Apr 3, 2026
Avramiea AE, Juarez-Martinez EL, Garcés P, Hipp JF, Poil SS, Diachenko M, Mansvelder HD, Jones E, Mason L, Murphy D, Loth E, Oakley B, Charman T, Banaschewski T, Oranje B, Buitelaar J, Bruining H, Linkenkaer-Hansen K.
Sci Rep. 2026 Apr 3. doi: 10.1038/s41598-026-42120-y. Online ahead of print.
Qualitative EEG abnormalities are common in Autism Spectrum Disorder (ASD) and hypothesized to reflect disrupted excitation/inhibition (E/I) balance. To test this, we recently introduced a functional measure of network-level E/I ratio (fE/I). Here, we applied fE/I and other EEG measures to alpha oscillations from source-reconstructed data in the EU-AIMS dataset (267 ASD, 209 controls). We analyzed these measures alongside qualitative EEG abnormalities ranging from slowing of activity to epileptiform patterns, aiming to replicate the findings from the SPACE-BAMBI study. Contrary to our previous report, we did not observe increased fE/I variability in ASD compared to controls. EEG abnormalities were rare in adults and could not be statistically assessed. ASD children-adolescents with EEG abnormalities exhibited lower relative alpha power and fE/I compared to those without. However, EEG-abnormality scoring did not stratify the behavioral heterogeneity of ASD using clinical measures. Surprisingly, several controls also exhibited qualitative EEG abnormalities with a strikingly similar anatomical distribution of reduced fE/I, reflecting inhibition-dominated network dynamics in sensory processing regions. The robustness of this association between EEG abnormalities and reduced fE/I was further supported by re-analysis of the SPACE-BAMBI study in source space. Stratification by the presence of EEG abnormalities and their effects on network activity may help understand neurodevelopmental physiological heterogeneity and the difficulties in implementing E/I targeting treatments in unselected cohorts.
PMID:41932958 | DOI:10.1038/s41598-026-42120-y
Mar 25, 2026
Pagano J, Perez Arevalo A, Nosanova A, Bauer HF, Loth E, Andres S, Becker F, Otto M, Stefanoni A, Verpelli C, Oeckl P, Schön M, Boeckers T.
Transl Psychiatry. 2026 Mar 24;16(1):201. doi: 10.1038/s41398-026-03932-8.
ABSTRACT
Phelan-McDermid syndrome (PMS) is a relatively frequent cause of syndromic intellectual disability (ID) and autism spectrum disorder (ASD). It is typically caused by genetic alterations in the 22q13 chromosomal region, most often involving heterozygous deletions or mutations in the SHANK3 gene. More than half of affected individuals exhibit functional impairments in speech, cognition, motor skills, and behavior. Despite multiple ongoing therapeutic programs, objective and scalable liquid biomarkers to support patient stratification and to monitor disease course or treatment response are still lacking. Here, in a pilot study involving 23 individuals with PMS, we identified two biomarkers that are significantly altered compared to a control group and are associated with symptom severity. First, SHANK3 protein was detectable in peripheral blood mononuclear cells (PBMCs) and was markedly reduced in PMS (mean -77% vs. controls), consistent with SHANK3 haploinsufficiency; lower PBMC SHANK3 levels were associated with the presence of developmental regression, supporting its potential utility as a target-engagement/monitoring biomarker rather than a diagnostic screen. Additionally, plasma levels of beta-synuclein, a neuron-specific synaptic protein, were elevated in PMS and positively correlated with the severity of speech impairment. Both biomarkers were successfully back-translated in a Shank3 transgenic mouse model, where beta-synuclein levels were normalized through modulation of the mGlu5 receptor. Together, these results provide initial evidence for SHANK3 in PBMCs and plasma beta-synuclein as complementary liquid biomarkers to aid prognosis and enable objective monitoring of therapeutic response in PMS, warranting validation in larger and pediatric longitudinal cohorts.
PMID:41876457 | PMC:PMC13039877 | DOI:10.1038/s41398-026-03932-8
Mar 9, 2026
Axelsson LL, Falck-Ytter T, Nyström P, Blom MA, Frick MA.
Scand J Psychol. 2026 Mar 9. doi: 10.1111/sjop.70088. Online ahead of print.
ABSTRACT
Autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and developmental language disorder (DLD) are neurodevelopmental conditions (NDCs) that share etiological factors and frequently co-occur. Despite this, they have rarely been studied together-particularly in relation to functional outcomes. In this study, we investigate the association between the developmental pattern of sustained visual attention in infancy and number of diagnoses, and map the clinical profile of 6-year-old children. A cohort of 6-year-olds, originally recruited in infancy due to elevated (n = 42) or low (n = 7) likelihood of ASD, were assessed for sustained visual attention, diagnostic outcomes, general adaptive functioning, intellectual abilities, and language skills. Participants were grouped based on the number of NDC diagnoses (ASD, ADHD, DLD, and/or Subthreshold ASD) they received at follow-up. We could not find statistical support for an association between sustained visual attention and number of diagnoses. Findings revealed no significant differences in adaptive functioning, intellectual abilities, or language skills between children with no diagnosis (n = 24) and those with a single diagnosis (n = 15). However, children with two or more diagnoses (n = 10) scored significantly lower in general adaptive functioning, intellectual ability, language production, and verbal comprehension compared to those with only one or no diagnosis. The results indicate that compared to children with only one diagnosis or no diagnosis, children with two or more diagnoses scored lower on several key functional domains, emphasizing the need to prioritize children with multiple diagnoses or confirmed functional impairment in clinical settings. Moreover, the findings indicate that a single diagnosis in preschool-aged children should not be a stand-alone outcome measure in sibling studies, if the goal is to identify early processes that predict meaningful differences in everyday functioning.
PMID:41802979 | DOI:10.1111/sjop.70088
Jan 28, 2026
Konke LA, Falck-Ytter T, Shragge I, Bölte S, Brocki K.
J Autism Dev Disord. 2026 Jan 28. doi: 10.1007/s10803-025-07165-4. Online ahead of print.
ABSTRACT
PURPOSE: The aim of the study is to examine (i) if young children with a family history of autism and/or ADHD differ on executive functions and deferred gratification in comparison to peers with no family history of autism or ADHD, (ii) the specificity of these domains in relation to early-life autistic and ADHD symptoms and adaptive functioning, and (iii) if deferred gratification and strong EF skills may function as protective factors in the association between symptoms and adaptive behaviour.
METHODS: A total of 77 infant siblings at 3 years of age with a family history of autism only, autism and co-occurring ADHD, or no family history of these conditions (FH-TL) were assessed on behavioural lab-tasks (EF and deferred gratification), parent-rated adaptive behaviour using Vineland, and clinician ratings using ADOS-2 (autistic symptoms) and ADHD DSM-5 symptom rating scale (ADHD RS).
RESULTS: Group comparisons showed that FH-autism and FH-autism + ADHD groups received lower scores on common EF, but not on deferred gratification in comparison to the FH-TL group. Lower levels of deferred gratification related to autistic symptoms, while lower level on EF was specific to ADHD symptoms. Finally, deferred gratification moderated the association between autistic symptoms and adaptive behaviour, in that stronger ability to defer gratification attenuated the association between autistic symptoms and adaptive functions.
CONCLUSIONS: These results are in line with the idea that strong ability to inhibit and defer gratification may act as a protective factor for children with a family history of autism and/or ADHD pointing to affective aspects of EF as particularly important.
PMID:41604129 | DOI:10.1007/s10803-025-07165-4
Jun 13, 2025
In early June 2025, the CANDY consortium met for its final General Assembly. From 3–6 June, partners from across Europe met in Castelldefels, a seaside town just south of Barcelona. With its calm beaches and Mediterranean atmosphere, the location offered the perfect setting to reflect on the journey so far and to look ahead at what lies beyond the project’s conclusion.
As a pre-event, again we organized the CANDY’s Early Career Researchers (ECRs) dedicated Master Class. This session provided space for learning, exchange, and mentoring, giving younger scientists the opportunity to sharpen their skills and connect with senior researchers in an open, supportive environment.
The General Assembly Meeting was then kikced-off by our Cooridnator Prof Jan K. Buitelaar from Radoud medical center and over the next sessions, the consortium immersed itself in updates and further discussions. Teams shared the latest analyses, results and final experiments, while aligning on the project’s closing steps. Conversations were lively and constructive. A key theme throughout the gathering was CANDY’s legacy. Beyond data and deliverables, partners reflected on how to ensure that the knowledge, tools and networks built within the project will continue to thrive. The group explored ways to carry forward the momentum, keeping alive the collaborations and advancing the shared mission of supporting children with neurodevelopmental conditions.
As each day ended, the consortium enjoyed the chance to reconnect in person, strengthening bonds, celebrating achievements, and simply enjoying being together after years of collaboration that had so often been virtual.
The Castelldefels meeting was more than a farewell. It was a moment of recognition for what CANDY has accomplished, and at the same time a beginning: a commitment to continue this important work, together, beyond the project’s official end.
As part of the “Horizon 2020” programme, the European Commission is funding the five-year CANDY research project with a total of six million Euro under grant agreement No. 847818.