Anhedonia reflects impairment in making relative value judgments ...

SCHRES-07709; No of Pages 6 Schizophrenia Research xxx (2018) xxx–xxx

Contents lists available at ScienceDirect

Schizophrenia Research journal homepage: www.elsevier.com/locate/schres

Anhedonia reflects impairment in making relative value judgments between positive and neutral stimuli in schizophrenia Gregory P. Strauss a,⁎, Katherine Frost Visser a, William R. Keller b, James M. Gold c, Robert W. Buchanan c a b c

University of Georgia, Department of Psychology, USA Dartmouth College, Geisel School of Medicine, Department of Psychiatry, USA University of Maryland School of Medicine, Department of Psychiatry, Maryland Psychiatric Research Center, USA

a r t i c l e

i n f o

Article history: Received 6 November 2017 Received in revised form 29 January 2018 Accepted 15 February 2018 Available online xxxx Keywords: Anhedonia Negative symptoms Psychosis Value representation

a b s t r a c t Anhedonia (i.e., diminished capacity to experience pleasure) has traditionally been viewed as a core symptom of schizophrenia (SZ). However, modern laboratory-based studies suggest that this definition may be incorrect, as hedonic capacity may be intact. Alternative conceptualizations have proposed that anhedonia may reflect an impairment in generating mental representations of affective value that are needed to guide decision-making and initiate motivated behavior. The current study evaluated this hypothesis in 42 outpatients with SZ and 19 healthy controls (CN) who completed two tasks: (a) an emotional experience task that required them to indicate how positive, negative, and calm/excited they felt in response to a single emotional or neutral photograph; (b) a relative value judgment task where they selected which of 2 photographs they preferred. Results indicated that SZ and CN reported similar levels of positive emotion and arousal in response to emotional and neutral stimuli; however, SZ reported higher negative affect for neutral and pleasant stimuli than CN. In the relative value judgment task, CN displayed clear preference for stimuli differing in valence; however, SZ showed less distinct preferences for positive over neutral stimuli. Findings suggest that although in-the-moment experiences of positive emotion to singular stimuli may be intact in SZ, the ability to make relative value judgments that are needed to guide decision-making is impaired. Original conceptualizations of anhedonia as a diminished capacity for pleasure in SZ may be inaccurate; anhedonia may more accurately reflect a deficit in relative value judgment that results from impaired value representation. © 2018 Elsevier B.V. All rights reserved.

1. Introduction Anhedonia has long been considered a core clinical feature of schizophrenia (SZ) (Bleuler, 1911; Kraepelin, 1919; Rado, 1953). However, modern empirical research calls into question whether the traditional conceptualization of anhedonia as a diminished capacity to experience pleasure accurately characterizes the nature of affective abnormalities in SZ (Barch and Dowd, 2010; Gold et al., 2008; Kring and Elis, 2013; Strauss and Gold, 2012). Specifically, during laboratory-based studies where participants are directly exposed to various types of pleasant stimuli (e.g., complex photographs, food, social interactions), people with SZ report levels of valence and arousal that are comparable to healthy controls (CN) (for meta-analyses see Cohen and Minor, 2010; Llerena et al., 2012). Several real-world experience sampling studies also indicate that people with SZ report increases in positive emotion that are comparable to CN when engaged in activities (Gard et al., 2007; Oorschot et al., 2013). Such findings have led some to suggest ⁎ Corresponding author at: University of Georgia, Department of Psychology, 125 Baldwin St., Athens, GA 30602, USA. E-mail address: [email protected] (G.P. Strauss).

that anhedonia should be reconceptualized in SZ and no longer considered a diminished capacity to experience pleasure (Barch and Dowd, 2010; Cohen et al., 2011; Gold et al., 2008; Kring and Elis, 2013; Kring and Moran, 2008; Strauss and Gold, 2012). An important question that has yet to be answered is why apparently normal hedonic responses do not translate into a normal frequency of reward-seeking behavior in SZ (Gard et al., 2014; Myin-Germeys et al., 2000). One possibility is that SZ patients have impairments in making “relative” value judgments that are needed to effectively guide decision-making. In most laboratory-based studies, participants are asked to make “absolute” value judgments, i.e., to report how positive they feel in response to a single stimulus. However, in most real-life situations, value is not assigned in absolute terms. Rather, the value of a stimulus is typically determined in relative terms after being considered alongside other stimuli. For example, at an ice-cream parlor, one might sample a spoonful of mint chocolate chip ice cream and a spoonful of vanilla ice cream prior to deciding which of these two options to select. The value of one option may increase or decrease as it is considered in relation to the other options that have been sampled. The ability to make nuanced distinctions between two or more stimuli has been associated with the orbitofrontal cortex (OFC), which is critical for encoding relative rather

https://doi.org/10.1016/j.schres.2018.02.016 0920-9964/© 2018 Elsevier B.V. All rights reserved.

Please cite this article as: Strauss, G.P., et al., Anhedonia reflects impairment in making relative value judgments between positive and neutral stimuli in schizophrenia, Schizophr. Res. (2018), https://doi.org/10.1016/j.schres.2018.02.016

2

G.P. Strauss et al. / Schizophrenia Research xxx (2018) xxx–xxx

than absolute value (Fellows and Farah, 2007; Wallis, 2007a, 2007b; Wallis and Miller, 2003). Given that structural and functional abnormalities of the OFC are well documented in SZ (Avsar et al., 2013; Barch and Dowd, 2010; Nakamura et al., 2008; Ohtani et al., 2014; Shenton et al., 2001) it is plausible that SZ patients would be impaired at making relative value judgments. In a prior study (Strauss et al., 2011), we examined this possibility by administering a well-validated test of preference transitivity (Fellows and Farah, 2007). Participants viewed a series of photographs within a given category of mildly pleasant stimuli (e.g., puppies, fruit) and were simply asked to select which of 2 simultaneously presented visual stimuli they preferred. From these individual selections, a preference hierarchy was formed that rank-ordered individual stimulus preferences of each participant. Transitivity among preferences (e.g., if a subject prefers A over B and B over C, then they should prefer A over C) was calculated, and instances where transitivity was violated reflect impairments in making relative value judgments. Results indicated that participants with SZ violated the rules of transitivity significantly more often than CN, and these violations were of greater magnitude. Furthermore, increased severity of anhedonia was associated with a greater number and magnitude of transitivity violations. Thus, findings suggested that SZ patients display impairment in making relative value judgments and that these deficits were associated with self-reported anhedonia. In the current study, we extended our prior experiment (Strauss et al., 2011) in several important ways. First, we had participants make preference judgments among pairs of stimuli that were rankordered in valence, not by the participant's own hierarchy, but by normative ratings from the International Affective Picture System (Lang et al., 2008). Second, whereas our prior study primarily allowed us to determine whether participants with SZ have deficits in making relative value judgments between pairs of mildly pleasant stimuli, this design allowed us to systematically pair stimuli within the same valence range and stimuli from different valence ranges to determine whether deficits in making relative value judgments cause stimuli from different categories to be less discriminable. Third, we directly compared preferences for social and non-social stimuli within the same valence range, as there has been some indication that anhedonia may primarily arise in relation to social stimuli or contexts (Blanchard et al., 2001; Cohen et al., 2011). This design therefore allowed us to examine whether impairments in making relative value judgments were primarily driven by reduced preference for social stimuli. Fourth, we also had participants make standard “absolute” value judgments, where they indicated how positive, how negative, and how calm/excited (i.e., arousal) they felt when exposed to a single social or non-social stimulus. Separate ratings of how positive and how negative participants felt in response to each stimulus were obtained because positivity and negativity are not diametric opposites (Larsen et al., 2001). Rather, they are separable and partially distinct components of the affect system that can be experienced simultaneously, allowing co-activations of positive and negative emotion to occur (Norris et al., 2010). The inclusion of absolute and relative value judgment tasks within the same experiment allowed us to directly test a hypothesized dissociation between intact absolute judgments and impaired relative value judgments, which has only been inferred in past studies (Strauss et al., 2011). The following hypotheses were made: 1) During the absolute value judgment phase, SZ and CN would display comparable ratings of how positive they felt in relation to pleasant and neutral stimuli; however, SZ would report greater experience of negative emotion to neutral and pleasant stimuli (Cohen and Minor, 2010). No differences in selfreported negative emotion to unpleasant stimuli were expected; however, based on prior studies (Trémeau et al., 2009), we expected SZ to report more positive emotion to unpleasant stimuli than CN; 2) Based on the meta-analysis by Llerena et al. (2012), arousal ratings were not expected to significantly differ between SZ and CN for pleasant and unpleasant, but SZ were expected to have higher arousal ratings for neutral stimuli; 3) To evaluate a “social-specific” anhedonia deficit (Cohen et al.,

2011), we compared social and non-social stimuli for self-reports of positive emotion, negative emotion, or arousal in the absolute judgment phase. These analyses were exploratory (i.e., directionality was not predicted) because it is unclear whether static images are really social in nature, or if they just convey social meaning; 4) SZ would display deficits in the relative value judgment task (Strauss et al., 2011), particularly while discriminating between pleasant and neutral stimuli; 5) Reduced preference for pleasant over neutral stimuli would be associated with greater severity of anhedonia in the SZ sample (Strauss et al., 2011).

2. Method 2.1. Participants Participants included 42 individuals meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM–IV– TR: American Psychiatric Association, 2000) criteria for schizophrenia or schizoaffective disorder (SZ) and 19 healthy controls. Individuals with SZ were recruited from the outpatient research program at the Maryland Psychiatric Research Center and evaluated during periods of clinical stability as determined by a minimum of 4-weeks of consistent medication dose and type. Consensus diagnosis was established via a best-estimate approach based on psychiatric history and multiple interviews and subsequently confirmed using the Structured Clinical Interview for DSM-IV (SCID: First et al., 1997), All patients met DSMIV lifetime diagnostic criteria for schizophrenia or schizoaffective disorder and were prescribed antipsychotic medications at the time of testing (see Table 1). Healthy control subjects (CN) were recruited through random-digit dialing and word of mouth among enrolled participants. All CN underwent a screening interview, including the SCID-I and SCID-II (Pfohl et al., 1997) and did not meet lifetime criteria for a psychotic disorder or any current Axis I or II disorder. CN also had no family history of psychosis. The SCID was used to determine that both SZ and CN participants did not meet DSM-IV criteria for substance abuse or dependence over the past 6 months, and lack of recent substance use was confirmed by urine toxicology at the time of testing. All participants were also screened for lifetime neurological disorders and were free from neurological conditions (e.g., traumatic brain injury, epilepsy).

Table 1 Demographic characteristics of sample.

Demographics Age Participant Education Parental Education % Male (n) Race % (n) Caucasian African-American American-Indian Mixed-Race Symptoms BPRS Positive BPRS Negative BPRS Disorganized BPRS Total BNSS Total BNSS Anhedonia LOF Total

SZ (n = 42)

CN (n = 19)

Test statistic, p-value

43.8 (11.5) 12.9 (2.05) 13.4 (2.05) 66.7% (28)

42.8 (9.11) 15.0 (1.86) 14.5 (2.42) 63.2% (12)

F = 0.12, p = 0.73 F = 14.06, p b 0.001 F = 2.71, p = 0.11 χ2 = 0.07, p = 0.79 χ2 = 1.94, p = 0.59

90.5% (38) 4.8% (2) 2.4% (1) 2.4% (1)

100.0% (19) 0% (0) 0% (0) 0% (0)

2.4 (1.1) 2.2 (1.1) 1.5 (0.4) 38.4 (9.5) 25.4 (17.3) 1.8 (1.2) 18.8 (7.6)

– – – – – – –

Note: SZ = schizophrenia; CN = control. SZ were prescribed a variety of antipsychotic medications, either alone (clozapine, n = 12; risperidone, n = 7; haloperidol, n = 3; ziprasidone, n = 3; fluphenazine, n = 2; haloperidol decanoate, n = 2; olanzapine, n = 2; aripiprazole, n = 1; chlorpromazine, n = 1; quetiapine, n = 1; thioridazine, n = 1) or in combination with another antipsychotic (clozapine and risperidone, n = 4; clozapine and haloperidol, n = 1; clozapine and quetiapine, n = 1; haloperidol, aripiprazole, n = 1).



Participants in the SZ and CN groups did not differ on age, parental education, gender, or race; however, SZ had significantly lower personal education than CN (see Table 1). 2.2. Procedures Participants first completed a standardized clinical interview administered by a clinical psychologist (GPS) trained to MPRC reliability standards (reliability N0.80), after which participants with SZ were rated on the Brief Psychiatric Rating Scale (BPRS) (Overall and Gorham, 1962), Brief Negative Symptom Scale (BNSS) (Kirkpatrick et al., 2011; Strauss et al., 2012a; Strauss et al., 2012b), Level of Functioning Scale (LOF) (Hawk et al., 1975), Calgary Depression Scale (CDS: Addington et al., 1993), and the Scale for the Assessment of Negative Symptoms (SANS: Andreasen, 1984). The emotional experience and preference judgment task was then administered in the context of a larger battery of tasks examining emotion processing. Chlorpromazine equivalent dosage (CPZ) was calculated according to Woods (2003). 2.3. Emotional experience and preference judgment task The Emotional Experience task had two phases. In the first phase (absolute value judgments), participants were exposed to a single pleasant, unpleasant, or neutral image from the International Affective Picture System (IAPS: (Lang et al., 2008) and asked to make three judgments on each trial: How positive does the picture make you feel?; How negative does the picture make you feel?; How calm/excited does the picture make you feel (i.e., subjective arousal)? The trial first started with a fixation point (1000 ms), which was followed by a prompt denoting the type of report (e.g., how positive?) (1000 ms), and then the participant had unlimited time to report their feeling to the image using the self-assessment manikin (SAM). SAM ratings were made on a 1 (not at all) to 9 (extremely) scale for ratings of positive and negative emotion and 1 (extremely calm) to 9 (extremely excited) for arousal.

3

Participants made manual responses on the keyboard for all 3 selfreports. The order of the 3 self-reports was kept constant on every trial to reduce cognitive demand (i.e., how positive, how negative, arousal). A sample trial sequence is presented in Fig. 1. Participants rated a total of 3 practice stimuli (1 pleasant, 1 unpleasant, 1 neutral) and 120 experimental stimuli. In the experimental phase, there were an equal number of social (n = 60) and nonsocial (n = 60) stimuli divided equally into pleasant, unpleasant, and neutral categories (i.e., 20 of each). Images were considered social if two or more people were present and interacting (e.g. children playing together in a pool), whereas nonsocial images depicted animals (e.g., snake, puppy) or objects (e.g., car, filing cabinet). Normative IAPS valence and arousal ratings indicated that the 40 pleasant, 40 unpleasant, and 40 neutral stimuli differed in valence (unpleasant b neutral b pleasant) and arousal (neutral b pleasant and unpleasant; however, the 40 pleasant and 40 unpleasant stimuli did not differ in arousal. In the second phase (relative value judgments), two IAPS stimuli were presented simultaneously on screen for an unlimited amount of time and participants were asked to select the one that they preferred by clicking on it with the mouse. After each selection, the mouse was automatically centered and the next pair appeared after a 1000 ms fixation cross. Mouse re-centering was done to prevent biased responding to one side of the screen. A total of 34 stimulus pairs were presented. Two types of contrast pairs were selected: valence contrast and social contrast. Valence pairs (n = 14 trials) were determined via normative IAPS ratings and selected to include a range of contrasts (2 pairs of each): highly pleasant vs. mildly pleasant, highly pleasant vs. neutral, moderately pleasant vs. neutral, mildly pleasant vs. neutral, extremely unpleasant vs. mildly unpleasant, unpleasant vs. neutral, and pleasant vs. unpleasant. A total of 20 social contrast pairs were also presented for each social contrast condition. Each pair was selected to be similar in valence and arousal, but one image was social and the other nonsocial in content. Ten of the social contrast pairs were neutral and 10 were pleasant. This design allowed for comparisons of both valence

Fig. 1. Trial Diagrams for the absolute and relative value judgment phases. Notes. Photographs presented in the trial diagram were not actually used in the experiment. These images are examples that are not part of the IAPS library. IAPS images could not be represented due to copyright standards.


4


Fig. 2. Absolute value judgments. SZ = schizophrenia; CN = control; A = How Positive rating; B = How negative rating; C = Arousal rating.

(i.e., collapsing across both social and non-social) and social preference judgments (i.e., collapsing across valence categories). A relative value judgment was considered correct when a subject selected the stimulus with normatively higher (more pleasant) valence based on IAPS normative ratings. 2.4. Data analysis Results of the absolute and relative preference judgment phases were analyzed separately. A series of analyses were conducted to determine whether groups differed with regard to the pattern of absolute (i.e., single stimulus) value judgments for reports of “How Positive?”, “How Negative?”, and “How Calm/Excited” participants reported feeling in response to pleasant, unpleasant, and neutral stimuli. Separate mixed-models ANOVAs were conducted for each rating type, first analyzing all stimuli (i.e., collapsing across social and non-social), and then separately for social and non-social. The Greenhouse-Geisser correction was applied in instances where Mauchly's test of Sphericity was violated. Significant interactions were followed-up by one-way ANOVAs to test hypothesized group differences. A series of nonparametric Mann-Whitney U tests were conducted to evaluate group differences across the aggregate positive vs. neutral contrast and the social vs. non-social contrasts for neutral and pleasant stimuli (i.e., collapsing across all valence categories to see whether the preferred stimulus was more likely to be social). Finally, spearman correlations were calculated to evaluate associations between task data and measures of symptom severity and functional outcome. 3. Results 3.1. Phase I: absolute value judgments Mean self-reported positive emotion, negative emotion, and arousal to pleasant, unpleasant, and neutral stimuli are presented in Fig. 2.

Consistent with prior studies, SZ and CN did not differ in self-reported positive emotion to pleasant stimuli. SZ patients reported significantly more negative emotion than CN for neutral and pleasant stimuli, but did not differ in negative emotion for unpleasant stimuli. Consistent with greater incongruency in emotional self-report, SZ reported more negative emotion to pleasant stimuli and positive emotion to unpleasant stimuli than CN. SZ reported less arousal than CN for unpleasant stimuli, but did not differ from CN in arousal to pleasant or neutral stimuli (see Table 2 for ANOVA and post hoc analyses). The pattern of selfreported positive emotion, negative emotion, and arousal was similar between social and nonsocial stimuli.

3.2. Phase II: relative value judgments Consistent with hypotheses, SZ demonstrated significantly reduced preference for pleasant over neutral stimuli compared to CN: U = 268.0, p = 0.03, z = −2.12: SZ = 75% (16%), CN = 84% (20%).1 Neither group displayed a preference for social over nonsocial stimuli greater than chance and the groups did not differ from each other.

3.3. Correlations Contrary to hypotheses, performance during the relative value judgment task for the pleasant vs. neutral preference score or the social vs nonsocial judgments was not associated with anhedonia rated on the BNSS or SANS. Exploratory analyses also indicated nonsignificant associations between relative value judgments for the positive-neutral contrast score and MCCB working memory, CDS depression, BPRS positive symptoms, BPRS negative symptoms, BPRS disorganization, BPRS total score, and CPZ equivalent dosage. 1

Exploratory analyses conducted on other valence contrasts were nonsignificant.



5

Table 2 ANOVAs for SZ and CN group differences for the absolute judgment phase Condition

Within-Subjects

Between-Subjects

Interaction

Post Hoc Between

How negative? How positive? Arousal

F (1, 134) = 1600.7*** F (1, 134) = 912.2*** F (1, 134) = 115.7***

F (1, 134) = 21.2*** F (1, 134) = 2.78 F (1, 134) = 0.02

F (1, 134) = 9.6** F (1, 134) = 9.8*** F (1, 134) = 7.32**

SZ N CN neutral, pleasant; SZ = CN unpleasant SZ N CN neutral, unpleasant; SZ = CN pleasant SZ b CN unpleasant; SZ = CN pleasant, neutral

Note. SZ = schizophrenia; CN = control; Note, post hoc contrasts did not withstand a strict bonferroni correction threshold b0.001. ** p b 0.01. *** p b 0.001.

4. Discussion Several important findings emerged. First, as hypothesized, SZ displayed an impairment in making relative value judgments when discriminating between pleasant and neutral stimuli. This result is consistent with our prior study using transitivity as a dependent variable (Strauss et al., 2011). Second, impairments in making relative value judgments were observed concurrently with intact reports of positive emotion and arousal to pleasant stimuli. The combination of these results provides the first direct evidence that hedonic capacity is intact, in the midst of impairments in making relative value judgments. Third, results of our study and most published empirical work in SZ suggests that participants with SZ are not anhedonic in the sense of having a diminished capacity for pleasure (Kring and Moran, 2008; Strauss and Gold, 2012). Rather, anhedonia may reflect a deficit in seeking out and engaging in activities that could be enjoyable. It is possible that impairments in value representation underlie this behavioral deficit. Simply put, if the value that could result from selecting potentially pleasurable vs. neutral activities is not clearly distinguishable, people with SZ may not be motivated to engage in actions aimed at obtaining rewards. However, other factors may also contribute to anhedonia in addition to, or perhaps via interaction with, deficits in making relative value judgments (e.g., effort-cost computation, social functioning, limited exposure to potential rewards, or limited resources). Fourth, contrary to the possibility of a social-specific anhedonic deficit in SZ (Blanchard et al., 2001; Cohen et al., 2011), we did not find evidence for reduced ratings of positive emotion to social stimuli or reduced preference of social compared to nonsocial stimuli. Fifth, consistent with prior research (Cohen and Minor, 2010), SZ reported more negative emotion than CN in response to neutral and pleasant pictures, which may reflect an emotion regulation abnormality that causes high levels of negative affect to bleed into situations that are more neutral and pleasant (Horan et al., 2013; Strauss et al., 2013; Strauss et al., 2015; Strauss et al., 2017). Certain limitations should be considered. First, a relatively restricted range of valence contrasts was examined during the relative value judgment phase. Future studies should examine a full range of contrasts across the spectrum of valence (e.g., selecting stimuli from each high valence anchor point from IAPS norms, e.g., 7–9, and pairing them with stimuli in the neutral range 4–6) and also disentangle the effects of arousal from valence, selecting pairs of equivalent valence but different arousal. Second, the relatively small number of trials used per condition in the relative value judgment phase is another limitation, reducing our ability to observe effects within individual conditions. Third, we suspect that our use of IAPS images did not provide a valid test of our exploratory aim related to social anhedonia. It is possible that static images are not really social in nature, but simply convey social meaning. It may be necessary to have participants engage in genuine social interactions to test the social anhedonia hypothesis. Fourth, the IAPS images themselves have certain limitations (e.g., norms based on college students may not be comparable for middle-aged community members or persons with lower education), and future studies should replicate these results using alternative stimulus types. Fifth, we also failed to find a significant correlation between clinically rated anhedonia and performance on the relative value judgment task. This may reflect restricted variance. Finally, the control and SZ groups had different sample sizes, potentially impacting power to observe group effects.

Despite these limitations, results provide support for the notion that SZ is associated with impairments in making relative value judgments. These findings are consistent with the notion that the nature of anhedonia in SZ should be reconceptualized and no longer considered a diminished capacity for pleasure (Strauss and Gold, 2012). Impairments in relative value judgment may be just one of several abnormalities that contribute to anhedonia in schizophrenia, including anticipatory pleasure, effort-cost computation, memory, and low pleasure beliefs (Strauss and Gold, 2012; Kring and Elis, 2013; Gard et al., 2007). Conflict of interest G.P.S. is one of the original developers of the Brief Negative Symptom Scale (BNSS) and receives royalties and consultation fees from ProPhase LLC in connection with commercial use of the BNSS and other professional activities. Contributors GPS, WRK, JMG, and RWB designed the study. GPS and KFV performed statistical analyses. GPS and KFV wrote the initial draft of the manuscript and all authors contributed to subsequent drafts of the manuscript. Role of funding source Research was supported by K23-MH092530 and a pilot grant from the VISN 5 of the Mental Illness Research, Education and Clinical Centers (MIRECC) to Dr. Strauss. Acknowledgments Thank you to the participants who dedicated their time to this research, as well as staff and students in Dr. Strauss' laboratory who conducted scheduling and carried out research assessments: Lauren Catalano, Adam Culbreth, Tehreem Galani, and Jamie Adams.

References Addington, D., Addington, J., Maticka-Tyndale, E., 1993. Assessing depression in schizophrenia: the Calgary Depression Scale. Br. J. Psychiatry 163 (Suppl 22), 39–44. American Psychiatric Association, 2000. Diagnostic and Statistical Manual of Mental Disorders. vol. 4 (text revised ed. Author, Washington, DC). Andreasen, N.C., 1984. Scale for the Assessment of Negative Symptoms (SANS). University of Iowa, Iowa City. Avsar, K.B., Weller, R.E., Cox, J.E., Reid, M.A., White, D.M., Lahti, A.C., 2013. An fMRI investigation of delay discounting in patients with schizophrenia. Brain Behav. 3, 384–401. Barch, D.M., Dowd, E.C., 2010. Goal representations and motivational drive in schizophrenia: the role of prefrontal-striatal interactions. Schizophr. Bull. 36, 919–934. Blanchard, J.J., Horan, W.P., Brown, S.A., 2001. Diagnostic differences in social anhedonia: a longitudinal study of schizophrenia and major depressive disorder. J. Abnorm. Psychol. 110, 363–371. Bleuler, E., 1911. Dementia Praecox or the Group of Schizophrenias. International Universities Press, New York. Cohen, A.S., Minor, K.S., 2010. Emotional experience in patients with schizophrenia revisited: meta-analysis of laboratory studies. Schizophr. Bull. 36, 143–150. Cohen, A.S., Najolia, G.M., Brown, L.A., Minor, K.S., 2011. The state-trait disjunction of anhedonia in schizophrenia: potential affective, cognitive and social-based mechanisms. Clin. Psychol. Rev. 31, 440–448. Fellows, L.K., Farah, M.J., 2007. The role of ventromedial prefrontal cortex in decision making: judgment under uncertainty or judgment per se? Cereb. Cortex 17, 2669–2674. First, M.B., Spitzer, R.L., Gibbon, M., Williams, J.B.W., 1997. Structural Clinical Interview for DSM-IV Axis I Disorders (SCID-IV). New York State Psychiatric Institute, Biometrics Research, New York. Gard, D.E., Kring, A.M., Gard, M.G., Horan, W.P., Green, M.F., 2007. Anhedonia in schizophrenia: distinctions between anticipatory and consummatory pleasure. Schizophr. Res. 93, 253–260. Gard, D.E., Sanchez, A.H., Cooper, K., Fisher, M., Garrett, C., Vinogradov, S., 2014. Do people with schizophrenia have difficulty anticipating pleasure, engaging in effortful behavior, or both? J. Abnorm. Psychol. 123, 771–782. Gold, J., Waltz, J., Prentice, K., Morris, S., Heerey, E., 2008. Reward processing in schizophrenia: a deficit in the representation of value. Schizophr. Bull. 34, 835–847. Hawk, A.B., Carpenter, W.T., Strauss, J.S., 1975. Diagnostic criteria and five-year outcome in schizophrenia. A report from the International Pilot Study of schizophrenia. Arch. Gen. Psychiatry 32, 343–347.


6


Horan, W.P., Hajcak, G., Wynn, J.K., Green, M.F., 2013. Impaired emotion regulation in schizophrenia: evidence from event-related potentials. Psychol. Med. 43, 2377–2391. Kirkpatrick, B., Strauss, G.P., Nguyen, L., Fischer, B.A., Daniel, D.G., Cienfuegos, A., et al., 2011. The brief negative symptom scale: psychometric properties. Schizophr. Bull. 37, 300–305. Kraepelin, E., 1919. Dementia Praecox and Paraphrenia. Robert E Krieger, New York. Kring, A.M., Elis, O., 2013. Emotion deficits in people with schizophrenia. Annu. Rev. Clin. Psychol. 9, 409–433. Kring, A.M., Moran, E.K., 2008. Emotional response deficits in schizophrenia: insights from affective science. Schizophr. Bull. 34, 819–834. Lang, P.J., Bradley, M.M., Cuthbert, B.N., 2008. International Affective Picture System (IAPS): Affective Ratings of Pictures and Instruction Manual. (Technical Report A8). University of Florida, Gainesville, FL. Larsen, J.T., McGraw, A.P., Cacioppo, J.T., 2001. Can people feel happy and sad at the same time? J. Pers. Soc. Psychol. 81, 684–696. Llerena, K., Strauss, G.P., Cohen, A.S., 2012. Looking at the other side of the coin: a metaanalysis of self-reported emotional arousal in people with schizophrenia. Schizophr. Res. 142, 65–70. Myin-Germeys, I., Delespaul, P.A., deVries, M.W., 2000. Schizophrenia patients are more emotionally active than is assumed based on their behavior. Schizophr. Bull. 26, 847–854. Nakamura, M., Nestor, P.G., Levitt, J.J., Cohen, A.S., Kawashima, T., Shenton, M.E., et al., 2008. Orbitofrontal volume deficit in schizophrenia and thought disorder. Brain 131, 180–195. Norris, C.J., Gollan, J., Berntson, G.G., Cacioppo, J.T., 2010. The current status of research on the structure of evaluative space. Biol. Psychol. 84, 422–436. Ohtani, T., Bouix, S., Hosokawa, T., Saito, Y., Eckbo, R., Ballinger, T., et al., 2014. Abnormalities in white matter connections between orbitofrontal cortex and anterior cingulate cortex and their associations with negative symptoms in schizophrenia: a DTI study. Schizophr. Res. 157, 190–197. Oorschot, M., Lataster, T., Thewissen, V., Lardinois, M., Wichers, M., van Os, J., et al., 2013. Emotional experience in negative symptoms of schizophrenia–no evidence for a generalized hedonic deficit. Schizophr. Bull. 39, 217–225. Overall, J.E., Gorham, D.R., 1962. The brief psychiatric rating scale. Psychol. Rep. 10, 799–812. Pfohl, B.M., Blum, N., Zimmerman, M., 1997. Structured Interview for DSM-IV Personality. 1st ed. American Psychiatric Publishing, Inc.

Rado, S., 1953. Dynamics and classification of disordered behaviors. Am. J. Psychiatry 110, 406–416. Shenton, M.E., Dickey, C.C., Frumin, M., McCarley, R.W., 2001. A review of MRI findings in schizophrenia. Schizophr. Res. 49, 1–52. Strauss, G.P., Gold, J.M., 2012. A new perspective on anhedonia in schizophrenia. Am. J. Psychiatry 169, 364–373. Strauss, G.P., Robinson, B.M., Waltz, J.A., Frank, M.J., Kasanova, Z., Herbener, E.S., et al., 2011. Patients with schizophrenia demonstrate inconsistent preference judgments for affective and nonaffective stimuli. Schizophr. Bull. 37, 1295–1304. Strauss, G.P., Hong, L.E., Gold, J.M., Buchanan, R.W., McMahon, R.P., Keller, W.R., et al., 2012a. Factor structure of the Brief Negative Symptom Scale. Schizophr. Res. 142, 96–98. Strauss, G.P., Keller, W.R., Buchanan, R.W., Gold, J.M., Fischer, B.A., McMahon, R.P., et al., 2012b. Next-generation negative symptom assessment for clinical trials: validation of the Brief Negative Symptom Scale. Schizophr. Res. 142, 88–92. Strauss, G.P., Kappenman, E.S., Culbreth, A.J., Catalano, L.T., Lee, B.G., Gold, J.M., 2013. Emotion regulation abnormalities in schizophrenia: cognitive change strategies fail to decrease the neural response to unpleasant stimuli. Schizophr. Bull. 39, 872–883. Strauss, G.P., Kappenman, E.S., Culbreth, A.J., Catalano, L.T., Ossenfort, K.L., Lee, B.G., et al., 2015. Emotion regulation abnormalities in schizophrenia: directed attention strategies fail to decrease the neurophysiological response to unpleasant stimuli. J. Abnorm. Psychol. 124, 288–301. Strauss, G.P., Visser, K.H., Lee, B.G., Gold, J.M., 2017. The positivity offset theory of anhedonia in schizophrenia. Clin. Psychol. Sci. 5, 226–238. Trémeau, F., Antonius, D., Cacioppo, J.T., Ziwich, R., Jalbrzikowski, M., Saccente, E., et al., 2009. In support of Bleuler: objective evidence for increased affective ambivalence in schizophrenia based upon evocative testing. Schizophr. Res. 107, 223–231. Wallis, J.D., 2007a. Neuronal mechanisms in prefrontal cortex underlying adaptive choice behavior. Ann. N. Y. Acad. Sci. 1121, 447–460. Wallis, J.D., 2007b. Orbitofrontal cortex and its contribution to decision-making. Annu. Rev. Neurosci. 30, 31–56. Wallis, J.D., Miller, E.K., 2003. Neuronal activity in primate dorsolateral and orbital prefrontal cortex during performance of a reward preference task. Eur. J. Neurosci. 18, 2069–2081. Woods, S.W., 2003. Chlorpromazine equivalent doses for the newer atypical antipsychotics. J. Clin. Psychol. 64 (6), 663–667.
