Schizophrenic disorders: neurodevelopmental and onset vulnerability factors

Structural magnetic resonance imaging (MRI) studies have examined the loci of volume alterations in the brains of schizophrenics with the full-blown syndrome. Our quantitative volumetric MRI techniques show regions with volume reductions include the medial temporal lobe (MTL-amygdala-hippocampus/parahippocampal gyrus) and left-lateralization abnormalities in language-related areas in the gray matter of the posterior superior temporal gyrus (STG, Shenton et al 1992) and inferior parietal lobule (IPL, preliminary data). Many of these regions with strong anatomical interconnectivity show a pattern of high intercorrelations of volume changes in the schizophrenic but not in the control groups. This suggests the possibility of a initial neurodevelopmental insult followed by a “use-dependent” and onset-related further neural damage, which we hypothesize may reflect an excitotoxic process governed by a lessened effectiveness of recurrent inhibition in cortical circuits. Supporting the occurrence of an ongoing process is the presence of a more rapidly increasing latency with age of the P300 evoked potential (an index of many neurotoxic processes) in schizophrenics than in controls (OʹDonnell et al 1995). What are the initial structural changes and what comes at, and after clinical onset? Preliminary data on MRI CSF features from first psychotic episode schizophrenic subjects, compared with controls and subjects with first psychotic episode affective disorder, show enlarged temporal horns, pointing to MTL as an area of initial involvement. Further, very preliminary MRI data from subjects with schizotypal personality disorder, who share the genetic diathesis but not the clinical symptomatology of schizophrenia, show temporal horn enlargement and reduced MTL gray matter. Data to be developed in these groups over the next several months will help determine the adequacy of a model that posits that MTL alterations may constitute much of the neurodevelopmental substrate, with further neocortical alterations occurring in the course of the illness.