Auditory event-related potentials in panic and generalised anxiety disorders

Auditory event-related potentials in panic and generalised anxiety disorders

Progress in Neuro-Psychopharmacology & Biological Psychiatry 26 (2002) 123 – 126 Auditory event-related potentials in panic and generalised anxiety d...

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Progress in Neuro-Psychopharmacology & Biological Psychiatry 26 (2002) 123 – 126

Auditory event-related potentials in panic and generalised anxiety disorders Tayfun Turan*, Ertugrul Esel, Fatih Karaaslan, Mustafa Basturk, Aslan Oguz, Ihsan Yabanoglu Department of Psychiatry, Erciyes University School of Medicine, Talas Road, 38039 Kayseri, Turkey

Abstract In this study, we aimed to investigate event-related potential (ERP) changes in panic disorder (PD) and generalised anxiety disorder (GAD) and to determine whether two disorders are different from each other in terms of endogenous potentials. A total of 35 outpatients who fully met DSM-III-R criteria for PD (8 males and 27 females) were included in this study as the PD group. The GAD group consisted of 30 subjects (5 males and 25 females) who met DSM-III-R GAD criteria. The control group consisted of 29 healthy age and sex-matched volunteers (5 males and 24 females) having no history of psychiatric or neurological illness. ERPs were recorded by using auditory ‘‘odd-ball two-tone discrimination task’’ method. It was found that there was significant prolongation in P3 latency in the PD group compared to the GAD and control groups. Our study suggests that there are some disturbances in early information processing in patients with PD but not with GAD. D 2001 Elsevier Science Inc. All rights reserved. Keywords: Event-related potentials; Generalised anxiety disorder; Panic disorder; P3

1. Introduction Late ( > 50 ms poststimulus onset) scalp recorded eventrelated potentials (ERPs) are elicited during the active process of discriminating one different stimulus the rest (Goodin, 1992). The significance of P3, a positive potential elicited approximately 300 ms after stimulus onset, is that it is a function of a psychological or cognitive variable like ‘‘uncertainty’’ (Bruder, 1992). It is claimed that the sources of these potentials are limbic structures such as hippocampus, amygdala or thalamus (Halgren et al., 1980; Yingling and Hosobuchi, 1984). These areas are also thought to be involved in the pathophysiology of anxiety disorders, especially panic disorder (PD) (Gorman et al., 2000; Reiman et al., 1984; Rosenberg et al., 1991). ERP studies are noninvasive methods that enable to investigate this relationship (Bruder, 1992).

Abbreviations: ERPs, Event-related potentials; GAD, Generalised anxiety disorder; PD, Panic disorder * Corresponding author. Tel./Fax: +90-352-4375702. E-mail address: [email protected] (T. Turan).

There are not many ERP studies in anxiety disorders, and the results of the previous ERP studies do not point to any consistent pattern with regard to anxiety. A study in which ERPs were recorded during a passive, nontask condition in 12 patients with PD revealed that the N1 (i.e., a negative potential elicited approximately 100 ms poststimulus onset) amplitude in the patient group was larger than that in the control group, but there was no difference in the P2 (a positive potential following N1) component (Knott et al., 1991). In a recent study, it was found that there was P3 enlargement in panic patients but no difference in the N1, P2 and N2 (a negative potential elicited approximately 200 ms poststimulus onset) components (Clark et al., 1996). In another study, Iwanami et al. (1997) reported that the N1 and N2 amplitudes for target tones were significantly larger in the panic patients than those in the controls. This group did not find any difference in P3 amplitude and latency. Drake et al. (1991) found that there were slightly but nonsignificantly prolonged N1, N2 and P2 latencies and decreased P3 latency in generalised anxiety disorder (GAD) patients. The auditory oddball task is a standard and wellestablished task used to examine early and late components of ERPs (Goodin, 1992). In the present study, the authors aimed to investigate ERP changes in patients with

0278-5846/02/$ – see front matter D 2001 Elsevier Science Inc. All rights reserved. PII: S 0 2 7 8 - 5 8 4 6 ( 0 1 ) 0 0 2 1 7 - 2

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Table 1 Demographic variables of the groups Panic patients, n = 35

GAD patients, n = 30

Control subjects, n = 29

Age (years) ± S.D. Range (years)

35.5 ± 1.5 18 – 55

36.1 ± 1.2 22 – 51

34.7 ± 1.5 19 – 54

Gender Male Female

8 27

5 25

5 24 Fig. 1. Mean P3 latencies in the control, GAD and PD groups.

PD and GAD, and whether two disorders are different from each other in terms of endogenous potential.

2. Methods

A total of 29 healthy age and sex-matched volunteers (5 males and 24 females) who had no history of psychiatric or neurological illness served as the control group (mean age ± S.D.: 34.7 ± 1.5; range: 19 –54). Their mean score in the Hamilton anxiety scale was 4.0 ± 0.3.

2.1. Subjects 2.2. ERP recording and procedure Table 1 shows demographic variables of all subjects. A total of 35 outpatients who fully met DSM-III-R criteria for PD (American Psychiatric Association, 1987) (8 males and 27 females) were recruited for the PD group. Their mean age was 35.5 ± 1.5 years (range: 18 –55), mean duration of illness ± S.D. was 2.8 ± 0.4 years (range: 6 months – 10 years), and mean score in the Hamilton anxiety scale was 8.8 ± 1.3 (Hamilton, 1969). Their mean ± S.D. frequency of panic attacks was 3.08 ± 1.12 per month (range: 2– 6). The GAD group consisted of 30 subjects (5 males and 25 females) who met DSM-III-R GAD criteria (American Psychiatric Association, 1987). Their mean age ± S.D. was 36.1 ± 1.2 years (range: 22 – 51), and mean duration of illness was 4.6 ± 0.7 years (range: 1– 15 years). Their mean score in the Hamilton anxiety scale was 8.9 ± 0.8. Exclusion criteria were if the subjects had any psychiatric disorder other than PD or GAD, neurological disorders, physical disorders, substance abuse disorders, head injury history and apparent decreased in hearing. All patients were drug free for at least 2 weeks at the time of recording, and written informed consent from all subjects was obtained. The study protocol was approved by the ethics committee of our hospital.

ERPs were recorded by using auditory ‘‘odd-ball twotone discrimination task’’ method in a soundproof room at 8:00 – 10:00 a.m. A Nihon Kohden Neuropack model MEB-530 4 K/6 EMG preamplificator was used. Active Ag/Ag – Cl disc electrodes were placed at Cz and Fz according to international 10 –20 electrode system. Earth electrodes were placed at Fpz, and earlobes were linked to each other. The electrode impedance was less than 5 kV. Sounds were delivered binaurally through headphones. Subjects were instructed to silently count infrequent high-pitch tones of 2000 Hz randomly presented in a series of low-pitch tones of 1000 Hz. The ratio of high- to low-pitch tones was 1:5. The stimulus rate was 2 s, intensity was 75 dB, and tone duration was 50 ms. Twenty artifact-free traces following high pitch were averaged with a sweep time of 1000 ms including the 100-ms prestimulus baseline. An artifact-reject circuit excluded from averaging all trials in which the voltage exceeded ± 40 mV. Two separate recordings were carried out at each testing. Individual peaks, which designated N1, P2, N2 and P3, were identified by visual inspection of the traces. N1 was

Table 2 Comparison of ERP values in the panic, GAD and control groups Panic patients, n = 35 (mean ± S.D.) Latency (ms) N1 96.29 ± 15.63 P2 184.06 ± 32.56 N2 225.60 ± 30.86 P3 329.60 ± 30.28a Amplitude (mV) P2 4.80 ± 4.31 N2 4.07 ± 3.28 P3 11.46 ± 5.75 a

GAD patients, n = 30 (mean ± S.D.)

Control subjects, n = 29 (mean ± S.D.)

F (df = 2,93)

P

101.93 ± 15.89 176.73 ± 22.41 216.66 ± 19.10 312.20 ± 25.39

92.76 ± 13.59 169.72 ± 17.16 212.21 ± 18.23 312.97 ± 25.67

2.77 2.52 2.61 4.41

>.05 >.05 >.05 < .05

5.73 ± 4.72 4.92 ± 5.14 12.42 ± 5.87

4.34 ± 3.07 3.72 ± 2.57 11.19 ± 6.07

0.87 0.78 0.63

>.05 >.05 >.05

Significantly different from those of the control and GAD groups.

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defined as the most negative peak between 70 and 120 ms poststimulus, P3 as the most positive peak between 265 and 600 ms poststimulus, P2 as the most positive peak between 140 and 230 ms and N2 as the most negative peak between N1 and P3. Peak latencies were measured using a cursor according to the points in which the amplitude was maximum. Amplitudes were measured from baseline to peak. 2.3. Data analyses Statistical analyses were performed using one-way ANOVA (post hoc Scheffe test) to compare each ERP variable between groups.

3. Results Table 2 shows the comparison of the ERP data in the panic, GAD and control groups. It was found that there was significant prolongation in P3 latency in the PD group compared to both the control and GAD groups ( F = 4.41, df = 2,93, P < .05) (Fig. 1). P2 and N2 latencies were also greater in the PD group than those in the controls, but these differences were not statistically significant. In the GAD group, there were no differences in any ERP components compared to those of the controls.

4. Discussion The significant finding of our study is P3 latency prolongation in the PD group in comparison with both the GAD and control groups. To our knowledge, P3 latency prolongation in panic patients was reported only in one previous study (Clark et al., 1996), but their method was different from ours. Taking into account the claims that propose that the source of P3 are limbic structures, especially the hippocampus (Halgren et al., 1980, Okada et al., 1983), our result supports the hypothesis that limbic structures such as the hippocampus and amygdala play a significant role in PD development (Gorman et al., 2000). Amygdala has dense reciprocal connections with sensory thalamus and some brainstem structures including locus ceruleus and parabrachial nucleus, which are also important in the development of symptoms of panic attacks (Gorman et al., 2000). In a brainstem auditory-evoked potentials study, it has been reported that a prolongation in early evoked potential passage from the pons, where the locus ceruleus is located, to the midbrain in patients with PD (Levy et al., 1996). Therefore, one can think that both the early brainstem evoked potentials and the late ERPs, which are believed to be mostly related to the limbic structures, may be delayed, which reflects a disruption in the connections between brainstem structures and the limbic lobe in PD. The prolongations in these two different evoked poten-

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tials (early brainstem and late) may be interrelated, but we cannot say which one is primary at this stage. The finding of no amplitude changes in ERPs in panic patients is inconsistent with some previous studies that reported amplitude alterations in early potentials such as N1 and N2 (Knott et al., 1991; Iwanami et al., 1997). This discrepancy may be due to methodological differences and small number of subjects in their studies. We did not find any difference in ERP components in GAD patients compared to controls. This finding is consistent with Drake et al.’s (1991) study, which reported no significant changes in late auditory evoked potentials in GAD patients. There has long been a debate as to whether PD is an entirely distinct entity from GAD or an excess form of it. The results of the earlier reports reveal that there are some differences between the two disorders. For example, parahippocampal asymmetry, which was detected in PD (Reiman et al., 1984, 1986) was not found in GAD (Wu et al., 1991). Noradrenergic neuronal hyperactivity was found as much as 50% in PD, but not in GAD (Charney et al., 1989). In EEG studies, 27% of panic patients but only 10% of GAD patients showed epileptic discharges (Lepola et al., 1990). Genetic component is more important in the generation of PD than GAD (Torgersen, 1983). GAD begins in younger ages and courses more chronically and with more somatic symptoms (Noyes et al., 1987). All of these data suggest that these two disorders are different illnesses. In our study, the two patient groups showed different ERP features from each other in that P3 latency was significantly prolonged in only the PD group, but not in the GAD group. Therefore, these two disorders seem to be different from each other in terms of information processing. Taken together, it can be thought that although two disorders may arise from limbic system, they may be rather distinct entities.

5. Conclusion We conclude that the patients with PD exhibit P3 abnormality, and this may point to information processing disturbances. However, GAD patients do not differ from the controls in terms of ERPs.

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