Integrating the Stress Systems and Neuroimaging in Depression
Abstract This chapter summarizes the associations between brain systems measured with imaging and biological markers of stress in major depressive disorder (MDD) Within the stress system, hippocampal volumes and altered brain function are associated with hypothalamic pituitary adrenal (HPA) axis dysregulation. There is also evidence that inflammatory markers that are associated with the stress system and HPA axis dysfunction are also associated with changes in brain structure and function. Changes in the neurotrophic and the neurotransmitter systems such as the serotonergic system have an impact on brain development, and associations between these systems and functional and structural brain changes in depression have been described. It seems very likely that a model integrating childhood maltreatment, HPA axis abnormalities, decreases in neurotrophic factors, and alterations in neurotransmission and inflammatory states, and moderated by genetics needs to be established to provide a cohesive explanation of all the findings. When one of these integrated systems gets altered, the whole functional balance is disturbed, probably resulting in psychiatric syndromes like depression. The hope would be that through disentangling these system changes, different subtypes of depression will be defined based on neurobiological pathways. Thus, a diagnosis might be based on pathophysiological changes rather than behavioral assessments.