Severe chronic stress leads to:
atrophy of apical dendrites in the CA3 region
mature granule cell death in the dentate gyrus (DG) of the hippocampus
due to elevated levels of glucocorticoids
reduced hippocampal volume in PTSD patients is localized to the CA3/DG region of the hippocampus
Rather than a consequence of the traumatic experience, reduced hippocampal volume may be a risk factor for developing PTSD
pathological avoidance symptoms increase with time after a trauma and parallel the trajectory of PTSD
dysfunction of the hippocampus may enhance the rate of avoidance acquisition and the development of persistent avoidant responding, thereby resulting in risk for anxiety disorders and PTSD
a dysfunctional hippocampus enhances the development of persistent avoidant responses.
persistent avoidant responding is set during acquisition due to abnormal learning of the avoidance response, and not specifically due to effects of hippocampal lesions on extinction learning
Depression and anxiety are commonly comorbid (Kessler et al., 2003), and a smaller hippocampus has been associated with both disorders
hippocampal dysfunction due to impaired synaptic plasticity and reduced volume leads to abnormally persistent avoidance learning, which in and of itself is a risk factor to develop anxiety disorders.
One specific process related to the lack of self-regulation suggested to underlie GD is cognitive inflexibility associated with reward learning. More specifically, we refer to a tendency to hold on to behavior that has been profitable before, but no longer leads to gain (Klanker et al., 2013). In patients with GD, this reward-based cognitive inflexibility presumably can be observed as some kind of continuous gambling even in the face of increasing losses.