Emerging principles of altered neural circuitry in schizophrenia

This paper presents an overview of recent microscopic studies that have sou ght to define how limbic circuitry may be altered in postmortem schizophren ic brain, The discussion is organized around several basic questions regard ing the manner in which interconnections within and between the anterior ci ngulate cortex and hippocampal formation and involving the glutamate, GABA and dopamine systems may contribute to the pathophysiology of this disorder . The answers to these questions are used to derive several conclusions reg arding circuitry changes in schizophrenia: 1) Schizophrenia is not a 'typic al' degenerative disorder, but rather it is one in which excitotoxicity may contribute to neuronal pathology, whether or not cell death occurs; 2) Thr ee or more neurotransmitter systems may be simultaneously altered within a single microcircuit; 3) Each transmitter system may show circuitry changes in more than one region, but such changes may vary on a region-by-region ba sis; 4) The pathophysiology of schizophrenia may involve 'mis-wirings' in i ntrinsic circuits (microcircuitry) within a given region, but significant c hanges are probably also present at the level of interconnections between t wo or more regions within a network (macrocircuitry); 5) While some microsc opic findings appear to be selectively present in schizophrenia and be rela ted to a susceptibility gene for this disorder, others may also be present in patients with bipolar disorder; 6) Although some of the circuitry change s seen in schizophrenia and bipolar disorder seem to be associated with neu roleptic exposure, most are not and may reflect the influence of non-specif ic environmental factors such as pre- and/or postnatal stress; 7) Normal po stnatal changes at the level of both macro- and microcircuitry within the l imbic system may serve as 'triggers' for the onset of schizophrenia during adolescence. Taken together, these emerging principles can provide a framew ork for future postmortem studies of schizophrenic brain. (C) 2000 Elsevier Science B.V. All rights reserved.