Excitation-inhibition balance as a framework for investigating mechanisms in neuropsychiatric disorders

Mol Psychiatry. 2019 Sep;24(9):1248-1257. doi: 10.1038/s41380-019-0426-0. Epub 2019 May 14.


In 2003 Rubenstein and Merzenich hypothesized that some forms of Autism (ASD) might be caused by a reduction in signal-to-noise in key neural circuits, which could be the result of changes in excitatory-inhibitory (E-I) balance. Here, we have clarified the concept of E-I balance, and updated the original hypothesis in light of the field's increasingly sophisticated understanding of neuronal circuits. We discuss how specific developmental mechanisms, which reduce inhibition, affect cortical and hippocampal functions. After describing how mutations of some ASD genes disrupt inhibition in mice, we close by suggesting that E-I balance represents an organizing framework for understanding findings related to pathophysiology and for identifying appropriate treatments.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autism Spectrum Disorder / genetics*
  • Autism Spectrum Disorder / physiopathology*
  • Brain / physiopathology
  • Disease Models, Animal
  • Hippocampus / physiopathology
  • Humans
  • Inhibition, Psychological
  • Mental Disorders / physiopathology
  • Mice
  • Nerve Net / physiology*
  • Neurons / physiology