From the evidence in the previous chapter, it is easy to see that adverse psychosocial events may interact with individual susceptibility or resistance to produce symptoms of depression. However, what factors influence the actual manifestation of disease is not often clear. After we review some basic brain communication, in the following sections, we will look at the evidence for the interaction of genetics, epigenetics, and the environment. Of particular relevance are the stress-related psychoneuroimmunological pathways.