Prevalence and Correlates of Depressive Symptoms Within 6 Months After First-Time Mild Traumatic Brain Injury
Publication: The Journal of Neuropsychiatry and Clinical Neurosciences
Abstract
Objective:
Depressive symptoms are among the most common neuropsychiatric sequelae of mild traumatic brain injury (mTBI). Very few studies have compared correlates of depressive symptoms within the first 6 months of injury in cohorts experiencing their first TBI. The authors investigated whether the correlates of depressive symptoms (being female, older, lower education, having brain lesions, experiencing worse postconcussive symptoms, and incomplete functional recovery) that have been established in populations with moderate to severe TBI were the same for individuals with first-time mTBI within the first 6 months of recovery.
Methods:
Two hundred seventeen individuals with first-time mTBI were divided into subgroups—new-onset depressive symptoms, recurrent depressive symptoms, prior depression history only, and never depressed—and compared on clinical and demographic variables and the presence of postconcussive symptoms and functional recovery at 3 and 6 months.
Results:
New-onset depressive symptoms developed in 12% of the cohort, whereas 11% of the cohort had recurrent depressive symptoms. Both depressive symptoms groups were more likely to comprise women and persons of color and were at higher risk for clinically significant postconcussive symptoms and incomplete functional recovery for the first 6 months postinjury.
Conclusions:
Presence of depressive symptoms after first-time mTBI was associated with persistent postconcussive symptoms and incomplete functional recovery in the first 6 months. Adding to the existing literature, these findings identified correlates of depressive symptom development and poor outcomes after mTBI, thus providing further evidence that mTBI may produce persistent symptoms and functional limitations that warrant clinical attention.
Traumatic brain injury (TBI) is a major public health problem, with more than 2.5 million people seeking medical care annually, of which 70%−90% experience mild TBI (mTBI) (1–6). It is further estimated that 5.3 million Americans are living with a TBI-related disability, costing the United States an estimated $75.6 billion in annual direct and indirect medical costs (7). mTBI constitutes a heterogeneous population for a variety of reasons, including a great variance in persistence and severity of symptoms postinjury. Patients with mTBI are found to have higher rates of neuropsychiatric symptoms, postconcussive symptoms (e.g., headaches, blurred vision, body pain, dizziness, and light sensitivity), and poorer global outcomes than those with more severe TBI (8–11). The presence of these symptoms can detrimentally affect recovery and quality of life postinjury (12–16).
Depressive symptoms are among the most common neuropsychiatric sequelae of mTBI and occur in 17%−31% of persons with such injuries (11, 17–27). Depressive symptoms include feelings of sadness, loss of interest, lethargy, amotivation, sleep disturbance, appetite changes, irritability, and suicidal thoughts. Depressive symptoms after TBI (regardless of TBI severity) increase suicide risk; interfere with engagement in activities of daily living; and impair rehabilitative, social, occupational, and interpersonal functioning, thereby adding to chronic TBI-related disability and increased global burden of disease (28–31).
Well-established demographic and clinical risk factors for depression after TBI include being older, being female, having less than a high school education, poor pre-TBI psychosocial functioning, higher TBI severity, substance use, comorbid sleep and cognitive disturbances, frontal lesions, and pre-TBI psychiatric illness (22, 23, 32–40). Although these studies have focused on cohorts of heterogeneous TBI severities (30, 40–47), correlates of developing depression after first-time mTBI have not been an area of research focus. Despite the growing literature on understanding neuropsychiatric consequences of mTBI (41), cohort studies have not focused on depression as a primary outcome within the first year postinjury and have primarily examined other measures, such as poor functional recovery and postconcussive symptoms (48–51). To understand why depressive symptoms might follow a single, first-time mTBI, it is useful to compare those who develop new-onset depressive symptoms after a single injury with those who do not and also with those with a preinjury depression history. By only including individuals for whom this is their first TBI (of any severity), any cumulative effect of multiple brain injuries can be ruled out as a contributor of persistent symptoms. Understanding correlates of first-time depressive symptoms that develop in the early TBI period (i.e., within the first 6 months) can help identify who is at risk and then apply interventions to prevent the subsequent progression of disease.
To date, only one study has examined the risk factors, prevalence, and correlates for new-onset depression specifically in mTBI (52). Rao et al. (52) longitudinally followed 43 participants for 1 year and found the prevalence of new-onset depression to be 18%. Older age and presence of frontal subdural hemorrhage were the only two significant findings noted in the depressed group compared with the nondepressed group. Our study aims to build on this knowledge through characterizing a cohort with first-time mTBI by analyzing demographic and clinical variables of those who develop depressive symptoms within the first 6 months postinjury as compared with those who do not. Given the findings in previous studies of individuals after TBIs (of all severities) who develop depression, we investigate whether individuals with first-time mTBI who develop depressive symptoms are more likely to be female, be older, have less education, have brain lesions, and experience worse postconcussive symptoms and incomplete functional recovery within the first 6 months postinjury as compared with individuals with first-time mTBI who are not depressed. Additionally, the prevalence of new-onset depressive symptoms versus recurrent depressive symptoms (those with a preinjury history of depression) will be established. It will be determined whether individuals who develop new-onset depressive symptoms differ from those who develop recurrent depressive symptoms as they relate to postconcussive symptoms and functional recovery and whether these two groups differ from those who do not develop any depressive symptoms after TBI.
Methods
We used participants with TBI from a prospective observational cohort study (the Head Injury Serum Markers for Assessing Response to Trauma, or HeadSMART, study) (53, 54). The study was approved by the institutional review board at Johns Hopkins University. We used the criteria of the American Congress of Rehabilitation Medicine (ACRM) to reach a diagnosis of mTBI, which is defined as experiencing at least one of the following: any period of loss of consciousness; any loss of memory for events immediately before or after the accident; any alteration in mental state at the time of the accident (e.g., feeling dazed, disoriented, or confused); and focal neurological deficit(s) that may or may not be transient but where the severity of the injury does not exceed the following: loss of consciousness of approximately ≤30 minutes; after 30 minutes, an initial Glasgow Coma Scale score of 13–15; and posttraumatic amnesia for not more than 24 hours (55–57).
Participants
Participants were recruited from two academic emergency departments (EDs) located in Baltimore: Johns Hopkins Bayview Medical Center, a level-2 trauma center, and Johns Hopkins Hospital, a level-1 trauma center. Eligible participants with TBI were 18 years or older and presented to the ED within 24 hours of blunt head injury, met the American College of Emergency Physicians criteria (58) for evaluation with an intracranial computerized tomography (CT) scan, and consented to research blood draws. Patients with brain tumor, severe dementia, history of intracranial hemorrhage or intracranial surgery, seizure-induced head injury, pregnancy, no working telephone number, inability to communicate in English, or blood transfusion before initial research blood draw was obtained were excluded. A detailed description of this cohort has been published previously (53, 54). For this particular study, individuals who met criteria for a more severe injury (moderate or severe TBI) were not included. Individuals with a past history of brain injury (of any severity) were excluded; therefore only individuals with first-time mTBI were included.
Procedures
Demographic and clinical data were collected by trained research coordinators using structured data collection tools recommended by the National Institute of Neurological Disorders and Stroke Common Data Elements (59). Eligible subjects were evaluated in the ED within 24 hours of injury. Outcome data were collected on the day of injury in person and then up to 6 months after injury either by telephone interview or in-person assessment. Data were managed using REDCap electronic data capture tools hosted at the Johns Hopkins School of Public Health. Intracranial CT images were read by one board-certified neuroradiologist (H.S.).
Measurements
Depressive symptoms.
Symptoms of depression were measured by the Patient Health Questionnaire–9 (PHQ-9) (60), a scale that has been validated for use in assessing TBI (61). Participants were considered to have clinically significant depressive symptoms if they reported symptoms that totaled a score ≥10 (indicative of moderate depressive symptoms) at either 3 or 6 months postinjury, and a maximum score during those two time points was used. A score ≥10 was chosen, as this cutoff has been deemed clinically meaningful in established TBI studies (62, 63). Participants with first-time mild TBI were categorized into two groups: those with at least moderate depressive symptoms (with a total PHQ-9 score ≥10 at 3 or 6 months after TBI; the depressive symptoms group) and those with no depressive symptoms (with total PHQ-9 scores <10 at both 3 or 6 months postinjury; the no depressive symptoms group). It is recognized that individuals with scores of 5–9 (mild depressive symptoms) may have been included in the no depressive symptoms group, but we maintained the cutoff score of ≥10 to define the presence of clinically meaningful depressive symptoms for individuals with TBI (as supported by previous studies). The cohort was then further divided into four subgroups on the basis of past depression history and current symptoms: those with new-onset depressive symptoms defined by the presence of maximum PHQ-9 scores ≥10 at 3 or 6 months postinjury and the absence of previous depression diagnosis (the new-onset depressive symptoms group); those with recurrent depressive symptoms defined by the presence of maximum PHQ-9 scores ≥10 at 3 or 6 months and the presence of a previous depression diagnosis (the recurrent depressive symptoms group); those with a past history of depression but no current depressive symptoms defined by the presence of maximum PHQ-9 scores <10 at 3 or 6 months and the presence of a previous depression diagnosis (the prior depression history only group); and those who were never depressed, as defined by the presence of maximum PHQ-9 scores <10 at 3 or 6 months and the absence of a previous depression diagnosis (the never depressed group). Participants with persistent depressive symptoms and those with PHQ-9 scores ≥10 and no prior depression history were referred to psychiatric services.
Postconcussive symptoms.
Postconcussive symptoms were measured with the Rivermead Post-Concussion Questionnaire (64), a 16-item scale scored from 16 to 64. By ICD-10 criteria, participants were deemed to have postconcussion symptoms if they reported mild to more severe problems in two or more of the following symptom groups: (a) headaches, dizziness, general malaise, excessive fatigue, or noise intolerance; (b) irritability, emotional lability, depression, or anxiety; (c) subjective complaints of concentration or memory difficulty; (d) insomnia; (e) reduced tolerance to alcohol; (f) preoccupation with these symptoms and fear of permanent brain damage. The total score was applied in the analysis as a continuous variable of all these items.
Functional recovery.
Return to daily life activities, such as working, community activities, and social activities (i.e., functional recovery) was captured with the Glasgow Outcome Scale–Extended (GOSE) (57), which characterizes recovery on a scale ranging from 1 (dead) to 8 (upper good recovery). Functional recovery was applied in the analysis as a categorical variable: complete functional recovery was defined as a GOSE score of 8, and incomplete functional recovery was defined as a GOSE score of 7 or less.
Statistical Analyses
Differences in demographic and injury characteristics between depressive symptoms across mTBI subgroups (the no depressive symptoms group versus the depressive symptoms group) were compared. Differences in the presence of postconcussive symptoms and functional recovery at 3 months and at 6 months were compared among the four subgroups: the new-onset depressive symptoms group, the recurrent depressive symptoms group, the prior depression history only group, and the never depressed group. Descriptive statistics were calculated, including Pearson’s chi-square test or Fisher’s exact test for categorical variables and t test or analysis of variance for continuous variables. Post hoc Tukey’s honestly significant difference was performed for the significant subgroup comparisons. Simple linear regression was used to test for group differences between the four subgroups for postconcussive symptoms. Fisher’s exact test was used to determine whether there was any association between incomplete functional recovery and depression status for those with first-time mTBI at 3 or 6 months postinjury. “Time-averaged” models were used to test the fit averaged over 3 or 6 months after injury with a random intercept for each subject to detect the relationship between the covariate, depression status 3 or 6 months after injury, and the outcomes, postconcussion symptoms and GOSE score, with the variable sex unadjusted and adjusted. For the mTBI subgroup comparisons, simple linear regression model fit was tested for outcome, postconcussion symptoms, and logistic regression modeling was used for the GOSE outcome at 3 or 6 months. Analyses were also unadjusted and adjusted for the variable sex. The criterion for statistical significance was set at p <0.05.
Results
Of 540 individuals who met criteria for the HeadSMART research program, 398 met ACRM criteria for mild TBI; of those, this was a first-time mild TBI for 278 individuals (Figure 1). Sixty-one individuals either were lost to follow-up by 3 months postinjury or did not have complete depression or outcome data for this study and therefore were excluded. There was only one demographic characteristic or injury characteristic difference between the individuals included in the study and those excluded from analyses because of missing data or being lost to follow-up. Individuals lost to follow-up or excluded from analyses because of missing data were more likely to be unemployed than those who engaged in the study. The total cohort for this study was 217 individuals with first-time mTBI.
FIGURE 1. Study flow diagrama
a ACRM=American Congress of Rehabilitation Medicine; mTBI=mild traumatic brain injury.
Comparison of the Depressive Symptoms and No Depressive Symptoms Groups
Forty-nine individuals (23% of the cohort) met criteria for the depressive symptoms group, and 168 individuals (77%) were included in the no depressive symptoms group. Demographic and injury characteristics of these two groups are summarized in Table 1. Of these characteristics, the groups only statistically significantly differed on race and sex in that within the depressive symptoms group, 30 (64%) individuals were not White (versus 74 [46%] in the no depressive symptoms group), and 29 (59%) were women, (versus 67 [40%] in the no depressive symptoms group). Of note, the groups did not differ on the percentage of individuals who had the presence of a brain lesion.
| No depressive symptoms (N=168) | Depressive symptoms (N=49) | |||||
|---|---|---|---|---|---|---|
| Characteristic | N | % | N | % | p | Statistical test |
| Age (years) (mean±SD) | 46.1 | 19.8 | 43.8 | 17.3 | 0.47 | t test |
| Sex | ||||||
| Female | 67 | 39.9 | 29 | 59.2 | 0.017 | Pearson’s chi-square |
| Male | 101 | 60.1 | 20 | 40.8 | 0.017 | Pearson’s chi-square |
| Education level (years) (mean±SD) | 13.0 | 2.7 | 12.5 | 2.1 | 0.23 | t test |
| Non-White race | 74 | 45.7 | 30 | 63.8 | 0.028 | Pearson’s chi-square |
| In intimate relationship | 60 | 35.7 | 15 | 30.6 | 0.43 | Pearson’s chi-square |
| Employment status | ||||||
| Full-time | 75 | 44.6 | 21 | 42.9 | 0.56 | Fisher’s exact |
| Part-time | 16 | 9.5 | 3 | 6.1 | ||
| Unemployed | 16 | 9.5 | 9 | 18.4 | ||
| Not in workforce | 61 | 36.3 | 16 | 32.7 | ||
| Primary breadwinner | ||||||
| Patient | 84 | 59.2 | 22 | 59.5 | 1.00 | Fisher’s exact |
| Other | 36 | 25.4 | 9 | 24.3 | ||
| Equally shared with another person | 22 | 15.5 | 6 | 16.2 | ||
| Mechanism of injury | ||||||
| Pedestrian struck by motor vehicle | 18 | 10.7 | 3 | 6.1 | 0.14 | Pearson’s chi-square |
| Vehicle-vehicle collision | 40 | 23.8 | 17 | 34.7 | ||
| Fall from elevation >3ft. | 15 | 8.9 | 5 | 10.2 | ||
| Fall from elevation <3ft. | 41 | 24.4 | 8 | 16.3 | ||
| Assault | 26 | 15.5 | 9 | 18.4 | ||
| Head struck by/against object | 10 | 6.0 | 1 | 2.0 | ||
| Bicyclist struck by motor vehicle | 4 | 2.4 | 0 | 0.0 | ||
| Motorcyclist (with helmet) struck by motor vehicle | 8 | 4.8 | 3 | 6.1 | ||
| Motorcyclist (without helmet) struck by motor vehicle | 6 | 3.6 | 1 | 2.0 | ||
| Other | 0 | 0.0 | 2 | 4.1 | ||
| Computerized tomography of brain findings | ||||||
| No abnormal findings | 129 | 76.8 | 41 | 83.7 | 0.33 | Pearson’s chi-square |
| Skull fracture alone | 6 | 3.6 | 0 | 0.0 | ||
| Brain lesion | 33 | 19.6 | 8 | 16.3 | ||
a
Bold denotes statistical significance.
When comparing the depressive symptoms group to the no depressive symptoms group on outcomes, a two-sample t test was calculated to assess group differences in postconcussive symptoms at each follow-up time point (i.e., at 3 months and 6 months postinjury). There was a statistically significant difference in postconcussive symptoms (p<0.001) (i.e., fewer postconcussive symptoms in the no depressive symptoms group) at 3 months and 6 months postinjury. The depressive symptoms group had a 22.53 higher mean score than the no depressive symptoms group at 3 months postinjury and a 26.01-point mean higher score at 6 months postinjury.
To test the relationship between group status (the depressive symptoms group versus the no depressive symptoms group) and functional outcome (complete functional recovery versus incomplete functional recovery), we performed a chi-square test of independence. The relation between these variables was significant at 3 months (N=201; χ2=22.92, df=1, p<0.001) and at 6 months (N=177; χ2=27.52, df=1, p<0.001). The depressive symptoms group was less likely to have a complete functional recovery than the no depressive symptoms group (Table 2).
| No depressive symptoms | Depressive symptoms | ||||
|---|---|---|---|---|---|
| Outcome | N | % | N | % | pb |
| Postconcussive symptoms (mean±SD) | 8.2 | 8.7 | 30.7 | 15.2 | <0.001 |
| Functional recovery | <0.001 | ||||
| Incomplete | 86 | 50.6 | 30 | 96.8 | |
| Complete | 84 | 49.4 | 1.0 | 3.2 | |
| Postconcussive symptoms (mean±SD) | 6.3 | 8.0 | 32.3 | 14.6 | <0.001 |
| Functional recovery | <0.001 | ||||
| Incomplete | 59 | 39.9 | 27 | 93.1 | |
| Complete | 89 | 60.1 | 2 | 6.9 | |
a
Out of the total cohort of 217 individuals represented in the table, 203 followed up at 3 months, and 181 followed up at 6 months. Some individuals followed up at both time points. At 3 months postinjury, the follow-up cohorts comprised the following: no depressive symptoms group, N=172; depressive symptoms group, N=31. At 6 months postinjury, the follow-up cohorts comprised the following: no depressive symptoms group, N=152; depressive symptoms group: N=29. Bold denotes statistical difference.
b
Comparisons for postconcussive symptoms were tested with two-sample t tests; comparisons for functional recovery were tested with Fisher’s exact test.
Group Comparisons
Twenty-six individuals (12.0% of the cohort) who had no history of depression endorsed at least moderately severe depressive symptoms postinjury (the new-onset depressive symptoms group), whereas 23 (10.6%) of individuals met criteria for the recurrent depressive symptoms group, 37 (17.1%) individuals met criteria for the prior depression history only group, and 131 (60.4%) individuals met criteria for the never depressed group. The demographics and injury characteristics of these four groups are summarized in Table 3.
| New-onset depressive symptoms (N=26) | Recurrent depressive symptoms (N=23) | Prior depression history only (N=37) | Never depressed (N=131) | |||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Characteristic | N | % | N | % | N | % | N | % | p | Statistical test |
| Age (years) (mean±SD) | 40.4 | 17.7 | 47.7 | 16.4 | 47.8 | 19.9 | 45.6 | 19.8 | 0.45 | ANOVA |
| Male | 10 | 38.5* | 10 | 43.5 | 12 | 32.4** | 89* | 67.9** | <0.001 | Pearson’s chi-square |
| Education level (years) (mean±SD) | 12.7 | 1.8 | 12.3 | 2.4 | 12.7 | 2.4 | 13.1 | 2.7 | 0.45 | ANOVA |
| Non-White race | 17 | 68.0*** | 13 | 59.1 | 11 | 29.7*** | 63 | 50.4 | 0.018 | Pearson’s chi-square |
| In intimate relationship | 5 | 19.2 | 10 | 43.5 | 14 | 37.8 | 46 | 35.1 | 0.30 | Pearson’s chi-square |
| Employment status | ||||||||||
| Full-time | 14 | 53.8 | 7 | 30.4 | 12 | 32.4 | 63 | 48.1 | 0.037 | Fisher’s exact |
| Part-time | 3 | 11.5 | 0 | 0.0 | 4 | 10.8 | 12 | 9.2 | ||
| Unemployed | 4 | 15.4 | 5 | 21.7 | 3 | 8.1 | 13 | 9.9 | ||
| Not in workforce | 5 | 19.2**** | 11 | 47.8**** | 18 | 48.6 | 43 | 32.8 | ||
| Breadwinner | ||||||||||
| Patient | 12 | 60.0 | 10 | 58.8 | 18 | 64.3 | 66 | 57.9 | 0.87 | Fisher’s exact |
| Other | 4 | 20.0 | 5 | 29.4 | 8 | 28.6 | 28 | 24.6 | ||
| Equally shared with another person | 4 | 20.0 | 2 | 11.8 | 2 | 7.1% | 20 | 17.5 | ||
| Mechanism of injury | ||||||||||
| Pedestrian struck by motor vehicle | 2 | 7.7***** | 1 | 4.3 | 8 | 21.6***** | 10 | 7.6 | 0.002 | Pearson’s chi-square |
| Vehicle-vehicle collision | 7 | 26.9 | 10 | 43.5 | 4 | 10.8 | 36 | 27.5 | ||
| Fall from elevation >3ft. | 1 | 3.8 | 4 | 17.4 | 9 | 24.3 | 6 | 4.6 | ||
| Fall from elevation <3 ft. | 4 | 15.4 | 4 | 17.4 | 7 | 18.9 | 34 | 26.0 | ||
| Assault | 6 | 23.1 | 3 | 13.0 | 7 | 18.9 | 19 | 14.5 | ||
| Head struck by/against object | 1 | 3.8 | 0 | 0.0 | 1 | 2.7 | 9 | 6.9 | ||
| Bicyclist struck by motor vehicle | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 4 | 3.1 | ||
| Motorcyclist (with helmet) struck by motor vehicle | 2 | 7.7 | 1 | 4.3 | 1 | 2.7 | 7 | 5.3 | ||
| Motorcyclist (without helmet) struck by motor vehicle | 1 | 3.8 | 0 | 0.0 | 0 | 0.0 | 6 | 4.6 | ||
| Other | 2 | 7.7 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | ||
| CT findings | ||||||||||
| No abnormal findings | 23 | 88.5 | 18 | 78.3% | 26 | 70.3 | 103 | 78.6 | 0.62 | Pearson’s chi-square |
| Skull fracture alone | 0 | 0.0 | 0 | 0.0 | 2 | 5.4 | 4 | 3.1 | ||
| Brain lesion | 3 | 11.5 | 5 | 21.7 | 9 | 24.3 | 24 | 18.3 | ||
a
Bold denotes statistical significance. ANOVA=analysis of variance; CT=computerized tomography.
*
Post hoc Tukey honestly significant difference (HSD), significant between never depressed and new-onset depressive symptoms.
**
Post hoc Tukey HSD, significant difference between never depressed group and prior depression history only group.
***
Post hoc Tukey HSD, significant difference between prior depression history only group and new-onset depressive symptoms group.
****
Post hoc Tukey HSD, significant difference between recurrent depressive symptoms group and new-onset depressive symptoms group.
*****
Post hoc Tukey HSD, significant difference between prior depression history only group and new-onset depressive symptoms group.
A new group was made by combining the never depressed group and the prior depression history only group to make the no depressive symptoms group. This allowed for group comparison of those who developed clinically meaningful depressive symptoms postinjury and those who did not. Given that those who developed clinically meaningful symptoms of depression postinjury were of primary interest in this study, particularly characterizing those who developed clinically meaningful depressive symptoms for the first time after injury, the new-onset depressive symptoms group and the recurrent depressive symptoms group were maintained as separate groups. Once the no depressive symptoms group was recreated, sex did not remain a statistically significant group difference but was included as a covariate in further analyses to keep as a convention for comparison with current literature. There was no statistically significant difference in race between the no depressive symptoms group and the other two groups (i.e., the new-onset depressive symptoms group and the recurrent depressive symptoms group). Given that there was a statistically significant difference in employment status between the four groups, employment status was used as a covariate to compare differences between the new-onset depressive symptoms group and the recurrent depressive symptoms group. There was no statistically significant difference in employment status between these two groups.
For comparison of the subgroups—the new-onset depressive symptoms, recurrent depressive symptoms, and no depressive symptoms groups—on postconcussive symptoms at 3 months and 6 months, respectively, we conducted the analyses using both an unadjusted model with no covariates considered and an adjusted model taking into consideration sex as the covariate. At 3 months, the new-onset depressive symptoms group and the recurrent depressive symptoms group had statistically significant greater postconcussive symptoms than the no depressive symptoms group (Table 4). A very similar pattern is shown for both unadjusted and adjusted models at 6 months postinjury. However, there are no statistically significant differences in postconcussive symptoms between the new-onset depressive symptoms group and the recurrent depressive symptoms group at either time point or using adjusted and unadjusted models.
| New-onset depressive symptoms (N=26) | Recurrent depressive symptoms (N=23) | New-onset depressive symptoms compared with recurrent depressive symptoms | |||||||
|---|---|---|---|---|---|---|---|---|---|
| Outcome | Beta | 95% CI | p | Beta | 95% CI | p | Beta | 95% CI | p |
| Postconcussive symptoms | |||||||||
| 3 months postinjury | |||||||||
| Unadjusted | 19.52 | 13.64, 25.40 | <0.001 | 25.35 | 19.47, 31.23 | <0.001 | –5.83 | –12.84, 1.17 | 0.10 |
| Adjusted for sex | 18.83 | 12.95, 24.71 | <0.001 | 24.80 | 18.92, 30.68 | <0.001 | –5.97 | –12.87, 0.93 | 0.09 |
| 6 months postinjury | |||||||||
| Unadjusted | 24.74 | 19.57, 29.91 | <0.001 | 27.20 | 22.19, 32.21 | <0.001 | –2.46 | –9.34, 4.42 | 0.48 |
| Adjusted for sex | 24.08 | 18.89, 29.27 | <0.001 | 26.65 | 21.63, 31.67 | <0.001 | –2.57 | –9.41, 4.27 | 0.46 |
| OR | 95% CI | p | OR | 95% CI | p | OR | 95% CI | p | |
| Complete functional recovery | |||||||||
| Unadjusted | 0.05 | 0.01, 0.40 | <0.005 | 0.05 | 0.01, 0.37 | <0.004 | 1.08 | 0.06, 19.05 | 0.96 |
| Adjusted for sex | 0.06 | 0.01, 0.46 | <0.007 | 0.05 | 0.01, 0.41 | <0.005 | 1.11 | 0.06, 19.96 | 0.94 |
a
The reference group in the model (i.e., unadjusted, adjusted) is the no depressive symptoms group (N=168). Bold denotes statistical significance.
For the binary outcome, complete functional recovery versus incomplete functional recovery at 3 months postinjury, small cell counts in the new-onset depressive symptoms group and the recurrent depressive symptoms group led to inadequate convergence of the logistic regression models. At the 6-month follow-up, in both the unadjusted and adjusted models, the new-onset depressive symptoms group and the recurrent depressive symptoms group were each less likely to have complete functional recovery as compared with the no depressive symptoms group (Table 4). However, there is no difference in functional recovery status between the new-onset depressive symptoms group and the recurrent depressive symptoms group, as these two groups have the similar odds to have complete functional recovery (Table 4).
Discussion
This study is one of the first, to our knowledge, to examine the prevalence and correlates of depressive symptoms within the first 6 months of first-time mTBI in a prospective cohort. Our findings revealed that individuals with depressive symptoms postinjury were more likely to be female and non-White (consistent with the broader TBI literature); those with depressive symptoms had higher postconcussive symptoms at 3 and 6 months compared with those with no depressive symptoms (consistent with the literature); and those with depressive symptoms were less likely to have complete functional recovery at 3 and 6 months, compared with those with no depressive symptoms; however, there was no statistically significant difference in postconcussive symptoms and functional recovery between those with new-onset depressive symptoms and those with recurrent depressive symptoms. The percentage of individuals with brain lesions did not differ between those who developed depressive symptoms and those who did not postinjury. Of note, these study findings reveal that there exists a subset of individuals (12% of our cohort) who developed clinically significant new-onset depressive symptoms after their first mTBI, which is consistent with the findings of a previous study examining depression after mTBI in a smaller cohort (52). These individuals did not differ demographically from those who had recurrent depressive symptoms after first-time mTBI (11% of the cohort). Individuals within both groups who developed clinically significant depressive symptoms were more likely to be women and persons of color than individuals who did not have significant depressive symptoms after injury. Individuals with depressive symptoms, whether new onset or recurrent, after mTBI are at higher risk for clinically significant postconcussive symptoms and incomplete functional recovery for the first 6 months postinjury.
The findings in this study of being female, being older, and not being White as correlates of the development of clinically significant depressive symptoms after mTBI are consistent with what has been established in the broader literature for TBI of all severities of injuries (majority moderate and severe TBI) (33–35, 38). Further, the findings that depressive symptoms after mTBI are associated with persistent postconcussive symptoms and higher risk for poor functional recovery in the first 6 months has also been reported in the TBI literature (65, 66). It has been postulated that women’s depressive symptoms during the early recovery period in mTBI and moderate TBI might be explained by higher symptom load and perceived stress, yet mechanisms responsible for these differences have not been explored (18, 22, 24). It has been shown that older patients have a higher risk of functional decline with a greater degree of disability 5 years postinjury compared with younger patients. This has been thought to be due to an increased number of actual and perceived health problems for older patients as compared with younger patients (67). Reasons why individuals who are not White are at higher risk for incomplete functional recovery have not been explored.
The findings of this study suggest that depressive symptoms may be associated with greater persistent postconcussive symptoms beyond 3 months and incomplete functional recovery in the early mTBI period. Those with new-onset depressive symptoms after first-time mTBI are at similar odds of incomplete functional recovery as those with recurrent depressive symptoms, suggesting that those with a preinjury diagnosis of depression are not the only patients at risk for impaired recovery in the chronic mTBI period. This study highlights the importance of monitoring for the presence of depressive symptoms across the first 6 months postinjury. It is important to note that the majority of those with mTBI recover from postconcussive symptoms within 7–10 days after injury; however, 10%−15% persist with chronic symptoms after 3 months (67, 68). In this minority of cases, functional impairment can exist in up to 53% of individuals at 1 year postinjury, as recently described in a report from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) research group (69). Impaired functional recovery may be affected by not only persistent postconcussive symptoms but also the presence of clinically significant mood and vegetative changes, emphasizing the importance of immediate and frequent monitoring of depressive symptoms in the early period after mTBI.
Although our study reports on a modest sample size when compared with larger multisite studies that examine civilian populations, the findings remain consistent with demographic and preinjury correlates that were found in these larger studies. For example, in the aforementioned TRACK-TBI study, Stein et al. (41) found that of 1,155 participants with mTBI, those with lower education, who were Black, and those who had a history of mental health problems were at substantially increased risk of depression. The Early Predictors of Outcome after Mild Traumatic Brain Injury (UPFRONT) study, which followed 910 participants with mTBI within the first 6 months postinjury, found that emotional distress and maladaptive coping experienced early after injury, in combination with preinjury mental health problems, education, and age, were important predictors for recovery at 6 months after mTBI (48). What is important to note is that, similar to our study, these larger studies also followed participants in the early TBI period (within the first 6 months of injury), reflecting the growing interest within the field to better understand symptom trajectories and predictors of outcomes immediately after mTBI. These larger studies did not however, examine the onset patterns of depressive symptoms (new onset versus recurrent) in the manner done in the present study.
Our study also underscores the importance of ensuring that clinicians are monitoring the concomitant trajectory of postconcussive and depressive symptoms in conjunction with functional status at the time of injury into and beyond the chronic injury phase (i.e., after 3 months postinjury). Proactive interventions early in the mTBI recovery period may help to prevent, or at least mitigate, the development of depressive symptoms. These may include psychoeducation, psychotherapy, psychosocial rehabilitation, neurorehabilitation, and psychotropic medication treatments to prevent the emergence of symptoms and associated disability.
It is important to note the limitations of our study. First, the PHQ-9 scale was used to assess depressive symptoms, but formal psychiatric assessments such as the SCID-5 to diagnose major depressive disorder were not completed (70, 71). Although in-person and telephone evaluations with semistructured psychiatric interviews were conducted by a neuropsychiatrist (M.P., D.R., or V.R.), psychiatric disorders were not formally assessed. As such, a true diagnosis of depression after mTBI could not be made, and we relied on depressive symptoms as a surrogate.
Second, this study only analyzed data from those with first-time mTBI; thus, the findings do not necessarily generalize to individuals who have a history of multiple mTBIs. Individuals with multiple TBIs are documented to have higher rates of neuropsychiatric conditions; therefore, it is likely that those with this type of mTBI history may have scored higher on the PHQ-9 and Rivermead scales (72–74).
Third, there is overlap in symptomatology between domains on the PHQ-9 and Rivermead scales (e.g., sleep disturbance, poor concentration, fatigue, and feeling depressed) (60, 61, 64). Although both scales have been validated for use with TBI symptoms, it is possible that some symptoms endorsed on the PHQ-9 were, in fact, reflective of the presence of postconcussive symptoms (e.g., sleep disturbance and feeling depressed) to some degree. We conducted post hoc analyses to address the potential construct overlap between the PHQ-9 and Rivermead scales with regard to depressive symptoms. In these post hoc analyses in which the overlapping symptoms were removed from the Rivermead questionnaire, the findings remained the same. Specifically, when comparing the depressive symptoms group to the no depressive symptoms group on postconcussive symptoms, a simple linear regression was calculated at each follow-up time point (i.e., 3 months and 6 months postinjury). There was a statistically significant difference in postconcussive symptoms (p<0.001; i.e., fewer postconcussive symptoms in the no depressive symptoms group) at 3 months and 6 months postinjury. The depressive symptoms group had a 13.8 higher score than the no depressive symptoms group at 3 months postinjury and a 15.5-point higher score at 6 months postinjury. These findings suggest that the relationship between the presence of depressive symptoms and postconcussive symptoms at follow-up time points is not due to overlap between the two constructs.
Fourth, the analyses did not consider body polytrauma or extracranial injuries as a factor that could result in a difficulty in performing self-care and daily activities and in returning to work, which are all factors that might exacerbate depressive symptoms. An analysis of body injury, however, was conducted previously on this cohort, focusing on the prevalence of incomplete functional and symptomatic recovery among patients with “head injury but brain injury debatable” (HIBRID) (75). Compared with trauma and healthy control subjects, the HIBRID group had a higher incidence of moderate/severe depressive symptoms and a similar incidence of moderate/severe postconcussive symptoms (53).
Fifth, the presence of alcohol and substance use was not included in this analysis. It is an important factor in the persistence of symptoms in previous studies and should be included as a factor in future studies (75, 76).
Sixth, it should be noted that those with past depression history but no depressive symptoms postinjury may have been receiving either pharmacologic or psychotherapeutic treatment. Although a pre-TBI history of depression would not be protective, being on such treatment would potentially mitigate the persistence of these symptoms after mTBI.
Despite these limitations, the primary strengths of this study are that it provides one of the first analyses of the development of depressive symptoms in a cohort of individuals with first-time mTBI, as well as the correlates of developing depressive symptoms. Being female and being non-White are associated with the development of depressive symptoms within the first 3 months after mTBI, and those with depressive symptoms are at higher risk for postconcussive symptoms and incomplete functional recovery within the first 6 months after injury. There is a rather notable cohort of individuals (12%) who develop new-onset depressive symptoms after mTBI. Taken together, these findings add to the existing literature by identifying correlates for the development of depressive symptoms and poor outcomes after mTBI, thus providing further evidence that “mild” injuries can result in clinically significant symptoms and functional decline that warrant clinical attention.
Conclusions
This study revealed that mTBI depressive symptoms after first-time injury are associated with persistent postconcussive symptoms and that the presence of depressive symptoms (either new in onset or recurrent) poses a higher risk for poor functional recovery in the first 6 months after first-time mTBI. This finding adds to the existing literature identification of risk factors for poor outcomes after mTBI and provides evidence of possible factors for identifying those patients who incur mTBI and need early interventions for psychiatric symptom management. Further observational studies examining a wider array of neuropsychiatric symptoms after TBI using additional clinical variables as predictors should be conducted longitudinally to study the relationship between these symptoms over an extended time course.
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Information & Authors
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Received: 16 August 2021
Revision received: 12 November 2021
Accepted: 15 November 2021
Published online: 21 March 2022
Published in print: Fall 2022
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Funding Information
HeadSMART was funded by ImmunArray, Inc.The authors report no financial relationships with commercial interests.
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