Chronic circadian misalignment in military personnel: a potential contributor to neuroinflammation risk

Circadian rhythm disruption is increasingly recognized as a key contributor to neurological disorders; however, its role is often viewed as a secondary consequence rather than a primary driver of brain dysfunction. We argue that chronic circadian misalignment should be reconceptualized as a potential, modifiable contributor to neuroinflammatory risk, rather than viewed solely as a secondary consequence. Military personnel represent a unique and underutilized human model in this context, as they are chronically exposed to predictable circadian stressors, including irregular training schedules, overseas travel, sleep restriction, and pre-operational stress. At the molecular level, circadian misalignment disrupts core clock gene regulation (e.g., CLOCK, BMAL1), leading to downstream alterations in mitochondrial function and redox homeostasis. These changes promote a sustained pro-inflammatory milieu, impair neuroimmune balance, and compromise synaptic plasticity and blood-brain barrier integrity. We propose that these mechanisms collectively increase vulnerability to cognitive dysfunction and mood disturbances, even in otherwise healthy and physically fit populations. Thus, circadian misalignment in military personnel is not merely a byproduct of performance demands, but a biologically plausible contributor to brain dysfunction that warrants targeted intervention and further mechanistic study. Reframing circadian disruption as a potential, modifiable neurobiological risk factor has significant implications for both research and practice.