“ If we can understand how these antibodies work, it may open a new path toward identifying who is most at risk after a TBI, and eventually, toward new ways to intervene.”
Issue 35.4 FALL 2026
25 % lower depression symptom scores and 22 % lower PTSD symptom scores after deployment than those with lower levels.
• These participants were also significantly less likely to report moderate-to-severe depression and they used fewer psychiatric medications after returning from deployment.
• These antibodies were detectable in blood for more than one year, suggesting that having high levels of these antibodies could be a relatively long-term trait.
• No association was found between anti- NMDAR1 levels and anxiety, suggesting these antibodies are associated with specific kinds of psychiatric symptoms.
The analysis was part of the Marine Resiliency Study II, a long-term research project investigating the factors that contribute to heightened risk for— or resilience to— PTSD.
“ We were excited to find that a naturally-occurring immune marker could act almost like a built-in protective factor against some of the most disabling consequences of brain injury,” said co-senior author Victoria B. Risbrough, PhD, professor and vice chair of academic affairs in the Department of Psychiatry at UC San Diego School of Medicine and VA Research Career Scientist at VA San Diego Healthcare System.“ If we can understand how these antibodies work, it may open a new path toward identifying who is most at risk after a TBI, and eventually, toward new ways to intervene.”
One hypothesis for the antibody’ s protective effect is that natural anti-NMDAR1 antibodies found in Marines are of a type called IgM, which are too large to fit into synapses— the tiny gaps between brain cells where chemical signals are transmitted. Instead, this version may only latch on to receptors outside of that gap. Because these outer receptors are primary drivers of brain damage after a TBI, being blocked by IgM anti-NMDAR1 may shield the brain from further injury.
In a previous study, the research team tried to mimic psychiatric symptoms of human anti- NMDAR encephalitis in mice. They found that the mice carrying anti-NMDAR1 antibodies in their blood exhibited impaired cognitive function. However, their antibodies were of a much smaller“ IgG” version than the naturally-occurring IgM antibodies found in Marines— small enough, in fact, to fit into the synaptic gaps. There is evidence that the smaller IgG version of anti-NMDAR1 may cause memory deficits in humans.
“ We suspected that size difference determines whether an antibody reaches the receptors involved in brain injury versus the ones needed for everyday brain function,” said co-senior author Xianjin Zhou, associate professor of psychiatry at UC San Diego School of Medicine and faculty member at VA Mental Illness Research and Clinical Center.“ When we tested that idea directly in mice, it held up: the smaller IgG antibodies impaired memory, while the larger IgM antibodies appeared to protect it.”
Ketamine, an FDA-approved treatment for depression and PTSD, is thought to work by blocking the same type of receptor, but unlike ketamine’ s short-lived effects, naturally-occurring anti-NMDAR1 appears to persist in the blood for a year or longer.
However, the authors caution that these findings are correlational, and more research needs to be done to determine if natural anti- NMDAR1 antibodies truly play a protective role following TBI. g
“ If we can understand how these antibodies work, it may open a new path toward identifying who is most at risk after a TBI, and eventually, toward new ways to intervene.”
8