The Shared Biology of PTSD and TBI

Inflammation, Genetic Vulnerability, and Why Symptoms Become Chronic

Posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI) frequently co-occur in military and veteran populations. While this overlap is often attributed to shared exposure to trauma, emerging research suggests a deeper biological connection. Increasing evidence points to chronic inflammation and genetic vulnerability as key drivers of persistent symptoms in individuals with PTSD, TBI, or both.

Understanding this shared biology helps explain why many people continue to struggle despite therapy, medication, and strong coping skills. It also reframes chronic symptoms not as psychological weakness, but as signs of a system under sustained biological load.

Inflammation as a Common Pathway

Both PTSD and TBI are associated with elevated inflammatory markers, including interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α). After injury or trauma, inflammation is a normal and protective response. The problem arises when this response does not fully resolve.

Research shows that in some individuals, immune activation persists long after the initial injury or threat has passed. This ongoing inflammatory signaling interferes with neurotransmitter balance, sleep regulation, mood stability, and cognitive efficiency. Over time, it can keep the nervous system locked in a defensive state, even in the absence of current danger (Moretti & Paternicò, 2014).

Genetic Vulnerability and Why Outcomes Differ

Not everyone exposed to trauma or brain injury develops chronic symptoms. Recent studies suggest that genetic differences influence how the immune system, stress response, and neuroplastic processes react to injury and trauma. Certain genetic profiles may predispose individuals to prolonged inflammation, heightened stress reactivity, or impaired recovery mechanisms.

This helps explain why two people with similar exposures can have very different long-term outcomes. In some cases, biology amplifies and sustains symptoms long after the original event.

What This Feels Like in Real Life

When PTSD and TBI share underlying biological drivers such as inflammation and genetic vulnerability, symptoms rarely remain isolated. Instead, individuals often describe feeling globally unwell, without a clear explanation that fully accounts for what they are experiencing.

Many people report a constant baseline of internal tension or agitation. The body feels keyed up even during calm moments, as if it is waiting for something to happen. Relaxation feels unfamiliar or fleeting, and rest does not restore energy the way it once did.

Fatigue is common, but it is not simple tiredness. It often feels heavy, systemic, and persistent, as though energy production itself is impaired. Sleep may be long but unrefreshing, or fragmented and shallow. Waking already exhausted becomes routine.

Mood symptoms may fluctuate without obvious triggers. Irritability, low frustration tolerance, emotional blunting, or sudden emotional spikes can occur out of proportion to circumstances. Many individuals describe feeling unlike themselves, but unable to explain why.

Cognitive symptoms frequently accompany this state. Brain fog, slowed thinking, difficulty concentrating, and reduced mental endurance are common. Tasks that require sustained attention or problem-solving can feel overwhelming, even when intellectual ability remains intact.

Physical symptoms may also emerge. Joint or muscle pain, headaches, gastrointestinal discomfort, temperature sensitivity, and increased susceptibility to illness can reflect ongoing immune activation rather than unrelated conditions. These symptoms often shift or migrate over time, adding to frustration.

Perhaps most difficult is the sense that nothing fully works. Therapy may help insight but not energy or regulation. Medications may blunt symptoms but introduce side effects. Lifestyle changes may provide temporary improvement without lasting stability. Many individuals are told their case is complex or treatment-resistant, when the underlying issue is sustained biological stress.

Why Symptoms Become Chronic

When inflammation remains elevated and stress-response systems stay activated, the brain and body operate in a state of chronic defense. Neurotransmitter signaling becomes less efficient, mitochondrial energy production is strained, and sleep regulation deteriorates. The nervous system loses flexibility.

In this state, symptoms are not separate problems. They are interconnected signals of a system under continuous load.

Why This Matters for Recovery

Recognizing the inflammatory and biological contributors to PTSD and TBI reframes recovery. When symptoms are driven by immune activation, metabolic strain, and genetic vulnerability, effective care must go beyond symptom management. The underlying drivers keeping the system activated must be identified and addressed.

This helps explain why medication or therapy alone may not produce sustained improvement for some individuals. Stabilization requires reducing biological load and supporting the systems that regulate energy, stress, and recovery.

At Brain Treatment Center NoVA, this understanding informs our integration of functional health evaluation with brain and nervous system–based therapies. By identifying inflammatory, metabolic, and cellular contributors, we work to reduce the biological burden that perpetuates symptoms and support a more resilient, regulated system.

References

Moretti, R., & Paternicò, D. (2014). Sleep disorders in patients with traumatic brain injury. Current Neurology and Neuroscience Reports, 14(8), 470. https://doi.org/10.1007/s11910-014-0470-4

Franzen, P. L., Siebern, A. T., Buysse, D. J., et al. (2021). Sleep apnea and posttraumatic stress disorder symptom severity in veterans with traumatic brain injury. Journal of Clinical Sleep Medicine, 17(8), 1651–1660. https://doi.org/10.5664/jcsm.9276