Snijder MIJ, Langerak IPC, Kaijadoe SPT, Buruma ME, Verschuur R, Dietz C, Buitelaar JK, Oosterling IJ.

J Autism Dev Disord. 2022 Aug;52(8):3473-3485. doi: 10.1007/s10803-021-05226-y. Epub 2021 Sep 1.

ABSTRACT

Whereas it is well documented how parents experience the diagnostic process of their child with autism spectrum disorder (ASD), less is known about parental experiences with the course of the early identification process and first steps in receiving care for their child with ASD symptoms. This mixed-method study investigated these experiences as well as barriers and improvement strategies regarding early detection in the Netherlands. A parental survey (N = 45) showed that, on average, initial concerns started at 22 months. A focus group (N = 10) revealed multiple barriers and proposed strategies of improvement in three domains: “Knowledge and Expertise”, “Attention to Parental Needs” and “System and Organization”. Strategies to improve early identification will be discussed based on parental perspectives and professional perspectives.

PMID:34468907 | PMC:PMC9296376 | DOI:10.1007/s10803-021-05226-y

Tamouza R, Volt F, Richard JR, Wu CL, Bouassida J, Boukouaci W, Lansiaux P, Cappelli B, Scigliuolo GM, Rafii H, Kenzey C, Mezouad E, Naamoune S, Chami L, Lejuste F, Farge D, Gluckman E.

Front Cell Dev Biol. 2022 Jul 5;10:809686. doi: 10.3389/fcell.2022.809686. eCollection 2022.

ABSTRACT

Autism spectrum disorder (ASD) represents a set of heterogeneous neurodevelopmental conditions defined by impaired social interactions and repetitive behaviors. The number of reported cases has increased over the past decades, and ASD is now a major public health burden. So far, only treatments to alleviate symptoms are available, with still unmet need for an effective disease treatment to reduce ASD core symptoms. Genetic predisposition alone can only explain a small fraction of the ASD cases. It has been reported that environmental factors interacting with specific inter-individual genetic background may induce immune dysfunctions and contribute to the incidence of ASD. Such dysfunctions can be observed at the central level, with increased microglial cells and activation in ASD brains or in the peripheral blood, as reflected by high circulating levels of pro-inflammatory cytokines, abnormal activation of T-cell subsets, presence of auto-antibodies and of dysregulated microbiota profiles. Altogether, the dysfunction of immune processes may result from immunogenetically-determined inefficient immune responses against a given challenge followed by chronic inflammation and autoimmunity. In this context, immunomodulatory therapies might offer a valid therapeutic option. Mesenchymal stromal cells (MSC) immunoregulatory and immunosuppressive properties constitute a strong rationale for their use to improve ASD clinical symptoms. In vitro studies and pre-clinical models have shown that MSC can induce synapse formation and enhance synaptic function with consequent improvement of ASD-like symptoms in mice. In addition, two preliminary human trials based on the infusion of cord blood-derived MSC showed the safety and tolerability of the procedure in children with ASD and reported promising clinical improvement of core symptoms. We review herein the immune dysfunctions associated with ASD provided, the rationale for using MSC to treat patients with ASD and summarize the current available studies addressing this subject.

PMID:35865626 | PMC:PMC9294632 | DOI:10.3389/fcell.2022.809686

Haartsen R, Mason L, Garces P, Gui A, Charman T, Tillmann J, Johnson MH, Buitelaar JK, Loth E, Murphy D, Jones EJH; EU-AIMS LEAP group.

Cortex. 2022 Jul 14;155:13-29. doi: 10.1016/j.cortex.2022.06.010. Online ahead of print.

ABSTRACT

BACKGROUND: Studying the neural processing of faces can illuminate the mechanisms of compromised social expertise in autism. To resolve a longstanding debate, we examined whether differences in configural face processing in autism are underpinned by quantitative differences in the activation of typical face processing pathways, or the recruitment of non-typical neural systems.

METHODS: We investigated spatial and temporal characteristics of event-related EEG responses to upright and inverted faces in a large sample of children, adolescents, and adults with and without autism. We examined topographic analyses of variance and global field power to identify group differences in the spatial and temporal response to face inversion. We then examined how quasi-stable spatiotemporal profiles – microstates – are modulated by face orientation and diagnostic group.

RESULTS: Upright and inverted faces produced distinct profiles of topography and strength in the topographical analyses. These topographical profiles differed between diagnostic groups in adolescents, but not in children or adults. In the microstate analysis, the autistic group showed differences in the activation strength of normative microstates during early-stage processing at all ages, suggesting consistent quantitative differences in the operation of typical processing pathways; qualitative differences in microstate topographies during late-stage processing became prominent in adults, suggesting the increasing involvement of non-typical neural systems with processing time and over development.

CONCLUSIONS: These findings suggest that early difficulties with configural face processing may trigger later compensatory processes in autism that emerge in later development.

PMID:35961249 | DOI:10.1016/j.cortex.2022.06.010

Lutz AK, Bauer HF, Ioannidis V, Schön M, Boeckers TM

Front Synaptic Neurosci. 2022 Jun 6;14:890231. doi: 10.3389/fnsyn.2022.890231. eCollection 2022.

ABSTRACT

SHANK3 is a scaffolding protein implicated in autism spectrum disorders (ASD). Its function at excitatory glutamatergic synapses has been studied for the last two decades, however, tissue-specific expression patterns as well as its subcellular localization need to be studied in further detail. Especially the close sequence homology of SHANK3 to its protein family members SHANK2 and SHANK1 raises the emerging need for specific antibodies that are validated for the desired methodology. With this study, we aim to validate a set of commercial as well as homemade SHANK3 antibodies in Western Blotting, and synaptic immunocyto- and immunohistochemistry. We found that only a small subset of the antibodies included in this study meet the criteria of quality and specificity. Therefore, we aim to share our findings on SHANK3 antibody validation but also raise awareness of the necessity of antibody specificity testing in the field.

PMID:35734418 | PMC:PMC9207774 | DOI:10.3389/fnsyn.2022.890231

Malara M, Lutz AK, Incearap B, Bauer HF, Cursano S, Volbracht K, Lerner JJ, Pandey R, Delling JP, Ioannidis V, Arévalo AP, von Bernhardi JE, Schön M, Bockmann J, Dimou L, Boeckers TM

Cell Mol Life Sci. 2022 Jun 20;79(7):371. doi: 10.1007/s00018-022-04400-4.

ABSTRACT

Mutations or deletions of the SHANK3 gene are causative for Phelan-McDermid syndrome (PMDS), a syndromic form of autism spectrum disorders (ASDs). We analyzed Shank3Δ11(-/-) mice and organoids from PMDS individuals to study effects on myelin. SHANK3 was found to be expressed in oligodendrocytes and Schwann cells, and MRI analysis of Shank3Δ11(-/-) mice revealed a reduced volume of the corpus callosum as seen in PMDS patients. Myelin proteins including myelin basic protein showed significant temporal and regional differences with lower levels in the CNS but increased amounts in the PNS of Shank3Δ11(-/-) animals. Node, as well as paranode, lengths were increased and ultrastructural analysis revealed region-specific alterations of the myelin sheaths. In PMDS hiPSC-derived cerebral organoids we observed an altered number and delayed maturation of myelinating cells. These findings provide evidence that, in addition to a synaptic deregulation, impairment of myelin might profoundly contribute to the clinical manifestation of SHANK3 deficiency.

PMID:35726031 | PMC:PMC9209365 | DOI:10.1007/s00018-022-04400-4