0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Original Article |

Association of Anhedonia With Recurrent Major Adverse Cardiac Events and Mortality 1 Year After Acute Coronary Syndrome FREE

Karina W. Davidson, PhD; Matthew M. Burg, PhD; Ian M. Kronish, MD; Daichi Shimbo, MD; Lucia Dettenborn, PhD; Roxana Mehran, MD; David Vorchheimer, MD; Lynn Clemow, PhD; Joseph E. Schwartz, PhD; Nina Rieckmann, PhD
[+] Author Affiliations

Author Affiliations: Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York (Drs Davidson, Burg, Shimbo, Mehran, Clemow, and Schwartz); Zena and Michael A. Wiener Cardiovascular Institute (Drs Davidson and Vorchheimer), and Divisions of General Internal Medicine (Dr Kronish) and Psychiatry (Dr Rieckmann), Mount Sinai School of Medicine, New York; Section of Cardiovascular Medicine, Yale University School of Medicine, New Haven, Connecticut (Dr Burg); Department of Biopsychology, Technische Universität Dresden, Dresden, Germany (Dr Dettenborn); Department of Psychiatry, University of Montreal, and Research Center, University of Montreal Hospital Center, Montreal, Quebec, Canada (Dr Lespérance); and Berlin School of Public Health, Charité University Medical Center, Berlin, Germany (Dr Rieckmann).


Arch Gen Psychiatry. 2010;67(5):480-488. doi:10.1001/archgenpsychiatry.2010.36.
Text Size: A A A
Published online

Context  Depression consistently predicts recurrent events and mortality in patients with acute coronary syndrome (ACS), but it has 2 core diagnostic criteria with distinct biological correlates—depressed mood and anhedonia (loss of pleasure or interest).

Objective  To determine if depressed mood and/or anhedonia predict 1-year medical outcomes for patients with ACS.

Design  Observational cohort study of post-ACS patients hospitalized between May 2003 and June 2005. Within 1 week of admission, patients underwent a structured psychiatric interview assessing clinically impairing depressed mood, anhedonia, and major depressive episode (MDE). Also assessed were the Global Registry of Acute Coronary Events risk score, Charlson comorbidity index, left ventricular ejection fraction, antidepressant use, and depressive symptom severity using the Beck Depression Inventory.

Setting  Cardiac units of 3 university hospitals in New York and Connecticut.

Participants  Consecutive sample of 453 patients with ACS (age, 25-93 years; 42% women).

Main Outcomes Measures  All-cause mortality (ACM) and documented major adverse cardiac events (MACEs)—myocardial infarction, hospitalization for unstable angina, or urgent/emergency coronary revascularization)—actively surveyed for 1 year after admission.

Results  There were 67 events (16 deaths and 51 MACEs; 14.8%): 108 (24%) and 77 (17%) patients had anhedonia and depressed mood, respectively. Controlling for sex, age, and medical covariates, anhedonia (adjusted hazard ratio, 1.58; 95% confidence interval, 1.16-2.14; P < .01) was a significant predictor of combined MACE and ACM, but depressed mood was not. Anhedonia continued to significantly predict outcomes (P < .05) when additionally controlling for MDE diagnosis or depressive symptom severity. Findings were confirmed using depressed mood and anhedonia subscores from the Beck Depression Inventory in place of clinician interview ratings.

Conclusions  Anhedonia identifies risk of MACE and ACM beyond that of established medical prognostic indicators, including MDE and depressive symptom severity. Correlates of anhedonia may add to the understanding of the link between depression and heart disease.

Figures in this Article

Systematic reviews have concluded that depression, identified either by self-reported depressive symptom severity or by psychiatric interview, confers an independent mortality and morbidity risk in patients with acute coronary syndrome (ACS).13 Despite growing acceptance of depression as a cardiac risk factor,4 initial attempts to prevent mortality or event recurrence by treating depression in ACS patients have not been successful.5,6

To better understand how depression contributes to cardiac risk, some have suggested searching for subtypes of depression that are especially cardiotoxic.1,7,8 Major depression is a complex phenotype encompassing a wide range of symptoms, not all of which are present in all patients. Furthermore, to receive a diagnosis of major depression, 1 of 2 core functionally impairing criteria must be present—depressed mood (sadness and the report of feeling depressed) or anhedonia (markedly diminished interest or pleasure in all, or almost all, activities). Evidence suggests that these 2 key components have distinct biological correlates. While depressed mood is typically associated with central serotonergic dysfunction, anhedonia has recently been linked to catecholaminergic dysfunction.9 Thus, depressed mood and/or anhedonia may differentially predict clinical outcomes in post-ACS patients.

The hypothesis of the present study was that 1 of the 2 core criteria of depression independently predicts major adverse cardiac events (MACEs)—myocardial infarction (MI), hospitalization for unstable angina, or urgent revascularization—or all-cause mortality (ACM) in ACS patients, independent of standard medical covariates. In addition, we tested whether depressed mood and/or anhedonia carried independent prognostic risk beyond that associated with previously established markers of depression—clinical diagnosis of major depressive episode (MDE) and self-reported depressive symptom severity.

STUDY SAMPLE

The study included post-ACS patients who were admitted to the coronary care and cardiac care telemetry units of 3 university hospitals (Mount Sinai Hospital, New York, New York, and Yale–New Haven Hospital and Hospital of St Raphael, New Haven, Connecticut) between May 2003 and June 2005. The institutional review boards of each hospital approved the study.

INCLUSION CRITERIA

Patients who were aged 18 years or older and spoke English or Spanish were asked to provide informed consent within 1 week of admission to the hospital for the index ACS event. Patients were eligible if they met the criteria for ACS (either acute MI with or without ST-segment elevation or unstable angina) verified by the study cardiologists using standard ACS criteria10 and had eligible scores (0-4, indicating minimal depressive symptoms, or ≥10, indicating at least mild depressive symptoms) on the Beck Depression Inventory (BDI)11 assessed within 1 week after the index ACS event.12 We chose the first version of the BDI as did the National Heart, Lung and Blood Institute consensus panel on this topic12 over the second version, which is preferred for cardiology epidemiology studies. We chose the timing of within 1 week, as this is when the BDI predicts 1-year MACE and ACM4,13; later administration results in missing data on those who experience early cardiac events, a critical subgroup to include. Patients with BDI scores between 5 and 9 were excluded to more clearly delineate depressed and nondepressed groups at baseline.1 Patients were also ineligible for study participation if they had a terminal illness (life expectancy <1 year), were active alcohol and/or substance abusers, or had cognitive impairment; if the screening could not be completed within 1 week of the initial hospitalization date; or if they were unavailable for follow-up visits.

DEPRESSION MEASURES

All patients underwent the semi-structured diagnostic interview developed for the Enhancing Recovery in Coronary Heart Disease Patients trial14 to determine the presence of MDE according to the criteria of the DSM-IV.15 When trained interviewers use this interview and quality assurance is conducted, the concordance with other structured psychiatric interviews is excellent.14 In our study, interviews were conducted by trained research staff, and 1 clinical psychologist and 1 psychiatrist independently reviewed the trained interviewers' audiotapes and written notes for each interview and verified all diagnoses. As patients were often interviewed on nights and weekends, it was not feasible for mental health specialists to be present at the time of the live interviews. The presence of depressed mood and anhedonia was determined for patients according to the standard criteria used in psychiatric interviews: that the symptom be clinically impairing and present for at least 2 weeks.

Depressed mood and anhedonia were also assessed by patient report with the BDI. Items 1 (sadness) and 10 (crying) of the BDI were summed, yielding a depressed mood score ranging from 0 (low depressed mood) to 6 (high depressed mood). The BDI items 4 (loss of enjoyment) and 12 (loss of interest in others), which assessed anhedonia, were also summed into a score from 0 to 6. Scores on both subscales were categorized to create 2 groups: low or medium (0 or 3) and high (4-6), the latter indicating severe depressed mood or anhedonia.

MEDICAL COVARIATES
GRACE Risk Score, Charlson Comorbidity Index, and Antidepressant Use

We used the Global Registry of Acute Coronary Events (GRACE) risk score to measure established mortality risk factors in post-ACS patients.16 Prognostic markers in the final GRACE model are advanced age, history of MI and heart failure, elevated pulse rate and systolic blood pressure at presentation to the hospital, elevated initial serum creatinine level, elevated initial cardiac enzyme level, ST-segment depression evident on electrocardiogram at presentation, and percutaneous coronary intervention performed in the hospital. The GRACE risk score ranges from 1 to 263 points, with higher scores indicating higher mortality risk. A GRACE risk score of 80 predicts a 1% mortality rate at 6 months; 100, a 2% mortality rate; and higher than 210, a mortality rate greater than 50%.16 Data for the GRACE risk score, the Charlson comorbidity index,17,18 and antidepressant use at discharge from the hospital were collected from medical records or patient history.

Left Ventricular Ejection Fraction

Values for left ventricular ejection fraction (LVEF) were measured quantitatively by left ventriculography during cardiac catheterization (43% of patients), by echocardiography (50% of patients), or by nuclear study (7% of patients). If multiple variables were available, the value from the ventriculogram was used. Values for LVEF were then categorized into 2 groups: normal to mild dysfunction (LVEF ≥ 40%) and moderate to severe dysfunction (LVEF < 40%).

Ascertainment of MACE and ACM

The primary end point of the study was either the first occurrence of a MACE (hospitalization for nonfatal MI, unstable angina, or urgent/emergency coronary revascularization procedures [percutaneous coronary intervention, coronary artery bypass grafting, or percutaneous transluminal coronary angioplasty] using standardardized cardiology classification)10 or ACM by 12 months. Study participants were proactively contacted to complete follow-up assessments at 1, 3, 6, and 18 months either by telephone or in person. For any patient-reported hospitalization, supporting documentation of the event was secured from the hospital's records. Additionally, all recruitment hospitals were proactively searched for any possible MACE hospitalization and death. An end point committee consisting of 2 board-certified cardiologists, blinded to depression status, independently reviewed and classified each hospitalization; in case of disagreement, a third board-certified cardiologist adjudicated the final end point. For participants who could not be contacted or were reported deceased by a relative, the Social Security Death Index was searched to verify vital status.

STATISTICAL ANALYSIS

The t test for continuous variables and χ2 test for categorical variables was used to compare those with and without depressed mood or anhedonia at baseline. When some items of a scale or index were missing, a regression-based approach was used to impute the best linear-predicted score based on the nonmissing items.

Cox proportional hazards models were used to estimate the hazard ratio (HR) for MACE and ACM, stratified by hospital. First, depressed mood, anhedonia, depressive symptom severity, and MDE were tested separately. Several additional models were tested to determine whether depressed mood and/or anhedonia were better predictors of outcomes than MDE, BDI score, or the BDI somatic scale score19; the last model was tested (1) to ensure that anhedonia and/or depressed mood were not simply marking this dimension of depression, and (2) because the somatic subscale has previously been found to predict clinical outcomes in post-MI patients.8,20 Finally, all analyses were repeated, using the patient-reported depressed mood and anhedonia measures from the BDI instead of the respective measures from the clinical interview, to see if these measures predicted MACE and ACM equally well.

We followed suggestions for a priori selection for covariate inclusion.21,22 Based on published findings of factors that might confound the depression–MACE/ACM association, age, sex, LVEF, medical comorbidities (Charlson), clinical prognostic index (GRACE), and antidepressant use were treated as covariates. We then repeated the primary analyses with the unique individual components of the GRACE index to ensure that differences in individual components were tested. Finally, we repeated the primary analysis without the urgent/emergency revascularizations considered to be part of the outcome measure, as we found that the anhedonic patients had significantly fewer baseline revascularizations than nonanhedonic patients.

Follow-up was censored at 12 months after the baseline interview. All analyses were performed using SPSS, version 16 (SPSS Inc, Chicago, Illinois).

Medical eligibility screening identified 677 patients. Of these, 211 (31%) had BDI scores of 5 to 9, 4 were suicidal and were referred for treatment, and 5 withdrew before the baseline examination was completed. Of the 457 enrolled patients, 4 were excluded from the current analysis because the psychiatric interview was not completed within the designated time. Patients who were unavailable or refused to be screened differed significantly from patients who participated in the study; they were older (mean [SD] age, 65.2 [11.9] vs 61.5 [12.2] years; P < .001) and more were Hispanic by self-report (24.3% vs 12.5%; P = .01). No other differences were noted.

The remaining 453 patients had a mean age of 61 years (range, 25-93 years); 42% were women; 80% were white; and 10% were Hispanic. Twenty-one percent of the patients were diagnosed with ST-segment elevation MI; 46% with unstable angina; and 33% with MI without ST-segment elevation. For the depression variables, 48 patients (11%) met the criteria for MDE, 108 (24%) were rated by clinical interview as having depressed mood, and 77 (17%) were rated as having anhedonia (Table 1). Anhedonia and depressed mood were highly associated (φ = 0.74, P < .001). Of 108 patients with depressed mood, 36 (33.3%) did not have anhedonia. Of 77 patients with anhedonia, 5 (6.5%) did not have depressed mood. In patients with MDE, 81.3% had depressed mood, and 72.9% had anhedonia (φ coefficients between MDE and depressed mood and MDE and anhedonia were φ = 0.46 and φ = 0.51, respectively, both P < .001).

Table Graphic Jump LocationTable 1 Demographic and Clinical Characteristics and Outcomes of 453 Patients With Acute Coronary Syndromea

Demographic and medical variables at baseline according to depressed mood and anhedonia status are shown in Table 1. As can be seen, numerous significant differences existed. Those with depressed mood were significantly more likely to be female, to have higher Charlson comorbidity index scores, to be younger, to have an MDE, to have higher rates of elevated depressive symptoms, and to have an antidepressant prescribed. They were also significantly more likely to have higher admission heart rates, lower systolic pressures, and to have received significantly fewer percutaneous interventions while in the hospital. Patients with anhedonia compared with those without had the same significant differences as were found between patients with and without depressed mood; additionally they had significantly lower GRACE scores (less cardiac risk).

During a mean follow-up of 10.4 months (range, <1-12 months), there were 67 confirmed events (14.8%; 17 deaths and 50 MACEs [11 MIs, 25 hospitalizations for unstable angina, and 14 urgent/emergency revascularizations]), which is comparable with findings of previous research (15.1% MACE and ACM during 1 year).23Table 2 displays age-adjusted associations of the covariates and MACE and ACM. As expected, all medical covariates were significant bivariate predictors of MACE and ACM within 12 months.

Table Graphic Jump LocationTable 2 Age-Adjusted Association of Covariates With 12-Month Major Adverse Cardiac Events and All-Cause Mortality in 453 Patients

Major adverse cardiac events and/or ACM occurred in 17 of 48 patients (35.4%) with MDE, compared with 50 of 405 patients (12.3%) without MDE. To compare our sample with previous samples, we conducted some preliminary analyses. Major depressive episode and depressive symptom severity assessed by BDI were significant predictors of age-adjusted MACE and/or ACM within 12 months, but only MDE remained a significant predictor after adjusting for age, sex, and the medical covariates (Table 3). The adjusted HR for MDE was comparable with that found in prior studies.24

Table Graphic Jump LocationTable 3 Adjusted HRs for 12-Month Major Adverse Cardiac Events and All-Cause Mortality
CLINICIAN-RATED DEPRESSED MOOD AND ANHEDONIA AS PREDICTORS OF CLINICAL OUTCOMES

Table 1 shows that the 1-year outcome rates differed by anhedonia and depressed mood groups and that there were few urgent or emergency revascularizations in either group. Both depressed mood and anhedonia significantly predicted MACE and ACM in the age-adjusted model (Table 3), but only anhedonia remained a significant predictor of MACE and ACM after adjusting for age, sex, and the medical covariates. When both anhedonia and depressed mood were in the multivariable-adjusted model, only anhedonia was a significant predictor of MACE and ACM (adjusted HR, 1.69; 95% confidence interval [CI], 1.07-2.68; P = .03; Figure). This association was strengthened when 1-year urgent or emergency revascularization events were not considered part of the MACE/ACM outcome (HR, 2.17; 95% CI, 1.26-3.73; P = .005), whereas depressed mood continued to be unrelated to outcomes (Table 3). Anhedonia remained a significant predictor after adjusting for MDE (HR, 1.45; 95% CI, 1.03-2.05; P = .04). Similarly, anhedonia remained significant when adjusting for severity of depressive symptoms (HR, 1.52; 95% CI, 1.09-2.11; P = .01). Furthermore, with anhedonia in the model, neither MDE (HR, 1.25; 95% CI, 0.87-1.79; P = .23) nor depressive symptom severity (HR, 1.09; 95% CI, 0.81-1.47; P = .57) were significant predictors of outcome. Finally, after adjusting for covariates and the somatic subscale of the BDI, anhedonia remained a significant predictor (HR, 1.99; 95% CI, 1.17-2.40; P = .01). With MDE, depressive symptom severity, or BDI somatic subscale in the model, depressed mood was not a significant predictor of outcome.

Place holder to copy figure label and caption
Figure

Cox regression predicted curves for patients with and without clinician-rated depressed mood (left) or anhedonia (right). Adjusted for site, age, sex, Charlson comorbidity index score, Global Registry of Acute Coronary Events risk score, left ventricular ejection fraction, and antidepressant use at discharge and the other depression core criteria.

Graphic Jump Location

When the analyses were repeated with individual medical covariates from the GRACE score as covariates, rather than using the GRACE composite index, the results were the same. Anhedonia was significant (HR, 1.79; 95% CI, 1.01-3.17; P = .048), while depressed mood was not (HR, 0.74; 95% CI, 042-1.32; P = .31).

PATIENT-REPORTED DEPRESSED MOOD AND ANHEDONIA AS PREDICTORS OF CLINICAL OUTCOMES

When anhedonia and depressed mood as assessed with the BDI were used as predictors instead of the clinician-diagnosed criteria, the results were again similar; patient-reported anhedonia was a significant predictor of MACE/ACM after controlling for demographic and medical covariates (HR, 2.26; 95% CI, 1.33-3.82; P = .002) and also after controlling for the somatic subscale of the BDI (data not shown), while patient-reported depressed mood was not (HR, 0.86; 95% CI, 0.51-1.43; P = .55).

The present study replicates and augments the finding of previous research in patients with established heart disease, that depression is a significant risk factor for adverse clinical outcomes,2,3 even when adjusting for demographic characteristics and known medical prognostic disease markers and comorbid conditions.25 We further demonstrated that of the 2 core criteria of depression—depressed mood and anhedonia—only anhedonia predicts the risk of MACE and ACM independent of the usual covariates and other depression indices.

IMPROVING RISK STRATIFICATION

Major depressive episode is a heterogeneous clinical entity with diverse somatic and cognitive symptoms that include fatigue, feelings of guilt, sleep problems, and weight gain or loss. Not all of these symptoms may mark individuals at increased risk of MACE or ACM. Also, because MDE criteria can be met through varying symptom patterns, the resulting heterogeneity may in part explain why previous depression treatment and observational studies in ACS patients have inconsistent results. As others have pointed out, it is important to move beyond the broad phenotype of depression and delineate its “cardiotoxic” components.26 In a previous study with post-MI patients, de Jonge and colleagues27 identified 3 symptom dimensions of the BDI—somatic/affective, cognitive/affective, and appetitive—and found that only somatic or affective symptoms predicted future death or cardiac events after controlling for somatic health indicators. The somatic/affective dimension, however, still contained symptoms that were clinically (and likely, etiologically) distinct, such as insomnia, indecisiveness, and both depressed mood and anhedonia. Recent analyses from the Women's Ischemia Syndrome Evaluation study used a similar approach to evaluate the cardiac prognostic impact of symptom dimensions from BDI in women with suspected myocardial ischemia.28 This study revealed that somatic/affective symptoms of depression predicted cardiovascular events and mortality, and cognitive/affective did not. We chose a different approach of analyzing the 2 core symptoms of depression that are also known as endophenotypes of depression in the psychiatry literature,9 which are thought to be clinically distinguishable and possibly have unique biological bases. Furthermore, when we controlled for the somatic depression subscale, anhedonia continued to predict MACE and ACM, while depressed mood did not.

Anhedonia is described as the loss of ability to experience pleasure in all or almost all activities,29 whereas depressed mood is marked by sadness, tearfulness, and sometimes visible distress. This clinical distinction within the complex phenotype of major depression has been noted for centuries.30,31 Anhedonia is not specific to depression; it occurs in other psychiatric disorders as well.32 Moreover, as with all symptoms of psychiatric disease, not all patients with anhedonia fulfill the diagnostic criteria for MDE. In fact, almost half the patients with anhedonia in our sample did not have MDE, yet anhedonia proved to be the most accurate predictor of MACE and ACM, better even than the clinical diagnosis of MDE.

When we created patient-reported subscales of anhedonia and depressed mood from the BDI, we replicated this finding, that anhedonia, not depressed mood, is uniquely predictive of medical outcomes. Other patient-report measures may assess anhedonia and depressed mood more accurately than post hoc subsets of the BDI (eg, Patient Health Questionnaire 233), and these more easily administered self-report measures should be tested for their usefulness in risk-stratifying cardiac patients. Should the present finding be confirmed in other samples, assessments of patient-reported anhedonia could easily be implemented in clinical practice.

Of note, when controlling for depressive symptom severity, anhedonia still predicted MACE or ACM, ruling out the possibility that patients with anhedonia are at increased risk merely because they have more severe depressive symptoms overall. These findings suggest that examining the particular criteria of anhedonia might provide new insights concerning mechanisms and treatments that increase the risk of adverse cardiac events and death in post-ACS patients.

BIOLOGICAL AND BEHAVIORAL CORRELATES OF ANHEDONIA IN PSYCHIATRIC PATIENTS

Psychiatric patients with anhedonia tend to have perturbations of sleep, satisfaction, appetite, weight, and libido. Perturbations in the dopaminergic system, inflammatory processes, circadian rhythms, and melatonin production have also been observed in anhedonic patients.30,34,35 Hasler and colleagues9 suggest that anhedonia, but not depressed mood, is associated with catecholaminergic dysfunction, a mechanism that has been proposed to explain increased morbidity and mortality owing to cardiovascular disease.36,37 High catecholamine levels are toxic to cardiac myocytes,38 can trigger tachyarrhythmia,3941 and promote platelet aggregation.42,43 Among patients with congestive heart failure, the extent of plasma catecholamine elevation correlates directly with cardiac mortality.44 It is also possible that the risk conferred by anhedonia in cardiac patients is mediated through behavior. A relatively stable feature of anhedonia is an impaired responsiveness to reinforcing, rewarding stimuli.9 This suggests that patients with anhedonia may be less likely to perceive the benefits of and engage in healthy cardioprotective behaviors, such as exercising, attending cardiac rehab, adhering to a healthy diet, and taking their medications regularly. It is even possible that anhedonia predicts less symptom reporting at the time of the ACS event. This might in turn impact physician behavior, because less urgency of symptom reporting sometimes leads to less aggressive medical or surgical management. More studies are therefore needed to understand the behavioral and biological aspects of anhedonia in cardiac patients.

IMPLICATIONS FOR CARDIAC PATIENTS WITH ANHEDONIA

Thus far, studies that have applied standard pharmacological and nonpharmacological depression treatments to cardiac patients with MDE have achieved modest reductions in depressive symptoms.24 They have failed, however, to significantly improve the cardiac prognosis of these patients. The present study shows that it is not only patients with MDE that are at increased risk, but that the endophenotype of anhedonia is a potent predictor, irrespective of the severity of depressive symptoms. To date, there are no studies that have directly compared the efficacy of various forms of antidepressant treatments in patients with and without anhedonia.

Understanding the behavioral and biological mechanisms underlying anhedonia in cardiac patients may provide insights into which treatments to best apply in these patients. For example, interventions involving behavioral activation may be a good choice for treatment should future studies show marked decreases in cardioprotective health behavior that is associated with the presence of anhedonia in cardiac patients. It may also be the case that patients with anhedonia need to be more rapidly treated with antidepressant medication, as the effects of pharmacotherapy on this specific feature of depression may take longer than on other features.45 Whether reducing anhedonia in post-ACS patients will reduce their risk of MACE or ACM is not yet known.

STUDY LIMITATIONS

There are a number of limitations in the present study. Although anhedonia has previously been found to predict in-hospital mortality in medical patients46 and major clinical events after stent placement,47 our finding that anhedonia is uniquely associated with increased risk of MACE and ACM in post-ACS patients must be replicated. Furthermore, the current study was insufficiently powered to rule out the possibility that depressed mood is a moderate predictor of medical outcomes. However, its HR in this sample was below 1, so it was trending toward being a protective, rather than a risk, factor. Events or deaths within this study occurred primarily within the first 3 months after discharge, so the association of depressed mood and anhedonia with longer-term outcomes was also not determined.

Ascertainment of cardiac events that required hospitalization was largely dependent on patients' reports, and there is a possibility that some patients may not have reported a hospitalization. We did search recruitment hospital records for all admissions, but patients readmitted to outside hospitals would not be found with this process.

It is possible that the post-ACS patients who reported loss of interest in activities are those with the most severe forms of heart disease and that it is the severity of their disease that is causing a poor prognosis, rather than a particular symptom of depression—anhedonia. Some doubt remains about the predictive power of depression, or its components, as an independent risk marker beyond the power of established clinical disease markers, as many prognostic studies have not adequately controlled for clinical and cardiovascular covariates, such as LVEF.25 In our study, anhedonic patients had higher medical comorbidities, as indicated by the Charlson comorbidity index score and differences in components of the GRACE risk score, but these differences were controlled for in the analyses. Furthermore, the significant differences found in resting heart rate and other cardiac risk factors were small and are not considered clinically significant within cardiology research. It remains possible, however, that anhedonia is a marker for some medical confounder not assessed in the current study that predicts clinical outcome.

We also excluded ACS patients with mild BDI scores (5-9) to more clearly delineate depression groups. It is possible that many patients within this range of depressive symptoms might have met criteria for anhedonia. In a small subsequent study (for which outcomes are not yet available), however, only 2% of ACS patients with BDI scores in this range meet clinical criteria for anhedonia. Nonetheless, this is a limitation of the study, and future studies should include the full range of BDI scores in their cohorts.

Finally, we used an a priori, composite medical outcome as is now common in cardiology clinical trials and registries.48 This included ACM, infarction, and standardized criteria for unstable angina and urgent or emergency revascularization procedures.10 Outcomes that incorporate coronary revascularization are at risk of including “softer” outcomes, such as target vessel revascularization, angiographic stenosis, and nonurgent revascularizations. To a certain extent, these latter outcomes can represent physician bias and variable practice patterns. Thus, we chose to include only urgent or emergency coronary revascularizations as part of the primary composite outcome, and excluded these others. When we tested our findings with urgent and emergency revascularizations removed from our 1-year outcome measure, the independent association between anhedonia and medical outcomes was strengthened; depressed mood remained nonsignificantly associated. Our inability to examine each outcome separately (because there were too few in each category) remains a limitation. A future study should examine whether the association of anhedonia is primarily with death or recurrent coronary events, as this too would suggest differential mechanistic pathways.

This study replicates the finding of prior research that MDE is a significant and independent risk factor for adverse clinical outcomes in patients with ACS. It also demonstrates that, of the 2 core criteria of MDE (depressed mood and anhedonia), only anhedonia was a significant predictor before and after adjusting for depression severity and MDE diagnosis. Focusing on anhedonia in post-ACS patients may better identify those at risk, may provide insight into the mechanisms underlying the association between depression and poor outcomes in patients with heart disease, and ultimately may inform the design of novel treatments to improve post-ACS prognosis.

Correspondence: Karina W. Davidson, PhD, Department of Medicine, Columbia University College of Physicians and Surgeons, Room 948, PH9 Center, 622 W 168th St, New York, NY 10032 (kd2124@columbia.edu).

Submitted for Publication: May 8, 2009; final revision received October 8, 2009; accepted November 11, 2009.

Author Contributions: Drs Davidson and Schwartz conducted the analyses and contributed to the interpretation of the data. Both are independent of any commercial funding agency, had full access to all of the data in the study, and take responsibility for the integrity of the data and the accuracy of the data analysis.

Financial Disclosure: Dr Lespérance receives unrestricted grant support from Isodis Natura. He is a consultant to Servier Canada.

Funding/Support: Data collection and manuscript preparation were financially supported by grants HC-25197, HL-076857, HL-084034, and HL-04458 from the National Heart, Lung and Blood Institute, Bethesda, Maryland.

Davidson  KWRieckmann  NRapp  M Definitions and distinctions among depressive syndromes and symptoms: implications for a better understanding of the depression–cardiovascular disease association. Psychosom Med 2005;67 ((suppl 1)) S6- S9
PubMed
Barth  JSchumacher  MHerrmann-Lingen  C Depression as a risk factor for mortality in patients with coronary heart disease: a meta-analysis. Psychosom Med 2004;66 (6) 802- 813
PubMed
van Melle  JPde Jonge  PSpijkerman  TATijssen  JGOrmel  Jvan Veldhuisen  DJvan den Brink  RHvan den Berg  MP Prognostic association of depression following myocardial infarction with mortality and cardiovascular events: a meta-analysis. Psychosom Med 2004;66 (6) 814- 822
PubMed
Lichtman  JHBigger  JT  JrBlumenthal  JAFrasure-Smith  NKaufmann  PGLespérance  FMark  DBSheps  DSTaylor  CBFroelicher  ESAmerican Heart Association Prevention Committee of the Council on Cardiovascular Nursing; American Heart Association Council on Clinical Cardiology; American Heart Association Council on Epidemiology and Prevention; American Heart Association Interdisciplinary Council on Quality of Care and Outcomes Research; American Psychiatric Association, Depression and coronary heart disease: recommendations for screening, referral, and treatment: a science advisory from the American Heart Association Prevention Committee of the Council on Cardiovascular Nursing, Council on Clinical Cardiology, Council on Epidemiology and Prevention, and Interdisciplinary Council on Quality of Care and Outcomes Research: endorsed by the American Psychiatric Association. Circulation 2008;118 (17) 1768- 1775
PubMed
Berkman  LFBlumenthal  JBurg  MCarney  RMCatellier  DCowan  MJCzajkowski  SMDeBusk  RHosking  JJaffe  AKaufmann  PGMitchell  PNorman  JPowell  LHRaczynski  JMSchneiderman  NEnhancing Recovery in Coronary Heart Disease Patients Investigators (ENRICHD), Effects of treating depression and low perceived social support on clinical events after myocardial infarction: the Enhancing Recovery in Coronary Heart Disease Patients (ENRICHD) Randomized Trial. JAMA 2003;289 (23) 3106- 3116
PubMed
Honig  AKuyper  ASchene  AHvan Melle  JPde Jonge  PTulner  DMSchins  ACrijns  HJKuijpers  PMVossen  HLousberg  ROrmel  JMIND-IT investigators, Treatment of post-myocardial infarction depressive disorder: a randomized, placebo-controlled trial with mirtazapine. Psychosom Med 2007;69 (7) 606- 613
PubMed
Rutledge  TReis  SEOlson  MBOwens  JKelsey  SFPepine  CJMankad  SRogers  WJMerz  CNSopko  GCornell  CESharaf  BMatthews  KAVaccarino  V Depression symptom severity and reported treatment history in the prediction of cardiac risk in women with suspected myocardial ischemia: the NHLBI-sponsored WISE study. Arch Gen Psychiatry 2006;63 (8) 874- 880
PubMed
de Jonge  POrmel  J Heterogeneity of patients with coronary artery disease and distress and the need to identify relevant subtypes. Arch Gen Psychiatry 2008;65 (7) 851- 853
PubMed
Hasler  GDrevets  WCManji  HKCharney  DS Discovering endophenotypes for major depression. Neuropsychopharmacology 2004;29 (10) 1765- 1781
PubMed
Cannon  CPBattler  ABrindis  RGCox  JLEllis  SGEvery  NRFlaherty  JTHarrington  RAKrumholz  HMSimoons  MLVan De Werf  FJWeintraub  WSMitchell  KRMorrisson  SLBrindis  RGAnderson  HVCannom  DSChitwood  WRCigarroa  JECollins-Nakai  RLEllis  SGGibbons  RJGrover  FLHeidenreich  PAKhandheria  BKKnoebel  SBKrumholz  HLMalenka  DJMark  DB McKay  CRPassamani  ERRadford  MJRiner  RNSchwartz  JBShaw  REShemin  RJVan Fossen  DBVerrier  EDWatkins  MWPhoubandith  DRFurnelli  T American College of Cardiology key data elements and definitions for measuring the clinical management and outcomes of patients with acute coronary syndromes: a report of the American College of Cardiology Task Force on Clinical Data Standards (Acute Coronary Syndromes Writing Committee). J Am Coll Cardiol 2001;38 (7) 2114- 2130
PubMed
Beck  ATWard  CHMendelson  MMock  JErbaugh  J An inventory for measuring depression. Arch Gen Psychiatry 1961;4561- 571
PubMed
Davidson  KWKupfer  DJBigger  JTCaliff  RMCarney  RMCoyne  JCCzajkowski  SMFrank  EFrasure-Smith  NFreedland  KEFroelicher  ESGlassman  AHKaton  WJKaufmann  PGKessler  RCKraemer  HCKrishnan  KRLespérance  FRieckmann  NSheps  DSSuls  JMNational Heart, Lung, and Blood Institute Working Group, Assessment and treatment of depression in patients with cardiovascular disease: National Heart, Lung, and Blood Institute Working Group Report. Psychosom Med 2006;68 (5) 645- 650
PubMed
Thombs  BDde Jonge  PCoyne  JCWhooley  MAFrasure-Smith  NMitchell  AJZuidersma  MEze-Nliam  CLima  BBSmith  CGSoderlund  KZiegelstein  RC Depression screening and patient outcomes in cardiovascular care: a systematic review. JAMA 2008;300 (18) 2161- 2171
PubMed
Freedland  KESkala  JACarney  RMRaczynski  JMTaylor  CBMendes de Leon  CFIronson  GYoungblood  MEKrishnan  KRVeith  RC The Depression Interview and Structured Hamilton (DISH): rationale, development, characteristics, and clinical validity. Psychosom Med 2002;64 (6) 897- 905
PubMed
American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders. 4th ed, text revision. Washington, DC: American Psychiatric Association; 2000
Eagle  KALim  MJDabbous  OHPieper  KSGoldberg  RJVan de Werf  FGoodman  SGGranger  CBSteg  PGGore  JMBudaj  AAvezum  AFlather  MDFox  KAGRACE Investigators, A validated prediction model for all forms of acute coronary syndrome: estimating the risk of 6-month postdischarge death in an international registry. JAMA 2004;291 (22) 2727- 2733
PubMed
Charlson  MEPompei  PAles  KLMacKenzie  CR A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 1987;40 (5) 373- 383
PubMed
Lespérance  FFrasure-Smith  NTalajic  MBourassa  MG Five-year risk of cardiac mortality in relation to initial severity and one-year changes in depression symptoms after myocardial infarction. Circulation 2002;105 (9) 1049- 1053
PubMed
Rapp  SRParisi  SAWalsh  DAWallace  CE Detecting depression in elderly medical inpatients. J Consult Clin Psychol 1988;56 (4) 509- 513
PubMed
Martens  EJHoen  PWMittelhaeuser  Mde Jonge  PDenollet  J Symptom dimensions of post-myocardial infarction depression, disease severity and cardiac prognosis. Psychol Meddoi:10.1017/S0033291709990997. Published August 20, 2009
PubMed
Babyak  MA What you see may not be what you get: a brief, nontechnical introduction to overfitting in regression-type models. Psychosom Med 2004;66 (3) 411- 421
PubMed
Steyerberg  EWEijkemans  MJCHarrell  FE  JrHabbema  JDF Prognostic modeling with logistic regression analysis: in search of a sensible strategy in small data sets. Med Decis Making 2001;21 (1) 45- 56
PubMed
de Araújo Gonçalves  PFerreira  JAguiar  CSeabra-Gomes  R TIMI, PURSUIT, and GRACE risk scores: sustained prognostic value and interaction with revascularization in NSTE-ACS. Eur Heart J 2005;26 (9) 865- 872
PubMed
Carney  RMFreedland  KE Depression in patients with coronary heart disease. Am J Med 2008;121 (11) ((suppl 2)) S20- S27
PubMed
Nicholson  AKuper  HHemingway  H Depression as an aetiologic and prognostic factor in coronary heart disease: a meta-analysis of 6362 events among 146 538 participants in 54 observational studies. Eur Heart J 2006;27 (23) 2763- 2774
PubMed
Denollet  JPedersen  SS Anger, depression, and anxiety in cardiac patients: the complexity of individual differences in psychological risk. J Am Coll Cardiol 2009;53 (11) 947- 949
PubMed
de Jonge  POrmel  Jvan den Brink  RHvan Melle  JPSpijkerman  TAKuijper  Avan Veldhuisen  DJvan den Berg  MPHonig  ACrijns  HJSchene  AH Symptom dimensions of depression following myocardial infarction and their relationship with somatic health status and cardiovascular prognosis. Am J Psychiatry 2006;163 (1) 138- 144
PubMed
Linke  SERutledge  TJohnson  BDVaccarino  VBittner  VCornell  CEEteiba  WSheps  DSKrantz  DSParashar  SBairey Merz  CN Depressive symptom dimensions and cardiovascular prognosis among women with suspected myocardial ischemia: a report from the National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation. Arch Gen Psychiatry 2009;66 (5) 499- 507
PubMed
Fawcett  JClark  DCScheftner  WAGibbons  RD Assessing anhedonia in psychiatric patients. Arch Gen Psychiatry 1983;40 (1) 79- 84
PubMed
Leventhal  AMRehm  LP The empirical status of melancholia: implications for psychology. Clin Psychol Rev 2005;25 (1) 25- 44
PubMed
Shorter  E The doctrine of the two depressions in historical perspective. Acta Psychiatr Scand Suppl 2007;433 (433) 5- 13
PubMed
Winograd-Gurvich  CFitzgerald  PBGeorgiou-Karistianis  NBradshaw  JLWhite  OB Negative symptoms: a review of schizophrenia, melancholic depression and Parkinson's disease. Brain Res Bull 2006;70 (4-6) 312- 321
PubMed
Kroenke  KSpitzer  RLWilliams  JB The Patient Health Questionnaire-2: validity of a two-item depression screener. Med Care 2003;41 (11) 1284- 1292
PubMed
Gorwood  P Neurobiological mechanisms of anhedonia. Dialogues Clin Neurosci 2008;10 (3) 291- 299
PubMed
Raison  CLCapuron  LMiller  AH Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol 2006;27 (1) 24- 31
PubMed
Carney  RMFreedland  KEVeith  RC Depression, the autonomic nervous system, and coronary heart disease. Psychosom Med 2005;67 ((suppl 1)) S29- S33
PubMed
Musselman  DLEvans  DLNemeroff  CB The relationship of depression to cardiovascular disease: epidemiology, biology, and treatment. Arch Gen Psychiatry 1998;55 (7) 580- 592
PubMed
Singh  KCommunal  CSawyer  DBColucci  WS Adrenergic regulation of myocardial apoptosis. Cardiovasc Res 2000;45 (3) 713- 719
PubMed
Mann  JJ McBride  PAAnderson  GMMieczkowski  TA Platelet and whole blood serotonin content in depressed inpatients: correlations with acute and life-time psychopathology. Biol Psychiatry 1992;32 (3) 243- 257
PubMed
Communal  CSingh  KPimentel  DRColucci  WS Norepinephrine stimulates apoptosis in adult rat ventricular myocytes by activation of the beta-adrenergic pathway. Circulation 1998;98 (13) 1329- 1334
PubMed
Lampert  RJain  DBurg  MMBatsford  WP McPherson  CA Destabilizing effects of mental stress on ventricular arrhythmias in patients with implantable cardioverter-defibrillators. Circulation 2000;101 (2) 158- 164
PubMed
Podrid  PJFuchs  TCandinas  R Role of the sympathetic nervous system in the genesis of ventricular arrhythmia. Circulation 1990;82 (2) ((suppl)) I103- I113
PubMed
Meredith  ITBroughton  AJennings  GLEsler  MD Evidence of a selective increase in cardiac sympathetic activity in patients with sustained ventricular arrhythmias. N Engl J Med 1991;325 (9) 618- 624
PubMed
Cohn  JNLevine  TBOlivari  MTGarberg  VLura  DFrancis  GSSimon  ABRector  T Plasma norepinephrine as a guide to prognosis in patients with chronic congestive heart failure. N Engl J Med 1984;311 (13) 819- 823
PubMed
Boyer  PTassin  JPFalissart  BTroy  S Sequential improvement of anxiety, depression and anhedonia with sertraline treatment in patients with major depression. J Clin Pharm Ther 2000;25 (5) 363- 371
PubMed
Furlanetto  LMvon Ammon Cavanaugh  SBueno  JRCreech  SDPowell  LH Association between depressive symptoms and mortality in medical inpatients. Psychosomatics 2000;41 (5) 426- 432
PubMed
Denollet  JPedersen  SSDaemen  Jde Jaegere  PSerruys  PWvan Domburg  RT Reduced positive affect (anhedonia) predicts major clinical events following implantation of coronary-artery stents. J Intern Med 2008;263 (2) 203- 211
PubMed
Stanley  K Design of randomized controlled trials. Circulation 2007;115 (9) 1164- 1169
PubMed

Figures

Place holder to copy figure label and caption
Figure

Cox regression predicted curves for patients with and without clinician-rated depressed mood (left) or anhedonia (right). Adjusted for site, age, sex, Charlson comorbidity index score, Global Registry of Acute Coronary Events risk score, left ventricular ejection fraction, and antidepressant use at discharge and the other depression core criteria.

Graphic Jump Location

Tables

Table Graphic Jump LocationTable 1 Demographic and Clinical Characteristics and Outcomes of 453 Patients With Acute Coronary Syndromea
Table Graphic Jump LocationTable 2 Age-Adjusted Association of Covariates With 12-Month Major Adverse Cardiac Events and All-Cause Mortality in 453 Patients
Table Graphic Jump LocationTable 3 Adjusted HRs for 12-Month Major Adverse Cardiac Events and All-Cause Mortality

References

Davidson  KWRieckmann  NRapp  M Definitions and distinctions among depressive syndromes and symptoms: implications for a better understanding of the depression–cardiovascular disease association. Psychosom Med 2005;67 ((suppl 1)) S6- S9
PubMed
Barth  JSchumacher  MHerrmann-Lingen  C Depression as a risk factor for mortality in patients with coronary heart disease: a meta-analysis. Psychosom Med 2004;66 (6) 802- 813
PubMed
van Melle  JPde Jonge  PSpijkerman  TATijssen  JGOrmel  Jvan Veldhuisen  DJvan den Brink  RHvan den Berg  MP Prognostic association of depression following myocardial infarction with mortality and cardiovascular events: a meta-analysis. Psychosom Med 2004;66 (6) 814- 822
PubMed
Lichtman  JHBigger  JT  JrBlumenthal  JAFrasure-Smith  NKaufmann  PGLespérance  FMark  DBSheps  DSTaylor  CBFroelicher  ESAmerican Heart Association Prevention Committee of the Council on Cardiovascular Nursing; American Heart Association Council on Clinical Cardiology; American Heart Association Council on Epidemiology and Prevention; American Heart Association Interdisciplinary Council on Quality of Care and Outcomes Research; American Psychiatric Association, Depression and coronary heart disease: recommendations for screening, referral, and treatment: a science advisory from the American Heart Association Prevention Committee of the Council on Cardiovascular Nursing, Council on Clinical Cardiology, Council on Epidemiology and Prevention, and Interdisciplinary Council on Quality of Care and Outcomes Research: endorsed by the American Psychiatric Association. Circulation 2008;118 (17) 1768- 1775
PubMed
Berkman  LFBlumenthal  JBurg  MCarney  RMCatellier  DCowan  MJCzajkowski  SMDeBusk  RHosking  JJaffe  AKaufmann  PGMitchell  PNorman  JPowell  LHRaczynski  JMSchneiderman  NEnhancing Recovery in Coronary Heart Disease Patients Investigators (ENRICHD), Effects of treating depression and low perceived social support on clinical events after myocardial infarction: the Enhancing Recovery in Coronary Heart Disease Patients (ENRICHD) Randomized Trial. JAMA 2003;289 (23) 3106- 3116
PubMed
Honig  AKuyper  ASchene  AHvan Melle  JPde Jonge  PTulner  DMSchins  ACrijns  HJKuijpers  PMVossen  HLousberg  ROrmel  JMIND-IT investigators, Treatment of post-myocardial infarction depressive disorder: a randomized, placebo-controlled trial with mirtazapine. Psychosom Med 2007;69 (7) 606- 613
PubMed
Rutledge  TReis  SEOlson  MBOwens  JKelsey  SFPepine  CJMankad  SRogers  WJMerz  CNSopko  GCornell  CESharaf  BMatthews  KAVaccarino  V Depression symptom severity and reported treatment history in the prediction of cardiac risk in women with suspected myocardial ischemia: the NHLBI-sponsored WISE study. Arch Gen Psychiatry 2006;63 (8) 874- 880
PubMed
de Jonge  POrmel  J Heterogeneity of patients with coronary artery disease and distress and the need to identify relevant subtypes. Arch Gen Psychiatry 2008;65 (7) 851- 853
PubMed
Hasler  GDrevets  WCManji  HKCharney  DS Discovering endophenotypes for major depression. Neuropsychopharmacology 2004;29 (10) 1765- 1781
PubMed
Cannon  CPBattler  ABrindis  RGCox  JLEllis  SGEvery  NRFlaherty  JTHarrington  RAKrumholz  HMSimoons  MLVan De Werf  FJWeintraub  WSMitchell  KRMorrisson  SLBrindis  RGAnderson  HVCannom  DSChitwood  WRCigarroa  JECollins-Nakai  RLEllis  SGGibbons  RJGrover  FLHeidenreich  PAKhandheria  BKKnoebel  SBKrumholz  HLMalenka  DJMark  DB McKay  CRPassamani  ERRadford  MJRiner  RNSchwartz  JBShaw  REShemin  RJVan Fossen  DBVerrier  EDWatkins  MWPhoubandith  DRFurnelli  T American College of Cardiology key data elements and definitions for measuring the clinical management and outcomes of patients with acute coronary syndromes: a report of the American College of Cardiology Task Force on Clinical Data Standards (Acute Coronary Syndromes Writing Committee). J Am Coll Cardiol 2001;38 (7) 2114- 2130
PubMed
Beck  ATWard  CHMendelson  MMock  JErbaugh  J An inventory for measuring depression. Arch Gen Psychiatry 1961;4561- 571
PubMed
Davidson  KWKupfer  DJBigger  JTCaliff  RMCarney  RMCoyne  JCCzajkowski  SMFrank  EFrasure-Smith  NFreedland  KEFroelicher  ESGlassman  AHKaton  WJKaufmann  PGKessler  RCKraemer  HCKrishnan  KRLespérance  FRieckmann  NSheps  DSSuls  JMNational Heart, Lung, and Blood Institute Working Group, Assessment and treatment of depression in patients with cardiovascular disease: National Heart, Lung, and Blood Institute Working Group Report. Psychosom Med 2006;68 (5) 645- 650
PubMed
Thombs  BDde Jonge  PCoyne  JCWhooley  MAFrasure-Smith  NMitchell  AJZuidersma  MEze-Nliam  CLima  BBSmith  CGSoderlund  KZiegelstein  RC Depression screening and patient outcomes in cardiovascular care: a systematic review. JAMA 2008;300 (18) 2161- 2171
PubMed
Freedland  KESkala  JACarney  RMRaczynski  JMTaylor  CBMendes de Leon  CFIronson  GYoungblood  MEKrishnan  KRVeith  RC The Depression Interview and Structured Hamilton (DISH): rationale, development, characteristics, and clinical validity. Psychosom Med 2002;64 (6) 897- 905
PubMed
American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders. 4th ed, text revision. Washington, DC: American Psychiatric Association; 2000
Eagle  KALim  MJDabbous  OHPieper  KSGoldberg  RJVan de Werf  FGoodman  SGGranger  CBSteg  PGGore  JMBudaj  AAvezum  AFlather  MDFox  KAGRACE Investigators, A validated prediction model for all forms of acute coronary syndrome: estimating the risk of 6-month postdischarge death in an international registry. JAMA 2004;291 (22) 2727- 2733
PubMed
Charlson  MEPompei  PAles  KLMacKenzie  CR A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 1987;40 (5) 373- 383
PubMed
Lespérance  FFrasure-Smith  NTalajic  MBourassa  MG Five-year risk of cardiac mortality in relation to initial severity and one-year changes in depression symptoms after myocardial infarction. Circulation 2002;105 (9) 1049- 1053
PubMed
Rapp  SRParisi  SAWalsh  DAWallace  CE Detecting depression in elderly medical inpatients. J Consult Clin Psychol 1988;56 (4) 509- 513
PubMed
Martens  EJHoen  PWMittelhaeuser  Mde Jonge  PDenollet  J Symptom dimensions of post-myocardial infarction depression, disease severity and cardiac prognosis. Psychol Meddoi:10.1017/S0033291709990997. Published August 20, 2009
PubMed
Babyak  MA What you see may not be what you get: a brief, nontechnical introduction to overfitting in regression-type models. Psychosom Med 2004;66 (3) 411- 421
PubMed
Steyerberg  EWEijkemans  MJCHarrell  FE  JrHabbema  JDF Prognostic modeling with logistic regression analysis: in search of a sensible strategy in small data sets. Med Decis Making 2001;21 (1) 45- 56
PubMed
de Araújo Gonçalves  PFerreira  JAguiar  CSeabra-Gomes  R TIMI, PURSUIT, and GRACE risk scores: sustained prognostic value and interaction with revascularization in NSTE-ACS. Eur Heart J 2005;26 (9) 865- 872
PubMed
Carney  RMFreedland  KE Depression in patients with coronary heart disease. Am J Med 2008;121 (11) ((suppl 2)) S20- S27
PubMed
Nicholson  AKuper  HHemingway  H Depression as an aetiologic and prognostic factor in coronary heart disease: a meta-analysis of 6362 events among 146 538 participants in 54 observational studies. Eur Heart J 2006;27 (23) 2763- 2774
PubMed
Denollet  JPedersen  SS Anger, depression, and anxiety in cardiac patients: the complexity of individual differences in psychological risk. J Am Coll Cardiol 2009;53 (11) 947- 949
PubMed
de Jonge  POrmel  Jvan den Brink  RHvan Melle  JPSpijkerman  TAKuijper  Avan Veldhuisen  DJvan den Berg  MPHonig  ACrijns  HJSchene  AH Symptom dimensions of depression following myocardial infarction and their relationship with somatic health status and cardiovascular prognosis. Am J Psychiatry 2006;163 (1) 138- 144
PubMed
Linke  SERutledge  TJohnson  BDVaccarino  VBittner  VCornell  CEEteiba  WSheps  DSKrantz  DSParashar  SBairey Merz  CN Depressive symptom dimensions and cardiovascular prognosis among women with suspected myocardial ischemia: a report from the National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation. Arch Gen Psychiatry 2009;66 (5) 499- 507
PubMed
Fawcett  JClark  DCScheftner  WAGibbons  RD Assessing anhedonia in psychiatric patients. Arch Gen Psychiatry 1983;40 (1) 79- 84
PubMed
Leventhal  AMRehm  LP The empirical status of melancholia: implications for psychology. Clin Psychol Rev 2005;25 (1) 25- 44
PubMed
Shorter  E The doctrine of the two depressions in historical perspective. Acta Psychiatr Scand Suppl 2007;433 (433) 5- 13
PubMed
Winograd-Gurvich  CFitzgerald  PBGeorgiou-Karistianis  NBradshaw  JLWhite  OB Negative symptoms: a review of schizophrenia, melancholic depression and Parkinson's disease. Brain Res Bull 2006;70 (4-6) 312- 321
PubMed
Kroenke  KSpitzer  RLWilliams  JB The Patient Health Questionnaire-2: validity of a two-item depression screener. Med Care 2003;41 (11) 1284- 1292
PubMed
Gorwood  P Neurobiological mechanisms of anhedonia. Dialogues Clin Neurosci 2008;10 (3) 291- 299
PubMed
Raison  CLCapuron  LMiller  AH Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol 2006;27 (1) 24- 31
PubMed
Carney  RMFreedland  KEVeith  RC Depression, the autonomic nervous system, and coronary heart disease. Psychosom Med 2005;67 ((suppl 1)) S29- S33
PubMed
Musselman  DLEvans  DLNemeroff  CB The relationship of depression to cardiovascular disease: epidemiology, biology, and treatment. Arch Gen Psychiatry 1998;55 (7) 580- 592
PubMed
Singh  KCommunal  CSawyer  DBColucci  WS Adrenergic regulation of myocardial apoptosis. Cardiovasc Res 2000;45 (3) 713- 719
PubMed
Mann  JJ McBride  PAAnderson  GMMieczkowski  TA Platelet and whole blood serotonin content in depressed inpatients: correlations with acute and life-time psychopathology. Biol Psychiatry 1992;32 (3) 243- 257
PubMed
Communal  CSingh  KPimentel  DRColucci  WS Norepinephrine stimulates apoptosis in adult rat ventricular myocytes by activation of the beta-adrenergic pathway. Circulation 1998;98 (13) 1329- 1334
PubMed
Lampert  RJain  DBurg  MMBatsford  WP McPherson  CA Destabilizing effects of mental stress on ventricular arrhythmias in patients with implantable cardioverter-defibrillators. Circulation 2000;101 (2) 158- 164
PubMed
Podrid  PJFuchs  TCandinas  R Role of the sympathetic nervous system in the genesis of ventricular arrhythmia. Circulation 1990;82 (2) ((suppl)) I103- I113
PubMed
Meredith  ITBroughton  AJennings  GLEsler  MD Evidence of a selective increase in cardiac sympathetic activity in patients with sustained ventricular arrhythmias. N Engl J Med 1991;325 (9) 618- 624
PubMed
Cohn  JNLevine  TBOlivari  MTGarberg  VLura  DFrancis  GSSimon  ABRector  T Plasma norepinephrine as a guide to prognosis in patients with chronic congestive heart failure. N Engl J Med 1984;311 (13) 819- 823
PubMed
Boyer  PTassin  JPFalissart  BTroy  S Sequential improvement of anxiety, depression and anhedonia with sertraline treatment in patients with major depression. J Clin Pharm Ther 2000;25 (5) 363- 371
PubMed
Furlanetto  LMvon Ammon Cavanaugh  SBueno  JRCreech  SDPowell  LH Association between depressive symptoms and mortality in medical inpatients. Psychosomatics 2000;41 (5) 426- 432
PubMed
Denollet  JPedersen  SSDaemen  Jde Jaegere  PSerruys  PWvan Domburg  RT Reduced positive affect (anhedonia) predicts major clinical events following implantation of coronary-artery stents. J Intern Med 2008;263 (2) 203- 211
PubMed
Stanley  K Design of randomized controlled trials. Circulation 2007;115 (9) 1164- 1169
PubMed

Correspondence

CME
Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
Submit a Comment
Might it be too premature to rule out a role for depressed mood in cardiovascular prognosis?
Posted on May 19, 2010
Frank Doyle, PhD
Royal College of Surgeons in Ireland
Conflict of Interest: None Declared
In the May issue of this journal, Davidson et al.(1) provide further evidence that specific depressive symptoms may be particularly ‘cardiotoxic’. They showed that anhedonia was a more consistent predictor than depressed mood of 1- year major adverse cardiac events (MACE) and all-cause mortality. Anhedonia was predictive of prognosis in adjusted analysis when considered both as clinician-rated and as self-reported symptoms. Clinician-rated depressed mood, although predictive in age-adjusted analyses, was no longer predictive in multivariate analysis, nor was self-reported depressed mood. The direction of the adjusted associations were however indicative of protective effects for depressed mood, albeit the findings were not statistically significant. The authors concluded that only anhedonia predicted prognosis.
Davidson et al. should be applauded for their attempt to disentangle the association between specific diagnostic symptoms of MDD and cardiovascular prognosis, with information from such studies likely enabling us to design more successful intervention trials in cardiac patients in the future.
However, in light of other recent and contrasting findings, we believe that the null finding with respect to depressed mood requires further exploration. As a measure of self-reported depressed mood, the authors combined items 1 (sadness) and 10 (crying) of the Beck Depression Inventory (BDI). There are a number of potential caveats with this approach. First, a recent systematic review indicates that crying has a somewhat variable relationship with depression.(2) Crying is only moderately associated with depression severity (mean r=.40, range r=.27-.61), is inconsistently considered by diagnostic criteria to be indicative of depression, is scored differentially by various scales (depending on whether the individual cries, or even demonstrates an inability to cry), and is largely dependant on sex.(2) Second, the authors did not provide any data to support the combination of these items (e.g. correlation, factor loadings, Loevinger’s H-value etc.). Is it possible that the true association between self-reported depressed mood (sadness) and cardiovascular prognosis is masked by the crying item, which may even have an opposite, and potentially stronger, association with the study endpoints?
Recently, we showed in independent cohorts that depressed mood, in conjunction with other symptoms, may be a stronger predictor of cardiovascular prognosis than anhedonia.(3-5) Pedersen et al.(3, 4) found that both anhedonia (HR, 1.74; 95% CI, 0.98–3.09) and feeling down, depressed or hopeless (HR, 2.05; 95% CI, 1.16–3.64), as measured with the Patient Health Questionnaire-2, were predictive of death or non-fatal myocardial infarction in percutaneous coronary intervention patients, but the relationship between depressive symptoms and prognosis was driven more by depressed mood than anhedonia. Doyle et al.(5) also showed that anhedonia (HR, 1.6; 95% CI, 0.9–2.8) was somewhat less important for prognosis than was a scale assessing fatigue/sadness/hopelessness (HR, 1.8; 95% CI, 1.1–3.0) in relation to MACE. The latter association was mainly driven by the single sadness item from the BDI Fast-Screen (HR, 1.68; 95% CI, 1.2–2.37). Hence, we would recommend that Davidson et al. also examine the individual associations for items 1 (sadness) and 10 (crying) with the study endpoints, as this might shed more light on the true association between depressed mood and prognosis.
Frank Doyle (PhD)1 Susanne S. Pedersen (PhD)2
Correspondence Dr Frank Doyle, Department of Psychology, Division of Population Health Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland (fdoyle4@rcsi.ie) Tel: +353 1 4022718, Fax: +353 1 4022329
Financial disclosure None
Author affiliations 1 Department of Psychology, Division of Population Health Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland 2 CoRPS-Center of Research on Psychology in Somatic diseases, Tilburg University, The Netherlands
References
1. Davidson KW, Burg MM, Kronish IM, et al. Association of anhedonia with recurrent major adverse cardiac events and mortality 1 year after acute coronary syndrome. Arch Gen Psychiatry. 2010;67(5):480-488.
2. Vingerhoets AJ, Rottenberg J, Cevaal A, Nelson JK. Is there a relationship between depression and crying? A review. Acta Psychiatr Scand. 2007;115(5):340-351.
3. Pedersen SS, Denollet J, de Jonge P, Simsek C, Serruys PW, van Domburg RT. Brief depression screening with the PHQ-2 associated with prognosis following percutaneous coronary intervention with paclitaxel-eluting stenting. J Gen Intern Med. 2009;24(9):1037-1042.
4. Pedersen SS, Denollet J, de Jonge P, Simsek C, Serruys PW, van Domburg RT. Erratum: Brief depression screening with the PHQ-2 associated with prognosis following percutaneous coronary intervention with paclitaxel- eluting stenting. J Gen Intern Med. 2009;24(12):1359.
5. Doyle F, Conroy RM, McGee HM, Delaney M. Depressive symptoms in persons with acute coronary syndrome: Specific symptom scales and prognosis. J Psychosom Res. 2010;68(2):121-130.
anhedonia and major adverse cardiac events in patients with acute coronary syndrome
Posted on June 10, 2010
gwenole loas, MD, PhD
CHu d'Amiens, France
Conflict of Interest: None Declared
In the May issue of the Archives of General Psychiatry Davidson et al (1) reported the results of a survey that investigated whether depressed mood and/or anhedonia are predictive of 1-year medical outcomes in patients with acute coronary syndromes (ACS). Four hundred and fifty three consecutive ACS patients from cardiac units of 3 university hospitals were actively surveyed for 1 year after admission. Within one week of admission, patients underwent a structured psychiatric interview assessing depressed mood, anhedonia and major depressive episode. Depressed mood and anhedonia were also assessed using two subscales extracted from the Beck Depression Inventory. The main outcome measures were all-cause mortality (ACM) and documented major adverse cardiac events (MACEs: myocardial infarction, hospitalization for unstable angina, or urgent/emergency coronary revascularization). 67 events were observed (16 deaths and 51 MACEs) (14.8 %) and anhedonia and depressed mood were diagnosed in 24 % and 17 % of the patients, respectively. Controlling for gender, age, and medical covariates, anhedonia (HR = 1.58; 95% CI (1.16-2.14), P < .01) was a significant predictor of combined MACE and ACM, but depressed mood was not. Anhedonia remained a significant predictor after controlling for major depressive episode or depressive symptom severity. Combined MACE and ACM were present in 29.9 % and 11.7 % of patients with and without anhedonia, respectively, and this difference was significant (P < .0001). The purpose of this letter is firstly to present two recent studies exploring the role of anhedonia on severe clinical outcomes in ACS patients that were not discussed by these authors and secondly to discuss the convergence and discrepancies between these two studies and the study by Davidson et al (1) in order to propose several guidelines for further research. The two recent studies
The first study (2) was designed to replicate and complete the study by Denollet et al (3) reporting that reduced positive affect (anhedonia), rated by a positive affect scale extracted from the depression subscale of the Hospital Anxiety and Depression Scale (HADS-D), was an independent predictor of death/myocardial infarction (MI) in a 2- year follow-up study of 874 patients following implantation of coronary artery stenting. Cox multiple regression analysis using categorical measures of positive affect showed that the incidence of death/myocardial infarction was 4% in adequate affect patients versus 11% in reduced positive affect patients (Hazard ratio = 2.55 (95 % CI 1.46-4.34)), after adjusting for clinical and demographic variables. This study presents several limitations. The positive scale may not be a typical measure of positive affect for several reasons. The positive affect scale was extracted from the HADS-D and comprised only two items rating anhedonia, while the other two items rated humor and cheerfulness. To control for the potential effect of depression the authors used the 7-item HAD-depression subscale comprising the four items of the Positive affect subscale. The use of independent measures of anhedonia and depression would be preferable from a methodological point of view to avoid multicolinearity when variables are redundant. We therefore conducted a prospective study taking these limitations into account (2). Consecutively admitted ACS patients (n = 291) completed the Chapman Physical Anhedonia Scale (PAS) and the Hospital Anxiety and Depression Scale depression subscale (HADS-D) at baseline (1-4 days after their admission). Two definitions of anhedonia were taken into account: a dimensional definition using PAS score and a categorical definition using several cutoff scores (Hedonics: PAS lower than 23 or 29; Anhedonics: PAS equal or higher than 23 (mean + SD) or 29 (mean + 2 SD). Patients were followed during 3 years for adverse clinical events, classified as severe cardiac events (mortality or MI), and clinical events (mortality, MI, recurrence of ACS, hospital readmission and onset or deterioration of heart failure (HF)). Dimensional anhedonia and depression were associated with poor prognosis, but anhedonia was the only predictor of severe cardiac events and clinical events after adjusting for demographic and clinical variables. In contrast with depression, categorical anhedonia (PAS > 23) was an independent and significant predictor of severe cardiac events after adjusting for clinical variables. The incidence of death/MI in hedonics versus anhedonics was 11.1 % vs 22.1 %; Hazard ratio = 2.18 (95 % CI 1.11-4.26).
The second study (4) was designed to identify which particular depressive symptoms were predictive of poorer prognosis in patients with acute coronary syndrome (ACS). 408 hospitalized ACS patients were followed for more than one year (median: 67 weeks). On inclusion, the patients filled out the depression subscale of the Hospital Anxiety and Depression Scale (HADS-D), the fast seven-item version of the Beck Depression Inventory (BDI-FS) and the brief 10-item version of the Maastricht Questionnaire (MQ-10) rating anergia. Mokken scaling based on these three rating scales was used to construct three derived depressive symptom scales evaluating fatigue-sadness, anhedonia and depressive cognitions, respectively. Major adverse cardiac events (MACE; cardiovascular mortality, recurrent ACS, unplanned revascularization) were assessed and univariate or multivariate Cox regressions were used to detect significant predictors of MACE. The MACE rate at the endpoint was 14.5 %. Using the recommended cutoff for the original scales and the top quartiles for the derived scales, only the HADS-D and Fatigue-sadness scales were significant predictors of MACE in univariate and multivariate analyses and the anhedonia scale was a significant predictor only in multivariate analysis. Moreover when both fatigue-sadness and anhedonia were included in the multivariate models, fatigue-sadness predicted MACE but anhedonia did not. The authors concluded that symptoms of fatigue-sadness, but not other symptoms, were associated with an increased risk of major cardiac events and that depression should be considered to be a multidimensional, rather than a unidimensional, entity.
Discussion of the three studies
The three studies reported that anhedonia was an independent predictor of severe cardiac events in ACS patients. Moreover, this effect remained significant after controlling for demographic and clinical variables and level of depression. Thus, anhedonia constitutes an independent predictor of severe cardiac events in ACS patients, with an effect not related to the level of depression.
Several limitations of the studies must be discussed.
Firstly, to explore the relative effects of anhedonia the authors used either a nonspecific anhedonia scale or ad hoc rating scales derived from existing rating scales. In the study of Davidson et al (1), two measures of anhedonia was used. First, anhedonia was rated using the DSM-IV criteria for major depressive episode. Second, the items n° 4 and 12 of the Beck Depression Inventory were summed to create an anhedonia subscale. In the Doyle et al study (4), anhedonia was rated using a 4-item subscale (3 items of the HAD-D, one item of the BDI-FS). The use of these rating scales could lead to poor reproductibility of the results. Moreover, subjects were divided into anhedonic or hedonic using ad hoc cutoff scores that have not been rigorously determined. There is a consensus in the psychiatric literature, notably based on meta-analyses of the existing anhedonia scales, in favor of the use of anhedonia scales presenting satisfactory psychometric properties (5, 6). The most widely used rating scales are the Chapman revised social (SAS) and physical anhedonia (PAS) scales and the Snaith and Hamilton Pleasure Scale (SHAPS). A new rating scale, the Temporal Experiences of Pleasure Scale (TEPS), allowing the distinction between anticipatory and consummatory anhedonia, has been recently proposed (7). These four rating scales have satisfactory psychometric properties particularly in foreign language versions. There is also a consensus in the psychiatric literature to define categories of anhedonia. Cutoff scores have been proposed notably for the SAS and the PAS. Anhedonic subjects are defined by a score on the SAS or PAS higher than 2 standard deviations above the mean calculated in healthy control groups. We therefore suggest that the above limitation should be taken into account to allow replication of studies. It would be useful to establish a consensus for each relevant psychological variable of the recommended rating scales studied in ACS patients by using the task force method. Numerous rating scales with satisfactory psychometric properties are available in psychiatric research. For example, in Parkinson's disease (PD), to harmonize data collection and to allow meta-analyses, the Movement Disorder Society (MDS) commissioned a task force to assess the clinimetric properties of anhedonia scales in PD allowing classification of rating scales as either “suggested” or “recommended” (8). The task force reviewed the psychometric properties of the PAS, SAS and SHAPS, particularly in Parkinson’s patients, and concluded that only the SHAPS was suggested.
Secondy, the dependent variable was relevant severe cardiac events at the endpoint, but different definitions for relevant events were used. In one study (4) Major Adverse Cardiac Events (MACEs) included cardiovascular mortality, recurrent ACS, and unplanned revascularization but did not include myocardial infarction and, in another study (1), MACE comprised myocardial infarction, hospitalization for unstable angina, or urgent/emergency coronary revascularization but did not include cardiovascular mortality although all-cause mortality was rated independently. The third study (2) defined severe cardiac events by all-cause mortality and myocardial infarction. As for anhedonia scales, a consensus should be reached concerning a unique definition of severe cardiac events.
Thirdly, durations of follow-up were variable. The end of follow-up was the endpoint in survival analyses. Long follow-up could therefore increase the number of clinical events. In the Davidson et al study (1) the duration of follow-up was one year in 453 patients with 67 severe clinical events (14.8 %). In the Leroy et al study (3) the duration of follow-up was 3 years with 291 patients with 44 severe clinical events (15 %). In the Doyle et al study (4) the duration of follow-up was one year and three months in 408 patients with 59 severe cardiac events (14.5 %). Follow-up was similar in the three studies, suggesting that major cardiac events could occur during the first year.
Fourthly, the nature and the number of socio-demographic and clinical covariables entered in the multivariate analyses varied between the studies. Selection criteria were based on either a priori selection or the significance of univariate analyses. The study by Davidson et al (1) used 6 covariables (age, gender, left ventricular ejection fraction, Charlson’s index of medical comorbidities, clinical prognostic index and antidepressant use) selected from previous published findings (forced covariables). Doyle et al (4) used 8 covariables (age, gender, smoking, diabetes, history of CHD, history of revascularization, length of hospital stay, left ventricular ejection fraction < 40%). Leroy et al (2) studied age, hypercholesterolemia, family history of ACS, and left ventricular hypertrophy. The number of covariables therefore ranged from 4 to 8. Guidelines must be defined concerning the modality of covariable selection. Fiftly, in all three studies, depression was controlled using depression rating scale scores. In two studies (1, 4) anhedonia was rated using a subscale extracted from the depression rating scale used to control the level of depression. Only one study (2) used different rating scales to rate anhedonia and depression. The use of separate scales should be recommended to avoid the risk of multicolinearity in multiple regressions. Finally, two important points must be discussed. Firstly, it is not clear whether anhedonia rated after the ACS is a symptom or a trait existing before ACS. Prospective studies must be conducted in subjects at risk of ACS. Secondly, recent studies have identified additional important distinctions between various aspects of pleasure, such as consummatory and anticipatory pleasures. Consummatory pleasure refers to satiation and resolution of desire, whereas anticipatory pleasure refers to motivation and goal-directed behavior. Significantly, this distinction between different aspects of pleasure has a basis in neurobiological activity (see review in 7). A new scale, the TEPS (7), has recently been developed to evaluate these two trait experiences of pleasure and several studies, notably using foreign-language versions of the scale, have reported satisfactory psychometric properties of this scale. By taking this distinction into account, it would be interesting to test the hypothesis that only anticipatory or consummatory anhedonia would be a risk factor for severe cardiac events in ACS patients.
Gwenolé Loas, Michel Leroy University Department of Psychiatry, CHU d’Amiens, University of Picardie, Amiens, France E-mail address: Loas.Gwenole@chu-amiens.fr Fernando Perez-Diaz
CNRS-UMR 7593, Hôpital de la Salpêtrière, Paris, France
References
1. Davidson KW, Burg MM, Kronish IM, Shimbo D, Dettenborn L, Mehran R, Vorcheimer D, Clemow L, Schwartz JE, Lespérance F, Rieckmann N. Association of anhedonia with recurrent major adverse cardiac events and mortality 1 year after acute coronary syndrome. Arch Gen Psychiatry 2010; 67(5):480-8. 2. Leroy M, Loas G, Perez-Diaz F. Anhedonia as predictor of clinical events after acute coronary syndromes: a 3-year prospective study. Compr Psychiatry 2010; 51(1):8-14. 3. Denollet J, Pedersen SS, Daemen J, de Jaegere P, Serruys PW, van Domburg RT. Reduced positive affect (anhedonia) predicts major clinical events following implantation of coronary-artery stents. J Intern Med 2008; 263(2):203-11. 4. Doyle F, Conroy R., McGee H, Delaney M. Depressive symptoms in persons with acute coronary syndrome: Specific symptom scales and prognosis J Psychosom Res 2010, 68: 121-130. 5. D’haenen H. Measurement of anhedonia. Eur Psychiatry. 1996; 11 (7):335- 43. 6. Loas G. measurement of anhedonia: additional remarks. Eur Psychiatry 1997; 12:266. 7. Gard DE, Germans Gard M, Kring AM, John OP. Anticipatory and consummatory components of the experience of pleasure: a scale development study. J Res Pers 2006; 40: 1086-1102. 8 Leentjens AF, Dujardin K, Marsh L, Martinez-Martin P, Richard IH, Starkstein SE, Weintraub D, Sampaio C, Poewe W, Rascol O, Stebbins GT, Goetz CG. Apathy and anhedonia rating scales in Parkinson's disease: critique and recommendations. Mov Disord. 2008; 23(14):2004-14.
Submit a Comment

Multimedia

Some tools below are only available to our subscribers or users with an online account.

Web of Science® Times Cited: 41

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
PubMed Articles
JAMAevidence.com

The Rational Clinical Examination
Evidence Summary and Review 2

The Rational Clinical Examination
Multivariate Findings for ACI Syndromes