1. Barrett AM, Olayinka-Amao O, Martin S, Doshi D, Bishop KM, Youakim JM. Assessing Experiences With Trofinetide for Rett Syndrome: Interviews With Caregivers of Participants in Clinical Trials. Clin Ther. 2025.

PURPOSE: Rett syndrome (RTT) is a rare neurodevelopmental disorder that mainly affects girls and women. Trofinetide is approved for the treatment of RTT in adults and children aged ≥2 years. To gain insight into experiences with RTT and effects of trofinetide treatment at different stages of RTT, interviews with caregivers of individuals with RTT were conducted upon their exit from the open-label trofinetide trials. METHODS: Interviews were conducted with caregivers of participants in the LILAC/LILAC-2 open-label extension trials of the phase 3 LAVENDER trial in participants aged 5 to 20 years, and in DAFFODIL, an open-label trial in participants aged 2 to 4 years. Caregivers were asked about the RTT effects, experiences with trofinetide, meaningfulness of treatment effects, and satisfaction. Qualitative thematic analysis was performed. FINDINGS: Caregivers of 33 participants from the open-label trials were interviewed, including 26 from LILAC/LILAC-2 (mean age, 12.3 years) and 7 from DAFFODIL (mean age, 4.5 years). The most commonly reported effects of RTT in LILAC/LILAC-2 were no verbal communication (24/26 [92.3%]), unable to use hands (15/26 [57.7%]), repetitive hand movements (15/26 [57.7%]), unable to walk (15/26 [57.7%]), and seizures (14/26 [53.8%]). In DAFFODIL, the most commonly reported effects of RTT were no verbal communication (7/7 [100%]), impaired balance (4/7 [57.1%]), unable to use hands (3/7 [42.9%]), repetitive hand movements (3/7 [42.9%]), mood disturbance (3/7 [42.9%]), constipation (3/7 [42.9%]), and limited ability to use hands (3/7 [42.9%]). Caregivers most commonly reported improvements in hand use (11/26 [42.3%]), engagement with others (11/26 [42.3%]), eye gaze (8/26 [30.8%]), use of the Tobii eye tracking device (7/26 [26.9%]), and attention/focus/concentration (7/26 [26.9%]) in LILAC/LILAC-2. In DAFFODIL, caregivers reported improvements in new words (5/7 [71.4%]), hand use (4/7 [57.1%]), and eye contact (4/7 [57.1%]). Nearly all (31/32) caregivers were very satisfied or satisfied with trofinetide. IMPLICATIONS: Caregivers of participants in open-label trofinetide trials reported improvements in RTT with meaningful impact in areas of motor function, communication, and engagement.

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2. Bölte S. Social cognition in autism and ADHD. Neurosci Biobehav Rev. 2025: 106022.

Social cognition is a crucial capacity for social functioning. The last decades have seen a plethora of social cognition research in neurodevelopmental conditions, foremost autism and, to a lesser extent, ADHD, both characterized by social challenges. Social cognition is a multifaceted construct comprising various overlapping subdomains, such as Theory of Mind/mentalizing, emotion recognition, and social perception. Mechanisms underpinning social cognition are complex, including implicit and explicit, cognitive and affective, and hyper- and hypo-social information processing. This review explores the intricacies of social cognition in the context of autism and ADHD. Research indicates altered performance on social cognition tests in autism, compared to neurotypical groups, with social cognition alterations having a small but robust effect on the defining features of autism. The nature of such alterations in autism appears primarily in relation to implicit processing. ADHD groups show intermediate social cognition performance, appearing to be influenced by executive function difficulties. Social cognition varies with intellectual and verbal abilities and seems to improve with age in autism and ADHD. Social skills interventions in autism, and stimulant medication in ADHD have been shown to improve social cognition test performance, while mentalizing training effects in autism are less conclusive. A limitation of the field is that social cognition constructs and tests are not well delineated. Further, most research has been embedded in a nativist approach rather than a constructivist approach. The former has been questioned for ignoring environmental contributions, especially the dimension of mutual miscommunication between neurodivergent and neurotypical individuals.

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3. Ellouk S, Zamstein O, Wainstock T, Sheiner E. The association between preterm delivery and autism spectrum disorder in childhood: A retrospective cohort study. Int J Gynaecol Obstet. 2025.

BACKGROUND: Prematurity complications are a leading cause of mortality and morbidity in offspring, including adverse neurodevelopmental outcomes. The association between preterm birth (PTB) and autism spectrum disorder (ASD) remains debated. OBJECTIVE: To investigate the association between PTB and ASD diagnosis during childhood. METHODS: This cohort study analyzed data from community clinics and a tertiary hospital, encompassing deliveries from 2005 to 2017. ASD incidence was compared across gestational age categories: extremely preterm (<28 weeks), very preterm (28-32 weeks), moderate to late preterm (32-37 weeks), and term (≥37 weeks). Additional comparisons were made between all preterm (<37 weeks) and term deliveries (≥37 weeks). Cumulative ASD incidence was assessed using Kaplan-Meier survival curves and a Cox proportional hazards model adjusted for potential confounders. RESULTS: Among 114 975 pregnancies, 0.3% delivered at <28 weeks, 0.6% at 28-32 weeks, and 6% at 32-37 weeks, with 6.9% preterm deliveries overall. Univariable analysis revealed a significant association between PTB and ASD (1.6% for <28 weeks vs 0.3% for 28-32 weeks vs 0.8% for 32-37 weeks vs 0.7% for term, P = 0.036). Crude ASD incidence was 0.8% (odds ratio [OR] 1.21, 95% confidence interval [CI] 0.93-1.56, P = 0.15). However, adjusted results showed no significant association: adjusted hazard ratio = 0.74 (95% CI 0.24-2.34, P = 0.61) for <28 weeks, 0.99 (95% CI 0.24-3.99, P = 0.98) for 28-32 weeks, and 1.07 (95% CI 0.81-1.43, P = 0.63) for 32-37 weeks. Kaplan-Meier analysis showed similar cumulative ASD incidence across groups (P = 0.855). CONCLUSION: This retrospective cohort study found no significant association between PTB and childhood ASD diagnosis.

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4. Eni M, Zigel Y, Ilan M, Michaelovski A, Golan HM, Meiri G, Menashe I, Dinstein I. Reliably quantifying the severity of social symptoms in children with autism using ASDSpeech. Transl Psychiatry. 2025; 15(1): 14.

Several studies have demonstrated that the severity of social communication problems, a core symptom of Autism Spectrum Disorder (ASD), is correlated with specific speech characteristics of ASD individuals. This suggests that it may be possible to develop speech analysis algorithms that can quantify ASD symptom severity from speech recordings in a direct and objective manner. Here we demonstrate the utility of a new open-source AI algorithm, ASDSpeech, which can analyze speech recordings of ASD children and reliably quantify their social communication difficulties across multiple developmental timepoints. The algorithm was trained and tested on the largest ASD speech dataset available to date, which contained 99,193 vocalizations from 197 ASD children recorded in 258 Autism Diagnostic Observation Schedule, Second edition (ADOS-2) assessments. ASDSpeech was trained with acoustic and conversational features extracted from the speech recordings of 136 children, who participated in a single ADOS-2 assessment, and tested with independent recordings of 61 additional children who completed two ADOS-2 assessments, separated by 1-2 years. Estimated total ADOS-2 scores in the test set were significantly correlated with actual scores when examining either the first (r(59) = 0.544, P < 0.0001) or second (r(59) = 0.605, P < 0.0001) assessment. Separate estimation of social communication and restricted and repetitive behavior symptoms revealed that ASDSpeech was particularly accurate at estimating social communication symptoms (i.e., ADOS-2 social affect scores). These results demonstrate the potential utility of ASDSpeech for enhancing basic and clinical ASD research as well as clinical management. We openly share both algorithm and speech feature dataset for use and further development by the community.

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5. Huang JR. Microexon in action: How tiny fragments in a protein tune function, drive disease. Mol Cell. 2025; 85(2): 202-4.

Intrinsically disordered regions (IDRs) of proteins can regulate function through phase separation. In a recent article in Nature, Garcia-Cabau et al. reveal that including or excluding a microexon within the IDR of CPEB4 alters its condensation properties, suggesting a potential mechanism underlying autism spectrum disorder.(1).

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6. Vasconcelos-Moreno MP, Prates-Baldez D, Santos-Terra J, Deckmann I, Di Gesu IN, Lemann RS, Riesgo R, Gottfried C, Kapczinski F. Clinical Interplay Between Autism Spectrum Disorder and Bipolar Disorder: A Narrative Review. Trends Psychiatry Psychother. 2025.

INTRODUCTION: Autism Spectrum Disorder (ASD) and Bipolar Disorder (BD) present significant challenges in diagnosis due to their complex nature. This review aims to examine the interface and overlapping features of these conditions. METHODS: We conducted a narrative review to examine clinical overlap, common psychiatric comorbidities, and shared neurobiological bases between ASD and BD. RESULTS: There is a notable convergence of symptoms in ASD and BD, including mood instability and emotional dysregulation; irritability, impulsivity, and aggressive behavior; deficits in social skills and social cognition; impairments in executive functions; sleep disturbances; problematic sexual behaviors; and sensory sensitivities. Common psychiatric comorbidities and shared neurobiological basis further underscore this potential interplay. CONCLUSION: Despite distinct clinical trajectories and diagnostic criteria, our findings indicate a significant overlap in symptoms and clinical presentations between ASD and BD. This complexity makes it challenging to identify the co-occurrence of ASD and BD, which can lead to difficulties in accurately diagnosing and managing both conditions simultaneously.

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7. Verhoeven WMA, Pfundt R, Engelke UFH, Kluijtmans LAJ, Egger JIM. X-Linked Autism Type 9 Caused by a Hemizygote Pathogenic Variant in the TMLHE Gene: Etiological Diagnosis in an Adult Male with Moderate Intellectual Disability. Int Med Case Rep J. 2025; 18: 111-6.

INTRODUCTION: Levocarnitine is essential for brain functioning and fatty acid metabolism and stems largely from dietary sources. The Epsilon-Trimethyllysine Hydroxylase (TMLHE) gene encodes the enzyme N-Trimethyllysine hydroxylase (TMLH) which catalyses the first step in the biosynthesis of carnitine. Lack of TMLH enzyme activity is associated with developmental delay and autistic behaviours described as X-linked recessive autism, type 6 (OMIM#300872). PATIENT AND METHODS: Here, an institutionalized adult male patient with intellectual disability, autism, and challenging behaviours is presented in whom genetic analysis disclosed a novel pathogenic variant in the TMLHE gene. Extensive somatic, neurological, psychiatric, and neuropsychological investigations were performed next to examination of hematological and biochemical parameters including plasma carnitine status. Also, Whole Exome Sequencing (WES) and Next-Generation Metabolic Screening (NGMS) were performed. RESULTS: Moderate intellectual disability along with obsessive and aggressive behaviour in the context of autism spectrum disorders was established as well as symptoms from the catatonic spectrum. With WES, a novel variant in the TMHLE gene was identified and using NGMS, increased concentration of trimethyllysine and decreased concentration of γ-butyrobetaine were found resulting in a significantly decreased BB/TML ratio, confirming the pathogenicity of this variant. CONCLUSION: X-linked autism type 6 is characterized by moderate intellectual disability and symptoms from the autism spectrum in the absence of any dysmorphisms. To prevent regressive autistic episodes in young children, it is highly recommended to consider next-generation sequencing techniques as the first step in the differential diagnostic process of autism.

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