Systematic Review on The Prevalence of Bipolar Disorder in Traumatic Brain Injury Patient as

The Leading Cause of Psychiatric Disorder

Johan Wibowo¹, Maria Gabrielle Vanessa¹, Caroline Wibowo¹, Jonathan Juniard Anurantha¹
¹ Faculty of Medicine, University of Pelita Harapan, Tangerang, Banten, Indonesia
Introduction
Bipolar disorders are described by the American Psychiatric Association’s Diagnostic and
Statistical Manual of Mental Disorders (DSM-5) as a group of brain disorders that cause extreme
fluctuation in a person’s mood, energy, and ability to function​¹​. There are three types of bipolar disorder.
All three types involve clear changes in mood, energy, and activity levels. These moods range from
periods of extremely “up,” elated, irritable, or energized behavior (known as manic episodes) to very
“down,” sad, indifferent, or hopeless periods (known as depressive episodes). Less severe manic periods
are known as hypomanic episodes. (1) Bipolar I disorder defined by manic episodes that last at least 7
days or by manic symptoms that are so severe that the person needs immediate hospital care. Usually,
depressive episodes occur as well, typically lasting at least 2 weeks. Episodes of depression with mixed
features (having depressive symptoms and manic symptoms at the same time) are also possible. (2)
Bipolar II disorder defined by a pattern of depressive episodes and hypomanic episodes, but not the
full-blown manic episodes that are typical of bipolar I disorder. Cyclothymic disorder (also called
cyclothymia) defined by periods of hypomanic symptoms as well as periods of depressive symptoms
lasting for at least 2 years (1 year in children and adolescents). However, the symptoms do not meet the
diagnostic requirements for a hypomanic episode and a depressive episode.
Diagnosing bipolar disorder was conducted by a doctor to perform physical examinations in order
to evaluate the condition that may trigger the symptoms. The doctor then will conduct a mental evaluation
to see if the patient’s symptoms match the specific criteria of DSM-5 to be diagnosed with bipolar. To be
considered with bipolar disorder, a patient must experience at least one episode of mania or hypomania
that last at least one week and present most of the day. The doctor will assess if the patient presents a
significant change from the usual behavior: (1) inflated self-esteem, (2) decreased need for sleep, (3)
increased talkativeness, (4) racing thoughts, (5) easily distracted, (6) increased psychomotor agitation, (7)
engaging in activities that hold the potential for painful consequences. The doctor will also assess the
depressive side of bipolar disorder: (1) depressed mood most of the day, nearly every day, (2) loss of
interest or pleasure in all, or almost all activities, (3) significant weight loss or decrease in appetite, (4)
engaging in purposeless movement, (5) fatigue or loss of energy, (6) feeling of worthlessness, (7)
diminished ability to think, (8) recurrent thoughts of death. To be diagnosed with bipolar, the patient must
have 3 or more characteristics of behavioral changes and must experience 5 or more depressive
characteristics.
 Epidemiological studies have suggested a lifetime prevalence of around 1% for bipolar type I in
the general population​³. A large cross-sectional survey of 11 countries found the overall lifetime
prevalence of bipolar spectrum disorders was 2.4%, with a prevalence of 0.6% for bipolar type I and 0.4%
for bipolar type II. According to the National Institute of Mental Health, the exact causes of bipolar
disorder are still unknown. However, the combination of several factors such as genes, brain structure,
and function may contribute to bipolar disorder.
According to the American Association of Neurological Surgeon​⁴​, a traumatic brain injury is
defined as a blow to the head or a penetrating head injury that disrupts the normal function of the brain.
TBI can result when the head suddenly and violently hits an object or when an object pierces the skull and
enters brain tissue. Symptoms of a TBI can be mild, moderate or severe, depending on the extent of
damage to the brain. Mild cases may result in a brief change in mental state or consciousness, while
severe cases may result in extended periods of unconsciousness, coma or even death.
Studies conducted by Robert van Reekum et al ​⁵. shows that there was a strong and growing body
of evidence to support the hypothesis that TBI frequently causes some, but not all, psychiatric disorders in
those who have suffered a TBI. There is a compelling evidence of causation for major depression, bipolar
affective disorder, and anxiety disorders after TBI.
In this systematic review, we wanted to evaluate the prevalence of bipolar disorder in the
traumatic brain patient as the leading cause of psychiatric disorder.

Methods
In our systematic review, we collected our data from online journals which include Pubmed,
Science Direct, Google Scholar and also Taylor and Francis Online Journal. Systematic Analysis
approach was used in this study, for example, the PICO method. For the People or Population (P), we
used “adult”. However, in this systematic review, we did not use any Intervention (I). For Comparison
(C), we used the terminology “Traumatic Brain Injury or TBI”. And for the outcome (O), we used
“Bipolar Disorder Incidence”. The hypothesis in this systematic review is “Can traumatic brain injury
cause bipolar disorder as a comprehensive biological factor?”. The inclusion criteria used in this
systematic review is a cross-sectional study, which focuses on these factors : traumatic brain injury,
bipolar disorder and adult population. The methods that are excluded (exclusion criterias) to make this
scientific paper are meta-analysis studies, literature reviews, case report studies, systematic reviews, and
animal studies. In addition, we mainly pay attention to adult population, not children.
Results and Discussion:
Using the PICO method without applying the interventions, we have acquired 5 cross-sectional
studies that will be analyzed. The diagram below shows the selection process of the articles.

Figure. 1​ Information of the flow chart through the different phases of the systematic review
Table. 1​ Summary of studies on the prevalence of the bipolar disorder in TBI

Authors Study Year Subject Result

Kiruthika ⁶ Cross-sectional 2019 Patients with There is no incidence of

radiological signs of bipolar disorder after a TBI
brain damage through
trauma

Drange et al ⁷. Cross-sectional 2018 Patients diagnosed with Premorbid TBI is not

bipolar disorder type I associated with hypomania or
and type II mania ratio

Walker et al ⁸. Cross-sectional 2015 Veterans with one or Historical blast in mTBI does
more blast experiences not have a relation with
within the past 2 years post-deployment psychiatric
while deployed in diagnosis including bipolar
OIF/OEF/OND disorder

Slaughter et al Cross-sectional 2003 Inmates incarcerated Higher prevalence of mood

⁹. consists of 25 who and anxiety disorders
reported having TBI including bipolar disorder
and 25 who denied among individuals with TBI
having TBI in 12
months

Bogner et al ¹⁰. Cross-sectional 2019 A 6996 random samples A sustained at least 1 TBI
in the with loss of consciousness in
noninstitutionalized a lifetime has an increased
population with risk for poor behavioral health
completed questions including depressive disorder
using OSU TBI-ID such as bipolar disorder

Note :
TBI : Traumatic Brain Injury
OIF : Operation Iraqi Freedom
OEF : Operation Enduring Freedom
OND : Operation New Dawn
mTBI : Mild Traumatic Brain Injury
OSU TBI-ID : Ohio State University Traumatic Brain Injury Identification Method
 A study assessed by Kiruthika for 6 months with Mini-International Neuropsychiatric Interview
(MINI) shows that a total of 100 patients (aged 18-60 years, 71 males and 29 females) attending
outpatient and inpatient departments of neurosurgery are confirmed to have a history of traumatic brain
damage. However, there are certain exclusion criterias for the chosen subjects. For instance, the patients
that had experienced either a psychiatric illness or neurological disorders before brain injury (like bipolar
disorders) and also having gross cognitive deficits that might affect the interview. The details of the
history were taken from the patient regarding the illness. Psychiatric morbidity was assessed using the
Hamilton Depression Rating Scale (HAMD-D), Hamilton Anxiety Rating Scale (HAM-A), Positive and
Negative Syndrome Scale (PANSS) for psychotic disorders DSM-V and ​International Statistical
Classification of Diseases and Related Health Problems (​ICD-10). All of those findings were correlated
with the radiological findings of the patient to know which region of the brain affected. Also, the severity
of the head injury was measured from the Glasgow Coma Scale (GCS). According to the results, most of
the patients had brain injury through road traffic accidents (92%) and the rest (8%) were caused by
accidental falls (6%) or assault (2). Based on the analysis, the long-term outcome of TBI patients is
primarily related to the severity of brain injury, type, and location of the intracranial lesion, patients' age,
the efficacy of acute medical and surgical treatment, socioeconomic status, educational level, previous
psychiatric disorders. This study does not have any incidence of post-traumatic manic illness unlike in the
previous studies which showed the incidence of mania. Bipolar illness with past history of psychiatric
illness before the injury was found and no new case of mania detected after injury. To sum everything up,
in the treatment of head injury (Apart from the treatment of physical symptoms), it is also important to
treat psychiatric symptoms because psychiatric comorbidity delays the social and functional outcome of
the patient. Clinicians had missed most of it and therefore affects the prognosis of the patient. Hence, it is
essential to identify the risk factors and understand the clinical features to give better treatment for the
patient. Not a single can predict the risk of psychiatric comorbidity and also found it has no relationship
with the severity and laterality of lesions consistently.
Drange et al. stated in their study that premorbid TBI was not associated with an increased
hypomania or mania’s depression ratio. However, premorbid TBI was associated with a higher Young
Mania Rating Scale (YMRS) disruptive component score (Odds Ratio [OR] 1.7, 95% Confidence Interval
[CI] 1.1–2.4, p = 0.0077) and more comorbid migraine (OR 4.6, 95% CI 1.9–11, p = 0.00090)
independently of several possible confounders. The sample was analyzed from five hundred and five
patients. Mean age was 42 years (SD 14), 286 (57%) were women, and 256 (53%) had BD type I.
Thirty-seven patients (7.3%) reported a premorbid TBI, of whom 23 (4.6%) had LOC. Age at TBI and
years from age at TBI to age at onset of BD had mean values of 10 years (SD 9.0) and 8.9 years (SD 7.3),
respectively. Clinicians judged the reliability of the patients’ answers as high in both groups (median 1 vs.
1 (interquartile range 1 vs. 1), p = 0.45). By applying bivariate analyses with correction for multiple
testing, they found more comorbid migraine (36 vs. 13%, p = 0.00030) among patients with premorbid
TBI. Also, using the logistic regression, they analyzed data for 395 of 505 participants (78%) were
complete and thereby included in the backward likelihood ratio logistic regression analysis. Among
clinical characteristics, the YMRS disruptive component score (OR 1.7, 95% CI 1.1–2.4, p = 0.0077) and
comorbid migraine (OR 4.6, 95% CI 1.9–11, p = 0.00090) were independently associated with premorbid
TBI. A family history of schizophrenia (OR 11, 95% CI 2.3–51, p = 0.0025) was also independently
associated with premorbid TBI. The associations between premorbid TBI and YMRS disruptive
component score and comorbid migraine remained significant after correction for BD subtypes, mood
states, and pharmacological treatments. Items on disruptive/aggressive behavior and irritability had the
highest loadings on the YMRS disruptive component. They found that premorbid TBI was associated
with comorbid migraine in bivariate analyses with correction for multiple comparisons. In a logistic
regression model, they found that premorbid TBI was associated with disruptive symptoms and comorbid
migraine independently of a range of possible confounders. A family history of schizophrenia was also
independently associated with premorbid TBI. So, They did not find associations between premorbid TBI
and any other clinical characteristics and specifically not with hypomania/mania: depression ratio.
A study conducted by Walker et al using structured interviews for Mild Traumatic Brain Injury
(mTBI), Post-Traumatic Stress Disorder (PTSD) and multiple moods and anxiety diagnoses, shows that a
total of 107 veterans that have undergone 2 years of blast exposures (at least 61%) were diagnosed with
either post-deployment mood or anxiety disorder episode. Moreover, depression was 43-times (95% CI ¼
11–165) more likely if an individual had PTSD. Post-Concussion Syndrome (PCS) symptoms were
greater in those with post-deployment PTSD or mood diagnosis. However, neither mTBI nor blast
exposure history had an effect on the odds of having PTSD, mood or anxiety condition. Based on the
analysis, current depression was the most common mood diagnosis, with 17 participants (16%) meeting
the criteria for clinical depression at the time of the interview. Of these depressed participants, it is also
important to highlight that six also had past hypomanic or manic episodes and so met study criteria for
bipolar disorder. ​These findings support that psychiatric conditions beyond PTSD are common after
military combat deployment with blast exposure. They also highlight the non-specificity of
post-concussion type symptoms. While some researchers have implicated mTBI history as a contributor
to post-deployment mental health conditions, no clear association was found. This may partly be due to
the more rigorous method of retrospective mTBI diagnosis determination.
 According to Slaughter et al. study using the X​2 ​analysis stated that from 91 individuals
approached, 69 (75.8%) consented to participate in the study, over one third (n=25, 36.2%) reported
sustaining a TBI in the 12 months immediately prior to interview. Of these, 20 (29.0%) reported mild TBI
and five (7.2%) reported moderate or severe TBI during the prior year. Sixty (87.0%) of the study sample
reported TBI sometime in their lifetime, with 20 (29.0%) reporting a lifetime history of moderate or
severe TBI. Comparing the two groups, one with recent TBI in 12 months prior to the interview, and the
other one is the group with no TBI in 12 months prior to the interview, and a sub-group of 50 subjects
who were administered neuropsychological tests and diagnostic psychiatric interviews. The two groups
differed significantly on Brief Anger and Aggression Questionnaire (BAAQ), with the group reporting
recent TBI showing higher levels of anger and aggression. On the other instruments, subjects with TBI in
the prior year performed worse on Controlled Oral Word Association Test (COWAT) and Trails B,
although these differences were not statistically significant. From the subgroup of 50 subjects who were
administered neuropsychological tests and diagnostic psychiatric interviews, 33 denied and 17 endorsed a
lifetime history of moderate/ severe TBI. The group reporting TBI in the prior year had a higher
prevalence of most of the psychiatric disorders including bipolar disorder assessed by Primary Care
Evaluation of Mental Disorders (PRIME-MD) as compared to the group with no TBI in the prior year,
although this difference was not significant when an X​2 analysis was performed [X​2 (1, n=36) = 0.49, p =
0.48]. A total of 21 (84%) subjects with recent TBI had at least one psychiatric disorder including bipolar
disorder, with 15 (60%) of subjects without recent TBI having a psychiatric disorder including bipolar
disorder.
A study from Bogner et al. stated, a total of 10.934 adults with the age of 18 years old or older
and live in a noninstitutionalized population were contacted and a random sample (n = 6996) completed
questions from the Ohio State University Traumatic Brain Injury Identification Method (OSU TBI-ID)
module. As reported, nearly 22% of noninstitutionalized Ohio adults sustained at least 1 TBI with LOC in
their lifetime. Reports confirmed a number and percentage of Ohio adults who were binge and heavy
drinking in the past 30 days, a current smoker, ever had a depressive disorder, and number of days of
mental health being not good (eg, ≥2 days and ≥14 days) were calculated as shown in the table below.
Table. 2​ Association between behavioral health outcomes and demographic life characteristics and lifetime history of TBI

After adjustment for age, gender, and, race, having a lifetime history of TBI with LOC was found
to be associated with increased odds of reported binge drinking (Adjusted Odds Ratios [AOR] = 1.5; 95%
CI = 1.1-2.0), heavy drinking (AOR = 1.7;95% CI=1.1-2.6), smoking (AOR = 1.7; 95% CI = 1.3-2.2),or a
depressive disorder (AOR = 2.1; 95% CI = 1.6-2.7). A history of TBI increased the likelihood of
reporting poor mental health for 2 or more days (AOR = 1.8; 95% CI = 1.5-2.3), as well as for 14 or more
days (AOR = 2.3; 95% CI = 1.7-3.0). The odds of reporting a depressive disorder and mental health not
being well such as bipolar disorder were increased across all levels of severity. Relationships between age
at rst TBI and behavioral health variables were unremarkable. Both age groups (having TBI before or
after age 15) were related to increased odds of almost all behavioral health issues, compared with those
without a history of TBI. Adult Ohioans who have sustained at least 1 TBI with LOC in their lifetime are
at increased risk for poor behavioral health including depressive disorder such as bipolar. While the
relationship between severity and number of TBIs is not consistent across behavioral health indicators, the
presence of any TBIs with LOC has strong associations with poor behavioral health.

Conclusion:
Based on 5 studies that we have analyzed, the study by Kiruthika, Drange et al. and Walker et al.
stated that there was no association between bipolar disorder in TBI. However, the study by Slaughter et
al. and Bogner et al. stated that there actually was an association between bipolar disorder in TBI. For this
reason, we may conclude that traumatic brain injury does not have a causative effect on bipolar disorder
as a comprehensive biological factor.
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