Anda di halaman 1dari 11


Characteristics of
Psychotic Disorder Due
to Traumatic Brain
Injury: An Analysis of
Case Studies in the
Daryl Fujii, Ph.D.
Iqbal Ahmed, M.D.

The authors analyzed data from 69 published case

studies of Psychotic Disorder Due to Traumatic P sychotic Disorder Due to Traumatic Brain Injury
(PDTBI) is the current DSM-IV diagnosis given to
individuals who develop a psychosis after a traumatic
Brain Injury (PDTBI) in order to describe its brain injury (TBI).1 Diagnostic criteria include 1) pres-
common characteristics and assist in its diagnosis ence of hallucinations or delusions; 2) evidence (history,
and differentiation from schizophrenia. The major- physical, or laboratory) that the psychosis is a direct
ity of these PDTBI patients were males with onset physiological consequence of TBI; 3) psychosis is not
of symptoms occurring within the first 2 years af- better accounted for by another mental disorder; and
ter moderate to severe head injury. A majority 4) psychosis does not occur exclusively during a state of
showed abnormalities on MRI/CT and EEG with Ahmed and Fujii2 argue that PDTBI is often difficult
localization in the frontal and temporal areas. The to diagnose because criteria are vague. This contention
general presentation included delusions and hallu- is supported by the wide range of incidence rates for
cinations without co-occurring negative symp- PDTBI cited in the literature. For example, retrospective
toms. The findings demonstrate that patients with chart reviews of World War II soldiers have yielded in-
PDTBI have a profile that distinguishes itself cidence rates of 0.7%, 7.5%, and 8.9%.3–5 By contrast, a
study with closed head injury medical patients reported
from schizophrenia. a 20% incidence rate.6
(The Journal of Neuropsychiatry and Clinical According to Ahmed and Fujii, diagnostic difficulties
Neurosciences 2002; 14:130–140) hinge on two aspects of the criteria: 1) establishing that
the psychosis is a direct physiological consequence of
TBI and 2) determining that the psychosis is not due to
another mental disorder.2
As to the first difficulty, there are several key issues
in establishing TBI as the etiology of a psychotic con-
dition. 1) What severity of TBI is significant enough to

Received May 25, 2000; revised September 18, 2000; accepted Septem-
ber 22, 2000. From the Department of Neuropsychology, Hawaii State
Hospital (D.F.) and Department of Psychiatry, John A. Burns School of
Medicine (I.A.). Address correspondence to Dr. Fujii, Department of
Neuropsychology, 45-710 Keaahala Road, Kaneohe, HI 96744. E-mail:
Copyright 䉷 2002 American Psychiatric Publishing, Inc.

130 J Neuropsychiatry Clin Neurosci 14:2, Spring 2002


cause a psychosis? 2) How long after an injury is the TBI from the secondary seizures. Thus the secondary seizure
considered to be etiologically relevant to the develop- disorder would be the intervening variable between TBI
ment of a psychosis? and 3) What laboratory findings and the development of psychosis.17 In such cases the
are associated with psychosis? differential between PDTBI and PDSD is difficult to de-
Reports vary as to the severity of TBI required to termine.
trigger a psychosis. Some studies suggest that individ- In addition to the differential diagnostic problems
uals who develop a psychosis after TBI had generally with the aforementioned mental disorders, there may be
sustained moderate to severe head injuries.5,7 By con- multiple factors contributing to psychotic symptoms—
trast, many case studies report development of a psy- for example, genetic risk, substance abuse, or other neu-
chosis after mild brain injuries with no loss of con- rological problems.18
sciousness8–11 So far, the literature examining PDTBI is sparse. Many
Another issue in determining the etiological signifi- case reports of PDTBI include neurological investiga-
cance of TBI in the development of psychosis is the la- tions such as brain imaging and EEG, but there are only
tency between the injury and onset of symptoms. One a few studies describing such data,7,12 and these are lim-
study reported latencies ranging from 2 days to 48 ited by small sample sizes. Thus the utility of the find-
years.4 Another reported latencies between 3 months to ings is questionable. Studies with large sample sizes ex-
19 years.7 In many cases, the combination of frequently ist, but the injuries are primarily missile wounds and
mild severity of injury and long latency in developing the lesion analysis is based on the location of the
PDTBI can raise doubts about whether the TBI was a wound.3–5 Given that the overwhelming majority of cur-
contributory factor in developing a psychosis. rent TBI patients have sustained closed head injuries,
The question of associated laboratory findings in de- the applicability of these finding to many of today’s pa-
termining PDTBI is probably less controversial. Prelim- tients may be limited.
inary evidence reports a preponderance of temporal The present study examines characteristics of PDTBI
lobe abnormalities on CT/MRI and EEG.7,12 Frontal lobe through an analysis of case studies in the literature. The
abnormalities on CT/MRI are also common but are less purpose of the study is to provide descriptive informa-
consistently found.7 The data, however, are sparse, and tion to assist in diagnosis of PDTBI. This information
studies are limited by small sample sizes. Still, the lo- would be useful in ruling out other mental conditions
calization of findings is generally consistent with earlier such as schizophrenia or seizure disorder when formu-
large sample studies that determined lesion site by area lating a diagnosis for a psychotic patient who has a his-
of missile wound.4,5,13 tory of TBI. Specifically, we focus on three questions:
The second difficulty in diagnosis of PDTBI is ruling 1) What are common characteristics of PDTBI? 2) What
out other mental disorders. Perhaps the most common historical, physical, or laboratory findings are associated
differential diagnosis would be with schizophrenia. with PDTBI? and 3) What are some characteristics that
Many schizophrenics sustain TBI during their lifetime.14 discriminate between PDTBI and schizophrenia, and
In people with schizophrenia it is often difficult to de- PDTBI and seizure disorder?
termine if a psychotic condition is a direct physiological
consequence of TBI or even if TBI contributes to or ex-
acerbates the psychotic process.14 METHODS
Another difficult differential is with Psychosis Due to
Seizure Disorder (PDSD). Schizophrenia-like psychosis A comprehensive literature search of psychiatric, psy-
occurs 6 to 12 times more frequently in patients with chological, neurological, and medical journals written in
seizure disorder than in the general population.15,16 At English and listed in the PubMed data base was made
the same time, seizure disorder is also a common se- from the year 1971 to 1997. The literature search focused
quela in patients with posttraumatic psychosis. Studies on cases in which a psychosis developed after a trau-
have found that 33% to 58% of patients with PDTBI also matic brain injury and which also reported results of
experienced seizures.7,13 In addition, EEG abnormalities neurological studies such as computed tomography
in the temporal lobes have been reported in patients (CT), magnetic resonance imaging (MRI), and electro-
without a documented history of seizure disorder. It is encephalography (EEG). Specific criteria for inclusion
also possible that these patients experienced seizures were based on DSM-IV criteria for PDTBI.1 In addition,
that were not reported.13 This high comorbidity between cases reporting a family history of mental disorder were
psychotic symptoms, head injury, and seizure disorder excluded.
has led some researchers to speculate that the subse- A total of 39 articles were included, yielding 69 cases.
quent psychosis in PDTBI patients may actually result The authors of articles are listed in Table 1.7,9–12,19–52

J Neuropsychiatry Clin Neurosci 14:2, Spring 2002 131


The following data were taken for each case: 1) gender, mined by reports of affective flattening, alogia, and avo-
2) etiology of TBI, 3) loss of consciousness, 4) age when lition. The absence of these behavioral descriptions
TBI was sustained, 5) age at onset of psychotic symp- resulted in the rating of “no” negative symptoms. Posi-
toms, 6) presence of seizure disorder, 7) family history tive symptoms of delusions and hallucinations were
of mental illness, 8) medications, 9) clinical outcome, based on reports and case descriptions. In several cases,
10) presence of negative symptoms, 11) inpatient/out- more than one type of delusion or hallucination was
patient status, 12) diagnosis, 13) presence and type of de- described; thus the total number of positive symptoms
lusions, 14) presence and type of hallucinations, 15) EEG exceeds the total number of subjects. Clinical outcome
findings, 16) MRI/CT findings, 17) presence of neurolog- was based on rating case descriptions of outcome. A
ical signs, and 18) neuropsychological test findings. three-point system was used to rate outcomes as fol-
Severity of TBI was based on criteria set by the Mild lows: 1) improved, 2) no improvement, or 3) decline in
Traumatic Brain Injury Committee of the Head Injury status.
Interdisciplinary Special Interest Group of the American Localization on EEG and CT/MRI was calculated by
Congress of Rehabilitation Medicine (ACRM).53 Accord- the system used by Fujii and Ahmed.7 In this system,
ing to their criteria, a head injury is considered mild if each occurrence of abnormalities is tallied individually.
the duration of loss of consciousness (LOC) is 30 min- Thus the total number of abnormalities exceeds the total
utes or less and moderate to severe if LOC is longer than number of subjects.
30 minutes. In many cases, there were missing data because of
Psychotic symptoms were rated in the following man- differences in reporting. All data points for each variable
ner. The presence of negative symptoms was deter- were included in individual analyses despite missing
data for the case. Thus for individual variables, the num-
ber of cases is often less than the sample size of 69. Given
TABLE 1. Authors of articles included in analysis that most data were nominal in nature, analyses were
1. Bamrah & Johnson 199119 primarily chi-squares. When base rates were known or
2. Barnhill & Gualteri 198920 appropriate, these figures were used in the chi-square
3. Benson & Stuss 199021
4. Bienenfeld & Brott 198922 calculations. All other calculations are based on chance
5. Bouvy et al 198823 differences. We also conducted t-tests when appropriate.
6. Buckley et al 199324 Because of the exploratory nature of the study and rela-
7. Cohen et al 199425
8. Dalby 198926 tively lower power of nonparametric (versus paramet-
9. Dolinar 199127 ric) statistics to detect significant differences between
10. Drake 198828 groups, a nonconservative significance level was set at
11. Feinstein & Ron 199012
12. Filley & Jarvis 198729 0.05.
13. Fujii & Ahmed 19967
14. Hayman & Abrams 197730
15. Ikemura et al 198731
16. Katz et al 19899 RESULTS
17. Levine & Finklestein 198232
18. Lloyd & Tsuang 198133 Demographics
19. Marshall et al 199011
20. Murai et al 199734 Known demographic data are presented in Table 2. The
21. Nasrallah et al 198135 sample was composed of 49 males and 11 females. The
22. O’Callaghan 198836 proportion of males to females was significantly differ-
23. O’Connor et al 199637
24. Prigatano et al 198838 ent from the expected (2:1) base rate for TBI (v2⳱6.07,
25. Puri et al 199439 df⳱1, P⬍0.02). The significant majority of our subjects
26. Rogers & Franzen 199240 sustained TBI from motor vehicles accidents (67%;
27. Sabhesan et al 198841
28. Sabhesan & Natarajan 198842 v2⳱116.20, df⳱4, P⬍0.001). The second most frequent
29. Sandel et al 199343 etiology of TBI was assault (13%), followed by gunshot
30. Signer & Cummings 198744 wounds (4%) and falls (4%). The etiology in 13% of the
31. Silva et al 198910
32. Silva et al 199345 cases was unspecified. Of the known cases, 92% sus-
33. Staton et al 198246 tained closed head injuries and 8% open head injuries
34. Tisher et al 199347 (v2⳱36.25, df⳱1, P⬍0.001).
35. Waldfogel et al 199448
36. Weston & Whitlock 197149 A significant majority of the sample (89%) sustained
37. White et al 198750 TBI with loss of consciousness (v2⳱6.55, df⳱1, P⬍0.01).
38. Will & Young 198851 Of the known cases, a significant proportion of subjects
39. Young et al 199252
sustained moderate to severe head injuries (v2⳱7.75,

132 J Neuropsychiatry Clin Neurosci 14:2, Spring 2002


df⳱1, P⬍0.01). Most of the subjects (87%) were seen in df⳱1, P⬍0.01). However, if compared with the highest
inpatient settings (v2⳱27.60, df⳱1, P⬍0.001). No differ- base rate reported in the TBI literature (12%), the pro-
ences were found for whether subjects came from psy- portion of patients with diagnosed seizure disorder is
chiatric or medical settings (v2⳱3.37, df⳱1, P⬍0.10). significantly higher (v2⳱21.03, df⳱1, P⬍0.001).16
The mean sample age for sustaining a TBI was A significant proportion of subjects experienced de-
29.1Ⳳ17.6 years (means and standard deviations re- lusions (47/60; v2⳱18.69, df⳱1, P⬍0.001). By far the
ported). The mean age for onset of psychosis after head most common type of delusion was persecutory (n⳱18),
trauma was 33.4Ⳳ15.4 years. The distribution of scores followed by grandiose and somatic (7 each); Capgras (5);
for mean delay for onset of psychotic symptoms was reduplicative paramnesia, religious, reference, stealing,
highly skewed, with a range of 0 to 34 years. The mean and erotomanic (3 each); Cotard’s (2); and jealousy (1).
number of years after trauma for onset of psychosis was In 4 cases the delusions were unspecified. The propor-
4.1Ⳳ6.6. The mode was less than 1 year (38%), and the tion of persecutory delusions was significantly higher
median was 1 year. Seventy-two percent of the cases than chance (v2⳱52.49, df⳱10, P⬍0.001).
reported an onset of psychosis before the mean. Roughly half the subjects experienced hallucinations
(28/60). The proportion of subjects demonstrating hal-
Clinical Presentation and Course lucinations was not significantly greater than chance
Data for the clinical presentation and course of psycho- (v2⳱0.27, df⳱1, P⬎0.10). The most common hallucina-
sis are presented in Table 3. Of the 59 known cases, 20 tion was auditory (26) followed by visual (9). There was
reported a history of seizure disorder. The resulting pro- a significantly higher proportion of auditory versus vi-
portion of patients sustaining secondary seizures is sig- sual hallucinations reported (v2⳱5.45, df⳱1, P⬍0.02).
nificantly smaller if compared with chance (v2⳱6.80, A comparison of the incidence of delusions versus hal-

TABLE 2. Demographic data

Variable Data v2
Gender (n⳱60) 49 males; 11 females 6.07*
Setting (n⳱58) 49 inpatient; 9 outpatient 27.60***
36 psychiatric; 22 medical 3.37
Etiology (n⳱55) 37 MVA; 7 assault; 2 gunshot wound; 2 falls; 7 unspecified 116.20***
Type (n⳱51) 47 closed head injury; 4 open head injury 36.25***
LOC (n⳱22) 17 yes; 5 no 6.55**
Severity (n⳱22) 7 mild; 22 moderate-severe 7.75**
Age at onset, years (n⳱60) mean⳱29.1, SD⳱17.6 (range 2–81)
Age at onset, years (n⳱60) mean⳱33.4, SD⳱15.4 (range 14–81)
Delay of onset, years (n⳱60) mean⳱4.1, SD⳱6.6 (range 0–34)

Note: TBI⳱traumatic brain injury; MVA⳱motor vehicle accident; LOC⳱loss of consciousness.

*P⬍0.05; **P⬍0.01; ***P⬍0.001.

TABLE 3. Clinical presentation and course

Variable Data v2
Seizure disorder (n⳱59) 20 yes; 39 no 6.80*
Delusions (n⳱60) 47 yes; 13 no 18.69***
Type (n⳱56) 18 persecutory; 7 grandiose; 7 somatic; 5 Capgras’; 52.49***
3 reduplicative paramnesia; 3 reference; 2 Cotard’s;
3 stealing; 3 erotomania; 1 jealousy; 4 unspecified
Hallucinations (n⳱60) 28 yes; 32 no 0.27
Type (n⳱35) 26 auditory; 9 visual 5.45*
Incidence, delusions vs. hallucinations (n⳱75) 47 delusions; 28 hallucinations 12.84***
Negative symptoms (n⳱55) 8 yes; 47 no 18.69***
Course (n⳱39) 25 improved; 11 no improvement; 3 worsening 19.08***
Efficacious medications (n⳱24) 13 neuroleptics; 5 anticonvulsants; 4 lithium; 21.03***
1 antidepressant; 1 propranolol

*P⬍0.05; **P⬍0.01; ***P⬍0.001.

J Neuropsychiatry Clin Neurosci 14:2, Spring 2002 133


lucinations indicates a significantly higher incidence of included CT or MRI data, 36 reported positive findings,
delusions in the sample (v2⳱12.84, df⳱1, P⬍0.001). which is significantly greater than chance (v2⳱5.15,
Of 55 subjects, only 8 reported negative symptoms. df⳱1, P⬍0.05). A trend was found in hemisphere loca-
The proportion negative symptoms is significantly tion of abnormalities (left⳱30, right⳱46; v2⳱3.37,
lower than chance (v2⳱18.69, df⳱1, P⬍0.001). df⳱1, P⬍0.10). The frequency in localization of findings
In the cases that described the course of psychosis, 25 was as follows; 23 frontal, 15 temporal, 11 ventricular
patients were reported to be improved, 11 reported no enlargement, 10 diffuse cortical, 8 parietal, 6 subcortical,
improvement, and 3 reported a progressive worsening 5 cerebellar, 3 central, and 3 brainstem. The proportion
of symptoms. The proportion of improved outcome was of localized findings was significantly greater than
significantly different from chance (v2⳱19.08, df⳱1, chance (v2⳱40.28, df⳱9, P⬍0.001). In cases that de-
P⬍0.001). In the cases that reported efficacious medi- scribed specific types of abnormalities, 34 reported focal
cations, neuroleptics were cited in 13 cases, anticonvul- lesions and 33 reported atrophy. No differences were
sants in 5 cases, lithium in 4 cases, antidepressants in 1 found in type of lesion (v2⳱0.00, df⳱1, P⬍0.10).
case, and propranolol in 1 case. The proportion of effi- In 24 cases, either results from a neurological exami-
cacious medications was significantly different from nation were reported or neurological symptoms were
chance (v2⳱21.03, df⳱4, P⬍0.001). described. Of these cases, 14 reported positive findings,
which was not different from chance (v2⳱1.78, df⳱1,
Neurological Investigations P⬎0.10). Neuropsychological test data were described
Data for neurological investigations are listed in Table in 17 cases, 15 of these reported impairments. The pro-
4. EEG data were reported in 41 cases. Of these cases, portion of findings of impairment on neuropsychologi-
29 (about 70%) reported positive findings, which is sig- cal test data was significantly greater than chance
nificantly greater than chance (v2⳱5.2, df⳱1, P⬍0.05). (v2⳱9.94, df⳱1, P⬍0.001). Specific areas of impairment
No differences were found in hemisphere location of on neuropsychological test data were as follows: 10
EEG findings (left⳱17, right⳱18; v2⳱0.03, df⳱1, memory, 7 executive functions, 7 visuospatial abilities,
P⬎0.10). Localization was as follows: 16 in the temporal 2 language, and 2 attention. The proportion of impaired
areas, 5 frontal, 2 parietal, 5 occipital, 1 central, and 6 cognitive areas in comparison to each other approached
diffuse. The proportion of localized findings for specific significance when compared with chance (v2⳱8.95,
cortical areas was greater than chance (v2⳱12.66, df⳱5, df⳱4, P⬍0.10).
P⬍0.05). In the cases that described the specific types of Overall, when data from EEG, CT/MRI, neurological
EEG abnormalities, 10 reported spiking, 24 slowing, and examination, and neuropsychological test data were
2 dysrhythmia. The proportion of each abnormality type combined, 57/63 or roughly 90% demonstrated at least
was greater than chance (v2⳱25.1, df⳱2, P⬍0.001). one abnormality or impaired cognitive function. This
Data for CT and MRI were combined because both proportion was significantly greater than chance
examine structural abnormalities. Of the 55 cases that (v2⳱41.28, df⳱1, P⬍0.001).

TABLE 4. Laboratory findings

Variable Data v2
Abnormalities (n⳱41) 29 yes; 12 no 5.2*
Hemisphere (n⳱35) 17 left; 18 right 0.03
Localization (n⳱35) 16 temporal; 6 diffuse; 5 frontal; 5 occipital; 2 parietal; 1 central 12.66*
Type of abnormality (n⳱36) 24 slowing; 10 spiking; 2 dysrhythmia 25.1***
Positive (n⳱55) 36 yes: 19 no 5.15*
Hemisphere (n⳱76) 30 left: 46 right 3.37
Localization (n⳱84) 23 frontal; 15 temporal; 11 ventricles; 10 diffuse cortical; 8 parietal; 40.28***
6 subcortical; 5 cerebellar; 3 central; 3 brainstem
Type of abnormality (n⳱67) 34 focal lesions: 33 atrophy 0.00
Neurological exam (n⳱24) 14 positive; 10 negative 1.78
Neuropsychological testing
Impairment (n⳱17) 15 yes; 2 no 9.94***
Domain (n⳱28) 10 memory; 7 executive functions; 7 visual spatial; 2 language; 8.95
2 attention
Any abnormality (n⳱63) 57 yes; 6 no 41.28***

*P⬍0.05; **P⬍0.01; ***P⬍0.001.

134 J Neuropsychiatry Clin Neurosci 14:2, Spring 2002


Gender Differences trend was found for the short-delay group to show a
Gender differences in PDTBI were examined. There higher proportion of visual hallucinations (v2⳱3.78,
were trends for females to have sustained TBI at a later df⳱1, P⬍0.10).
age than males (t⳱–1.81, df⳱58, P⳱0.10), and to have No significant differences were found for gender
developed psychosis at a later age (t⳱–1.89, df⳱58, (v2⳱0.11, df⳱1, P⬎0.10), clinical outcome (v2⳱3.03,
P⳱0.08). No differences were found for time of delayed df⳱2, P⬎0.10), proportion demonstrating delusions
onset in developing a psychosis (t⳱0.38, df⳱58, (v2⳱0.30, df⳱1, P⬎0.10), seizure disorder (v2⳱0.94,
P⳱0.71) or for severity of TBI (v2⳱0.37, df⳱1, P⬎0.05). df⳱1, P⬎0.10), negative symptoms (v2⳱1.59, df⳱1,
In terms of clinical presentation, no differences were P⬎0.10), successful medications (v2⳱3.47, df⳱3,
found for proportion of seizure disorder (v2⳱0.51, P⬎0.10), positive EEG findings (v2⳱0.31, df⳱1, P⬎0.10),
df⳱1, P⬎0.05), delusions (v2⳱0.15, df⳱1, P⬎0.05), hal- EEG hemispheric localization (v2⳱0.05, df⳱1, P⬎0.10),
lucinations (v2⳱1.98, df⳱1, P⬎0.05), or negative symp- EEG lobe localization (v2⳱7.12, df⳱4, P⬎0.10), CT/MRI
toms (v2⳱0.48, df⳱1, P⬎0.05). No differences were positive findings (v2⳱0.13, df⳱1, P⬎0.10), CT/MRI
found on laboratory findings for EEG (v2⳱1.22, df⳱1, hemispheric localization (v2⳱2.57, df⳱1, P⬎0.10),
P⬎0.05), CT/MRI (v2⳱0.44, df⳱1, P⬎0.05), or neuro- temporal lobe abnormalities (v2⳱2.57, df⳱1, P⬎0.10),
logical signs (v2⳱0.01, df⳱1, P⬎0.05). ventricular abnormalities (v2⳱2.27, df⳱1, P⬎1.0), neu-
rological signs (v2⳱0.02, df⳱1, P⬎0.10), or neuropsy-
Delay in Onset of Psychotic Symptoms chological testing (v2⳱0.08, df⳱1, P⬎0.10).
Comparisons were also made for patients with a short
versus long delay in onset of psychotic symptoms. Pa- Seizure Disorder
tients were divided into two groups based on scores in Specific analyses were also conducted for subjects with
relation to the median (1 year). Those with onset of a diagnosis of seizure disorder versus those without a
symptoms 1 year and less after TBI were compared to diagnosis. Data are presented in Table 5. No differences
those with onset of symptoms of more than 1 year. Re- were found in age at time of TBI (t⳱0.35, P⬎0.10), age
sults are presented in Table 5. at onset of psychosis (t⳱0.56, P⬎0.10), or delay in onset
Analyses reveal several significant differences be- of psychosis (t⳱0.52, P⬎0.10). In terms of clinical pre-
tween the groups. Differences were found in the setting sentation, there were no differences in proportion of
at the time of evaluation, with the short-delay group subjects presenting with hallucinations (v2⳱1.88, df⳱1,
having a higher proportion of inpatient medical versus P⬎0.10); however, nonseizure patients demonstrated a
psychiatry setting than the long-delay group (v2⳱16.17, significantly higher proportion of delusions (v2⳱4.15,
df⳱1, P⬍0.001). Significant differences were found for df⳱1, P⬎0.05). On laboratory tests, no differences were
proportion of mild versus moderate/severe TBI, with found in proportion of positive findings on EEG
the brief-delay group having more mild brain injury (v2⳱0.0, df⳱1, P⬎0.10) or type of finding on EEG
(v2⳱4.79, df⳱1, P⬍0.05). The long-delay group showed (v2⳱4.02, df⳱2, P⬎0.05). No differences were found in
a higher proportion of hallucinations than the short- proportion of positive CT/MRI findings (v2⳱0.45,
delay group (v2⳱4.07, df⳱1, P⬍0.05). By contrast, a df⳱1, P⬎0.10).

TABLE 5. Summary of positive findings for comparisons of specific clinical groups

Grouping Data v2
Delay in onset of psychosis
Setting 16.17***
Short delay (n⳱24) 9 psychiatric; 15 medical
Long delay (n⳱25) 23 psychiatric; 2 medical
TBI severity 4.79*
Short delay (n⳱15) 8 mild; 7 moderate-severe
Long delay (n⳱17) 14 mild; 2 moderate-severe
Hallucinations 4.07*
Short delay (n⳱39) 11 yes; 18 no
Long delay (n⳱28) 18 yes; 10 no
Seizure disorder
Delusions 4.15*
Positive seizure (n⳱11) 7 yes; 4 no
Negative seizure (n⳱37) 35 yes; 2 no

*P⬍0.05; **P⬍0.01; ***P⬍0.001.

J Neuropsychiatry Clin Neurosci 14:2, Spring 2002 135


DISCUSSION of psychosis after TBI, or diagnosis of a seizure disorder.

The most common class of efficacious medication ap-
What are typical characteristics of PDTBI? pears to be neuroleptics. Neuroleptics appeared to be
efficacious in these patients regardless of diagnosis of
Our data indicate that males are significantly over- seizure disorder.
represented in cases of PDTBI even after correcting for Results from other PDTBI studies reporting data on
the base rate of males to females in TBI (2:1). This result course of illness are not as favorable. A study with
is consistent with other studies reporting gender differ- World War II veterans reported a relatively poor prog-
ences.7,15,54 The robustness of this finding may suggest nosis: 40% of patients with delusional disorders and
that males are at higher risk for developing PDTBI. Males 63% of schizophrenic patients demonstrated a chronic
are reported to have a higher incidence of other neurod- course.5 Another study with general psychiatric patients
evelopmental disorders such as learning disabilities.1,55 reported an uncertain course that was not related to se-
They are also believed to have poorer prognosis for re- verity of TBI.54
covery from aphasia after a cerebral vascular accident,
because of the increased hemispheric lateralization in or- What historical, physical, or laboratory findings are
ganization of the male brain.56–59 In addition, males gen- associated with PDTBI?
erally develop schizophrenia at an earlier age than fe-
males.1 What severity of TBI is significant enough to cause a psycho-
In terms of clinical presentation, our data indicated sis? A significant proportion of known cases reported
that delusions appear to be more common than hallu- moderate to severe TBI as defined by ACRM criteria.
cinations. The most common delusion is the persecutory However, the majority of cases reported LOC of unspe-
type, although there was a wide variety of subtypes. The cific duration, and thus severity could not be deter-
most common hallucination was auditory. The presence mined. There were cases in which PDTBI occurred with-
and type of hallucinations appeared to be associated out LOC. For these subjects, the onset of psychosis was
with delay in onset of psychosis after TBI. Patients with generally early, within the first year after trauma. Our
later onset of symptoms (2 years or longer after the results are similar to other findings that the majority of
trauma) were more likely to have hallucinations than patients who develop a PDTBI sustained a moderate to
early-onset patients (onset less than 2 years after severe head injury.4,7,15,61 Still, in all of these studies
trauma). However, early-onset patients were more likely there were patients who developed PDTBI after a mild
than late-onset patients to have visual hallucinations. TBI, including some who did not lose consciousness.
This occurrence would be consistent with the presence
of possible delirium and/or types of hallucinations that How long after an injury is the TBI considered to be etiolog-
are secondary to neurological and medical causes.60 ically relevant to the development of a psychosis? In gen-
Negative symptoms such as alogia, affective flattening, eral, our results indicate a wide range in time between
and avolition are uncommon sequelae. TBI and the onset of psychosis (range 0–34 years). The
Our results are very similar to findings in three of four mean age for sustaining TBI was 29.1Ⳳ17.6 years,
previous studies that examined different data sources, whereas the mean age for developing psychosis was
including a general psychiatric sample, head-injured 33.4Ⳳ15.4 years. The majority of subjects had a delayed
war veterans, and a previous meta-analysis of the lit- onset, the mean length of delay being 4.1Ⳳ6.6 years.
erature.4,15,54 These studies reported a preponderance of Half of the subjects demonstrated psychotic symptoms
paranoid delusions and schizophreniform disorders. before the second year after TBI, and 72% reported an
The lone study in which the presentation was not highly onset of psychosis before 4 years—that is, before the
consistent was based at a state hospital.7 Results from mean length of delay.
the state hospital study reported slightly more halluci- Our results are similar to those of all other studies
nations. Paranoid delusions were, however, still the reviewed in finding a wide range of delay in the onset
most prevalent subtype. Negative symptoms were not of psychotic symptoms.4,5,7,15 The studies differ, how-
reported. It is possible that the greater frequency of hal- ever, in terms of tendencies for onset of symptoms. Our
lucinations in the state hospital study may be due to the results are very similar to those in a previous meta-
likely greater severity of illness or injury in that popu- analysis of the literature, which reported that most
lation. closed head injury patients who demonstrate psychotic
The course of illness for a significant majority of sub- symptoms do so within the first year (52%) and the ma-
jects in our analysis was good. Prognosis did not appear jority within 5 years (85%), while the majority of mod-
to be affected by variables such as gender, delay in onset erate to severe TBI patients who report psychotic symp-

136 J Neuropsychiatry Clin Neurosci 14:2, Spring 2002


toms do so within the first year (67%).15 Another study of the literature, and World War II veterans) consistently
with predominantly closed head injury patients reported reported temporal lobes abnormalities in their pa-
a mean onset of 5.9 years.7 Contradictory findings were tients.4,15,54 The meta-analytic study also reported a pre-
reported for two studies consisting of World War II vet- ponderance of left-sided lesions, which contradicts our
erans, many of whom sustained open head injuries.4,5 findings indicating equal occurrence of left and right
One of these studies reported 60% who developed a psy- hemispheric lesions.15 The study on the war veterans
chosis had onsets after 5 years; the other reported a ma- reported 23.8% frontal lesions, 20% temporal, 15.3% pa-
jority of delusional psychoses occurring between 15 and rietal, and 14.3% basal lesions.4
19 years post injury. It is possible that differences in onset
after TBI may be due to type of head injury. What are some characteristics that may discriminate
between PDTBI and schizophrenia?
What laboratory findings are associated with psychosis?
Abnormal EEGs were reported in about 70% of the A comparison of our data and the literature on schizo-
cases. A significant majority of abnormalities were phrenia suggests that several characteristics distinguish
found in the temporal lobes. The most common abnor- between the two disorders (Table 6).
mality was slowing followed by spiking. There were no First, PDTBI patients appear less likely to demon-
differences in laterality of positive findings. strate negative symptoms than schizophrenic patients.
About 65% of the cases reported positive findings on In our sample, only 14% reported the presence of neg-
MRI/CT. The most common location of findings was the ative symptoms, whereas the prevalence rate of negative
frontal lobes, followed by the temporal lobes and ventri- symptoms in schizophrenia has been reported to range
cles. There were no differences in laterality of findings. from 25% to 84%.62,63
Among the cases that reported type of abnormalities, fo- Patients with PDTBI and schizophrenia also appear to
cal lesions and atrophy were about equally represented. demonstrate differences on neurological studies. On
About 88% of cases reported impairments on neuro- MRI/CT, a higher percentage of PDTBI than schizo-
psychological testing. The most common impaired func- phrenic patients demonstrate positive findings, and the
tion was memory, followed by executive and visuospa- types of findings appear to be qualitatively different. In
tial functions. About 58% of cases reported positive our study, positive findings were found in 65% of the
neurological symptoms, which was not significantly dif- PDTBI sample. This percentage is much larger than in
ferent from chance. Aggregating data from different studies on schizophrenia that report rate of abnormali-
sources, we found that temporal and frontal lobes ap- ties (12.5%–35%).64–68 For PDTBI patients, there ap-
pear to be the most commonly affected areas in PDTBI. peared to be an equal distribution of focal signs (62%)
Findings from MRI/CT indicated enlarged ventricles and general atrophy (60%). Focal lesions were most
were also common. common in the frontal (42%) and temporal lobes (27%).
As we mentioned above, research with neurological About 20% of PDTBI patients demonstrated enlarged
studies on patients with PDTBI is scarce. Data from the ventricles. By contrast, atrophy/volume loss is the most
two such studies, both with small sample sizes, are in- common type of MRI/CT finding for schizophrenia pa-
corporated in our findings.7,12 Three other studies with tients,69,70 whereas unspecified focal findings are re-
different data bases (general psychiatry, meta-analysis ported in only 6% to 9% of patients.71,72 The most com-

TABLE 6. Characteristics potentially discriminating between PDTBI and schizophrenia

Characteristic PDTBI Schizophrenia
Presence of negative symptoms 14% 25%–84%61,62
Positive findings 65% 12%–35%63–67
Atrophy 60% 12%–35%68,69
Focal abnormalities 62% 6%–9%70,71
Most common finding 42% frontal 22%–35%63–65 enlarged ventricles
27% temporal
20% ventricles
Positive findings 70% 20%–60%72
Most common finding Temporal slowing Frontal slowing74

Note: PDTBI⳱psychotic disorder due to traumatic brain injury.

J Neuropsychiatry Clin Neurosci 14:2, Spring 2002 137


mon findings in schizophrenic patients are enlarged agnosis, we found no differences in proportion of posi-
ventricles (22%–35%)64–70 and atrophy in the temporal tive findings or type of findings on EEG, proportion of
lobes.69,70 positive MRI/CT findings, age at time of TBI, age at
In addition, 70% of the PDTBI patients in our study onset of psychosis, or delay in onset of psychosis. The
demonstrated EEG abnormalities. In studies with lone difference between the two groups was that non-
schizophrenic patients, EEG abnormalities were found seizure subjects reported a higher proportion of delu-
in 20% to 60% of the subjects.73 The percentage of EEG sions (95%) than seizure patients (63%).
abnormalities in our sample resembles that of nonfa-
milial schizophrenic patients (72.3%).74 This higher per-
centage of EEG findings may suggest that TBI or seizure
Our study is exploratory and descriptive, and thus the
disorder may be a factor for developing a psychosis in
findings should be viewed as preliminary. Its major lim-
nonfamilial schizophrenics.
itation is the use of archival data that are subject to bi-
Roughly half (55%) of the EEG abnormalities in our
ases in data collection. For example, there could have
sample were localized findings, with the modal abnor-
been a selection bias for more early-onset PDTBI cases
mality being temporal slowing. The most common find-
because it would be easier to justify the relationship be-
ings across studies of schizophrenia are delta and theta
tween TBI and the onset of psychosis. We also looked
waves in the frontal areas, a decreased mean frequency
only at PDTBI cases in which there were neurological
in alpha, and increased beta power.75
and neuropsychological investigations. Likewise, there
could have been a bias toward positive findings on im-
What are some characteristics that may discriminate
aging data because negative findings are less likely to
between PDTBI patients with or without a diagnosed
be submitted or selected for publication. Another prob-
seizure disorder?
lem is with the comparability of findings between cases
because of differences in researcher ratings and obser-
About 34% of the subjects had received diagnoses of a
vations. A specific problem in our data set involved
seizure disorder. This prevalence rate is similar to the
missing data points due to differences in reporting. To
rates in other studies on posttraumatic psychosis7 and is
address these weaknesses, future studies should use
significantly higher than the highest estimate of seizure
prospective data and address potential problems of in-
disorder after all closed head injuries (12%).16 This higher
terrater reliability.
incidence provides some corroborative support for an as-
sociation between seizure disorder and PDTBI.7,15,16,17
The presence of seizure disorder did not appear to be The authors thank Lisa Anne Matsumoto, Casey Pinter,
a strong discriminating factor in our sample. In com- and Mary Church for their assistance in obtaining articles
paring subjects with and without a seizure disorder di- and in data preparation.


1. American Psychiatric Association: Diagnostic and Statistical of two cases with onset of symptoms precipitated by head
Manual of Mental Disorders, 4th edition. Washington, DC, trauma. Br J Psychiatry 1988; 152:410–412
American Psychiatric Association, 1994 9. Katz DI, Alexander MP, Seliger GM, et al: Traumatic basal gan-
2. Ahmed I, Fujii DE: Posttraumatic psychosis. Semin Clin Neu- glia hemorrhage: clinicopathologic features and outcome. Neu-
ropsychiatry 1998; 3:23–33 rology 1989; 39:897–904
3. Lishman WA: The psychiatric sequelae of head injury: a review. 10. Silva JA, Leong GB, Thi Luong M: Split body and self: an unusual
Psychol Med 1973; 3:304–318 case of misidentification. Can J Psychiatry 1989; 34:728–730
4. Achte KA, Hillbom E, Aalberg V: Psychoses following war in- 11. Marshall JC, Halligan PW, Wade DT: Reduplication of an event
juries. Acta Psychiatr Scand 1969; 45:1–18 after head injury? A cautionary case report. Cortex 1995; 31:183–
5. Achte K, Jarho L, Kyykka T, et al: Paranoid disorders following 190
war brain damage. Psychopathology 1991; 24:309–315 12. Feinstein A, Ron M: Psychosis associated with demonstrable
6. Koufen DI, Hagel KH: Systematic EEG follow-up study of trau- brain disease. Psychol Med 1990; 20:793–803
matic psychosis. Eur Arch Psychiatry 1987; 237:2–7 13. Hillbom E: After-effects of brain injuries. Acta Psychiatr Neurol
7. Fujii DE, Ahmed I: Psychosis secondary to traumatic brain in- Scand Suppl 1960; 142:1–195
jury. Neuropsychiatry Neuropsychol Behav Neurol 1996; 9:133– 14. Burg JS, McGuire LM, Burright RG, et al: Prevalence of traumatic
138 brain injury in an inpatient psychiatric population. Journal of
8. Will RG, Young JPR, Thomas DJ: Kleine-Levin syndrome: report Clinical Psychology in Medical Settings 1996; 3:245–251

138 J Neuropsychiatry Clin Neurosci 14:2, Spring 2002


15. Davison K, Bagley CR: Schizophrenia-like psychoses associated 40. Rogers MJC, Franzen MD: Delusional reduplication following
with organic disorders of the central nervous system: a review closed head injury. Brain Inj 1992; 6:469–476
of the literature. Br J Psychiatry 1969 (suppl); 114:113–162 41. Sabhesan S, Arumugan R, Natarajan M: Paraamnesic delusions
16. McKenna Kane JM, Parrish K: Psychotic syndromes in epilepsy. following head injury. Indian Journal of Psychiatry 1988; 30:177–
Am J Psychiatry 1985; 142:895–904 181
17. Annegers JF, Gradow JD, Kurland LT, et al: The incidence, 42. Sabhesan S, Natarajan M: Delusional disorders after head injury.
causes, and secular trends of head trauma in Olmstead County, Indian Journal of Psychiatry 1988; 30:39–45
Minnesota 1935–1974. Neurol 1980; 30:912–919 43. Sandel ME, Olive DA, Rader MA: Chlorpromazine-induced psy-
18. Nasrallah HA: The neuropsychiatry of schizophrenia, in Text- chosis after brain injury. Brain Inj 1993; 7:77–83
book of Neuropsychiatry, 2nd edition, edited by Yudofsky S, 44. Signer SF, Cummings JL: De Clerambault’s syndrome in organic
Hales R. Washington DC, American Psychiatric Press, 1992, affective disorder: two cases. Br J Psychiatry 1987; 151:404–407
pp 621–638 45. Silva JA, Leong GB, Wine DB: Misidentification delusions, facial
19. Bamrah JS, Johnson J: Bipolar affective disorder following head misrecognition, and right brain injury. Can J Psychiatry 1993;
injury. Br J Psychiatry 1991; 153:117–119 38:239–241
20. Barnhill LJ, Gualteri CT: Two cases of late-onset psychosis after 46. Staton RD, Brumback RA, Wilson H: Reduplicative paramnesia:
closed head injury. Neuropsychiatry Neuropsychol Behav Neu- a disconnection syndrome in memory. Cortex 1982; 18:23–35
rol 1989; 2:211–217 47. Tisher PW, Holzer JC, Greenberg M, et al: Psychiatry presenta-
21. Benson DF, Stuss DT: Frontal lobe influences of delusions: a clini- tions of epilepsy. Harv Rev Psychiatry 1993; 1:219–228
cal perspective. Schizophr Bull 1990; 16:403–412 48. Waldfogel S, Field HL, Wu L: Oedipism in a patient with frontal
22. Bienenfeld D, Brott T: Capgras’ syndrome following minor head lobe encephalomalacia. Brain Inj 1994; 8:377–381
trauma. J Clin Psychiatry 1989; 2:68–69 49. Weston MJ, Whitlock FA: The Capgras syndrome following head
23. Bouvy PF, van de Wetering JD, Meerwaldt JD, et al: A case of or- injury. Br J Psychiatry 1971; 119:25–31
ganic brain syndrome following head injury successfully treated 50. White AC, Armstrong D, Rowan D: Compensation psychosis. Br
with carbamazepine. Acta Psychiatr Scand 1988; 77:361–363 J Psychiatry 1987; 150:692–694
24. Buckley P, Stack JP, Madigan C, et al: Magnetic resonance im- 51. Will RG, Young JPR: Kleine-Levin syndrome: report of two cases
aging of schizophrenia-like psychoses associated with cerebral with onset of symptoms precipitated by head injury. Br J Psy-
trauma: clinicopathological correlates. Am J Psychiatry 1993; chiatry 1988; 152:410–412
150:146–148 52. Young AW, Robertson IH, Helawell DJ, et al: Cotard delusion
25. Cohen MA, Alfonso CA, Haque MM: Lilliputian hallucinations after brain injury. Psychol Med 1992; 22:799–804
and medical illness. Gen Hosp Psychiatry 1994; 16:141–143 53. Mild Traumatic Brain Injury Committee of the Head Injury In-
26. Dalby JT, Arboleda-Florez J, Seland TP: Somatic delusions fol- terdisciplinary Special Interest Group of the American Congress
lowing left parietal lobe injury. Neuropsychiatry Neuropsychol of Rehabilitation Medicine: Definition of mild traumatic brain
Behav Neurol 1989; 2:306–311 injury. J Head Trauma Rehabil 1993; 8:86–87
27. Dolinar LJ: Delusions in a patient with post-traumatic headache. 54. Violin A, Violin A, De Mol J: Psychological sequelae after head
Psychosomatics 1991; 32:460–462 traumas in adults. Acta Neurochir (Wien) 1987; 85:96–102
28. Drake ME: Cotard’s syndrome and temporal lobe epilepsy. Psy- 55. Geschwind N, Galaburda AM: Cerebral lateralization, biological
chiatry J Univ Ottawa 1988; 13:36–39 mechanisms, associations, and pathology. Arch Neurol 1985;
29. Filley CM, Jarvis PE: Delayed reduplicative paramnesia. Neurol 42:428–459
1987; 37:701–703 56. Gur RC, Gur RE, Obrist WD, et al: Sex and handedness differ-
30. Hayman MA, Abrams R: Capgras’ syndrome and cerebral dys- ences in cerebral blood flow during test and cognitive activity.
function. Br J Psychiatry 1977; 130:68–71 Science 1982; 217:659–660
31. Ikemura Y, Akena H, Iida M, et al: Psychiatry of diencephalon 57. Levy J, Heller W: Gender differences in human neuropsycho-
damages: a case report. Funct Neurol 1987; 11:87–91 logical functioning. in Handbook of Behavioral Neurobiology,
32. Levine DN, Finklestein S: Delayed psychosis after right tempo- vol 11, Sexual Differentiation, edited by Geralm AA, Ward IL.
roparietal stroke or trauma: relation to epilepsy. Neurology 1982; New York, Plenum, 1992, pp 245–274
32:267–273 58. Pizzamiglio L, Mammucari A, Razzano C: Evidence for sex dif-
33. Lloyd DW, Tsuang MT: A snake lady: post-concussion syndrome ferences in brain organization in recovery in aphasia. Brain Lang
manifesting visual hallucinations of snakes. J Clin Psychiatry 1985; 25:213–223
1981; 42:246–247 59. Basso A, Capitani E, Moraschini S: Sex differences in recovery
34. Murai T, Toichi M, Sengoku A, et al: Reduplicative paramnesia from aphasia. Cortex 1982; 18:469–475
in patients with focal brain damage. Neuropsychiatry Neuro- 60. Cummings JL: Clinical Neuropsychiatry. New York, Grune and
psychol Behav Neurol 1997; 10:190–196 Stratton, 1985
35. Nasrallah HA, Fowler RC, Judd LL: Schizophrenia-like illness 61. Sabhesan S, Arumughan R, Natarajan M: Neuroanatomical cor-
following head injury. Psychosomatics 1981; 22:359–361 relates of delusions in head injury. Indian Journal of Psychiatry
36. O’Callaghan E: Early onset schizophrenia after teenage head in- 1990; 32:180–184
jury. Br J Psychiatry 1988; 153:394–396 62. Fenton WS: Longitudinal course and outcome of schizophrenia,
37. O’Connor M, Wallbridge M, Sandson T, et al: A neuropsycho- in Handbook of Mental Health Economics and Health Policy,
logical analysis of Capgras syndrome. Neuropsychiatry Neuro- vol 1, edited by Moscarelli M, Rupp A, Sartorius N. New York,
psychol Behav Neurol 1996; 4:265–271 Wiley, 1996, pp 79–91
38. Prigatano GP, O’Brien KP, Klonoff PS: The clinical management 63. Breier A, Schrieber JL, Dyer J, et al: National Institute of Mental
of paranoid delusions in postacute traumatic brain-injured pa- Health longitudinal study of chronic schizophrenia. Arch Gen
tients. J Head Trauma Rehabil 1988; 3:23–32 Psychiatry 1991; 48:239–246
39. Puri BK, El-Dosoky A, Barrett JS: Self-inflicted intracranial in- 64. Cazzullo CL, Vita A, Sacchetti E, et al: Brain morphology in
jury. Br J Psychiatry 1994; 164:841–842 schizophrenic disorder: prevalence and correlates of diffuse (cor-

J Neuropsychiatry Clin Neurosci 14:2, Spring 2002 139


tical and subcortical) brain atrophy. Psychiatry Res 1989; 29:257– 70. McCarley RW, Wible CG, Frumin M, et al: MRI anatomy of
259 schizophrenia. Biol Psychiatry 1999; 45:1099–1119
65. Vita A, Sacchetti E, Calzeroni A, et al: Cortical atrophy in schizo- 71. Cunningham-Owen DG, Johnstone EC, Bydder GM, et al: Un-
phrenia: prevalence and associated features. Schizophr Res 1988; suspected organic disease in chronic schizophrenia demon-
1:329–337 strated by computed tomography. J Neurol Neurosurg Psychi-
66. Sacchetti E, Calzeroni A, Vita C, et al: The brain damage hy- atry 1980; 43:1065–1069
pothesis of the seasonality of births in schizophrenia and major 72. Lewis SW: Computerised tomography in schizophrenia 15 years
affective disorders: evidence from computerised tomography. Br on. Br J Psychiatry 1990; 157(suppl):16–24
J Psychiatry 1992; 160:390–39 73. Gerez M, Tello A: Selected quantitative EEG (QEEG) and event-
67. Nasrallah HA, Kuperman S, Hamra BJ, et al: Clinical differences related potential (ERP) variables as discriminators for positive
between schizophrenic patients with and without large cerebral and negative schizophrenia. Biol Psychiatry 1995; 38:34–49
ventricles. J Clin Psychiatry 1983; 44:407–410 74. Kendler KS, Hays P: Familial and sporadic schizophrenia: a
68. Vita A, Dieci M, Giobbio GM, et al: CT scan abnormalities and symptomatic, prognostic, and EEG comparison. Am J Psychiatry
outcome in chronic schizophrenia. Am J Psychiatry 1991; 1982; 139:1557–1562
148:1577–1579 75. Hughes JR, John ER: Conventional and quantitative electroen-
69. Pearlson GD, Marsh L: Structural brain imaging in schizophre- cephalography in psychiatry. J Neuropsychiatry Clin Neurosci
nia: a selective review. Biol Psychiatry 1999; 46:627–649 1999; 11:190–208

140 J Neuropsychiatry Clin Neurosci 14:2, Spring 2002