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*Corresponding author: Email: dranandsharma100123@gmail.co;

www.sciencedomain.org

Study of Generalized Anxiety Disorder in Traumatic

Brain Injury

Anand Sharma

1*

, Achal Sharma

1

, Akhilesh Jain

2

, R. S. Mittal

1

and I. D. Gupta

1

1

Department of Neurosurgery, Sawai Man Singh Medical College, Jaipur, Rajasthan, India.

2

ESIC Model Hospital, Jaipur, Rajasthan, India.

Authors’ contributions

This work was carried out in collaboration between all authors. Author Anand Sharma participated in the design of the study and performed the statistical analysis. Author Achal Sharma participated in the design and conception of the study and its coordination, acquisition of data, carried out statistical analysis and drafted the manuscript. Author AJ participated in the conception of the study and participated in the design of the study, acquisition of data and manuscript revision. Authors RSM and IDG participated in reviewing of article. All authors read and approved the final manuscript.

Article Information

DOI: 10.9734/BJMMR/2015/20370 Editor(s): (1) Domenico De Berardis, Department of Mental Health, National Health Service, Psychiatric Service of Diagnosis and Treatment, “G. Mazzini” Hospital, Italy. Reviewers: (1) OR Cohen-Inbar, University of Virginia Health Care Center, USA. (2)Arturo Solís Herrera, Director del Centro de Estudios de la Fotosíntesis Humana,

Mexico. Complete Peer review History:http://sciencedomain.org/review-history/11385

Received 24th July 2015 Accepted 24th August 2015 Published 12th September 2015

ABSTRACT

Objective: This cross-sectional study was design to investigate prevalence and risk factors of

generalized anxiety disorder in traumatic brain injury (TBI).

Materials and Methods: The Group studied consists of 204 patients of mild and moderate TBI

between 14- days to one-year post injury. Demographic characteristics of the participants were assessed on a self-designed semi structured performa. Interviews focused on assessment of severity of TBI, generalized anxiety disorder (GAD) and quality of life (Qol) using GCS, GAD-7 and WHOBREF-QOL respectively.

Results: Total 204 patients were included. 11.76% participants were found to have generalized

anxiety disorder. None of the demographic variables were associated with GAD except injury severity. Mild TBI patient (75.00%) had higher occurrence of GAD than the moderate cases (25.00%). GAD patients also had poor Qol than those without GAD in all domains except physical

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and social health domain. Neuroanatomical localization was also correlated with GAD. Left frontal contusions were the most common (37.50 %) lesions associated with GAD.

Conclusion: GAD is commonly associated, yet under diagnosed clinical entities in head injury and

have tremendous impact in overall outcome measures. Every patient of head injury warrants psychiatric evaluation and concomitant treatment if required to ensure the attainment of not only neuroanatomical intact but overall productive and qualitative life vindicating the holistic and multidisciplinary treatment approach.

Keywords: Traumatic brain Injury; generalized anxiety disorder; quality of life.

1. INTRODUCTION

Traumatic brain injury (TBI) is a predominant cause of death and disability, particularly for persons age 35 years and younger [1]. Injuries often involve the brain and cause neurological impairment, cognitive deficits, and alterations in consciousness and personality. Three main pathological pathways are involved in traumatic brain injury (TBI): (i) focal contusional damage resulting from local impact, (ii) diffuse axonal injury (DAI) resulting from head acceleration, especially rotational, and (iii) secondary damage, resulting, for example, from mass compressive effects through edema or hemorrhage [2]. Severity of cognitive changes depends on degree of diffuse axonal injury, as well as volume and location of focal injuries [3]. With regard to emotional functioning, anxiety disorders are often a significant clinical concern. Generalized anxiety disorder (GAD) may be the common and disabling psychiatric condition in individuals with TBI.

The term “anxiety” is also used to refer to more severe disorders, for which there are accepted diagnostic criteria. Anxiety disorders seriously affect a person’s quality of life and often require clinical assessment and treatment [4], with generalized anxiety disorder (GAD) and posttraumatic stress disorder (PTSD) being common diagnoses following TBI. However, the most recent DSM (DSM–5; American Psychiatric Association [APA], 2013) [5] has reclassified PTSD as a trauma and stressor-related disorder, rather than an anxiety disorder, because the symptoms are not necessarily anxiety/fear based. In addition, there are concerns that TBIs sustained in psychologically traumatizing circumstances (e.g., assaults) may impact outcomes, even when PTSD is not evident. The current study therefore only focused on GAD.

Anxiety disorders occur in a significant proportion of patients with a TBI and frequently coexist with depressive disorders [6]. The frequency of

anxiety disorders has been reported to range from 18% to 60% [7], and generalized anxiety disorder is the most commonly reported anxiety disorder after TBI, ranging from 24% to 27% [8]. The frequency of GAD is particularly noteworthy when contrasted with base rates of 5.1% in community-based samples [9].

Anxiety disorders may manifest as symptomatology, which is frequently linked to the process of adjustment to the injury and may present as a feeling of apprehension or fear, and negatively impacting upon rehabilitation outcomes, functional ability, interpersonal relationships and employment outlook. A bio-psychosocial model of adjustment after injury has been proposed for the development of post-TBI anxiety [10].

Despite researchers’ best efforts, the rates, predictors, and outcomes of GAD after TBI remain uncertain. Incidence of GAD has varied widely, ranging from 24% to 27%. More elaborative studies may prove more informative and credible in recognition of this important secondary condition. The present study was designed to investigate the prevalence and determinants of GAD in TBI and its correlation with quality of life. We have also implored the connection between neuroanatomical localization of TBI and GAD.

2. MATERIALS AND METHOD

2.1 Study Design

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2.2 Participants

The Group studied consists of 204 patients of mild and moderate TBI between 14- days to one-year post injury. Sample was recruited through the follow up in neurosurgery OPD and Indoor of SMSH. Definition of mild traumatic brain injury was adopted as developed by the mild traumatic brain injury committee of the Head injury [11]. Mild TBI was defined as ``a person who has had a traumatically induced physiological disruption of brain function, as manifested by one or more of the following 1. Any period of loss of consciousness for up to 30 minutes 2. Any loss of memory for events immediately before or after the accident for as much as 24 hours, 3.Any alteration of mental state at the time of the accident (e.g., feeling dazed, disoriented, or confused), 4.Focal neurological deficit(s) that may or may not be transient``. Moderate head injury was classified as if the lowest post resuscitation GCS score was 9±12 with or without evidence of lesion on CT. To be included in the study, participants had to be 18 years or older, and be able to comprehend or answer verbal or written questionnaires. Participants with severe head injury and history of current or past psychosis, substance abuse disorder were excluded from the study as these factors can affect outcome independently.

The nature and purpose of the study was explained to the participants and written informed consent was obtained. Demographic characteristics of the participants were recorded on a self-designed semi structured per-forma by interviewing the participants by psychiatrist and exploring the medical records and neuro-radiological investigations. The interview was focused on assessment of severity of TBI, GAD and Quality of life (Qol) measured on post injury GCS, GAD -7 and WHOQOL-BREF respectively.

2.3 Instruments

GCS[12]is an extensively used clinical scale for assessing the depth and duration of impaired consciousness and coma. Three aspects of behavior are independently measured—motor responsiveness, verbal performance, and eye opening. These can be evaluated consistently by doctors and nurses and recorded on a simple chart, which has proved practical both in a neurosurgical unit and in a general hospital. The

scale facilitates consultations between general and special units in cases of recent brain damage, and is useful also in defining the duration of prolonged coma.

Generalized anxiety disorders were assessed on GAD-7 anxiety severity [13,14]. This is calculated by assigning scores of 0, 1, 2, and 3, to the response categories of ―not at all several

days, ―more than half the days, and nearly

every day, respectively. GAD-7 total score for the seven items ranges from 0 to 21. The internal consistency of the GAD-7 was excellent (Cronbach α = .92). Test-retest reliability was

also good (intraclass correlation = 0.83). Though designed primarily as a screening and severity measure for generalized anxiety disorder, the GAD-7 also has moderately good operating characteristics for three other common anxiety disorders – panic disorder, social anxiety disorder, and post-traumatic stress disorder. In this study Hindi version of GAD-7 anxiety severity was used. It has been validated in Indian population and is considered to be reliable tool for diagnosis of anxiety disorders. When screening for anxiety disorders, a recommended cut point for further evaluation is a score of 10 or greater.

The WHOQOL-BREF was developed by the World Health Organization Quality of Life Group, in 15 international field centers[15]. It is a self-report questionnaire that contains 26 items, and each item represents one facet. Among the 26 items, 24 of them make up the 4 domains of physical health (7 items), psychological health (6 items), social relationships (3 items), and environment (8 items). The other 2 items measure overall quality of life and general health. In this study Hindi version [16] was used. The scale has been shown to have good discriminant validity, sound content validity and good test-retest reliability at several international WHOQOL centers.

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2.4 Statistical Analyses

Data were analyzed using SPSS version 20, with a 2-tailed α level of 5%. Statistical analyses were

performed by correlation analyses (Pearson and Spearman), and independent t test analyses. The criterion for statistical significance was set at p_0.05, and for statistical trend at p_0.10.

3. RESULTS

3.1 Participants and Prevalence

Total 204 patients were included in study, median age of patients were 30.00, range from18-70) year. 77.9 percent were males (N=159) and 22.1 percent (N=45) were female. Motor vehicle accidents were the most common cause (52.9%, N=108) of TBI, followed by falls and assaults each accounted for 19.6 %( N=40) and 21.1% (N=43) respectively. 24 of the 204 participants (11.76%) were found to have GAD

as measured by GAD-7 with a cut off score of 10 and above (Table 1).

3.2 Relationship between Demographic Variables, Injury Characteristics with GAD

GAD was found in 83.33 % of male patients against 16.66 % females and this difference was statistically insignificant (P=. 615). Other sociodemographic variables did not appear to have significant association with GAD. Amongst injury characteristics, time since injury and severity of TBI also did not revealed significant association with GAD. Mild TBI patients (75.00%) had higher occurrence of GAD than the moderate cases (25.00%). (P=0.107). Two third (75.00%) of the patients with GAD had lesser duration post injury (< 3-month) compare to longer duration since injury. This was found statistically insignificant (P<0.575) (Table 1).

Table 1. Correlation of GAD and No GAD with demographic and Injury-Related Factors

No GAD GAD P valve

N % N %

Sex R -.035, P=.615

Male 142 78.88 20 83.33

Female 38 21.11 4 16.66

Age (years)

18–24 47 26.11 7 29.16 R -.012, P =.861

25–34 62 34.44 5 20.83

35–44 35 19.44 8 33.33

45–54 16 8.88 3 12.50

55–64 16 8.88 1 4.16

65 or older 4 2.22 0 0

Type of injury R .068, P =.379

RTA 100 55.55 8 33.33

FFH 35 19.44 5 20.83

Assault 34 18.88 9 37.5

Other injury 11 6.11 2 8.33

GCS R-.113, P=.107

Mild 104 57.77 18 75.00

Moderate 76 42.22 6 25.00

Duration of head injury R-.040, P=.575

Less <3 Month 119 66.11 18 75.00

3-6 Month 39 21.66 3 12.50

>6 Month 22 12.22 3 12.50

Monthly income R .044, P= .534

<50000 114 63.33 15 62.50

5000-10000 51 28.33 7 29.16

10000-20000 15 8.33 0 0

200000 0 0 2 8.33

Marital status R .021, P= .761

Married 140 77.77 18 75.00

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3.3 Distributions of CT Finding In Individuals with GAD

Neuroanatomical localization was also correlated with GAD. 33.30% of GAD patients had cerebral contusion followed by multiple lesion including contusions as well in 29.20% of the cases. Other injury like SDH, SAH and even fracture were also found to be involved although in lesser frequency with GAD. A very few patients with GAD were also found to have normal CT Brain (Table 2). We further tried to explore the distribution of cerebral contusion in patients with GAD and observed left frontal contusions in most (37.50%) of the patients, although multiple lobe contusion were also associated with GAD (Table 3).

Table 2. Distribution of CT Finding in GAD patients

SN CT finding Frequency Percent

1 Contusion 8 33.30

2 Multiple lesion 7 29.20

3 SDH 1 4.2

4 EDH 0 0

5 Fracture 2 8.3

6 SAH 1 4.2

7 NAD 5 20.8

Total

3.4 Assessment of Qol in Individuals with or without GAD

Patients with GAD scored lower than those without GAD in all four domains of QOL including physical health, psychological health, social relationship and environmental health. This finding was statistically significant in respect of psychological and environmental domains (Table 4).

4. DISCUSSION

Compiling the results of our study on the prevalence of GAD following TBI, a cumulative total of 11.7% (24 of 204) of patients were diagnosed with the disorder. Interestingly, this is exactly double the lifetime prevalence for GAD (5.1%) found in the general population in the National Co-morbidity Study by Kessler et al. [9]. These data suggest that, compared to the general population, people with TBI have twice the risk of developing GAD. This rate was virtually identical to that reported by Jorge et al [17] who found 7 (11%) to have GAD in 66 patients (all with co-morbid major depression). This finding was considerably less than the 22%

reported by Van Reekum et al. [18] in 18 TBI sample, conversely, these findings were considerably more than the 2.5% reported by Deb et al. [19] in 120 TBI. This variation in prevalence rates may have been caused by differences in cultural traditions of describing distress and cultural differences in the diagnosis of GAD, methodological issues including differences in GAD assessment tools used in the research, the time course of GAD assessment, and differences in injury severity of persons with TBI (mild vs. severe injuries).

Table 3. Distribution of cerebral contusions in patients with GAD

1 Distribution of

contusions

Frequency Percent

2 Multiple lobe

contusions

2 25

3 Right frontal lobe 0 0

4 Left frontal lobe 3 37.50

5 Right temporal

lobe

1 12.5

6 Left temporal lobe 0 0

7 Left subcortical 1 12.5

8 Right parietal lobe 1 12.5

9 Left parietal lobe 0 0

10 Right occipital 0 0

11 Left occipital 0 0

12 Right subcortical 0 0

13 Cerebellum and brain stem

0 0

Total

Factors associated with GAD were investigated in this study. None of the sociodemographic variables were associated with GAD in TBI. GAD was more common in mild TBI patients than those with moderate severity. This may be explained by the fact that mild TBI patients are more likely to retain their cognitive functions intact, thus are capable of acknowledging their deficits caused by trauma. They may also explain their mood symptoms explicitly as they experience it, which may not be the case with moderate or severe trauma.

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anatomic lesion locations [20] and GAD, of interest, however, Jorge et al. [17] found that those with anxious depression were associated with right hemisphere lesions whereas those with major depression alone had left anterior lesions. Grafman et al. [21] found right orbito-frontal lesions to be associated with anxiety and depression. Gray and McNaughton [22,23] present a complex model of anxiety by integrating neuropsychological mechanisms, the function of specific brain structures and their combined contribution to the varied manifestations of anxiety. They postulate that activity in a ‘behavioral inhibition system’ in the brain produces anxious symptoms. This sophisticated system is comprised mainly of the septo-hippocampal system, but also includes, among other areas, the anterior thalamus, ‘Papez circuit’, cingulate cortex, pre-frontal cortex and ascending noradrenergic fibres of the locus coeruleus. A variety of studies [24] have found associations between right orbital cortex, left occipital lobe and temporal lobe injuries and the regulation of anxiety. Evidence also indicates that even much more general lateralization of a TBI may influence the degree and nature of anxiety sequelae. Anxiety has been reported to be a common feature of left-hemisphere damage and is manifested as over-sensitivity, excessive cautiousness and exaggerated appraisal of one’s own impairment [24]. Conversely, participants with brain injuries localized in the right hemisphere, including those with mild TBIs, have been reported to demonstrate fewer anxiety symptoms that would be expected, often exhibiting indifference and lack of insight in their place [24,25].

We also tried to understand the association between injury presences of GAD with QOL. GAD patients had poor quality of life than those without GAD in all domains. Anxiety has a greater impact than cognitive impairment on social and occupational functioning following brain injuries. Elevated levels of suicidality are additionally associated with anxiety following a TBI [26] further highlighting its importance. In the community, general anxiety disorders are associated with relationship breakdowns [27], increased reliance on disability benefits, and lower annual incomes [28]; findings that are likely to be mirrored in a TBI setting. Many studies[29] in recent past have also reported significant association between psychiatric disorders including anxiety and poor Qol in TBI [30]. This finding implies that long-term rehabilitation intervention programs for preventing the occurrence of depression and its deterioration are required.

5. LIMITATIONS OF THE STUDY

There are multiple limitations in the current investigation. Patient complaints were based on self-reported questionnaire, which may have resulted in underreporting or over reporting of symptoms. Severe TBI cases were not included in our study owing to their inability to comprehend the directions, and hence present study does not give overall picture of TBI population. Medication taken by the patient that could affect the emotional state of patient was not considered. Another limitation of study was the underling pathology like DAI could have been batter elucidated if the patient undergone MRI as well.

Table 4. Quality of life in-patient with anxiety and without anxiety

Domains No GAD

(Mean/ Median/ Range)

SD GAD

(Mean/ Median/ Range)

SD T test P value

Physical health 58.67

56.00 87.00

19.20 52.91

50.00 75.00

21.14 .118 P=.174

Psychological health

61.07 56.50 85.00

18.71 57.29

53.00 75.00

23.45 .901 P=.03

Social relationship 60.30 56.50 94.00

20.46 54.83

60.50 75.00

22.57 1.2 P=.220

Environmental health

59.15 56.00 855.20

19.65 50.70

50.00 75.00

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6. CONCLUSION

Generalized anxiety disorder after TBI is prevalent condition and associated with adverse impact on QOL. Because GAD after TBI is an invisible disorder within invisible injury, aggressive and scrupulous efforts are needed to educate the clinician about the importance of symptoms in this population to promote integrated system of detection and multidisciplinary care.

COMPETING INTERESTS

Authors have declared that no competing interests exist.

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© 2015 Sharma et al.; This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Peer-review history:

Figure

Table 4. Quality of life in-patient with anxiety and without anxiety

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