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.