Evidence for a compromised dorsolateral prefrontal cortical parallel circuit in schizophrenia

Evidence is reviewed that one of the cognitive-affective parallel circuits in the brain, the dorsolateral prefrontal circuit, is compromised at the le vel of anatomical, neuropathological and transmitter-related molecules in a subgroup of schizophrenic patients. The dorsolateral prefrontal cortex (DL PFC) comprises a key structure in this circuit. Data supporting a compromis ed DLPFC includes cognitive deficits, decreased regional metabolism and blo od flow activation; disruption of cortical subplate activity (inferred from maldistribution of neurons from the cortical subplate which are required f or the orderly neuronal migration during the second trimester and for conne ctivity of the thalamocortical neurons): decrease in major components of th e conical inhibitory neurotransmitter system; and alterations in the molecu les critical for NMDA-receptor mediated neural transmission. Thus a great d eal of evidence accumulated over the last decade has definitively implicate d the dorsolateral prefrontal cortex in the pathophysiology of schizophreni a. Emerging data also confirms neuropathology in the mediodorsal nucleus of the thalamus that projects to the DLPFC. There is currently a consensus th at schizophrenia involves epigenetic factors interacting with genetic infor mation in the cells to produce abnormal molecules which when they are assoc iated with abnormal circuits such as the DLPFC, may result in abnormal beha vior. Thus, abnormal conical connections and or altered neurotransmitter re lated molecules in the DLPFC could explain some of the prominent frontal co gnitive disruptions seen in schizophrenia. (C) 2000 Elsevier Science B.V. A il rights reserved.