Evaluation of Anxiety Sensitivity, Anxiety, Depression, and Attention Deficit Hyperactivity Disorder in Patients with Tinnitus.

Context: There may be a connection between tinnitus, a common disease in society, and psychiatric disorders. When the literature is reviewed, it has been realized that more data are needed to elucidate this issue. Aims: The aim of this study is to compare the symptoms of anxiety sensitivity, anxiety, depression, and attention-deficit/hyperactivity disorder (ADHD) symptoms in patients with tinnitus with healthy individuals and to investigate the relationship between tinnitus and psychiatric disorder symptoms. Settings and design: This study was designed as a case-control study. Materials and methods: Fifty-one patients with tinnitus and 51 healthy controls were enrolled in this study. Clinical severity of the psychiatric variables were evaluated by Beck depression inventory, Beck anxiety inventory (BAI), anxiety sensitivity index-3, and adult ADHD self-report scale (ASRS) in patient and control groups. Statistical analysis used: Variables are presented as either a number, a percentage, a mean ± standard deviation, or frequency. Chi-squared, Student t tests, and logistic regression analysis were used to examine the relationship between variables.
Results: Logistic regression analysis results indicated that a significant predictive power of BAI for the presence of tinnitus. Based on a backward-elimination regression analysis, ASRSs (inattention subscale scores) were considered to predict a higher tinnitus handicap inventory score.
Conclusion: These findings provide additional evidence that anxiety and attention-deficit (inattentive) symptoms could contribute to the pathophysiology of tinnitus.

INTRODUCTION

Tinnitus is a common audiologic condition in which a person hears an internal sound when there is no external sound source present. A global prevalence of tinnitus ranges from 5.1% to 42.7% in the study of all adult demographic research accessible over a period of 35 years, with its prevalence increasing with age and noise sensitivity.[1] Despite the fact that tinnitus is common and causes problems for sufferers, experts believe that the mechanism that causes and sustains tinnitus is not well known.[2] There have been several biomedical models that describe the relationship between tinnitus and potential physiologic, neurologic, and immunologic mechanisms, which have been confirmed by empirical studies. These models revealed shortcomings in determining the cause and effect of tinnitus, and since then, more focus has been placed on causes other than biomedical models.[3] Psychologic factors are one of the models focused on in this study.

There have been numerous research on the association between tinnitus and depression. Salazar et al. found a 33% prevalence of depression in patients with tinnitus in their study and recommended that patients with tinnitus be evaluated for depression.[4] However, the precise mechanism behind the connection between tinnitus and depression remains unknown, and clarifying this connection is critical importance. The most widely recognized theory regarding the connection between tinnitus and depression is that tinnitus-induced depression in people who are predisposed to depression. Another theory is that the link is bidirectional, with psychologic mechanisms leading to increasing tinnitus awareness and severity in a cyclical pattern.[5] As a result, more research is needed to better understand the connection and directionality between tinnitus and depression symptoms.

Anxiety sensitivity (AS) is a psychiatric disorder marked by a fear of physiologic sensations that are similar to physical experiences often connected with death or loss of sanity.[6] The fear of anxious sensations can increase one’s attention to their bodily changes, which are then misinterpreted as a danger, leading to an exacerbation of the fear reaction.[78] AS has been thought to be a vulnerability factor for specific fears that are anxiety related as well as in the development and persistence of common fears. According to a rising number of studies, AS is connected to an expanding variety of chronic health problems, including asthma, vestibular abnormalities, and chronic pain.[9] Despite growing interest in AS in somatic diseases,[1011] few research have been conducted to investigate the link between tinnitus and AS.[121314] However, the available evidence suggests that the level of AS is higher in tinnitus sufferers than in controls.

The AS is widely believed to predispose to certain psychopathologies.[15] For example, it has been shown in various studies that AS is a predictive factor for the development of anxiety disorders. A recent comprehensive study revealed a significant increase in the lifetime and current prevalence of anxiety in people with tinnitus, as well as evidence that both conditions share similar neural networks.[16] The link between tinnitus and anxiety has been studied, and it has been shown to have a moderate relationship, with approximately 60% of participants reporting above average state and trait anxiety.[17] In a sample of 75 tinnitus outpatients, 29% met the diagnostic criterion for anxiety.[18] The high rate of anxiety symptoms in patients diagnosed with tinnitus brings to mind the question of whether the symptoms of anxiety disorder are a predictive factor in terms of the presence of tinnitus.

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disease that develops in childhood with inattention, hyperactivity, and impulsiveness.[1920] The clinical heterogeneity of ADHD symptoms has been studied in both clinical and population samples, establishing that people with ADHD are more likely than controls to have a variety of comorbid medical and psychologic disorders. Epilepsy, headaches/migraine, atopic disorders, asthma, hyperacusis, and hearing loss are among the chronic medical conditions recorded with greater prevalence among adults and children with ADHD.[212223] To the best of the knowledge of this study group, no research has been carried out on ADHD symptoms experienced by patients with tinnitus.

There is very little research that has investigated the relationships between depression, anxiety, AS, and ADHD symptoms in the context of tinnitus. To investigate this relationship clearly, it is first necessary to make the most accurate diagnosis of tinnitus. Therefore, this study made use of tinnitus matching tests [constitute of tinnitus pitch matching (TPM) and tinnitus loudness matching (TLM)], which are the most objective tests when diagnosing tinnitus.[24] We also used tinnitus handicap inventory (THI) to assess the relationship between tinnitus and psychiatric variables.[25]

We hypothesized that patients with tinnitus would show increased attention deficit, anxiety, depression, and AS relative to controls. Furthermore, we hypothesized a positive relationship between THI scores and the severity of attention deficit, anxiety, depression, and AS. The purpose of this study is to examine the symptoms of depression, anxiety, AS, and ADHD in patients with tinnitus and healthy controls, as well as to evaluate the link between tinnitus and psychiatric disorder symptoms.

MATERIALS AND METHODS

Patient selection

The protocol for the study was accepted by the Ethics Committee of the institution (date: July 27, 2020, Number: 208), and the study adhered to the Declaration of Helsinki. The study was conducted between August 2020 and November 2020 in a university hospital. After securing informed consent, the participants were included in the study. Tinnitus and control groups were formed to conduct the study. Patients with subjective tinnitus were included in the study in accordance with the following inclusion criteria: (1) >18 and <65 years old, (2) normal examination of ear, nose, and throat (ENT), (3) complaints of tinnitus for at least 6 months, and (4) pure tone average ranging from 0 to 25 dB. The control group (age range: 18–65 years) was created from patients who had been admitted to the ENT outpatient clinic for a hearing examination, and whose pure tone average ranged from 0 to 25 dB. In both groups, patients with otologic disease (chronic otitis media, Meniere disease, barotrauma, etc.), comorbid disease (hypertension, diabetes mellitus, chronic renal failure, etc.), autoimmune disease (ankylosing spondylitis, systemic lupus erythematosus, etc.), malignancy, chronic drug use, and/or a history of neuropsychiatric treatment were all excluded from the study. To avoid a gender imbalance between the groups, equal numbers of males and females were included in both groups. Patients in the tinnitus and control groups filled out the Beck depression inventory (BDI), Beck anxiety inventory (BAI), anxiety sensitivity index-3 (ASI-3), and adult ADHD self-report scale (ASRS). In addition, the cases in the tinnitus group filled out the THI. Moreover, TPM and TLM tests were applied by the same audiometrist to the subjects in the tinnitus group.

Audiologic evaluation and measurement of tinnitus

Otoscopic examination, including pure tone audiometry (AC 40; Interacoustics, Middelfart, Denmark), was carried out with the study groups. Hearing thresholds were measured at 0.25, 0.5, 1, 2, 4, and 8 kHz frequencies, and pure tone averages were determined according to 0.5, 1, 2, and 4 kHz frequencies.

A diagnosis of tinnitus was confirmed by applying TPM and TLM tests to the patients in the tinnitus group. The sensory characteristics of the tinnitus experience were measured using TPM and TLM in an acoustic booth using the same audiometry. Patients were informed about how to perform tinnitus tests prior to the procedure. The tone was sent to the contralateral ear, whereas the tinnitus was unilateral. If the tinnitus was bilateral, the tone was sent to the ear with the lower tinnitus loudness. First, the pitch was assessed: the patient was asked to choose between two tones, such as a 125 Hz sound and an 8000 Hz sound, and the patient was asked, “Which of these sounds is closest to the sound of your tinnitus?” The pitch was measured in Hz, which corresponded to the frequency of tinnitus perception. Following that, the degree of loudness was measured, with a 1-dB rise in sound loudness. The results were shown in dB.[24]

The THI was applied to the tinnitus group after TPM and TLM tests had been performed. THI is a self-report metric, created by Newman et al. to assess the impact of tinnitus on daily life.[25] THI was administered in the form of an interview, with each of the 25 questions having three potential answers: “yes” (4 points), “no” (0 points), or “sometimes” (2 points).[25] THI was validated for the Turkish population by Aksoy et al., as the Turkish version of the THI is considered to be a consistent and reliable measurement tool for assessing the symptoms of patients with tinnitus.[26]

Measurement of psychiatric variables

Beck depression inventory: BDI which was created by Beck et al. was used to assess the severity of depression among the subjects.[27] Hisli performed the validity and reliability analysis for the Turkish version.[28] It is a 21-item self-report scale with a 4-point Likert scale. It received a score ranging from 0 to 3 points, with a maximum score of 63.

Beck anxiety inventory: BAI was used to evaluate anxiety of the volunteers. Beck et al. created the BAI and Ulusoy et al. validated BAI for the Turkish population.[2930] It has 21 items and items are rated between 0 and 3. The total score for the BAI varies from 0 to 63. Higher scores of BAI indicate higher anxiety levels.

Anxiety sensitivity index-3: The AS levels of the participants were evaluated via the ASI-3. The ASI-3 was created by Taylor et al. AS is best conceptualized as a higher order construct, composed of three lower order dimensions; physical concerns (i.e., fear of physiologic responses of anxiety), cognitive concerns (i.e., fear of cognitive dyscontrol), and social concerns (i.e., fear of publicly observable symptoms of anxiety).[31] The ASI-3 was adapted to Turkish and analyzed for validity and reliability by Mantar et al.[32]

Adult ADHD self-report scale: The ASRS is a self-report inventory of 18 items on a 5-point scale ranging from “never” to “very often” for each item. It consists of 18 items divided into subscales for inattention and hyperactivity.[33] The ASRS is used by participants to measure the severity of their present ADHD symptoms. In university students, the Turkish version of ASRS has proved to be both reliable and valid.[34]

Statistical analysis

Data were analyzed using the SPSS 21.0 statistical software (SPSS, Chicago, IL, USA). All variables were inspected for normality using the Kolmogorov–Smirnov test of normality. Variables are presented as either a number (n), a percentage (%), a mean ± standard deviation, or frequency. Chi-squared and Student t tests were employed to assess group differences in variables, as and when appropriate. To determine the best predictive model for subjective tinnitus via psychiatric symptoms, this study group conducted a logistic regression analysis using a forward stepwise (Wald) elimination model selection method. Factors presumed to affect the THI were evaluated by composing models using backward linear regression. A P-value of less than 0.05 was considered to be statistically significant.

RESULTS

There were 51 subjects (36 males and 15 females) in the study group and 51 subjects (36 males and 15 females) in the control group. The mean age did not differ significantly between the patient (45.4 ± 13 years) and control (43.9 ± 10 years) groups (range: 19–64 years; t = –0.679; P = 0.499) [Table 1]. The pure tone averages of the subjects and the tinnitus matching test results of the tinnitus group are summarized in Table 1.

Table 1

Demographic and audiologic data of tinnitus and control groups

		Patients (n = 51)			Controls (n = 51)
Age (years)		45.4 ± 13.0			43.9 ± 10.0		0.499
Sex
Male		36 (70.6%)			36 (70.6%)		1.000
Female		15 (29.4%)			15 (29.4%)
PTA (dB)
Right		14.13 ± 6.77			11.00 ± 6.22
Left		14.80 ± 7.04			11.39 ± 6.47
		Min-Max	Mean ± SD
Duration of tinnitus (month)		6–240	33.25 ± 54.67
TLM (dB)		5–87	42.78 ± 19.97
Side of tinnitus
Right		16
Left		23
Bilateral		12
Distribution of tinnitus frequencies according to TPM test (n = 51)
250 Hz	500 Hz	1000 Hz		2000 Hz	4000 Hz	6000 Hz	8000 Hz
5	1	1		1	14	28	1

SD, standard deviation; PTA, pure tone average; TLM, tinnitus loudness matching; TPM, tinnitus pitch matching; dB, decibel.

Psychiatric disorder symptoms in tinnitus and control groups are presented and compared in Table 2. Severity of ASI-3 cognitive concern subscale (t = 2.061, P = 0.042) and the BAI scores (t = 2.435, P = 0.017) were statistically higher among those with patients with tinnitus, whereas ASI-3 physical (t = 0.626, P = 0.533) and social subscales (t = 1.001, P = 0.319), the BDI score (t = 1.224, P = 0.224), ASRS inattentive (IA; t = 1.386, P = 0.169), ASRS hyperactive-impulsivity (H-I) subscales (t = 1.227, P = 0.223), and ASRS total scores (t = 1.426, P = 0.157) were not statistically differ.

Table 2

Comparison of patient with tinnitus and controls in terms of psychiatric variables

	Patients	Controls	t	P
BDI	9.72 ± 8.61	7.84 ± 6.81	−1.224	0.224
BAI	15.05 ± 12.18	10.17 ± 7.52	−2.435	0.017
ASI-3/physical	8.07 ± 6.04	7.41 ± 4.61	−0.626	0.533
ASI-3/cognitive	8.52 ± 5.54	6.43 ± 4.70	−2.061	0.042
ASI-3/social	6.15 ± 4.60	5.27 ± 4.28	−1.001	0.319
ASI-3/total	22.75 ± 14.74	19.19 ± 11.51	−1.377	0.171
ASRS/IA	12.07 ± 6.86	10.39 ± 5.32	−1.386	0.169
ASRS/H-I	12.13 ± 5.05	10.84 ± 5.58	−1.227	0.223
ASRS/total	24.21 ± 11.17	21.23 ± 9.89	−1.426	0.157

BDI, Beck depression inventory; BAI, Beck anxiety inventory; ASI-3, anxiety sensitivity index-3; ASRS, the adult ADHD self-report scale; IA, inattentive; H-I: hyperactivity–impulsivity. Bold and italic values were accepted as statistically significant; P<0.05.

Taking the participants’ group assignment as the dependent variable in forward stepwise logistic regression and including BDI, BAI, ASI-3, and ASRS subscales in the model as independent variables, the results indicated a significant predictive power of BAI for the presence of tinnitus [Table 3].

Table 3

Logistic regression analysis results for tinnitus

	SE	Wald	Exp B	P	95% CI
					Lower	Upper
BAI	0.021	5.316	1.051	0.021	1.007	1.096

BAI, Beck anxiety inventory; SE, standard error; CI, confidence interval. Bold and italic values were accepted as statistically significant; P<0.05.

Backward linear regression was used to examine the cross-sectional connection between THI score and depression, anxiety, AS, and ADHD symptoms. Backward elimination regression findings are summarized in Table 4, with the following variables remaining as significantly predicting higher THI scores: BAI and ASRS IA.

Table 4

Backward elimination regression analyses results in which psychiatric variables remained as significantly predicting higher THI score (model 5: THI, P < 0.001; R 2 = 0.484)

	β	SE	P	95% CI
				Lower	Upper
BAI	0.282	0.317	0.055	−0.014	1.262
ASRS/IA	0.338	0.451	0.005	0.419	2.235

THI, tinnitus handicap inventory; BAI, Beck anxiety inventory; ASRS, the adult ADHD self-report scale; IA, inattentive; SE, standard error; CI, confidence interval. Bold and italic values were accepted as statistically significant; P<0.05.

DISCUSSION

The findings of this study provide evidence for a potential increased effect of anxiety symptoms on tinnitus. This study also showed a positive relationship between the inattention subscale score to THI. In addition, AS cognitive concern and anxiety scores of patients with tinnitus were significantly higher than the control group.

To the knowledge of the study team, this research is the first to evaluate the connection between ADHD symptoms and tinnitus. It has been discussed in the existing academic literature that many comorbidities can accompany adult ADHD. For example, there can be comorbidity with psychiatric (e.g., anxiety disorders, substance abuse disorders) and somatic (e.g., asthma, obesity) disorders.[3536] In their research on accompanying comorbities in 465 patients with ADHD, Adler et al. found depression in 58% of the patients, sleep disturbance in 37% and posttraumatic stress disorder, panic disorder, heart burn, and insomnia are reported in approximately 20% for each.[37] In particular, the coexistence of ADHD and depression and/or anxiety was important to test the hypothesis that “tinnitus develops in patients with ADHD.” In fact, the term “vicious circle” is used to describe the relationship between tinnitus and depression–anxiety in some studies.[38] Although the ASRS scores in the tinnitus group were higher than the control group in this study, no statistically significant difference observed. An interesting point is that the ASRS/IA test is instrumental in backward elimination regression analysis to predict high THI scores (P = 0.005). These results show that attention problems may increase with tinnitus severity in patients where tinnitus has been diagnosed. To fully understand the link between tinnitus and ADHD symptoms, more research is needed.

Academic research has formerly looked into the link between tinnitus and anxiety. It has been reported that 24% to 28% of patients diagnosed with tinnitus also experience moderate or severe anxiety.[3940] Kehrle et al. reported that the presence of tinnitus is associated with high levels of anxiety and depression.[41] Bhatt et al. reported in their large population-based study that 26.1% of 21.4 million patients with tinnitus in the last 12 months also had anxiety problems in the same period.[42] For the purposes of comparison, they reported the anxiety problem as 9.2% in patients without tinnitus complaint. In addition, those who reported tinnitus as a “big-very big” problem and those who did not complain of tinnitus nor did not accept tinnitus as a big problem, reported the anxiety rate as 40.4% and 10.6%, respectively.[42] The state trait anxiety inventory was used to assess the association between tinnitus and anxiety in the study carried out by Gül et al. and patients with tinnitus had higher anxiety levels than the control group (P < 0.001).[12] One of the most important results of this study demonstrates that the anxiety scores in the tinnitus group were higher and statistically significant in comparison with the control group [Table 2]. In addition, according to the results of the regression analysis in this study, the results indicated a significant predictive power of BAI for the presence of tinnitus (Exp B: 1.051, P = 0.021). According to the studies mentioned earlier, there is a clear association between tinnitus and anxiety symptoms. At this point, the following questions comes to mind: does tinnitus trigger anxiety, or does anxiety trigger tinnitus? What is the nature of the directionality between tinnitus and anxiety?

The underlying mechanisms regarding the relationship between anxiety and tinnitus relation still remain unknown. On the other hand, recent neurophysiology studies have provided some clues to clarify the connection between tinnitus and anxiety. Interactions of the dorsal cochlear nucleus with brainstem areas that are critical locations for serotonin and norepinephrine production could explain the prevalence of anxiety disorders generally linked with tinnitus. The dorsal cochlear nucleus hyperactivity, which is frequently induced by cochlear injury, stimulates the locus coeruleus, resulting in the “anxious” reaction to tinnitus.[14] This plausible explanation still awaits to be supported by further studies.

Although the number of studies investigating the association of anxiety and somatic symptoms is increasing day by day, few studies have investigated specifically at the link between AS and tinnitus. Gül et al. found there to be higher ASI-3 scores of patients with tinnitus than the control group (P < 0.001).[12] Tinnitus and AS were found to have a strong association in a study of 146 participants with tinnitus.[13] The authors also showed that AS predicted tinnitus distress when they controlled symptoms of other psychiatric disorders.[13] In a research by Karaaslan et al., tinnitus sufferers had higher ASI-3 scores than the control group, although there was no statistically significant difference. The tinnitus group had higher ASI-3 scores than the control group in our study, but the difference was not statistically significant. The results of our study were similar to the study carried out by Karaaslan et al. in terms of AS. Moreover, ASI-3 concerns (physical, cognitive, social) were not examined separately in the studies mentioned earlier.[43] In this study, when the ASI-3 factors were examined separately, the averages of cognitive concerns were statistically different in both groups. Therefore, patients with tinnitus with high cognitive concerns may feel tinnitus more and this feeling may disturb them more. As a result, there seems to be no consensus between the results of the studies examining the link about AS and tinnitus.

Studies examining the relationship between tinnitus and depressive disorder mostly reveal the proportion of depressive disorder in patients with tinnitus. In a study, it was reported that patients with tinnitus were accompanied by depression at a rate of 36.1%.[44] In the study carried out by Folmer et al., 27% of patients with tinnitus were currently experiencing depression.[45] As the rate of depression with pretinnitus onset was 11%, the rate of depression with posttinnitus onset was found to be 39%.[46] It seems obvious that depressive symptoms accompany tinnitus to varying degrees.

Trevis et al. examined the relationship between tinnitus and depressive symptoms, and the average of depressive symptoms was found to be 9.95 according to the BDI (72% minimal, 16% mild, 6% moderate, and 6% severe depressive symptoms).[47] Weidt et al. found that clinical depression in 24 (BDI ≥ 18) of 208 patients with tinnitus and a mean BDI of 9.2.[48] In summary, they concluded that depressive symptoms are significantly higher compared to the general population. However, a control group was not used in these studies. In this study, the depressive symptom average of the tinnitus group was found to be 9.72, and the results are similar to the studies of Trevis et al. and Weidt et al.[4748] In the study of Karaaslan et al., the BDI averages of the control and tinnitus groups were compared statistically and a significant difference was found.[43] In our study, we could not find a statistical difference compared to the general population. There are inconsistent aspects as well as the aspects that the studies on this subject are consistent with each other. Therefore, it is observed that more data are needed on the relationship between depression and tinnitus, as in the relationship between AS and tinnitus.

The findings of our study should be interpreted in light of its limitations. Firstly, the cross-sectional nature of our study means that causality cannot be established. To address this issue, prospective longitudinal studies are needed. Secondly, as the hormonal/menstrual status of the females in both groups was not examined in the study, there may have been changes in the scores of the scales assessing depression and anxiety symptoms. Finally, although the control group consisted of cases who applied for routine health examinations for job applications, it is not a sample from the general population. Anxiety and depression scores of patients admitted to the hospital may be higher than the general population. As the control group was not selected from the general sample, it can prevent the generalization of the data.

CONCLUSION

This study found that anxiety symptoms are associated with tinnitus. In addition, this study found a significant relationship between THI score and attention deficit symptoms in cases where tinnitus had been diagnosed. This study also determined that tinnitus sufferers had higher ASI-3 cognitive concerns and anxiety symptoms than the control group. These findings provide additional evidence that anxiety, attention deficit, and AS cognitive concerns could play a role in the psychopathophysiology of tinnitus. Further data are needed on the potential role of psychiatric variables in tinnitus and whether these variables are psychiatric determinants for tinnitus.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.