Abstract
Background: The hippocampus plays an important role in the pathophysiology of posttraumatic stress disorder (PTSD) and its prognosis. Accumulating findings suggest that individuals with larger pretreatment hippocampal volume are more likely to benefit from PTSD treatment, but the mechanism underlying this effect is unknown. We investigated whether further increase in hippocampal volume during treatment explains the better prognosis of individuals with greater pretreatment hippocampal volume. Methods: We collected structural magnetic resonance imagesfrom patients with PTSD before and after treatment. We examined whether larger hippocampal volume moderates the effect of increased hippocampal volume during treatment on symptom reduction. Given the relatively small sample sizes of treatment studies with pre- and posttreatment magnetic resonance imaging, we focused on effect sizes and sought to replicate findings in an external sample. We tested our hypothesis in study 1 (N = 38; prolonged exposure therapy) and then tested whether the results could be externally replicated in study 2 (N = 20; ketamine infusion followed by exposure therapy). Results: Findings from study 1 revealed that increased right hippocampal volume during treatment was associated with greater PTSD symptom reduction only in patients with greater pretreatment right hippocampal volume (p = .03; η2 = 0.13, a large effect). Findings were partially replicated in study 2 for depressive symptoms (p = .034; η2 = 0.25, a very large effect) and for PTSD symptoms (p = .15; η2 = 0.15, a large effect). Conclusions: Elucidating increased hippocampal volume as one of the neural mechanisms predictive of therapeutic outcome for individuals with larger pretreatment hippocampal volume may help identify clinical targets for this subgroup.
Original language | English |
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Pages (from-to) | 867-874 |
Number of pages | 8 |
Journal | Biological Psychiatry Global Open Science |
Volume | 3 |
Issue number | 4 |
DOIs | |
State | Published - Oct 2023 |
Bibliographical note
Funding Information:This work was supported by the National Institute of Mental Health (Grant Nos. R01MH105355 and R01MH072833 [to YN]); by an Independent Investigator Grant from the Brain and Behavior Research Foundation (to IH-R); by the Clinical Neurosciences Division of the National Center for PTSD (to IH-R); a donation from the American Brain Society (to IH-R); and by the Yale Center for Clinical Investigation supported by a Clinical and Translational Science Awards grant from the National Center for Advancing Translational Sciences, a component of the National Institutes of Health (to IH-R). The authors report no biomedical financial interests or potential conflicts of interest. ClinicalTrials.gov: Brain Circuitry and Psychosocial Predictors of PTSD; https://clinicaltrials.gov/ct2/show/NCT01576510; NCT01576510. ClinicalTrials.gov: Combining Neurobiology and New Learning: Ketamine and Prolonged Exposure: A Potential Rapid Treatment for Post Traumatic Stress Disorder (PTSD); https://clinicaltrials.gov/ct2/show/NCT02727998; NCT02727998.
Funding Information:
This work was supported by the National Institute of Mental Health (Grant Nos. R01MH105355 and R01MH072833 [to YN]); by an Independent Investigator Grant from the Brain and Behavior Research Foundation (to IH-R); by the Clinical Neurosciences Division of the National Center for PTSD (to IH-R); a donation from the American Brain Society (to IH-R); and by the Yale Center for Clinical Investigation supported by a Clinical and Translational Science Awards grant from the National Center for Advancing Translational Sciences , a component of the National Institutes of Health (to IH-R).
Publisher Copyright:
© 2023 The Authors
Keywords
- Hippocampal volume
- Hippocampus
- Ketamine
- Neural mechanisms
- PTSD
- Prolonged exposure therapy
ASJC Scopus subject areas
- Clinical Neurology
- Psychiatry and Mental health
- Biological Psychiatry
- Psychiatric Mental Health