Hippocampal network connectivity and activation differentiates post-traumatic stress disorder from generalized anxiety disorder
Open accessAbstract
Anxiety disorders are a diverse group of clinical states. Post-traumatic stress disorder (PTSD) and generalized anxiety disorder (GAD), eg, 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 among 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, whereas 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 magnetic resonance imaging-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 vs different features of two major anxiety disorders, through a translational framework built on animal work and carefully selected clinical disorders.
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With respect to GAD and MDD, resting state fMRI studies clearly implicate disruption in DN regions.
“With respect to GAD and MDD, resting state fMRI studies clearly implicate disruption in DN regions (e.g., Hamilton et al., 2011, 2013; Chen and Etkin, 2013; Andreescu et al., 2014; Wang et al., 2016).”
From Distinct functional connectivities predict clinical response with emotion regulation therapy (2017) · cites this paper as Chen and Etkin, 2013
In “Testing the ‘Disorder-Specific Deficit’ Hypothesis” (page unavailable), the paper reports that GAD patients did not differ from healthy controls in connectivity to the posterior hippocampal default-mode targets; diminished connectivity was specific to PTSD. The study compared PTSD, GAD, and healthy controls, not MDD, so it cannot establish the MDD part of the claim. (LLM, conf=0.88)
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References 72 · Cited by 212
Research works printed but not linked: 4
- Aggleton JP, Wright NF, Vann SD, Saunders RC (2012). Medial temporal lobe projections to the retrosplenial cortex of the macaque monkey. Hippocampus 22: 1883-1900.
- Amaral DG (1987). Memory: anatomical organization of candidate brain regions. In Handbook of Physiology, the Nervous System. Waverly Press: Baltimore, pp 211-294.
- Mesulam M (2000). Principles of Cognitive and Behavioral Neurology. 2nd edn. Oxford University Press: New York.
- Spielberger CD, Gorsuch RL, Lushene RE (1970). Manual for the State-Trait Anxiety Inventory. Consulting Psychologists Press: Palo Alto, CA.
- Authors
- Chen, A. C., & Etkin, A.
- Affiliations
- Stanford University (US)
- VA Palo Alto Health Care System (US)
- Corresponding author
- Chen, Ashley C
- Etkin, Amit
- ORCID
- Etkin, Amit
- Venue
- Neuropsychopharmacology
- Published
- 2013-05-15
- Volume
- 38
- Issue
- 10
- Pages
- 1889-1898
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC3746693
- OpenAlex
- W1979540844
- Cited by
- 212
- References
- 72
- Citations by year
- 2026: 11 · 2025: 7 · 2024: 7 · 2023: 19 · 2022: 11 · 2021: 22 · 2020: 24 · 2019: 26 · 2018: 15 · 2017: 19 · 2016: 18 · 2015: 14 · 2014: 16 · 2013: 3
- FWCI
- 9.32
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (R01MH091860, P30MH089888)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- post-traumatic stress disorder, generalized anxiety disorder, hippocampus, posterior hippocampus, anterior hippocampus, default mode network, resting-state functional connectivity, fear memory, anxiety disorders, neural circuit dysfunction
- MeSH terms
- Adult, Anxiety Disorders, Brain Mapping, Female, Hippocampus, Humans, Limbic System, Male, Neural Pathways, Psychomotor Performance, Stress Disorders, Post-Traumatic, Case-Control Studies, Prefrontal Cortex
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