A predicted cortical serotonergic/cholinergic/GABAergic interface as a site of pathology in schizophrenia.
1. The pathological process that precipitates schizophrenia has yet to be identified. However, many lines of evidence suggest that a change in the functioning of the frontal cortex is an important abnormality that underlies schizophrenia. 2. Studies in Brodmann's area 9, obtained post-mortem, have shown changes in 5-hydroxytryptamine 5-HT2A, muscarinic M1 and GABA(A) receptors in tissue from subjects with schizophrenia. 3. Animal studies suggest a site in the cortex where there would be an interaction between serotonergic and cholinergic innervation and that this interaction would involve the 5-HT2A and the M1 receptor. This site, in turn, would be a potent modulator of GABA activity and, hence, levels of GABA(A) receptors. 4. From combining these data, a theoretical site is proposed that, if proven to exist in human cortex, is likely to be central to the pathology of that illness.
Dean
B
B
The Rebecca L Cooper Research Laboratories, The Mental Health Research Institute of Victoria, Parkville, Australia. B.Dean@papyrus.mhri.edu.au
D005625:Frontal Lobe / Q000378:metabolism*; D006801:Humans; D007650:Ketanserin / Q000378:metabolism; D008959:Models, Neurological; D010890:Pirenzepine / Q000378:metabolism; D043643:Receptor, Muscarinic M1; D011963:Receptors, GABA-A / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism*; D044263:Receptors, Serotonin, 5-HT1; D012559:Schizophrenia / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000378:metabolism
D043643:Receptor, Muscarinic M1; D011963:Receptors, GABA-A; D011976:Receptors, Muscarinic; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D010890:Pirenzepine; D007650:Ketanserin