The effects of omega-3 fatty acids on Wnt activity in iPSC-derived neural stem cells from adult ADHD patients

Cristine M. Yde Ohki; Natalie M. Walter; Louisa C. Dury; Letizia Del Campana; Romane Lasmarrigues; Rhiannon V. McNeill; Zora Schickardt; Lukasz Smigielski; Susanne Walitza; Sarah Kittel-Schneider; E. Grünblatt

doi:10.1016/j.nsa.2026.107005

The effects of omega-3 fatty acids on Wnt activity in iPSC-derived neural stem cells from adult ADHD patients

Cristine M. Yde Ohki
, Natalie M. Walter
, Louisa C. Dury
, Letizia Del Campana
, Romane Lasmarrigues
, Rhiannon V. McNeill
, Zora Schickardt
, Lukasz Smigielski
, Susanne Walitza
, Sarah Kittel-Schneider
, E. Grünblatt

Research output: Contribution to journal › Article › peer-review

Abstract

The canonical Wnt signaling pathway plays a key role in neurodevelopment and in maintaining cellular homeostasis of the central nervous system in adulthood. It regulates essential processes, such as cell proliferation, differentiation, and synaptogenesis. In vivo and genetic evidence suggests an association between attention-deficit/hyperactivity disorder (ADHD) and abnormalities in the Wnt pathway. Prior research from our group indicated heightened basal Wnt activity in neural stem cells (NSCs) derived from induced pluripotent stem cells (iPSCs) of pediatric ADHD patients and showed that methylphenidate (MPH) and omega-3 polyunsaturated fatty acids (ω-3 PUFAs) can modulate this pathway. While MPH is a first-line treatment for ADHD, ω-3 PUFAs are under investigation as a potential non-pharmacological supplement. Using the same functionality-based reporter technology, we assessed Wnt activity in iPSC-derived NSCs from 5 adult ADHD patients and 5 healthy controls. We examined whether ω-3 fatty acids (EPA and DHA), alone or combined, and DHA with MPH can modulate Wnt activity in these NSCs. Basal Wnt responsiveness did not differ between adult ADHD and control lines, although genetic risk for ADHD was associated with increased Wnt activity. EPA showed no statistically significant effects, while DHA strongly increased Wnt activity in both groups. DHA combined with EPA increased Wnt activity in ADHD lines, whereas DHA with MPH caused group-specific responses: enhancing Wnt signaling in ADHD but reducing it in controls. Compared to NSCs derived from children, adult-derived NSCs behave differently and show distinct responses to EPA and DHA, suggesting a potential route toward refined therapeutic strategies for adults. © 2026 The Authors. Published by Elsevier B.V. on behalf of European College of Neuropsychopharmacology. This is an open access article under the CC BY license. http://creativecommons.org/licenses/by/4.0/

Original language	English
Article number	107005
Pages (from-to)	1-9
Number of pages	9
Journal	Neuroscience Applied
Volume	5
DOIs	https://doi.org/10.1016/j.nsa.2026.107005
Publication status	Published - 7 May 2026

Keywords

Attention-deficit/hyperactivity disorder
Docosahexaenoic acid
Methylphenidate
Neural stem cells
Omega-3
Wnt signaling
[APCMicrobiome]
[Medicine]

Access to Document

10.1016/j.nsa.2026.107005Licence: CC BY

1-s2.0-S2772408526001249-mainFinal published version, 1.94 MBLicence: CC BY
Appendix A - Supplementary DataFinal published version, 39.1 MBLicence: CC BY

https://www.scopus.com/pages/publications/105037954815?origin=resultslist

Cite this

Yde Ohki, C. M., Walter, N. M., Dury, L. C., Del Campana, L., Lasmarrigues, R., McNeill, R. V., Schickardt, Z., Smigielski, L., Walitza, S., Kittel-Schneider, S., & Grünblatt, E. (2026). The effects of omega-3 fatty acids on Wnt activity in iPSC-derived neural stem cells from adult ADHD patients. Neuroscience Applied, 5, 1-9. Article 107005. https://doi.org/10.1016/j.nsa.2026.107005

@article{726038c3015145f1b75592e25619c116,

title = "The effects of omega-3 fatty acids on Wnt activity in iPSC-derived neural stem cells from adult ADHD patients",

abstract = "The canonical Wnt signaling pathway plays a key role in neurodevelopment and in maintaining cellular homeostasis of the central nervous system in adulthood. It regulates essential processes, such as cell proliferation, differentiation, and synaptogenesis. In vivo and genetic evidence suggests an association between attention-deficit/hyperactivity disorder (ADHD) and abnormalities in the Wnt pathway. Prior research from our group indicated heightened basal Wnt activity in neural stem cells (NSCs) derived from induced pluripotent stem cells (iPSCs) of pediatric ADHD patients and showed that methylphenidate (MPH) and omega-3 polyunsaturated fatty acids (ω-3 PUFAs) can modulate this pathway. While MPH is a first-line treatment for ADHD, ω-3 PUFAs are under investigation as a potential non-pharmacological supplement. Using the same functionality-based reporter technology, we assessed Wnt activity in iPSC-derived NSCs from 5 adult ADHD patients and 5 healthy controls. We examined whether ω-3 fatty acids (EPA and DHA), alone or combined, and DHA with MPH can modulate Wnt activity in these NSCs. Basal Wnt responsiveness did not differ between adult ADHD and control lines, although genetic risk for ADHD was associated with increased Wnt activity. EPA showed no statistically significant effects, while DHA strongly increased Wnt activity in both groups. DHA combined with EPA increased Wnt activity in ADHD lines, whereas DHA with MPH caused group-specific responses: enhancing Wnt signaling in ADHD but reducing it in controls. Compared to NSCs derived from children, adult-derived NSCs behave differently and show distinct responses to EPA and DHA, suggesting a potential route toward refined therapeutic strategies for adults. {\textcopyright} 2026 The Authors. Published by Elsevier B.V. on behalf of European College of Neuropsychopharmacology. This is an open access article under the CC BY license. http://creativecommons.org/licenses/by/4.0/",

keywords = "Attention-deficit/hyperactivity disorder, Docosahexaenoic acid, Methylphenidate, Neural stem cells, Omega-3, Wnt signaling, [APCMicrobiome], [Medicine]",

author = "\{Yde Ohki\}, \{Cristine M.\} and Walter, \{Natalie M.\} and Dury, \{Louisa C.\} and \{Del Campana\}, Letizia and Romane Lasmarrigues and McNeill, \{Rhiannon V.\} and Zora Schickardt and Lukasz Smigielski and Susanne Walitza and Sarah Kittel-Schneider and E. Gr{\"u}nblatt",

note = "{\textcopyright} 2026 The Authors. Published by Elsevier B.V. on behalf of European College of Neuropsychopharmacology. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ ).",

year = "2026",

month = may,

day = "7",

doi = "10.1016/j.nsa.2026.107005",

language = "English",

volume = "5",

pages = "1--9",

journal = "Neuroscience Applied",

issn = "2772-4085",

publisher = "Elsevier B.V.",

}

TY - JOUR

T1 - The effects of omega-3 fatty acids on Wnt activity in iPSC-derived neural stem cells from adult ADHD patients

AU - Yde Ohki, Cristine M.

AU - Walter, Natalie M.

AU - Dury, Louisa C.

AU - Del Campana, Letizia

AU - Lasmarrigues, Romane

AU - McNeill, Rhiannon V.

AU - Schickardt, Zora

AU - Smigielski, Lukasz

AU - Walitza, Susanne

AU - Kittel-Schneider, Sarah

AU - Grünblatt, E.

N1 - © 2026 The Authors. Published by Elsevier B.V. on behalf of European College of Neuropsychopharmacology. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ ).

PY - 2026/5/7

Y1 - 2026/5/7

N2 - The canonical Wnt signaling pathway plays a key role in neurodevelopment and in maintaining cellular homeostasis of the central nervous system in adulthood. It regulates essential processes, such as cell proliferation, differentiation, and synaptogenesis. In vivo and genetic evidence suggests an association between attention-deficit/hyperactivity disorder (ADHD) and abnormalities in the Wnt pathway. Prior research from our group indicated heightened basal Wnt activity in neural stem cells (NSCs) derived from induced pluripotent stem cells (iPSCs) of pediatric ADHD patients and showed that methylphenidate (MPH) and omega-3 polyunsaturated fatty acids (ω-3 PUFAs) can modulate this pathway. While MPH is a first-line treatment for ADHD, ω-3 PUFAs are under investigation as a potential non-pharmacological supplement. Using the same functionality-based reporter technology, we assessed Wnt activity in iPSC-derived NSCs from 5 adult ADHD patients and 5 healthy controls. We examined whether ω-3 fatty acids (EPA and DHA), alone or combined, and DHA with MPH can modulate Wnt activity in these NSCs. Basal Wnt responsiveness did not differ between adult ADHD and control lines, although genetic risk for ADHD was associated with increased Wnt activity. EPA showed no statistically significant effects, while DHA strongly increased Wnt activity in both groups. DHA combined with EPA increased Wnt activity in ADHD lines, whereas DHA with MPH caused group-specific responses: enhancing Wnt signaling in ADHD but reducing it in controls. Compared to NSCs derived from children, adult-derived NSCs behave differently and show distinct responses to EPA and DHA, suggesting a potential route toward refined therapeutic strategies for adults. © 2026 The Authors. Published by Elsevier B.V. on behalf of European College of Neuropsychopharmacology. This is an open access article under the CC BY license. http://creativecommons.org/licenses/by/4.0/

AB - The canonical Wnt signaling pathway plays a key role in neurodevelopment and in maintaining cellular homeostasis of the central nervous system in adulthood. It regulates essential processes, such as cell proliferation, differentiation, and synaptogenesis. In vivo and genetic evidence suggests an association between attention-deficit/hyperactivity disorder (ADHD) and abnormalities in the Wnt pathway. Prior research from our group indicated heightened basal Wnt activity in neural stem cells (NSCs) derived from induced pluripotent stem cells (iPSCs) of pediatric ADHD patients and showed that methylphenidate (MPH) and omega-3 polyunsaturated fatty acids (ω-3 PUFAs) can modulate this pathway. While MPH is a first-line treatment for ADHD, ω-3 PUFAs are under investigation as a potential non-pharmacological supplement. Using the same functionality-based reporter technology, we assessed Wnt activity in iPSC-derived NSCs from 5 adult ADHD patients and 5 healthy controls. We examined whether ω-3 fatty acids (EPA and DHA), alone or combined, and DHA with MPH can modulate Wnt activity in these NSCs. Basal Wnt responsiveness did not differ between adult ADHD and control lines, although genetic risk for ADHD was associated with increased Wnt activity. EPA showed no statistically significant effects, while DHA strongly increased Wnt activity in both groups. DHA combined with EPA increased Wnt activity in ADHD lines, whereas DHA with MPH caused group-specific responses: enhancing Wnt signaling in ADHD but reducing it in controls. Compared to NSCs derived from children, adult-derived NSCs behave differently and show distinct responses to EPA and DHA, suggesting a potential route toward refined therapeutic strategies for adults. © 2026 The Authors. Published by Elsevier B.V. on behalf of European College of Neuropsychopharmacology. This is an open access article under the CC BY license. http://creativecommons.org/licenses/by/4.0/

KW - Attention-deficit/hyperactivity disorder

KW - Docosahexaenoic acid

KW - Methylphenidate

KW - Neural stem cells

KW - Omega-3

KW - Wnt signaling

KW - [APCMicrobiome]

KW - [Medicine]

U2 - 10.1016/j.nsa.2026.107005

DO - 10.1016/j.nsa.2026.107005

M3 - Article

SN - 2772-4085

VL - 5

SP - 1

EP - 9

JO - Neuroscience Applied

JF - Neuroscience Applied

M1 - 107005

ER -

The effects of omega-3 fatty acids on Wnt activity in iPSC-derived neural stem cells from adult ADHD patients

Abstract

Keywords

Access to Document

Fingerprint

Cite this