Traumatic brain injury (TBI) in children and adolescents is a major public health problem in the United States; more than 837,000 TBI-related emergency department visits, hospitalizations, and deaths occurred among children 17 years old and younger in 2014 alone (
1). New-onset postinjury psychiatric disorders, also termed novel psychiatric disorders, occur commonly and have been studied with regard to their biopsychosocial predictors or correlates (
2–
7). The present study, informed by a biopsychosocial model (
8), is the first prospective study, to our knowledge, of a consecutively recruited sample of children and adolescents with TBI that examines DSM-IV-TR (
9) postinjury-onset of oppositional defiant disorder (ODD), conduct disorder, or disruptive behavior disorder not otherwise specified (DBD NOS) assessed 6 months after injury, with the latter disorder meeting criteria for “other specified disruptive, impulse-control, and conduct disorders” in DSM-5 (
10). Our approach was to study children with any of these new-onset disorders as a single group—novel ODD or conduct disorder or DBD NOS—because of anticipated low incidence and phenomenological similarities. However, 6 months postinjury, there were no cases of novel conduct disorder or DBD NOS. Therefore, for simplicity’s sake, our outcome of interest is termed novel ODD.
To our knowledge, only two prospective longitudinal psychiatric standardized-interview pediatric TBI studies have previously investigated novel ODD or novel conduct disorder symptomatology. One of these studies examined postinjury ODD symptom counts and change in ODD symptom counts in consecutively hospitalized children with mild to severe TBI (N=50) over the first 2 years postinjury (
11). The other study investigated symptom counts and categorical diagnoses of novel ODD and novel conduct disorder in a referred sample of inpatient rehabilitation center patients with severe TBI (N=94) 1 year postinjury (
3). Despite their different designs, these studies had overlapping first postinjury-year findings that implicated psychosocial risk factors (e.g., socioeconomic status, preinjury family function, psychosocial adversity, preinjury ODD symptomatology, and preinjury aggression and delinquency), as well as overlapping comorbidities (e.g., emotional lability or personality change due to TBI and novel attention deficit hyperactivity disorder [ADHD]) (
12–
15); only one of the studies (
11) reported a potential biological risk factor, a smaller bicaudate ratio identified on the day-of-injury computerized tomography scan in exploratory analyses. Neither study found a significant relationship of first-year postinjury ODD with the lowest postresuscitation Glasgow Coma Scale (GCS) score (
16), which is the primary acute measure of brain injury severity.
We examined two hypotheses consistent with the existing literature. First, we investigated whether novel ODD would be significantly correlated with psychosocial adversity measures (socioeconomic status, preinjury psychosocial adversity score, preinjury family function). Second, we examined whether slower processing speed, a sensitive marker of brain damage, measured as soon as possible after TBI (baseline assessment), would be significantly associated with novel ODD independent of the presence of preinjury ADHD. In related fashion, we hypothesized that processing speed, as a marker of brain damage, would be significantly associated with injury severity measured by the GCS. Given the rare nature of prospective longitudinal psychiatric studies of pediatric TBI, we performed exploratory analyses focused on the relationship of novel ODD with demographic variables (age, sex), other psychosocial variables (preinjury adaptive function, family psychiatric history, preinjury ADHD, preinjury lifetime psychiatric disorder), comorbid novel internalizing psychiatric disorders (novel anxiety disorder and novel depressive disorder), and other injury variables (GCS, frontal lobe white matter/network lesions).
DISCUSSION
The main findings from this study are that new-onset ODD, also called novel ODD, occurs in the first 6 months after TBI in children and adolescents, and it appears to have rather robust biopsychosocial clinical correlates. Our results generally coincide with but also expand findings from the very few related previous studies. Specifically, novel ODD occurred in 8% of children and adolescents aged 5–14 years at the time of injury and was significantly correlated with preinjury psychosocial risk factors (low socioeconomic status, psychosocial adversity, and low family function) and injury-severity-associated slow processing speed measured in the early weeks after TBI.
The incidence of novel ODD was similar to that reported at the 12-month follow-up of a sample of patients treated consecutively at a rehabilitation center (8% versus 9%). This compatible finding is remarkable given the important differences in the studies. The respective differences between the present study and the earlier study include consecutively hospitalized patients for TBI compared with patients with TBI consecutively treated at a rehabilitation center, a range of severity being mild to severe versus severe TBI only, and use of impairment criteria to define ODD versus using symptom counts without impairment criteria. An important difference between the studies was that the present study found no cases of novel conduct disorder, whereas the earlier study found the rate of novel conduct disorder to be 8%. The reason for this difference is unclear, although we believe it is most likely related to methodological differences in applying impairment criteria.
The association of novel ODD with preinjury psychosocial variables (hypothesis 1) is a consistent characteristic across all related studies (
3). In the present study, we found that novel ODD was significantly associated with lower preinjury socioeconomic status, higher preinjury psychosocial adversity, and lower preinjury family function. Novel ODD in the inpatient rehabilitation sample was significantly associated with psychosocial adversity in univariable analyses; however, in that study, only preinjury special education status was significant in multivariable analyses (
3). Our earlier study of consecutively hospitalized children with mild to severe TBI, which examined ODD symptoms postinjury rather than novel ODD, found that total ODD symptoms 6 months postinjury were significantly related to preinjury family function, preinjury ODD symptom count, and socioeconomic status in a regression analysis (
11). A closer comparison of our earlier study with the present study was the examination of change in ODD symptom count from preinjury to 6 months postinjury, which was significantly associated with only socioeconomic status in a regression analysis (
11).
Consistent with hypothesis 2, novel ODD was associated with slower processing speed. This association remained significant following a regression analysis that controlled for the presence of preinjury ADHD. This is the first time that a significant neurocognitive association of novel ODD has been demonstrated in a pediatric TBI cohort; this finding is not surprising, given neurocognitive differences in children with and without ODD in uninjured cohorts (
30). The finding is intriguing because processing speed was significantly correlated with brain injury severity (GCS score) and has been shown in other studies to be sensitive to brain injury (
31). Therefore, it may be that relatively crude clinical measures of injury severity (GCS score) and macroscopic lesions on structural imaging, neither of which were significantly related to novel ODD, are less sensitive than this neurocognitive measure in reflecting brain damage. Regression analysis demonstrated that novel ODD was significantly and independently associated with both processing speed and socioeconomic status, and therefore the finding could not be attributed to the known association between processing speed and socioeconomic status (
29). Therefore, these findings may underscore the role of psychosocial variables (e.g., socioeconomic status) and biological variables (e.g., brain injury-related slower processing speed) in the presentation of novel ODD 6 months postinjury. It is this biological variable that is a new finding because in neither of the previous studies was novel ODD, ODD symptoms, or change in ODD symptoms at 6-months postinjury related to severity of injury (
3,
11). Nevertheless, one of the earlier studies (
11) found a significant negative correlation of change in ODD symptoms and the “bicaudate ratio” recorded from the day-of-injury computerized tomography scan; this was presumed to reflect brain parenchymal edema and a degree of ventricular compression, which may be associated with eventual damage to frontal lobe structures and connections possibly implicated in the pathophysiology of ODD.
It is notable that while distal (family) psychosocial measures such as socioeconomic status, psychosocial adversity, and family function were significantly related to novel ODD, the only proximal (child) preinjury psychosocial variable that even approached significance was preinjury child adaptive functioning. It will be of interest in longer-term follow-up of this and other cohorts whether preinjury adaptive function as a measure of behavioral “reserve” akin to the concept of “cognitive reserve” (
13,
32) will be predictive of later or chronic novel ODD outcome.
Exploratory analyses of novel ODD and comorbid novel psychiatric disorders found an association with novel depressive disorder that nearly reached significance, limited possibly by insufficient power. There was no association with novel anxiety disorder. However, as we have noted in previous reports from this cohort that focused on personality change due to TBI (
12,
13) and review of the literature, there is extensive agreement across existing studies with regard to comorbidity of novel ODD or ODD symptoms and emotional lability captured categorically with the diagnosis of personality change due to TBI or continuously with specific questionnaire scales (
3). There is similar agreement across studies, including previous novel ADHD-focused reports from the same cohort studied here (
14,
15), regarding the association of novel ODD or ODD symptoms and novel ADHD or ADHD symptoms (
3,
11). This is not surprising given that emotional lability, ADHD, and ODD are typically related in non-TBI samples (
33). Despite these significant comorbidities, novel ODD and personality change following TBI at 6 months postinjury, as well as novel ODD and novel ADHD 6-months postinjury, have incomplete overlap with regard to their respective statistically significant clinical correlates (
2,
12,
15,
34–
37). Specifically, personality change following TBI 6 months postinjury is related to severity of injury and dorsal frontal lobe lesions, but not to psychosocial variables. Furthermore, novel ADHD or change in ADHD symptoms is often related to indices of injury severity or specific lesions such as orbitofrontal gyrus lesions or putamen lesions, in addition to psychosocial variables (
15,
34,
35).
Several limitations in study methodology are important to acknowledge. First, we did not include a nonbrain-related injury control group to compare with the TBI group. Without this control group, it is difficult to establish a causal pathway between brain injury in children and development of ODD. Second, we did not directly test interrater reliability for psychiatric diagnoses within and across testing sites. However, there were specific procedures of quality control and training, as described in the Methods section, to mitigate this issue. Third, image analyses did not include volumetric or tissue-segmentation measurements. Fourth, sample attrition was approximately 20%; children who had lower postinjury baseline processing speed and lower preinjury adaptive function were less likely to return for their 6-month assessment. These variables were associated with a significant and nearly significant association with novel ODD, respectively; therefore, it is possible that our findings would have been even more robust had they participated in the 6-month assessment. However, the participants and nonparticipants were no different on multiple demographic variables such as age, sex, race, socioeconomic status, preinjury psychosocial adversity, preinjury family function, preinjury psychiatric status, and injury severity. Fifth, diagnoses were determined using the DSM-IV-TR, the version that was current at the time of the study, rather than DSM-5; however, the classification of ODD, including meeting at least four of eight criteria to qualify for ODD, did not change between the two versions, aside from minor semantic differences (
38). Sixth, potential variability in the natural history of postinjury treatment-seeking by the families of participants could influence outcome. Finally, this study is limited to only measuring the effect of TBI at 6 months postinjury as opposed to multiple time points as some other studies have done. The persistence or lack thereof of the TBI effect on novel ODD outcome noted here is unclear from this report taken in isolation.
There are several notable strengths of this study. Perhaps most importantly, this study fills a gap in the literature: It is the only prospective TBI study of novel ODD to use a semistructured psychiatric assessment to make a diagnosis that requires clinical judgment to document impairment. The breadth and depth of assessments were extensive and included interview assessments of adaptive functioning, family psychiatric history, and psychopathology. In addition, this study accounts for preinjury diagnoses assessed by semistructured interviews in all study participants. The documentation of preinjury diagnoses is vital for measuring novel psychiatric outcomes. Furthermore, expert neuroradiologists coded the lesions to ensure accurate brain imaging results, despite lesion correlates being a negative finding. Finally, this study examined children with TBI ranging in severity from mild to severe versus severe TBI only, making the results more generalizable to a wider pediatric TBI population.