Excitatory/inhibitory imbalance in autism spectrum disorders: Implications for interventions and therapeutics

Genoveva Uzunova, Stefano Pallanti, Eric Hollander

Research output: Contribution to journalReview articlepeer-review

123 Scopus citations


Objectives: Imbalance between excitation and inhibition and increased excitatory-inhibitory (E-I) ratio is a common mechanism in autism spectrum disorders (ASD) that is responsible for the learning and memory, cognitive, sensory, motor deficits, and seizures occurring in these disorders. ASD are very heterogeneous and better understanding of E-I imbalance in brain will lead to better diagnosis and treatments. Methods: We perform a critical literature review of the causes and presentations of E-I imbalance in ASD. Results: E-I imbalance in ASD is due primarily to abnormal glutamatergic and GABAergic neurotransmission in key brain regions such as neocortex, hippocampus, amygdala, and cerebellum. Other causes are due to dysfunction of neuropeptides (oxytocin), synaptic proteins (neuroligins), and immune system molecules (cytokines). At the neuropathological level E-I imbalance in ASD is presented as a “minicolumnopathy”. E-I imbalance alters the manner by which the brain processes information and regulates behaviour. New developments for investigating E-I imbalance such as optogenetics and transcranial magnetic stimulation (TMS) are presented. Non-invasive brain stimulation methods such as TMS for treatment of the core symptoms of ASD are discussed. Conclusions: Understanding E-I imbalance has important implications for developing better pharmacological and behavioural treatments for ASD, including TMS, new drugs, biomarkers and patient stratification.

Original languageEnglish
Pages (from-to)174-186
Number of pages13
JournalWorld Journal of Biological Psychiatry
Issue number3
StatePublished - 2 Apr 2016


  • Autistic disorder
  • Biomarkers
  • Electroencephalography
  • Transcranial magnetic stimulation
  • Translational medical research


Dive into the research topics of 'Excitatory/inhibitory imbalance in autism spectrum disorders: Implications for interventions and therapeutics'. Together they form a unique fingerprint.

Cite this