Psychiatric morbidity is one of the most common and socially disabling consequences in adults with mild traumatic brain injury (mTBI), yet poorly studied in youth. According to the International Collaboration in mTBI Prognosis, prediction of psychiatric morbidity in mTBI remains a challenge. Post-concussion symptoms are highly aspecific and significantly overlap with psychiatric symptoms. In fact, depression, anxiety, mood lability, and irritability are common after injury. Yet, a clear link between pathophysiologic mechanisms of mTBI and the subsequent onset of post-TBI psychiatric symptoms remains unclear. This relationship is of utmost importance in the study of developing brains, where brain lesions have the potential to mine the normative development of neural circuitries involved in emotional regulation. An imbalance in fronto-temporo-limbic systems has been proposed as a neural mechanism of emotional dysregulation in pediatric psychiatric disorders. Yet, no study has examined the relationship between fronto-temporo-limbic lesions and the onset of post-TBI psychiatric symptoms. The rational for the proposed research is that abnormalities in fronto-temporo- limbic regions in youth with mTBI might represent the structural basis for the vulnerability of emotional regulation circuitries, possibly leading to a heightened risk for post-TBI psychiatric morbidity. The objective of this application is to use multimodal neuroimaging techniques to characterize the brain structure and functioning of emotional regulation circuitries in 200 youth 1 week after injury. Five clinical assessments will define 1-year trajectories of depressive symptoms, anxiety, mood lability and irritability in each participant. Based on the extant literature and our preliminary findings, our overall hypothesis is that acute injury quantifiable with neuroimaging measures of brain structure and functioning predates the onset and course of post-TBI psychiatric symptoms in youth prospectively characterized for up to 1 year after injury. Specifically, this proposal aims to 1) examine if mTBI-related lesions in fronto-temporo-limbic regions predict the severity of post-TBI psychiatric symptoms 3 weeks after injury. This proposal also aims to 2) identify demographic and clinical risk factors predicting 1-year trajectories of post-TBI psychiatric symptoms. This approach is innovative because no study examined if mTBI- related lesions in emotional regulation circuitries relate to the acute onset of post-TBI psychiatric symptoms in youth with mTBI. The identification of 1-year trajectories of post-TBI psychiatric symptoms is also innovative and will allow to examine if the combined use of neuroimaging measures and clinical risk factors can help predict these symptoms up to 1-year after mTBI. Finally, by collecting a second scan in a subsample of youth (n=100) 6 months after mTBI, we will examine if neuroimaging measures at 6-month, more than neuroimaging measures at-injury, can help predict 1-year trajectories of post-TBI psychiatric symptoms. This contribution is anticipated to be significant because this strategy has the potential to identify a subset of youth at-risk for developing post-TBI psychiatric morbidity, who might benefit from early intervention strategies.
The proposed research is relevant to public health because unraveling a neuroanatomical vulnerability in key regions of emotional regulation circuitries may help identify mTBI youth at-risk for developing acute, or chronic, psychiatric symptoms after injury, and, thus, aid early intervention strategies and, possibly, change the long-term functional outcomes of these youth. In addition, the identification of objective biomarkers of post-TBI psychiatric morbidity in youth is likely to promote a better understanding of some of the pathophysiologic underpinnings of psychiatric illness in general. As such, the proposed research is also relevant to the part of the NIH's mission that pertains `to developing fundamental knowledge to enhance health and reduce illness and disability'.
