Antibody may protect against depression and PTSD after brain injury

A naturally occurring antibody was linked to lower depression and PTSD symptoms after traumatic brain injury in a study of US Marines.

Among participants with a lifetime history of traumatic brain injury (TBI), those in the top quarter for antibody levels had about 25 per cent lower depression symptom scores and 22 per cent lower PTSD symptom scores after deployment than those with lower levels.

The antibody, known as anti-NMDAR1, targets NMDA receptors, proteins in the brain involved in storing new information and forming memories.

Victoria B. Risbrough, co-senior author of the study, said: “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.

“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.”

Researchers at the University of California San Diego School of Medicine and Veterans Affairs San Diego Healthcare System analysed blood samples and psychiatric assessments from 1,025 active-duty US Marines.

Samples and assessments were collected before and after a seven-month combat deployment to Afghanistan between 2011 and 2013 as part of the Marine Resiliency Study II.

Those participants were also significantly less likely to report moderate-to-severe depression and used fewer psychiatric medications after returning from deployment.

The antibodies remained detectable in blood for more than a year, suggesting that having high levels could be a relatively long-term trait.

No association was found between anti-NMDAR1 levels and anxiety.

The researchers proposed that the antibody’s effects may depend on its type and size.

The naturally occurring antibodies identified in the Marines were a type called IgM. Researchers suggested they are too large to enter synapses, the small gaps between brain cells where chemical signals are transmitted.

Instead, they may bind to receptors outside these gaps. The researchers said these receptors are primary drivers of brain damage after TBI, raising the possibility that IgM anti-NMDAR1 could help protect the brain from further injury.

Earlier research in mice found that animals carrying smaller IgG anti-NMDAR1 antibodies in their blood showed impaired cognitive function. These antibodies were small enough to fit into synaptic gaps.

Xianjin Zhou, co-senior author of the study, said: “We suspected that size difference determines whether an antibody reaches the receptors involved in brain injury versus the ones needed for everyday brain function.

“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.”

The researchers noted that ketamine, an FDA-approved treatment for depression and PTSD, is thought to act by blocking the same type of receptor, although its effects are shorter-lived than the persistence observed for natural anti-NMDAR1 antibodies in blood.

The authors cautioned that the findings are correlational and do not establish that natural anti-NMDAR1 antibodies protect against depression or PTSD following TBI.

They said further research is needed to determine whether the antibodies have a protective role after brain injury.