Implications for antidepressant treatment and novel therapeutic strategies after traumatic brain injury: preliminary results of the CAROLINA-MTC study

Objectives

There is increasing evidence that traumatic brain injury (TBI) induces dysregulation of the gut-brain axis (GBA) long-term, and depression may be bidirectionally linked to gut-brain dysfunction. We investigated the prevalence of depression after TBI and concussion, and whether depression after TBI is associated with comorbid gastrointestinal symptoms and post-concussive symptoms.

Design

We are conducting a cross-sectional, observational study of 100 participants post-TBI, capturing data via clinical notes and questionnaires at 3 weeks from admission or regaining capacity, and 12 weeks follow-up. This preliminary analysis includes 35 participants.

Subjects We included participants who were admitted or transferred to King’s College Hospital’s Emergency Department with a confirmed new TBI or concussion, age ≥16, and were able to provide informed consent. Those without a confirmed TBI or concussion, un-survivable injury and prisoners or those in custody were excluded.

Methods

Using unadjusted logistic regression models, we tested whether depressive symptoms, measured as PHQ-9 score ≥10, were associated with gastrointestinal symptoms (PAGI-SYM), food avoidance (avoidant/restrictive food intake disorder [ARFID]), post-concussion symptoms (Rivermead Post-Concussion Symptoms Questionnaire [RPCSQ]; Concussion Symptom Inventory [CSI]), and surrounding clinical and demographic factors. New symptom onset was also clarified.

Results

12/35 patients (34.3%) had depressive symptoms after TBI. History of anxiety/depression (p=0.003) and current antidepressant use (p<0.001) were associated with depressive symptoms, with no significant differences in age, gender, or other clinical characteristics. The depressed group scored significantly higher on: CSI moderate/severe-extreme (p<0.001); ARFID low interest in eating (p=0.007) and fear of eating (p=0.009); RPCSQ early post-concussive symptoms (p=0.015) and later cognitive/emotional/somatic symptoms (p<0.001); and PAGI-SYM total (p<0.001), including nausea (p=0.007), vomiting (p<0.001), early fullness (p=0.017), and reflux (p=0.046).

New depressive symptom onset was observed across both groups, i.e. whether TBI itself may precipitate depressive symptoms independent of a pre-existing diagnosis. Rates were substantially higher in the depressed group for anhedonia (58% vs 6%), appetite (75% vs 12%), concentration (67% vs 24%) and psychomotor symptoms (83% vs 47%).

New symptom onset was significantly higher in the depressive group across all domains: new post-concussion symptoms in dizziness (92% vs 59%), nausea/vomiting (75% vs 29%), poor memory (92% vs 53%), poor concentration (92% vs 41%), and sleep disturbance (75% vs 29%). New central sensitization symptoms were elevated in diarrhea/constipation (75% vs 18%) and stress-worsened symptoms (58% vs 18%) and new gastrointestinal symptom onset was substantially higher in nausea (83% vs 44%), loss of appetite (83% vs 19%), inability to finish meals (83% vs 19%), and excessive fullness (75% vs 0%).

Conclusions

These preliminary findings suggest that TBI and concussion may induce gut-brain axis dysfunction, leading to development of depressive symptoms, post-concussive symptoms and gastrointestinal symptoms. The pattern of new depressive symptom onset across both groups supports a TBI-precipitated model of post-injury depression. Antidepressant treatment after TBI could be tailored according to comorbid gut symptoms, for example using of mirtazapine in those with insomnia and loss of appetite, whilst using duloxetine preferentially in those with gastrointestinal pain. Meanwhile, novel treatments such as probiotics could be trialled to restore the gut-brain-axis after TBI.

References

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