In our Forum Discussion “journal club” series, journal editors provide access to the full text of a recent article—or in this case, two articles. We thank the Society for Biological Psychiatry, not to mention Elsevier Journals, for providing six months’ open access to a research report by Erin Dowd and Deanna Barch of Washington University, St. Louis, Missouri, and a related commentary by Diego Pizzagalli, Harvard University.
An introduction by James Gold gets us started, and then it's up to our readers to share their ideas and insights, questions and reactions to these papers.
Send in your comments now! The papers under discussion:
Dowd EC, Barch DM. Anhedonia and emotional experience in schizophrenia: neural and behavioral indicators. Biol Psychiatry . 2010 May 15 ; 67(10):902-11. Abstract
By James Gold, Professor of Psychiatry, Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore
Many patients with schizophrenia show a lack of sustained goal-directed behavior. Such motivational deficits in schizophrenia might be explained by a failure to experience pleasure upon goal attainment or reward receipt. This explanation has such high clinical face validity and crisp logic that it has escaped empirical research attention until recently. In his highly focused and helpful commentary on the study by Dowd and Barch, Diego Pizzagalli discusses this “anhedonia paradox” and reviews the efforts of several groups to find an explanation for the following observation: In the laboratory, more often than not, patients with schizophrenia report surprisingly normative experiences to emotionally evocative stimuli, whereas, on instruments like the Chapman Anhedonia Scales (Chapman et al., 1976), their self-reports suggest that they are less able than healthy volunteers to experience pleasure (Horan et al., 2008). Interestingly, patients’ normative self-reports are sometimes accompanied by abnormally muted neural responses (Waltz et al., 2009), suggesting that the story may be more complicated.
Several recent studies have focused on this apparent contradiction between patients’ normative responses to evocative stimuli and their increased anhedonia based on patient self-reports and clinician ratings. For example, Gard et al. (Gard et al., 2007) have suggested that patients have deficits in anticipatory pleasure rather than consummatory pleasure. Such a formulation would easily account for motivational deficits: It is the anticipation of reward that initiates goal-directed behavior.
In a related conceptual vein, we have suggested that patients have difficulty in representing the value of potential rewards and of the responses associated with rewards. This formulation suggests that the genesis of clinically rated anhedonia might not involve a simple reduction in the ability to experience pleasure. Further, we have documented a dissociation between self-reported pleasure and physiology, raising the possibility that the neural response needed to fully mediate reward experience may be muted in schizophrenia (Waltz et al., 2009).
The elegant study by Dowd and Barch captures all of these nuances and leaves the reader facing the need to determine whether the evoked affective-normalcy glass is half-full or half-empty in patients with schizophrenia. In this study, participants made valence and arousal judgments to a series of words, faces, and pictures while being scanned. Compared to healthy volunteers, patients demonstrated a very similar overall pattern of responses on all measures: valence, arousal, and evoked brain activity. Here the glass is more than half-full.
However, there were some differences. Compared to controls, patients rated pleasant stimuli as being less pleasant (perhaps reflecting the use of only three response alternatives—unpleasant, neutral, and pleasant) and neutral stimuli as being more arousing. In addition, patients showed reduced ventral striatal and left putamen response to pleasant stimuli. Here, the glass is at least half-empty, with subtle but reliable abnormalities in both behavior and physiology that are central to the concept of anhedonia and the neural circuitry that mediates reward experience.
Where Dowd and Barch make a unique contribution is in showing that these abnormalities are mediated by self-reported anhedonia (from the Chapman Scales). That is, the abnormal physiology is best explained not on the basis of diagnosis, but by trait anhedonia. Indeed, trait anhedonia was related to physiology in healthy subjects as well.
At the end of the day, we are left with a complex story: While the overall pattern of reported experience and brain physiology is more normal than not in patients as a group, there are important exceptions to this “normalcy,” exceptions that appear to be related to trait anhedonia. Future research is needed to address several questions that remain, such as the following:
1. Might the field make faster progress if we use more specific behavioral phenotypes rather than diagnostic categories? And if this appears likely, do we have reliable methods to define such phenotypes? In the area of anhedonia, are the Chapman Scales, designed to identify young people at potential risk for the illness, optimal for the study of patients whose life experience is so different from that of college students?
2. How much abnormality is enough to be clinically significant? While the overall pattern of results, both behavioral and physiological, was largely normative, there were also exceptions. If the affective experience and neural machinery glass is just a little short of full, is it still too empty to support normal engagement with the environment and the pursuit of goals?
Chapman LJ, Chapman JP, Raulin ML. Scales for physical and social anhedonia. J Abnorm Psychol. 1976 Aug;85(4):374-82. Abstract
Horan WP, Reise SP, Subotnik KL, Ventura J, Nuechterlein KH. The validity of Psychosis Proneness Scales as vulnerability indicators in recent-onset schizophrenia patients. Schizophr Res. 2008 Mar;100(1-3):224-36. Abstract
Waltz JA, Schweitzer JB, Gold JM, Kurup PK, Ross TJ, Salmeron BJ, Rose EJ, McClure SM, Stein EA. Patients with schizophrenia have a reduced neural response to both unpredictable and predictable primary reinforcers. Neuropsychopharmacology. 2009 May;34(6):1567-77. Abstract
Gard DE, Kring AM, Gard MG, Horan WP, Green MF. Anhedonia in schizophrenia: distinctions between anticipatory and consummatory pleasure. Schizophr Res. 2007 Jul;93(1-3):253-60. Abstract