Changes in gyrification over 4 years in bipolar disorder and their association with the brain-derived neurotrophic factor valine(66) methionine variant

• Published in: Biological psychiatry (1969) 2009-08, Vol.66 (3), p.293-297
• Main Authors: Mirakhur, Ajay, Moorhead, T William J, Stanfield, Andrew C, McKirdy, James, Sussmann, Jessika E D, Hall, Jeremy, Lawrie, Stephen M, Johnstone, Eve C, McIntosh, Andrew M
• Format: Article
• Language: English
• Subjects: Adult; Analysis of Variance; Automatic Data Processing - methods; Bipolar Disorder - genetics; Bipolar Disorder - pathology; Brain-Derived Neurotrophic Factor - genetics; Disease Progression; Female; Gene Frequency; Genotype; Humans; Longitudinal Studies; Magnetic Resonance Imaging - methods; Male; Methionine - genetics; Middle Aged; Neuropsychological Tests; Polymorphism, Single Nucleotide - genetics; Prefrontal Cortex - pathology; Valine - genetics
• ISSN: 1873-2402
• DOI: 10.1016/j.biopsych.2008.12.006

Evidence suggests that structural brain changes occur over time in bipolar disorder but few studies have examined this longitudinally. Additional work implicates brain-derived neurotrophic factor (BDNF) valine (val)(66)methionine (met) variant in these changes. The present study examined longitudinal trends in prefrontal gyrification index (GI) in bipolar disorder and the effect of BDNF genotype. Eighteen patients with bipolar I disorder and 18 control subjects underwent magnetic resonance imaging at study entry and after 4 years. Prefrontal GI was computed as the ratio of folded inner contour to exposed outer contour. Ventral and dorsal GI decreased significantly with time in both cohorts; the rate did not differ for bipolar patients. Within the bipolar cohort, individuals with one or more BDNF met alleles showed greater losses in GI, an effect that correlated with gray matter loss in the left hemisphere. Gyrification index may be sensitive to atrophy, as well as being a neurodevelopmental measure. While the loss of prefrontal gyrification over time is not accelerated in bipolar disorder, a greater rate of loss is associated with the possession of one or more BDNF met alleles.