Alterations of central GABAergic activity in neurologic and psychiatric disorders: evaluation through measurements of GABA and GAD activity in cerebrospinal fluid.

Abstract

Glutamic acid decarboxylase (GAD) is generally thought to be the primary catalyst mediating the formation of γ-aminobutyric acid (GABA), which in turn is thought to be the main inhibitory neurotransmitter in the central nervous system (CNS) (1). For this reason GAD activity in CNS tissue has been widely investigated because of the possibilities that it may serve a role in the regulation of central GABAergic activity or that it may provide a reflection of CNS GABAergic alterations associated with certain neurologic or psychiatric disorders. Efforts to elucidate the involvement of GAD alterations in the pathology of CNS disorders have benefitted from studies of animal models and human autopsy tissue (e.g., 2–8). However, in many instances it has not been possible to develop entirely suitable animal models. The diseased human would be the only perfect model for these disorders except, of course, human brain tissue can seldom be studied except at autopsy. Thus, especially in clinical studies, variables are difficult to control and great care must be exercised in extrapolating data to the living human condition.