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Research Digest

Biomedical research, treatable look-alikes, and medical treatments for ASD.

21 articles · page 1 / 3

  1. mdpi:children Unknown Journal Biomarkers & Diagnosis

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    Background/Objectives: Auditory processing disorders (APDs), defined as impaired neural processing of acoustic stimuli despite normal peripheral hearing, often co-occur with neurodevelopmental disorders (NDDs) and may contribute to language, attentional, and learning difficulties. Emerging evidence suggests that shared neurotransmitter systems may represent a common neurobiological substrate underlying these conditions. The aim of this study is to integrate current evidence on glutamatergic, GABAergic, and monoaminergic systems in neurodevelopmental and auditory processing disorders in children and adolescents, and to evaluate the hypothesis that shared neurotransmitter dysregulation may underlie their clinical overlap. Methods: A narrative review of the literature was conducted through electronic searches in PubMed and Embase up to 31 December 2025, using keywords related to neurotransmitters, NDDs and APDs. Results: Available evidence indicates that an imbalance between excitatory glutamatergic and inhibitory GABAergic neurotransmission has been proposed as a central mechanism in NDDs and may also contribute to auditory processing difficulties through altered neural synchrony, sensory gating and temporal auditory coding. Findings collectively suggest the hypothesis of shared neurotransmitter dysregulation across NDDs and APDs. Conclusions: Auditory processing difficulties may represent sensory-level expressions of shared neurochemical vulnerability across neurodevelopmental conditions. Future longitudinal and multimodal studies are needed to clarify causal relationships and to identify clinically useful biomarkers.

    • Neurodevelopmental delay
    • Synaptic & Neurotransmitter
    • Biomarkers & Diagnosis
  2. mdpi:ijms International Journal of Molecular Sciences Biomarkers & Diagnosis

    Analytical Methods for Fluid Biomarkers in Alzheimer’s Disease from Discovery to Clinical Implementation

    Luisa Agnello, Roberto Dominici, Caterina Maria Gambino

    Alzheimer’s disease (AD) is increasingly recognized as a biological continuum characterized by early neuropathological and molecular changes that precede the onset of clinical symptoms. Fluid biomarkers have transformed the diagnostic landscape by enabling the in vivo detection of core AD pathologies, particularly amyloid-β deposition and tau-related neurodegeneration. Despite the rapid expansion of candidate biomarkers, however, only a limited number have successfully translated into clinical practice. Discovery-phase approaches, primarily driven by mass spectrometry-based proteomics, enable the unbiased identification of novel biomarker candidates across multiple biological pathways. Research-phase methods, including immunoassays such as enzyme-linked immunosorbent assay (ELISA), electrochemiluminescence immunoassays (ECLIA), microfluidic platforms, and ultrasensitive technologies such as single-molecule array (SIMOA), support analytical and clinical validation in well-characterized cohorts. Clinical implementation has been advanced by fully automated platforms, including Lumipulse and Elecsys, which have obtained regulatory approval for cerebrospinal fluid biomarkers and, more recently, blood-based biomarkers. These developments represent a paradigm shift toward minimally invasive and scalable diagnostic strategies that may reduce dependence on neuroimaging techniques. Nevertheless, major challenges remain, including assay standardization, inter-platform variability, demonstration of clinical utility, and barriers to widespread clinical adoption. This review provides a comprehensive overview of analytical methods used to measure AD fluid biomarkers in cerebrospinal fluid and plasma, structured according to the biomarker development pipeline from discovery to clinical implementation. Overall, the review highlights a fit-for-purpose approach to biomarker development and emphasizes the complementary roles of diverse analytical technologies across the different phases of biomarker translation.

    • Treatable look-alike
    • Biomarkers & Diagnosis
  3. mdpi:ijms International Journal of Molecular Sciences Comorbidities

    Functional Characterization of Loss of RNF43 Reveals Neuronal Defects in a Caenorhabditis elegans Model

    Kaan Sonmez, Sinem Güzel, Hasan Huseyin Kazan

    Ring finger protein 43 (RNF43) encodes a transmembrane E3 ubiquitin ligase that negatively regulates canonical Wnt signaling and is classically associated with serrated polyposis syndrome and colorectal cancer. In this study, regarding a homozygous truncating RNF43 variant (NM_001305545.1:c.1906C>T; p.Gln636Ter) in a patient segregating with a severe neurodevelopmental phenotype characterized by developmental delay, neonatal hypotonia, recurrent seizures, progressive microcephaly, and bilateral optic atrophy, the loss of polarity defective 1 (plr-1), an ortholog of RNF43, was modeled in Caenorhabditis elegans and the phenotype was primarily characterized. The results demonstrated that loss of the plr-1 disrupted gamma aminobutyric acid (GABA)ergic axon organization, reduced locomotor speed calculated from 60 s recordings, and altered developmental growth. These findings expand the phenotypic spectrum of RNF43 and support a dosage-dependent developmental role.

    • Neurodevelopmental delay
    • Synaptic & Neurotransmitter
  4. mdpi:brainsci Brain Sciences Pharmacological Treatment

    Human-Derived Cellular Models in Psychiatry: A Focus on the Olfactory Neuroepithelium

    Tommaso Toffanin, Mario Angelo Pagano, Carlo Idotta

    Severe mental disorders, including schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD), are leading causes of global disability, yet current treatments remain largely symptomatic and fail to alter disease trajectories. Converging evidence from genetics, longitudinal studies, and systems neuroscience supports a dimensional and transdiagnostic architecture of psychopathology, involving shared polygenic risk and overlapping neurodevelopmental and circuit-level alterations. Traditional approaches—such as post-mortem brain analysis, neuroimaging, and animal models—have delineated core molecular perturbations (e.g., dopaminergic, glutamatergic, and GABAergic dysfunction), as well as informed translational frameworks for mechanistic investigation, but remain constrained by restricted access to dynamic processes and incomplete recapitulation of human-specific biology. The advent of human-derived cellular models, particularly human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs), has partially addressed these limitations, enabling the study of patient-specific neurodevelopment and synaptic function in vitro. Within this evolving landscape, the olfactory neuroepithelium (ONE) has emerged as an accessible source of neural progenitors, obtainable through minimally invasive procedures, providing a window into living human neurobiology. ONE-derived cells retain donor-specific genetic and epigenetic signatures while recapitulating disease-relevant phenotypes across major psychiatric disorders, including altered neurodevelopmental dynamics, synaptic gene expression, and inflammatory profiles. Here, we present a narrative review of the principal cellular and tissue models used in biological psychiatry, examining their respective strengths, limitations, and translational relevance across experimental contexts. By situating these approaches within a unified framework, we aim to clarify their complementarity, identify current gaps, and outline future directions, highlighting the emerging potential of ONE-based models to bridge genetic risk, cellular dysfunction, and clinical phenotype, thereby advancing precision psychiatry.

    • Neurodevelopmental delay
    • Synaptic & Neurotransmitter
    • Pharmacological treatment
  5. mdpi:brainsci Brain Sciences Biomarkers & Diagnosis

    Unifying Divergent Conceptions in Nonfluent/Agrammatic and Semantic Primary Progressive Aphasia

    Marc Teichmann, Kimihiro Nakamura

    The nonfluent/agrammatic variant of primary progressive aphasia (nfav-PPA) and primary progressive apraxia of speech (PPAOS) are neurodegenerative syndromes that raise diagnostic challenges related to several issues. First, there are two divergent conceptions, one stipulating that (i) nfav-APP and PPAOS are distinct entities, and the other (ii) that PPAOS has to be integrated into the nfav-APP spectrum. A second related issue concerns the consideration of phonological dimensions, lying at the language interface with speech, which could potentially help overcome the nfva-PPA/PPAOS controversy. Third, there is a lack of internationally validated clinical tests assessing apraxia of speech and syntactic abilities with sufficient specificity and sensitivity. This narrative review discusses these issues taking into account clinical, neurocognitive and neurobiological dimensions. It proposes a conceptual-integrative framework conciliating competing nfav-APP/PPAOS accounts while suggesting a graded continuum with subdivisions, related to neurodegenerative expansion throughout language/speech production systems, ranging from syntactic to phonological to phonetic-articulatory impairments. A second controversy in the field of PPA arises from divergent conceptions of semantic PPA (sv-PPA), defined by primary damage to verbal semantics, and of semantic dementia (SD) characterized by multimodal semantic impairments. The current consensus criteria of PPA have deconstructed the initial SD conception by absorbing it into sv-PPA, hence leaving mixed and some non-verbal semantic phenotypes nosologically orphaned. Again, the article proposes a conceptual and integrative model, built on findings from clinical research and cognitive neuroscience, suggesting a graded continuum with subdivisions spanning from verbal to different non-verbal semantic impairments including social-semantic/behavioral phenotypes.

    • Treatable look-alike
  6. digest-2026-03-18 Psychology Today

    Has Broadening the Autism Spectrum Led to Overdiagnosis?

    Autism researcher Dame Uta Frith has raised concerns that broadening diagnostic criteria may be leading to overdiagnosis, particularly in milder cases. Evidence supports this concern: approximately 13% of children who received an autism diagnosis later lost it, and 23% did not meet stricter research standards upon reassessment. However, diagnostic expansion has also benefited many individuals previously overlooked. The debate highlights the need for nuanced statistical approaches and careful diagnostic practices to capture autism's full complexity without over-classification.

    • ASD
    • Treatable look-alike
    • Biomarkers & Diagnosis
  7. digest-2026-03-18 The Transmitter (Spectrum)

    Revised statistical bar extracts less-common variants from autism genetics studies

    Researchers at SickKids Research Institute found that standard genome-wide association study (GWAS) thresholds may be missing low-frequency autism variants. By lowering the significance threshold from the conventional 5 × 10⁻⁸ to 2.03 × 10⁻⁷ using Bonferroni correction, the team identified three novel low-frequency variants linked to autism genes. This approach could help explain some of autism's "missing heritability." The team plans to replicate findings in diverse populations and create whole-genome sequence databases to optimize detection of less-common variants.

    • ASD
  8. digest-2026-03-18 Psychology Today - The Neurodivergent Psychologist

    When Autism and ADHD Travel Together (AuDHD)

    Research shows that 50-70% of autistic individuals also meet criteria for ADHD, while 20-65% of those with ADHD show clinically significant autistic traits. The combination creates unique challenges: restless exhaustion, tension between routine and novelty needs, and simultaneous hyper- and hypo-sensitivity. A key problem is diagnostic overshadowing—when ADHD is diagnosed first, autism recognition is delayed by an average of 1.8 years (2.6 years for girls). Understanding AuDHD as an interaction rather than just a sum of traits improves support and self-understanding.

    • ASD
  9. digest-2026-03-18 The Transmitter (Spectrum)

    New autism committee positions itself as science-backed alternative to government group

    The Independent Autism Coordinating Committee (I-ACC), formed by the Autism Science Foundation and Coalition of Autism Scientists, launched to counter concerns about the federal Interagency Autism Coordinating Committee (IACC). I-ACC members worry that the IACC continues promoting discredited theories (vaccines as autism cause) and potentially dangerous interventions (hyperbaric oxygen, chelation). I-ACC aims to propose science-backed research priorities focused on understanding causes, treatments, and supports for autistic people. The group held its first meeting on March 19, 2026, and plans to influence both federal agencies and private funding bodies.

    • ASD
    • Pharmacological treatment
  10. digest-2026-03-18 Psychology Today - Mood by Microbe

    Is the Gut-Autism Link Overblown?

    While some researchers question gut-autism research quality, evidence suggests microbiome interventions can help manage autism symptoms. Autistic children have lower levels of specific bacteria (Prevotella, Coprococcus, Veillonella) that produce GABA and serotonin. Key findings: oral microbiome signatures predict autism development with 80% accuracy; probiotic supplements reduced gastric distress and autism scores by ~50% in one study; fecal microbe transfer from autistic individuals induced autism-like behaviors in mice. The focus should shift from proving causality to leveraging microbiome modifications for symptom amelioration.

    • ASD
    • Gut & Microbiome
    • Synaptic & Neurotransmitter
    • Dietary intervention