Focal gray matter density changes in schizophrenia

Hilleke E. Hulshoff Pol*, Hugo G. Schnack, René C.W. Mandl, Neeltje E.M. Van Haren, Hilde Koning, D. Louis Collins, Alan C. Evans, René S. Kahn

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

230 Citations (Scopus)


Background: The view that schizophrenia is a brain disease particularly involving decrements in gray matter is supported by findings from many imaging studies. However, it is unknown whether the (progressive) loss of tissue affects the brain globally or whether tissue loss is more prominent in some areas than in others. Methods: Magnetic resonance whole brain images were acquired from 159 patients with schizophrenia or a schizophreniform disorder and 158 healthy subjects across a 55-year age span. Gray matter density maps were made and analyzed using voxel-based morphometry. Results: Compared with healthy subjects, decreases in gray matter density were found in the left amygdala; left hippocampus; right supramarginal gyrus; thalamus; (orbito) frontal, (superior) temporal, occipitotemporal, precuneate, posterior cingulate, and insular cortices bilaterally in patients with schizophrenia or schizophreniform disorder. Compared with healthy subjects, increases in gray matter density were exclusively found in the right caudate and globus pallidus in patients with schizophrenia or schizophreniform disorder. A group-by-age interaction for density was found in the left amygdala, owing to a negative regression slope of gray matter density on age in the left amygdala in patients compared with healthy subjects. Conclusions: Gray matter density is decreased in distinct focal areas in the brains of patients with schizophrenia or schizophreniform disorder. The decreased density in the left amygdala is more pronounced in older patients with schizophrenia.

Original languageEnglish
Pages (from-to)1118-1125
Number of pages8
JournalArchives of General Psychiatry
Issue number12
Publication statusPublished - 2001
Externally publishedYes


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