Tag: Autism

Posted on

Brain Protein in Mice Offers Insights Into Brain Development and ADHD

Attention-deficit/hyperactivity disorder (ADHD), marked by excessive activity and impulsivity, is linked to changes in the brain’s dopamine system, though the mechanisms remain unclear. Researchers at the University of Fukui have now found that in genetically modified, conditional knockout mice, loss of a protein called N-ethylmaleimide-sensitive factor (NSF)—which is linked to dopamine receptors—in D2 receptor-expressing cells led to lower dopamine levels and ADHD-like behaviors. Their results also pointed to a potential therapeutic strategy.

The team, headed by assistant professor Min-Jue Xie, PhD, at the Division of Development of Mental Functions, Research Centre for Child Mental Development, suggests that the results offer insight into how brain changes may contribute to ADHD and informing future treatments.

“This is basic research and will not immediately lead to a new treatment,” Xie acknowledged. “However, it provides important clues for understanding how dopaminergic dysfunction may contribute to ADHD. In the future, these findings may help develop new therapeutic strategies targeting D2R function and striatal dopamine signaling, especially for treatment-resistant ADHD.”

Xie is first and corresponding author of the researchers’ published paper in Neuropsychopharmacology, titled “Deletion of N-ethylmaleimide-sensitive factor in dopamine D2 receptor-expressing cells impairs striatal development and dopaminergic function and induces ADHD-like behaviors in mice.”

ADHD is a neurodevelopmental disorder that can affect attention, activity levels, and impulse control, with symptoms often beginning in childhood and sometimes continuing into adulthood. Although the exact causes of ADHD are not fully understood, changes in the brain’s dopamine system have long been linked to the condition. Dopamine is a chemical messenger that helps brain cells communicate and plays an important role in movement, motivation, and behavior.

While dopamine-related changes have been associated with ADHD, it remains unclear how the brain cells that respond to dopamine are maintained and how their disruption may contribute to ADHD-related behaviors. This is particularly relevant to dopamine D2 receptor (D2R)-expressing cells, which are found in the striatum, a brain region involved in movement and behavioral control. Understanding what helps these cells develop and function normally could provide new insights into the biological processes involved in ADHD. “Although D2R has been extensively studied, the upstream mechanisms regulating its function and localization remain unclear,” the authors wrote.

Against this backdrop, a research team from Japan, led by Xie, set out to investigate the role of NSF in these dopamine-related brain cells. NSF regulates membrane fusion, helping brain cells release chemical messengers and move proteins within their membranes. “NSF dysfunction is implicated in neuropsychiatric disorders, with reduced expression in autism spectrum disorder (ASD) and schizophrenia and aggregates in Parkinson’s disease,” the investigators noted.

“The motivation for this study came from previous findings suggesting that NSF may be involved in neurodevelopmental and neuropsychiatric disorders,” Xie explained. “NSF was known to interact with D2R; however, the role of this interaction in vivo remained unclear. Because ADHD is thought to involve reduced striatal dopaminergic function and D2R dysfunction, we hypothesized that NSF may be important for maintaining D2R-expressing neurons and dopaminergic function. This led us to initiate the present study.”

For their study the team created knockout mice in which NSF was removed specifically from D2R-expressing neurons. “… we generated D2R-specific Nsf conditional knockout (Nsf f/f;D2R-Cre) mice to examine NSF function in D2R-expressing cells in vivo,” they explained. They then studied the animals’ brain development, dopamine levels, and behavior. The team also tested whether drugs that affect dopamine signaling could reduce the behavioral changes seen in the modified mice.

The loss of NSF affected the developing brain, resulting in fewer dopamine D2R-expressing cells, increased early developmental cell death, and a smaller striatum. The mice also had markedly lower dopamine levels in this brain region. Together, these findings suggest that NSF helps maintain dopamine-related cells and supports normal development and dopamine function.

The brain changes were accompanied by ADHD-like behaviors. “Nsf f/f;D2R-Cre mice exhibited attention-deficit/hyperactivity disorder (ADHD)-like behaviors, including hyperactivity and impulsivity,” the team reported. The knockout mice were more hyperactive than control mice and showed more impulsive-like behavior in a test that measured how quickly they jumped from an elevated platform. By the end of the seven-minute test, 86% of the experimental group mice had jumped, compared with 31% of the control group mice. “These findings indicate that a reduction in D2R-expressing cells coincides with ADHD-like behaviors, suggesting a link between D2R dysfunction and these abnormalities.”

The researchers then explored whether these behaviors could be reduced by changing dopamine signaling. Methylphenidate, a medicine commonly used to treat ADHD, did not significantly reduce hyperactivity when given alone to the modified mice. However, when it was given together with quinpirole, a drug that activates D2R, the mice became less hyperactive and showed less impulsive-like behavior. During the seven-minute test, the proportion of knockout mice that jumped fell from 78% without treatment to 11% after the two drugs were given together. “Combined administration of methylphenidate and a D2R agonist, quinpirole, alleviated both behaviors, suggesting a potential complementary approach for ADHD treatment,” the investigators wrote.

“This study supports the translational relevance of the Nsf f/f;D2R-Cre model for ADHD and indicates that targeting D2R dysfunction, particularly in treatment-resistant ADHD, may be a promising therapeutic strategy.”

The post Brain Protein in Mice Offers Insights Into Brain Development and ADHD appeared first on GEN – Genetic Engineering and Biotechnology News.

Posted on

Leveraging Scalable Non-Mammalian Systems for Large-Scale Studies of Autism Risk Gene Function

There are over 100 large-effect genes strongly associated with autism spectrum disorder (ASD), yet advancing from risk genes to the discovery of common biological pathways and pharmacological targets remains a central challenge. Scalable non-mammalian systems, including Caenorhabditis elegans (roundworm), Drosophila melanogaster (fruit fly), Danio rerio (zebrafish), and Xenopus tropicalis (frog), provide critical advantages for the functional analysis of ASD genes due to their amenability to high-throughput screens, relatively low cost, and ease of genetic manipulation.

Posted on

Exploration of the relationship between social cognition and PTSD using data from the ALSPAC cohort

Background and hypothesisPrevious studies have shown an association between social cognition (emotion recognition, social perception, attributional style, and mentalization) and post-traumatic stress disorder (PTSD), but there have been no longitudinal studies on this topic. We hypothesize that childhood social cognitive differences are associated with subsequent trauma exposure and PTSD.Study designData from the Longitudinal Study of Parents and Children (ALSPAC) were used. The Social Communications Disorder Checklist (SCDC) at age 7.5 years, the Diagnostic Analysis of Non-Verbal Accuracy Scale (DANVA) Receptive Facial Expressions Subtest at 8 years, and the Emotional Triangles task at 13.5 years were used. Outcome measures were trauma ages 14–23 years using the LEC-5 and screening positive for PTSD at 23 years of age using the PCL-5. Logistic regression analyses were used and adjusted for sex, socioeconomic status, verbal IQ, and autism diagnosis for the trauma outcome and, additionally, childhood trauma ages 0–10 years for the PTSD outcome. A sensitivity analysis examined whether an association remained with adolescent/adult trauma after excluding those with childhood trauma.Study resultsGlobal social cognition differences measured via the SCDC were associated with trauma in the main and sensitivity analyses (ORadj 1.09, 95% CI 1.08, 1.11, p-value <0.001) as were errors on the Triangles task (ORadj 1.04, 95% CI 1.03, 1.06, p-value <0.001). The SCDC was also associated with PTSD (ORadj 1.15, 95% CI 1.12, 1.18, p-value <0.001) as were errors on the Triangles task (ORadj 1.16, 95% CI 1.13, 1.20, p-value <0.001). No association was found with the DANVA task and the outcomes measured.ConclusionsThese results support a temporal relationship between social cognitive variation and subsequent trauma and PTSD.
Posted on

Autistic traits and obsessive–compulsive symptom severity: a retrospective six-month follow-up study

Autistic traits have been increasingly associated with obsessive–compulsive disorder (OCD), yet their influence on longitudinal symptom severity and treatment-related change remains poorly understood. This retrospective longitudinal study included 38 adults with DSM-5 OCD who completed six months of guideline-based pharmacological treatment. Obsessive–compulsive symptom severity was assessed using the Yale–Brown Obsessive–Compulsive Scale (Y-BOCS) at baseline, one month, and six months. Autistic traits were evaluated at the six-month follow-up using the Autism Spectrum Quotient (AQ). Linear mixed-effects models served as the primary analyses, while repeated-measures analyses of covariance were performed as sensitivity analyses. Exploratory analyses examined the contribution of individual AQ subscales. Higher autistic trait levels were independently associated with persistently greater OCD symptom severity across the six-month follow-up, whereas the rate of treatment-related improvement did not differ according to autistic trait levels. This association was primarily driven by compulsive rather than obsessive symptoms. Exploratory analyses further identified social skills and attention switching as the AQ dimensions most strongly associated with overall OCD severity and compulsive symptom burden, whereas attention to detail was not significantly associated with symptom severity. These findings suggest that autistic traits represent stable markers of greater clinical burden in OCD without necessarily conferring poorer pharmacological treatment responsiveness. The results further support a dimensional conceptualization of autistic traits and highlight social functioning as a potentially important contributor to OCD symptom burden.
Posted on

Association of iron deficiency and iron-deficiency anemia with behavioral problems in children with autism: a cross-sectional study

PurposeIron deficiency (ID) and iron deficiency anemia (IDA) are common in children with autism spectrum disorder (ASD) and may contribute to behavioral problems. We examined their association with internalizing and externalizing behavioral problems.MethodsThis cross-sectional study (October 2023 to March 2025) was conducted at a tertiary hospital in India. Of 179 children aged 2 to 18 years with newly diagnosed ASD (DSM-5 criteria), 173 were analyzed after six exclusions for missing data. ID and IDA were defined using age-specific World Health Organization thresholds and modeled as a three-category variable with normal iron status as the reference. The Child Behavior Checklist was used to assess internalizing and externalizing problems (T-score > 63). Multivariable logistic regression was used to estimate adjusted odds ratios (aORs), controlling for age, sex, maternal education and family type; ferritin and hemoglobin were modeled using restricted cubic splines. Bonferroni correction was applied across the six adjusted comparisons.ResultsAmong 173 children (median age 4.0 years [IQR 3.0–5.0]; 79.8% male), 19.7% had ID, 22.5% had IDA and 42.2% had either; internalizing and externalizing problems occurred in 39.9% and 35.8% of the children, respectively. Compared with normal iron status, both ID and IDA were associated with higher odds of internalizing problems (ID aOR 3.03, 95% confidence interval [CI] 1.34–6.86; IDA aOR 2.73, 95% CI 1.23–6.05) and externalizing problems (ID aOR 3.71, 95% CI 1.63–8.46; IDA aOR 3.24, 95% CI 1.45–7.24), corresponding to prevalence differences of 25 to 29 percentage points. An interquartile increase in ferritin (9.2 to 21.4 µg/L) was associated with lower odds of both outcomes (internalizing aOR 0.23, 95% CI 0.11–0.46; externalizing aOR 0.30, 95% CI 0.15–0.60). Five of six associations survived Bonferroni correction; IDA with internalizing problems did not. Hemoglobin was not consistently associated with either outcome.ConclusionsID and IDA are prevalent in Indian children with ASD and are associated with clinically significant behavioral problems, with higher serum ferritin inversely associated with both outcomes. Routine iron screening may be considered during initial ASD evaluation, particularly in high-burden settings, although randomized trials are needed to determine whether correcting deficiency improves behavioral outcomes.
Posted on

Neurodiversity as an epistemic stress test for psychotherapy and health care: a neuroaffirmative conceptual analysis of relational-proximity priors in clinical, institutional, and AI-supported models

Neurodiversity-affirming mental health care requires not only adapting support to neurodivergent people but also examining the relational assumptions through which alliance, empathy, cooperation, progress, and risk are interpreted. This Conceptual Analysis develops the heuristic concept of relational-proximity priors: implicit assumptions that emotional closeness, rapid reciprocity, eye contact, visible warmth, and ready acceptance of help are generally reliable indicators of therapeutic fit or improvement. Drawing primarily on autism research and, more cautiously, on broader neurodivergence-informed literature, the paper synthesizes work on neurodiversity, double empathy, minority stress, healthcare accessibility, interpersonal distance, epistemic injustice, and psychotherapy process. The argument is that when such priors remain unaudited, clinically meaningful behaviors such as distance, reduced affect display, written communication, slower pacing, or literal style may be misread as resistance, poor alliance, or lack of insight. The paper further proposes that these priors can become sedimented in service routines, documentation practices, and AI-supported systems if observation and interpretation are not adequately separated. The article does not present a validated empirical construct or a systematic review; rather, it offers a theory-anchored conceptual synthesis and a set of heuristic audit tools intended to slow interpretation and widen clinically plausible hypotheses. Implications are discussed for psychotherapy, service design, documentation, participatory evaluation, and AI governance in public mental health.
Posted on

Autistic traits in unaffected first-degree relatives of individuals with schizophrenia and bipolar disorder: implications for shared familial neurodevelopmental vulnerability

BackgroundAutistic traits have increasingly been linked to schizophrenia (SCH) and bipolar disorder (BD) within a shared neurodevelopmental framework. However, whether these traits are similarly expressed in unaffected first-degree relatives of individuals with SCH and BD remains poorly understood.MethodsThis cross-sectional study included 135 participants: first-degree relatives of individuals with schizophrenia (SCH-FDR, n=45), first-degree relatives of individuals with bipolar disorder (BD-FDR, n=45), and healthy controls (HCs, n=45). Autistic traits were assessed using the Autism Spectrum Quotient (AQ). Participants also underwent clinical psychiatric evaluation, including structured diagnostic assessment, to exclude psychiatric disorders and autism spectrum disorder.ResultsSignificant group differences were observed for AQ total score (p=0.002), Communication (p=0.004), and Imagination (p<0.001) subscales. Communication scores were significantly higher in SCH-FDR than in HCs (p=0.003). Imagination scores were higher in both BD-FDR (p=0.016) and SCH-FDR (p<0.001) groups compared with HCs. Total AQ scores were also higher in both relative groups than in HCs (BD-FDR: p=0.015; SCH-FDR: p=0.003). The proportion of participants with AQ scores ≥26 was higher in SCH-FDR (17.8%) and BD-FDR (13.3%) than in HCs (2.2%; p=0.045).ConclusionsAutistic traits were more pronounced in SCH-FDR and BD-FDR than in healthy controls. Differences were most evident in total AQ scores and the Imagination subscale across both relative groups, whereas communication difficulties were specifically elevated in schizophrenia relatives. These findings are consistent with the concept of shared familial neurodevelopmental vulnerability across schizophrenia and bipolar disorder.