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Abstract
Anxiety disorders are a diverse group of clinical states. Post-traumatic stress disorder (PTSD) and generalized anxiety disorder (GAD), for example, share elevated anxiety symptoms, but differ with respect to fear-related memory dysregulation. As the hippocampus is implicated in both general anxiety and fear memory, it may be an important brain locus for mapping the similarities and differences amongst anxiety disorders. Anxiety and fear also functionally associate with different subdivisions of the hippocampus along its longitudinal axis: the human posterior (rodent dorsal) hippocampus is involved in memory, through connectivity with the medial prefrontal-medial parietal default-mode network, while the anterior (rodent ventral) hippocampus is involved in anxiety, through connectivity with limbic-prefrontal circuits. We examined whether differential hippocampal network functioning may help account for similarities and differences in symptoms in PTSD and GAD. Network-sensitive functional MRI-based resting-state intrinsic connectivity methods, along with task-based assessment of posterior hippocampal/default-mode network function were used. As predicted, in healthy subjects resting-state connectivity dissociated between posterior hippocampal connectivity with the default-mode network, and anterior hippocampal connectivity to limbic-prefrontal circuitry. The posterior hippocampus and the associated default-mode network, across both resting-state connectivity and task-based measures, were perturbed in PTSD relative to each of the other groups. By contrast, we found only modest support for similarly blunted anterior hippocampal connectivity across both patient groups. These findings provide new insights into the neural circuit-level dysfunctions that account for similar versus different features of two major anxiety disorders, through a translational framework built on animal work and carefully-selected clinical disorders.Neuropsychopharmacology accepted article preview online, 15 May 2013; doi:10.1038/npp.2013.122.
View details for DOI 10.1038/npp.2013.122
View details for Web of Science ID 000323165500007
View details for PubMedID 23673864