Pathways of risk for depression: BDNFVal66Met, stress and emotional brain systems

  • Prof Leanne Williams, Westmead Millennium Institute and University of Sydney, Australia
  • Dr Justine Gatt, Westmead Millennium Institute and University of Sydney, Australia
  • Prof Peter Schofield, Prince of Wales Medical Research Institute, Australia
  • Prof Charles Nemeroff, Emory University, United States
  • Dr Evian Gordon, Brain Resource; Westmead Millennium Institute and University of Sydney, Australia

    • For Symposium: Chair, Maarten van den Buuse

    The BDNF Val66Met polymorphism has been implicated in depression and anxiety, and associated cognitive features. It may contribute to risk for these conditions via an impact on emotional brain and arousal systems. This study was undertaken within the framework of the INTEGRATE Model (1). We examined the interaction of BDNF Val66Met and early life stress (ELS) in 374 European volunteers from the Brain Resource International Database, who completed symptom, cognitive, autonomic and MRI (n=89 subset) assessments (2). The interaction of BDNF Met status and ELS predicted lower hippocampal and lateral frontal grey matter (p<.001) and higher depression (p=.005). Higher depression in this group was associated with poorer working memory and slowed response speed (p<.005). The BDNF Met-ELS interaction also predicted emotional instability and higher depression and anxiety via elevations in heart rate (p<.001). In contrast, the BDNF V/V-ELS interaction predicted higher amygdala and medial frontal grey matter (p<.005) and in turn, heart rate variability (p=.026) and higher anxiety, linked to impulsivity. These effects were not evident for the 5HTT-LPR polymorphism. BDNFVal66Met variants may contribute to partially differentiated gene-brain pathways to depression and anxiety, even in a non-clinical sample.

    1. Williams LM et al. (2008). The INTEGRATE Model of Emotion, Thinking and Self Regulation: An application to the ‘paradox of aging’. J Integrative Neuroscience 7, 367-404.
    2. Gatt JM et al. (in revision). Interactions between BDNF Val66Met polymorphism and early life stress predict brain and arousal pathways to syndromal depression and anxiety. Mol. Psychiatry