy in autistic individuals and to consider the impact of study quality on findings. Electronic databases were systematically searched on October 2nd, 2020 and records retrieved were limited to those published from 2000 onwards. Study quality was categorised as ‘good’, ‘moderate’ or ‘weak’. Fifty-three studies were included and in studies where the prevalence of epilepsy was reported (n = 257,892), 18,254 (7%) had co-occurring epilepsy. Intellectual disability/cognitive impairment was the most commonly reported risk factor associated with occurrence of epilepsy in autistic individuals. The evidence supporting other, potentially relevant factors was weak and inconsistent and requires further evaluation. Only 9/53 studies were considered ‘good’ quality.

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