Lithium, a key material used in electric vehicle batteries, is the substance that has been used longest to treat bipolar disorder, which involves cycles of mania and depression in medical settings. Domestic researchers have applied lithium to the treatment of autism spectrum disorder (ASD).
Kim Eun-jun, Director General of the Institute for Basic Science (IBS) Synapse Brain Disease Research Center and chair professor at the Korea Advanced Institute of Science and Technology (KAIST), noted on the 23rd that "specific gene deficiencies have been revealed to trigger symptoms of autism spectrum disorder, and lithium has been used to recover neural damage and normalize behavioral abnormalities." The research results were published online in the journal "Molecular Psychiatry" on the 5th.
Autism spectrum disorder is accompanied by various symptoms, including difficulties in social interaction, increased repetitive behaviors, as well as intellectual disabilities, anxiety disorders, and hyperactivity. Although genetic factors are known to account for approximately 80% of autism onset, the associated genes are so diverse, numbering over 1,000, that it is difficult to clarify the exact onset process.
The research team focused on Dyrk1a, known as a causative gene for Down syndrome. Previous studies have reported that the Dyrk1a gene frequently causes autism. Mutations in this gene are associated with language development disorders, intellectual disabilities, and microcephaly, collectively referred to as "Dyrk1a syndrome." Like other forms of autism, no clear treatment has yet been found for Dyrk1a syndrome.
The researchers used mice to analyze the structure and excitability of neurons, synaptic functions, and changes in brain size due to Dyrk1a gene deficiency from various angles. The study found that Dyrk1a gene deficiency led to a reduction in synapse density and the function of excitatory synapses, resulting in serious changes to the structure and function of the brain, including a decrease in neuronal dendrite structure.
Additionally, inhibiting the mTOR enzyme's signaling pathway, which regulates cell development and function, resulted in impaired brain growth and neural development, ultimately leading to microcephaly. Consequently, symptoms similar to autism, such as memory impairment, communication difficulties, and decreased social interaction, were observed. The offspring mice separated from their mother showed increased anxiety behavior and sought their mother more frequently, while male mice exhibited reduced frequency and complexity of courtship behavior. The decline in social interaction was evident.
The research team confirmed the effects of lithium, which increases the activity of the mTOR pathway, by administering it to the mice during their early years. In young mice, lithium was administered through breast milk and later mixed with drinking water after weaning, with observations continuing until adulthood. As a result, not only were the neuronal signaling and the structure of neurons as well as autism-like behavioral symptoms restored to normal levels, but microcephaly also showed surprising improvement. Most importantly, the effects of short-term lithium administration during childhood persisted into adulthood. The researchers stated that the effects of lithium demonstrate that it does not merely temporarily alleviate neurological problems but also restores the brain's structure and function in the long term.
No Jun-yup, a co-first author and senior researcher at IBS, explained, "When the Dyrk1a gene is damaged, it creates a situation similar to excessive congestion or disconnection in a road network inside the brain, leading to impaired vehicle flow." He added, "Lithium regulates the imbalance of synaptic functions and stabilizes the brain's signaling system to facilitate vehicle flow within the brain."
Director General Kim Eun-jun remarked that "the persistence of the short-term effects of lithium treatment during childhood into adulthood is an encouraging result suggesting that autism can be mitigated through short-term drug treatment after early diagnosis of the disorder." He noted, "Lithium has been widely used to treat various psychiatric disorders, including bipolar disorder, and there is ample clinical experience regarding its efficacy and safety," adding, "Follow-up research is needed to develop personalized optimal treatment strategies considering the diverse genetic characteristics and conditions of patients."
Reference materials
Molecular Psychiatry (2024), DOI: https://doi.org/10.1038/s41380-024-02865-2