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Reward functioning in PTSD: A systematic review exploring the mechanisms underlying anhedonia
Accepted Manuscript Title: REWARD FUNCTIONING IN PTSD: A SYSTEMATIC REVIEW EXPLORING THE MECHANISMS UNDERLYING ANHEDONIA Author: Laura Nawijn Mirjam van Zuiden Jessie L. Frijling Saskia B. Koch Dick J. Veltman Miranda Olff PII: DOI: Reference:
S0149-7634(15)00030-5 http://dx.doi.org/doi:10.1016/j.neubiorev.2015.01.019 NBR 2126
To appear in: Received date: Revised date: Accepted date:
3-9-2014 20-1-2015 21-1-2015
Please cite this article as: NAWIJN, L., van Zuiden, M., Frijling, J.L., Koch, S.B., Veltman, D.J., Olff, M.,REWARD FUNCTIONING IN PTSD: A SYSTEMATIC REVIEW EXPLORING THE MECHANISMS UNDERLYING ANHEDONIA, Neuroscience and Biobehavioral Reviews (2015), http://dx.doi.org/10.1016/j.neubiorev.2015.01.019 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
HIGHLIGHTS Anhedonia in PTSD may result from deficits in reward functioning Results of this systematic review suggest reduced reward functioning in PTSD
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Reduced reward functioning seems more prevalent in female PTSD patients Reduced reward functioning is most clearly present in response to social stimuli
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Reward functioning should receive more attention in PTSD research
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REWARD FUNCTIONING IN PTSD: A SYSTEMATIC REVIEW EXPLORING THE MECHANISMS UNDERLYING ANHEDONIA
a,c
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Miranda Olff
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LAURA NAWIJN*,a, Mirjam van Zuiden a, Jessie L. Frijling a, Saskia B. Koch a, Dick J. Veltman b,
a. Department of Psychiatry, Academic Medical Center, University of Amsterdam, PO box 22660,
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1100 DD, Amsterdam, The Netherlands
b. Department of Psychiatry, VU University Medical Center, PO box 7057, 1007 MB, Amsterdam,
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The Netherlands
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c. Arq Psychotrauma Expert Group, Nienoord 5, 1112 XE, Diemen, The Netherlands
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[email protected]
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* Corresponding author: Tel: +31-20 89 13 667, Fax: +31-20 89 13 701, E-mail:
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ABSTRACT
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LAURA NAWIJN, Mirjam van Zuiden, Jessie L. Frijling, Saskia B. Koch, Dick J. Veltman,
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Miranda Olff
Reward functioning in PTSD: A systematic review exploring the mechanisms underlying
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NEUROSCI BIOBEHAV REV xxx (2015) xxx-xxx
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anhedonia.
Post-traumatic stress disorder (PTSD) is a debilitating psychiatric disorder. An important
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diagnostic feature of PTSD is anhedonia, which may result from deficits in reward functioning. This has however never been studied systematically in PTSD. To determine if PTSD is
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associated with reward impairments, we conducted a systematic review of studies in which
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reward functioning was compared between PTSD patients and healthy control participants, or investigated in relation to PTSD symptom severity. A total of 29 studies were included, covering reward anticipation and approach (‘wanting’), and hedonic responses to reward (‘liking’). Overall, results were mixed, although decreased reward anticipation and approach and reduced hedonic responses were repeatedly observed in PTSD patients compared to healthy controls. Decreased reward functioning was seen more often in female than in male PTSD samples and most often in response to social positive stimuli. Though more research is needed, these findings are a first step in understanding the possible mechanisms underlying anhedonia in PTSD.
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KEYWORDS PTSD; Reward; Systematic review; Anhedonia; Trauma; Positive stimuli
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MAIN TEXT INTRODUCTION
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Post-traumatic stress disorder (PTSD) is a psychiatric disorder that can develop after experiencing a traumatic event. The lifetime prevalence of PTSD in Western countries is high (7
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to 10%) (de Vries and Olff, 2009; Kessler et al., 2012). PTSD not only severely compromises the well-being of patients and their relatives, but also represents a major economic burden on
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society. Anhedonia, or diminished interest in pleasurable activities and the inability to experience positive emotions, is a key feature of PTSD (American Psychiatric Association,
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2013) as well as several other psychiatric disorders. Anhedonic symptoms are present in about two-thirds of PTSD patients, independent of comorbid major depressive disorder (MDD);
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‘diminished interest in activities’ was endorsed by 63 to 75% of PTSD patients and ‘inability to
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experience positive emotions’ by 56 to 65% (Carmassi et al., 2014; Franklin and Zimmerman,
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2001). Anhedonic symptoms are related to adverse outcomes in PTSD such as increased chronicity, suicidality and healthcare utilization (Hassija et al., 2012). Anhedonia is thought to result from deficits in reward functioning (Der-Avakian and Markou, 2012; Treadway and Zald, 2013). Reward functioning is defined as the ability to seek out and enjoy stimuli of positive motivational valence and is associated with specific neurocircuitries. It is a crucial driving force of behavior, and can guide us towards positive and rewarding experiences in everyday life, ranging from food and sex to money and positive social interaction. Reward functioning is a multi-faceted construct and anhedonia can theoretically arise from deficits in different phases of reward functioning (Der-Avakian and Markou, 2012; Schultz, 2006). An important phase in reward functioning is reward motivation (‘wanting’), marked by anticipation and approach of reward (Berridge et al., 2009). Reward anticipation 4
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should elicit a sense of desire, and motivate to pursue a reward by carrying out the necessary goal-directed approach behavior. From a neurobiological perspective, cues signaling potential reward activate the mesocorticolimbic reward pathway by dopamine projections from the ventral
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tegmental area (VTA) to the ventral striatum and amygdala. These in turn connect to frontal brain structures such as the orbitofrontal cortex (OFC), anterior insula (AI) and anterior cingulate
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cortex (ACC), areas important for valence assessment, and to the dorsal prefrontal cortex,
important for information integration and decision making. Subsequently, approach behavior is
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initiated through dopaminergic activation of the dorsal striatum and motor cortices (Der-Avakian and Markou, 2012; Liu et al., 2011). A second phase of reward functioning is reward
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consumption (‘liking’), marked by a hedonic response and being able to enjoy a reward once it is obtained (Berridge et al., 2009). Obtaining a reward should elicit a feeling of pleasure or
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enjoyment, a hedonic positive affective response. The experience of pleasure in response to a reward is mediated in part by the same brain areas also involved in ‘wanting’, such as the
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striatum, amygdala, OFC and AI, though ‘liking’ is mainly mediated by opioid and GABA
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receptors (Der-Avakian and Markou, 2012; Liu et al., 2011). Appropriate reward functioning will
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stimulate to pursue rewards based on previous experiences and adjust one’s behavior to maximize reward collection and positive experiences from the environment. In its classic sense, anhedonia would be defined as deficits in the reward consumption phase or ‘liking’ (Ribot, 1896). However, deficits in the motivational phase or ‘wanting’ could also result in anhedonic symptoms (Treadway and Zald, 2013). To distinguish between deficits in ‘wanting’ and ‘liking’, the terms ‘motivational anhedonia’ and ‘consummatory anhedonia’ have been proposed (Der-Avakian and Markou, 2012; Treadway and Zald, 2011). To fully understand possible reward-related deficits in psychiatric disorders including PTSD it is therefore relevant to distinguish between the different phases of reward functioning. Also important to note is that a number of areas involved in ‘wanting’ and ‘liking’ of positive stimuli, such as the ventral striatum, amygdala, OFC and AI, are also involved in the processing of negative stimuli, implicating a 5
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broader role in salience processing, and approach- as well as avoidance-related behavior (Hayes et al., 2014). This dual role is important to keep in mind when assessing and interpreting neural responses to reward, such that responses to positive stimuli should be evaluated
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separately from negative stimuli. A further distinction can be made based on the type of stimuli presented. In
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schizophrenia research, a distinction is made between social anhedonia and non-social or
physical anhedonia, distinguishing responses to social positive stimuli (e.g. happy faces or
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positive social interaction) relative to non-social physical or sensory positive stimuli (e.g. pleasant smells, tastes or images) (Chapman et al., 1976). Especially social anhedonia has
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been related to more severe psychopathology, such as increased depressive and anxiety symptoms (Gooding et al., 2005; Rey et al., 2009). Social and non-social anhedonia may relate
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to distinct affective, behavioral and biological phenotypes, and it is possible that different types of rewarding stimuli are differentially affected in PTSD.
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Reward processing is a functional domain extensively investigated in psychopathology.
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In MDD for example, a disorder comorbid with PTSD in up to 50% of patients (e.g. Keane &
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Kaloupek, 1997), a recent meta-analysis showed aberrant neural reactivity in patients with MDD compared to healthy participants in differential brain areas during reward anticipation (‘wanting’) and reward consumption (‘liking’) (Zhang et al., 2013). Furthermore, increased anhedonia scores in MDD patients were associated with reduced amygdala, ACC and AI responses to positive stimuli (Henderson et al., 2014; Stuhrmann et al., 2013). Also in healthy subjects, trait anhedonia has been related to reduced subjective pleasantness ratings to positive stimuli and reduced neural responses in the ventral striatum, OFC, ACC and AI (Keller et al., 2013). These findings suggest that neural dysregulation in reward processing areas underlies anhedonic symptoms in psychiatric and non-psychiatric populations. Over the course of the last decade, a growing body of research has focused on reward functioning in PTSD. Five years ago, Stein and Paulus (2009) suggested that PTSD involves an 6
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imbalance between approach and avoidance systems (Stein and Paulus, 2009). This was based on the first reports of reward deficits in PTSD, together with findings of increased responses to negative stimuli in PTSD compared to controls. Although previous meta-analyses
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have consistently shown increased neural and behavioral sensitivity to negative stimuli in PTSD (Hayes et al., 2012a, 2012b), thus far, the available research literature on reward functioning in
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PTSD has never been reviewed. Our objective was therefore to perform a systematic review of studies investigating reward functioning in PTSD, and to address the following questions: Do
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PTSD patients have altered reward functioning compared to healthy controls, and if so: which
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specific phases of reward functioning are affected in PTSD patients?
METHODS
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For the purpose of the current review, we included all questionnaires of self-report, behavioral, physiological or neural measures of anticipatory, approach and consummatory
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responses towards positive stimuli, i.e. stimuli that are generally experienced as positive or
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rewarding. Publications were selected if responses to positive stimuli were compared between
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adults diagnosed with current PTSD and adult control participants without PTSD, or if responses to positive stimuli were correlated with PTSD symptom severity in adult participants. Other inclusion criteria were publication in peer-reviewed scientific journals in English, Dutch, German or French, and reporting results of statistical analyses. Case-studies were excluded but otherwise no limits were set to sample size. Using keywords for PTSD (e.g. posttraumatic stress disorder, posttraumatic stress symptoms, posttraumatic, stress disorder, traumatic stress, psychotrauma) and reward (e.g. reward, behavioral activation, behavioral approach, reinforcement, positive stimuli, positive picture, motivation, pleasure, pleasant, happy, hedonic), literature searches were conducted for studies published before June 2 2014 in the online literature databases PubMed, Embase, PsychINFO and PILOTS. Each publication was screened independently by two of four qualified 7
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researchers (LN, MVZ, JLF, SBK) for selection based on the inclusion criteria. Any selection discrepancies between the two researchers were discussed until consensus was reached. Of the 1185 articles found in the initial search, 29 articles were included based on the
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inclusion criteria (see table 1 for an overview). Of note, 13 neuroimaging studies were excluded because responses to positive stimuli were compared to negative stimuli, but not neutral stimuli,
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so that it could not be established if the observed results were related to differential responses
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to positive or to negative stimuli, or both (for a further discussion, see section 4.6).
RESULTS
The selected studies investigated motivational or consummatory phases of reward
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functioning, using different modalities ranging from self-report questionnaires and behavioral measurements to physiological and neuroimaging data (see table 1a for motivational studies,
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reward functioning.
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table 1b for hedonic studies). Results will be discussed separately for the different phases of
3.1
Reward motivation (‘wanting’)
3.1.1
Anticipation
One behavioral study investigated anticipation of monetary reward in PTSD patients using a Wheel-of-Fortune task (Hopper et al., 2008). This task consists of a reward anticipation and a reward consumption phase in which money can be won or lost at different probabilities (responses to reward consumption are discussed in section 3.2.1). Hopper et al (2008) found that male veteran PTSD patients reported lower expectations of winning monetary reward compared to healthy trauma-exposed controls, given the same probability of winning a reward.
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Though reduced anticipation is suggested by Hopper et al (2008), this was a relatively small study and more research is needed to confirm and extend these findings.
Approach: Questionnaires
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3.1.2
A number of studies have investigated reward approach according to the reinforcement
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sensitivity theory, which proposes that behavior is controlled by the behavioral approach system (BAS) and the behavioral inhibition system (BIS) (Gray and Mcnaughton, 2000). BAS is related
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to reward sensitivity and positive stimuli, leading to response activation and approach behavior. BIS is related to punishment sensitivity and negative stimuli, leading to response inhibition and
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avoidant behavior. In this review we focused on measurements of the BAS as a representation of reward approach.
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The BIS/BAS scale is a self-report questionnaire of BIS and BAS sensitivity (Carver and White, 1994). A study in 291 predominantly female trauma-exposed undergraduate students
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found no association between probable PTSD status and any of the BAS subscales using
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bivariate correlations (Maack et al., 2011). Dretsch et al (2013) investigated the BAS-Reward
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Responsiveness subscale in a small sample of predominantly male combat veterans with and without PTSD, but found no differences between groups (Dretsch et al., 2013). A study in 851 trauma-exposed female undergraduate students found that overall PTSD symptom severity was negatively related to BAS-reward responsiveness, a subscale measuring responses to anticipation and consumption of rewarding events, but only when accounting for experiential avoidance, i.e. the avoidance of unwanted negative feelings, thoughts or memories (Pickett et al., 2011). Also, overall PTSD symptom severity was positively related to BAS-Drive, a subscale measuring motivation to pursue rewards, when accounting for experiential avoidance. PTSD severity was not related to BAS-Fun Seeking, a subscale measuring the desire for new rewarding experiences, or total BAS score (Pickett et al., 2011).
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Contractor et al (2013) used the Sensitivity to Punishment and Sensitivity to Reward Questionnaire (SPSRQ, (Torrubia et al., 2001), a questionnaire similar to the BIS/BAS scale, measuring BAS with the Sensitivity to Reward subscale (SR). PTSD symptoms were divided
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into four clusters according to the PTSD-symptoms model of Simms et al (Simms et al., 2002); Re-experiencing, avoidance, dysphoria and hyperarousal. The dysphoria cluster consisted of
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the anhedonia symptoms from the DSM-IV avoidance cluster, taken together with irritability, sleeping and concentration problems from the DSM-IV hyperarousal symptom cluster. In a
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community sample of 306 male and female trauma-exposed primary care patients, PTSD avoidance and hyperarousal scores were positively correlated with SR, while PTSD re-
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experiencing and dysphoria scores were not correlated with SR. However, PTSD avoidance had a mediating role between SR and PTSD dysphoria, such that increased PTSD avoidance and
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increased SR were related to increased PTSD dysphoria scores, suggesting that patients with
dysphoria (Contractor et al., 2013).
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increased sensitivity to reward show more avoidance symptoms, which is related to increased
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The finding that PTSD avoidance symptoms were positively related to reward approach
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behavior suggests that reward approach may be used as a strategy for avoidance of traumarelated memories (Contractor et al., 2013). Interestingly, after controlling for the effects of experiential avoidance, reward responsiveness was negatively related to overall PTSD symptom severity (Pickett et al., 2011). Furthermore, the presence of reward seeking behavior in combination with PTSD avoidance symptoms was related to increased PTSD dysphoria symptoms, suggesting that increased reward seeking is not related to increased positive emotions (Contractor et al., 2013). This supports the hypothesis that PTSD patients use reward approach behavior as an avoidance strategy, but that actual reward responsiveness is decreased in PTSD (Contractor et al., 2013; Pickett et al., 2011). These findings exemplify the complex relationship between reward approach, avoidance behavior and PTSD.
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With regard to the use of reward approach behavior as avoidance strategy, it is interesting to note that alcohol and substance abuse are also used to avoid or numb negative emotions in PTSD (O’Hare and Sherrer, 2011). Also, previous research by Weiss et al (2012)
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suggests that the increased impulsive behavior such as risk-seeking behavior, a concept related to fun-seeking and approach behavior, that has been found in PTSD, can be explained by
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emotional dysregulation, i.e. problems with dealing with negative emotions, instead of trait
impulsivity. The suggestion that problems with emotion regulation may lead to risk-seeking and
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reward-approach behavior as a strategy to alleviate or avoid negative emotions (Weiss et al.,
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2012) fits with the findings of Pickett et al (2011) and Contractor et al. (2013).
Approach: Behavioral tasks
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Seven studies investigated approach behavior with Go-No Go or Stop-Signal tasks, two similar behavioral measures of BIS/BAS. During Go-trials, participants have to press a button as
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fast as possible, reaction speed providing a measure for BAS; during Stop- or No Go-trials
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participants have to inhibit their button-press response, targeting BIS. For this review, we
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focused on responses to Go-trials as a representation of approach behavior. The results of a number of studies investigating Go-No Go tasks show no differences in RT towards Go-trials between male veteran PTSD patients and trauma-exposed controls (Depue et al., 2014; Swick et al., 2012), nor between PTSD patients with childhood trauma, childhood trauma-exposed controls and non-trauma-exposed controls (Li et al., 2013). In line with this, PTSD symptom severity were also not related to RT during Go-trials in a group of trauma-exposed combat veterans (Amick et al., 2013). Also, using the slightly different StopSignal Anticipation Task, male veteran PTSD patients did not differ in RT from trauma- and nontrauma-exposed controls in response to go-trials (van Rooij et al., 2014a). Together, these studies indicate that BAS function in PTSD patients is similar to trauma- and non-traumaexposed controls. Similar findings were seen by Casada et al (2005, 2006) in a mixed-gender 11
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community-sample: In response to Go-trials there were no differences in reaction times (RT) between PTSD patients and trauma-exposed controls (Casada and Roache, 2005). However, PTSD patients showed a progressive slowing of RT towards Go-trials over time, compared to
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trauma-exposed controls. This may suggest that PTSD patients show increasingly stronger behavioral inhibition when learning the task, such that they would rather give up reward (correct
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response to Go-trial) to avoid punishment (incorrect response to No Go-trials), compared with controls. Another explanation may be that PTSD patients had more problems with sustained
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task-motivation, compared to controls. Furthermore, when monetary rewards were introduced for correct responses, both controls and PTSD patients showed similar acceleration of RT
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during Go-trials. However, when monetary rewards were then replaced by positive feedback again, controls would still respond as fast as if monetary reward was still given, whereas PTSD
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patients would temporarily slow down their responses. This suggests lower sustained taskmotivation for non-rewarded trials in PTSD compared to controls (Casada and Roache, 2005).
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Additionally, in the same sample PTSD patients exhibited lower increases in heart-rate (HR)
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and skin conductance (SC) in response to monetary rewarded trials compared to controls,
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reflecting reduced physiological arousal (Casada and Roache, 2006). The authors suggested that this dissociation of autonomic responses and motivational behavior in PTSD patients may reflect emotional numbing.
Elman et al (2005) investigated approach behavior towards attractive faces in male Vietnam veterans with and without PTSD (attractiveness ratings are discussed in section 3.2.3). Participants were presented with attractive and average male and female faces and could prolong or shorten presentation-times with button presses. Participants with PTSD made less button presses to prolong presentation-time of attractive female faces, compared to controls. PTSD patients and controls did not differ in approach behavior towards attractive male, or average male and female faces (Elman et al., 2005).
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Dretsch et al (2013) investigated reward approach in a group of predominantly male veterans with the Iowa Gambling Task (IGT). In the IGT, participants can win money by selecting cards from card decks with different reward probabilities and magnitudes. PTSD
suggesting normal reward sensitivity (Dretsch et al., 2013).
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patients did not differ in IGT performance compared to trauma-exposed healthy controls
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In sum, six studies employing Go-No Go type tasks consistently failed to observe
differences between PTSD patients and trauma- and non-trauma-exposed controls on approach
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behavior (Amick et al., 2013; Casada and Roache, 2005; Depue et al., 2014; Li et al., 2013; Swick et al., 2012; van Rooij et al., 2014a). As the Go-No Go task is primarily designed to
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measure response inhibition, it is possible that this task is not sensitive enough to pick up more subtle differences in approach behavior between PTSD patients and controls. Indeed, when
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approach behavior was investigated in more detail, PTSD patients showed declining approach behavior over consecutive trials, and reduced approach behavior during non-monetary
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rewarded trials compared to monetary rewarded trials (Casada and Roache, 2005). Also, the
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findings by Elman et al (2005) indicate reduced motivation to actively pursue positive stimuli.
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Together, this may suggest that reduced motivational approach behavior in PTSD only manifests itself when more effort is needed, or when the balance between effort and reward is less advantageous. This is similar to previous findings in MDD patients, who were less willing to expend effort for monetary reward compared to controls (Treadway et al., 2012). However, as the studies by Casada et al (2005) and Elman et al (2005) were both relatively small, more research is needed to confirm these findings.
3.2
Reward consumption (‘liking’) Studies investigating responses to reward consumption have been grouped according to
stimulus type.
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3.2.1
Monetary reward Hopper et al (2008) investigated responses to reward using a Wheel-of-Fortune task
(see also section 3.1.1). When receiving monetary rewards, male Vietnam veterans with PTSD
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reported less subjective satisfaction with the received rewards, compared to male Vietnam veterans without PTSD (Hopper et al., 2008). This study was the only included study that
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investigated hedonic responses to monetary reward. Reduced satisfaction is suggested, but as
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the sample size of this study was rather small, more research is needed to confirm this finding.
Positive images
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Responses towards images of positive affective scenes were investigated in four studies in male combat veterans (Amdur et al., 2000; Litz et al., 2000; van Rooij et al., 2014b; Wolf et
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al., 2009), two mixed-gender samples of war and torture survivors (Adenauer et al., 2010; Spahic-Mihajlovic, Crayton, & Neafsey, 2005) and a mixed-gender civilian trauma sample
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(Roberts et al., 2012). Six studies investigated self-reported valence (pleasant – unpleasant)
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and arousal (calming – arousing). Adenauer et al (2010) found that PTSD patients scored lower
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on pleasantness ratings of positive images compared to trauma-exposed controls, though this was present towards all images (including neutral and negative), and Spahic-Mihajlovic et al (2005) observed reduced pleasantness in female but not in male PTSD patients. However, these findings are in contrast to the lack of group differences in valence ratings in the other four studies (Amdur et al., 2000; Litz et al., 2000; Roberts et al., 2012; Wolf et al., 2009). SpahicMihajlovic et al (2005) found decreased arousal ratings of positive images in PTSD patients compared to trauma-exposed controls. Roberts et al (2012) on the other hand found increased arousal ratings to positive images in PTSD patients compared to trauma-exposed controls. Other studies found no group differences in arousal ratings of positive images (Adenauer et al., 2010; Amdur et al., 2000; Litz et al., 2000; Wolf et al., 2009).
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In several of these studies physiological responses were also measured. No group differences between male veterans with PTSD and combat- and non-combat-exposed controls were observed in HR, SC and frontalis muscle tension (“frowning”) responses when viewing
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positive images (Amdur et al., 2000). Also, Roberts et al (2012) did not observe any differences in cardiovascular responses to positive images between predominantly female civilian PTSD
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patients and controls. Litz et al (2000) found that male veterans with PTSD had a higher HR across all conditions (negative, neutral and positive images), suggesting a more general
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increase in physiological response, irrespective of image presentation. Van Rooij et al (2014) investigated neural responses to positive vs neutral images in male veterans with and without
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PTSD and non-combat-exposed controls, but did not observe any differences between PTSD patients and the control groups (van Rooij et al., 2014b).
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Although some studies show inconsistent results, the overall pattern suggests that PTSD patients and controls do not differ in self-reported arousal and valence-ratings in response to
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positive images, nor in physiological arousal or neural reactivity (Adenauer et al., 2010; Amdur
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et al., 2000; Litz et al., 2000; Roberts et al., 2012; Spahic-Mihajlovic et al., 2005; van Rooij et
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al., 2014b; Wolf et al., 2009). As three studies compared both trauma- and non-trauma-exposed controls to PTSD patients, neither trauma nor PTSD seems to affect subjective ratings, physiological or neural responses to positive pictures (Adenauer et al., 2010; Amdur et al., 2000; van Rooij et al., 2014b).
3.2.3
Positive faces
Several studies investigated subjective responses to pictures of positive faces in PTSD patients. In a sample of male veterans, Elman et al (2005) observed that attractiveness ratings of attractive and average male and female faces did not differ between male PTSD patients and trauma-exposed controls (Elman et al., 2005) (see also section 3.1.3). In another study, women with child abuse-related PTSD rated the emotional expressions of happy faces as less positive 15
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compared to healthy non-trauma-exposed controls. The PTSD patients also reported less positive feelings compared to controls when asked how they felt while watching happy faces (Steuwe et al., 2014). No group differences were seen in response to neutral faces. Since PTSD
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patients also labeled happy faces as expressing less positive emotions, the reduced positive feelings reported by PTSD patients may be due to differential labeling of emotions, and not to
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hedonic deficits. As Elman et al (2005) and Steuwe et al (2014) were the only studies looking at subjective responses to positive faces, and both had relatively small sample sizes, more
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research is needed to further elucidate these findings in PTSD patients.
Two studies investigated neurophysiological responses to happy faces using EEG. An
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EEG study in predominantly female Native Americans showed that PTSD patients had slower P3 event related potentials (ERP) in midline posterior and frontal areas in response to happy
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faces compared to trauma-exposed controls (Ehlers et al., 2006), whereas P3 amplitude did not differ between groups. As P3 ERP’s are thought to reflect attentional processing of salient
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stimuli, these findings suggest slowed processing of positive faces in PTSD patients compared
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to controls. Although this was a study with a large sample size, the majority of participants
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reported (lifetime) alcohol dependence (63%), which is known to affect P3 ERP latency (Porjesz et al., 2005) but was unfortunately not controlled for. A second EEG study in male veterans showed decreased vertex positive potentials (VPP) towards happy faces in PTSD patients compared to combat-exposed healthy controls, but not in response to neutral shapes (MacNamara et al., 2013). Decreased VPP are thought to reflect decreased initial perceptual responses originating from the fusiform gyrus (FFG). No group differences in latent positive potentials (LPP) were seen towards happy faces or neutral shapes, which are thought to reflect sustained processing of perceived salience of stimuli. Together, the reduced EEG responses to positive stimuli observed in PTSD patients suggest reduced attention to and processing of positive stimuli (Ehlers et al., 2006; MacNamara et al., 2013). 16
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Two fMRI studies explored responses to implicitly shown positive faces. In an implicit processing task positive or negative stimuli are presented very briefly or masked with a different stimulus, resulting in amygdala processing in the absence of conscious cognitive control
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(Killgore et al., 2013; Whalen et al., 1998). In a sample of male veterans overall PTSD symptom severity was not related to neural reactivity to implicit happy faces vs. neutral shapes (Herringa
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et al., 2013). In contrast, another fMRI study in a predominantly male sample showed increased amygdala responses towards implicit happy faces vs. neutral faces in PTSD patients compared
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to healthy controls, suggesting increased responsiveness towards social positive stimuli (Killgore et al., 2013). Thus, amygdala responses to implicit happy faces seem to be similar or
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increased in PTSD patients compared to controls (Herringa et al., 2013; Killgore et al., 2013). The observations of decreased FFG and increased amygdala responses in PTSD are in
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line with results from a recent meta-analysis of neuroimaging studies, showing decreased FFG and increased amygdala activity in PTSD patients compared to controls (Hayes et al., 2012a).
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Though Hayes et al (2012) included mainly studies on negative stimuli, MacNamara et al (2013)
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and Killgore et al (2013) observed a decrease in FFG and increase in amygdala responses to
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both positive and negative faces. As this effect was absent in response to neutral stimuli, these findings suggest that PTSD may be related to decreased FFG and increased amygdala responses to all emotionally salient facial stimuli, irrespective of valence. MacNamara et al (2013) suggest increased amygdala responses reflect high levels of arousal in PTSD, which may result in impaired attention and stimulus discrimination, reflected by reduced FFG responses towards salient stimuli. Recently however, Patel et al (2012) have argued that increased amygdala responses may be related to trauma-exposure and not to PTSD specific, based on a meta-analysis of neuroimaging studies (Patel et al., 2012). Decreased FFG responses were specific to PTSD though. As trauma-exposure of the control group was not reported by Killgore et al (2013), trauma-exposure might also explain the reported increases in amygdala responses in PTSD patients compared to controls. Another possible explanation has 17
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been put forward by Frewen et al (2010), who found that PTSD patients responded with more negative emotions to positive stimuli compared to controls, and that these increased negative emotions were associated with increased amygdala responses to positive stimuli. Thus, the
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PTSD-related increased amygdala responses seen by Killgore et al (2013) could also reflect a negative interpretation of positive faces, i.e. seeing them as threatening or aversive (‘negative
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affective interference’, see also paragraph 3.2.4) (Frewen et al., 2012b).
Together, these findings suggests that PTSD is related to decreased hedonic responses
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to happy faces, and decreased FFG and increased amygdala responses to emotional faces irrespective of valence. The reduced hedonic responses and increased amygdala responses
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however may (in part) be explained by trauma-exposure. As the studies discussed in this section had relatively small samples, more research is needed to extend and confirm these
Other positive stimuli
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3.2.4
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findings.
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In response to a positive odor (vanilla), male combat veterans with PTSD did not differ in
Ac ce p
pleasantness ratings or emotional responses compared to combat-exposed controls (Vermetten et al., 2007). However, it is questionable whether the vanilla smell was actually a valid positive stimulus in this study, as both PTSD and control groups rated the vanilla odor as neutral instead of pleasant. Another possibility is that trauma-exposure influences pleasantness ratings equally in both groups. Furthermore, this was a small study with eight controls and eight PTSD patients. Using fMRI, Jatzko et al (2006) investigated neural activity in response to a positively valenced video clip vs. a fixation cross in PTSD patients and non-trauma-exposed controls. PTSD patients showed increased neural reactivity in the posterior temporal, precentral gyrus and dlPFC, and decreased responses in the temporal pole (TP), FFG and parahippocampal gyrus, compared to controls (Jatzko et al., 2006). However, the sample size was small.
18
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Frewen et al (2012a) investigated self-reported positive responses to pleasurable events in female victims of childhood maltreatment with PTSD and healthy participants without childhood maltreatment or PTSD. On both the Snaith-Hamilton Pleasure Scale (SHAPS) (Snaith
ip t
et al., 1995) and Fawcett-Clark Pleasure Capacity Scale (FCPCS) (Fawcett et al., 1983) PTSD patients reported lower experience of pleasure in response to pleasurable activities, compared
cr
to controls (Frewen et al., 2012a). In a similar population, Frewen et al (2010) investigated
affective and neural responses to positive autobiographical audio-scripts compared to implicit
us
baseline activity. PTSD patients reported less positive emotions in response to audio-scripts of social and non-social positive autobiographical events compared to controls. Moreover, PTSD
an
patients showed increased negative emotions in response to positive audio-scripts, compared to controls. Also, compared to controls, PTSD patients had lower neural reactivity in the left
M
dorsomedial prefrontal cortex (dmPFC) and left TP in response to audio-scripts of positive social autobiographical events relative to implicit baseline activity. In response to audio-scripts of non-
te
insula (Frewen et al., 2010).
d
social positive autobiographical events, PTSD patients had higher neural reactivity in the left
Ac ce p
Taken together, PTSD was related to reduced TP reactivity (Frewen et al., 2010; Jatzko et al., 2006), reduced FFG reactivity (Jatzko et al., 2006; also reported by MacNamara et al., 2013), reduced dmPFC and increased insula reactivity (Frewen et al., 2010) in response to positive stimuli. As these brain areas are all important for processing of affective (social) stimuli and valence-assessment (e.g. Olson et al., 2007; Hayes et al., 2014), these findings suggest neural disturbances in affective processing of positive (social) stimuli in PTSD patients. This fits with the reduced self-reported experience of pleasure seen in PTSD patients compared to controls (Frewen et al., 2012a). However, as the studies by Jatzko et al (2006) and Frewen et al (2010, 2012a) all compared PTSD patients to non-trauma-exposed controls, trauma-exposure is a possible confounder. A recent study in victims of childhood maltreatment showed reduced dmPFC responses in response to positive words were related to childhood abuse but not 19
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psychopathology (van Harmelen et al., 2014). On the other hand, a different study by Frewen et al (2012b) reported that reduced dmPFC activity in response to a positive social audio-script was related to higher severity of the PTSD symptom ‘inability to experience positive emotions’
ip t
(Frewen et al., 2012b), suggesting that PTSD symptoms do play a role in the altered dmPFC responses. In the same study, increased insula responses were related to decreased positive
cr
affect in response to positive stimuli within PTSD patients. This notion is supported by an extensive neuroimaging meta-analysis, showing decreased dmPFC and increased insula
us
activity in PTSD patients compared to both trauma- and non-trauma-exposed controls (Patel et al., 2012). As the studies included by Patel et al (2012) mainly investigated responses to
an
negative stimuli, these aberrant dmPFC and insula responses in PTSD patients seem to occur to both positive and negative stimuli, irrespective of valence.
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An interesting notion was put forward by Frewen and colleagues (2010; 2012b), who showed that PTSD patients did not only report reduced positive emotions such as happiness
d
and pleasure, but also increased negative emotions such as fear and shame, in response to
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positive stimuli. This process was labeled as ‘negative affective interference’ by the authors, and
Ac ce p
suggests that PTSD patients, in particular victims of severe interpersonal or childhood trauma, may perceive positive stimuli as threatening or aversive. Both reduced positive and increased negative emotions were related with PTSD anhedonia severity. Furthermore, negative emotional responses to positive stimuli were associated with increased amygdala responses. This hypothesis should be considered when interpreting aberrant responses to positive stimuli, as decreased positive and increased negative emotional responses might result in similar behavioral outcomes (e.g. reduced approach) but arise from distinct psychological and neurobiological mechanisms (Frewen et al., 2010; 2012a; 2012b). Taken together, the studies by Jatzko et al (2006) and Frewen et al (2010, 2012a) suggest reduced hedonic responses and altered neural responses to positive stimuli in PTSD
20
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patients. Still, more research is needed to say whether these deficits are specific to PTSD, specific to trauma-exposure or the result of a combination of both.
DISCUSSION
ip t
4
The broad concept of reward functioning is reflected by the diversity of experiments and
cr
processes described in the 29 articles selected for this systematic review. Although findings are not wholly consistent, there seems to be a tendency towards both reduced motivational
us
(‘wanting’) and reduced consummatory (‘liking’) reward functioning in PTSD patients compared to healthy controls (see figure 1).
an
Given the PTSD symptom ‘diminished interest in pleasurable activities’, we expected PTSD to be related to motivational anhedonia, or reduced reward anticipation and approach
M
(‘wanting’). With regard to this phase of reward functioning, findings suggest that PTSD is related to specific deficits in reward anticipation and motivation; i.e. behavioural approach is
d
reduced when more effort is needed to pursue reward (Casada and Roache, 2005; Elman et al.,
te
2005). Furthermore, PTSD symptom severity was related to reduced self-reported BAS reward
Ac ce p
responsiveness, though only after controlling for the effects of experiential avoidance (Pickett et al., 2011). Interestingly, despite reduced reward responsiveness, reward-seeking behavior may be increased in PTSD, functioning as an avoidance strategy (Contractor et al., 2013; Pickett et al., 2011).
Based on the PTSD symptom ‘inability to experience positive emotions’, we expected PTSD to be related to consummatory anhedonia, or reduced hedonic responses to positive stimuli (‘liking’). With regard to this phase of reward functioning, converging evidence suggests that arousal and valence ratings of positive images are not affected in PTSD patients compared to controls, nor are physiological or neural responses to positive images (Adenauer et al., 2010; Amdur et al., 2000; Litz et al., 2000; Roberts et al., 2012; Spahic-Mihajlovic et al., 2005; van Rooij et al., 2014b; Wolf et al., 2009). However, PTSD patients did report reduced experience of 21
Page 21 of 44
pleasure and positive emotions in response to positive stimuli (Frewen et al., 2010; Frewen et al., 2012a; Steuwe et al., 2014). Furthermore, neural responses to positive stimuli seem to be reduced in PTSD patients in the FFG, TP and dmPFC compared to controls (Ehlers et al., 2006;
ip t
Frewen et al., 2010; Jatzko et al., 2006; MacNamara et al., 2013), whereas responses in the insula and possibly the amygdala are increased in PTSD patients (Frewen et al., 2010; Killgore
cr
et al., 2013), suggesting both increased and decreased processing of positive stimuli in different brain areas important for processing of affective stimuli, valence-assessment and emotion
an
4.2
us
regulation.
Neurobiology
Seeing the strong neurobiological basis of reward functioning, the observed deficits in
M
reward motivation and consumption in PTSD may well be explained by alterations in the reward pathway in the brain. Previous research has shown increased dopamine transporter (DAT)
d
availability in the striatum in PTSD patients (Hoexter et al., 2012). Increased DAT availability is
te
suggested to result in hyposensitivity to reward by lowering dopaminergic transmission. Striatal
Ac ce p
responses to reward have previously been related to resilience to trauma-exposure. Vythilingam et al (2009) showed that resilient trauma-exposed male veterans had lower ventral striatal responses to reward compared to non-trauma-exposed civilians (Vythilingam et al., 2009). Therefore, these authors suggested that dampened striatal responses are a sign of resilience, though striatal reward numbing may also well be the result of trauma-exposure. In opposition of the first explanation, a recent fMRI study in 200 civilian participants showed that high ventral striatal responses to positive feedback were related to resilience to the effect of life stress on positive affect (Nikolova et al., 2012). In line with the latter explanation, prolonged stress exposure is known to reduce striatal dopamine responses to reward (e.g. Pizzagalli, 2014). However, results from several studies included in this review suggest trauma-exposure in itself does not explain the observed reduced reward functioning in PTSD patients. It is possible that 22
Page 22 of 44
trauma-exposure reduces striatal responses to reward but that these effects are most strongly present in patients with PTSD. Indeed, this hypothesis is seemingly supported by three excluded fMRI studies, which showed that compared to trauma-exposed controls, PTSD was
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related to decreased striatal responses to reward outcomes, relative to loss (Admon et al., 2013; Elman et al., 2009; Sailer et al., 2008). Furthermore, this PTSD-related decrease in striatal
cr
responses to reward, as measured after deployment, was not present during measurements prior to deployment (Admon et al., 2013). Interestingly, striatal responses to reward relative to
us
loss were negatively related to anhedonic PTSD symptom severity (Elman et al., 2009).
are difficult to make based on these studies.
an
However, due to the comparison of reward vs, loss, conclusions on reward-specific alterations
The studies that did compare positive relative to neutral stimuli found reduced FFG, TP
M
and dmPFC responses and increased AI and amygdala responses to positive stimuli in PTSD patients compared to controls (Ehlers et al., 2006; Frewen et al., 2010; Jatzko et al., 2006;
d
Killgore et al., 2013; MacNamara et al., 2013). Interestingly, the majority of these studies used
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social positive stimuli. Indeed, the FFG and TP are important in detecting and processing of
Ac ce p
salient social stimuli, and the dmPFC is involved in reward evaluation and social emotional processing, together suggesting reduced social reward processing. This is in line with previous findings of reduced FFG and dmPFC responses in social anhedonia (Germine et al., 2011), but in contrast with meta-analysis findings of increased FFG responses to positive (social) stimuli in MDD (Zhang et al., 2013). Increased AI and amygdala responses to positive stimuli might reflect decreased positive or increased negative emotional responses to positive stimuli in PTSD patients (Frewen et al., 2012a). The fact that especially in studies investigating social stimuli, such as happy or attractive faces or positive social interactions, dysfunctional reward functioning in PTSD patients were reported, may indicate that PTSD is specifically related to social anhedonia. This fits in with significant social deficits seen in PTSD, such as social isolation and feelings of detachment and 23
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estrangement (American Psychiatric Association, 2013). However, reduced reward functioning was also observed in the few studies in which responses to monetary reward were investigated, suggesting it is not only social reward functioning that is affected. More research is needed to
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systematically compare responses to social vs. non-social stimuli in PTSD. Taken together, reduced reward motivation and reduced hedonic responses to reward in
cr
PTSD are possibly coupled with hyporesponsiveness of the striatum and of PFC regions
important in (social) reward functioning. PTSD patients may be more sensitive to trauma- or
us
stress-induced reduction of dopamine signaling in the striatum, specifically in response to social stimuli. Studies including both trauma- and non-trauma-exposed controls are needed to
4.3
M
an
disentangle the effects of trauma and PTSD on reward functioning.
The role of sex
d
Sex (or gender) is known to affect PTSD prevalence, with women showing two to three times higher rates (Olff et al., 2007; Tolin and Foa, 2006). Furthermore, anhedonic symptoms
te
may be more prevalent in female PTSD patients compared to male PTSD patients: the PTSD
Ac ce p
symptom ‘diminished interest in pleasurable activities’ was reported significantly more often in female patients (81%) than in male patients (65%), although no sex-differences were seen in symptom prevalence of ‘inability to experience positive emotions’ (Carmassi et al., 2014). However, little research has focused on whether this sex difference is related to differences in reward functioning. In the current review, PTSD-related decreases in reward functioning were found primarily in studies with mixed-gender or predominantly female samples, whereas null findings seem to be found more often in male samples. This may suggest that PTSD-related differences in reward functioning are moderated by sex. Of the studies currently published only Spahic-Mihajlovic et al (2005) addressed sex differences. They observed reward deficits in females but not in males, but as female PTSD patients had higher PTSD symptom severity
24
Page 24 of 44
scores than men, more research is needed to confirm whether sex-specific effects are indeed present. Sex differences in reward functioning have been studied extensively in healthy
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individuals. Although a meta-analysis of reward questionnaire studies showed men and women do not differ in sensitivity to reward, women were found to be more sensitive to negative events
cr
(Cross et al., 2011). On a neural and behavioral level however, sex differences in reward functioning have been shown. For example, men showed stronger striatal responses in
us
anticipation of money compared to women, whereas women responded stronger to anticipation of social reward (Spreckelmeyer et al., 2009). Research suggests that men may have stronger
an
prefrontal emotional and cognitive regulation (OFC, dlPFC) during reward tasks compared to women (van den Bos et al., 2013a). Stress may further enhance these sex differences: several
M
studies reported increased reward sensitivity and approach under stress in men, whereas in women, decreased reward sensitivity and approach were observed under stress (e.g. Lighthall
d
et al., 2012; Lighthall, Mather, & Gorlick, 2009), although opposite effects have also been
te
observed (Preston et al., 2007). These sex differences in reward functioning under stress may
Ac ce p
be mediated by differential cortisol and dopamine responses under stress (Trainor, 2011; van den Bos et al., 2013b). Thus, sex differences in reward functioning may increase after traumaexposure and lead to a stronger imbalance in sensitivity towards negative and positive stimuli in women compared to men, such that men will have a stronger focus on reward approach, whereas women will focus more on loss avoidance. Olff et al (2007) suggested several factors to explain sex differences in PTSD that may also explain PTSD-related differences in reward functioning between male and female samples. Compared to men, women more frequently experience sexual trauma and are typically exposed at a younger age, leading to a higher chance of developing PTSD and higher PTSD severity compared to men (Olff et al., 2007; Tolin and Foa, 2006). Indeed, a number of studies included in this review with all female samples investigated women with childhood abuse-related PTSD 25
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(Frewen et al., 2010; Frewen et al., 2012a; Steuwe et al., 2014). As childhood trauma-exposure also affects reward functioning (Goff et al., 2013; Guyer et al., 2006; Mehta et al., 2010), sex differences in reward functioning may be mediated by age at trauma exposure. Thus, if women
ip t
with PTSD are exposed to trauma at a younger age compared to men with PTSD, and if trauma-exposure leads to stronger decreases in reward sensitivity in women compared to men,
cr
this may explain the reduced reward functioning seen in women with PTSD compared to men. It should be noted that several factors are confounded with sex in the studies reported in
us
this review, as most studies with predominantly male samples included participants exposed to combat trauma, whereas participants in mixed-gender and predominantly female studies were
an
mainly exposed to civilian trauma. This reflects existing sex differences in type of traumaexposure (Tolin and Foa, 2006).
M
In sum, stronger reward deficits are apparently present in women with PTSD compared to men. However, we cannot rule out the possibility that sample-specific factors such as trauma
Comorbid psychiatric disorders
Ac ce p
4.4
te
d
type explain (part of) this sex difference.
As reward deficits are clearly present in MDD (e.g. Zhang et al., 2013), and MDD is highly comorbid with PTSD (Keane and Kaloupek, 1997), this is an important confounder to consider while interpreting the results of the included studies. The fact that anhedonia is a symptom of both PTSD and MDD is likely not simply an epiphenomenon of comorbidity; anhedonic symptoms were equally present in PTSD patients with and without MDD (Franklin and Zimmerman, 2001). A number of studies reporting reward differences between PTSD and controls included a PTSD sample with significant levels of comorbidity with MDD or did not mention comorbidity rates (see table 1a & 1b). Although most studies did not control for comorbid MDD, the studies that that did control for MDD or depressive symptoms showed reward deficits in PTSD were still 26
Page 26 of 44
present after correcting for comorbid MDD (Elman et al., 2005; Hopper et al., 2008; MacNamara et al., 2013). The only exception is the study by Van Rooij et al (2014), who did not find PTSDrelated differences in responses to positive images, but did find that PTSD patient with comorbid
ip t
MDD had decreased ACC responses to positive images compared to PTSD patients without MDD, suggesting stronger reward deficits in PTSD patients with MDD. This may be explained
cr
by the fact that PTSD patients with MDD had higher scores on PTSD anhedonic symptoms (van Rooij et al., 2014b). Together, the included studies suggest that although diminished reward
us
functioning in PTSD may be similar to diminished reward functioning in MDD, findings are not driven solely by comorbid MDD.
an
Additionally, substance abuse and use of antidepressants, anxiolytics and other psychoactive medication by PTSD patients may influence reward functioning. As most studies in
M
the current review excluded alcohol and substance-related disorders or had samples with relatively low levels of comorbidity (see table 1a & 1b), this is no significant confounder of our
d
results. Although most studies did not control for possible confounding effects of psychoactive
te
medication, no effect of psychoactive medication on reward outcomes was found in studies that
Ac ce p
did control for medication use (Elman et al., 2005; Hopper et al., 2008; Roberts et al., 2012; Swick et al., 2012). Only Dretsch et al (2013) found higher reward sensitivity in PTSD patients using antidepressants compared to PTSD patients not using antidepressants. It is likely that when PTSD symptoms are still present despite the use of psychoactive medication, rewardrelated deficits remain.
In sum, although confounding effects of comorbid depression and use of psychostimulants on reward functioning in PTSD cannot be ruled out, these do not seem to alter the observed deficits in reward functioning.
4.5
Clinical implications
27
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Currently, the evidence-based psychotherapies available for PTSD mainly focus on the regulation of negative emotions. Based on the deficits in reward functioning as suggested by this review, PTSD psychotherapy may put more emphasis on positive affect. Dunn (2012)
ip t
suggests that psychotherapy outcome in MDD can substantially improve by putting more emphasis on positive emotion experience (Dunn, 2012), especially when patients report
cr
significant anhedonic symptoms. In MDD patients, psychotherapy specifically aimed at
increasing approach and positive experience of rewarding stimuli resulted in a significant
us
reduction of depressive symptoms. Interestingly, these observed clinical changes were accompanied by increased striatal reward responses to reward anticipation, and increased OFC
an
responses to receiving reward (Dichter et al., 2009). This type of psychotherapy might also be effective for PTSD patients. In PTSD following severe interpersonal trauma, the presence of
M
negative affective interference (elicitation of negative emotions in response to positive stimuli) could warrant a different therapeutic approach, by focusing on reducing negative emotions to
d
reward before attending to increasing positive emotions (Frewen et al., 2012b). Furthermore,
te
the degree of reward dysfunction at the time of treatment initiation may be informative to predict
Ac ce p
therapy success, as neural responses in the striatum and PFC to Go-trials during the Go-No go task predicted response to cognitive behavioral therapy in PTSD patients (Falconer et al., 2013).
Deficits in reward functioning may also be restored by pharmacological agents working on the reward pathway. Selective serotonin reuptake inhibitors (SSRI) used for treatment of PTSD are known to enhance striatal function and may exert part of their therapeutic effects through improvement of reward functioning (Heller et al., 2013). Other pharmacological agents are also promising to improve (social) reward-related deficits in PTSD patients. For example, administration of oxytocin can increase reward sensitivity to social positive stimuli, such as happy faces, by altering responses in the brain reward pathway (Scheele et al., 2012). Oxytocin administration is suggested as a promising agent for medication-enhanced psychotherapy in 28
Page 28 of 44
PTSD for various reasons (Koch et al., 2014; Olff et al., 2010). Increasing sensitivity to social positive stimuli may also enhance therapeutic engagement. Moreover, patients could become more sensitive to social support, a protective factor known to improve cognitive behavioral
Limitations and directions for future research
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4.6
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therapy and exposure treatment outcome in PTSD (Thrasher et al., 2010).
There are some methodological issues that must be kept in mind while interpreting the
us
results of this systematic review; especially the small number of available studies per phase of reward functioning, as well as the small sample size of most studies. The included participant
an
groups were diverse, differing in sex, trauma type and levels of comorbid depression, reflecting
conclusions must be drawn with caution.
M
the heterogeneity of the PTSD patient population. Considering the fragmentation of the data,
PTSD is a heterogeneous disorder and symptom profiles differ between patients (e.g.
d
Galatzer-Levy & Bryant, 2013). It is probable that different symptom clusters are differentially
te
related to reward functioning, such that the presence of dysregulations in reward functioning
Ac ce p
may depend on whether patients report anhedonic PTSD symptoms. This may explain some of the observed inconsistent findings in reward functioning in PTSD patients. Relating reward functioning to anhedonic PTSD symptoms may lead to further insights in the specific mechanisms underlying reward deficits and may be more sensitive than relating overall PTSD severity or dichotomous PTSD diagnosis to reward functioning. Despite obvious sex differences in PTSD (Olff et al., 2007), few of the currently available studies investigated the role of sex. Thus, there is a need for studies that address sex differences. If sex differences can be addressed in both civilian and veteran PTSD populations, this will also further clarify the possible confounding effect of trauma type on sex differences. Furthermore, studies using both trauma-exposed and non-trauma-exposed control groups are
29
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needed to see which differences in reward functioning are specific to PTSD, and which are trauma-related. In addition, in order to translate current observations on deficits in reward functioning in
ip t
PTSD to clinical practice aimed at improving PTSD treatment, more knowledge about the precise nature of reward deficits and mechanisms that underlie anhedonic symptoms in PTSD is
cr
needed. As different neural and psychological processes underlie motivational anhedonia
(‘wanting’) and consummatory anhedonia (‘liking’), they would require different therapeutic
us
approaches both from a pharmacological and a psychological point of view (e.g. focus on starting pleasurable activities vs. focus on enjoying pleasurable activities). Therefore, future
an
studies are advised to use measurements that distinguish between the different phases of reward functioning. The DSM 5 partly provides for this distinction by differentiating between
M
symptoms of diminished interest in significant activities (motivational or ‘wanting’) and the persistent inability to experience positive emotions (consummatory or ‘liking’). However, besides
d
consummatory anhedonia the latter item also includes aspects of dysphoria (reduction of
te
positive affect in general), resulting in a blurred measure of anhedonia.
Ac ce p
The concept of negative affective interference should also be investigated further; increased negative emotions in response to reward could result in behaviorally similar reward dysfunction as decreased positive emotions, but would require a different therapeutic approach (Frewen et al., 2012b). Also, systematic comparison of different types of positive stimuli, such as social and monetary reward, would be interesting to further establish specificity of reward dysfunction. To properly investigate specific deficits in reward functioning, it is important to distinguish between responses to positive and negative stimuli. Most previous neuroimaging studies investigated the difference between responses to positive relative to negative stimuli. However, for the investigation of specific reward-related deficits comparing positive to neutral conditions is advised for future studies. When reward conditions are contrasted against negative conditions, it is difficult to infer whether differences between patients and controls reflect 30
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different responses towards positive stimuli, negative stimuli or both. Furthermore, as many brain areas involved in reward functioning, such as the striatum and amygdala, react to both positive and negative stimuli, a contrast relative to neutral events may not only be more
ip t
meaningful but also more powerful. The study by Killgore et al (2013) exemplifies the benefits of contrasting to neutral stimuli; PTSD patients showed increased amygdala reactivity compared to
cr
healthy controls towards both fearful and happy faces relative to neutral stimuli, but no
difference was seen when fearful faces were contrasted relative to happy faces. In line with the
us
evidence that similar brain regions respond to positive and negative stimuli, a final suggestion would be to relate neural responses to behavioural and affective responses, to be able to better
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4.7
an
interpret the findings in terms of valence.
Conclusions
Although findings are not wholly consistent and more research is needed to further
d
elucidate the reward-related mechanisms underlying anhedonic symptoms in PTSD, the results
te
of this review suggest the presence of deficits in both motivational reward functioning and
Ac ce p
consummatory reward functioning in PTSD, such that PTSD patients exhibit reduced anticipation, approach and hedonic responses towards positive stimuli. These deficits in reward functioning were observed as reduced self-reported affective responses, behavioural, physiological and neural responses. Thus, PTSD patients seem to show hyporesponsivity to positive stimuli, although this effect seems less pronounced and less consistent than the hyperresponsivity to negative stimuli previously reported in PTSD (Hayes et al., 2012a, 2012b). Overall, reward deficits were seen more often in studies looking at social positive stimuli compared to studies looking at non-social stimuli, suggestive of social anhedonia. Also, reward deficits seem to be present more often in samples with female PTSD patients, although sex differences are intertwined with differences in trauma type. Which factors are responsible for the apparent sex difference in reward functioning in PTSD patients needs to be investigated further 31
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by future studies. Together, these findings are a first step in understanding the mechanisms underlying the frequent anhedonic symptoms in PTSD and encourage the investigation of new
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treatment targets aimed at improving reward functioning.
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ACKNOWLEDGEMENTS
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The study is supported by grants from ZonMw, the Netherlands organization for Health Research and Development (grant no. 91210041) and the Academic Medical Center Research
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Council (grant no. 110614).
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FIGURE CAPTIONS Figure 1 Title: Reward functioning in PTSD Description: Overview of the different phases of reward functioning, and the findings of differences in reward functioning in PTSD patients compared to controls. Abbreviations: PTSD:
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post-traumatic stress disorder; ↓: decreased in PTSD; ↑: increased in PTSD; =: no differences
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between PTSD and healthy control participants.
TABLES
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Title: Overview of studies investigating reward motivation in PTSD.
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Table 1a.
Table 1b.
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Title: Overview of studies investigating reward consumption in PTSD.
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Description: Abb: N: number of participants; PTSD: participants with post-traumatic stress disorder; TC: trauma-exposed control participants; NTC: non-trauma-exposed control
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participants; C: control participants, trauma-exposure unknown; T: trauma-exposed participants
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(PTSD status unknown); M: male participants; D: depressive disorder; S: substance-related or
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alcohol disorder; EEG: electro-encephalogram; fMRI: functional magnetic resonance imaging; SPSRQ: sensitivity to punishment sensitivity to reward questionnaire; BIS: behavioral inhibition system; BAS: behavioral approach system; IAPS: International Affective Picture System; SHAPS: Snaith-Hamilton Pleasure Scale; FCPCS: Fawcett-Clark Pleasure Capacity Scale; ROI: Region of interest analysis; SVC: small volume corrected for multiple comparisons; BA: Brodmann area; PFC: prefrontal cortex.
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Table(s)
Trauma type
Comorbidity Medication use
Modality
15 PTSD (100% M), 11 TC (100% M)
Combat
27% D, 0% S 67%
Questionnaire PTSD < TC: Lower self-reported reward expectation of monetary reward in Wheel-ofFortune task.
Cilivian, mixed
Unknown
Unknown
23 PTSD (91%M), 23 Combat TC (65%M) 35 PTSD, 256 TC Cilivian, (25% M) mixed
Unknown
43%
Unknown
Unknown
Questionnaire PTSD avoidance and PTSD hyperarousal symptoms positively correlated to Sensitivity to Increased Reward score on the SPSRQ questionnaire. PTSD reexperiencing and PTSD dysphoria symptoms not correlated to Sensitivity to Reward score. PTSD avoidance mediated positive relation between sensitivity to reward and PTSD dysphoria. Questionnaire PTSD = TC, no difference on BAS-Reward Responsiveness subscale of the BIS/BAS self- No report questionniare. Questionnaire PTSD total symptom score not related to BAS total score, BAS reward responsiveness, No BAS drive or BAS fun-seeking subscales of the BIS/BAS self-report questionniare.
Cilivian, mixed
Unknown
Unknown
Questionnaire PTSD total symptom scores negatively related to BAS-reward responsiveness and positively related to BAS-drive when accounting for avoidance, and not related to BAS-fun seeking or BAS total score of the BIS/BAS self-report questionniare.
Reduced / Increased
Combat
Unknown
Unknown
Behavioral
No
Cilivian, mixed
70% D, 0% S 0%
Behavioral
PTSD total symptom scores not related to reaction times in approach trials on an affective Go-No go task. PTSD = TC: No general difference in reaction times on approach trials on a Stop-signal task. PTSD < TC: Progressively slower reaction times during approach trials over time. PTSD = TC: No difference in reaction times on monetary-rewarded approach trials. PTSD < TC: Slower reaction times in non-monetary-rewarded approach trials (transient effect).
10 PTSD (50% M), Cilivian, 13 TC (62%M) mixed 21 PTSD (95%M), 16 Combat TC (88%M)
70% D, 0% S 0%
PTSD < TC: Lower increase in heart rate & skin conductance in response to monetary reward on a Stop-signal task. PTSD = TC: no difference in reaction time to approach trials on a Go-No go task.
Reduced
Unknown
Behavioral, physiological Behavioral
Unknown
Behavioral
PTSD = TC = NTC: No difference in reaction times on approach trials on a Stop-signal task.
No
58%
Behavioral
PTSD = TC: No difference in reaction times on approach trials on a Go-No go task.
No
PTSD = TC = NTC: no differences in reaction time to approach trials on a Stop-signal anticipation task. No differences in brain responses during approach trials vs rest, whole brain or ROI (striatum, inferior frontal gyrus, precentral gyrus). PTSD < TC: Lower amount of key presses to prolong watchtime of attractive female faces (valence specific) on a beautiful faces paradigm. PTSD = TC: no differences in approach to monetary reward on the Iowa gambling task.
No
Approach: Questionnaires Contractor et al (2013) 138 PTSD, 170 TC (36% M)
Dretsch et al (2013) Maack et al (2012)
Pickett et al (2011)
851 T (N PTSD unknown) (0% M)
Approach: Behavioral tasks Amick et al (2013) 47 PTSD, 25 TC (88% M) Casada & Roache 10 PTSD (50% M), (2005) 13 TC (62%M)
Behavioral 43% Behavioral
Reduced No
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Dretsch et al (2013)
58%
an
Elman et al (2005)
0% Behavioral
No
M
Van Rooij et al (2014)
Reduced / No
ed
Swick et al (2012)
Reduced
ce pt
Li et al (2013)
D unknown, 0% S, 100% mTBI 26 PTSD (12%M), 38 Childhood Unknown TC (3%M), 36 NTC trauma (6%M) 40 PTSD (98% M), Combat Unknown 33 TC (94%M) 28 PTSD (100%M), Combat 54% D, 0% S 26 TC (100%M), 25 NTC (100%M) 12 PTSD (100% M), Combat 25% D, 0% S 11 TC (100%M) 23 PTSD (91%M), 23 Combat Unknown TC (65%M)
Reward affected?
Ac
Casada & Roache (2006) Depue et al (2014)
Findings
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Anticipation Hopper et al (2008)
N (% males)
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Study
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Table(s)
Trauma type
Comorbidity in PTSD Medication use in group PTSD group
Modality
Findings
Reward affected?
15 PTSD (100% M), 11 TC (100% M)
Combat
27% D, 0% S
67%
Questionnaire
PTSD < TC: Lower self-reported reward satisfaction with monetary reward in Wheel-ofFortune task (group by expectation interaction).
Reduced
36 PTSD (58% M), 21 TC (43% M), 16 NTC (44% M) 17 PTSD (100% M), 11 TC (100% M), 14 NTC (100% M)
War, torture
83% D, 0% S
22-42%
Questionnaire
PTSD < TC & NTC: Lower pleasantness ratings of positive images in an affective image response task. PTSD = TC & NTC: No difference in arousal ratings of positive images.
Reduced / No
Combat
32%D, 12% S (>2 weeks free of substance use)
0%
Questionnaire, PTSD = TC & NTC: No differences in pleasantness or arousal ratings of positive images in No physiological an IAPS image rating task. PTSD = TC & NTC: No differences in physiological responses to positive images (heart rate, skin conductance, frontalis muscle tension).
Litz et al (2000)
32 PTSD (100% M), 29 TC (100% M)
Combat
59% D, 18% S
Unknown
Roberts et al (2012)
18 PTSD (17%M), 18 Cilivian, mixed D unknown, 0% S, TC (17%M) 100% epilipsy
56-100%
Spahic-Milajhovic et al (2005)
21 PTSD (48% M), 21 TC (52% M)
War, torture
0% D, 0% S
Unknown
Van Rooij et al (2014)
29 PTSD (100% M), 28 TC (100% M), 25 NTC (100% M) 49 PTSD (100%M), 75 TC (100%)
Combat
55% D, 0% S
Combat
Unknown
Combat
Wolf et al (2009)
Positive Faces Elman et al (2005)
Other positive stimuli Frewen et al (2012)
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Questionnaire, PTSD = TC: No differences in pleasantness or arousal rating of positive images on an IAPS physiological image rating task. PTSD = TC: No difference in zygomatic expressive-motor response or skin conductance to positive images. Questionnaire, PTSD = TC: No difference in pleasantness ratings, positive emotional behavior or physiological cardiovascular responses to positive images on Lang's looking-at-pictures test. PTSD > TC: Higher arousal ratings to positive pictures. Questionnaire PTSD < TC: Lower arousal ratings of positive images in males and females on Lang's looking-at-pictures test. PTSD = TC: No difference in pleasantness rating for positive images in males. PTSD < TC: Lower pleasantness ratings for positive images in females.
0%
fMRI
Unknown
Questionnaire
25% D, 0% S
58%
Questionnaire
Childhood maltreatment Combat
56% D, 6% S
Unknown
Questionnaire
21%D, 16% S
0%
EEG
Mainly interpersonal violence
unknown in PTSD group (whole sample: 63% lifetime S, 17% mood and anxiety disorders) Whole group: 14% D, 0% S
Unknown
EEG
0%
14 PTSD (71%M), 22 Cilivian, mixed 0%D, 0% S C (trauma exposure unknown) (64%M)
55 PTSD (0% M), 35 Childhood NTC (0% M) maltreatment
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12 PTSD (100% M), 11 TC (100% M) Steuwe et al (2014) 16 PTSD (0%M), 16 NTC (0%M) MacNamara et al (2013) 19 PTSD (100%M), 14 TC (100%M) Ehlers et al (2006) 19 PTSD (% M unknown, 34% in whole group), 127 TC (% M unknown, 34% in whole group) Herringa et al (2013) Continuous: 28 T, of which 18 PTSD (100% M) Killgore et al (2013)
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Admur et al (2000)
M
Positive Images Adenauer et al (2010)
ed
Money Hopper et al (2008)
t
N (% males)
ce pt
Study
Combat
29% D, 4% S
No
Increased / No Reduced / No
PTSD = TC & NTC: No difference in neural reactivity towards positive vs neutral pictures on No an IAPS image rating task (no differences observed on whole brain level nor in ROI's amygdala, hippocampus, insula, and anterior cingulate cortex, SVC). PTSD = TC: No difference in pleasantness or arousal ratings of positive pictures on Lang's No looking-at-pictures test.
PTSD = TC: No differences in attractiveness ratings of attractive faces of opposite sex in a beautiful faces paradigm. PTSD < NTC: Lower positive rating of happy faces and lower positive feeling in response to happy faces in a direct/averted gaze to facial expressions task. PTSD < TC: Lower vertex positive potentials to happy faces in an emotional face-matching task. PTSD = TC: No difference in late positive potentials to happy faces. PTSD < TC: Slower event related potentials to happy faces in the midline posterior and right frontal EEG leads in an emotional face-recognition task. PTSD = TC: No difference in height of event related potentials to happy faces.
No
fMRI
PTSD symptoms not related to neural reactivity to implicitly shown happy faces vs neutral shapes (no differeces on whole brain level nor in ROI's anteromedial PFC, amygdala, hippocampus and insula, SVC) in an implicit facial expression processing task.
No
0%
fMRI
PTSD > C: Higher amygdala reactivity to happy faces vs neutral faces in a masked facial affect paradigm (no difference observed in ROI's insula, hippocampus/parahippocampal gyrus, nor ventromedial PFC, orbitofrontal cortex and anterior cingulate cortex, SVC).
Increased
0%
Questionnaire
PTSD < NTC: Lower self-reported experience of pleasure towards pleasurable activities on the SHAPS and FCPCS hedonia questionnaires.
Reduced
Reduced Reduced Reduced
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S0149-7634(15)00030-5 http://dx.doi.org/doi:10.1016/j.neubiorev.2015.01.019 NBR 2126
To appear in: Received date: Revised date: Accepted date:
3-9-2014 20-1-2015 21-1-2015
Please cite this article as: NAWIJN, L., van Zuiden, M., Frijling, J.L., Koch, S.B., Veltman, D.J., Olff, M.,REWARD FUNCTIONING IN PTSD: A SYSTEMATIC REVIEW EXPLORING THE MECHANISMS UNDERLYING ANHEDONIA, Neuroscience and Biobehavioral Reviews (2015), http://dx.doi.org/10.1016/j.neubiorev.2015.01.019 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
HIGHLIGHTS Anhedonia in PTSD may result from deficits in reward functioning Results of this systematic review suggest reduced reward functioning in PTSD
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Reduced reward functioning seems more prevalent in female PTSD patients Reduced reward functioning is most clearly present in response to social stimuli
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Reward functioning should receive more attention in PTSD research
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REWARD FUNCTIONING IN PTSD: A SYSTEMATIC REVIEW EXPLORING THE MECHANISMS UNDERLYING ANHEDONIA
a,c
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Miranda Olff
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LAURA NAWIJN*,a, Mirjam van Zuiden a, Jessie L. Frijling a, Saskia B. Koch a, Dick J. Veltman b,
a. Department of Psychiatry, Academic Medical Center, University of Amsterdam, PO box 22660,
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1100 DD, Amsterdam, The Netherlands
b. Department of Psychiatry, VU University Medical Center, PO box 7057, 1007 MB, Amsterdam,
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The Netherlands
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c. Arq Psychotrauma Expert Group, Nienoord 5, 1112 XE, Diemen, The Netherlands
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[email protected]
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* Corresponding author: Tel: +31-20 89 13 667, Fax: +31-20 89 13 701, E-mail:
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ABSTRACT
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LAURA NAWIJN, Mirjam van Zuiden, Jessie L. Frijling, Saskia B. Koch, Dick J. Veltman,
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Miranda Olff
Reward functioning in PTSD: A systematic review exploring the mechanisms underlying
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NEUROSCI BIOBEHAV REV xxx (2015) xxx-xxx
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anhedonia.
Post-traumatic stress disorder (PTSD) is a debilitating psychiatric disorder. An important
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diagnostic feature of PTSD is anhedonia, which may result from deficits in reward functioning. This has however never been studied systematically in PTSD. To determine if PTSD is
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associated with reward impairments, we conducted a systematic review of studies in which
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reward functioning was compared between PTSD patients and healthy control participants, or investigated in relation to PTSD symptom severity. A total of 29 studies were included, covering reward anticipation and approach (‘wanting’), and hedonic responses to reward (‘liking’). Overall, results were mixed, although decreased reward anticipation and approach and reduced hedonic responses were repeatedly observed in PTSD patients compared to healthy controls. Decreased reward functioning was seen more often in female than in male PTSD samples and most often in response to social positive stimuli. Though more research is needed, these findings are a first step in understanding the possible mechanisms underlying anhedonia in PTSD.
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KEYWORDS PTSD; Reward; Systematic review; Anhedonia; Trauma; Positive stimuli
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MAIN TEXT INTRODUCTION
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Post-traumatic stress disorder (PTSD) is a psychiatric disorder that can develop after experiencing a traumatic event. The lifetime prevalence of PTSD in Western countries is high (7
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to 10%) (de Vries and Olff, 2009; Kessler et al., 2012). PTSD not only severely compromises the well-being of patients and their relatives, but also represents a major economic burden on
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society. Anhedonia, or diminished interest in pleasurable activities and the inability to experience positive emotions, is a key feature of PTSD (American Psychiatric Association,
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2013) as well as several other psychiatric disorders. Anhedonic symptoms are present in about two-thirds of PTSD patients, independent of comorbid major depressive disorder (MDD);
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‘diminished interest in activities’ was endorsed by 63 to 75% of PTSD patients and ‘inability to
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experience positive emotions’ by 56 to 65% (Carmassi et al., 2014; Franklin and Zimmerman,
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2001). Anhedonic symptoms are related to adverse outcomes in PTSD such as increased chronicity, suicidality and healthcare utilization (Hassija et al., 2012). Anhedonia is thought to result from deficits in reward functioning (Der-Avakian and Markou, 2012; Treadway and Zald, 2013). Reward functioning is defined as the ability to seek out and enjoy stimuli of positive motivational valence and is associated with specific neurocircuitries. It is a crucial driving force of behavior, and can guide us towards positive and rewarding experiences in everyday life, ranging from food and sex to money and positive social interaction. Reward functioning is a multi-faceted construct and anhedonia can theoretically arise from deficits in different phases of reward functioning (Der-Avakian and Markou, 2012; Schultz, 2006). An important phase in reward functioning is reward motivation (‘wanting’), marked by anticipation and approach of reward (Berridge et al., 2009). Reward anticipation 4
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should elicit a sense of desire, and motivate to pursue a reward by carrying out the necessary goal-directed approach behavior. From a neurobiological perspective, cues signaling potential reward activate the mesocorticolimbic reward pathway by dopamine projections from the ventral
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tegmental area (VTA) to the ventral striatum and amygdala. These in turn connect to frontal brain structures such as the orbitofrontal cortex (OFC), anterior insula (AI) and anterior cingulate
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cortex (ACC), areas important for valence assessment, and to the dorsal prefrontal cortex,
important for information integration and decision making. Subsequently, approach behavior is
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initiated through dopaminergic activation of the dorsal striatum and motor cortices (Der-Avakian and Markou, 2012; Liu et al., 2011). A second phase of reward functioning is reward
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consumption (‘liking’), marked by a hedonic response and being able to enjoy a reward once it is obtained (Berridge et al., 2009). Obtaining a reward should elicit a feeling of pleasure or
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enjoyment, a hedonic positive affective response. The experience of pleasure in response to a reward is mediated in part by the same brain areas also involved in ‘wanting’, such as the
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striatum, amygdala, OFC and AI, though ‘liking’ is mainly mediated by opioid and GABA
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receptors (Der-Avakian and Markou, 2012; Liu et al., 2011). Appropriate reward functioning will
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stimulate to pursue rewards based on previous experiences and adjust one’s behavior to maximize reward collection and positive experiences from the environment. In its classic sense, anhedonia would be defined as deficits in the reward consumption phase or ‘liking’ (Ribot, 1896). However, deficits in the motivational phase or ‘wanting’ could also result in anhedonic symptoms (Treadway and Zald, 2013). To distinguish between deficits in ‘wanting’ and ‘liking’, the terms ‘motivational anhedonia’ and ‘consummatory anhedonia’ have been proposed (Der-Avakian and Markou, 2012; Treadway and Zald, 2011). To fully understand possible reward-related deficits in psychiatric disorders including PTSD it is therefore relevant to distinguish between the different phases of reward functioning. Also important to note is that a number of areas involved in ‘wanting’ and ‘liking’ of positive stimuli, such as the ventral striatum, amygdala, OFC and AI, are also involved in the processing of negative stimuli, implicating a 5
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broader role in salience processing, and approach- as well as avoidance-related behavior (Hayes et al., 2014). This dual role is important to keep in mind when assessing and interpreting neural responses to reward, such that responses to positive stimuli should be evaluated
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separately from negative stimuli. A further distinction can be made based on the type of stimuli presented. In
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schizophrenia research, a distinction is made between social anhedonia and non-social or
physical anhedonia, distinguishing responses to social positive stimuli (e.g. happy faces or
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positive social interaction) relative to non-social physical or sensory positive stimuli (e.g. pleasant smells, tastes or images) (Chapman et al., 1976). Especially social anhedonia has
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been related to more severe psychopathology, such as increased depressive and anxiety symptoms (Gooding et al., 2005; Rey et al., 2009). Social and non-social anhedonia may relate
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to distinct affective, behavioral and biological phenotypes, and it is possible that different types of rewarding stimuli are differentially affected in PTSD.
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Reward processing is a functional domain extensively investigated in psychopathology.
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In MDD for example, a disorder comorbid with PTSD in up to 50% of patients (e.g. Keane &
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Kaloupek, 1997), a recent meta-analysis showed aberrant neural reactivity in patients with MDD compared to healthy participants in differential brain areas during reward anticipation (‘wanting’) and reward consumption (‘liking’) (Zhang et al., 2013). Furthermore, increased anhedonia scores in MDD patients were associated with reduced amygdala, ACC and AI responses to positive stimuli (Henderson et al., 2014; Stuhrmann et al., 2013). Also in healthy subjects, trait anhedonia has been related to reduced subjective pleasantness ratings to positive stimuli and reduced neural responses in the ventral striatum, OFC, ACC and AI (Keller et al., 2013). These findings suggest that neural dysregulation in reward processing areas underlies anhedonic symptoms in psychiatric and non-psychiatric populations. Over the course of the last decade, a growing body of research has focused on reward functioning in PTSD. Five years ago, Stein and Paulus (2009) suggested that PTSD involves an 6
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imbalance between approach and avoidance systems (Stein and Paulus, 2009). This was based on the first reports of reward deficits in PTSD, together with findings of increased responses to negative stimuli in PTSD compared to controls. Although previous meta-analyses
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have consistently shown increased neural and behavioral sensitivity to negative stimuli in PTSD (Hayes et al., 2012a, 2012b), thus far, the available research literature on reward functioning in
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PTSD has never been reviewed. Our objective was therefore to perform a systematic review of studies investigating reward functioning in PTSD, and to address the following questions: Do
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PTSD patients have altered reward functioning compared to healthy controls, and if so: which
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specific phases of reward functioning are affected in PTSD patients?
METHODS
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For the purpose of the current review, we included all questionnaires of self-report, behavioral, physiological or neural measures of anticipatory, approach and consummatory
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responses towards positive stimuli, i.e. stimuli that are generally experienced as positive or
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rewarding. Publications were selected if responses to positive stimuli were compared between
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adults diagnosed with current PTSD and adult control participants without PTSD, or if responses to positive stimuli were correlated with PTSD symptom severity in adult participants. Other inclusion criteria were publication in peer-reviewed scientific journals in English, Dutch, German or French, and reporting results of statistical analyses. Case-studies were excluded but otherwise no limits were set to sample size. Using keywords for PTSD (e.g. posttraumatic stress disorder, posttraumatic stress symptoms, posttraumatic, stress disorder, traumatic stress, psychotrauma) and reward (e.g. reward, behavioral activation, behavioral approach, reinforcement, positive stimuli, positive picture, motivation, pleasure, pleasant, happy, hedonic), literature searches were conducted for studies published before June 2 2014 in the online literature databases PubMed, Embase, PsychINFO and PILOTS. Each publication was screened independently by two of four qualified 7
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researchers (LN, MVZ, JLF, SBK) for selection based on the inclusion criteria. Any selection discrepancies between the two researchers were discussed until consensus was reached. Of the 1185 articles found in the initial search, 29 articles were included based on the
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inclusion criteria (see table 1 for an overview). Of note, 13 neuroimaging studies were excluded because responses to positive stimuli were compared to negative stimuli, but not neutral stimuli,
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so that it could not be established if the observed results were related to differential responses
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to positive or to negative stimuli, or both (for a further discussion, see section 4.6).
RESULTS
The selected studies investigated motivational or consummatory phases of reward
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functioning, using different modalities ranging from self-report questionnaires and behavioral measurements to physiological and neuroimaging data (see table 1a for motivational studies,
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reward functioning.
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table 1b for hedonic studies). Results will be discussed separately for the different phases of
3.1
Reward motivation (‘wanting’)
3.1.1
Anticipation
One behavioral study investigated anticipation of monetary reward in PTSD patients using a Wheel-of-Fortune task (Hopper et al., 2008). This task consists of a reward anticipation and a reward consumption phase in which money can be won or lost at different probabilities (responses to reward consumption are discussed in section 3.2.1). Hopper et al (2008) found that male veteran PTSD patients reported lower expectations of winning monetary reward compared to healthy trauma-exposed controls, given the same probability of winning a reward.
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Though reduced anticipation is suggested by Hopper et al (2008), this was a relatively small study and more research is needed to confirm and extend these findings.
Approach: Questionnaires
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3.1.2
A number of studies have investigated reward approach according to the reinforcement
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sensitivity theory, which proposes that behavior is controlled by the behavioral approach system (BAS) and the behavioral inhibition system (BIS) (Gray and Mcnaughton, 2000). BAS is related
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to reward sensitivity and positive stimuli, leading to response activation and approach behavior. BIS is related to punishment sensitivity and negative stimuli, leading to response inhibition and
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avoidant behavior. In this review we focused on measurements of the BAS as a representation of reward approach.
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The BIS/BAS scale is a self-report questionnaire of BIS and BAS sensitivity (Carver and White, 1994). A study in 291 predominantly female trauma-exposed undergraduate students
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found no association between probable PTSD status and any of the BAS subscales using
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bivariate correlations (Maack et al., 2011). Dretsch et al (2013) investigated the BAS-Reward
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Responsiveness subscale in a small sample of predominantly male combat veterans with and without PTSD, but found no differences between groups (Dretsch et al., 2013). A study in 851 trauma-exposed female undergraduate students found that overall PTSD symptom severity was negatively related to BAS-reward responsiveness, a subscale measuring responses to anticipation and consumption of rewarding events, but only when accounting for experiential avoidance, i.e. the avoidance of unwanted negative feelings, thoughts or memories (Pickett et al., 2011). Also, overall PTSD symptom severity was positively related to BAS-Drive, a subscale measuring motivation to pursue rewards, when accounting for experiential avoidance. PTSD severity was not related to BAS-Fun Seeking, a subscale measuring the desire for new rewarding experiences, or total BAS score (Pickett et al., 2011).
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Contractor et al (2013) used the Sensitivity to Punishment and Sensitivity to Reward Questionnaire (SPSRQ, (Torrubia et al., 2001), a questionnaire similar to the BIS/BAS scale, measuring BAS with the Sensitivity to Reward subscale (SR). PTSD symptoms were divided
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into four clusters according to the PTSD-symptoms model of Simms et al (Simms et al., 2002); Re-experiencing, avoidance, dysphoria and hyperarousal. The dysphoria cluster consisted of
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the anhedonia symptoms from the DSM-IV avoidance cluster, taken together with irritability, sleeping and concentration problems from the DSM-IV hyperarousal symptom cluster. In a
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community sample of 306 male and female trauma-exposed primary care patients, PTSD avoidance and hyperarousal scores were positively correlated with SR, while PTSD re-
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experiencing and dysphoria scores were not correlated with SR. However, PTSD avoidance had a mediating role between SR and PTSD dysphoria, such that increased PTSD avoidance and
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increased SR were related to increased PTSD dysphoria scores, suggesting that patients with
dysphoria (Contractor et al., 2013).
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increased sensitivity to reward show more avoidance symptoms, which is related to increased
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The finding that PTSD avoidance symptoms were positively related to reward approach
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behavior suggests that reward approach may be used as a strategy for avoidance of traumarelated memories (Contractor et al., 2013). Interestingly, after controlling for the effects of experiential avoidance, reward responsiveness was negatively related to overall PTSD symptom severity (Pickett et al., 2011). Furthermore, the presence of reward seeking behavior in combination with PTSD avoidance symptoms was related to increased PTSD dysphoria symptoms, suggesting that increased reward seeking is not related to increased positive emotions (Contractor et al., 2013). This supports the hypothesis that PTSD patients use reward approach behavior as an avoidance strategy, but that actual reward responsiveness is decreased in PTSD (Contractor et al., 2013; Pickett et al., 2011). These findings exemplify the complex relationship between reward approach, avoidance behavior and PTSD.
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With regard to the use of reward approach behavior as avoidance strategy, it is interesting to note that alcohol and substance abuse are also used to avoid or numb negative emotions in PTSD (O’Hare and Sherrer, 2011). Also, previous research by Weiss et al (2012)
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suggests that the increased impulsive behavior such as risk-seeking behavior, a concept related to fun-seeking and approach behavior, that has been found in PTSD, can be explained by
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emotional dysregulation, i.e. problems with dealing with negative emotions, instead of trait
impulsivity. The suggestion that problems with emotion regulation may lead to risk-seeking and
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reward-approach behavior as a strategy to alleviate or avoid negative emotions (Weiss et al.,
3.1.3
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2012) fits with the findings of Pickett et al (2011) and Contractor et al. (2013).
Approach: Behavioral tasks
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Seven studies investigated approach behavior with Go-No Go or Stop-Signal tasks, two similar behavioral measures of BIS/BAS. During Go-trials, participants have to press a button as
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fast as possible, reaction speed providing a measure for BAS; during Stop- or No Go-trials
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participants have to inhibit their button-press response, targeting BIS. For this review, we
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focused on responses to Go-trials as a representation of approach behavior. The results of a number of studies investigating Go-No Go tasks show no differences in RT towards Go-trials between male veteran PTSD patients and trauma-exposed controls (Depue et al., 2014; Swick et al., 2012), nor between PTSD patients with childhood trauma, childhood trauma-exposed controls and non-trauma-exposed controls (Li et al., 2013). In line with this, PTSD symptom severity were also not related to RT during Go-trials in a group of trauma-exposed combat veterans (Amick et al., 2013). Also, using the slightly different StopSignal Anticipation Task, male veteran PTSD patients did not differ in RT from trauma- and nontrauma-exposed controls in response to go-trials (van Rooij et al., 2014a). Together, these studies indicate that BAS function in PTSD patients is similar to trauma- and non-traumaexposed controls. Similar findings were seen by Casada et al (2005, 2006) in a mixed-gender 11
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community-sample: In response to Go-trials there were no differences in reaction times (RT) between PTSD patients and trauma-exposed controls (Casada and Roache, 2005). However, PTSD patients showed a progressive slowing of RT towards Go-trials over time, compared to
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trauma-exposed controls. This may suggest that PTSD patients show increasingly stronger behavioral inhibition when learning the task, such that they would rather give up reward (correct
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response to Go-trial) to avoid punishment (incorrect response to No Go-trials), compared with controls. Another explanation may be that PTSD patients had more problems with sustained
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task-motivation, compared to controls. Furthermore, when monetary rewards were introduced for correct responses, both controls and PTSD patients showed similar acceleration of RT
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during Go-trials. However, when monetary rewards were then replaced by positive feedback again, controls would still respond as fast as if monetary reward was still given, whereas PTSD
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patients would temporarily slow down their responses. This suggests lower sustained taskmotivation for non-rewarded trials in PTSD compared to controls (Casada and Roache, 2005).
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Additionally, in the same sample PTSD patients exhibited lower increases in heart-rate (HR)
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and skin conductance (SC) in response to monetary rewarded trials compared to controls,
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reflecting reduced physiological arousal (Casada and Roache, 2006). The authors suggested that this dissociation of autonomic responses and motivational behavior in PTSD patients may reflect emotional numbing.
Elman et al (2005) investigated approach behavior towards attractive faces in male Vietnam veterans with and without PTSD (attractiveness ratings are discussed in section 3.2.3). Participants were presented with attractive and average male and female faces and could prolong or shorten presentation-times with button presses. Participants with PTSD made less button presses to prolong presentation-time of attractive female faces, compared to controls. PTSD patients and controls did not differ in approach behavior towards attractive male, or average male and female faces (Elman et al., 2005).
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Dretsch et al (2013) investigated reward approach in a group of predominantly male veterans with the Iowa Gambling Task (IGT). In the IGT, participants can win money by selecting cards from card decks with different reward probabilities and magnitudes. PTSD
suggesting normal reward sensitivity (Dretsch et al., 2013).
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patients did not differ in IGT performance compared to trauma-exposed healthy controls
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In sum, six studies employing Go-No Go type tasks consistently failed to observe
differences between PTSD patients and trauma- and non-trauma-exposed controls on approach
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behavior (Amick et al., 2013; Casada and Roache, 2005; Depue et al., 2014; Li et al., 2013; Swick et al., 2012; van Rooij et al., 2014a). As the Go-No Go task is primarily designed to
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measure response inhibition, it is possible that this task is not sensitive enough to pick up more subtle differences in approach behavior between PTSD patients and controls. Indeed, when
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approach behavior was investigated in more detail, PTSD patients showed declining approach behavior over consecutive trials, and reduced approach behavior during non-monetary
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rewarded trials compared to monetary rewarded trials (Casada and Roache, 2005). Also, the
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findings by Elman et al (2005) indicate reduced motivation to actively pursue positive stimuli.
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Together, this may suggest that reduced motivational approach behavior in PTSD only manifests itself when more effort is needed, or when the balance between effort and reward is less advantageous. This is similar to previous findings in MDD patients, who were less willing to expend effort for monetary reward compared to controls (Treadway et al., 2012). However, as the studies by Casada et al (2005) and Elman et al (2005) were both relatively small, more research is needed to confirm these findings.
3.2
Reward consumption (‘liking’) Studies investigating responses to reward consumption have been grouped according to
stimulus type.
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3.2.1
Monetary reward Hopper et al (2008) investigated responses to reward using a Wheel-of-Fortune task
(see also section 3.1.1). When receiving monetary rewards, male Vietnam veterans with PTSD
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reported less subjective satisfaction with the received rewards, compared to male Vietnam veterans without PTSD (Hopper et al., 2008). This study was the only included study that
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investigated hedonic responses to monetary reward. Reduced satisfaction is suggested, but as
3.2.2
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the sample size of this study was rather small, more research is needed to confirm this finding.
Positive images
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Responses towards images of positive affective scenes were investigated in four studies in male combat veterans (Amdur et al., 2000; Litz et al., 2000; van Rooij et al., 2014b; Wolf et
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al., 2009), two mixed-gender samples of war and torture survivors (Adenauer et al., 2010; Spahic-Mihajlovic, Crayton, & Neafsey, 2005) and a mixed-gender civilian trauma sample
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(Roberts et al., 2012). Six studies investigated self-reported valence (pleasant – unpleasant)
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and arousal (calming – arousing). Adenauer et al (2010) found that PTSD patients scored lower
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on pleasantness ratings of positive images compared to trauma-exposed controls, though this was present towards all images (including neutral and negative), and Spahic-Mihajlovic et al (2005) observed reduced pleasantness in female but not in male PTSD patients. However, these findings are in contrast to the lack of group differences in valence ratings in the other four studies (Amdur et al., 2000; Litz et al., 2000; Roberts et al., 2012; Wolf et al., 2009). SpahicMihajlovic et al (2005) found decreased arousal ratings of positive images in PTSD patients compared to trauma-exposed controls. Roberts et al (2012) on the other hand found increased arousal ratings to positive images in PTSD patients compared to trauma-exposed controls. Other studies found no group differences in arousal ratings of positive images (Adenauer et al., 2010; Amdur et al., 2000; Litz et al., 2000; Wolf et al., 2009).
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In several of these studies physiological responses were also measured. No group differences between male veterans with PTSD and combat- and non-combat-exposed controls were observed in HR, SC and frontalis muscle tension (“frowning”) responses when viewing
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positive images (Amdur et al., 2000). Also, Roberts et al (2012) did not observe any differences in cardiovascular responses to positive images between predominantly female civilian PTSD
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patients and controls. Litz et al (2000) found that male veterans with PTSD had a higher HR across all conditions (negative, neutral and positive images), suggesting a more general
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increase in physiological response, irrespective of image presentation. Van Rooij et al (2014) investigated neural responses to positive vs neutral images in male veterans with and without
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PTSD and non-combat-exposed controls, but did not observe any differences between PTSD patients and the control groups (van Rooij et al., 2014b).
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Although some studies show inconsistent results, the overall pattern suggests that PTSD patients and controls do not differ in self-reported arousal and valence-ratings in response to
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positive images, nor in physiological arousal or neural reactivity (Adenauer et al., 2010; Amdur
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et al., 2000; Litz et al., 2000; Roberts et al., 2012; Spahic-Mihajlovic et al., 2005; van Rooij et
Ac ce p
al., 2014b; Wolf et al., 2009). As three studies compared both trauma- and non-trauma-exposed controls to PTSD patients, neither trauma nor PTSD seems to affect subjective ratings, physiological or neural responses to positive pictures (Adenauer et al., 2010; Amdur et al., 2000; van Rooij et al., 2014b).
3.2.3
Positive faces
Several studies investigated subjective responses to pictures of positive faces in PTSD patients. In a sample of male veterans, Elman et al (2005) observed that attractiveness ratings of attractive and average male and female faces did not differ between male PTSD patients and trauma-exposed controls (Elman et al., 2005) (see also section 3.1.3). In another study, women with child abuse-related PTSD rated the emotional expressions of happy faces as less positive 15
Page 15 of 44
compared to healthy non-trauma-exposed controls. The PTSD patients also reported less positive feelings compared to controls when asked how they felt while watching happy faces (Steuwe et al., 2014). No group differences were seen in response to neutral faces. Since PTSD
ip t
patients also labeled happy faces as expressing less positive emotions, the reduced positive feelings reported by PTSD patients may be due to differential labeling of emotions, and not to
cr
hedonic deficits. As Elman et al (2005) and Steuwe et al (2014) were the only studies looking at subjective responses to positive faces, and both had relatively small sample sizes, more
us
research is needed to further elucidate these findings in PTSD patients.
Two studies investigated neurophysiological responses to happy faces using EEG. An
an
EEG study in predominantly female Native Americans showed that PTSD patients had slower P3 event related potentials (ERP) in midline posterior and frontal areas in response to happy
M
faces compared to trauma-exposed controls (Ehlers et al., 2006), whereas P3 amplitude did not differ between groups. As P3 ERP’s are thought to reflect attentional processing of salient
d
stimuli, these findings suggest slowed processing of positive faces in PTSD patients compared
te
to controls. Although this was a study with a large sample size, the majority of participants
Ac ce p
reported (lifetime) alcohol dependence (63%), which is known to affect P3 ERP latency (Porjesz et al., 2005) but was unfortunately not controlled for. A second EEG study in male veterans showed decreased vertex positive potentials (VPP) towards happy faces in PTSD patients compared to combat-exposed healthy controls, but not in response to neutral shapes (MacNamara et al., 2013). Decreased VPP are thought to reflect decreased initial perceptual responses originating from the fusiform gyrus (FFG). No group differences in latent positive potentials (LPP) were seen towards happy faces or neutral shapes, which are thought to reflect sustained processing of perceived salience of stimuli. Together, the reduced EEG responses to positive stimuli observed in PTSD patients suggest reduced attention to and processing of positive stimuli (Ehlers et al., 2006; MacNamara et al., 2013). 16
Page 16 of 44
Two fMRI studies explored responses to implicitly shown positive faces. In an implicit processing task positive or negative stimuli are presented very briefly or masked with a different stimulus, resulting in amygdala processing in the absence of conscious cognitive control
ip t
(Killgore et al., 2013; Whalen et al., 1998). In a sample of male veterans overall PTSD symptom severity was not related to neural reactivity to implicit happy faces vs. neutral shapes (Herringa
cr
et al., 2013). In contrast, another fMRI study in a predominantly male sample showed increased amygdala responses towards implicit happy faces vs. neutral faces in PTSD patients compared
us
to healthy controls, suggesting increased responsiveness towards social positive stimuli (Killgore et al., 2013). Thus, amygdala responses to implicit happy faces seem to be similar or
an
increased in PTSD patients compared to controls (Herringa et al., 2013; Killgore et al., 2013). The observations of decreased FFG and increased amygdala responses in PTSD are in
M
line with results from a recent meta-analysis of neuroimaging studies, showing decreased FFG and increased amygdala activity in PTSD patients compared to controls (Hayes et al., 2012a).
d
Though Hayes et al (2012) included mainly studies on negative stimuli, MacNamara et al (2013)
te
and Killgore et al (2013) observed a decrease in FFG and increase in amygdala responses to
Ac ce p
both positive and negative faces. As this effect was absent in response to neutral stimuli, these findings suggest that PTSD may be related to decreased FFG and increased amygdala responses to all emotionally salient facial stimuli, irrespective of valence. MacNamara et al (2013) suggest increased amygdala responses reflect high levels of arousal in PTSD, which may result in impaired attention and stimulus discrimination, reflected by reduced FFG responses towards salient stimuli. Recently however, Patel et al (2012) have argued that increased amygdala responses may be related to trauma-exposure and not to PTSD specific, based on a meta-analysis of neuroimaging studies (Patel et al., 2012). Decreased FFG responses were specific to PTSD though. As trauma-exposure of the control group was not reported by Killgore et al (2013), trauma-exposure might also explain the reported increases in amygdala responses in PTSD patients compared to controls. Another possible explanation has 17
Page 17 of 44
been put forward by Frewen et al (2010), who found that PTSD patients responded with more negative emotions to positive stimuli compared to controls, and that these increased negative emotions were associated with increased amygdala responses to positive stimuli. Thus, the
ip t
PTSD-related increased amygdala responses seen by Killgore et al (2013) could also reflect a negative interpretation of positive faces, i.e. seeing them as threatening or aversive (‘negative
cr
affective interference’, see also paragraph 3.2.4) (Frewen et al., 2012b).
Together, these findings suggests that PTSD is related to decreased hedonic responses
us
to happy faces, and decreased FFG and increased amygdala responses to emotional faces irrespective of valence. The reduced hedonic responses and increased amygdala responses
an
however may (in part) be explained by trauma-exposure. As the studies discussed in this section had relatively small samples, more research is needed to extend and confirm these
Other positive stimuli
d
3.2.4
M
findings.
te
In response to a positive odor (vanilla), male combat veterans with PTSD did not differ in
Ac ce p
pleasantness ratings or emotional responses compared to combat-exposed controls (Vermetten et al., 2007). However, it is questionable whether the vanilla smell was actually a valid positive stimulus in this study, as both PTSD and control groups rated the vanilla odor as neutral instead of pleasant. Another possibility is that trauma-exposure influences pleasantness ratings equally in both groups. Furthermore, this was a small study with eight controls and eight PTSD patients. Using fMRI, Jatzko et al (2006) investigated neural activity in response to a positively valenced video clip vs. a fixation cross in PTSD patients and non-trauma-exposed controls. PTSD patients showed increased neural reactivity in the posterior temporal, precentral gyrus and dlPFC, and decreased responses in the temporal pole (TP), FFG and parahippocampal gyrus, compared to controls (Jatzko et al., 2006). However, the sample size was small.
18
Page 18 of 44
Frewen et al (2012a) investigated self-reported positive responses to pleasurable events in female victims of childhood maltreatment with PTSD and healthy participants without childhood maltreatment or PTSD. On both the Snaith-Hamilton Pleasure Scale (SHAPS) (Snaith
ip t
et al., 1995) and Fawcett-Clark Pleasure Capacity Scale (FCPCS) (Fawcett et al., 1983) PTSD patients reported lower experience of pleasure in response to pleasurable activities, compared
cr
to controls (Frewen et al., 2012a). In a similar population, Frewen et al (2010) investigated
affective and neural responses to positive autobiographical audio-scripts compared to implicit
us
baseline activity. PTSD patients reported less positive emotions in response to audio-scripts of social and non-social positive autobiographical events compared to controls. Moreover, PTSD
an
patients showed increased negative emotions in response to positive audio-scripts, compared to controls. Also, compared to controls, PTSD patients had lower neural reactivity in the left
M
dorsomedial prefrontal cortex (dmPFC) and left TP in response to audio-scripts of positive social autobiographical events relative to implicit baseline activity. In response to audio-scripts of non-
te
insula (Frewen et al., 2010).
d
social positive autobiographical events, PTSD patients had higher neural reactivity in the left
Ac ce p
Taken together, PTSD was related to reduced TP reactivity (Frewen et al., 2010; Jatzko et al., 2006), reduced FFG reactivity (Jatzko et al., 2006; also reported by MacNamara et al., 2013), reduced dmPFC and increased insula reactivity (Frewen et al., 2010) in response to positive stimuli. As these brain areas are all important for processing of affective (social) stimuli and valence-assessment (e.g. Olson et al., 2007; Hayes et al., 2014), these findings suggest neural disturbances in affective processing of positive (social) stimuli in PTSD patients. This fits with the reduced self-reported experience of pleasure seen in PTSD patients compared to controls (Frewen et al., 2012a). However, as the studies by Jatzko et al (2006) and Frewen et al (2010, 2012a) all compared PTSD patients to non-trauma-exposed controls, trauma-exposure is a possible confounder. A recent study in victims of childhood maltreatment showed reduced dmPFC responses in response to positive words were related to childhood abuse but not 19
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psychopathology (van Harmelen et al., 2014). On the other hand, a different study by Frewen et al (2012b) reported that reduced dmPFC activity in response to a positive social audio-script was related to higher severity of the PTSD symptom ‘inability to experience positive emotions’
ip t
(Frewen et al., 2012b), suggesting that PTSD symptoms do play a role in the altered dmPFC responses. In the same study, increased insula responses were related to decreased positive
cr
affect in response to positive stimuli within PTSD patients. This notion is supported by an extensive neuroimaging meta-analysis, showing decreased dmPFC and increased insula
us
activity in PTSD patients compared to both trauma- and non-trauma-exposed controls (Patel et al., 2012). As the studies included by Patel et al (2012) mainly investigated responses to
an
negative stimuli, these aberrant dmPFC and insula responses in PTSD patients seem to occur to both positive and negative stimuli, irrespective of valence.
M
An interesting notion was put forward by Frewen and colleagues (2010; 2012b), who showed that PTSD patients did not only report reduced positive emotions such as happiness
d
and pleasure, but also increased negative emotions such as fear and shame, in response to
te
positive stimuli. This process was labeled as ‘negative affective interference’ by the authors, and
Ac ce p
suggests that PTSD patients, in particular victims of severe interpersonal or childhood trauma, may perceive positive stimuli as threatening or aversive. Both reduced positive and increased negative emotions were related with PTSD anhedonia severity. Furthermore, negative emotional responses to positive stimuli were associated with increased amygdala responses. This hypothesis should be considered when interpreting aberrant responses to positive stimuli, as decreased positive and increased negative emotional responses might result in similar behavioral outcomes (e.g. reduced approach) but arise from distinct psychological and neurobiological mechanisms (Frewen et al., 2010; 2012a; 2012b). Taken together, the studies by Jatzko et al (2006) and Frewen et al (2010, 2012a) suggest reduced hedonic responses and altered neural responses to positive stimuli in PTSD
20
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patients. Still, more research is needed to say whether these deficits are specific to PTSD, specific to trauma-exposure or the result of a combination of both.
DISCUSSION
ip t
4
The broad concept of reward functioning is reflected by the diversity of experiments and
cr
processes described in the 29 articles selected for this systematic review. Although findings are not wholly consistent, there seems to be a tendency towards both reduced motivational
us
(‘wanting’) and reduced consummatory (‘liking’) reward functioning in PTSD patients compared to healthy controls (see figure 1).
an
Given the PTSD symptom ‘diminished interest in pleasurable activities’, we expected PTSD to be related to motivational anhedonia, or reduced reward anticipation and approach
M
(‘wanting’). With regard to this phase of reward functioning, findings suggest that PTSD is related to specific deficits in reward anticipation and motivation; i.e. behavioural approach is
d
reduced when more effort is needed to pursue reward (Casada and Roache, 2005; Elman et al.,
te
2005). Furthermore, PTSD symptom severity was related to reduced self-reported BAS reward
Ac ce p
responsiveness, though only after controlling for the effects of experiential avoidance (Pickett et al., 2011). Interestingly, despite reduced reward responsiveness, reward-seeking behavior may be increased in PTSD, functioning as an avoidance strategy (Contractor et al., 2013; Pickett et al., 2011).
Based on the PTSD symptom ‘inability to experience positive emotions’, we expected PTSD to be related to consummatory anhedonia, or reduced hedonic responses to positive stimuli (‘liking’). With regard to this phase of reward functioning, converging evidence suggests that arousal and valence ratings of positive images are not affected in PTSD patients compared to controls, nor are physiological or neural responses to positive images (Adenauer et al., 2010; Amdur et al., 2000; Litz et al., 2000; Roberts et al., 2012; Spahic-Mihajlovic et al., 2005; van Rooij et al., 2014b; Wolf et al., 2009). However, PTSD patients did report reduced experience of 21
Page 21 of 44
pleasure and positive emotions in response to positive stimuli (Frewen et al., 2010; Frewen et al., 2012a; Steuwe et al., 2014). Furthermore, neural responses to positive stimuli seem to be reduced in PTSD patients in the FFG, TP and dmPFC compared to controls (Ehlers et al., 2006;
ip t
Frewen et al., 2010; Jatzko et al., 2006; MacNamara et al., 2013), whereas responses in the insula and possibly the amygdala are increased in PTSD patients (Frewen et al., 2010; Killgore
cr
et al., 2013), suggesting both increased and decreased processing of positive stimuli in different brain areas important for processing of affective stimuli, valence-assessment and emotion
an
4.2
us
regulation.
Neurobiology
Seeing the strong neurobiological basis of reward functioning, the observed deficits in
M
reward motivation and consumption in PTSD may well be explained by alterations in the reward pathway in the brain. Previous research has shown increased dopamine transporter (DAT)
d
availability in the striatum in PTSD patients (Hoexter et al., 2012). Increased DAT availability is
te
suggested to result in hyposensitivity to reward by lowering dopaminergic transmission. Striatal
Ac ce p
responses to reward have previously been related to resilience to trauma-exposure. Vythilingam et al (2009) showed that resilient trauma-exposed male veterans had lower ventral striatal responses to reward compared to non-trauma-exposed civilians (Vythilingam et al., 2009). Therefore, these authors suggested that dampened striatal responses are a sign of resilience, though striatal reward numbing may also well be the result of trauma-exposure. In opposition of the first explanation, a recent fMRI study in 200 civilian participants showed that high ventral striatal responses to positive feedback were related to resilience to the effect of life stress on positive affect (Nikolova et al., 2012). In line with the latter explanation, prolonged stress exposure is known to reduce striatal dopamine responses to reward (e.g. Pizzagalli, 2014). However, results from several studies included in this review suggest trauma-exposure in itself does not explain the observed reduced reward functioning in PTSD patients. It is possible that 22
Page 22 of 44
trauma-exposure reduces striatal responses to reward but that these effects are most strongly present in patients with PTSD. Indeed, this hypothesis is seemingly supported by three excluded fMRI studies, which showed that compared to trauma-exposed controls, PTSD was
ip t
related to decreased striatal responses to reward outcomes, relative to loss (Admon et al., 2013; Elman et al., 2009; Sailer et al., 2008). Furthermore, this PTSD-related decrease in striatal
cr
responses to reward, as measured after deployment, was not present during measurements prior to deployment (Admon et al., 2013). Interestingly, striatal responses to reward relative to
us
loss were negatively related to anhedonic PTSD symptom severity (Elman et al., 2009).
are difficult to make based on these studies.
an
However, due to the comparison of reward vs, loss, conclusions on reward-specific alterations
The studies that did compare positive relative to neutral stimuli found reduced FFG, TP
M
and dmPFC responses and increased AI and amygdala responses to positive stimuli in PTSD patients compared to controls (Ehlers et al., 2006; Frewen et al., 2010; Jatzko et al., 2006;
d
Killgore et al., 2013; MacNamara et al., 2013). Interestingly, the majority of these studies used
te
social positive stimuli. Indeed, the FFG and TP are important in detecting and processing of
Ac ce p
salient social stimuli, and the dmPFC is involved in reward evaluation and social emotional processing, together suggesting reduced social reward processing. This is in line with previous findings of reduced FFG and dmPFC responses in social anhedonia (Germine et al., 2011), but in contrast with meta-analysis findings of increased FFG responses to positive (social) stimuli in MDD (Zhang et al., 2013). Increased AI and amygdala responses to positive stimuli might reflect decreased positive or increased negative emotional responses to positive stimuli in PTSD patients (Frewen et al., 2012a). The fact that especially in studies investigating social stimuli, such as happy or attractive faces or positive social interactions, dysfunctional reward functioning in PTSD patients were reported, may indicate that PTSD is specifically related to social anhedonia. This fits in with significant social deficits seen in PTSD, such as social isolation and feelings of detachment and 23
Page 23 of 44
estrangement (American Psychiatric Association, 2013). However, reduced reward functioning was also observed in the few studies in which responses to monetary reward were investigated, suggesting it is not only social reward functioning that is affected. More research is needed to
ip t
systematically compare responses to social vs. non-social stimuli in PTSD. Taken together, reduced reward motivation and reduced hedonic responses to reward in
cr
PTSD are possibly coupled with hyporesponsiveness of the striatum and of PFC regions
important in (social) reward functioning. PTSD patients may be more sensitive to trauma- or
us
stress-induced reduction of dopamine signaling in the striatum, specifically in response to social stimuli. Studies including both trauma- and non-trauma-exposed controls are needed to
4.3
M
an
disentangle the effects of trauma and PTSD on reward functioning.
The role of sex
d
Sex (or gender) is known to affect PTSD prevalence, with women showing two to three times higher rates (Olff et al., 2007; Tolin and Foa, 2006). Furthermore, anhedonic symptoms
te
may be more prevalent in female PTSD patients compared to male PTSD patients: the PTSD
Ac ce p
symptom ‘diminished interest in pleasurable activities’ was reported significantly more often in female patients (81%) than in male patients (65%), although no sex-differences were seen in symptom prevalence of ‘inability to experience positive emotions’ (Carmassi et al., 2014). However, little research has focused on whether this sex difference is related to differences in reward functioning. In the current review, PTSD-related decreases in reward functioning were found primarily in studies with mixed-gender or predominantly female samples, whereas null findings seem to be found more often in male samples. This may suggest that PTSD-related differences in reward functioning are moderated by sex. Of the studies currently published only Spahic-Mihajlovic et al (2005) addressed sex differences. They observed reward deficits in females but not in males, but as female PTSD patients had higher PTSD symptom severity
24
Page 24 of 44
scores than men, more research is needed to confirm whether sex-specific effects are indeed present. Sex differences in reward functioning have been studied extensively in healthy
ip t
individuals. Although a meta-analysis of reward questionnaire studies showed men and women do not differ in sensitivity to reward, women were found to be more sensitive to negative events
cr
(Cross et al., 2011). On a neural and behavioral level however, sex differences in reward functioning have been shown. For example, men showed stronger striatal responses in
us
anticipation of money compared to women, whereas women responded stronger to anticipation of social reward (Spreckelmeyer et al., 2009). Research suggests that men may have stronger
an
prefrontal emotional and cognitive regulation (OFC, dlPFC) during reward tasks compared to women (van den Bos et al., 2013a). Stress may further enhance these sex differences: several
M
studies reported increased reward sensitivity and approach under stress in men, whereas in women, decreased reward sensitivity and approach were observed under stress (e.g. Lighthall
d
et al., 2012; Lighthall, Mather, & Gorlick, 2009), although opposite effects have also been
te
observed (Preston et al., 2007). These sex differences in reward functioning under stress may
Ac ce p
be mediated by differential cortisol and dopamine responses under stress (Trainor, 2011; van den Bos et al., 2013b). Thus, sex differences in reward functioning may increase after traumaexposure and lead to a stronger imbalance in sensitivity towards negative and positive stimuli in women compared to men, such that men will have a stronger focus on reward approach, whereas women will focus more on loss avoidance. Olff et al (2007) suggested several factors to explain sex differences in PTSD that may also explain PTSD-related differences in reward functioning between male and female samples. Compared to men, women more frequently experience sexual trauma and are typically exposed at a younger age, leading to a higher chance of developing PTSD and higher PTSD severity compared to men (Olff et al., 2007; Tolin and Foa, 2006). Indeed, a number of studies included in this review with all female samples investigated women with childhood abuse-related PTSD 25
Page 25 of 44
(Frewen et al., 2010; Frewen et al., 2012a; Steuwe et al., 2014). As childhood trauma-exposure also affects reward functioning (Goff et al., 2013; Guyer et al., 2006; Mehta et al., 2010), sex differences in reward functioning may be mediated by age at trauma exposure. Thus, if women
ip t
with PTSD are exposed to trauma at a younger age compared to men with PTSD, and if trauma-exposure leads to stronger decreases in reward sensitivity in women compared to men,
cr
this may explain the reduced reward functioning seen in women with PTSD compared to men. It should be noted that several factors are confounded with sex in the studies reported in
us
this review, as most studies with predominantly male samples included participants exposed to combat trauma, whereas participants in mixed-gender and predominantly female studies were
an
mainly exposed to civilian trauma. This reflects existing sex differences in type of traumaexposure (Tolin and Foa, 2006).
M
In sum, stronger reward deficits are apparently present in women with PTSD compared to men. However, we cannot rule out the possibility that sample-specific factors such as trauma
Comorbid psychiatric disorders
Ac ce p
4.4
te
d
type explain (part of) this sex difference.
As reward deficits are clearly present in MDD (e.g. Zhang et al., 2013), and MDD is highly comorbid with PTSD (Keane and Kaloupek, 1997), this is an important confounder to consider while interpreting the results of the included studies. The fact that anhedonia is a symptom of both PTSD and MDD is likely not simply an epiphenomenon of comorbidity; anhedonic symptoms were equally present in PTSD patients with and without MDD (Franklin and Zimmerman, 2001). A number of studies reporting reward differences between PTSD and controls included a PTSD sample with significant levels of comorbidity with MDD or did not mention comorbidity rates (see table 1a & 1b). Although most studies did not control for comorbid MDD, the studies that that did control for MDD or depressive symptoms showed reward deficits in PTSD were still 26
Page 26 of 44
present after correcting for comorbid MDD (Elman et al., 2005; Hopper et al., 2008; MacNamara et al., 2013). The only exception is the study by Van Rooij et al (2014), who did not find PTSDrelated differences in responses to positive images, but did find that PTSD patient with comorbid
ip t
MDD had decreased ACC responses to positive images compared to PTSD patients without MDD, suggesting stronger reward deficits in PTSD patients with MDD. This may be explained
cr
by the fact that PTSD patients with MDD had higher scores on PTSD anhedonic symptoms (van Rooij et al., 2014b). Together, the included studies suggest that although diminished reward
us
functioning in PTSD may be similar to diminished reward functioning in MDD, findings are not driven solely by comorbid MDD.
an
Additionally, substance abuse and use of antidepressants, anxiolytics and other psychoactive medication by PTSD patients may influence reward functioning. As most studies in
M
the current review excluded alcohol and substance-related disorders or had samples with relatively low levels of comorbidity (see table 1a & 1b), this is no significant confounder of our
d
results. Although most studies did not control for possible confounding effects of psychoactive
te
medication, no effect of psychoactive medication on reward outcomes was found in studies that
Ac ce p
did control for medication use (Elman et al., 2005; Hopper et al., 2008; Roberts et al., 2012; Swick et al., 2012). Only Dretsch et al (2013) found higher reward sensitivity in PTSD patients using antidepressants compared to PTSD patients not using antidepressants. It is likely that when PTSD symptoms are still present despite the use of psychoactive medication, rewardrelated deficits remain.
In sum, although confounding effects of comorbid depression and use of psychostimulants on reward functioning in PTSD cannot be ruled out, these do not seem to alter the observed deficits in reward functioning.
4.5
Clinical implications
27
Page 27 of 44
Currently, the evidence-based psychotherapies available for PTSD mainly focus on the regulation of negative emotions. Based on the deficits in reward functioning as suggested by this review, PTSD psychotherapy may put more emphasis on positive affect. Dunn (2012)
ip t
suggests that psychotherapy outcome in MDD can substantially improve by putting more emphasis on positive emotion experience (Dunn, 2012), especially when patients report
cr
significant anhedonic symptoms. In MDD patients, psychotherapy specifically aimed at
increasing approach and positive experience of rewarding stimuli resulted in a significant
us
reduction of depressive symptoms. Interestingly, these observed clinical changes were accompanied by increased striatal reward responses to reward anticipation, and increased OFC
an
responses to receiving reward (Dichter et al., 2009). This type of psychotherapy might also be effective for PTSD patients. In PTSD following severe interpersonal trauma, the presence of
M
negative affective interference (elicitation of negative emotions in response to positive stimuli) could warrant a different therapeutic approach, by focusing on reducing negative emotions to
d
reward before attending to increasing positive emotions (Frewen et al., 2012b). Furthermore,
te
the degree of reward dysfunction at the time of treatment initiation may be informative to predict
Ac ce p
therapy success, as neural responses in the striatum and PFC to Go-trials during the Go-No go task predicted response to cognitive behavioral therapy in PTSD patients (Falconer et al., 2013).
Deficits in reward functioning may also be restored by pharmacological agents working on the reward pathway. Selective serotonin reuptake inhibitors (SSRI) used for treatment of PTSD are known to enhance striatal function and may exert part of their therapeutic effects through improvement of reward functioning (Heller et al., 2013). Other pharmacological agents are also promising to improve (social) reward-related deficits in PTSD patients. For example, administration of oxytocin can increase reward sensitivity to social positive stimuli, such as happy faces, by altering responses in the brain reward pathway (Scheele et al., 2012). Oxytocin administration is suggested as a promising agent for medication-enhanced psychotherapy in 28
Page 28 of 44
PTSD for various reasons (Koch et al., 2014; Olff et al., 2010). Increasing sensitivity to social positive stimuli may also enhance therapeutic engagement. Moreover, patients could become more sensitive to social support, a protective factor known to improve cognitive behavioral
Limitations and directions for future research
cr
4.6
ip t
therapy and exposure treatment outcome in PTSD (Thrasher et al., 2010).
There are some methodological issues that must be kept in mind while interpreting the
us
results of this systematic review; especially the small number of available studies per phase of reward functioning, as well as the small sample size of most studies. The included participant
an
groups were diverse, differing in sex, trauma type and levels of comorbid depression, reflecting
conclusions must be drawn with caution.
M
the heterogeneity of the PTSD patient population. Considering the fragmentation of the data,
PTSD is a heterogeneous disorder and symptom profiles differ between patients (e.g.
d
Galatzer-Levy & Bryant, 2013). It is probable that different symptom clusters are differentially
te
related to reward functioning, such that the presence of dysregulations in reward functioning
Ac ce p
may depend on whether patients report anhedonic PTSD symptoms. This may explain some of the observed inconsistent findings in reward functioning in PTSD patients. Relating reward functioning to anhedonic PTSD symptoms may lead to further insights in the specific mechanisms underlying reward deficits and may be more sensitive than relating overall PTSD severity or dichotomous PTSD diagnosis to reward functioning. Despite obvious sex differences in PTSD (Olff et al., 2007), few of the currently available studies investigated the role of sex. Thus, there is a need for studies that address sex differences. If sex differences can be addressed in both civilian and veteran PTSD populations, this will also further clarify the possible confounding effect of trauma type on sex differences. Furthermore, studies using both trauma-exposed and non-trauma-exposed control groups are
29
Page 29 of 44
needed to see which differences in reward functioning are specific to PTSD, and which are trauma-related. In addition, in order to translate current observations on deficits in reward functioning in
ip t
PTSD to clinical practice aimed at improving PTSD treatment, more knowledge about the precise nature of reward deficits and mechanisms that underlie anhedonic symptoms in PTSD is
cr
needed. As different neural and psychological processes underlie motivational anhedonia
(‘wanting’) and consummatory anhedonia (‘liking’), they would require different therapeutic
us
approaches both from a pharmacological and a psychological point of view (e.g. focus on starting pleasurable activities vs. focus on enjoying pleasurable activities). Therefore, future
an
studies are advised to use measurements that distinguish between the different phases of reward functioning. The DSM 5 partly provides for this distinction by differentiating between
M
symptoms of diminished interest in significant activities (motivational or ‘wanting’) and the persistent inability to experience positive emotions (consummatory or ‘liking’). However, besides
d
consummatory anhedonia the latter item also includes aspects of dysphoria (reduction of
te
positive affect in general), resulting in a blurred measure of anhedonia.
Ac ce p
The concept of negative affective interference should also be investigated further; increased negative emotions in response to reward could result in behaviorally similar reward dysfunction as decreased positive emotions, but would require a different therapeutic approach (Frewen et al., 2012b). Also, systematic comparison of different types of positive stimuli, such as social and monetary reward, would be interesting to further establish specificity of reward dysfunction. To properly investigate specific deficits in reward functioning, it is important to distinguish between responses to positive and negative stimuli. Most previous neuroimaging studies investigated the difference between responses to positive relative to negative stimuli. However, for the investigation of specific reward-related deficits comparing positive to neutral conditions is advised for future studies. When reward conditions are contrasted against negative conditions, it is difficult to infer whether differences between patients and controls reflect 30
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different responses towards positive stimuli, negative stimuli or both. Furthermore, as many brain areas involved in reward functioning, such as the striatum and amygdala, react to both positive and negative stimuli, a contrast relative to neutral events may not only be more
ip t
meaningful but also more powerful. The study by Killgore et al (2013) exemplifies the benefits of contrasting to neutral stimuli; PTSD patients showed increased amygdala reactivity compared to
cr
healthy controls towards both fearful and happy faces relative to neutral stimuli, but no
difference was seen when fearful faces were contrasted relative to happy faces. In line with the
us
evidence that similar brain regions respond to positive and negative stimuli, a final suggestion would be to relate neural responses to behavioural and affective responses, to be able to better
M
4.7
an
interpret the findings in terms of valence.
Conclusions
Although findings are not wholly consistent and more research is needed to further
d
elucidate the reward-related mechanisms underlying anhedonic symptoms in PTSD, the results
te
of this review suggest the presence of deficits in both motivational reward functioning and
Ac ce p
consummatory reward functioning in PTSD, such that PTSD patients exhibit reduced anticipation, approach and hedonic responses towards positive stimuli. These deficits in reward functioning were observed as reduced self-reported affective responses, behavioural, physiological and neural responses. Thus, PTSD patients seem to show hyporesponsivity to positive stimuli, although this effect seems less pronounced and less consistent than the hyperresponsivity to negative stimuli previously reported in PTSD (Hayes et al., 2012a, 2012b). Overall, reward deficits were seen more often in studies looking at social positive stimuli compared to studies looking at non-social stimuli, suggestive of social anhedonia. Also, reward deficits seem to be present more often in samples with female PTSD patients, although sex differences are intertwined with differences in trauma type. Which factors are responsible for the apparent sex difference in reward functioning in PTSD patients needs to be investigated further 31
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by future studies. Together, these findings are a first step in understanding the mechanisms underlying the frequent anhedonic symptoms in PTSD and encourage the investigation of new
ip t
treatment targets aimed at improving reward functioning.
cr
ACKNOWLEDGEMENTS
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The study is supported by grants from ZonMw, the Netherlands organization for Health Research and Development (grant no. 91210041) and the Academic Medical Center Research
M
an
Council (grant no. 110614).
REFERENCES
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FIGURE CAPTIONS Figure 1 Title: Reward functioning in PTSD Description: Overview of the different phases of reward functioning, and the findings of differences in reward functioning in PTSD patients compared to controls. Abbreviations: PTSD:
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post-traumatic stress disorder; ↓: decreased in PTSD; ↑: increased in PTSD; =: no differences
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between PTSD and healthy control participants.
TABLES
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Title: Overview of studies investigating reward motivation in PTSD.
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Table 1a.
Table 1b.
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Title: Overview of studies investigating reward consumption in PTSD.
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Description: Abb: N: number of participants; PTSD: participants with post-traumatic stress disorder; TC: trauma-exposed control participants; NTC: non-trauma-exposed control
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participants; C: control participants, trauma-exposure unknown; T: trauma-exposed participants
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(PTSD status unknown); M: male participants; D: depressive disorder; S: substance-related or
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alcohol disorder; EEG: electro-encephalogram; fMRI: functional magnetic resonance imaging; SPSRQ: sensitivity to punishment sensitivity to reward questionnaire; BIS: behavioral inhibition system; BAS: behavioral approach system; IAPS: International Affective Picture System; SHAPS: Snaith-Hamilton Pleasure Scale; FCPCS: Fawcett-Clark Pleasure Capacity Scale; ROI: Region of interest analysis; SVC: small volume corrected for multiple comparisons; BA: Brodmann area; PFC: prefrontal cortex.
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Table(s)
Trauma type
Comorbidity Medication use
Modality
15 PTSD (100% M), 11 TC (100% M)
Combat
27% D, 0% S 67%
Questionnaire PTSD < TC: Lower self-reported reward expectation of monetary reward in Wheel-ofFortune task.
Cilivian, mixed
Unknown
Unknown
23 PTSD (91%M), 23 Combat TC (65%M) 35 PTSD, 256 TC Cilivian, (25% M) mixed
Unknown
43%
Unknown
Unknown
Questionnaire PTSD avoidance and PTSD hyperarousal symptoms positively correlated to Sensitivity to Increased Reward score on the SPSRQ questionnaire. PTSD reexperiencing and PTSD dysphoria symptoms not correlated to Sensitivity to Reward score. PTSD avoidance mediated positive relation between sensitivity to reward and PTSD dysphoria. Questionnaire PTSD = TC, no difference on BAS-Reward Responsiveness subscale of the BIS/BAS self- No report questionniare. Questionnaire PTSD total symptom score not related to BAS total score, BAS reward responsiveness, No BAS drive or BAS fun-seeking subscales of the BIS/BAS self-report questionniare.
Cilivian, mixed
Unknown
Unknown
Questionnaire PTSD total symptom scores negatively related to BAS-reward responsiveness and positively related to BAS-drive when accounting for avoidance, and not related to BAS-fun seeking or BAS total score of the BIS/BAS self-report questionniare.
Reduced / Increased
Combat
Unknown
Unknown
Behavioral
No
Cilivian, mixed
70% D, 0% S 0%
Behavioral
PTSD total symptom scores not related to reaction times in approach trials on an affective Go-No go task. PTSD = TC: No general difference in reaction times on approach trials on a Stop-signal task. PTSD < TC: Progressively slower reaction times during approach trials over time. PTSD = TC: No difference in reaction times on monetary-rewarded approach trials. PTSD < TC: Slower reaction times in non-monetary-rewarded approach trials (transient effect).
10 PTSD (50% M), Cilivian, 13 TC (62%M) mixed 21 PTSD (95%M), 16 Combat TC (88%M)
70% D, 0% S 0%
PTSD < TC: Lower increase in heart rate & skin conductance in response to monetary reward on a Stop-signal task. PTSD = TC: no difference in reaction time to approach trials on a Go-No go task.
Reduced
Unknown
Behavioral, physiological Behavioral
Unknown
Behavioral
PTSD = TC = NTC: No difference in reaction times on approach trials on a Stop-signal task.
No
58%
Behavioral
PTSD = TC: No difference in reaction times on approach trials on a Go-No go task.
No
PTSD = TC = NTC: no differences in reaction time to approach trials on a Stop-signal anticipation task. No differences in brain responses during approach trials vs rest, whole brain or ROI (striatum, inferior frontal gyrus, precentral gyrus). PTSD < TC: Lower amount of key presses to prolong watchtime of attractive female faces (valence specific) on a beautiful faces paradigm. PTSD = TC: no differences in approach to monetary reward on the Iowa gambling task.
No
Approach: Questionnaires Contractor et al (2013) 138 PTSD, 170 TC (36% M)
Dretsch et al (2013) Maack et al (2012)
Pickett et al (2011)
851 T (N PTSD unknown) (0% M)
Approach: Behavioral tasks Amick et al (2013) 47 PTSD, 25 TC (88% M) Casada & Roache 10 PTSD (50% M), (2005) 13 TC (62%M)
Behavioral 43% Behavioral
Reduced No
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Dretsch et al (2013)
58%
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Elman et al (2005)
0% Behavioral
No
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Van Rooij et al (2014)
Reduced / No
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Swick et al (2012)
Reduced
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Li et al (2013)
D unknown, 0% S, 100% mTBI 26 PTSD (12%M), 38 Childhood Unknown TC (3%M), 36 NTC trauma (6%M) 40 PTSD (98% M), Combat Unknown 33 TC (94%M) 28 PTSD (100%M), Combat 54% D, 0% S 26 TC (100%M), 25 NTC (100%M) 12 PTSD (100% M), Combat 25% D, 0% S 11 TC (100%M) 23 PTSD (91%M), 23 Combat Unknown TC (65%M)
Reward affected?
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Casada & Roache (2006) Depue et al (2014)
Findings
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Anticipation Hopper et al (2008)
N (% males)
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Study
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Table(s)
Trauma type
Comorbidity in PTSD Medication use in group PTSD group
Modality
Findings
Reward affected?
15 PTSD (100% M), 11 TC (100% M)
Combat
27% D, 0% S
67%
Questionnaire
PTSD < TC: Lower self-reported reward satisfaction with monetary reward in Wheel-ofFortune task (group by expectation interaction).
Reduced
36 PTSD (58% M), 21 TC (43% M), 16 NTC (44% M) 17 PTSD (100% M), 11 TC (100% M), 14 NTC (100% M)
War, torture
83% D, 0% S
22-42%
Questionnaire
PTSD < TC & NTC: Lower pleasantness ratings of positive images in an affective image response task. PTSD = TC & NTC: No difference in arousal ratings of positive images.
Reduced / No
Combat
32%D, 12% S (>2 weeks free of substance use)
0%
Questionnaire, PTSD = TC & NTC: No differences in pleasantness or arousal ratings of positive images in No physiological an IAPS image rating task. PTSD = TC & NTC: No differences in physiological responses to positive images (heart rate, skin conductance, frontalis muscle tension).
Litz et al (2000)
32 PTSD (100% M), 29 TC (100% M)
Combat
59% D, 18% S
Unknown
Roberts et al (2012)
18 PTSD (17%M), 18 Cilivian, mixed D unknown, 0% S, TC (17%M) 100% epilipsy
56-100%
Spahic-Milajhovic et al (2005)
21 PTSD (48% M), 21 TC (52% M)
War, torture
0% D, 0% S
Unknown
Van Rooij et al (2014)
29 PTSD (100% M), 28 TC (100% M), 25 NTC (100% M) 49 PTSD (100%M), 75 TC (100%)
Combat
55% D, 0% S
Combat
Unknown
Combat
Wolf et al (2009)
Positive Faces Elman et al (2005)
Other positive stimuli Frewen et al (2012)
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Questionnaire, PTSD = TC: No differences in pleasantness or arousal rating of positive images on an IAPS physiological image rating task. PTSD = TC: No difference in zygomatic expressive-motor response or skin conductance to positive images. Questionnaire, PTSD = TC: No difference in pleasantness ratings, positive emotional behavior or physiological cardiovascular responses to positive images on Lang's looking-at-pictures test. PTSD > TC: Higher arousal ratings to positive pictures. Questionnaire PTSD < TC: Lower arousal ratings of positive images in males and females on Lang's looking-at-pictures test. PTSD = TC: No difference in pleasantness rating for positive images in males. PTSD < TC: Lower pleasantness ratings for positive images in females.
0%
fMRI
Unknown
Questionnaire
25% D, 0% S
58%
Questionnaire
Childhood maltreatment Combat
56% D, 6% S
Unknown
Questionnaire
21%D, 16% S
0%
EEG
Mainly interpersonal violence
unknown in PTSD group (whole sample: 63% lifetime S, 17% mood and anxiety disorders) Whole group: 14% D, 0% S
Unknown
EEG
0%
14 PTSD (71%M), 22 Cilivian, mixed 0%D, 0% S C (trauma exposure unknown) (64%M)
55 PTSD (0% M), 35 Childhood NTC (0% M) maltreatment
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12 PTSD (100% M), 11 TC (100% M) Steuwe et al (2014) 16 PTSD (0%M), 16 NTC (0%M) MacNamara et al (2013) 19 PTSD (100%M), 14 TC (100%M) Ehlers et al (2006) 19 PTSD (% M unknown, 34% in whole group), 127 TC (% M unknown, 34% in whole group) Herringa et al (2013) Continuous: 28 T, of which 18 PTSD (100% M) Killgore et al (2013)
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Admur et al (2000)
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Positive Images Adenauer et al (2010)
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Money Hopper et al (2008)
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N (% males)
ce pt
Study
Combat
29% D, 4% S
No
Increased / No Reduced / No
PTSD = TC & NTC: No difference in neural reactivity towards positive vs neutral pictures on No an IAPS image rating task (no differences observed on whole brain level nor in ROI's amygdala, hippocampus, insula, and anterior cingulate cortex, SVC). PTSD = TC: No difference in pleasantness or arousal ratings of positive pictures on Lang's No looking-at-pictures test.
PTSD = TC: No differences in attractiveness ratings of attractive faces of opposite sex in a beautiful faces paradigm. PTSD < NTC: Lower positive rating of happy faces and lower positive feeling in response to happy faces in a direct/averted gaze to facial expressions task. PTSD < TC: Lower vertex positive potentials to happy faces in an emotional face-matching task. PTSD = TC: No difference in late positive potentials to happy faces. PTSD < TC: Slower event related potentials to happy faces in the midline posterior and right frontal EEG leads in an emotional face-recognition task. PTSD = TC: No difference in height of event related potentials to happy faces.
No
fMRI
PTSD symptoms not related to neural reactivity to implicitly shown happy faces vs neutral shapes (no differeces on whole brain level nor in ROI's anteromedial PFC, amygdala, hippocampus and insula, SVC) in an implicit facial expression processing task.
No
0%
fMRI
PTSD > C: Higher amygdala reactivity to happy faces vs neutral faces in a masked facial affect paradigm (no difference observed in ROI's insula, hippocampus/parahippocampal gyrus, nor ventromedial PFC, orbitofrontal cortex and anterior cingulate cortex, SVC).
Increased
0%
Questionnaire
PTSD < NTC: Lower self-reported experience of pleasure towards pleasurable activities on the SHAPS and FCPCS hedonia questionnaires.
Reduced
Reduced Reduced Reduced
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