The goals of the present study were to: 1) test whether acute stress impairs reward responsiveness, an empirical measure of hedonic capacity, in healthy female controls; 2) assess the effects of two different psychosocial stress manipulations on reward responsiveness; and 3) evaluate associations between self-reported anhedonia and levels of reward responsiveness under stress and no-stress conditions. Consistent with prior research, both stress manipulations successfully induced negative affect and anxiety (Grillon et al 1993
; Rhudy and Meagher 2003
; Stroud et al 2002
). As in prior studies from our laboratory, which assessed subject samples different from the one considered here (Pizzagalli et al 2005a
; Pizzagalli, Ratner, Jahn, unpublished observation), reliable response bias development and stimulus-dependent changes in accuracy indicated that participants modified their behavior according to reinforcement history. Thus, both the stress induction and reward responsiveness task were successful.
Consistent with our main hypothesis, preclinical investigations (Anisman and Matheson 2005
; Henn and Vollmayr 2005
; Willner 2005
) and limited human research (Berenbaum and Connelly 1993
), subjects, particularly in the threat-of-shock manipulation, displayed significantly lower response bias in the stress compared to the no-stress condition indicating that acute stress reduced reward responsiveness in healthy female controls. Notably, for both stress manipulations, analyses on discriminability scores revealed no significant differences between the stress and no-stress condition suggesting no global effects of stress on task performance. Further highlighting specific hedonic impairments rather than a global performance deficit, the stress condition was associated with significantly lower accuracy for the rich stimulus but significantly higher accuracy for the lean stimulus.
Interestingly, negative correlations emerged between self report measures of anhedonia and response bias during the stress, but not no-stress, condition. Accordingly, individuals reporting greater anhedonic symptoms in their daily life showed the strongest hedonic deficits in the face of an acute stressor. Highlighting the specificity of this link, anhedonic symptoms predicted stress-induced hedonic deficits even after controlling for response bias in the no-stress condition and anxiety symptoms.
Collectively these findings suggest that acute psychosocial stressors with evaluative and dependent features4 led to transiently blunted hedonic capacity in psychiatrically healthy female participants, particularly in those reporting hedonic deficits. In light of the observations that both stress (Monroe and Hadjiyannakis 2002
) and anhedonia (Dryman and Eaton 1991
) often precede depression onset, the present findings provide a potential mechanism—stress-induced hedonic deficits—by which stress may lead to depression onset. In addition to this study, two independent lines of evidence suggest that these effects might be particularly deleterious for individuals with biological vulnerabilities featuring anhedonic traits (Farmer et al 2003
; Oquendo et al 2004
). First, a family history of depression has been found to confer an increased vulnerability to stress-induced hedonic deficits (Berenbaum and Connelly 1993
). Second, animals bred for depression demonstrate increased stress-induced anhedonic-like behavior (Overstreet et al 1997
) and blunted dopamine responses to reward (Yadid et al 2001
Interestingly, in a recent study using the same signal-detection task without any acute stressor, we observed that subjects who appraised recent situations in their life as stressful, unpredictable, and uncontrollable had significantly lower reward responsiveness than comparison subjects (Pizzagalli, Ratner, Jahn, unpublished observation). Although in the present study we did not assess the participants’ appraisal of how uncontrollable or unpredictable the acute stressors were, findings from these independent studies suggest that both sustained laboratory stressors with psychosocial components as well as perceived stress in daily events were associated with similar reductions in hedonic capacity. In addition to providing important convergent evidence, these findings emphasize the ecological validity of laboratory stressor paradigms.
Candidate Neurobiological Mechanisms
Due to the purely behavioral nature of this study, no conclusive statements about putative neurobiological mechanisms underlying the link between acute stress and anhedonia can be advanced. Extrapolating from extensive preclinical findings, we suggest, however, that stress may induce hedonic deficits by altering the rewarding properties of stimuli through dysfunction within dopaminergic tracts and structures associated with reward processing, most notably the mesocorticolimbic pathways (Anisman and Matheson 2005
). Generally, animal research suggests that enhanced mesolimbic dopamine transmission promotes approach-related behaviors while stress-related dysfunctions are associated with decreased hedonic capacity (Cabib and Puglisi-Allegra 1996
; Di Chiara et al 1999
; Pani et al 2000
). Interestingly, stress-induced mesolimbic hypodopaminergic but mesocortical hyperdopaminergic transmission have been associated with deficits in motivated behavior (Cabib et al 2002
). Neuroimaging techniques probing neurochemical (Koepp et al 1998
; Pruessner et al 2004
) and functional (e.g., Knutson et al 2001
) aspects of the mesocorticolimbic system will be needed to test whether the present stress-induced hedonic deficits may be due to transiently decreased mesolimbic and/or increased mesocortical dopamine function. In addition to potential modulation within mesocorticolimbic pathways, a second, but not mutually exclusive, mechanism linking stress and anhedonia might involve prefrontal cortex (PFC) regions. Specifically, a large body of electroencephalographic (EEG) literature suggests that the left and right PFC are critically implicated in approach-related and withdrawal-related affect, respectively (Davidson 2004
; Gotlib et al 1998
; Henriques and Davidson 2000
; Pizzagalli et al 2002
). Consistent with an asymmetrical involvement in approach-related affect, we recently found that resting (task-free) EEG hypoactivity in left dorsolateral PFC regions (as well as medial orbitofrontal regions) was associated with decreased reward bias in a monetarily reinforced task (Pizzagalli et al 2005b
). Based on these EEG findings as well as animal data indicating asymmetrical dopaminergic activation in response to stressors (Carlson et al 1988
), we speculate that acute stressors may induce hypoactivation in the left prefrontal cortex and thus induce blunted reward responsiveness. Alternatively, based on reports that acute administration of the stress hormone cortisol leads to increased right PFC activation (Tops et al 2005
), a region critically implicated in anxiety and withdrawal-related affect (Davidson 2004
; Pizzagalli et al 2002
), reduced appetitive behavior during acute stressors may arise due to increased inhibitory effects of right PFC regions over homologous left PFC regions subserving approach-related affect (Daskalakis et al 2002
; Allison et al 2000
; Sullivan 2004
). Measurements of brain electrical activity in similar laboratory based reward task in conjunction with acute stressors will be needed to test these alternative hypotheses.
Limitations and Future Directions
The limitations of this study deserve mention. First, although the affective responses to the stress manipulations were as hypothesized, no physiological measures (e.g., skin conductance and cortisol) were collected to confirm the effects of the stress manipulation. Second, although the present findings are in line with extensive preclinical evidence emphasizing stress-mediated hedonic deficits, due to their purely behavioral nature, they cannot provide any evidence about putative neural mechanisms linking stress and blunted hedonic capacity. Third, only female participants were considered, a choice motivated by the increased prevalence of depression in women compared with men following stressful life events (Maciejewski et al 2001
). Although the present findings highlight a potential vulnerability to stress induced hedonic deficits in females, future studies will be needed to evaluate whether these findings extend to males. Fourth, although both stressor manipulations led to similar decreases in hedonic capacity during the stressful condition, this reduction was not statistical significant for the performance feedback manipulation. The reasons for this null finding are not entirely clear. Possibly, the anxiety and negative affect generated by the threat-of-shock manipulation coupled with the evaluative aspects of the stressor may be required to induce hedonic deficits. Future studies will be needed to identify the specific aspects of psychosocial stressors that lead to hedonic deficits. Limitations notwithstanding, the present findings indicate that acute stress impaired hedonic capacity, particularly in subjects reporting elevated levels of anhedonic symptoms, raising the possibility that stress-induced hedonic deficits may be a candidate mechanism underlying the etiology and pathophysiology of depression.