Research paperDoors P300 moderates the relationship between reward positivity and current depression status in adults
Introduction
Depressive disorders are common and associated with impairments in occupational functioning (i.e., workdays lost), psychosocial functioning, and increasing risk for suicide (Lépine, and Briley, 2011). Dysfunctions in both reward (i.e., hyposensitivity to reward) and basic cognitive processes (e.g., indecision, memory deficits, attention and concentration difficulties) are implicated in the etiology of depressive disorders (Whitton et al., 2015; Treadway and Zald, 2011; Clark et al., 2009; Roiser et al., 2009). Currently, there is limited knowledge regarding whether these deficits reflect distinct or overlapping pathophysiological mechanisms—and utilization of reliable neural markers might provide important insight into the relationship between reward and cognitive dysfunctions in depression.
Event-related potentials (ERPs), recorded via electroencephalogram (EEG), are cost-effective and direct measures of brain activity that can be utilized for clinical research, including the identification of risk and the prediction of mental health outcomes (Hajcak et al., 2019; Proudfit, 2015). Previous ERP research investigating individual differences in reward processing has focused on the reward positivity (RewP), which is a positive component that typically peaks between 250 and 350 ms at frontal-central electrode sites (i.e., FCz) following presentation of gain compared to loss feedback in guessing tasks. Specifically, in the doors task, participants are presented with two identical doors and are told to select either door in order to win or lose money (Proudfit, 2015). Reduced RewP amplitudes have been found in adults with depression (e.g., Keren et al., 2018; Brush et al., 2018; Carlson et al., 2011; Liu et al., 2014; (Klawohn et al., 2020b), and to prospectively predict onset of depressive disorders and course of depression in younger samples (Bress et al., 2013; Nelson et al., 2018). Overall, this line of research suggests that reductions in RewP amplitude are associated with deficits in reward processing that are central to the etiology of depressive disorders (Satterthwaite et al., 2015; Pizzagalli et al., 2005; Pizzagalli et al., 2009; Treadway and Zald, 2011; Whitton et al., 2015).
A separate line of research has examined cognitive functioning utilizing the P300 component. The P300 is a positive-going ERP that arises approximately 300 ms after stimulus presentation and is thought to reflect processes such as attentional allocation, evaluative processing, memory and context updating (Polich, 2012; Hajcak and Foti, 2020). P300 amplitude has frequently been found to be reduced among adults with depression (Bruder et al., 2012; Zhou et al., 2019; Bruder et al., 2009; Gangadhar et al., 1993; Nan et al., 2018; Roschke and Wagner, 2003; Urretavizcaya et al., 2003; (Klawohn et al., 2020c), and has been shown to predict increases in depressive symptoms across different populations, including adults with clinical depression (Santopetro et al., 2021) and female adolescents (Santopetro et al., 2020). Previous research would suggest that deficits in P300 amplitude reflect general impairments in processing salient target stimuli, which is in line with broader cognitive impairments common in depressive disorders (Clark et al., 2009; Roiser et al., 2009; Bruder et al., 2012; American Psychiatric Association, 2013).
Although the RewP has consistently been observed as a neural correlate of depression using the doors task (e.g., Proudfit, 2015), there is a limited understanding of whether the P300 elicited from the doors task might relate to depression. Insofar as salient stimuli elicit a P300 (Hajcak and Foti, 2020), there are two possible ways to examine the P300 within guessing paradigms, such as the doors task. First, it is possible to examine feedback-locked P300s (i.e., to gain and loss feedback) in relation to depression. However, past studies have reported inconsistent results regarding the relationship between depression and outcome-locked P300s in guessing tasks (Chang et al., 2020; Thoma et al., 2015; Foti and Hajcak, 2009). Second, given that the presentation of the doors are an imperative stimulus on each trial that requires a response, it is possible that the doors-locked P300 could be examined in relation to depression.
Indeed, the most robust relationships between P300 and depression are observed when utilizing visual oddball tasks in which visual stimuli require a response (e.g., button press or counting; Bruder et al., 2012; Kropotov, 2009). Thus, the current study sought to investigate the possibility that depression might be related to the doors-locked, but not the feedback-locked, P300. Furthermore, considering that reduced P300 in depression has been related to higher levels of anhedonia (e.g., Ancy et al., 1996; Urretavizcaya et al., 2003; Gangadhar et al., 1993), suicidal behaviors (e.g., Hansenne et al., 1996), psychotic symptoms (e.g., Karaaslan et al., 2003; Kaustio et al., 2002) and severity of depressive symptoms (e.g., Nan et al., 2018)—a secondary goal was to examine more specific correlations between P300 and depressive symptoms. An additional goal of the current study was to examine whether the RewP and P300 index overlapping or unique variance in depression; that is, if the RewP and P300 could be utilized in tandem to better differentiate depression. To date, the RewP and P300 have been studied in isolation, so it is unclear whether deficits in reward processing and cognitive function might co-occur, or interact, to explain individual differences in depression.
In the current study, we examined the relationship between clinical depression and multiple P300 components (i.e., doors presentation, gain and loss feedback) elicited from the doors task. We also examined relationships between the P300s and specific depressive symptoms (i.e., anhedonia, cognitive, and somatic symptoms) among adults with current depression. Because we have previously reported a reduced RewP among depressed individuals in this sample (see (Klawohn et al., 2020b), we then sought to investigate whether utilizing a combination of RewP and P300 would explain additional variance in current depression diagnoses.
Based on previous research that has found a reduced P300 in depression using tasks that require a response (see Bruder et al., 2012 for a review), we hypothesized that only the doors P300 would be reduced in depression. Given the mixed findings of previous studies (e.g., Ancy et al., 1996; Gangadhar et al., 1993; Urretavizcaya et al., 2003; Karaaslan et al., 2003; Kaustio et al., 2002; Hansenne et al., 1996; Nan et al., 2018; Santopetro et al., 2021), we had no specific a priori hypotheses related to whether any of these P300s would relate to specific symptoms of depression. Finally, based on previous research that finds reduced RewP and P300s in depression (e.g., Brush et al., 2018; Carlson et al., 2011; Liu et al., 2014; (Klawohn et al., 2020b, Klawohn et al., 2020c) ; Zhou et al., 2019; Bruder et al., 2009); we predicted that using both RewP and P300s from the doors task would explain more variance in depression compared to using either ERP alone; we had no specific hypothesis regarding whether RewP and doors P300 would interact to predict depression.
Section snippets
Participants
Participants were recruited from the Tallahassee, Florida, USA community via online advertisements (i.e., Facebook), word of mouth, and through the Florida State University (FSU) psychology clinic. Participants were included in the DEP group if they met diagnostic criteria for a current depressive disorder (i.e., major depressive episode [MDE] and/or persistent depressive disorder [PDD]) and had a Beck Depression Inventory, Second Edition (BDI-II; Beck et al., 1996) total score of 13 or higher.
Clinical interviews
Presence of current and lifetime mood disorders was assessed using the Structured Clinical Interview for DSM-5 (SCID-5-RV; First et al., 2015) by two clinical psychologists. To decrease the total duration of the clinical interviews, other current and lifetime psychopathology was evaluated using the Mini-International Neuropsychiatric Interview (M.I.N.I.; Sheehan et al., 1998), updated for DSM-5 (version 7.0.2, Sheehan, 2016). Both the SCID and M.I.N.I. are highly reliable structured interviews
Doors task
The doors task was administered using Presentation software (Neurobehavioral Systems, Albany, California) and consisted of three, 20 trial blocks (60 trials total), with each trial beginning with the presentation of two identical images of doors. Participants were instructed to select the left or right door by clicking the left or right mouse button, respectively. Participants were informed that they could win $0.50 or lose $0.25 on each trial, and that they would be paid their total winnings
Demographic & clinical results
There were no differences between the HC and DEP groups in terms of age, gender, education, or ethnic composition (Table 1). The DEP group consisted of 40 (50%) participants that met criteria for a current MDE, 4 (5%) that met for current PDD, and the remaining 36 (45%) had met criteria for both current MDE and PDD. In the DEP group, 42 individuals (52.5%) were currently taking psychotropic medication (antidepressants: n = 36; anxiolytics: n = 14; anticonvulsants: n = 7; stimulants: n = 5;
Discussion
In the present study, we first examined the doors and feedback-locked P300 from the doors guessing task in relation to current depression status. Consistent with past P300 research reporting reduced P300 amplitudes among individuals with current depressive disorders or heightened depressive symptoms using oddball and flankers tasks (e.g., Zhou et al., 2019; Bruder et al., 2009; Gangadhar et al., 1993; Nan et al., 2018; Roschke and Wagner, 2003; Urretavizcaya et al., 2003; (Klawohn et al., 2020c
Declaration of Competing Interest
none.
Data statement
Data or other materials are available through correspondence with the author.
Authorship contribution statement
Nicholas Santopetro: conceptualization, statistical analysis, writing- original draft. C.J. Brush: conceptualization, statistical analysis, review, and editing. Kreshnik Burani: conceptualization, review, and editing. Alec Bruchnak: conceptualization, review, and editing. Greg Hajcak: supervision, conceptualization, review, and editing. All authors have read and approve of the final version of the manuscript.
Declaration of interests
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgments
The authors wish to thank Dr. Kristen Schmidt and Dr. Julia Klawohn for contributing their clinical expertise.
Funding
Portions of this study were funded by Google LLC. Kreshnik Burani was supported by the National Institutes Health under grant 5T32 MH093311-09. The funding sources had no influence on study conduction or result evaluation.
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2022, Journal of Affective DisordersCitation Excerpt :Reduced P300 amplitude has frequently been found as a neural characteristic of adults with current depression compared to controls with no depression (Bruder et al., 2012; Zhou et al., 2019; Bruder et al., 2009; Gangadhar et al., 1993; Nan et al., 2018; Roschke and Wagner, 2003; Urretavizcaya et al., 2003, Klawohn et al., 2020; Santopetro et al., 2021a,b; White et al., 2021). Furthermore, P300 amplitude demonstrates predictive utility within depression: smaller baseline P300 amplitude predicts increases in depressive symptoms over nine months among adults with clinical depression (Santopetro et al., 2021a,b; see also, Santopetro et al., 2020). In sum, previous literature suggests that depression, and poorer course of depression, is characterized by reduced P300 amplitude – in line with broader cognitive deficits common in depressive disorders (Clark et al., 2009; Roiser et al., 2009; Bruder et al., 2012; American Psychiatric Association, 2013).
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