1. Arman S. What is the overall prognosis of preschool autism spectrum disorder diagnoses? A Cochrane Review summary with commentary. Developmental medicine and child neurology. 2023.

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2. Jia H, Wu X, Zhang X, Guo M, Yang C, Wang E. Resting-state EEG Microstate Features Can Quantitatively Predict Autistic Traits in Typically Developing Individuals. Brain topography. 2023.

Autism spectrum disorder (ASD) is not a discrete disorder and that symptoms of ASD (i.e., so-called « autistic traits ») are found to varying degrees in the general population. Typically developing individuals with sub-clinical yet high-level autistic traits have similar abnormities both in behavioral performances and cortical activation patterns to individuals diagnosed with ASD. Thus it’s crucial to develop objective and efficient tools that could be used in the assessment of autistic traits. Here, we proposed a novel machine learning-based assessment of the autistic traits using EEG microstate features derived from a brief resting-state EEG recording. The results showed that: (1) through the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm and correlation analysis, the mean duration of microstate class D, the occurrence rate of microstate class A, the time coverage of microstate class D and the transition rate from microstate class B to D were selected to be crucial microstate features which could be used in autistic traits prediction; (2) in the support vector regression (SVR) model, which was constructed to predict the participants’ autistic trait scores using these four microstate features, the out-of-sample predicted autistic trait scores showed a significant and good match with the self-reported scores. These results suggest that the resting-state EEG microstate analysis technique can be used to predict autistic trait to some extent.

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3. Licinio J, Wong ML. Psychosis and autism spectrum disorder: a special issue of Molecular Psychiatry. Molecular psychiatry. 2023; 28(5): 1830-2.

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4. Maussion G, Rocha C, Abdian N, Yang D, Turk J, Carrillo Valenzuela D, Pimentel L, You Z, Morquette B, Nicouleau M, Deneault E, Higgins S, Chen CX, Reintsch WE, Ho S, Soubannier V, Lépine S, Modrusan Z, Lund J, Stephenson W, Schubert R, Durcan TM. Transcriptional Dysregulation and Impaired Neuronal Activity in FMR1 Knock-Out and Fragile X Patients’ iPSC-Derived Models. International journal of molecular sciences. 2023; 24(19).

Fragile X syndrome (FXS) is caused by a repression of the FMR1 gene that codes the Fragile X mental retardation protein (FMRP), an RNA binding protein involved in processes that are crucial for proper brain development. To better understand the consequences of the absence of FMRP, we analyzed gene expression profiles and activities of cortical neural progenitor cells (NPCs) and neurons obtained from FXS patients’ induced pluripotent stem cells (IPSCs) and IPSC-derived cells from FMR1 knock-out engineered using CRISPR-CAS9 technology. Multielectrode array recordings revealed in FMR1 KO and FXS patient cells, decreased mean firing rates; activities blocked by tetrodotoxin application. Increased expression of presynaptic mRNA and transcription factors involved in the forebrain specification and decreased levels of mRNA coding AMPA and NMDA subunits were observed using RNA sequencing on FMR1 KO neurons and validated using quantitative PCR in both models. Intriguingly, 40% of the differentially expressed genes were commonly deregulated between NPCs and differentiating neurons with significant enrichments in FMRP targets and autism-related genes found amongst downregulated genes. Our findings suggest that the absence of FMRP affects transcriptional profiles since the NPC stage, and leads to impaired activity and neuronal differentiation over time, which illustrates the critical role of FMRP protein in neuronal development.

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5. Neul JL, Benke TA, Marsh ED, Suter B, Silveira L, Fu C, Peters SU, Percy AK. Top caregiver concerns in Rett syndrome and related disorders: data from the US natural history study. Journal of neurodevelopmental disorders. 2023; 15(1): 33.

OBJECTIVE: Recent advances in the understanding of neurodevelopmental disorders such as Rett syndrome (RTT) have enabled the discovery of novel therapeutic approaches that require formal clinical evaluation of efficacy. Clinical trial success depends on outcome measures that assess clinical features that are most impactful for affected individuals. To determine the top concerns in RTT and RTT-related disorders we asked caregivers to list the top caregiver concerns to guide the development and selection of appropriate clinical trial outcome measures for these disorders. METHODS: Caregivers of participants enrolled in the US Natural History Study of RTT and RTT-related disorders (n = 925) were asked to identify the top 3 concerning problems impacting the affected participant. We generated a weighted list of top caregiver concerns for each of the diagnostic categories and compared results between the disorders. Further, for classic RTT, caregiver concerns were analyzed by age, clinical severity, and common RTT-causing mutations in MECP2. RESULTS: The top caregiver concerns for classic RTT were effective communication, seizures, walking/balance issues, lack of hand use, and constipation. The frequency of the top caregiver concerns for classic RTT varied by age, clinical severity, and specific mutations, consistent with known variation in the frequency of clinical features across these domains. Caregivers of participants with increased seizure severity often ranked seizures as the first concern, whereas caregivers of participants without active seizures often ranked hand use or communication as the top concern. Comparison across disorders found commonalities in the top caregiver concerns between classic RTT, atypical RTT, MECP2 duplication syndrome, CDKL5 deficiency disorder, and FOXG1 syndrome; however, distinct differences in caregiver concerns between these disorders are consistent with the relative prevalence and impact of specific clinical features. CONCLUSION: The top caregiver concerns for individuals with RTT and RTT-related disorders reflect the impact of the primary clinical symptoms of these disorders. This work is critical in the development of meaningful therapies, as optimal therapy should address these concerns. Further, outcome measures to be utilized in clinical trials should assess these clinical issues identified as most concerning by caregivers.

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6. Sipowicz K, Pietras T, Kosmalski M. Feelings of loneliness and meaning in life in subjects with Asperger’s syndrome: a pilot study. Scientific reports. 2023; 13(1): 17453.

Subjects with Asperger’s syndrome without intellectual disabilities have significant difficulties in establishing social relationships despite their IQ being within the normal range. One of the effects of social deficit is depression. The question arises whether loneliness and dimensions of meaning in life correlate with the severity of depression and whether the average severity of depression, loneliness and dimensions of meaning in life differentiate the following groups: people with Asperger’s syndrome and depression, people with Asperger’s syndrome without depression, people with depression without Asperger’s syndrome and healthy subjects. The study was conducted on a total of 170 people, including: 43 people with Asperger’s syndrome and depression, 41 people with Asperger’s syndrome without depression, 40 people with depression without Asperger’s syndrome and 46 healthy people (without Asperger’s syndrome and without depression). All were administered a demographic survey, Beck Depression Inventory II (BDI-II), De Jong Gierveld Loneliness Scale, Life Attitude Profile-Revised. Asperger’s syndrome and depressive episodes were diagnosed on the basis of ICD-10 research criteria still applicable in Poland. In the group with Asperger’s syndrome and depression the highest levels of loneliness and the lowest values of the dimensions of the sense of meaning in life, except for the acceptance of death, were observed. This result was significantly different from the results obtained in the other study groups. Both in people with Asperger’s syndrome without depression and in people with depression without Asperger’s syndrome, the values of the dimensions of the sense of meaning in life and the level of loneliness differ significantly from the results obtained in the control group. The BDI-II scores correlated positively with the loneliness values and negatively with the sense of meaning in life values in all groups. The results indicate that both suffering from depression and having Asperger’s syndrome are associated with an increased sense of loneliness and a reduced sense of meaning in life. People with Asperger’s syndrome and depression have the highest values of loneliness and the lowest values of dimensions of the sense of meaning of life compared to the other groups studied. The limitation of the work is the deliberate selection of groups, because it would be interesting to answer the question whether Asperger’s syndrome is a risk factor for depression in the population.

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7. Stecher C, Pagni BA, Cloonan S, Vink S, Hill E, Ogbeama D, Delaney S, Braden BB. App-based meditation habits maintain reductions in depression symptoms among autistic adults. Autism : the international journal of research and practice. 2023: 13623613231200679.

Existing research has identified an increased risk of depression among autistic adults, which can negatively impact their adaptive functioning abilities and socioeconomic outcomes. Mobile app-based meditation is a feasible, accessible, and effective self-care solution for depression among neurotypical adults, but there is limited evidence for the long-term benefits of app-based meditation among autistic adults. Habits are a key behavioral strategy for maintaining behavior change, and anchoring is one effective habit formation intervention that has yet to be tested among autistic adults. This study demonstrates that it is both feasible and effective to integrate the anchoring habit formation strategy into an app-based meditation intervention for establishing meditation habits among autistic adults. In addition, the study shows that app-based meditation habits were successful at maintaining reductions in depressive symptoms over 6 months. These results demonstrate the power of anchoring-based habit formation interventions for establishing healthy habits among autistic adults, which offers a promising behavioral intervention technique for establishing other healthy habits among autistic adults. The study also shows that app-based meditation habits are an effective long-term self-care solution for managing depressive symptoms among autistic adults that should be used by mental health providers and policymakers. Future research should test this combined anchoring and app-based meditation intervention technique among larger samples of autistic adults and over longer durations to better understand the mechanisms underlying the success of this intervention.

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8. Wang M, Xu D, Zhang L, Jiang H. Application of Multimodal MRI in the Early Diagnosis of Autism Spectrum Disorders: A Review. Diagnostics (Basel, Switzerland). 2023; 13(19).

Autism spectrum disorder (ASD) is a neurodevelopmental disorder in children. Early diagnosis and intervention can remodel the neural structure of the brain and improve quality of life but may be inaccurate if based solely on clinical symptoms and assessment scales. Therefore, we aimed to analyze multimodal magnetic resonance imaging (MRI) data from the existing literature and review the abnormal changes in brain structural-functional networks, perfusion, neuronal metabolism, and the glymphatic system in children with ASD, which could help in early diagnosis and precise intervention. Structural MRI revealed morphological differences, abnormal developmental trajectories, and network connectivity changes in the brain at different ages. Functional MRI revealed disruption of functional networks, abnormal perfusion, and neurovascular decoupling associated with core ASD symptoms. Proton magnetic resonance spectroscopy revealed abnormal changes in the neuronal metabolites during different periods. Decreased diffusion tensor imaging signals along the perivascular space index reflected impaired glymphatic system function in children with ASD. Differences in age, subtype, degree of brain damage, and remodeling in children with ASD led to heterogeneity in research results. Multimodal MRI is expected to further assist in early and accurate clinical diagnosis of ASD through deep learning combined with genomics and artificial intelligence.

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9. Westmark PR, Gholston AK, Swietlik TJ, Maganti RK, Westmark CJ. Ketogenic Diet Affects Sleep Architecture in C57BL/6J Wild Type and Fragile X Mice. International journal of molecular sciences. 2023; 24(19).

Nearly half of children with fragile X syndrome experience sleep problems including trouble falling asleep and frequent nighttime awakenings. The goals here were to assess sleep-wake cycles in mice in response to Fmr1 genotype and a dietary intervention that reduces hyperactivity. Electroencephalography (EEG) results were compared with published rest-activity patterns to determine if actigraphy is a viable surrogate for sleep EEG. Specifically, sleep-wake patterns in adult wild type and Fmr1(KO) littermate mice were recorded after EEG electrode implantation and the recordings manually scored for vigilance states. The data indicated that Fmr1(KO) mice exhibited sleep-wake patterns similar to wild type littermates when maintained on a control purified ingredient diet. Treatment with a high-fat, low-carbohydrate ketogenic diet increased the percentage of non-rapid eye movement (NREM) sleep in both wild type and Fmr1(KO) mice during the dark cycle, which corresponded to decreased activity levels. Treatment with a ketogenic diet flattened diurnal sleep periodicity in both wild type and Fmr1(KO) mice. Differences in several sleep microstructure outcomes (number and length of sleep and wake bouts) supported the altered sleep states in response to a ketogenic diet and were correlated with altered rest-activity cycles. While actigraphy may be a less expensive, reduced labor surrogate for sleep EEG during the dark cycle, daytime resting in mice did not correlate with EEG sleep states.

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10. Yui K, Imataka G, Shiohama T. Lipid Peroxidation of the Docosahexaenoic Acid/Arachidonic Acid Ratio Relating to the Social Behaviors of Individuals with Autism Spectrum Disorder: The Relationship with Ferroptosis. International journal of molecular sciences. 2023; 24(19).

Polyunsaturated fatty acids (PUFAs) undergo lipid peroxidation and conversion into malondialdehyde (MDA). MDA reacts with acetaldehyde to form malondialdehyde-modified low-density lipoprotein (MDA-LDL). We studied unsettled issues in the association between MDA-LDL and the pathophysiology of ASD in 18 individuals with autism spectrum disorders (ASD) and eight age-matched controls. Social behaviors were assessed using the social responsiveness scale (SRS). To overcome the problem of using small samples, adaptive Lasso was used to enhance the interpretability accuracy, and a coefficient of variation was used for variable selections. Plasma levels of the MDA-LDL levels (91.00 ± 16.70 vs. 74.50 ± 18.88) and the DHA/arachidonic acid (ARA) ratio (0.57 ± 0.16 vs. 0.37 ± 0.07) were significantly higher and the superoxide dismutase levels were significantly lower in the ASD group than those in the control group. Total SRS scores in the ASD group were significantly higher than those in the control group. The unbeneficial DHA/ARA ratio induced ferroptosis via lipid peroxidation. Multiple linear regression analysis and adaptive Lasso revealed an association of the DHA/ARA ratio with total SRS scores and increased MDA-LDL levels in plasma, resulting in neuronal deficiencies. This unbeneficial DHA/ARA-ratio-induced ferroptosis contributes to autistic social behaviors and is available for therapy.

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