Prefrontal cortex, negative symptoms, and schizophrenia: an MRI study

Abstract

The present study measured prefrontal cortical gray and white matter volume in chronic, male schizophrenic subjects who were characterized by a higher proportion of mixed or negative symptoms than previous patients that we have evaluated. Seventeen chronic male schizophrenic subjects and 17 male control subjects were matched on age and handedness. Regions of interest (ROI) were measured using high-resolution magnetic resonance (MR) acquisitions consisting of contiguous 1.5-mm slices of the entire brain. No significant differences were found between schizophrenic and control subjects in mean values for prefrontal gray matter volume in either hemisphere. However, right prefrontal white matter was significantly reduced in the schizophrenic group. In addition, right prefrontal gray matter volume was significantly correlated with right hippocampal volume in the schizophrenic, but not in the control group. Furthermore, an analysis in which the current data were combined with those from a previous study showed that schizophrenic subjects with high negative symptom scores had significantly smaller bilateral white matter volumes than those with low negative symptom scores. White matter was significantly reduced in the right hemisphere in this group of schizophrenic subjects. Prefrontal volumes were also associated with negative symptom severity and with volumes of medial-temporal lobe regions - two results that were also found previously in schizophrenic subjects with mostly positive symptoms. These results underscore the importance of temporal-prefrontal pathways in the symptomatology of schizophrenia, and they suggest an association between prefrontal abnormalities and negative symptoms.

Fig. 1

The most posterior slice in which prefrontal gray matter was measured in relationship to the ventricles and the white matter. Panel 1A: left lateral view of the most posterior slice in which gray matter was measured, shown in relationship to the ventricles with segmented prefrontal gray matter shown in green overlay on the MRI slice. Panel 1B: left lateral view of a three-dimensional reconstruction of the prefrontal white matter in relationship to the ventricles and to the slice shown in Panels A and B.

Fig. 2

Relative volumes of average left and right (combined) prefrontal white matter for schizophrenic subjects with high and low SANS scores. The subject data shown are from a combination of the current study and our previous study of prefrontal volume in schizophrenia. The low and high SANS groups were determined by ranking all schizophrenic subjects and doing a median split to obtain two groups.