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Trends Neurosci. 2007 Oct;30(10):497-503. Epub 2007 Sep 6.

Over-inhibition: a model for developmental intellectual disability.

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Department of Psychiatry and Behavioral Sciences, Nancy Pritzker Laboratory, Stanford University, 1201 Welch Rd, Palo Alto, CA 94304-5485, USA.


Developmental intellectual disability (DID) is a daunting societal problem. Although tremendous progress has been made in defining the genetic causes of DID, therapeutic strategies remain limited. In particular, there is a marked absence of a unified approach to treating cognitive impairments associated with DID. Here, we suggest that the brain in many DID-related disorders is subject to a basic imbalance in neuronal activity, with an increased contribution of inhibition to neural circuits. This over-inhibition, in turn, is predicted to lead to deficits in synaptic plasticity and learning and memory. We further discuss possibilities for pharmacological intervention in DID, focusing on the concept of drug-induced 'therapeutic neuroadaptation' as a means of stably enhancing constitutive circuit excitability and cognition over time.

[Indexed for MEDLINE]

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