Macro- and Microscale Stress–Associated Alterations in Brain Structure: Translational Link With Depression

Major depressive disorder (MDD) is a stress-related disorder associated with many cytoarchitectural and neurochemical changes. However, the majority of these changes cannot be reliably detected in the living brain. The examination of animal stress models and postmortem human brain tissue has significantly contributed to our understanding of the pathophysiology of MDD. Ronald Duman's work in humans and in rodent models was critical to the investigation of the contribution of synaptic deficits to MDD and chronic stress pathology, their role in the development and expression of depressive-like behavior, and reversal by novel drugs. Here, we review evidence from magnetic resonance imaging in humans and animals that suggests that corticolimbic alterations are associated with depression symptomatology. We also discuss evidence of cytoarchitectural alterations affecting neurons, astroglia, and synapses in MDD and highlight how similar changes are described in rodent chronic stress models and are linked to the emotion-related behavioral deficits. Finally, we report on the latest approaches developed to measure the synaptic and astroglial alterations in vivo, using positron emission tomography, and how it can inform on the contribution of MDD-associated cytoarchitectural alterations to the symptomatology and the treatment of stress-related disorders.