Pathophysiological Bases of Comorbidity: Traumatic Brain Injury and Post-Traumatic Stress Disorder.

Area of Science:

• Neuroscience
• Psychiatry
• Veterans Health

Background:

• High rates of traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) in veterans highlight the need to understand their comorbidity.
• Common neuropsychiatric symptoms and overlapping pathophysiological changes complicate diagnosis and treatment.
• Both conditions disrupt neural connections within the brain's connectome.

Purpose of the Study:

• To analyze the neural mechanisms underlying the TBI/PTSD comorbidity.
• To identify shared neural disruptions and pathophysiological changes.
• To explore potential neurorestorative therapeutic targets.

Main Methods:

• Review of experimental models of TBI (fluid percussion, blast injuries) and PTSD (fear conditioning, retention, extinction).
• Analysis of neuroimaging and pathological findings in TBI and PTSD.
• Examination of cellular and molecular mechanisms including neuroinflammation, excitotoxicity, and oxidative damage.

Main Results:

• Shared neural disruptions include white matter abnormalities and gray matter changes in the amygdala, hippocampus, and prefrontal cortex.
• Both TBI and PTSD exhibit neuroinflammation, excitotoxicity, and oxidative damage, leading to neuronal degeneration and altered morphology.
• Experimental models show that pharmacological and psychological treatments can reverse detrimental processes and promote neurorestoration.

Conclusions:

• TBI and PTSD comorbidity involves shared disruptions in neural circuitry and pathophysiology.
• Neuroinflammation, excitotoxicity, and oxidative damage are key mechanisms underlying TBI/PTSD.
• Novel neurorestorative therapeutics targeting these mechanisms offer promise for treating comorbid TBI and PTSD.