A quarterly publication of the Autism Research Institute
Summer 2026 | Number 3, Volume 40
Researchers in Japan report evidence that copper deficiency may play a role in autism spectrum disorders (ASD).
Noriyoshi Usui and colleagues measured 21 elements in the plasma of 112 people with ASD and 115 neurotypical controls and detected a significant association be tween lower plasma copper levels and higher scores on clinical measures of ASD symptoms. Brain MRI scans also showed that participants with ASD had reduced white matter volume, which was associated with social symptoms.
The researchers note that white matter is composed largely of nerve fibers wrapped in insulating myelin, which is produced by a type of glial cell called oligodendrocytes. Their findings suggest, they say, that low lev els of copper could affect the way in which glial cells support brain circuit development.
To test this idea, the researchers created a mouse model of developmental copper de ficiency. The copper-deficient mice exhib ited altered social behavior and repetitive behaviors. Copper deficiency also reduced oligodendrocyte-lineage cells in the brain, impaired these cells’ maturation, and decreased myelin formation.
The researchers were able to identify a molecular pathway connecting copper deficiency to the brain changes seen in the mice. They found that copper deficiency disrupted regulation of blood vessel formation and metabolic responses in the developing brain, leading to oxidative stress, mitochondrial dysfunction, and altered mitophagy (removal of damaged mitochondria). These changes, in turn, led to suppressed mTOR signaling. The mTOR pathway is a cellular signaling pathway that plays crucial roles in cell growth, metabolism, and oligodendrocyte development. Activating mTOR signaling in the copper-deficient mice restored oligodendrocyte maturation and improved social behavior.
The researchers comment, “To our knowledge, this is the first study to mechanistically link copper deficiency to ASD-related glial and behavioral phenotypes using an integrative human-animal model approach.” Their findings, they say, offer insight into how systemic metal imbalances can contribute to ASD by disrupting trace element-dependent neurodevelopmental processes.
They stress, however, that their findings do not indicate that individuals with ASD should be taking copper supplements, noting that the population with ASD is diverse and copper deficiency may play a role in only a subgroup of individuals.
“Copper deficiency impairs oligodendrocyte maturation and social behavior via mitophagy and mTOR suppression in ASD,” Noriyoshi Usui, Miyuki Doi, Stefano Berto, Kiwamu Matsuoka, Rio Ishida, Hana Miyauchi, Yuuki Fujiwara, Koichiro Irie, Michihiro Toritsuka, Takahira Yamauchi, Takaharu Hirai, Min-Jue Xie, Yoshinori Kayashima, Naoko Umeda, Keiko Iwata, Kazuki Okumura, Taeko Harada, Taiichi Katayama, Masatsugu Tsujii, Hideo Matsuzaki, Manabu Makinodan, and Shoichi Shimada, Science Advances, April 2026 (free online). Address: Noriyoshi Usui, Department of Developmental Neuroscience, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951- 8510, Japan, [email protected].
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“Copper imbalance tied to autism’s social symptoms and white matter development,” news release, Niigata University, June 2, 2026.
