The panic disorder (PD) literature provides evidence for both physiologic rigidity and instability as pathognomonic features of this disorder. This ambiguity may be a result of viewing PD at differential levels of temporal analysis. We assessed cardiac variability across three levels of temporal scale in PD patients, post-traumatic stress disorder (PTSD) patients, and healthy controls. Sixteen healthy controls, 14 PD patients, 23 PTSD patients, and 16 PTSD + PD patients presented for a polysomnogram. Differences were assessed in respiratory sinus arrhythmia (RSA), autoregressive stability of heart rate (HR), and the number of nonspecific accelerations in HR over the night. No differences in RSA were found between groups; however, PD patients exhibited significantly lower autoregressive HR stability, and all patients had significantly more HR accelerations than controls. These data reinforce prior findings demonstrating physiologic instability in PD and indicate that prior equivocalities regarding physiologic variability in PD may be due to limited temporal scaling of measurements.

Recent findings suggest the formation of myelin in the central nervous system by oligodendrocytes is a continuous process that can be modified with experience. For example, a recent study showed that immobilization stress increased oligodendrogensis in the dentate gyrus of adult rat hippocampus. Because changes in myelination represents an adaptive form of brain plasticity that has a greater reach in the adult brain than other forms of plasticity (e.g., neurogenesis), the objective of this "proof of concept" study was to examine whether there are differences in myelination in the hippocampi of humans with and without post-traumatic stress disorder (PTSD). We used the ratio of T1-weighted/T2-weighted magnetic resonance image (MRI) intensity to estimate the degree of hippocampal myelination in 19 male veterans with PTSD and 19 matched trauma-exposed male veterans without PTSD (mean age: 43 ± 12 years). We found that veterans with PTSD had significantly more hippocampal myelin than trauma-exposed controls. There was also found a positive correlation between estimates of hippocampal myelination and PTSD and depressive symptom severity. To our knowledge, this is the first study to examine hippocampal myelination in humans with PTSD. These results provide preliminary evidence for stress-induced hippocampal myelin formation as a potential mechanism underlying the brain abnormalities associated with vulnerability to stress.

Individual reactions to traumatic stress vary dramatically, yet the biological basis of this variation remains poorly understood. Recent studies demonstrate the surprising plasticity of oligodendrocytes and myelin with stress and experience, providing a potential mechanism by which trauma induces aberrant structural and functional changes in the adult brain. In this study, we utilized a translational approach to test the hypothesis that gray matter oligodendrocytes contribute to traumatic-stress-induced behavioral variation in both rats and humans. We exposed adult, male rats to a single, severe stressor and used a multimodal approach to characterize avoidance, startle, and fear-learning behavior, as well as oligodendrocyte and myelin basic protein (MBP) content in multiple brain areas. We found that oligodendrocyte cell density and MBP were correlated with behavioral outcomes in a region-specific manner. Specifically, stress-induced avoidance positively correlated with hippocampal dentate gyrus oligodendrocytes and MBP. Viral overexpression of the oligodendrogenic factor Olig1 in the dentate gyrus was sufficient to induce an anxiety-like behavioral phenotype. In contrast, contextual fear learning positively correlated with MBP in the amygdala and spatial-processing regions of the hippocampus. In a group of trauma-exposed US veterans, T1-/T2-weighted magnetic resonance imaging estimates of hippocampal and amygdala myelin associated with symptom profiles in a region-specific manner that mirrored the findings in rats. These results demonstrate a species-independent relationship between region-specific, gray matter oligodendrocytes and differential behavioral phenotypes following traumatic stress exposure. This study suggests a novel mechanism for brain plasticity that underlies individual variance in sensitivity to traumatic stress.