Progressive deformation of deep brain nuclei and hippocampal-amygdala formation in schizophrenia.
BACKGROUND
Progressive decreases in cortical gray matter volume have been reported in schizophrenia. However, studies of progressive change in deep brain nuclei and hippocampal-amygdala formation have not yielded consistent findings.


METHODS
Two high-resolution, T1-weighted magnetic resonance images were collected 2 years apart in 56 schizophrenia and 62 control subjects. Large-deformation high-dimensional brain mapping was used to generate surfaces for deep brain nuclei and hippocampal-amygdala formation at baseline and follow-up. Repeated-measures analysis of variance was used to test for longitudinal changes in volume and shape.


RESULTS
The pattern of progressive changes in the deep brain nuclei and hippocampal-amygdala formation in schizophrenia and control subjects was variable. Of the structures that receive direct projections from the cortex, the thalamus, caudate nucleus, nucleus accumbens, and hippocampus showed changes specific to subjects with schizophrenia, and changes in the amygdala and putamen were similar in both groups. Although different at baseline, no progressive change was observed in the globus pallidus, which does not receive direct projections from the cortex.


CONCLUSIONS
These findings suggest that the disease process of schizophrenia is associated with progressive effects on brain structure and that brain structures that receive direct, excitatory connections from the cortex may be more likely to show progressive changes, compared with brain structures that receive indirect, inhibitory connections from the cortex. These findings are also somewhat consistent with the hypothesis that overactivity of excitatory pathways in the brain may contribute to the neural degeneration that occurs in at least a subgroup of individuals with schizophrenia.
Wang
Lei
L
Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA. leiwang1@northwestern.edu
Mamah
Daniel
D
Harms
Michael P
MP
Karnik
Meghana
M
Price
Joseph L
JL
Gado
Mokhtar H
MH
Thompson
Paul A
PA
Barch
Deanna M
DM
Miller
Michael I
MI
Csernansky
John G
JG
D000328:Adult; D000679:Amygdala / Q000473:pathology; D000704:Analysis of Variance; D014150:Antipsychotic Agents / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000473:pathology*; D001931:Brain Mapping; D002421:Caudate Nucleus / Q000187:drug effects / Q000473:pathology; D003072:Cognition Disorders / Q000209:etiology / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D012559:Schizophrenia / Q000473:pathology* / Q000503:physiopathology*; D055815:Young Adult
D014150:Antipsychotic Agents