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Abstract

Objective:

The investigators examined the factors predictive of novel oppositional defiant disorder in the 6–12 months following traumatic brain injury (TBI).

Methods:

Children ages 5–14 years old who experienced a TBI were recruited from consecutive admissions to five hospitals. Participants were evaluated soon after injury (baseline) for preinjury characteristics, including psychiatric disorders, adaptive function, family function, psychosocial adversity, family psychiatric history, socioeconomic status, and injury severity, to develop a biopsychosocial predictive model for development of novel oppositional defiant disorder. MRI analyses were conducted to examine potential brain lesions. Psychiatric outcome, including that of novel oppositional defiant disorder, was assessed 12 months after injury.

Results:

Although 177 children were recruited for the study, 120 children without preinjury oppositional defiant disorder, conduct disorder, or disruptive behavior disorder not otherwise specified (DBD NOS) returned for the 12-month assessment. Of these 120 children, seven (5.8%) exhibited novel oppositional defiant disorder, and none developed conduct disorder or DBD NOS in the 6–12 months postinjury. Novel oppositional defiant disorder was significantly associated with lower socioeconomic status, higher psychosocial adversity, and lower preinjury adaptive functioning.

Conclusions:

These results demonstrate that novel oppositional defiant disorder following TBI selectively and negatively affects an identifiable group of children. Both proximal (preinjury adaptive function) and distal (socioeconomic status and psychosocial adversity) psychosocial variables significantly increase risk for this outcome.

In the United States, children 17 years of age and younger experienced more than 837,000 traumatic brain injury (TBI)-related emergency department visits, hospitalizations, and deaths in 2014 alone, qualifying TBI in this population as a major public health problem (1). New-onset postinjury psychiatric disorders, otherwise termed novel psychiatric disorders, occur commonly, and the biopsychosocial predictors or correlates of these disorders have been well studied (27). However, studies of postinjury onset of oppositional defiant disorder, conduct disorder, and disruptive behavior disorder not otherwise specified (DBD NOS) are sparse; more research is needed to better understand and proactively address deficits that could emerge from TBI. The present study is an extension of a 12-month follow-up of our published work examining novel oppositional defiant disorder, conduct disorder, or DBD NOS in the first 6 months postinjury. This study, which is informed by a biopsychosocial model (8), is the first prospective study to our knowledge of a consecutively hospitalized sample of children with TBI that examines DSM-IV-TR novel oppositional defiant disorder, conduct disorder, or DBD NOS assessed 12 months postinjury (9). We chose to study children with any of these new-onset disorders as a single group because of the anticipated low incidence and phenomenological similarities between these diagnoses. However, in the 6–12 months postinjury interval, there were no cases of novel conduct disorder or DBD NOS. Therefore, we have simplified our outcome of interest to novel oppositional defiant disorder.

Our investigation of predictors of novel oppositional defiant disorder in the first 6 months postinjury in the same cohort examined here revealed that 11 out of 134 (8.2%) of prospectively studied children developed novel oppositional defiant disorder (10). The significant correlates of novel oppositional defiant disorder were lower socioeconomic status, lower preinjury family functioning, and higher preinjury psychosocial adversity, as well as lower postinjury processing speed (which was associated with severity of injury) (10). Besides the present study, only two prospective longitudinal psychiatric standardized-interview pediatric TBI studies, to our knowledge, have investigated the symptomatology of novel oppositional defiant disorder or novel conduct disorder. One study examined postinjury oppositional defiant disorder symptom counts and change in oppositional defiant disorder 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 oppositional defiant disorder and novel conduct disorder using parent report in a referred sample of inpatient rehabilitation center patients with severe TBI (N=94) and 1 year postinjury (4). While these studies differed in design, both found overlapping psychosocial risk factors (e.g., socioeconomic status, preinjury family function, psychosocial adversity, preinjury oppositional defiant disorder symptomatology, preinjury aggression, and delinquency) and comorbidities (e.g., emotional lability or personality change due to TBI and novel attention deficit hyperactivity disorder [ADHD]) implicated in novel oppositional defiant disorder symptomatology (4, 1115). Only one study found a potential biological risk factor: a smaller bicaudate ratio identified on the day-of-injury computerized tomography scan in exploratory analyses (11). Neither study had a significant relationship between first-year postinjury oppositional defiant disorder and lowest postresuscitation Glasgow Coma Scale (GCS) score (16), a primary acute measure of brain injury severity. However, another prospective study (which did not use a psychiatric interview assessment approach) suggested that preschool children with mild TBI (mTBI) who were hospitalized for their injury had increased oppositional defiant disorder or conduct disorder symptomatology as adolescents compared with outpatient-treated children with mTBI and children with no history of mTBI (17). The assumption was that the inpatient-outpatient treatment difference reflected severity of injury, which was associated with adverse outcomes.

The current literature of pediatric TBI and novel oppositional defiant disorder symptomatology is limited in several ways. Among the limitations are that only three relevant studies exist (4, 11, 17), only one of which examined consecutively treated children presenting with TBI; the TBI sample sizes are relatively small (<100); and there are minimal data on a relationship between novel oppositional defiant disorder and brain injury indices. Here, we attempted to address these limitations and current knowledge gaps in the field. Therefore, we endeavored to extend the follow-up of our existing cohort from 6 months postinjury to 12 months postinjury, as well as replicate findings from earlier studies with respect to the preinjury psychosocial variable relationship with novel oppositional defiant disorder in a larger sample of consecutively treated injured children. In addition, we planned to study the relationship between novel oppositional defiant disorder and injury severity.

Consistent with a biopsychosocial model of risk for novel psychiatric disorders (8), the following hypotheses were tested: novel oppositional defiant disorder would be significantly related to preinjury distal psychosocial variables (socioeconomic status, psychosocial adversity, and family function) and a preinjury proximal psychosocial variable (adaptive function), and novel oppositional defiant disorder would be significantly related to severity of TBI (lowest postresuscitation GCS score). Given the dearth of prospective longitudinal psychiatric studies of pediatric TBI, we designed exploratory analyses focusing on the relationship of novel oppositional defiant disorder with demographic variables (age, sex, and race), other psychosocial variables (family psychiatric history, preinjury ADHD, preinjury lifetime psychiatric disorder, comorbid novel anxiety disorder, and novel depressive disorder), and other injury variables (frontal lobe white matter/network lesions and baseline postinjury processing speed).

Methods

Recruitment

There were 177 participants recruited between the ages of 5 and 14 who experienced a TBI between 1998 and 2003 and were identified from admissions to three academic medical centers in Texas (Baylor College of Medicine, Houston; University of Texas, Houston; and University of Texas, Dallas), Rady Children’s Hospital in San Diego, and The Hospital for Sick Children in Toronto. Children with mild to severe TBI were recruited at all hospitals except San Diego, where only complicated mild to severe TBI patients were included in the study. Children with preexisting autistic disorder or schizophrenia, intellectual deficiency, and injury due to child abuse or penetrating missile injury were excluded from the study. In San Diego only, children were excluded if they had preexisting ADHD. Parents and guardians of children were not required to answer eligibility questions before deciding to participate in the study; therefore, data regarding the number of children approached, the proportion eligible for recruitment, and the participation rate of those who were eligible for recruitment are missing. As required by the institutional review boards, all children signed assent or consent forms to participate in the study, and their legal guardians provided informed consent. Demographic information, preinjury psychosocial variables, and injury indices for these participants studied at the 12-month follow-up period are presented in Table 1.

TABLE 1. Demographic, psychosocial, and injury variables among children assessed 12 months after traumatic brain injury (N=120)

VariableN%
Demographic
 Age at injury (years) (mean±SD)9.992.78
 Male7965.8
 Socioeconomic status (mean±SD)37.2312.65
Psychosocial
 Preinjury lifetime psychiatric disorders2823.3
 Preinjury Vineland Adaptive Behavior Scales composite score (mean±SD)95.7814.26
 Preinjury Family Assessment Device General Functioning Scale score (mean±SD)a1.620.50
Injury
 Glasgow Coma Scale score (lowest postresuscitation) (mean±SD)10.934.14
 Glasgow Coma Scale score
  3–84436.7
  9–121512.5
  13–156150.8

aFor average scores in reference populations, see the Methods section in the article text.

TABLE 1. Demographic, psychosocial, and injury variables among children assessed 12 months after traumatic brain injury (N=120)

Enlarge table

Measures

Psychiatric outcome (novel oppositional defiant disorder) and psychiatric mediating diagnoses.

DSM-IV (9) psychiatric diagnoses, including our outcome psychiatric measure of novel oppositional defiant disorder, several potential preinjury psychiatric predictor variables (preinjury ADHD and preinjury lifetime psychiatric disorder), and concurrent novel psychiatric disorder mediator variables (novel anxiety disorder and novel depressive disorder) were made using the Schedule for Affective Disorders and Schizophrenia for School-Age Children–Present and Lifetime Version (K-SADS-PL) (18) and the Neuropsychiatric Rating Schedule (NPRS) (19). Baseline measurements (soon after injury) recorded preinjury diagnoses, and assessments were repeated at 6 months and 12 months postinjury to record any diagnoses that were not present before injury but were present in the 6- to 12-month postinjury interval. The K-SADS-PL is a semistructured, integrated parent-child interview developed to make diagnoses in both children and adolescents using DSM-IV criteria (9). Although the NPRS is structured similarly to the K-SADS-PL, it is more specific in that it assesses for personality change due to TBI. All interviewers were master’s-level or doctoral-level clinicians trained by J.E.M. in prestudy and mid-study workshops. A child psychiatrist supervised the assessments at four sites, and a child psychologist oversaw one site. In addition to this supervision, written summaries compiled by the interviewers were reviewed by J.E.M., who also held monthly teleconferences with the interviewers to discuss the cases. The central questions of the study involved present and lifetime symptoms and timing of the onset of these symptoms in relation to the TBI. Novel oppositional defiant disorder in the 6- to 12-month postinjury interval was recorded if the child had no preinjury disorder but later developed oppositional defiant disorder after the injury. Novel oppositional defiant disorder also could occur when a child developed the disorder but had a different preinjury psychiatric disorder, such as generalized anxiety disorder or ADHD.

Socioeconomic status.

The Four-Factor Index was used to measure socioeconomic status (20). Classification is based on a formula that accounts for both maternal and paternal educational and occupational levels. The scores range from 8 to 66, with a higher score representing a higher socioeconomic status.

Family function.

The general functioning 12-item subscale of the McMaster Family Assessment Device assesses global family functioning (21). The scale consists of 12 questions, scored on a 4-point scale, with lower scores representing healthier family functioning. The child’s primary caretaker completed this scale. Preinjury family function was rated at the baseline assessment. Scores in families of nonclinical, psychiatric, and medical probands were 1.84 (SD=0.43), 2.27 (SD=0.51), and 1.89 (SD=0.45), respectively (22).

Psychosocial adversity.

The psychosocial adversity measure used was similar to that used in a pioneering pediatric TBI study (2). Six areas of adversity were assessed: the child not living with biological or adoptive parents, siblingship of at least four children or a person-to-room ratio exceeding 1, family difficulties leading to admission of the child into local authority care, maternal malaise inventory score ≥7, paternal criminality, and father or mother with an unskilled or semiskilled job. A score of 1 indicated adversity, and a score of 0 indicated no adversity in each area.

Family psychiatric history.

The Family History Research Diagnostic Criteria interview was conducted by trained research assistants at the baseline assessment (23, 24). At least one parent for each child answered questions that were aimed at documenting the presence and severity of psychiatric disorders in the child’s first-degree relatives. Scores ranged from 0 to 3 with increasing severity (5).

Adaptive function.

The Vineland Adaptive Behavior Scales were used to measure adaptive functioning at baseline assessment after the injury (25). This assessment is a structured interview conducted with the child’s primary caretaker. It accounts for the kinds of behaviors a child displays in his or her environment and then provides an overall adaptive-behavior composite score (mean=100 [SD=15]).

Neurological assessments.

The GCS, which is the standard measure of severity of acute brain injury associated with closed head trauma, was used to assess the severity of the children’s brain injuries (16). The GCS has three different classifications with their respective score ranges: severe (38), moderate (912), and mild (1315).

MRI (1.5-T) was completed for the vast majority of children about 3 months postinjury. The procedure included a T1-volumetric spoiled gradient-recalled echo (1.5-mm slices) and fluid-attenuated-inversion recovery sequences (3-mm slices) obtained in coronal and sagittal planes per research protocol guidelines. A neuroradiologist coded the different lesions from a list of brain structures using the multiple-slice, hard-copy films at each site. The anatomical locations included white matter, cortical gray matter (frontal, temporal, parietal, and occipital), and subcortical gray matter (thalamus and basal ganglia) (12). Images were not registered, tissue types were not segmented, and volumetric analyses were not performed.

Neuropsychological assessment.

The Wechsler Intelligence Scale for Children–Third Edition coding and symbol search subtests were performed to measure processing speed (26). In the coding subtest, children are requested to transcribe the correct geometric designs below numbers guided by a key. The number of symbols transcribed correctly in 2 minutes was recorded. The symbol search subtest required the participant, when presented with target stimuli, to check a “yes” or “no” box as quickly as possible to specify whether the target or targets appeared among the presented stimuli (total trials, N=45). The symbol search score was the number of correct responses minus the number of errors completed in 120 seconds. A scaled processing speed score was obtained and averaged for both subtests.

Statistical analyses.

To assess the representativeness of the cohort that participated versus the cohort that did not participate in the 12-month assessment, independent sample t tests and chi-square analyses or Fisher’s exact tests were performed, depending on whether the variables of interest were continuous or categorical variables, respectively. To test the associations of 12-month novel oppositional defiant disorder with the hypothesized continuous and categorical variables, logistic regression univariable analyses were conducted. To determine the relative importance of variables associated with novel oppositional defiant disorder, a stepwise logistic regression analysis was conducted with novel oppositional defiant disorder as the dependent variable. The baseline predictors were included in the model using backward model selection with a p value <0.15 inclusion criterion using the likelihood ratio test. Statistical significance was considered at an alpha level of 0.05. All tests were two-sided. All analyses were conducted in SPSS.

Results

Occurrence

Of the original 177 children, 11 were excluded from the analyses because their preinjury oppositional defiant disorder (N=7, including three resolved cases), conduct disorder (N=2), and DBD NOS (N=2) precluded them from developing a novel oppositional defiant disorder, conduct disorder, or DBD NOS diagnosis. Additionally, one child experienced a second TBI between the 6- and 12-month assessments and thus was excluded from the analyses. Of the remaining 165 children, 120 (72.7%) returned for the 12-month psychiatric assessment. However, termination of the funding cycle resulted in nine children who did not return; therefore, the effective participation was 120 out 156 children (76.9%). Female participants were more likely to participate at the 12-month follow-up compared with male participants (N=41/48 [85%] versus N=79/117 [68%]; Fisher’s exact test, p=0.021). Participation was significantly related to race (Fisher’s exact test, p=0.028), and inspection of the data suggested higher attrition among African Americans (N=14/30 [47%]). Those lost to follow-up had significantly lower baseline postinjury processing speed standard scores (mean=91.8 [SD=20.3; N=36] versus mean=100.1 [SD=18.5; N=102]; t=−2.2, df=136, p=0.027). Participation was not significantly related to age at injury, injury severity (lowest postresuscitation GCS score), socioeconomic status, psychosocial adversity, family function, preinjury lifetime psychiatric disorder, preinjury ADHD, preinjury depressive disorder, preinjury anxiety disorder, or preinjury adaptive function (p>0.05). Of the 120 children who returned for the 12-month assessment, seven (5.8%) developed novel oppositional defiant disorder, conduct disorder, or DBD NOS. The specific novel psychiatric disorder in these children included oppositional defiant disorder (N=7), conduct disorder (N=0), and DBD NOS (N=0). Therefore, we refer to the outcome of interest as novel oppositional defiant disorder. Six of the seven cases of novel oppositional defiant disorder reported in this 6- to 12-month postinjury interval also had novel oppositional defiant disorder in the first 6 months postinjury. The seventh case of novel oppositional defiant disorder developed de novo during the second 6 months postinjury. The following analyses are limited to the seven patients who had novel oppositional defiant disorder during the 6–12 months postinjury. Of the 11 cases of novel oppositional defiant disorder reported in the first 6-month postinjury interval, nine participated in the 12-month assessment. Three of these nine cases (33%) showed resolution of their novel oppositional defiant disorder.

Psychosocial and Biological Correlates of Novel Oppositional Defiant Disorder

The relationship of psychosocial variables and novel oppositional defiant disorder is summarized in Table 2. Logistic regression univariable analyses demonstrated that socioeconomic status (odds ratio=0.871, 95% CI=0.795, 0.953, p=0.003), preinjury adaptive function (odds ratio=0.929, 95% CI=0.867, 0.996, p=0.038), and psychosocial adversity score (odds ratio=2.367, 95% CI=1.217, 4.604, p=0.011) were significantly associated with novel oppositional defiant disorder. Furthermore, the logistic regression univariable analysis examining the relationship of preinjury family function to novel oppositional defiant disorder had a p value under the predetermined threshold for additional multivariable analyses (odds ratio=1.104, 95% CI=0.977, 1.246, p=0.112).

TABLE 2. Results of logistic univariable regression analyses of psychosocial and biological correlates of novel oppositional defiant disorder among children assessed 12 months after traumatic brain injurya

Novel oppositional defiant disorder (N=7)No novel oppositional defiant disorder (N=113)
VariableMeanSDNMeanSDNOdds ratio95% CIpb
Socioeconomic statusc20.5011.2438.2812.021110.8710.795, 0.9530.003
Preinjury family functioning1.980.4351.610.501051.1040.977, 1.2460.112
Preinjury psychosocial adversity score1.861.350.750.951102.3671.217, 4.6040.011
Preinjury adaptive functioning83.6710.73696.4614.171070.9290.867, 0.9960.038
Glasgow Coma Scale score8.575.5311.084.020.8690.724, 1.0440.133

aThe values are expressed for children with novel oppositional defiant disorder and children with no novel oppositional defiant disorder unless otherwise indicated due to missing data. Bold indicates statistical significance.

bThe p value was determined using the Wald test.

cSocioeconomic status was the only variable included in the multivariable model, after backward model selection.

TABLE 2. Results of logistic univariable regression analyses of psychosocial and biological correlates of novel oppositional defiant disorder among children assessed 12 months after traumatic brain injurya

Enlarge table

Table 2 also shows the relationship of injury severity and novel oppositional defiant disorder. The logistic regression univariable analysis examining the relationship of the lowest postresuscitation GCS score and novel oppositional defiant disorder had a p value under the predetermined threshold for additional multivariable analyses (odds ratio=0.869, 95% CI=0.724, 1.044, p=0.133).

As planned, a backward stepwise likelihood ratio logistic regression analysis was conducted with novel oppositional defiant disorder as the dependent variable, and the independent variables consisted of the baseline measures that were associated with novel oppositional defiant disorder at the p<0.15 level in univariable analyses (socioeconomic status, preinjury adaptive functioning, psychosocial adversity score, preinjury family function, and lowest postresuscitation GCS score) to determine which of these variables were independently related to developing novel oppositional defiant disorder. The final model included only lower socioeconomic status, and therefore socioeconomic status values presented in Table 2 reflect the multivariable analyses. This result suggests that of the array of significant individual preinjury and injury biopsychosocial predictors, socioeconomic status is the most important variable predictive of novel oppositional defiant disorder outcome at 12 months.

Exploratory Analyses

The planned exploratory analyses related to novel oppositional defiant disorder is presented in Table 3. Novel oppositional defiant disorder was not significantly related to demographic variables (age, sex, and race), family psychiatric history, preinjury lifetime psychiatric disorder, preinjury ADHD, novel anxiety disorder, novel depressive disorder, presence of a frontal lobe white matter lesion, and baseline postinjury processing score (all p values >0.05).

TABLE 3. Exploratory logistic univariable regression analyses of the relationship of demographic, family psychiatric history, psychiatric diagnoses, and injury variables with novel oppositional defiant disorder among children assessed 12 months after traumatic brain injurya

Novel oppositional defiant disorder (N=7)No novel oppositional defiant disorder (N=113)
VariableN%N%Odds ratio95% CIpb
Age at injury (years) (mean±SD)9.692.6410.012.810.96c0.73, 1.27n.s.
Male57174660.760.14, 4.09n.s.
Race0.086
 White22966581
 Hispanic45723205.740.99, 33.44
 Black or African American001614
 Asian1143311.000.77. 158.01
 Other0054
Family psychiatric history (mean±SD)d1.501.221.111.061.40.65, 2.98n.s.
Preinjury lifetime psychiatric disorder11427241.880.21, 16.35n.s.
Preinjury ADHD11417151.060.12, 9.39n.s.
Novel anxiety disorder11411100.650.07, 5.88n.s.
Novel depressive disordere114652.920.30, 28.27n.s.
Injury data
 Frontal white matter lesionf0021200.00, >1.0000.084
 Baseline processing speed standard score (mean±SD)g91.0017.22100.5318.540.970.92, 1.02n.s.

an.s.=not significant.

bThe p value was determined with the likelihood ratio test.

cPer additional year.

dData were missing for one participant in the novel oppositional defiant disorder group and 21 participants in the no novel oppositional defiant disorder group.

eThe denominator in the no novel oppositional defiant disorder group was 111 because preinjury depressive disorder for two participants precluded development of novel depressive disorder.

fData were missing for seven participants in the no novel oppositional defiant disorder group.

gData were missing for two participants in the novel oppositional defiant disorder group and 16 participants in the no novel oppositional defiant disorder group.

TABLE 3. Exploratory logistic univariable regression analyses of the relationship of demographic, family psychiatric history, psychiatric diagnoses, and injury variables with novel oppositional defiant disorder among children assessed 12 months after traumatic brain injurya

Enlarge table

Postinjury Outcome for Children With Preinjury Oppositional Defiant Disorder, Conduct Disorder, or DBD NOS

Because the effect of TBI on children with preexisting oppositional defiant disorder, conduct disorder, or DBD NOS is of interest to clinicians and researchers, these data are provided. Two of the four children with unresolved preinjury oppositional defiant disorder continued to manifest the disorder, and a third progressed to conduct disorder by 12 months. The fourth child with unresolved preinjury oppositional defiant disorder did not return for the 12-month assessment. None of the three children with resolved preinjury oppositional defiant disorder returned for assessment at 12 months. Two children had preinjury conduct disorder, which resolved in one, while the other did not return for assessment. Similarly, two children had preinjury DBD NOS; the disorder resolved in one child following TBI, and the other child did not return for assessment.

Discussion

The main finding of this prospective study of pediatric TBI is that clinically significant novel oppositional defiant disorder present in the 6- to 12-month postinjury interval has significant preinjury psychosocial predictors that coincide generally with and expand results of the scarce related existing studies. Specifically, novel oppositional defiant disorder was present in 6% of children who were 5–14 years old when they were injured and was significantly associated with preinjury psychosocial risk factors (lower socioeconomic status, higher psychosocial adversity, and lower adaptive function). There was no significant association of novel oppositional defiant disorder with injury severity.

The rate of novel oppositional defiant disorder was similar to that documented at the 1-year follow-up of a consecutively treated rehabilitation center cohort (6% versus 9%). This similarity is especially noteworthy because of study design differences. The differences between the present study and the rehabilitation center study include consecutively hospitalized children for TBI compared with children consecutively treated at a rehabilitation facility; TBI severity ranging from mild to severe compared with severe only; and novel oppositional defiant disorder diagnoses made using impairment criteria, compared with not using impairment criteria. An important divergent finding between studies was the 0% versus 8% rate of novel conduct disorder in the present study versus the rehabilitation-sample study. We suspect that this divergence is related to methodological differences in the application of impairment criteria.

The significant relationship of novel oppositional defiant disorder with preinjury psychosocial variables (hypothesis 1) extends the timeline of this association from the first 6 months postinjury to 12 months postinjury in the present cohort. Our 12-month follow-up findings were that in univariable analyses, novel oppositional defiant disorder was significantly predicted by distal preinjury psychosocial variables (lower preinjury socioeconomic status and higher preinjury psychosocial adversity) and a proximal preinjury psychosocial variable (lower preinjury adaptive function). These results are similar to our 6-month follow-up findings, except for the earlier finding of a significant relationship of novel oppositional defiant disorder and preinjury family function, whereas the relationship with preinjury adaptive function fell short of statistical significance. At both the 6-month and 12-month assessment points, the only independently significant preinjury psychosocial predictor of novel oppositional defiant disorder in multivariable analyses was lower socioeconomic status (10).

These predictive variable findings replicate findings in the few previous related studies. Novel oppositional defiant disorder in a rehabilitation study was significantly related to psychosocial adversity in univariable analyses, but only preinjury history of special education was associated in multivariable analyses (4). Our earlier study of consecutively hospitalized children with mild to severe TBI examining oppositional defiant disorder symptoms postinjury rather than novel oppositional defiant disorder found that total symptoms 12 months postinjury were significantly related to preinjury family function, socioeconomic status, and preinjury oppositional defiant disorder symptom count in a regression analysis, with model R2 increasing from 0.23 to 0.32 to 0.49 with addition of each significant predictor (11). A closer comparison of our earlier study with the present study was the examination of change in oppositional defiant disorder symptom count from preinjury to 12 months postinjury, which was significantly associated with only socioeconomic status in a regression analysis with a model R2=0.36 (11).

To our knowledge, the significant association of novel oppositional defiant disorder and preinjury adaptive function, a proximal preinjury psychosocial predictor, has not previously been detected. This adaptive functional domain may be considered as a measure of behavioral reserve, not unlike the construct of cognitive reserve (13, 27). Thus, we offer the operative principle that in the face of a given level of brain insult, behavioral reserve measured as higher preinjury adaptive function serves as a buffer or protective factor in terms of transcending the level of impairment threshold for the categorical diagnosis of novel oppositional defiant disorder. This principle may encompass protective behavioral trajectories that reach beyond prevention of the development of novel oppositional defiant disorder. Other empirically testable trajectories could include a scenario in which children with greater preinjury-learned socialization, communication, and daily living skills recover more readily, resulting in improved behavior, modulation of affect, and aggression following TBI. It is also conceivable that preinjury adaptive function may not be directly involved from a mechanistic point of view but rather may be a marker for the ability to relearn inhibitory control of aggression or irritability and regulation of mood. The delayed emergence of significance for preinjury adaptive function in the 6- to 12-month postinjury interval rather than the 6-month postinjury interval suggests that over time, behavioral reserve may become a more cogent variable for determining novel oppositional defiant disorder outcome. This behavioral reserve concept is not unique to novel oppositional defiant disorder, as preinjury adaptive function has been found to significantly predict other novel disorders, including personality change due to TBI and novel ADHD at various postinjury intervals (13, 14).

Hypothesis 2—that novel oppositional defiant disorder would be significantly associated with severity of TBI measured by the lowest postresuscitation GCS score—was not supported. This is generally consistent with some previous studies, the findings of which are characterized by significant preinjury psychosocial predictive variables (4, 11), but inconsistent with others (17). It is likely that the present study had insufficient power to detect a significant difference. This is suggested by the observation of a moderate effect size (Cohen’s d=0.52) regarding the comparison of lowest postresuscitation GCS scores between children with and without novel oppositional defiant disorder. Exploratory analyses of the postinjury baseline processing score, which is reflective of injury severity (10, 28), were also not significant. However, limited power was also likely responsible for this result, as there was a comparable moderate effect size (Cohen’s d=0.53). Additionally, the fact that the children lost to attrition had significantly lower baseline postinjury processing speed scores suggested that this injury severity-related variable should not be ruled out as a potential predictor of novel oppositional defiant disorder in adequately powered studies.

Other exploratory analyses did not show any significant association between novel oppositional defiant disorder and age, sex, race, family psychiatric history, preinjury lifetime psychiatric disorder, preinjury ADHD, and presence of a frontal lobe white matter lesion. Although we did not find a significant association of novel oppositional defiant disorder with novel depressive disorder and novel anxiety disorder, we have previously shown significant comorbidity of novel oppositional defiant disorder with personality change due to TBI and also with novel ADHD in the 6- to 12-month postinjury interval with the present cohort (13, 14).

The findings of this study must be viewed within its limitations. First, we did not include a non-brain-related injury control group to compare with the TBI group. Establishing causality between TBI in children and developing oppositional defiant disorder is difficult without a control group. Second, interrater reliability for psychiatric diagnoses was not directly tested within and across testing sites. However, the outlined specific quality control and training procedures diminished this issue. Third, neuroimaging analyses were rudimentary and did not include volumetric or tissue-segmentation measures. Fourth, sample attrition was approximately 27% due to attrition of a 12-month follow-up. Attrition was significantly related to sex and race (more males and African Americans were lost to follow-up), and nonparticipants had lower postinjury processing speed performance. However, the participants and nonparticipants were no different on multiple variables such as age, socioeconomic status, preinjury psychosocial adversity, preinjury adaptive function, preinjury family function, preinjury psychiatric status, and injury severity. Fifth, diagnostic criteria from DSM-IV (the version that was current at the time of this study) were used to define each diagnosis. However, the classification of oppositional defiant disorder, including meeting at least four of eight criteria to qualify for diagnosis of the disorder, remained the same between DSM-IV and DSM-5, aside from minor semantic differences (29). Sixth, the natural history of postinjury treatment seeking by the families of participants may be a variable and could influence the outcome. Finally, this study was limited to only measuring the impact of TBI at one time point, 12 months postinjury, as opposed to multiple time points as some other studies have done.

This study has several notable strengths. Importantly, to our knowledge, this is the largest prospective pediatric TBI study to use a clinician-administered semistructured psychiatric assessment on a consecutively admitted nonreferred population assessing outcomes considered to be clinically significant. The extensive range of measures included interview assessments of psychopathology, adaptive function, and family psychiatric history, in addition to rating scales measuring injury and other psychosocial risk factors for new-onset psychopathology. Additionally, lesion analysis was based on readings by expert neuroradiologists, despite lesion correlates being a negative finding. Finally, the results from this study are generalizable to a wide pediatric TBI population due to examining a spectrum of mild to severe TBI.

Conclusions

The postinjury sequela of clinically significant novel oppositional defiant disorder occurred in a small (6%) but important proportion of children who were consecutively admitted for mild to severe TBI. A proportion of cases of novel oppositional defiant disorder (N=3/9; 33%) resolved after the 6-month postinjury mark; de novo novel oppositional defiant disorder occurred after the 6-month mark but was rare. These findings suggest that clinicians can offer reassurance to some degree regarding resolution of novel oppositional defiant disorder but should also be vigilant for delayed onset of the disorder after 6 months postinjury and perhaps follow more closely at regular intervals to intervene as indicated. Earlier data have established an association of novel oppositional defiant disorder with both novel ADHD and personality change due to TBI. Therefore, to facilitate comprehensive treatment, clinicians should be on high alert for all three of these novel disorders when one of the disorders is more readily apparent. Novel oppositional defiant disorder was significantly associated with preinjury distal psychosocial risk factors (lower socioeconomic status and higher psychosocial adversity) and with a preinjury proximal psychosocial risk factor (lower adaptive function). Although the biological risk factor, severity of injury, was not significantly related to novel oppositional defiant disorder, it should not be ruled out because of the present study’s insufficient power. Finally, an important implication of our biopsychosocial risk factor findings is that children who are at higher risk for developing novel oppositional defiant disorder may be identified soon after injury and monitored for the purposes of decreasing this specific complication with timely interventions.

Department of Psychiatry, University of California, San Diego (Lowet, Max), Herbert Wertheim School of Public Health, Division of Biostatistics and Bioinformatics, University of California, San Diego (Vaida); Department of Radiology, University of California, San Diego (Hesselink); Department of Physical Medicine and Rehabilitation, Baylor College of Medicine, Houston (Levin); Department of Pediatrics, University of Texas Health Science Center, Houston (Ewing-Cobbs); Department of Psychiatry, University of Texas Health Science Center, Houston (Saunders); The Hospital for Sick Children, University of Toronto (Schachar); Center for BrainHealth, University of Texas, Dallas (Chapman); Department of Psychology, Brigham Young University, Provo, Utah (Bigler); Department of Neurology, Traumatic Brain Injury and Concussion Center, University of Utah, Salt Lake City (Bigler, Wilde); Department of Psychiatry and Behavioral Sciences, Division of Child and Adolescent Psychiatry, Weill Institute for Neurosciences, University of California, San Francisco (Yang); Department of Radiology and Biomedical Imaging, University of California, San Francisco (Tymofiyeva); and Rady Children’s Hospital, San Diego (Max).
Send correspondence to Dr. Max ().

Dr. Ewing-Cobbs provides expert testimony in cases of traumatic brain injury on an ad hoc basis, largely for plaintiffs, at <5% of professional activities. Dr. Schachar serves as a consultant to Ehave and Highland Therapeutics. Dr. Bigler provides expert testimony in cases of traumatic brain injury. Dr. Max provides expert testimony in cases of traumatic brain injury on an ad hoc basis for plaintiffs and defendants on a more or less equal ratio, constituting approximately 5%–10% of his professional activities. The other authors report no financial relationships with commercial interests.

Supported by NIMH (grant K-08 MH01800 to Dr. Max); the National Institute of Child Health and Development (grant HD088438 to Dr. Max); the National Institute of Neurological Disorders and Stroke (grant NS-21889 to Dr. Levin); and the National Center for Complementary and Integrative Health (grant 1R61AT009864-01A1 to Drs. Tymofiyeva and Yang).

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