|Year : 2021 | Volume
| Issue : 3 | Page : 145-148
Cognitive deficits correlated with increased latency of event-related potentials in drug-free patients with generalized anxiety disorder
Shuo- En Hsu M.D 1, Lan- Ting Lee M.D 1, Hsin- Chun Tsai M.D 1, Mei Hung Chi M.D 2, Kao Chin Chen M.D., Ph.D 2, I Hui Lee M.D 2, Po See Chen M.D., Ph.D 3, Yen Kuang Yang M.D 4
1 Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan; Department of Psychiatry, National Cheng Kung University Hospital, Dou-Liou Branch, Yunlin, Taiwan
2 Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
3 Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University; Institute of Behavioral Medicine, College of Medicine, National Cheng Kung Universit, Tainan; Department of Psychiatry, National Cheng Kung University Hospital, Dou-Liou Branch, Yunlin, Taiwan
4 Department of Psychiatry, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University; Institute of Behavioral Medicine, College of Medicine, National Cheng Kung University; Department of Psychiatry, Tainan Hospital, Ministry of Health and Welfare, Tainan, Taiwan
|Date of Submission||28-Apr-2021|
|Date of Decision||16-Jun-2021|
|Date of Acceptance||18-Jun-2021|
|Date of Web Publication||24-Sep-2021|
Yen Kuang Yang
No 138, Sheng Li Road, Tainan 704
Source of Support: None, Conflict of Interest: None
Objective: Few studies have identified a relationship between cognitive deficits and altered event-related potentials (ERPs), which measure the synchronous activity of neurons in response to a stimulus in patients with generalized anxiety disorder (GAD). In this study, we intended to explore the relation between cognitive function and ERP in patients with GAD. Methods: Fourteen drug-free participants with GAD and 14 healthy controls were recruited. ERPs were measured, and neuropsychological tests were administered. We compared the differences of the data between two groups of the study participants. Results: Poor performances of full IQ and the numbers of the categories completed on the Wisconsin Card Sorting Test were found significantly correlated with increased frontal lobe latency in the patients with GAD (Spearman's ρ = −0.70, p < 0.05; Spearman's ρ = −0.85, p < 0.01), respectively, but not in the controls. Conclusion: As ERPs represent an index of information speed, we propose that patients with GAD could exhibit deficits in tasks requiring mental speed.
Keywords: electroencephalogram, mental speed, Wechsler Adult Intelligence Scale-Revised, Wisconsin Card Sorting Test
|How to cite this article:|
Hsu SE, Lee LT, Tsai HC, Chi MH, Chen KC, Lee I H, Chen PS, Yang YK. Cognitive deficits correlated with increased latency of event-related potentials in drug-free patients with generalized anxiety disorder. Taiwan J Psychiatry 2021;35:145-8
|How to cite this URL:|
Hsu SE, Lee LT, Tsai HC, Chi MH, Chen KC, Lee I H, Chen PS, Yang YK. Cognitive deficits correlated with increased latency of event-related potentials in drug-free patients with generalized anxiety disorder. Taiwan J Psychiatry [serial online] 2021 [cited 2023 Jan 28];35:145-8. Available from: http://www.e-tjp.org/text.asp?2021/35/3/145/326578
| Introduction|| |
Event-related potentials (ERPs) are voltage fluctuations that are associated in time with some physical or mental occurrence. These potentials can be recorded from the human scalp and extracted from the ongoing electroencephalogram (EEG) by means of filtering and signal averaging . Cognitive deficits among old adult patients have been identified with generalized anxiety disorder (GAD) .
By studying ERPs, researchers may clarify the neurobiological basis of GAD. We know that monoamines such as serotonin and dopamine can influence the activities of ERPs, and individuals with GAD who are medicated can exhibit changes in ERPs . To our knowledge, the results of those studies remain inconclusive. In a study on the N270 component of ERPs, the investigators have found a decreased N270 amplitude in the left hemisphere of patients with GAD, indicating that the smaller amplitude is related to more severe anxiety symptoms . Meanwhile, decreased N270 amplitude in ERPs in the left hemisphere has been found in patients with GAD, suggesting that the smaller amplitude is related to more severe anxiety symptoms . MacNamara and Proudfit  reported that the effect of working memory load in reducing the late positive potential has been decreased in patients with GAD, indicating less flexible modulation of attention.
In the literature, only a few studies have probed the P300 among patients with GAD. Xu et al.  studied the passive P3 component of ERPs and have identified a decreased P3 amplitude among patients with GAD and patients with major depressive disorder. In this study, we intended to explore the relationship between cognitive function and ERPs in patients with GAD.
| Methods|| |
We enrolled 14 drug-free patients (five males and nine females) with GAD from psychiatry outpatient clinics. The inclusion criteria were patients who (a) fulfilled the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for GAD, (b) were aged between 20 and 60 years, and (c) had no evidence of substance abuse/dependence. We also enrolled a comparable group of healthy controls (n = 14) from the community. Patients with other comorbid psychiatric illnesses or neurological illnesses were excluded from the study.
The institutional review board of National Cheng Kung University Hospital approved the study protocol (protocol number = BR-100-009 and date of approval = December 13, 2011) with the need of obtaining the signed informed consents from the study participants.
ERPs were recorded using an auditory oddball paradigm, based on methods that have been established previously . EEGs were recorded using NuAmps recording apparatus (Compumedics Neuroscan, El Paso, Texas, USA). Recordings were done using an electrocap in a sound-attenuated, electrically shielded environment with an acoustic celotex board. The number of EEG channels was 32. The EEG and eye channels were appropriately amplified (EEG Gain = 19, sampling = 1000/s, 22-bit A-to-D conversion) and filtered (band pass = 0.1–30 Hz). Eye movements were recorded using an electrode lateral to both eyes, which was near the outer regions of the canthus. Auditory stimuli were delivered binaurally through headphones, and the interstimulus interval was between one and two seconds. Random target tones (2000 Hz; probability, 0.2) that differed from the nontarget events (1000 Hz; probability, 0.8) in pitch were established. Participants were instructed to look at the “+” target on the screen and press the button as soon as possible when they identified one of the target tones. P300 potentials were recorded from the electrodes referenced linked to the mastoids. EEG epochs starting 150 ms before stimulus onset were averaged offline using a computer. We excluded trials with electrooculographic amplitudes over 50 μV from the average. Subjects undertook 200 trials in total, those who completed fewer than 20 accepted trials for the target were excluded. The P300 amplitude was measured relative to the mean of the 100-ms prestimulus baseline, with peak latency defined as the time point associated with the maximum positive amplitude during the 200–400-ms interval following the stimulus. The technicians recorded both the amplitudes and the latencies.
The Wechsler Adult Intelligence Scale-Revised (WAIS-R)  and the Wisconsin Card Sorting Test (WCST)  were administered. The WAIS-R is used to evaluate the individuals' intelligence. This test gives a full-scale IQ and two different dimensions of IQ. The six-subtest short-form combination consists of digit symbol, block design, object assembly, digit span, similarity, and arithmetic tests. We used the former three subtests to obtain an estimated performance IQ, while the latter three subtests were used to obtain an estimated verbal IQ.
The study data of patients with GAD and matched healthy controls were presented as mean ± standard deviations. We used Wilcoxon signed-rank tests to test the differences between those two groups. Spearman's ρ correlations were carried out to examine the associations between ERPs and cognitive function.
All study data were computed using Statistical Package for the Social Science software version 22.0 for Windows (SPSS Inc., Chicago, Illinois, USA). The differences between two groups were considered significant if p-values were smaller than 0.05.
| Results|| |
As shown in [Table 1], the subjects with GAD did poorer than the controls in the WAIS-R and numbers of categories completed on the WCST. The P300 ERP latency was higher in the patients with GAD (p < 0.05) in the parietal, central, and frontal lobe [Table 1]. Poor performances in full IQ (ρ = −0.70, p < 0.05) and numbers of WCST categories completed (ρ = −0.85, p < 0.01) were significantly correlated with an increased frontal lobe latency in the patients with GAD but not in the controls (full IQ and frontal lobe latency (ρ = 0.01, nonsignificance); number of WCST categories completed and frontal lobe latency (ρ = −0.16, nonsignificance)). [Table 2] shows the association of ERP and IQ.
|Table 1: Demographic data, event.related potential measurements, and cognitive function assessment of the patients with generalized anxiety disorder and their matched healthy controls|
Click here to view
|Table 2: Spearman's ρ correlations between event-related potential measurements and cognitive function in the patients with generalized anxiety disorder and their matched healthy controls|
Click here to view
| Discussion|| |
As shown in [Table 1], we found that significantly poorer performance on the WAIS-R (performance IQ, verbal IQ, and full IQ) and one important domain of WCST, namely categories completed in the GAD patient group. This finding confirmed a poor global executive function and poor cognitive flexibility among these patients. Altered pattern of P300 (slower latency) was noted in the GAD patient group. This finding is similar to that in previous studies ,,. The association between the WAIS-R and the P300 ERP latency in the parietal region among patients with GAD (p < 0.05), but not among controls, might be a novel finding.
This finding is in agreement with that in previous studies that demonstrated altered ERPs (late positive potential, P300, and N270) among patients with GAD ,,. But unlike the findings of an altered amplitude ,, our results demonstrated that the latency was longer among the patients with GAD, the mechanism of this discrepancy being unclear. To the best of our knowledge, only a few studies with P300 have reported a slower ERP among individuals with a tendency toward anxiety during certain emotional tasks . Our findings may imply that an altered ERP latency during neutral tasks could be a characteristic of patients with GAD. Difficulty in completing a cognitive task due to visual distractors has been found to influence performance , whether this mechanism may decrease the ERP amplitude, is unclear. On the other hand, working memory load may reduce the late positive potential among individuals with a lower state of anxiety . This finding may be compatible to future ERP studies. More importantly, we also found that the patients with GAD did more poorly in the numbers of categories completed in WCST, which was negatively correlated with the P300 ERP latency in the frontal region in the patients with GAD. The results of the WCST are related to cognitive flexibility , which is important factor of anxiety.
The readers are warned not to overinterpret the study results because this study has two major limitations:
- The sample size was small.
- This study was of a cross-sectional design, and the causal relationship between poor attention and increased P300 latency could not be clarified in this study.
More future studies are needed to duplicate and strengthen the study findings.
In this study, impaired executive function was found, and a slower ERP P300 latency was identified among the patients with GAD. We suggest that the slower latency could be related to poor executive function among patients with GAD.
| Acknowledgments|| |
The authors thank Shih-Hsien Lin for his advice and Tsai Hua Chang for her administrative support. The funders had no rôle in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
| Financial Support and Sponsorship|| |
This study was supported by the National Science Council of Taiwan (NSC 93-2314-B-006-107, NSC 95-2314-B-006-115-MY2, NSC 97-2314-B-006-006-MY3, NSC 100-2314-B-006-041-MY3) and the Atomic Energy Council of Taiwan (NSC 99-NU-E-006-003).
| Conflicts of Interest|| |
The authors declare that they have no conflicts of interest in reporting this work.
Yen Kuang Yang, associate editor, I Hui Lee, a member of executive editorial board of the Taiwanese Journal of Psychiatry, had no rôle in the peer review process or decision to publish this article.
| References|| |
Picton TW, Bentin S, Berg P, et al.: Guidelines for using human event-related potentials to study cognition: recording standards and publication criteria. Psychophysiology
2000; 37: 127-52.
Butters MA, Bhalla RK, Andreescu C, et al.: Changes in neuropsychological functioning following treatment for late-life generalised anxiety disorder. Br J Psychiatry
2011; 199: 211-8.
Lee IH, Yang YK, Chen PS, et al.: Loudness dependence of auditory evoked potentials (LDAEP) correlates with the availability of dopamine transporters and serotonin transporters in healthy volunteers-a two isotopes SPECT study. Psychopharmacology
(Berlin) 2011; 214: 617-24.
Yang Y, Zhang X, Zhu Y, et al.: Cognitive impairment in generalized anxiety disorder revealed by event-related potential N270. Neuropsychiatr Dis Treat
2015; 11: 1405-11.
MacNamara A, Proudfit GH: Cognitive load and emotional processing in generalized anxiety disorder: electrocortical evidence for increased distractibility. J Abnorm Psychol
2014; 123: 557-65.
Xu S, Chai H, Hu J, et al.: Passive event-related potentials to a single tone in treatment-resistant depression, generalized anxiety disorder, and borderline personality disorder patients. J Clin Neurophysiol
2014; 31: 488-92.
Wechsler D: Wechsler Adult Intelligence Scale-Revised Manual
. Anglicized edition
. London: Psychological Corporation, 1986.
Heaton RK, Chelune G, Talley L, et al.: Wisconsin Card Sorting Test (WCST): Manual Revised and Expanded.
Odessa, Florida, USA: Psychological Assessment Resources, 1993.
De Pascalis V, Strippoli E, Riccardi P, et al.: Personality, event-related potential (ERP) and heart rate (HR) in emotional word processing. Pers Individ Dif
2004; 36: 873-91.
Qi S, Zeng Q, Luo Y, et al.: Impact of working memory load on cognitive control in trait anxiety: an ERP study. PLoS One
2014; 9: e111791.
MacNamara A, Ferri J, Hajcak G: Working memory load reduces the late positive potential and this effect is attenuated with increasing anxiety. Cogn Affect Behav Neurosci
2011; 11: 321-31.
[Table 1], [Table 2]