Figure 2.
A putative model linking trauma and brainderived neurotrophic factor (BDNF) function to the development of bipolar disorder and post-traumatic stress disorder. Patients may carry genetic risk factors, including BDNF val66met single-nucleotide polymorphism (SNP) variants, BDNF-linked complex polymorphic region (LCPR) allelic variants and other unidentified markers increasing their risk for altered BDNF protein production66,67 and bipolar illness.115,134,147 Exposure to early childhood trauma may induce epigenetic modification in the form of histone and DNA acetylation and methylation, leading to further reductions of BDNF protein production.61 This may trigger the onset of bipolar illness in the form of depressive and manic episodes.101–103 Adulthood trauma may occur, once again interrupting BDNF production.62–64 Reduced BDNF function may interfere with fear extinction leading to the development of post-traumatic stress disorder (PTSD)82–84 and increased emotion dysregulation. This could lead to a worsening course of bipolar illness, in the form of increased mood episodes over time, followed by further reductions in BDNF levels. Abbreviations: D, depressive episodes; M, manic episodes.