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Journal of Neural Transmission
Article . 2025 . Peer-reviewed
License: CC BY
Data sources: Crossref
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Research Collection
Article . 2025
License: CC BY
ETH Zürich Research Collection
Article . 2025
License: CC BY
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The link between Wnt-related, stress-related, and circadian genes in the dermal fibroblasts of individuals with attention-deficit hyperactivity disorder

Authors: Denise Palm; Lukasz Smigielski; Adriana Uzoni; Oliver Tucha; Johannes Thome; Edna Grünblatt;

The link between Wnt-related, stress-related, and circadian genes in the dermal fibroblasts of individuals with attention-deficit hyperactivity disorder

Abstract

Abstract Attention-deficit/hyperactivity disorder (ADHD) has been associated with circadian rhythm disturbances, altered stress responses, and, in neural stem cells from ADHD patients, aberrant Wnt signaling. However, little is known about how these molecular pathways interact. This study aimed to investigate rhythmic expression of circadian, Wnt signaling, and stress-related genes in the context of ADHD. Human dermal fibroblasts were obtained via skin biopsy from participants diagnosed with ADHD (n = 13) and healthy controls (n = 13). Fibroblast cultures were synchronized using dexamethasone, with samples collected every 4 h over 28 h. Gene expression of Wnt signaling, stress-related, and circadian clock genes was quantified by qRT-PCR. Harmonic regression was applied to estimate rhythmicity (amplitude and phase), followed by mixed-effects modeling and likelihood ratio tests to assess between-group differences and gene–gene associations. Circular statistics (Rayleigh test, Watson two-sample test, circular correlations) were employed to test the uniformity and synchronicity of phase distributions. BMAL1, CRY1, PER2, PER3, and DKK1 exhibited significant rhythmicity within each group. DKK3 was rhythmic only in the ADHD group. Although between-group differences did not reach statistical significance, BMAL1 and CRY1 expression peaked later, while PER2 and PER3 expression peaked earlier in the ADHD group. Depending on data filtering, gene–gene rhythmicity associations included CRY1–SIRT1, PER3–FOXO1, and CLOCK–CTNNB1 in ADHD subjects, as well as CLOCK–DKK1 (ADHD) and BMAL1–DKK1 in controls. The phase and amplitude of core clock genes were correlated with donors’ ADHD symptoms and subjective sleep measures. Our data indicate ADHD is associated with subtly altered circadian gene expression and distinct integration of Wnt signaling and stress-related pathways, supporting the hypothesis of broader molecular dysregulation underlying ADHD.

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Keywords

ADHD; Gene expression; Circadian rhythms; Clock genes; Wnt signaling; DKK1, DKK1, ADHD, Circadian rhythms, Gene expression, Clock genes, Wnt signaling

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
0
Average
Average
Average
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hybrid