GABA-ergic neurons and the neurobiology of schizophrenia and other psychoses

There are a number of disorders in the Diagnostic and Statistical Manual of Mental Disorders (DSM IV) that are characterised by having psychotic symptoms as the defining feature [17]. The narrowest definition of psychosis is restricted to delusions or prominent hallucinations, with the hallucinations occurring in the absence of insight into their pathological nature, Schizophrenia is the most prevalent form of psychosis, but this may also occur due to other medical conditions (e.g,, Prader-Willi syndrome, epilepsy), in the early post-partum period, at menopause, and as a result of drug use. This article attempts to draw together an underlying causation across the various forms of psychotic disorder and, by integrating this with what is known about the genetics, neuroanatomy and neuropharmacology of the positive symptoms in schizophrenia, produce a broader understanding. At the cellular level, gamma-aminobutyric acid (GABA)-ergic interneurons are a common feature in psychotic states, and are a principal focus for serotonin and dopamine innervations, as well as playing an important role in cortical development. At the systems level, prefrontal and medial temporal cortices are implicated with activity levels out of synchrony in schizophrenics, How these vast areas of disparately functioning cortical networks are "bound" together to provide coherent conscious experiences is again a function of GABA-ergic interneurons. These interneurons have highly divergent inhibitory projections to large numbers of pyramidal neurons and are themselves synchronised by the ascending dopamine and serotonin innervations. (C) 1999 Elsevier Science Inc.