The GABAergic system in schizophrenia.
A defect in neurotransmission involving gamma-amino butyric acid (GABA) in schizophrenia was first proposed in the early 1970s. Since that time, a considerable effort has been made to find such a defect in components of the GABAergic system. After a brief introduction focusing on historical perspectives, this paper reviews post-mortem and other biological studies examining the following components of the GABAergic system in schizophrenic subjects: the GABA biosynthetic enzyme, glutamate decarboxylase; free GABA; the GABA transporter; the GABAA, GABAB and benzodiazepine receptors; and the catabolic enzyme GABA transaminase. Additionally, post-mortem studies using morphology or calcium-binding protein to identify GABAergic neurons are also reviewed. Substantial evidence argues for a defect in the GABAergic system of the frontal cortex in schizophrenia which is limited to the parvalbumin-class of GABAergic interneurons.
Columbia University College of Physicians and Surgeons, Department of Psychiatry, New York State Psychiatric Institute, Department of Neuroscience, New York 10032, USA. bb453@columbia.edu
Brian Paul
BP
Blum
J John
JJ
Mann
D000612:4-Aminobutyrate Transaminase / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002452:Cell Count; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006801:Humans; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism; D012559:Schizophrenia / Q000134:cerebrospinal fluid / Q000378:metabolism / Q000503:physiopathology*; D005680:gamma-Aminobutyric Acid / Q000134:cerebrospinal fluid / Q000378:metabolism / Q000502:physiology*
D002135:Calcium-Binding Proteins; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D000612:4-Aminobutyrate Transaminase; D005968:Glutamate Decarboxylase