Fronto-temporal dysfunction in schizophrenia: A selective review.

Abstract

Schizophrenia is conceptualized as a disorder of aberrant neurodevelopment, with evident stigmata such as minor physical anomalies (MPA), neurological soft signs (NSS), and abnormalities of brain structure and function, proposed as disease endophenotypes. We have examined the neurobiology of schizophrenia using neurodevelopmental markers, structural MRI (sMRI), EEG spectral power, and coherence as well as neuropsychological testing in neuroleptic-naïve, recent-onset schizophrenia (NRS) subjects. It has been our focus to link the positive and negative symptom dimensions of schizophrenia with their underlying neural correlates specifically reflecting fronto-temporal circuitry dysfunction. We found that MPAs and NSSs constituted independent neurodevelopmental markers of schizophrenia and would afford greater predictive validity when used as a composite endophenotype. In an exploratory factor analytic study of the dimensionality of psychopathology, we noted that the symptoms segregated into three dimensions, viz., positive, negative, and disorganization, even in NRS subjects. Executive function tests as well as EEG spectral power and coherence studies revealed that the symptom dimensions of schizophrenia could be linked to specific neural correlates. In an attempt to study the relationship between the symptom dimensions and brain structure and function using MRI, we have proposed neuroanatomical definitions with cytoarchitectonic meaning for parcellation of the prefrontal sub-divisions. Using sMRI, we have found specific corpus callosal abnormalities that possibly link the temporo-parietal association cortices with the positive symptom dimension. Recently, we also found evidence for neurodevelopmental deviance in schizophrenia possibly involving the frontal pole (FP)-driven cortical network, in a sMRI study linking FP volume and total brain volume with age in NRS subjects and age-, gender- and education-matched healthy subjects. Overall, our findings highlight the potential significance of linking the homogeneous symptom dimensions of schizophrenia with dysfunctional connectivity in the fronto-temporal region.