TY - JOUR
T1 - Neurodevelopmental effects of omega-3 fatty acids and its combination with Methylphenidate in iPSC models of ADHD
AU - Walter, Natalie M.
AU - Yde Ohki, Cristine M.
AU - Ruhstaller, Sina
AU - Del Campana, Letizia
AU - Salazar Campos, José Maria
AU - Smigielski, Lukasz
AU - Rubio, Belén
AU - Walitza, Susanne
AU - Grünblatt, Edna
N1 - Publisher Copyright:
© 2025 The Authors
PY - 2025/4
Y1 - 2025/4
N2 - Attention-Deficit/Hyperactivity Disorder (ADHD) has been linked to altered neurodevelopmental processes, including proliferation and differentiation of neural stem cells (NSC). We aimed to investigate the role of Wnt signaling, a pathway critical for brain development, in ADHD and to determine if modulation of this pathway using ω-3/6 polyunsaturated fatty acids (PUFAs) may provide a beneficial treatment approach. Given the symptom heterogeneity in ADHD and the limited response to conventional therapies for some patients, we examined the effects of ω-3/6 PUFA treatment combined with Methylphenidate (MPH) on neurodevelopmental mechanisms using induced pluripotent stem cell (iPSC)-derived NSCs, comparing controls to ADHD patients. Our results show that ω-3/6 PUFAs differentially regulate Wnt activity in NSCs depending on the patient's condition and the composition of the treatments. These findings highlight the potential of ω-3 PUFA treatment as personalized support for neurodevelopmental processes in ADHD. They also emphasize the importance of investigating ADHD subgroups, including those unresponsive to stimulant treatments, as they may exhibit distinct phenotypes.
AB - Attention-Deficit/Hyperactivity Disorder (ADHD) has been linked to altered neurodevelopmental processes, including proliferation and differentiation of neural stem cells (NSC). We aimed to investigate the role of Wnt signaling, a pathway critical for brain development, in ADHD and to determine if modulation of this pathway using ω-3/6 polyunsaturated fatty acids (PUFAs) may provide a beneficial treatment approach. Given the symptom heterogeneity in ADHD and the limited response to conventional therapies for some patients, we examined the effects of ω-3/6 PUFA treatment combined with Methylphenidate (MPH) on neurodevelopmental mechanisms using induced pluripotent stem cell (iPSC)-derived NSCs, comparing controls to ADHD patients. Our results show that ω-3/6 PUFAs differentially regulate Wnt activity in NSCs depending on the patient's condition and the composition of the treatments. These findings highlight the potential of ω-3 PUFA treatment as personalized support for neurodevelopmental processes in ADHD. They also emphasize the importance of investigating ADHD subgroups, including those unresponsive to stimulant treatments, as they may exhibit distinct phenotypes.
KW - Attention-deficit/hyperactivity disorder
KW - Growth rates
KW - Induced pluripotent stem cells
KW - Neural stem cells
KW - Polyunsaturated fatty acids
KW - Wnt signaling
UR - https://www.scopus.com/pages/publications/85219100178
U2 - 10.1016/j.jpsychires.2025.02.035
DO - 10.1016/j.jpsychires.2025.02.035
M3 - Article
C2 - 40043588
AN - SCOPUS:85219100178
SN - 0022-3956
VL - 184
SP - 78
EP - 90
JO - Journal of Psychiatric Research
JF - Journal of Psychiatric Research
ER -