Reduced fronto-temporal connectivity is associated with frontal gray matter density reduction and neuropsychological deficit in schizophrenia.

OBJECTIVES A "disconnectivity model" of schizophrenia has been proposed, but it is still unclear if white matter abnormalities are associated with gray matter changes and if they may be the anatomic substrate of cognitive impairment, which is a core symptom of the disorder. The first objective was to detect if white matter microstructure alterations in schizophrenia are associated with or independent of gray matter change, using an optimized method for white matter (Tract-Based Spatial Statistics) and gray matter analyses (whole-brain voxel-wise approach). The second objective was to identify the neuropsychological correlates of white matter abnormalities in the schizophrenic group, using a comprehensive neuropsychological battery. METHODS In this case-control study 43 schizophrenic patients and 43 healthy volunteers were consecutively enrolled and matched for age and gender. RESULTS Fractional anisotropy reduction was found in 6 fronto-temporal clusters (corrected p-values <0.05) in schizophrenic group in comparison with healthy volunteers, and 3 clusters showed fractional anisotropy increase (corrected p-values <0.05). Two of the clusters showing reduced fractional anisotropy were associated with reduced gray matter density in neuroanatomically-related regions in schizophrenic subjects (p-values ranging from 0.001 to 0.026). Executive, constructional-praxis, and working memory deficits were significant predictors of fractional anisotropy reduction in 4 clusters in the schizophrenic group (p-values ranging from <0.0001 to 0.0017). CONCLUSIONS Our data support the disconnectivity hypothesis in schizophrenia, enlightening a link between reduced fronto-temporal connectivity and "frontal" cognitive deficits. Reduced gray matter density may be involved primarily in the pathogenesis of some of these disconnected areas.