Expression alteration of Neuroligin family gene in attention deficit and hyperactivity disorder and autism spectrum disorder.
A simple blood draw can reveal low Neuroligin gene activity in both autism and ADHD, giving clinicians an extra biological clue for differential diagnosis.
01Research in Context
What this study did
Bay et al. (2023) drew blood from three groups: kids with autism, kids with ADHD, and kids with neither.
They measured how much mRNA the Neuroligin 1, 2, and 3 genes made. These genes help build the glue that holds brain synapses together.
What they found
All three Neuroligin genes were quieter in the autism group than in typical kids.
Kids with ADHD also showed lower Neuroligin 2 and 3 activity, with Neuroligin 2 even lower than in the autism group.
How this fits with other research
Yu et al. (2025) looked at the same three groups with brain scans instead of blood. They found clear picture differences between autism and ADHD in the anterior cingulate, while Hanie found shared gene dips. The studies differ because one tool shows structure and the other shows molecules; together they hint that shared gene changes can still lead to different brain wiring.
Q et al. (2023) also hunted autism markers in blood, but they tracked cord blood taken at birth and followed babies for years. They found four different genes that predict later autism, while Hanie found Neuroligin changes after diagnosis. The genes do not clash; they simply mark different time points.
Ng et al. (2019) warn that parent ratings and lab tests often disagree when separating autism from ADHD. Hanie’s blood result gives you one more lab datapoint to pair with those ratings, not to replace them.
Why it matters
You now have a quick blood hint that may flag both autism and ADHD: low Neuroligin 2. It is not a stand-alone test, but it can nudge you to look deeper when a child’s profile is mixed. Pair the finding with pragmatic-language checks from Mammarella et al. (2022) and with the fMRI pattern seen by Yu et al. (2025) when you need clearer lines between the two diagnoses.
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02At a glance
03Original abstract
BACKGROUND: Autism spectrum disorder (ASD) is a complex neurodevelopment disorder with social and communicational deficiency, language impairment, and ritualistic behaviors. Attention deficit hyperactivity disorder (ADHD) is a pediatric psychiatric disorder with symptoms, including attention deficit, hyperactivity, and impulsiveness. ADHD is a childhood-onset disorder that can persist into adult life. Neuroligins are post-synaptic cell-adhesion molecules that connect neurons and have an essential role in the mediation of trans-synaptic signaling and shaping the synapse and circuits and neural network functioning. AIMS: Present study aimed to shed light on the role of the Neuroligin gene family in ASD and ADHD. METHODS AND PROCEDURES: mRNA levels of the Neuroligin gene family (NLGN1, NLGN2, NLGN3, and NLGN4X) were studied in the peripheral blood of 450 unrelated ASD patients, 450 unrelated ADHD patients, and the normal group included 490 unrelated non-psychiatric children by quantitative PCR. Also, clinical situations were considered. OUTCOMES AND RESULTS: Results showed that mRNA levels of NLGN1, NLGN2, and NLGN3 were significantly down-regulated in the ASD group vs. control subjects. In ADHD, a significant reduction of NLGN2 and NLGN3 was detected in comparison with normal children. A comparison of ASD and ADHD subjects revealed that NLGN2 was significantly down-regulated in ASD subjects. CONCLUSIONS: The Neuroligin family gene may play an essential role in the etiology of ASD and ADHD and thus be a source for a better understanding of neurodevelopment disorders. IMPLICATIONS: Similar patterns of deficiency of Neuroligin family genes in ASDs and ADHDs may indicate the role of these genes in functions that have been affected in both disorders.
Research in developmental disabilities, 2023 · doi:10.1016/j.ridd.2023.104558