Abstract
Introduction
Altered perceptions of the self and the environment are termed “dissociation phenomena” [1], including depersonalization, which is defined as a subjective experience of unreality and detachment from the self, and derealisation, the experience of the external world appearing strange or unreal [1]. Evidence suggests that these phenomena may be related to disruptions in functioning along hierarchical sensory association areas responsible for the processing of incoming perceptions against pre-existing brain templates [32].
Depersonalization/derealization (DD) symptoms have been described in healthy subjects and in patients with a variety of psychiatric and neurological disorders [7, 20], as well as associated to sensory dysfunction, particularly in patients with visual or vestibular dysfunction [14, 21]. Even more, patients with peripheral vestibular dysfunction and symptoms of unsteadiness may report symptoms of detachment from reality more frequently and more severely than patients without recent symptoms of unsteadiness [14, 19].
Interaction with the environment requires continuous updating of the relationship of the body and the body parts with the surrounding [26]. The orientation of the visual world and the head is mainly perceived through vision and the vestibular system, and the posture of the trunk is mainly perceived through sense organs in the trunk itself [23]. Since graviceptors are primarily required for the perception of the upright, vestibular afferents provide a frame of reference within which spatial information from other senses may be interpreted.
Although feelings of unreality have been provoked in normal healthy subjects undergoing caloric vestibular stimulation of the semicircular canals [6, 27], no studies have assessed the influence of the vestibular graviceptors on DD symptoms. To test vestibular graviceptors, the unilateral centrifugation test [8, 9] is a standardized tool to stimulate the utricules, where the subjective visual vertical can be used to assess the response to the gravity inertial acceleration [4].
The present study was designed to assess DD symptoms induced by utricular stimulation during unilateral centrifugation in healthy adults.
Methods
Subjects
100 healthy subjects gave their informed consent to participate in the study (age range 19 to 83 years; average±S.D. 41±17 years). They were 53 females (42±18 years old) and 47 males (40±17 years old). All of them denied having a history of otology, neurology, psychiatry, or orthopedic disorders, or vertigo, unsteadiness or exposure to ototoxic medication or unsafe noise levels.
Procedures
After a clinical evaluation, each subject completed the following questionnaires, which were administered for self-report: A standardized questionnaire of symptoms related to balance [16], which includes nine items with no/ yes answers to report symptoms related to balance (Fig. 1), where a “no” response was scored 0 points and a “yes” response was scored 1 point, except for vertigo which was scored 2 points; frequent falls were considered when occurring at least once per month, and frequent stumbles when occurring at least once per week. The total score was calculated by adding-up all the points, range from 0 to 10; a score≥4 has been related to balance disorders [16, 17]. The 17 item-Hamilton Depression Rating Scale [15]. The 17 items were rated on a 5-point (0–4) scale as 0 = absent; 1 = doubtful to mild; 2 = mild to moderate; 3 = moderate to severe; 4 = very severe. The final score range from 0 to 48, a score between 0 to 7 points was considered in the normality range, 8–13 was considered mild, 14–18 was moderate, 19–22 was severe and > 23 was very severe. The Zung Instrument for Anxiety Disorders [34]. It is a 20-item scale, with some of the items keyed positively and some negatively, on a four-point scale ranging from 1 “none or a little of the time” to 4 “most or all of the time”. The final score range from 20 to 80, a score between 20 and 44 was considered in the normality range, 45–59 mild to moderate, 60–74 severe, 75–80 very severe. The 28 item depersonalization/ derealization inventory (DD) by Cox and Swinson (2002) [11], which was designed to assess symptoms of DD in clinical anxiety states. Severity of each item was coded on a scale where 0 = does not occur, 1 = mild, 2 = moderate, 3 = severe and 4 = very severe. The total score was calculated by adding-up all the points (range 0 to 112), no cutoff score has been suggested.
After completing the questionnaires, vestibular evaluation was performed including sinusoidal rotation at 0.16 Hz and at 1.28 Hz (60°/s peak velocity), static visual vertical (average of 10 trials) and dynamic visual vertical during unilateral centrifugation (300°/s at 3.5 cm) (I-Portal-NOCT-Professional, Neuro-Kinetics, Pittsburgh). Immediately after unilateral centrifugation the DD inventory by Cox and Swinson (2002) [11] was administered for a second time.
Data analysis
Statistical analysis was performed using “t” test, ANCOVA and Pearson’s correlation coefficient. Significance was set at the 0.05 level for two tails.
Results
Characteristics of the subjects
The general characteristics of the subjects are described in Table 1. Forty six percent of the subjects had a University degree, 46% were married and none of them was divorced. Tobacco and alcohol consumption were low, 12% and 34% respectively. A total of 71 subjects (71%) reported that they were using eyeglasses because of refraction errors.
Vestibular function tests
Eye movements and vestibular responses were normal in all the participants. Sinusoidal rotation at 0.16 Hz & 1.28 Hz showed a vestibular gain of 0.54±0.17 and 0.94±0.12, respectively. The static visual vertical was from –1.8° to 1.7° (–0.08°±0.8°), which was consistent with the subjective visual vertical during rotation in-axis (–0.06°±0.9°). The visual vertical during unilateral centrifugation to the right was –4.98°±1.2°, and to the left it was 5.1°±1.0°. However, one subject vomited during the last centrifugation (to the left), so that average was calculated on the responses from 99 subjects.
Symptoms related to balance
Subjects reported from 0 to 3 symptoms related to balance (median 1), with an average total score of 1 (95% C.I. 0.7–1.1). None of them reported vertigo or falling (Fig. 1). The most frequent symptoms were reported by less than one quarter of the participants, they were: unsteadiness when moving the head (23%, 95% C.I. 15%–31%), dizziness (22%, 95% C.I. 14%–28%) and unsteadiness when changing posture (21%, 95% C.I. 13%–29%).
Anxiety and depression symptoms
Subjects reported from 0 to 13 symptoms (median 3.5) of the 17 item-Hamilton Depression Rating Scale, with an average of the total score of 5.1 (95% C.I. 4.2–6.1), and 30 of them had a score > 7: suggesting mild depression in 19 subjects and moderate depression in 11 subjects. Subjects also reported on all the 20 symptoms of the 20 item Zung Instrument for Anxiety Disorders, with an average of the total score of 33.6 (95% C.I. 33–34.3); only one of them had a score > 44, suggesting mild to moderate anxiety (47 points).
DD Symptoms before unilateral centrifugation
Prior to unilateral centrifugation, the number of symptoms reported by the subjects in the DD inventory ranged from 0 to 25 (median 4) and the range of the total score was from 0 to 51 (average 6.2, 95% C.I. 4.7–8.0). Individual scores on each item are described in Table 2. The most frequent symptoms were: “D é j à vu” (53%, 95% C.I. 44%–62%), “Difficulty concentrating” (51%, 95% C.I. 42%–60%), “Difficulty focusing attention” (38%, 95% C.I.29%–47%), “Vision is dulled” (32%, 95% C.I. 23%–41%), “Dizziness” (27%, 95% C.I. 18%–36%) and “Time seems to pass very slowly” (26%, 95% C.I. 18%–34%). A bivariate analysis showed an inverse correlation between the age of the subjects and the report of “d é j à vu” (Pearson’s r = –0.38, p < 0.0001), “Difficulty focusing attention” (Pearson’s r = –0.29, 0.003) and “Feel as though in a dream” (Pearson’s r=–0.23, p = 0.01), but no correlation was observed with the total score of DD symptoms. Also, correlation was observed between the DD total score and the total score of the questionnaires of symptoms related to balance (Pearson’s r = 0.40, p = 0.0001), depression (Pearson’s r = 0.55, p < 0.0001), and anxiety (Pearson’s r = 0.33, p = 0.001). Multivariate analysis confirmed the relationship between the total score of the DD symptoms with the total score of the symptoms related to balance and the depression inventory, but no other relationships or interactions were observed (ANCOVA, p > 0.05).
Bivariate analysis also showed linear correlations between specific item scores, which were the less frequent for the report of “déjà vu” that was related to 11 of the other 27 items (Pearson’s r from 0.2 to 0.34, p < 0.05); while the item “Feel confused or bewildered” showed correlation to all the other 27 items (Pearson’s r from 0.22 to 0.52, p < 0.05).
DD symptoms after unilateral centrifugation
The number of symptoms reported by the subjects ranged from 0 to 28 (median 8) and the range of the total score was from 0 to 73 (average 12.1, 95 C.I. 9.5–14.7). Apart from dizziness, which was reported by 47% (95% C.I. 38%–56%) of the subjects, the most frequent symptoms were (Table 2): “Body feels strange or different in some way” (56%. 95% C.I. 45%–65%), “Time seems to pass very slowly” (55%, 95% C.I. 46%–64%), “Events seem to happen in slow motion” (49%, 95% C.I. 40%–58%), “Surroundings seem strange and unreal” (43%, 95% C.I. 34%–52%), “Difficulty focusing attention “ (41%, 95% C.I. 32%–50%) and “Feeling of detachment or separation from surroundings” (40%, 95% C.I. 31%–49%).
A bivariate analysis showed an inverse correlation between the age of the subjects and the total score (Pearson’s r = –0.19, p = 0.04), with an inverse correlation of the age with 5 of the symptoms: “Body feels strange or different in some way” (Pearson’s r = –0.26, p = 0.007) “Feel as though in a dream” (Pearson’s r = –0.21, p = 0.03) ” Body feels numb” (Pearson’s r = –0.19, p = 0.05), “Difficulty focusing attention” (Pearson’s r = –0.21, p = 0.02), and “Feel confused or bewildered” (Pearson’s r = –0.21, p = 0.03). Also, correlation was observed between the DD total score and the total score of the questionnaire of: symptoms related to balance (Pearson’s r = 0.31, p = 0.002) and the depression inventory (Pearson’s r = 0.30, p < 0.002), but no correlation was observed with the anxiety inventory. Multivariate analysis confirmed the relationship between the total score of the DD symptoms with the total score of the symptoms related to balance and the depression inventory, but no other relationships or interactions were observed, either with the general characteristics of the subjects or to the response to vestibular function test (ANCOVA, p > 0.05). Bivariate analysis also showed linear correlations between specific item scores, which were the less frequent for the report of “déjà vu” that was related to 9 of the other 27 items (Pearson’s r from 0.25 to 0.52, p < 0.05); while the item “Feel as though in a dream” showed correlation to all the other 27 items (Pearson’s r from 0.27 to 0.67, p < 0.05).
Comparison between the symptoms reported before and during centrifugation,
There was an increase on the frequency and severity of most of the symptoms (Table 2), with an increase of the total score (paired “t” test, p < 0.0001). Twenty out of the 28 symptoms showed a significant frequency/severity increase, and the frequency of two symptoms decreased “(déjà vu” and “difficulty concentrating”) (Table 2).
The difference between the DD symptoms and the total score before and after centrifugation showed no correlation to any of the general characteristics of the subjects or to the response to vestibular function test or to any of the questionnaires (ANCOVA, p > 0.05).
The frequency and strength of correlation between the individual scores of the individual items increased for most of the symptoms, but was more evident for the following symptoms: “Feel as if walking on shifting ground” with correlation to the other 27 items (Pearson’s r from 0.31 to 0.67, p < 0.01) “Feel as though in a dream” that was related to the other 27 items (Pearson’s r from 0.27 to 0.67, p < 0.01), “People appear strange or unreal” with correlation to the other 27 items (Pearson’s r from 0.20 to 0.67, p < 0.05), and “Feeling detached or separated from your body” that was related to 26 of the other 27 items (Pearson’s r from 0.29 to 0.67, p < 0.01),
Discussion
Unilateral centrifugation provoked symptoms which subjects previously denied. The total score of DD symptoms showed a moderate correlation to symptoms related to balance and to depression symptoms, but not to anxiety symptoms. The frequency of correlation between the scores of individual items increased, particularly for symptoms related to derealisation and to vestibular function.
About half of the subjects experienced feelings of unreality of both the body and the environment. The two most frequent symptoms were “body feels strange or different in some way” and “time seems to pass very slowly”. The results are consistent with previous studies, using the same DD inventory, in one of them, during caloric stimulation, healthy subjects reported an increase of the frequency/severity of the DD symptoms, while patients with peripheral vestibular disease reported similar DD symptoms than those they have been experiencing during the clinical evolution of their vestibular disease [27]; in a second study, patients with vestibular disease and patients with retinal disease reported these symptoms more frequently than patients with hearing disorders or healthy subjects [19].
The high frequency to report “body feels strange or different in some way” is consistent with the results of studies supporting that the vestibular system contributes to the definition of the self [25]. In this study, utricular stimulation in healthy subjects provoked symptoms of derealization similar to those observed during semicircular canal stimulation by caloric test and those reported by patients with peripheral vestibular disease, with no influence of the general characteristics of the subjects [14, 27]. The results consistency with other studies performed in different populations suggest that the socio-cultural characteristics of the subjects have not interfered with the report of the experiences of unreality. However, the low numbers of high alcohol consumers or heavy smokers in the sample precluded assessment of any influence on the report of DD symptoms from alcohol or tobacco consumption, as it has been reported for substance abuse [28, 29].
The altered perception of time during utricular stimulation is in agreement with the evidence showing an influence of vestibular stimulation on the perception of time. Since 1960, Frankenhaeuser described that, during 3g centrifugal acceleration, subjects reproduced temporal intervals systematically shorter than when stationary [12]. More recently, it was shown that the timing of self-paced repetitive movements is altered in microgravity [30], and interval regularity is impaired during self-motion in darkness, compared to immobility [5]; also, evidence support that timing computations of motor outputs are tuned to the velocity of body displacements [3]. These findings are in agreement with neuroimage evidence showing that dissociation and depersonalization scores in subjects with depersonalization disorder are significantly related to metabolic activity in the parietal cortex [31], while the posterior parietal cortex is involved in temporal information processing [2, 24], and area OP2 is the primary candidate for the human vestibular cortex [33].
Interestingly, during unilateral centrifugation, a decrease of the frequency/severity of the item “difficulty concentrating” was observed. Although this item is unspecific, evidence support that otolithic stimulation may interfere with cognitive processing [13], and patients with an acute unilateral vestibular lesion may report difficulty concentrating, which may improve during the following weeks [14]. However, in this study, in healthy subjects, the report of “difficulty concentrating” decreased during centrifugation instead of increasing. This finding might be related to the fact that, during centrifugation, subjects were performing a task that made them focus in the sensory input from the otoliths, instead of an independent second task. Additionally, the effect might be related to an increased arousal due to the complexity of the task. However, since no independent second task or arousal assessment were performed, these hypotheses would require further investigation.
In this study, no influence of anxiety symptoms on the report of DD symptoms was observed. However, a relationship with depression symptoms was evident both, before and after centrifugation. This result is in agreement with clinical evidence supporting that mood, anxiety and personality disorders are often co-morbid with depersonalization but none predict symptom severity and the most common immediate precipitants of depersonalization disorder are severe stress, depression and panic [32].
Conclusions
Unilateral centrifugation provokes derealisation symptoms. The results support the hypothesis that distorted vestibular signals, either by otolith or canal stimulation [27], may create a misleading frame of reference which mismatch with the other senses, giving rise to ‘unreal’ perceptions.
Conflict of interest
No competing interests.