Likewise, Harrison and Weinberger51 have pointed out that “schizophrenia genes” and their expression may converge on critical neuronal synaptic

and glial populations in crucial brain areas, such as the hippocampus, dorsal thalamus, and dorsolateral prefrontal cortex. These structures are all part of the cortico-striato-pallido-thalamic (CSPT) circuitry. This CSPT circuitry involves complex loops and connections that are Inhibitors,research,lifescience,medical derived from Penney and Young’s56 examination of the neural substrate of motor functions. The finding of distributed neural network abnormalities in the CSPT circuitry was described in psychiatric populations in a definitive manner by Swerdlow and Koob57 and has led to many neurophysiological and “brain connectivity” hypotheses. These hypotheses include Andreason’s concept of cognitive Inhibitors,research,lifescience,medical dysmetria,58 which attempts to “connect the dots” of brain dysfunction in schizophrenia patients,59 and the evolution

of corticocortical coherence measures to assess functional connectivity deficits to probe the multiple cognitive deficits of Inhibitors,research,lifescience,medical schizophrenia patients.60 As Harrison and Weinberger point out, “a way forward is provided by the recent identification of several putative susceptibility genes including neuroregulin, dysdindin, COMT, DISCI, RGS4, GRN3, G72.”51 These authors discuss the evidence for these and other genes as vulnerability vectors along dimensions of their expression profiles and neurobiological roles. While the evidence for genetic abnormalities in these critical genes with their Inhibitors,research,lifescience,medical important integrative functions is attractive, the causative allele or mechanism that results in the development of schizophrenia is unknown. Harrison and Weinberger51 Inhibitors,research,lifescience,medical also point out that COMT may be an exception where

a causative allele may have been identified. Nevertheless, in the area of brain connectivity and synaptic plasticity, they have proposed that the genes cited above may all converge functionally via an signaling pathway influence upon synaptic plasticity and the development and stabilization of functionally important cortical microcircuitry.51 Thus, at the most basic level, these neurodevelopmental genes may oxyclozanide characterize a molecular biological basis for a genetic cytoarchitecture that has the potential to incrementally advance our understanding of schizophrenia. Neurophysiological endophenotypes: gating abnormalities Many neurophysiological endophenotypes have undergone extensive study and analysis (Table I).15-47 These endophenotypic measures include antisaccade oculomotor functioning, smooth pursuit eye movement, P50 suppression, prepulse inhibition (PPI) of the startle response, P300 ERPs, and visual backward masking.