Plasma brain-derived neurotrophic factor and prefrontal white matter integrity in late-onset depression and normal aging Dalby RB, Elfving B, Poulsen PHP, Foldager L, Frandsen J, Videbech P, Rosenberg R. Plasma brain-derived neurotrophic factor and prefrontal white matter integrity in late-onset depression and normal aging. Objective: To explore the relationship between brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF), cerebral deep white matter lesions (DWMLs), and measures of white matter integrity in patients with late-onset depression, with respect to vascular risk factors. Method: We examined 22 patients with late-onset depression and 22 matched controls. Quantification of plasma BDNF and VEGF levels were performed with enzyme-linked immunosorbent assay (ELISA) kits. Measures of white matter integrity comprised apparent diffusion coefficient (ADC) and fractional anisotropy (FA), obtained by diffusion tensor imaging (DTI). Effects of DWMLs, FA, ADC, and vascular risk factors on BDNF and VEGF were assessed using multiple linear regression. Results: The BDNF and VEGF levels did not differ significantly between groups. With pooled data for patients and controls, the BDNF level was positively associated with both number (t = 2.14, P = 0.039) and volume (t = 2.04, P = 0.048) of prefrontal DWMLs and negatively associated with FA in prefrontal normal-appearing white matter (t = 2.40, P = 0.02), adjusted for age and gender. Smoking and hypercholesterolemia was positively associated with the BDNF (t = 2.36, P = 0.023) and VEGF levels (t = 2.28, P = 0.028), respectively. Conclusion: Our results suggest a role for BDNF in the complex pathophysiologic mechanisms underlying DWMLs in both normal aging and late-onset depression. R. B. Dalby 1,2 , B. Elfving 1 , P. H. P. Poulsen 1 , L. Foldager 1,3 , J. Frandsen 4 , P. Videbech 1 , R. Rosenberg 1 1 Centre for Psychiatric Research, Aarhus University Hospital, Risskov, Denmark, 2 MINDLab, Aarhus University, Aarhus, Denmark, 3 Bioinformatics Research Centre, Aarhus University, Aarhus, Denmark and 4 Center of Functionally Integrative Neuroscience (CFIN), Aarhus University Hospital, Aarhus, Denmark Key words: BDNF; VEGF; depression; diffusion tensor imaging; white matter lesions Dr. Rikke B. Dalby, Centre for Psychiatric Research, Skovagervej 2, DK-8240 Risskov, Denmark. E-mail: rbdalby@dadlnet.dk Accepted for publication December 20, 2012 Significant outcomes • This study demonstrates a positive association between plasma brain-derived neurotrophic factor (BDNF) level and cerebral white matter lesion load in the prefrontal region and a negative associa- tion between plasma BDNF level and the integrity of prefrontal normal-appearing white matter. • These associations suggest an important role for BDNF in the repair mechanisms of neural damage due to deep white matter lesions (DWMLs), reflecting underlying small vessel disease primarily affect- ing prefrontal regions. Limitations • The study approach is exploratory with use of multiple testing. • The negative association between brain-derived neurotrophic factor (BDNF) and fractional aniso- tropy (FA) in the prefrontal normal-appearing white matter did not survive the Bonferroni correction for multiple comparisons. • The study sample is relatively small. 387 Acta Psychiatr Scand 2013: 128: 387–396 © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd All rights reserved DOI: 10.1111/acps.12085 ACTA PSYCHIATRICA SCANDINAVICA