Using a standard waking auditory oddball task pre-and post-sleep, this study replicated previous findings by Hulse et al. (13
) with a separate group of healthy individuals, showing that auditory evoked potential (AEP) N1 and P2 amplitudes decline after a night of sleep and that the overnight change in N1 amplitude is proportional to the amount of slow wave activity (SWA) from that night. When applying the same technique to a group of participants with major depressive disorder (MDD), however, neither a comparable overnight decline in N1 or P2 amplitude, nor a relationship between overnight AEP amplitude change and SWA was observed.
According to PSG variables from the experimental night, MDD and HC groups showed comparable sleep profiles. The elevated arousal index and REM sleep amount in MDD compared to HC are consistent with previous studies (1
). Despite these differences, none of the PSG variables correlated with the overnight change in AEP amplitude, suggesting that overall sleep architecture was not differentially impacting the AEP results across groups.
Varying states of vigilance or attention, such as sleep inertia experienced in the morning after awakening (32
), could have impacted AEP amplitude or latency, but all participants were given sufficient time in the morning before beginning the tasks (19
), supported by equivalent PVT and AEP latency values pre-vs. post-sleep and between groups (21
). Moreover, PVT values did not correlate with pre-or post-sleep AEP amplitude values. Studies have also demonstrated an impact of antidepressant medication on auditory processing in animals and humans (35
). Because MDD participants were free of pharmacological treatment for at least 6 months prior to the study, it is unlikely that antidepressant medication biased the results observed in this study. In addition, although the MDD group included two more females than the HC group, no differences were observed in terms of overnight change in AEP amplitude when conducting stratified analyses. However, because prior literature has suggested SWA in MDD may be different in women versus men (11
), sex-related effects on homeostatic processes, including overnight change in AEP, may be an important area of future investigation.
Previous literature regarding baseline comparisons of AEP N1 and P2 components between MDD and healthy controls has yielded conflicting results. Increased N1 latency and amplitude (39
), and decreased P2 amplitude have been demonstrated (39
), whereas other studies have shown no difference in N1 amplitude and increased P2 amplitude (41
). It is possible that unmeasured factors such as time of day of the recordings, which may affect both circadian and/or homeostatic processes (43
), influenced the observed AEP amplitude and latency in previous studies. For example, Kerkhof and colleagues (45
) previously demonstrated that morning-type individuals had greater N1-P2 amplitude overall compared to evening-types, suggesting that intrinsic circadian preference may affect AEP amplitude. Although AEP recordings and sleep times were similar between MDD and HC groups in this investigation, circadian phase was not rigorously measured in our study design, and thus differential circadian modulation of AEP amplitude between groups could potentially explain the observed difference in pre-to post-sleep amplitude changes. However, bed times and waking times, as well as time of administering the oddball task did not significantly differ between groups. To clarify the degree to which circadian and homeostatic factors contribute to overnight changes in AEP amplitude, the use of constant routine and/or forced desynchrony protocols may be beneficial in future research.
This study replicates previous work (13
) demonstrating the overnight decline in N1 amplitude correlates with SWA in healthy controls, which suggests that this AEP measure reflects a sleep homeostatic process. However, it is noteworthy that in this study, MDD and HC had similar SWA values, both all-night and across NREM episodes, despite lack of overnight decline in N1 amplitude in the MDD group. Because SWA has been widely used as a measure of sleep homeostasis (6
), one might expect alterations in sleep homeostasis to be reflected by different SWA values between HC and MDD groups. However, our results of similar SWA values between HC and MDD groups are not dissimilar with other reports that have failed to demonstrate significant differences in baseline SWA in MDD relative to healthy subjects (12
). In addition, SWA in MDD is moderated by effects of age and sex (11
), and thus the lack of difference in SWA between HC and MDD groups in this study may have been due to the narrow age range of participants, different sex distributions, and/or inadequate power to detect such differences between groups. An alternative hypothesis for our findings would be that SWA may be present, but dysfunctional in MDD, which could explain the lack of relationship between overnight change in N1 amplitude and SWA for the MDD group. In this case, overnight change in AEP amplitude could be a more sensitive measure for or reflect a different aspect of sleep homeostasis in MDD that is not fully captured by SWA. To more critically examine the homeostatic nature of AEP amplitude and its relationship to SWA, future studies would benefit from delivering a challenge to normal sleep, such as sleep delay or restriction protocols (12
), in both MDD and control samples.
Several studies have linked both AEP N1 and P2 components with central auditory plasticity (49
). In the present study, a greater decline in N1, but not P2, amplitude was associated with greater SWA from that night in healthy controls. In accordance with previous literature (13
), it is likely that the N1 and P2 components involve separate processes, especially when considering their relationship to sleep. Given that sleep SWA has also been linked to synaptic plasticity (8
), and MDD may involve deficiencies in plastic processes (56
), it is possible that the present findings, particularly involving the AEP N1 component, reflect alterations in sleep-regulated synaptic plasticity in MDD.
This study was designed to be an initial investigation of the overnight change in AEP amplitude in a broad sample of unipolar, non-psychotic MDD participants. Given the heterogeneous nature of MDD (59
), we investigated the pattern of overnight AEP change in the subgroup of MDD individuals with comorbid anxiety. However, when comparing this subgroup with the entire MDD sample, similar patterns were observed, suggesting that the alterations in the overnight change in AEP were likely related to the primary diagnosis of MDD, rather than comorbid disorders. Furthermore, although no correlations between HRSD-17 scores and AEP values were found in this study, it is possible that global severity or specific symptomatology, such as suicidality, may play a role in sleep-related regulation of auditory processing in MDD (42
). Thus, examination of overnight changes in AEP amplitude in more severe MDD participants without comorbidity may further clarify the relationship between homeostatic regulation of AEP components and MDD.
Along with sleep and spontaneous waking EEG measures of homeostatic processes (3
), waking AEP techniques have been shown to predict response to therapeutic sleep deprivation (64
), and, particularly when measuring the loudness-dependence of the AEP (LDAEP), response to pharmacotherapy (66
). Given the robust findings of research using LDAEP measures, in combination with the results of the present study, it would be intriguing to examine whether overnight changes in the LDAEP could further reveal MDD subgroups of diagnostic or prognostic value.