Autism spectrum disorder (ASD) (autism)
- is a condition that begins in childhood
- core symptoms include persistent difficulties with social communication (e.g. difficulties with back‐and‐forth conversations, communication without words, and in developing and maintaining relationships), and repetitive and restricted interests and behaviours (e.g. repetitive mannerisms, restricted interests and behaviours, resistance to change and sensory sensitivities)
- about 1% to 2% of children have autism (1)
- the pregenual anterior cingulate cortex (pgACC) is a brain region rich in glutamate neurotransmission, subserves social processing, emotional awareness, mentalizing, and self-reflection functions that are impaired in individuals with ASD (2)
- autistic people often have other conditions such as attention deficit hyperactivity disorder (ADHD), anxiety, language impairments (e.g. difficulties understanding and using grammar) and intellectual disability (1)
Memantine
- is a pharmacological agent that acts as a non‐competitive antagonist of glutamatergic N‐methyl‐D‐aspartate (NMDA)‐type receptors
- works by inhibiting pathological overactivation and subsequent neuroexcitation and cell death of NMDA receptor cells by glutamate (an amino acid normally found in the brain)
- there is evidence that autistic people have pathologically increased activity levels of glutamate and NMDA receptors, hence the aim to modulate this biochemical effect to potentially reduce the core symptoms of autism (1)
A systematic review concluded that it was unclear whether memantine is an effective treatment for autistic children (1).
A more recent study investigated whether memantine improved social functioning in youths with autism spectrum disorder (ASD) without intellectual disability (2):
- in this randomized clinical trial that included 42 youths with ASD, memantine was well tolerated and significantly improved social impairment
- as an exploratory outcome, glutamate levels in the pgACC region of the brain were assessed by acquiring 1H-MRS imaging prior to initiating treatment in participants with ASD and twice at 12-week intervals in healthy control participants
- the study authors concluded:
- memantine was well tolerated and significantly improved social impairments in youths with ASD
- elevated pgACC glutamate levels were associated with a favourable treatment response, supporting their potential as a biomarker for assessing memantine efficacy in individuals with ASD
References:
- Brignell A, Marraffa C, Williams K, May T. Memantine for autism spectrum disorder. Cochrane Database Syst Rev. 2022 Aug 25;8(8):CD013845.
- Joshi G, Gönenc A, DiSalvo M, et al. Memantine to Treat Social Impairment in Youths With Autism Spectrum Disorder: A Randomized Clinical Trial. JAMA Netw Open. 2025;8(10):e2534927.