Jenny L Patterson1, J. Bruce Barber2, Daniel W. O’Connor3 and Samia R Toukhsati4*
1School of Psychology and Psychiatry, Monash University, Clayton, VIC 3800, Australia
2National Ageing Research Institute, Parkville, VIC 3052, Australia
3Institute for Health and Ageing, Australian Catholic University, Melbourne, VIC 3000, Australia
4University of Melbourne and Department of Cardiology, Austin Health, Heidelberg, VIC 3084, Australia
Received: 26 April, 2016; Accepted: 21 July, 2016; Published: 23 July, 2016
Samia Rachael Toukhsati , University of Melbourne, Department of Cardiology, Austin Health, Heidelberg, 3084 Victoria, Australia, Tel: +61 3 9496 3209; Fax: +61 3 9496 5026; E-mail:
Patterson JL, Barber JB, O’Connor DW, Toukhsati SR (2016) Electrophysiological Profiling of Depression in the Elderly. Arch Depress Anxiety 2(1): 031-036. DOI: 10.17352/2455-5460.000012
© 2016 Patterson JL, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Frontostriatal system functioning has been proposed to underpin performance on executive functioning tasks; these structures are abnormally activated in adults with depression. In this study, the P200 and P300 event-related potentials (ERPs) were elicited during a classic two-tone auditory oddball task to compare the electrophysiological profiles of elderly people (N = 54; Mean age = 85.46 ± 6.21) diagnosed with clinical depression (n = 17), subthreshold depression (n = 25) or no depression (n = 12). The P200 results revealed higher amplitude and significantly longer latencies in depressed groups relative to non-depressed participants. Higher P300 amplitude, but shorter latencies, were observed in depressed relative to non-depressed participants. Findings are discussed in terms of cognitive information processing models of ERPs and the potential for non-cognitive factors to impact on the resulting electrophysiological profile.
Executive functioning is impaired in the setting of depression . Frontostriatal system functioning has been proposed to underpin performance on executive functioning tasks and research has shown that these structures are abnormally activated in adults with depression [2-4]. These structures have also been implicated in generating the P200 and P300 event-related potentials (ERPs), which provide an electrophysiological index of cognitive functioning. Corresponding with the known disruption to executive functioning in depressed cohorts, research amongst young adults with depression has tended to reveal lower P300 amplitude relative to their non-depressed counterparts [5-8]. The research is less consistent with regard to latency; however, prolonged latency has been observed in specific subtypes of depression in which psychomotor retardation is a prominent feature .
Collectively, ERP and neuropsychological data appear to provide converging evidence of prefrontal dysfunction in depression amongst young cohorts; however, little research has utilized electrophysiological methods to explore cognitive dysfunction arising in the context of depression amongst the elderly. Early reports found no significant differences in P300 latency for depressed elderly [9-12], however, these studies tended to be poorly controlled with regard to stimulus (i.e., probability, inter-stimulus interval) and sample (i.e., age, medication status) variables. More recent findings from studies that control for such factors have revealed prolonged P300 latency amongst depressed elderly relative to their age-matched, non-depressed counterparts [13-15]. Moreover, such abnormalities have been associated with poorer performance on tasks of executive functioning, psychomotor retardation and poorer treatment response [13,14].
Presently, the influence of depression on ERP amplitude in the elderly is largely unknown. This is notable because it is the most consistent cognitive marker of depression in younger cohorts . As a general principle, age-related structural changes in the brain and other physiological factors have been shown to produce differences in ERPs between young and older adults. Indeed, research has revealed differences in the spatial distribution of ERP components, temporal properties (i.e., lower amplitude and longer latency in the elderly), as well as a general increase in the degree of individual ERP variability in older cohorts . For example, elderly samples typically demonstrate a more ‘U-shaped’ P300 spatial distribution, with higher amplitude at the frontal and posterior sites, as opposed to the singular maximal posterior P300 distribution seen in younger samples . Such differences in ERPs between young and old suggest that the characterization of ERPs in elderly with and without depression is an important area of inquiry.
From a cognitive perspective, the high temporal resolution of ERPs means that this technique has the potential to provide important information about the stage of information processing that may be disrupted in elderly with depression. To date, the limited available data has revealed significant increases in P200 amplitude, consistent with over-processing of irrelevant stimuli, which may explain downstream P300 abnormalities [18,19]. Further research that examines early ERP components will provide a more comprehensive insight into the electrophysiological profile of geriatric depression. To this end, the aim of this study was to explore the electrophysiological profile of elderly individuals with varying severity of depression, with a specific focus on latency and amplitude of the P200 and P300 auditory ERPs.
Following ethics approval by the Monash University Human Research Ethics Committee (Project number CF07/4928 – 2007002107), participants were recruited from 15 Residential Aged Care facilities (RACFs) in Melbourne, Australia. Exclusion criteria were (1) a formal diagnosis of dementia or delirium; (2) legal blindness; (3) deafness or severe hearing impairment; (4) lack of English fluency. Participants were screened using the Standardized Mini-Mental State Examination (SMMSE) and the Geriatric Depression Scale (GDS-15). To account for lowered scores on the SMMSE due to depression, individuals with scores of 20-24 were retained for preliminary analyses. Individuals with SMMSE scores below 20 were excluded from further participation in the study (n = 33). This yielded a total sample of 73 participants. Depression was diagnosed using the Depression module from the non-patient version of the Structured Clinical Interview for the DSM-IV-TR (SCID-I). Participants were grouped according to their severity of depression: non-depressed was defined as no SCID-I diagnosis of depression and a Geriatric Depression Scale – 15 (GDS-15) score < 2 (n=12); subthreshold depression was defined as no SCID-I diagnosis of depression and a score of 2 or more on the GDS-15 (n=25); and clinical depression was defined a SCID-I diagnosis of major or minor depression (n=17).
Post-hoc exclusion criteria excluded 11 participants on the basis of biological factors (for example, a history of neurological disease or left handedness); 4 participants were excluded due to having fewer than 20 (out of a possible 60) artifact-free ERP trials ; and finally, data from 4 participants was removed at the data cleaning stage due to being classified as outliers. Following these exclusions, a total of 54 participants were included in the final analysis.
A diagnosis of major or minor depression was made using a semi-structured clinical interview schedule which is based on criteria outlined for Axis I disorders in the DSM-IV-TR . This tool is considered the gold-standard for diagnosis of mental illness and has been extensively used in both clinical and research settings . In terms of validity, the SCID-I has been shown to be superior to standard clinical interviews .
Depressive symptoms were assessed using the 15-item Geriatric Depression Scale [24,25], (GDS-15), which is the most widely used screening measure for depression among the elderly . This test utilizes a dichotomous response format whereby participants are required to respond with a ‘yes’ or ‘no’ as to whether they have experienced a given symptom in the two weeks prior to assessment. One-point is scored for each item in which a symptom is endorsed, with higher scores indicative of a greater likelihood of a depressive illness. Examples of items included are “Have you dropped many of your activities and interests?”, “Do you feel that your life is empty?” and “Do you experience any feelings of worthlessness right now?”
General cognition was measured using the Standardized Mini-Mental State Examination [26,27] (SMMSE), which is a variation of the widely used original MMSE cognitive screening test. It comprises the same 30 items included in the MMSE which broadly assess orientation, attention and calculation, immediate and short-term recall, language and the ability to follow basic written and verbal commands. The standardized version of the MMSE provides expanded guidelines for administration (such as time limits for responding) and scoring (such as stricter guidelines for scoring near misses on items). The use of the expanded guidelines has been shown to improve reliability (0.69 for the original MMSE versus 0.90 for the standardized version) , and decrease testing time relative to the original version of the MMSE.
Electroencephalogram (EEG) testing was conducted with the use of a portable 40-channel NuAmps amplifier and Scan 4.3 Acquisition software was used to acquire EEG data in a single continuous file from which P200 and P300 ERP data were later extracted offline. In accordance with the NuAmps International 10-20 system, scalp EEG was recorded from 16 lateral, homologous pairs of electrodes (FP1/2, F7/8, F3/4, FC3/4, T3/4, C3/4, CP3/4, T5/6, P3/4, O1/2) and 6 midline electrodes (Fz, FCz, Cz, CPz, Pz, Oz) using a QuikCap with sintered Ag/AgCl electrodes and a linked ears (A1, A2) reference. Electrodes at supra- and infra-orbital sites surrounding the left eye were used to record blinks and vertical eye movements (bipolar), and right and left outer canthi electrodes were used to monitor horizontal eye movements (bipolar). Impedances were generally maintained below 5 kΩ .
ERPs were elicited using the classic two-tone auditory oddball paradigm (Kemp et al., 2009). In this task participants were presented with a series of ‘non-target’ or standard tones (500Hz) that are randomly interspersed with ‘target tones’ (1000Hz). Target probability was set at approximately 20%, consistent with past research [18,29]. As such, there were a total of 280 non-target tones and 60 target tones, with each tone lasting a total of 50ms, and an inter-stimulus interval of one second. Tones were set at a comfortable sound pressure level.
The Compumedics Neuroscan EDIT program version 4.4 was used to filter raw EEG data using a low pass, zero-phase shift filter set at 30Hz (24dB). Electrooculogram (EOG) corrections were conducted offline whereby a positive threshold of 10%, with a minimum of 20 sweeps and duration of 400ms, was applied to the data with the vertical EOG labelled as the blink channel. Epochs from -200 to 700ms were created and any that were found to overlap rejected blocks were discarded at this stage. Baseline correction was applied for all electrodes, with artefacts with voltages in excess of +/-100µVs rejected.
Upon completion of data extraction and correction procedures, P200 and P300 ERP data were extracted from EEG recordings. A single averaged waveform associated with target and non-target stimuli was extracted for each recording site using the Average procedure in Scan 4.4. Peaks were then identified using the Peak Detection procedure with the peak window set at 140-270ms for the P200 and 270 ms to 550 ms for the P300 (relative to the stimulus onset) .
Testing was conducted in private and participants were comfortably seated directly in front of a laptop used to present the auditory stimulus. The distance from the participant’s nasion to the inion was measured and the EEG QuikCap was then placed on the participants head so that the FP1 electrode was positioned approximately 10% of this distance. A water-based gel was injected into each electrode site using a blunt syringe.
Following set-up, the oddball task was explained to the participant and they completed a one-minute practice trial. Participants were instructed to ignore the non-target tones and to respond to the target tones by pressing a labelled button on the laptop directly in front of them. A small cross appeared on the laptop screen and participants were instructed to focus on this during trials to minimize eye movements. Following the practice session, participants completed four oddball trials, each lasting a total of two minutes, with two minute resting trials (eyes open and eyes closed) interspersed between each oddball trial, yielding a total EEG testing time of approximately 16 minutes.
Participant demographic and affective indices are presented in Table 1.
As can be seen in Table 1, there were no significant differences in the ratio of males to females, age, medication usage, caffeine consumption, total years of education and SMMSE scores across the three participant groups. As expected, participants with no depression, subthreshold depression and clinical depression each differed significantly on the GDS-15.
ERP Behavioural data
The means and standard deviations for reaction time and accuracy of participants in identifying the target odd-ball tones when eliciting the ERPs are presented in Table 2.
Table 2 reveals that participants with no depression responded faster to the target tones on the oddball task compared to participants with depression. A similar level of accuracy was achieved by all groups identifying the target tones. ANCOVAs with anti-depressant medication (ADM) and central nervous system medication (CNSM) held constant revealed no significant differences in reaction time or accuracy between groups. Grand average event-related potentials for P300 at the Pz site are provided in Figure 1 to illustrate the different wave forms elicited for the non-target and target tones for non-depressed (n = 12), subthreshold (n=25) and clinically depressed (n=17) groups.
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