Anhedonia, the loss of interest and lack of reactivity to pleasurable stimuli, has been considered a potential trait marker related to vulnerability to depression (Costello, 1972
; Meehl, 1975
). In line with this hypothesis, studies have found that anhedonia can precede the onset of depression (Dryman and Eaton, 1991
); shows temporal stability (Oquendo et al., 2004
); predicts poor outcome 12 months later (Spijker et al., 2001
); and is associated with dysfunctions within the brain reward system (Keedwell et al., 2005
; Tremblay et al., 2002
). Moreover, reward dependence, a putatively heritable trait associated with maintenance of behavior in response to reward cues, shows trait-like features associated with familiality of depression (Farmer et al., 2003
). Collectively, these findings suggest that anhedonia is among the most promising endophenotypes of depression (Hasler et al., 2004
). Still, little is know about which aspects of hedonic processing might be dysfunctional in depression. Using a laboratory-based measure of hedonic capacity, the present findings indicate that major depression is characterized by impairments in the ability to modulate behavior as a function of prior reinforcement history. Since positive reinforcers are stimuli that increase the likelihood of behavior (Rescorla and Wagner, 1972
), blunted responsiveness to reinforcers may lead to diminished engagement in pleasurable activities and decreased motivational drive to pursue future rewards. These dysfunctions may in turn foster the generation, maintenance, and/or exacerbation of depressive symptoms, particularly lack of interest in the environment and loss of pleasure. Studies using self-report measures have indeed shown that anhedonia and blunted behavioral activation predicted (1) future depressive symptoms (Hundt et al., 2007
; Kimbrel et al., 2007
), (2) course of depression and time to recovery (McFarland et al., 2006
), and (3) poor treatment outcome 8–12 months later (Kasch et al., 2002
; Spijker et al., 2001
). Moreover, low positive affect has been identified as a risk factor for the development and maintenance of depressive symptoms in children (Hayden et al., 2006
; Joiner and Lonigan, 2000
; Lonigan et al., 1999
In the present unmedicated MDD sample, blunted response bias was mainly due to a reduced tendency to misclassify the lean stimulus as the more frequently rewarded (rich) stimulus. Notably, this dysfunction emerged only in trials following omission of reward for a correctly identified rich stimulus. Moreover, relative to control subjects, MDD subjects showed a higher likelihood of missing the more frequently rewarded stimulus (rich misses) but only in trials immediately following a rewarded lean stimulus. In addition, the rate of rich misses correlated with anhedonic symptoms experienced by the MDD subjects during the past week. As above, these findings were specific to trials following non-rewarded rich stimuli. Finally, hierarchical regression analyses indicated that anhedonic symptoms uniquely predicted higher rates of rich misses even after controlling for anxiety symptoms and general distress. Taken together, these findings suggest that clinically depressed subjects, while responsive to single rewards, were impaired at integrating reinforcement history over time and expressing a response bias toward a more frequently rewarded cue in the absence of immediate reward. Of note, this blunted hedonic capacity emerged in the absence of any general impairment in task performance (no group differences emerged for discriminability), indicating the reduced hedonic capacity was not due to global cognitive impairments in the MDD sample.
The findings emerging from the present study are consistent with and extend prior reports in depression of reduced reactivity to pleasant cues (e.g., Sloan et al., 2001
; Suslow et al., 2001
), blunted reward responsiveness (e.g., Henriques and Davidson, 2000
), and diminished attentional positivity bias (e.g., McCabe and Gotlib, 1995
; Wang et al., 2006
). Unlike prior studies, however, the current work provides initial evidence that clinically depressed subjects show a diminished propensity to modulate behavior as a function of reinforcement history, particularly in the absence of immediate reinforcement. Considering that many forms of behavior are acquired through intermittent reinforcement schedules (e.g., Hamburg, 1998
), it is reasonable to assume that dysfunctions in integrating reinforcements over time might lead in depression to pervasive difficulty initiating and maintaining goal-directed behavior. This in turn might contribute to the diminished “intrinsic” motivation that is often seen clinically, that is, a difficulty in engaging in “actions […] for their own sake that do not require external support or reinforcements to be initiated or sustained” (Barch, 2005
, p. 877).
The present report of reduced response bias toward the more frequently rewarded stimulus is intriguing given emerging neurobiological evidence that highlights potential dopaminergic dysfunctions in depression. Although findings derived from experimental animal studies and functional neuroimaging are far from being consistent, recent reviews have raised the possibility that depression might be characterized by decreased sensitivity of dopaminergic receptors and decreased dopaminergic release within ventral striatal regions know to be critically implicated in incentive processing (D’Aquila et al., 2000
; Dunlop and Nemeroff, 2007
; Gershon et al., 2007
). Of relevance to the present findings, in a recent pharmacological challenge study using the same probabilistic reward task, we found that a single dose of a dopamine D2 agonist (pramipexole) – hypothesized to activate presynaptic dopaminergic autoreceptors and thus reduce phasic dopaminergic bursts (e.g., Fuller et al., 1982
; Tissari et al., 1983
) – impaired the development of response bias and reduced the differentiation between rich and lean hit rates in healthy subjects (Pizzagalli et al., 2008
). Future neuroimaging studies in depressed samples are warranted to test the hypothesis that disrupted phasic dopaminergic signaling might underline reduced hedonic capacity in depression.
The present study has several important limitations. First, MDD subjects were recruited from treatment studies conducted at a large academic hospital, and future studies should evaluate the generalizability of our findings. Moreover, among the MDD group, the length of the current depressive episode and the depression severity scores ranged broadly, indicating that this relatively small sample of MDD subjects was quite heterogeneous.
Second, the MASQ and BDI-II were used to assess anhedonic symptoms. Although these scales provide a reliable assessment of depression severity and contain items probing anhedonia, it is important to emphasize that other scales have been developed to specifically assess anhedonia, including the Snaith-Hamilton Pleasure Scale, the Fawcett-Clark Pleasure Capacity Scale, and the Revised Chapman Physical Anhedonia Scale (see Leventhal et al., 2006
for a recent review and psychometric comparison). Accordingly, future studies will be needed to evaluate whether the present findings extend to reports of anhedonic symptoms as assessed by these other scales.
Third, unlike prior studies using the probabilistic reward task in student samples (e.g., Pizzagalli et al., 2005
), the community control subjects investigated in the present study did not show increases of response bias across blocks. Instead, at the end of block 1 these control subjects had a response bias (mean: 0.19) similar to the one achieved by low BDI-II subjects (mean: 0.21) in block 3 of our prior study (Pizzagalli et al., 2005
). Thus, it is possible that the lack of systematic response bias development in the current sample was due to ceiling effects. The observation that the present hit rates were somewhat higher than the ones described in Pizzagalli et al. (2005)
supports this speculation and suggests that the two studies, which were conducted in two different laboratories, were not fully psychometrically matched. These methodological differences might also explain the lack of correlation between response bias and anhedonic symptoms. Although a reliable correlation emerged when considering a secondary variable (rates of rich misses) that contributes to reduced response bias (see denominator in Equation 1
), the lack of correlation with overall response bias represents an additional limitation of the present study.
Fourth, because only a reward manipulation was used, we cannot determine whether depressed subjects might show dysfunctional responsiveness to other types of feedback (e.g., punishments) or whether findings were due to procedural (implicit) learning deficits (e.g., difficulties in learning the association between a particular stimulus and increased frequency of reward). Moreover, it is possible that blunted response bias in MDD subjects might be partially explained by an impairment in learning that the lean stimulus is not
associated with frequent reward (cf. Frank, 2005
). Although future studies will be required for conclusive tests of these alternative interpretations, a convergence of findings points to blunted reward responsiveness in depression.
First, in the present as well as two prior studies, blunted reward responsiveness specifically correlated with self-reported anhedonic symptoms (e.g., loss of pleasure, energy, interest, and libido; Bogdan and Pizzagalli, 2006
; Pizzagalli et al., 2005
) and predicted anhedonic symptoms one month later (Pizzagalli et al., 2005
). Second, the current MDD subjects showed lower lean miss rates (i.e., a lower propensity to select “rich” when a lean stimulus was actually presented) and a smaller differentiation between the two stimuli relative to control subjects. When seen within the widely accepted view that positive reinforcers are stimuli that increase the likelihood of subsequent behavior (Rescorla and Wagner, 1972
; Schultz, 2007
), these findings suggest that task performance in MDD subjects was less influenced by the asymmetrical reinforcement schedule favoring the rich stimulus compared to control subjects. Third, procedural leaning (Joel et al., 2005
; Vakil et al., 2000
; but see Naismith et al., 2006
) and punishment responsiveness (Henriques and Davidson, 2000
; Henriques et al., 1994
) have been found to be unaffected in depression. Finally, and more importantly, the probability analyses highlighted that MDD subjects were characterized by specific impairments in expressing response bias towards the more frequently rewarded stimulus in trials following omission of rewards, whereas they showed no dysfunctions in responses to single reward. Critically, although this impairment was seen on a group level, patients reporting anhedonic symptoms in the past week showed the lowest hedonic capacity.
In sum, the present findings indicate that unmedicated subjects with major depression are characterized by an impaired tendency to modulate behavior as a function of prior reinforcements, particularly in the absence of immediate rewards, and thus offer initial clues about which aspects of hedonic processing might be dysfunctional in this debilitating disease.