Natural anti-NMDAR1 autoantibodies are associated with lower risk for depression and PTSD symptoms after traumatic brain injury.

Authors

Melonie N Vaughn, Dean T Acheson, Susan B Powell, Jenna M DeWit, Kate A Yurgil, Caroline M Nievergelt, Dewleen Baker, Victoria B Risbrough, Xianjin Zhou

Published in

Molecular psychiatry. Sep 08, 2026. Epub Sep 08, 2026.

Abstract

Exposure to a traumatic brain injury (TBI) increases risk of developing psychiatric symptoms including depression, anxiety, and post‑traumatic stress disorder (PTSD). However, biological risk and resiliency factors that help explain the heterogeneity in outcomes are limited. Although ~10% of the population was reported to carry natural autoantibodies to the NMDA receptor, it remains unknown whether carrying anti-NMDAR1 autoantibodies modifies risk for psychiatric outcomes after TBI. Plasma anti-NMDAR1 autoantibody levels were quantified in male active-duty service members before a combat deployment. Outcome measures included post-deployment PTSD (Clinician Administered PTSD Scale-IV), depression (Beck Depression Inventory-2) and anxiety symptoms (Beck Anxiety Inventory). Lifetime TBI was associated with increased predicted depression, PTSD and anxiety symptoms after a combat deployment (N = 606 with TBI, N = 419 without TBI). Higher pre-deployment plasma levels of natural anti-NMDAR1 autoantibodies were modestly but significantly associated with lower predicted post-deployment depression (p = 0.0008) and PTSD symptoms (p = 0.0075), but not anxiety, among individuals with TBI. Within the TBI group, high autoantibody group membership (top quartile) lowered predicted post-deployment CAPS-IV and BDI-II scores by 22% ( ~ 4 points) and 25% ( ~ 2 points), respectively and overall prevalence of psychotropic medication use (p = 0.006). High autoantibody group membership predicted lower odds of reporting post‑deployment moderate-severe depression symptoms (BDI-II > 19) (OR = 0.14, 95% CI 0.01-0.69, p = 0.014). Natural anti-NMDAR1 autoantibodies may be a "resiliency" factor for TBI-associated risk for depression and PTSD symptoms, suggesting potential neuroprotective effects. Future studies should determine if anti-NMDAR1 autoantibodies reach the CNS to suppress glutamate excitotoxicity associated with TBI and if these results generalize across different populations.

PMID:
42711406
Bibliographic data and abstract were imported from PubMed on 09 Sep 2026.

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