Journal
AMERICAN JOURNAL OF PSYCHIATRY
Volume 164, Issue 12, Pages 1890-1899Publisher
AMER PSYCHIATRIC PUBLISHING, INC
DOI: 10.1176/appi.ajp.2007.05111903
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Funding
- NIMH NIH HHS [MH 43271, MH 31593, K23 MH068380, MH 40856, R01 MH040856, K23 MH068380-01A2, R01 MH031593, R37 MH031593, MH 68380] Funding Source: Medline
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Objective: Factors underlying progressive brain volume changes in schizophrenia remain poorly understood. The authors investigated whether a gene polymorphism influencing neuroplasticity may contribute to longitudinal brain volume alterations. Method: High-resolution magnetic resonance (MR) images of the whole brain were obtained for 119 patients with recent-onset schizophrenia spectrum disorders. Changes in brain volumes over an average of 3 years were compared between brain-derived neurotrophic factor (BDNF) va166met genotype groupings. Exploratory analyses were conducted to examine relationships between antipsychotic treatment and brain volume changes as well as the effects of BDNF genotype on changes in cognition and symptoms. Results: Significant genotype effects were observed on within-subject changes in volumes of frontal lobe gray matter, lateral ventricles, and sulcal CSF. Met allele carriers had significantly greater reductions in frontal gray matter volume, with reciprocal volume increases in the lateral ventricles and sulcal (especially frontal and temporal) CSF than Val homozygous patients. Independent of BDNF genotype, more antipsychotic exposure between MRI scans correlated with greater volume reductions in frontal gray matter, particularly among patients who were initially treatment naive. There were no statistically significant genotype effects on within-subject changes in cognition or symptoms. Conclusions: BDNFMet variant may be one of several factors affecting progressive brain volume changes in schizophrenia.
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