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8 PSYCHIATRIC OUTCOMES Psychiatric disorders after traumatic brain injury (TBI) have been well documented. Rogers and Read (2007) note that survivors of brain injury are at particularly increased risk for depression, generalized anxiety disorder, and posttraumatic stress disorder (PTSD), although the etiology is unclear. They further note that psychiatric sequelae are often among the most disabling consequences of a TBI and can adversely affect recovery and psychosocial outcome. As advances in neuroscience have begun to elucidate the pathophysiology of psychiatric disorders, there is progress toward delineating the specific regional brain structures, functions, and chemistry underlying the conditions (Drevets, 2001; Rauch et al., 2006). The Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV), which is considered the gold standard for psychiatric diagnosis, explicitly distinguishes between psychiatric disorders that emerge in a primary fashion (for example, major depressive disorder) and those attributable to a specific medical cause, such as an endocrine disturbance, stroke, or TBI (for example, mood disorder due to a general medical condition). Taylor and Jung (1998) postulate that a personâs decreased ability to function at work and at home after a TBI leads to psychologic distress that in turn leads to the development of mood disorders with greater frequency than in the general population. In such cases of nonspecific effects of psychologic stress, a primary psychiatric diagnosis in accordance with DSM-IV would be appropriate. In contrast, if the psychiatric condition were deemed to be a direct consequence of the TBI because of disruption of brain functionâfor example, as is believed to occur when stroke affects specific brain distributions (Spalletta et al., 2006)âthe diagnosis of mood disorder due to a general medical condition might be more appropriate. In addition to the possibility that TBI leads to psychiatric sequelae through nonspecific psychologic factors or through more specific brain injuryârelated factors, there is evidence that prior psychiatric illness may predispose to TBI, which in turn could increase the risk of recurrence or exacerbation of previous psychiatric conditions (Fann et al., 2002). Thus, given the uncertainty regarding the mechanisms that link TBI and psychiatric diagnoses, we have chosen to use the terminology of primary psychiatric disorders, as has been the custom in the TBI literature on psychiatric outcomes. The committee reviewed approximately 350 studies of mood and anxiety disorders and other psychiatric outcomes after brain injury. Few studies, however, met the committeeâs criteria for a primary study. 265
266 GULF WAR AND HEALTH MOOD DISORDERS Mood disorders are a cluster of mental disorders that are characterized by mood swings or an abnormally depressed (low) or manic (elevated or irritable) mood. The most common mood disorder is major depression; others include bipolar disorder (or manic-depressive disorder), cyclothymia, and dysthymia (United States Department of Health and Human Services, 2006). Major depression is characterized by persistent feelings of sadness accompanied by several symptoms related to changes in appetite or sleeping patterns, loss of interest in activities, fatigue, inability to concentrate, and hopelessness or suicidal thoughts. Bipolar disorder is characterized by at least one manic episode and often by recurring episodes of mood disturbance, including both depressed and manic episodes. Bipolar disorder typically begins in a personâs middle twenties, tends to appear in families, and is a lifelong disorder. There are few published data on an association of TBI with bipolar disorder. Suicidal behavior is one of the most serious consequences of mood disorders and may consist of suicidal ideation (thoughts), suicide attempts, or completed suicide; suicide is discussed in the next section of this chapter. Primary Studies The committee identified four primary studies that examined an association between TBI and mood disorders. Fann et al. (2004) conducted a prospective cohort study to determine the risk of psychiatric illness after TBI. Patients were drawn from a health maintenance organization, Group Health Cooperative of Puget Sound, and received care in its facilities in six different counties in Washington. Computerized records of 939 health-plan members, 15 years old or older who had a diagnosis of a TBI in 1993, were available. Each patient was matched on sex, age, and reference date to three randomly selected unexposed health-plan members. TBI was ascertained in an emergency room, hospital or outpatient clinic, and severity of TBI was established by using the Centers for Disease Control and Prevention criteria. Psychiatric illnesses were ascertained by using the presence of psychiatric diagnoses, filling of prescriptions for psychiatric medications, and utilization of psychiatric services. In the first year after a moderate to severe TBI, 49% of the patients had evidence of psychiatric illnesses compared with 34% in the mild-TBI group and 18% in the comparison group; this reflected a significantly increasing risk of psychiatric illness with severity of TBI. The authors also found the risk of psychiatric illness to be greatest in the 6â12 months after the TBI in analyses that separately considered whether or not psychiatric illness had occurred in the year before injury. In patients without psychiatric illness in the year before injury, there was a 4-fold increased risk for developing a psychiatric disorder in the 6 months after a moderate to severe TBI (95% confidence interval [CI], 2.4â6.8) and a 2.8-fold increased risk after a mild TBI (95% CI, 2.1â3.7) compared with the risk in patients without a TBI. In patients with prior psychiatric illness, the corresponding increases in risk of psychiatric illness were factors of 2.1 (95% CI, 1.3â3.3) and 1.6 (95% CI, 1.2â2.2), respectively. The limitations of the study include the possible lack of precision in TBI exposure measurement, uncertainty regarding past psychiatric diagnosis occurring more than 1 year before ascertainment, and possible confounding by socioeconomic status. Holsinger et al. (2002) examined the association between TBI and lifetime and current depression in a nested caseâcontrol study of World War II veterans. Cases were World War II veterans who had been hospitalized for TBI in 1944â1945 and controls were veterans who had been hospitalized during the same period with either pneumonia or serious laceration or other
PSYCHIATRIC OUTCOMES 267 wounds but without TBI. Veterans were identified 50 years after the war on the basis of the diagnosis reported on their âF-cardsâ in their medical records. Of the 3,460 veterans with reported head injuries (combat and non-combat-related), 1,422 met the authorsâ criteria for TBIâdocumented TBI in a military record; occurrence during military service; produced loss of consciousness (LOC), posttraumatic amnesia (PTA), or nondepressed skull facture; failure to penetrate the dura mater; and lack of significant cognitive impairment or neurological sequelae more than 3 months after the traumaâand 520 were included in the study. TBI was categorized as mild, moderate, or severe on the basis of the duration of LOC or PTA. Motor- vehicle crashes (26%), falls (19%), and blast concussions (17%) were the leading causes of head injuries. Among the 4,022 potential controls, 1,198 were included in the study. A lifetime history of depression was assessed on the basis of a structured telephone interview with the veteran or his proxy; participants who responded affirmatively to any of three questions regarding mood also were given a modified version of the Diagnostic Interview Schedule for depression to decide on a DSM-IV diagnosis of major depression. The lifetime odds of major depression was significantly increased in veterans with TBI compared with controls (odds ratio [OR], 1.54, 95% CI, 1.17â2.04). Current major depression was also significantly increased in veterans with TBI (OR, 1.63, 95% CI, 1.07â2.50). The odds of lifetime depression also varied with TBI severity with ORs of 1.99 (95% CI, 1.11â3.57) for severe TBI, 1.40 (95% CI, 0.97â1.83) for moderate TBI, and 1.49 (95% CI, 0.96â2.31) for mild TBI. Alcohol abuse, myocardial infarction, and cerebrovascular accident did not appear to influence the association between TBI and lifetime risk of major depression. However, the odds did increase with age: ORs were 0.81 (95% CI, 0.45â1.43) for men aged 65â69 years old, 1.45 (95% CI, 1.07â1.97) for men 70â74 years old, 2.61 (95% CI, 1.58â4.30) for men 75â79 years old, and 5.95 (95% CI, 2.05â17.23) for men 80 years old and older. One important limitation of this study was the failure to specifically ascertain the presence of major depression before TBI. Jorge et al. (2004) assessed the presence of comorbid psychiatric disorders in 91 consecutive patients with closed TBI and a comparison group of 27 patients with multiple trauma but without evidence of central nervous system injury who were admitted at injury to two Iowa medical facilities. Patients with peripheral nerve injuries or spinal-cord injuries were excluded. All included patients were assessed at 3, 6, and 12 months after injury. A modified version of the Present State Examination and the Structured Clinical Interview for DSM-IV diagnoses were used to make a DSM-IV diagnosis of mood and anxiety disorder. The severity of symptoms of depression and anxiety was assessed with the Hamilton Depression Rating Scale and the Hamilton Anxiety Scale; aggressive behavior was assessed with the Overt Aggression Scale. Neuroimaging was done with computed tomography scans or magnetic resonance imaging, and a neuropsychologic assessment was conducted at 3 months. Of the 91 TBI patients, 47 (51.6%) developed a mood disorder in the 12 months after their injury, 30 (33%) of whom had major depressive disorder. There was no significant between-group difference with respect to prior history of depression or anxiety disorders. Mood disorder was statistically significantly more common in the TBI group than in the comparison group during the first year after injury (51.6% vs 22.2%, p = 0.006). Of the patients who met DSM-IV criteria for mood disorder, 30 of the TBI patients presented with major depression compared with controls (p = 0.008). The authors compared the 30 TBI patients who had major depressive disorder with the 44 TBI patients who did not develop any mood disorder in the 12 months after injury. Of the 30 TBI patients with major depression, 23 (76.7%) also met the criteria for an anxiety disorder compared
268 GULF WAR AND HEALTH with 9 (20.5%) of the 44 TBI patients without major depression (p < 0.001). Of the 23 patients with both major depression and an anxiety disorder, 14 had generalized anxiety features, 2 had generalized anxiety and panic attacks, and 7 met the criteria for PTSD. Significant aggressive behavior was seen in 17 (56.7%) of the 30 patients with TBI and major depression compared with 10 (22.7%) of the 44 TBI controls (p = 0.003). Half the 30 patients with TBI and major depression received the diagnosis at their initial evaluation, and an additional 9 patients received the diagnosis at the 3-month follow-up. There were no significant differences between TBI patients with and without major depression in demographic variables or the use of alcohol or other drugs. Those with TBI and major depression had a significantly higher frequency of a personal history of mood disorders (p = 0.01) and anxiety disorders (p = 0.05). A recent study by Hoge et al. (2008) examined consequences of mild TBI in US soldiers that saw a high level of combat during a year-long deployment in Iraq. About 3â4 months after return from Iraq, soldiers were sent a questionnaire covering injury, combat intensity, physical symptoms, major depression, and PTSD. Soldiers were considered to have mild TBI if they answered yes to any of three questionsâabout losing consciousness, being dazed or confused, or not recalling the injury. The answers to those questions were used to form two subgroups within the mild-TBI group to determine whether LOC was a stronger predictor (that is, one that had LOC and one that had dazing or confusion or did not recall the injuryâthe second made up the altered-mental-status group). The final samples were 124 with mild TBI and LOC, 260 with mild TBI and altered mental status, 435 with other injury, and 1,706 with no injury. PTSD was present in 43.9% with LOC, in 27.3% with altered mental status, in 16.2% with other injury, and 9.1% without injury (p < 0.001). Major depression was associated with LOC more than with other injury (22.9% vs 6.6%, p < 0.001) but was not associated with altered mental status more than with other injury (8.4% vs 6.6%, p = 0.39). Limitations of this study included a failure to control analyses for major depression before TBI. Furthermore, groups were not well matched for combat intensity. Finally, it is unclear how one could effectively distinguish between a history of LOC or altered mental status attributable to TBI and similar phenomena attributable to dissociation 4 in the face of emotional trauma. Secondary Studies The committee identified five secondary studies that looked at the association between TBI and mood disorders, specifically, depression. Limitations of these studies include the self- reported diagnosis of TBI and retrospective assessment of mood disorders. Vanderploeg et al. (2007) conducted a cross-sectional study of the long-term psychiatric, neurologic, and psychosocial outcomes associated with self-reported mild TBI. A subsample of 4,384 veterans was categorized into three groups: no motor-vehicle accident and no TBI (normal control, n = 3,214); injured in a motor-vehicle accident but no TBI (motor-vehicle accident control; n = 539); and TBI with altered consciousness (mild-TBI group; n = 254). Results indicate that the mild-TBI group had a higher frequency of depression than the normal control group (OR, 1.77, 95% CI, 1.13â2.78). The mild-TBI group also had a higher frequency of prior depression than the normal control group, but the adjusted OR was virtually identical (1.78; 95% 4 Dissociation is a mental state in which a personâs thoughts, emotions, or memories are compartmentalized, usually in response to a traumatic event. Some dissociative disorders include psychogenic amnesia, psychogenic fugue, and multiple personality.
PSYCHIATRIC OUTCOMES 269 CI, 1.06â3.00) when the analysis was restricted to those who had no prior history of depression. Three other secondary studies also found that depression was associated with TBI (Masson et al., 1996; Hibbard et al., 1998, Deb et al., 1999). In contrast, Malec et al. (2007) examined 51 patients who had moderate to severe TBI, 42 patients who had mild TBI, and 42 controls who had orthopedic injuries and found no difference in depression rates among the three groups. Summary and Conclusion The committee reviewed four primary and five secondary studies of mood disordersâ major depressionâand findings were consistent. The preponderance of studies found that groups with TBI (mild, moderate, or severe) had higher rates of major depression 6 months or longer after TBI than did appropriate comparison groups (including non-TBI injured controls). Three studies (Fann et al., 2004; Jorge et al., 2004; Vanderploeg et al., 2007) provided some control for differences in depression before TBI; all three provided data suggesting that the observed association between TBI and major depression could not be explained by prior depression. Nevertheless, it should be noted that the available data suggest that prior mood disorder may predispose to TBI (Fann et al., 2002; Vassallo et al., 2007) and that post-TBI major depression is more frequent in people who had major depression before TBI than in people who did not (Fann et al., 2004). In contrast to depression, there are few studies on the relationship between mania or bipolar disorder and TBI (Koponen et al., 2002; Sagduyu, 2002; Silver et al., 2001). Koponen et al. (2002) and Silver et al. (2001) reported a prevalence rate of 1.7% and 1.6%, respectively, of TBI patients who met criteria for bipolar disorder. They concluded that the prevalence did not differ significantly from that found in control populations. Sagduyu (2002) examined 535 patients who had bipolar disorder. Of the 126 patients who reported a history of mild TBI, 72 reported symptoms of bipolar disorder prior before the injury, and 54 reported symptoms after the injury. Those studies do not provide consistent or compelling evidence regarding an association between TBI and mania or bipolar disorder. The committee concludes, on the basis of its evaluation, that there is sufficient evidence of an association between TBI and depression. The committee concludes, on the basis of its evaluation, that there is inadequate/insufficient evidence to determine whether an association exists between TBI and mania or bipolar disorder.
270 TABLE 8.1 Psychologic OutcomesâMood-Disorder Studies Health Outcomes or Outcome Comments or Reference Study Design Population Type of TBI Measures Results Adjustments Limitations Fann et al., Prospective 939 HMO enrollees Severity Psychiatric illness Increased rates of Age, sex, TBI Limitation: control 2004 cohort (479 women, 460 dichotomized determined with psychiatric illness in reference date, group is general HMO men) with diagnosis with CDC three major year after TBI (49% logarithm of population, not an of TBI in 1993 categorization indicators: ICD-9- in moderate to costs in year injury population enrolled in health criteria into mild CM codes, severe, 34% in mild, before reference plan for at least 1 (803), moderate prescriptions, use of 18% in non-TBI date, comorbid year before injury, 3 to severe (136); psychiatric service comparisons) injuries to 1 match with injury identified year before TBI, 1â health-plan controls; with ICD-9-CM 12, 13â24, 25â36 TBI associated with cases, controls categories, codes mo after injury; higher risk of any followed for 3 years (fracture of vault affective disorders psychiatric illness 6 after enrollment in base of skull; included depression, mo after trauma in study other, anxiety subjects with or unqualified, without prior multiple psychiatric illness fractures of skull; No prior psychiatric intracranial illness (p < 0.001): injury) mild TBI, RR, 2.8 (95% CI, 2.1â3.7); moderate to severe TBI, RR, 4.0 (95% CI, 2.4â6.8) Prior psychiatric illness (p , 0.005): mild TBI, RR, 1.6 (95% CI, 1.2â2.0); moderate to severe TBI, RR, 2.1 (95% CI, 1.3â3.3) Subjects with mild TBI showed chronic likelihood of psychiatric illness
Health Outcomes or Outcome Comments or Reference Study Design Population Type of TBI Measures Results Adjustments Limitations even in absence of prior psychiatric problems Affective disorders fairly common in TBI group with no prior psychiatric illness, particularly in persons who had mild TBI 1â6 mo: mild TBI, RR, 2.7 (95% CI, 1.5â4.8); moderate to severe TBI, RR, 1.0 (95% CI, 0.1â 7.6) 7â12 mo: mild TBI, RR, 2.2 (95% CI, 1.4â3.6); moderate to severe TBI, RR, 4.6 (95% CI, 1.8â 11.7) 13â18 mo: mild TBI, RR, 1.9 (95% CI, 1.3â2.6); moderate to severe TBI, RR, 2.2 (95% CI, 1.0â 4.9) 19â24 mo: mild TBI, RR, 1.6 (95% CI, 1.2â2.1); moderate 271 to severe TBI, RR,
272 Health Outcomes or Outcome Comments or Reference Study Design Population Type of TBI Measures Results Adjustments Limitations 1.1 (95% CI, 0.4â 3.0) Holsinger et Population- 520 head-injured Closed head Depressive illness Lifetime prevalence Age, education, Only male veterans al., 2002 based male veterans who injuries: mild, ascertained of depression: history of alcohol used in study; limited retrospective were hospitalized moderate, severe withmodified DIS Head-injured, abuse, information on age at cohort for head injury, that (1) was for DSM-IV 18.5%; non-head- myocardial onset of depression, 1,198 non-head- documented in injured, infraction, but it is unlikely that injured WWII male military medical 13.4%; OR, 1.54 cerebrovascular there was history of veterans records; (2) (95% CI, 1.17â2.04) accident major depression at hospitalized with occurred during time of enlistment pneumonia or military service; Lifetime risk of laceration, puncture, (3) produced depression increased Excluded penetrating or incision wounds; LOC, PTA, or with severity of head TBI all were on active nondepressed injury: severe, OR, duty during 1944â skull fracture; 1.99 (95% CI, 1.11â 1945 in Navy or (4) did not 3.57); moderate, OR, Marine Corps and penetrate dura 1.40 (95% CI, 0.97â were followed at 50 mater; (5) did 2.03); mild, OR, 1.49 years after injury not result in (95% CI, 0.96â2.31) significant cognitive impairment or neurologic sequelae 3 mo after injury Head-injury severity: mild, LOC or PTA for <30 min; moderate, LOC or PTA 30 minâ 24 h and/or skull fracture; severe, LOC or PTA 24 h or more
Health Outcomes or Outcome Comments or Reference Study Design Population Type of TBI Measures Results Adjustments Limitations Sources of head injuries: MVA (26%), blast concussion (17%), fights with peers (7%), falls (19%), sports injuries, including boxing (12%), miscellaneous other wartime happenings (19%) Jorge et al., Cohort 91 consecutive Closed head Major depression Mood disorders, None 2004 patients with TBI injury (mild, associated with major depressive but without spinal- moderate, anxiety symptoms, disorders cord injury severe) Present State significantly more compared with 27 Examination, SCID frequent in TBI injured patients Severe TBI: clinical, patients than in without TBI also GCS, 3â8; neuropsychologic, patients without consecutively moderate TBI: brain-imaging brain injuries: after admitted into two GCS 9â12 or variables TBI, 47 (51.6%) university hospitals GCS 13â15 with developed mood and followed up at intracranial disorder compared 3, 6, 12 mo after surgical with six controls trauma procedures or (22.2%) group (p, focal lesions 0.006); major greater than 15 depressive disorder mL; mild TBI: occurred in 30 TBI GCS 13â15 patients (33%) vs without surgery two non-TBI injured or major focal (7.4%) (p, 0.008) lesions History of past 273
274 Health Outcomes or Outcome Comments or Reference Study Design Population Type of TBI Measures Results Adjustments Limitations depression more common in patients with TBI and depression than in those with other injury and depression (36.7% vs 11.4%; p < 0.01); similarly, history of past anxiety more common in patients with TBI and depression than in those with other injury and depression (20% vs 4.6%; p < 0.05) Major depression significantly associated with comorbid anxiety disorder (76.7% vs 20.4%; p < 0.001) and decreased frontal brain volume and left frontal gray matter in first year after injury Hoge et al., Cohort Anonymous survey Mild PTSD Of 124 with LOC, 95% males; After adjustment for 2008 of 4,618 soldiers, of 43.9% met criteria 55.5% under 30 PTSD and depression, whom 2,714 (59%) 124 (4.9%) with for PTSD compared years old; 47.5% mild TBI no longer completed LOC with 27.3% of those junior enlisted significantly associated questionnaire; of reporting altered rank with physical health 2,714, 149 excluded 260 (10.3%) mental status, 16.2% outcomes or symptoms because of missing with altered with injuries, and except headache data, 40 because mental status 9.1% with no injury
Health Outcomes or Outcome Comments or Reference Study Design Population Type of TBI Measures Results Adjustments Limitations they had head injury (such as dazed Soldiers with mild without LOC or confused) TBI and LOC more likely to report poor Remaining 2,525 435 (17.2%) general health, US Army soldiers with other missed workdays, responded 3â4 mo injuries more doctor visits, after return from 1- higher numbers of year Iraqi outcomes or deployment symptoms NOTE: CDC = Centers for Disease Control and Prevention, CI = confidence interval, DIS = Diagnostic Interview Schedule, DSM-IV = Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, GCS = Glasgow Coma Scale, HMO = health-maintenance organization, ICD-9-CM = International Classification of Diseases, Ninth Revision, Clinical Modification, LOC = loss of consciousness, PTA = posttraumatic amnesia, SCID = Structured Clinical Interview for DSM-IV diagnoses, TBI = traumatic brain injury, WWII = World War II. 275
276 GULF WAR AND HEALTH SUICIDE Suicidal behavior is one of the most serious consequences of mood disorders and may consist of suicidal ideation (thoughts), suicide attempts, and/or completed suicide. It is often associated with psychological conditions such as difficulty of coping with depression or other mental disorders. It is the 11th most common cause of death in the United States (Medline Plus, 2008); in the Western world, females attempt suicide more frequently than males, but males die more often than females. Few studies have examined the association between TBI and suicide; they are summarized below. Primary Studies The committee reviewed two primary studies of the association between TBI and suicide. In a population-based study, Teasdale and Engberg (2001) followed a group of patients who were admitted to a hospital with either a concussion (n = 126,114), a cranial fracture (n = 7,560), or a cerebral contusion or traumatic intracranial hemorrhage (n = 11,766). The groups were identified from all hospital admissions in 1979â1993 in the database of the Danish National Bureau of Health; patients younger than 15 years old and those who died in the hospital or within a month after discharge were excluded. Patients identified on the basis of hospital admissions were compared with the national register of deaths. At the end of 1993, there were 895 recorded suicide deaths: 750 (0.59%) among those with concussions, 46 (0.61%) among those with cranial fractures, and 99 (0.84%) among those with cerebral lesions. More than 68% of all suicides occurred in men and had a median time from injury or lesion to suicide of 3â3.5 years regardless of diagnosis. The higher percentage of completed suicide in males than in females is consistent with the finding that males tend to use more lethal means (such as firearms) than females (CDC, 2008). The standardized mortality ratios (SMRs) were statistically significantly increased for all three diagnoses of concussion, fracture, and lesion in both men and women (3.0, 2.7, and 4.1, respectively). Patients who had comorbid substance use had an increased suicide rates in all diagnosis groups. The authors conclude that concomitant risk factors (such as psychiatric illness and psychosocial disadvantage) might predispose to completed suicide in the mild-TBI group. They suggested that the physical, psychologic, and social consequences of more serious TBI pose a greater risk of suicide. Of 7,000 consecutive patients who had been admitted to a hospital in Oxford, England, between 10â24 years previously, Lewin et al. (1979) studied 291 patients who had been amnesic or unconscious for a week or longer as a result of a TBI. To increase the number of severe-TBI patients, they included 64 selected patients from other sources. Each patient underwent a neurologic examination, and 217 were given a selected series of tests of cognitive function. The cause of death of 75 of the patients with severe TBI who had recovered sufficiently to leave the hospital and walk unassisted was compared with the 1960 death rates in a population of similar sized in England and Wales. Three of the TBI patients died of suicide compared with one in the general population (SMR, 3ânot significant).
PSYCHIATRIC OUTCOMES 277 Secondary Studies Shavelle et al. (2001) studied the occurrence of suicide in 168,461 severely disabled individuals who had received services from the California Department of Development Services in 1988â1997. From that group, they selected 2,320 who had a disability resulting from a motor- vehicle accident or cranial injury, were more than 10 years old, and had survived 12 months after injury. Termination of followup was defined as date of death, the end of the study in 1997, or 3 years after the last Client Development Evaluation Report; the latter was to minimize bias in connection with subjects who may have left California during the study period. Mortality information was obtained from computer tapes of state death certificates that included the International Classification of Diseases (ICD) codes for cause of death. During the study period, 119 subjects died. During the previous 5 years, 3% of the 2,320 people with long-term cognitive or communication disability had attempted suicide, including 4% of the 1,107 with the most ambulation; whether this tendency existed before the injury could not be determined. Two people committed suicide during the study period, for an SMR of 1.0; the authors reported that neither of the two persons who completed suicide appeared to have attempted suicide previously. Simpson and Tate (2002) recruited 172 consecutive outpatients with TBI over a 24- month period at the Brain Injury Rehabilitation Unit of the Liverpool Hospital in Sydney, Australia. All patients were 16â65 years old, had sustained their injuries at least 12 months earlier, and were able to able to respond to questions in English. It was possible to categorize TBI severity in 94 patients for whom a Glasgow Coma Scale (GCS) was available; TBI was mild in 21 patients, moderate in 20, and severe in 53; 76% of the patients had closed head injuries. The Beck Hopelessness Scale and the Beck Scale for Suicide Ideation (BSS) were administered, and the patients were interviewed about alcohol abuse, drug use, and emotional and psychiatric disturbance before and after injury. Moderate to severe hopelessness was seen in 35% of the patients, and 23% reported clinically significant suicide ideation within the previous 7 days; neither score correlated with age at injury, TBI severity, or time after injury. Of the 94 patients, 54 completed the BSS items indicative of suicide ideation, and 28 scored high enough to be considered âclinical.â Postinjury suicide attempts were seen in 30 (17.4%) of the 172 patients over a mean period of 5 years, and 26% of all patients attempted suicide at least once in their lifetime; however, only three made attempts both before and after injury. There were no correlations between age, level of hopelessness, and suicide ideation, although significantly more men attempted suicide than would be expected on basis of general population rates (p < 0.005). A limitation of this study is the lack of a control group. Summary and Conclusion The committee reviewed two primary and two secondary studies of suicide, and findings were consistent among studies, although not all the studies found a statistically significant association between TBI and suicide. The findings are consistent with an association between TBI and major depression. However, the study by Simpson and Tate (2002) did not report correlations of TBI with level of hopelessness, suicide ideation, or other concomitant risk factors (such as psychiatric illness). The committee concludes, on the basis of its evaluation, that there is limited/ suggestive evidence of an association between TBI and completed suicide.
278 GULF WAR AND HEALTH The committee concludes, on the basis of its evaluation, that there is inadequate/insufficient evidence to determine whether an association exists between TBI and attempted suicide.
TABLE 8.2 Psychologic OutcomesâTBI and Suicide Health Outcomes Study or Outcome Comments or Reference Design Population Type of TBI Measures Results Adjustments Limitations Lewin et al., Retrospective Consecutive series of Severe, in mostly Vital status; for N, 3; SMR, 3.0 (not Age, maximal Only 2% loss to 1979 cohort 7,000 patients with closed, but 178 (consecutive significant) central neural followup head injuries complicated by series), 28 disability score, admitted into John compression or (selected series) maximal mental Developed model for Radcliffe Infirmary, penetration who died, cause of disability score, predicting long-term Oxford, 10â24 years (traumatic or death; duration of PTA outcome based on earlier (1955â1969), surgical for for 331 survivors, for model age at injury, worst of whom 479 were internal neurologic category of mental amnesic or decompression) in examination (all), and neurophysical unconscious >1week 77 and 14 of 331 test of cognitive disability, length of survivors function (217) PT amnesia in Additional selected selected series series: 64 cases unconscious >1 mo admitted into this or other facility 3â25 years earlier (including 24 from first set) Causes of death in 78 patients discharged from initial hospitalization alive were compared with causes of death in general population of England and Wales in 1960 (not age- or sex-adjusted) 279
280 Health Outcomes Study or Outcome Comments or Reference Design Population Type of TBI Measures Results Adjustments Limitations Teasdale and SMR 145,440 people Mild TBI Suicide as function Suicide in TBI Stratified by age, Nationally Engberg, discharged from according to of diagnosis discharge group sex; controlled for representative 2001 hospital with primary following (concussion, compared with substance use sample or secondary diagnostic fracture, lesion); Danish population diagnosis of TBI who categories: from National Possible survived 1 mo after concussion Cause of Death Concussion: SMR, underreporting of discharge, sampled (126,114), cranial Registry 3.02 (95% CI 2.82â suicides; accuracy of from Danish fracture (7,560), 3.25); fracture: hospital records National Hospital cerebral contusion SMR, 2.69 (95% CI Registry in 1979â or traumatic 2.01â3.59); lesion: No uninjured control 1993, compared with intracranial SMR, 4.05 (95% CI group general population hemorrhage 3.33â4.93) (11,766) Women had higher rates of suicide than men in three diagnostic groups; mortality greater in patients injured at age of 21â60 years than in those injured when younger or older NOTE: CI = confidence interval, ICD = International Classification of Diseases, MVC = motor-vehicle crash, PTA = posttraumatic amnesia, SMR = standardized mortality ratio, TBI = traumatic brain injury.
PSYCHIATRIC OUTCOMES 281 ANXIETY DISORDERS Anxiety disorders encompass psychiatric conditions that include generalized anxiety disorder (GAD), obsessiveâcompulsive disorder, panic disorder, acute stress disorder (ASD), PTSD, and social phobias (National Institute of Mental Health, 2008). According to Kessler et al. (2005), about 40 million Americans 18 years old and older suffer from anxiety disorders, which are often comorbid with alcohol or drug abuse. Several types of anxiety disordersâ including PTSD, GAD, and panic disorderâthat could be associated with service in the Gulf War have been studied in relation to TBI. They are described briefly below. PTSD is a psychiatric disorder that can develop after the direct, personal experience of or witnessing of an often life-threatening event. Symptoms that characterize PTSD include re- experiencing of an extremely traumatic event through flashbacks and nightmares, avoidance of things associated with the trauma, and hyperarousal (difficulty in sleeping and in concentrating) (IOM, 2006). GAD is characterized by chronic anxiety and exaggerated worry. Often, the worries are accompanied by physical symptoms, such as fatigue, headaches, and irritability. Like GAD, panic disorder is accompanied by physical symptoms that may include chest pain, heart palpitations, shortness of breath, dizziness, or abdominal distress due to unexpected and repeated episodes of acute intense fear. Primary Studies Bryant and Harvey (1999a) conducted a prospective cohort study to compare rates of ASD and PTSD in motor-vehicle-accident survivors who sustained a mild TBI with rates in survivors without a TBI. Patients were consecutively identified at a major trauma center in New South Wales, Australia, over a 10-month period. Mild TBI was defined on the basis of PTA of less than 24 hours. The study included 79 mild-TBI patients (55 males and 24 females) and 92 patients without TBI (61 males and 31 females) who were evaluated for ASD 2â25 days after trauma. A psychiatric assessment at 6 months after injury included an assessment of ASD through the Acute Stress Disorder Interview and of PTSD through the PTSD module of the Composite International Diagnostic Interview (CIDI). Interviews were completed for 63 (80%) mild-TBI patients and 71 (77%) of the controls. Injury severity score (ISS) was greater in mild- TBI (9.28) than in controls (4.0; p < 0.001). During the acute and 6-month followup evaluations, controls reported fear and helplessness more often than patients with mild TBI. They were also more likely to report intrusive memories during the acute phase. There was no significant difference between mild-TBI patients and controls in the rates of ASDâ11 patients (14%) and12 patients (13%), respectivelyâor the rate of PTSDâ15 patients (24%) and 18 patients (25%), respectively. In a separate analysis of the same mild-TBI population, Bryant and Harvey (1999b) evaluated the relationship between PTSD and postconcussive symptoms (PCSs). The analysis included 105 survivors of motor-vehicle accidents who either sustained a mild TBI or did not. At the 6-month followup, 46 mild-TBI patients (32 male and 14 female; mean ISS, 8.96; standard deviation [SD], 6.08) and 59 controls (31 male and 28 female; mean ISS, 3.92; SD, 3.74) were evaluated. Assessments administered at 6 months were the PTSD module from the CIDI and the
282 GULF WAR AND HEALTH Postconcussion Symptom Checklist. Criteria for PTSD were met by 9 (20%) of the mild-TBI patients and 15 (25%) of the controls. In analyses comparing patients who had mild TBI and PTSD with those who had mild TBI alone, concentration deficits, dizziness, fatigue, headache, sensitivity to sound, and visual disturbances occurred statistically significantly more often in the mild-TBI patients who had PTSD. Among controls, concentration deficits and irritability were reported statistically significantly more often in PTSD patients than in those without PTSD. In the mild-TBI group, irritability was more common in individuals diagnosed with PTSD than in those who did not. Creamer et al. (2005) studied 307 individuals who were admitted to a level 1 trauma center to determine the occurrence of PTSD and to assess the relationship between mild TBI, amnesia, and PTSD. Study criteria for mild TBI included LOC of up to 30 minutes, a GCS of 13 or more after 30 minutes, and PTA for up to 24 hours; these criteria were met by 189 (62%) of the subjects. Twelve months after injury, PTSD was diagnosed by trained mental-health clinicians using the Clinician-Administered PTSD Scale for DSM-IV. At 12 months after injury, 10% of the sample met criteria for PTSD: 15% with mild TBI and 7% without TBI (p = 0.1). To the degree that mild TBI is being operationalized as altered mental status or brief LOC marked by âlosing time,â that raises concern about differential diagnosis of dissociative phenomena, which can characteristically follow an emotional trauma in the absence of a TBI. Dissociation is characterized by a disruption in the integrated functions of consciousness, memory, identity, or perception of the environment. Consequently, ascertainment of mild TBI in contexts in which emotional trauma is likely to co-occur is complicated by potential misclassification of dissociation. That is of particular concern because dissociation at the time of trauma is a known risk factor for PTSD, and the co-occurrence constitutes a potential limitation of both the mild-TBI studies that follow. A recent study by Hoge et al. (2008) examined consequences of mild TBI in US soldiers in two brigades in Iraq that saw a high level of combat during a year-long deployment. About 3â4 months after returning from Iraq, 4,618 soldiers were sent a questionnaire covering injury sustained during combat, combat intensity, physical symptoms, major depression, and PTSD. Mild TBI sustained during combat was determined on the basis of the occurrence of at least one of the following three symptoms: losing consciousness (knocked out), being dazed or confused or âseeing stars,â or failure to recall the injury. Of the 2,714 soldiers who returned the questionnaire, 2,525 had complete responses: 124 reported mild TBI and LOC, 260 mild TBI and altered mental status, 435 other injury, and 1,706 no injury. There was a statistically significant association between mild TBI and high combat intensity, a blast mechanism of injury, more than one exposure to an explosion, and hospitalization during deployment. PTSD was present in almost 15% of the soldiers: 43.9% of those with mild TBI and LOC, 27.3% of those with mild TBI and altered mental status, 16.2% of those with other injury and 9.1% of those without injury (p < 0.001). After adjustment, PTSD was associated with mild TBI with LOC (OR, 2.98; 95% CI, 1.70â5.24) and with the highest quartile combat intensity compared to the lowest (OR, 11.58; 95% CI, 2.99â44.83). Schneiderman et al. (2008) conducted a cross-sectional study of military personnel who had served in the conflicts in Iraq or Afghanistan to estimate the occurrence of mild TBI and the prevalence of PTSD and PCS and to examine associations of injury with PTSD and with PCS. The eligible study population included 7,259 veterans of Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF) who had left combat theaters by September 30, 2004, and were living in Northern Virginia, Maryland, Washington, DC, or eastern West Virginia in
PSYCHIATRIC OUTCOMES 283 February 2005. Of those veterans, 2,235 (34%) returned the questionnaire, which included the Brief Traumatic Brain Injury Screen to detect mild TBI and the 17-item PTSD checklist. Twelve percent of the veterans who returned the questionnaire reported a history consistent with mild TBI. Mild TBI was most common among veterans injured by bullets or shrapnel, by blasts, in motor-vehicle crashes, in air or water transport, and in falls. About 11%(n, 250) of veterans were classified as having PTSD. Factors associated with PTSD included multiple injuries (prevalence ratio, 3.71 for three or more, 95% CI, 2.23â6.91) and combat mild TBI (prevalence ratio, 2.37, 95% CI, 1.72â3.28). PCSs were also associated with PTSD (prevalence ratio, 3.79, 95% CI, 2.57â5.59). Secondary Studies The committee identified 10 secondary studies that looked at the association between TBI and anxiety disorders, including PTSD, GAD, and panic disorder. The major limitation of many of these studies was a failure to include a comparison or control group. Other limitations include short followup time and use of small samples. Three of the secondary studies examined PTSD occurrence after injury but lacked a control group or combined the mild TBI group with other injuries (O'Donnell et al., 2004; Gaylord et al., 2008; Sayer et al., 2008). OâDonnell et al. (2004) reported that 12 months after injury, approximately 20% of patients with mild TBI or other injury met criteria for one or more psychiatric diagnoses; PTSD and major depression were the most common. Similar numbers were reported by Gaylord et al. (2008); 18% of 76 service members had both mild TBI and PTSD. Warden et al. (1997) studied 47 active-duty service members who sustained moderate TBI and neurogenic amnesia for the event and found that none of the patients met the full DSM- III-R criteria for PTSD. The nature of traumatic memories and their presence or absence may influence whether PTSD develops. Three secondary studies assessed what factors were associated with the development of PTSD after TBI. Gil et al. (2005) assessed the relationship between explicit memory of the traumatic event and the development of PTSD. They observed that respondents who recalled the traumatic event were 4.6 times more likely to have PTSD than those without memory of the event (95% CI, 1.1-9.9). Two studies report on potential underlying mechanisms of PTSD in TBI. In a brain- imaging study, Koenigs et al. (2007) evaluated which specific areas of the brain were associated with PTSD in Vietnam veterans participating in the Vietnam Head Injury Study. They reported that PTSD was significantly less frequent in veterans who suffered damage to the ventromedial prefrontal cortex (18%) and amygdala (0%) than in those with damage outside these areas (40%) or those with no brain damage (47%). OâDonnell et al. (2007) examined whether tonic and phasic heart rate (HR) was predictive of PTSD in those who suffered trauma (including TBI). The authors observed that phasic HR relative to tonic HR and somatic arousal were the two predictors of subsequent PTSD. That suggests that the extent to which a personâs HR increases from resting when recalling the traumatic event is associated with the increased likelihood of PTSD. Four secondary studies examined anxiety after TBI. Patients with mild TBI were more likely than limb-injured patients to report anxiety in one study (47.4% vs 14.1%; p < 0.0001) (Masson et al., 1996). Two other studies observed a similar prevalence of anxiety disorders after
284 GULF WAR AND HEALTH TBI (Schnyder et al., 2001; Jorge et al., 1993). A recent study by Sayer et al. (2008) of 188 service members who sustained blast or other injuries during OIF or OEF found no difference in the prevalence of anxiety between soldiers exposed to blasts and those exposed to other sources of injury. Only one study examined the prevalence of panic disorders after TBI (Deb et al., 1999). The authors reported that panic disorder was present in 9% compared with 0.8% of the general population. Summary and Conclusion The committee reviewed six primary studies and 10 secondary studies of TBI and PTSD and concluded that the association between a mild TBI and PTSD appears to be different between military and civilian populations. Two of the primary studies and three of the secondary studies were conducted in military populations. The primary studies, which were conducted in military personnel who served in the Gulf War, reported statistically significant associations between TBI and PTSD, but two of the secondary studies found no difference in prevalence with anxiety disorders or PTSD. In contrast, the primary studies conducted in civilian populations did not find an association between TBI and PTSD although an association could not be excluded on the basis of the findings of the secondary studies. The committee concludes, on the basis of its evaluation, that there is limited/suggestive evidence of an association between mild TBI and PTSD in Gulf War military populations. The committee concludes, on the basis of its evaluation, that there is inadequate/insufficient evidence to determine whether an association exists between mild TBI and PTSD in civilian populations.
TABLE 8.3 Psychologic OutcomesâAnxiety Disorder Studies Health Outcomes or Study Outcome Comments or Reference Design Population Type of TBI Measures Results Adjustments Limitations Bryant and Prospective 79 mild TBI (55 Mild, defined PTSD ISS greater in None Head injury ascertained Harvey, cohort males, 24 females), as PTA for less diagnosed with mild-TBI than at time arrived at hospital 1999a 92 non-TBI patients than 24 h CIDI at 6 mo in non-TBI from MVA (61 males, 31 group (9.28 vs females) 16â65 years 4.0; p < 0.001) old involved in MVAs, No significant Good followup over 6- consecutively difference in mo period admitted into major rates of PTSD trauma hospital for at between Limitations include lack least 1 day groups with of control for associated mild TBI and injuries, lack of Patients ascertained no TBI (24%, assessment of duration of sequentially over 10- n, 15; 25%, n, LOC on occurrence of mo period at hospital 18, PTSD admission; all respectively; p assessed at 1 mo; 63 value not mild TBI (80%), 71 reported) non-TBI (77%) evaluated at 6 mo after trauma Exclusions: drug or narcotic analgesia (except codeine) for first 4 weeks after injury, inability to answer questions, non-English- speaking Bryant and Prospective 46 TBI (32 male, 14 Mild TBI with PTSD module At 6 mo after None Head injury ascertained Harvey, cohort female), 59 non-TBI LOC, PTA <24 from CIDI and trauma, 20% of at time arrived at hospital 1999b (31 male, 28 female) h PCS checklist mild-TBI from MVA 285 involved in MVAs, patients, 25.4%
286 Health Outcomes or Study Outcome Comments or Reference Design Population Type of TBI Measures Results Adjustments Limitations Same consecutively of non-TBI Good followup over 6- population as admitted into major patients met mo period Bryant and trauma hospital, criteria for Harvey, followed up 6 mo PTSD (p value Overlapping of PCS, 1999a after trauma; 83% of not reported) PTSD symptoms cohort followed to 6 mo No difference between those Exclusions: drug or with and those narcotic analgesia without PTSD (except codeine) for with respect to first 4 weeks after age, time from injury, inability to trauma to answer questions, assessment, non-English- ISS, length of speaking hospitalization PTSD associated with concentration, dizziness, fatigue, headaches, irritability, visual disturbances (p < 0.01 after Bonferroni adjustment) Creamer et Prospective 307 patients Mildâ PTSD Chronic PTSD Opioid Substance-use data not al., 2005 cohort consecutively included those (determined diagnosed in analgesic available at time of admitted into level 1 with LOC 30 with CAPS for 10% of sample administration assessment trauma center with min, GCS 13 DSM-IV) (15% in TBI vs physical injury after 30 min, associated with 7% in other No control for associated requiring admission PTA 24 h PTA (full, injury; p, 0.1) injuries
Health Outcomes or Study Outcome Comments or Reference Design Population Type of TBI Measures Results Adjustments Limitations of at least 24 h who partial, and no experienced mild recall of event) Only recall of injury TBI (189) or no event examined brain injury (118) and were 18â70 Data on mild TBI and years old were non-TBI controls pooled; followed 1 year after relationship between injury recall and PTSD assessed; therefore, Exclusions: injuries uninformative for mild due to self-harm, IV TBI drug use, current psychotic disorder Hoge et al., Cohort Anonymous survey Mild PTSD Of 124 (4.9%) 95% males, After adjustment for 2008 of 4,618 soldiers, of with LOC, 55.5% under PTSD, depression, mild whom 2,714 (59%) 124 (4.9%) 43.9% met 30 years old, TBI no longer completed LOC criteria for 47.5% junior significantly associated questionnaire; of the 260 (10.3%) PTSD enlisted rank with physical health 2,714, 149 m altered mental compared with outcomes or symptoms excluded because of status (such as 27.3% of those except for headache missing data, 40 dazed or reporting excluded because confused) altered mental they had head injury status, 16.2% without LOC 435 (17.2%) with injuries, other injuries 9.1% with no Remaining 2,525 US injury Army soldiers responded 3â4 mo Soldiers with after return from 1 mild TBI, LOC year of Iraqi more likely to deployment report poor general health, missed workdays, 287 more doctor
288 Health Outcomes or Study Outcome Comments or Reference Design Population Type of TBI Measures Results Adjustments Limitations visits, higher numbers of outcomes or symptoms Schneiderman Cross- 7,259 veterans of Mild PTSD, 11% of Self-reported et al., 2008 sectional OIF, OEF living in postconcussive respondents Northern Virginia, symptoms screened Maryland, positive for Washington, DC, or PTSD; factors eastern West associated with Virginia; 2,235 PTSD included (31%) returned sustained questionnaires multiple injuries (prevalence ratio, 3.71 for three or more; 95% CI, 2.23â 6.19), combat mild TBI (prevalence ratio, 2.37; 95% CI, 1.72â 3.28) Postconcussive symptoms strongly associated with PTSD score NOTE: CAPS = Clinician-Administered PTSD Scale, CIDI = Composite International Diagnostic Interview, ISS = Injury Severity Score, IV = intravenous, LOC = loss of consciousness, MVA = motor-vehicle accident, OEF = Operation Enduring Freedom, OIF = Operation Iraqi Freedom, PCS = postconcussive symptom, PTA = posttraumatic amnesia, PTSD = posttraumatic stress disorder, TBI = traumatic brain injury.
PSYCHIATRIC OUTCOMES 289 OTHER PSYCHIATRIC OUTCOMES The cost of TBI is enormous from a public-health perspective and likely to be underestimated. There is a high financial cost, determined by a host of acute and chronic injuries in the context of broad and extended personal disability, and the fact that TBI often occurs to soldiers in the course of their duties in war makes this an issue of even greater national concern. The psychiatric aspects of TBI that are most often identified and studied are the related risks of depressive and anxiety disorders, as discussed see above, and well-controlled outcome studies are available from which conclusions regarding associations can be drawn. TBI has been implicated in other personality and behavioral outcomes, but on the basis of fewer studies, which are likely to have been conducted with less methodological rigor. The other outcomes include aggression, irritability, emotional reactivity, sleep disorders, sexual dysfunction, reduction in insight, and personality disorders, all converging on poor psychosocial function. Complicating the interpretation of the studies is the fact that many studies have been poorly controlled, may have been biased, and may have overlooked premorbid factors in the behavioral outcomes. The committee reviewed the literature in this area and found primary studies whose methods were scientific and whose outcomes can be accepted with confidence; these studies are supplemented by secondary studies of suitable rigor that are not definitive. AGGRESSIVE BEHAVIORS Primary Studies Two primary studies found that TBI is associated with subsequent aggressive behavior, but one primary study found no effect of TBI on criminal conviction. A primary study by Ommaya et al. (1996) examined the relationship between aggressive personality traits in TBI. They used military populations and identified âadverse personnel actionâ and âdischarge from military serviceâ as two overall markers of poor outcome in an attempt to understand the relationship between premorbid behavior, TBI, and postinjury behavior. The study cohorts consisted of 1,617 active-duty Army personnel who were hospitalized in FY 1992 and FY 1993 for head injuries caused by fighting or for other trauma; the comparison group was all 4,626 active-duty Army personnel who were hospitalized for orthopedic injuries caused by fighting or other means; a ânormalâ active-duty population of 9,997 (without injury) was a second reference group. The outcomes were âmilitary service dischargeâ (administrative-behavioral, administrative-criminal, or medical) and other âadverse personnel action.â Several variables were found to be important confounding factors for behavioral discharge and criminal convictionâage, marital status, educational level, pay grade, time in pay grade, and years of active serviceâand were controlled for in the analyses. Individuals who sustained TBI had a worse behavioral outcome than those who had orthopedic injury, in âadverse actionâ and âdischarge for behavioral criteria or criminal conviction,â whereas TBI did not affect âmedical discharge.â Specifically, the percentage of individuals encountering âadverse actionâ was 21% in the TBI group (overall) and 13% in the orthopedic-injury group (overall); the percentage encountering âdischarge for behavioral disturbance or criminal convictionâ was 11% and 6%, respectively; and the percentage encountering âmedical dischargeâ was 9% and 11%,
290 GULF WAR AND HEALTH respectively. When the subpopulation of each group that contracted their injury through fighting was examined, the corresponding percentages were 34% and 28%, 17%, and 15%, 1% and 6%, respectivelyâincreased percentages of adverse outcomes in the TBI groups and an attenuation of the TBI effect in each âfightingâ subgroup. Overall, TBI increased the risk of behavioral discharge 4 times and of criminal conviction 5 times compared with the normal group; it increased the risk of postinjury adverse action by 1.3 times and decreased the risk of medical discharge by 0.64 times compared with the orthopedic-injury group. âAdverse actionsâ increased in both the TBI and orthopedic-injury groups 1.75â3 times, but they increased more in the TBI group (3.0 times) than in the orthopedic-injury group (2.1 times). The differences between outcomes in the TBI (fighting) and the orthopedic-injury (fighting) subgroups were not statistically significant. The results of the study suggest that any person sustaining a TBI has a higher risk of later aggressive-behavior problems. Because the outcome measures in the study selected the more severe cases of behavioral impairment, the results may show only the peak of the full problem. Premorbid problems (such as fighting) are a risk factor for postinjury behavioral problems but did not produce worse outcomes in the TBI than in the orthopedic- injury group. In another primary study, Tateno et al. (2003) assessed aggressive behaviors in 89 TBI cases and 26 multiple-trauma cases (without TBI) consecutively admitted into two Iowa hospitals. Severity of brain injury was measured according to the GCS and PTA and classified with the TCDB. Aggressivity was assessed with the Overt Aggression Scale (OAS) and premorbid aggressive behavior was estimated from premorbid police contact and legal actions. Psychiatric assessments were done by a psychiatrist using the PSE and the Structured Clinical Interview for DSM-IV, along with other standard psychiatric rating scales. Structural neuroimaging scans were also collected. Of the TBI group, 33.7% met the criteria for aggressive behavior in the 6 months after injury (called the aggressive group), compared with 11.5% of the non-TBI injured group; the remaining 66.3% of the TBI group showed low aggressive traits (the nonaggressive group). When the aggressive and nonaggressive TBI subjects were compared major depressive disorder was more frequent in the aggressive group (X2, 6.54; df, 1; p = 0.01), and the group had a higher Hamilton Depression Rating Score (t, -3.51; df, 87; p = 0.0007) and a higher Hamilton Anxiety Scale scores (t, -3.37; df, 87; p = 0.001). Focal frontal lobe lesions on a magnetic resonance scan occurred more frequently in the aggressive TBI group than in the nonaggressive group (X2, 8.05; df, 1; p = 0.005), whereas a more diffuse lesion was more frequent in the nonaggressive TBI group. Virkkunen et al. (1977) examined 1,830 Finnish World Ward II veterans who had received penetrating head injuries and 500 noninjured veteran controls; both groups were followed for up to 37 years. Of the TBI group, 33.1% sustained frontal, 19.5% temporal, 37.7% parietal, and 9.7% occipital lesions. Most veterans in both groups had lifelong employment, despite their injuries. Criminal convictions were no more common in the TBI veterans (5.5%) than in the veteran controls (4.2%), and crimes of violence were not more common in the TBI veterans (0.9%) than in the noninjured veteran group (0.6%). Crimes did not tend to be recurrent in either group. Secondary Study Grafman et al. (1996) studied aggression and violence in Vietnam veterans who had TBI and non-brain-injured Vietnam veterans to show that mediofrontal and orbitofrontal lesions of
PSYCHIATRIC OUTCOMES 291 the prefrontal cortex are the ones associated with aggression and violence and especially with verbal confrontations. That demonstration of an association between a localized frontal lobe injury and TBI is especially important in light of the considerable literature documenting loss of inhibition and greater aggressive behavior after frontal lobe injury. They hypothesized that lesions to the prefrontal cortex impair the ability to sustain âmanagerial knowledgeâ and bias behavior away from plans and social rules toward aggressive and violent behavior. DRUG AND ALCOHOL ABUSE DISORDERS Secondary Studies Many studies have shown a relationship between drug and alcohol use and TBI, and it is generally accepted that drug and alcohol use precedes the TBI and increases the risk of head injury. Therefore, studies have examined post-TBI alcohol use only in the context of previous drug and alcohol use estimated as closely as possible. Horner et al. (2005) focused on the assessment of alcohol abuse and dependence (AA/D) in a 1-year period in a sample of 1,606 TBI patients, randomly sampled from a large state-wide sample of all TBI patients discharged from South Carolina hospitals in 1999â2002 and fully assessed at the time of the incident. A telephone interview a year after TBI was used to obtain information on alcohol use for the month preceding assessment. Overall, 15.4% were heavy drinkers, 14.3% moderate drinkers, and 70.3% infrequent drinkers or abstainers. Almost all interviewed (99.8%) reported drinking the same or less than a year before; half the current heavy and moderate drinkers were consuming less than they were a year before. Risk factors for heavy drinking were male sex, lower age, substance abuse before TBI, and a diagnosis of depression since TBI. Jorge et al. (2005) studied 158 Level I TBI patients of whom 24.1% were alcohol- dependent and 10.8% were alcohol abusers; alcohol use during the year before TBI was 34.8%. Of the 55 TBI patients with premorbid AA/D, 30 completed 1 year of followup and 60% of the group followed up resumed their alcohol use; of those 55, 60% developed a mood disorder during the post-TBI year compared with 36.9% of the non-AA/D group. Patients with pre- existing AA/D had reduced cerebral grey matter (GM) volumes compared with patients without AA/D, and post-TBI relapsers had even greater reductions in GM volumes. Moreover, vocational outcome was lower in those with AA/D, especially if it coexisted with mood disorders. Bombardier et al. (2003) followed a group of consecutively admitted TBI patients over the course of a year. They showed that drinking decreased considerably from before injury to 1 year after TBI: abstinence rates increased from 14% to 36%; people without substantial alcohol- related problems increased from 64% to 84%; and remission of substantial alcohol problems ranged from 30.8% to 56%. However, there was a subset of survivors (about 25%) who drank heavily at 1 year after TBI, and the level of pre-TBI alcohol use predicted who would be in the post-TBI heavy-drinking group. That suggests that drug and alcohol use should still be monitored after TBI.
292 GULF WAR AND HEALTH PSYCHOTIC DISORDERS Primary Studies Fann et al. (2004) used the Group Health Cooperative (GHC) of Puget Sound (450,000 members) in a prospective cohort study of TBI. All GHC members with a new diagnosis of TBI in 1993 who had been GHC members for at least a year were examined, evaluated for severity and matched with randomly selected GHC non-TBI members by sex, age, and enrollment date. Psychiatric illness was assessed for the year preceding TBI and for the 3-year period after TBI, as noted by the presence of a psychiatric diagnosis, filling of a prescription for a psychiatric medication, or use of psychiatric services. Psychiatric diagnoses were made according to ICD-9- CM by primary-care physicians. The authors collected 939 cases of TBI in 1993, for an overall annual TBI incidence of 475.2 per 100,000 person-years; 85.5% of the TBIs were mild. The risk of psychiatric illness was significantly increased after mild and moderate-severe TBI. Increased ORs were observed especially in patients with no prior history of psychiatric illness, within the first year after TBI: the OR was 2.1 (95% CI, 1.6â2.6) in those with mild TBI and 3.4 (95% CI, 1.9â5.8) in those with moderate to severe TBI. An approximate 1.5-fold increase in risk of psychiatric illness was also observed in the following 3 years in patients who had a diagnosis of a psychiatric illness before sustaining a mild TBI; no association was observed in such patients who sustained a moderate to severe TBI. Specifically, the new onset of a psychotic disorder was no greater after mild TBI in the following 3 years than in the year before the TBI, whereas after moderate to severe TBI, a diagnosis of psychosis were greater but not until the second and third years: 1â12 months after TBI, the OR was 2.8 (not significant); 13â24 months after TBI the OR was 5.9 (95% CI, 1.6â22.1); and 25â36 months after TBI the OR was 3.6 (95% CI, 1.0â12.3). The OR for any psychiatric diagnosis during the 3-year followup was increased considerably if there was a prior psychiatric illness. Secondary Studies A study by Achte et al. (1969) also found an association between TBI and psychosis. Data were collected in a Finnish hospital for brain injuries that housed all central nervous systemâinjured war veterans of the 1939â1945 Finnish Wars; 3,552 men comprise this cohort followed for 22â26 years. About 42% had a penetrating head wounds (shell splinters and gun shot wounds), and 58% had closed TBI. In this population, 317 (8.9%) out of the 3,552 veterans had had a diagnosis of psychosis (a rate that is 2â3 times the usual population-based rate of approximately 3â4%). In addition, 30.4% had epilepsy (44.2% of those with penetrating head injuries and 20.3% of those with closed TBIs), and 8.9% had aphasias (16.1% of those with penetrating head injuries and 3.7% of those with closed TBIs). Godfrey et al. (1993), in a small but well-controlled study focusing on insight, found poor insight regarding behavioral impairment at 6 months after TBI. The defect appeared to attenuate with time. Increased insight regarding behavioral impairment was accompanied by emotional dysfunction. Henry et al. (2006) compared a group of TBI patients with their friends and close relativse for their ability to identify their own emotions (an aspect of insight) and found the TBI group impaired, less able to recognize emotion in others, externally oriented and less fluent on tests of semantic fluency.
PSYCHIATRIC OUTCOMES 293 Summary and Conclusions Aggressive Behaviors The committee concludes, on the basis of its evaluation, that there is sufficient evidence of an association between TBI and subsequent development of aggressive behaviors. Additional evidence that aggression is associated with TBI primarily when frontal cortical lesions are sustained is consistent with a large literature associating frontal lobe damage with loss of behavioral control. Alcohol and Drug Abuse The committee concludes, on the basis of its evaluation, that there is limited/suggestive evidence of an association between TBI and decreased drug and alcohol use, as compared with preinjury levels, in the 1â3-year period following the TBI. Psychosis The committee concludes, on the basis of its evaluation, that there is limited/suggestive evidence of an association between moderate or severe TBI and psychosis. However, even if the TBI is severe, the psychosis does not appear during the first post-TBI year, but rather, becomes apparent in the second and third post- TBI years.
294 TABLE 8.4 Psychologic OutcomesâPersonality Disorder Studies Health Outcomes or Outcome Comments or Reference Study Design Population Type of TBI Measures Results Adjustments Limitations Fann et al., Prospective 939 HMO enrollees Mild (803), Psychiatric illness Increased rates Age, sex, TBI Possible 2004 cohort (479 women, 460 moderate to determined with of psychiatric reference date, misclassification of men) with diagnosed severe (136); three major illness in year logarithm of diagnoses; lack of TBI in 1993 enrolled injury indicators: ICD-9- after TBI (49% costs in year precision in in health plan for at identified with CM codes, in moderate to before TBI measurement of TBI least 1 year before ICD-9-CM prescriptions, severe, 34% in reference date, exposure injury, 3 to 1 match categories, psychiatric-service mild, 18% in comorbid injuries with health plan codes (fracture use in year before non-TBI Control group is controls; followed up of vault base of TBI, 1â12 mo, 13â comparisons) general HMO to 3 years after skull; other, 24 mo, 25â36 mo population, not injury enrollment in study unqualified, after injury TBI associated population multiple with higher fractures of risk of Had preinjury data skull; adjustment intracranial reaction in injury) year after TBI: mild, 7.2%; moderate to severe, 7.4%; controls, 4.6% TBI associated with higher risk of psychotic disorder in year after TBI: mild, 3.0%; moderate to severe, 13.0%; controls, 1.9% Ommaya et Retrospective 2,243 TBI military TBI severity Post-TBI Behavioral: Stratified by Alcohol use not al., 1996 cohort hospital patients determined discharge from mild TBI, whether injuries considered from discharge with ICD-9 to active-duty service OR, 1.8 (95% arose from fights records for all compute AIS for: behavioral CI, 1.4â2.2); Normal orthopedic military hospitals vs and ISS; mild reasons, criminal moderate TBI, controls
Health Outcomes or Outcome Comments or Reference Study Design Population Type of TBI Measures Results Adjustments Limitations active-duty (1,778), conviction, alcohol NS; severe population moderate and drug abuse, TBI, (1,879,724), (174), severe medical disability, NS followed up 2.7 (274) death years after injury Alcohol, drug abuse: mild TBI, OR, 2.6 (95% CI, 1.6â 4.3); moderate TBI, OR, 5.4 (95% CI, 1.7â 16.9); severe TBI, NS Criminal conviction: mild TBI, OR 2.7 (95% CI, 1.9â3.9); moderate TBI, NS; severe TBI, NS Tateno et Retrospective 89 patients with TBI severity Aggressive 30 (33.7%) al., 2003 cohort closed head injury determined behavior assessed TBI patients admitted into with GCS, with Overt presented with University of Iowa Traumatic Aggression Scale; aggressive hospitals and clinics, Coma Data mood, anxiety behavior Iowa Methodist Bank; mild disorders assessed during first 6 Medical Center; 26 (50), moderate by psychiatrist mo compared patients with (19), severe with three multiple traumas but (19), 1 missing (11.5%) without brain controls (p < damage or spinal- 0.03) cord injury 295
296 Health Outcomes or Outcome Comments or Reference Study Design Population Type of TBI Measures Results Adjustments Limitations Virkkunen Retrospective 1,830 Finnish Criminal 100 (5.5%) et al., 1977 cohort veterans of WWII convictions in TBI patients, with penetrating Finland collected 21 (4.2%) brain injuries, 500 from Criminal controls noninjured Finnish Register convicted of WWII veterans as crimes (NS) controls NOTE: AIS = Abbreviated Injury Scale, CI = confidence interval, GCS = Glasgow Coma Scale, HMO = health-maintenance organization, ICD-9-CM = International Classification of Diseases, Ninth Revision, Clinical Modification, ISS = Injury Severity Score, NS = not significant, OR = odds ratio, TBI = traumatic brain injury, WWII = World War II.
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