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"Major" Depressive Disorder, Coronary Heart Disease, and the DSM–IV Threshold Problem

Received August 21, 2004; revised December 29, 2004; accepted March 7, 2005. From the Heart and Vascular Institute, Henry Ford Hospital & Wayne State University; and Consultation/Liaison Psychiatry, University of Cincinnati. Address correspondence and reprint requests to Dr. Ketterer, Henry Ford Hospital/CFP6, 2799 West Grand Blvd., Detroit MI 48202. e-mail: MarkWKetterer{at}cs.com

ABSTRACT

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Seventy-seven patients with documented coronary heart disease (CHD) were evaluated for demographic/risk factor characteristics, Major Depressive Disorder (MDD) according to the Patient’s Health Questionnaire (PHQ – Diagnostic and Statistical Manual IV criteria), and emotional distress by the Symptom Checklist 90–Revised (SCL-90-R). Early age at initial diagnosis for coronary heart disease (AAID) was used as a proxy for disease malignancy because early AAID is a known predictor of early mortality. MDD was unrelated to early AAID despite being strongly associated with all the scales of the SCL-90-R. Several of the SCL-90-R scales were significantly associated with early AAID in the sample as a whole (Depression, Interpersonal Sensitivity, Anxiety, Paranoia, and Psychoticism) and after removal of the patients meeting criteria for MDD (residual N=54). Our results suggest a new criterion for determining whether depression, or any mental disorder, is "major": onset or aggravation of serious medical illness.

INTRODUCTION

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The threshold at which a biobehavioral variable becomes a "disorder" or "risk factor" is unclear.^1–13 For cardiac risk factors (e.g., blood pressure or cholesterol), the threshold has been determined by prospective, epidemiological evidence that increased risk accrues to individuals displaying values above a given number. For historical and paradigmatic reasons, the threshold for determining "disorder" status in the DSM system has relied on expert-consensus panels, rather than objective outcomes. For mental disorders, such objective outcomes might conceivably include death by suicide, attempted suicide, psychosocial dysfunction (e.g., inability to hold a job), and self-injurious behavior (e.g., cutting). In recent years, consideration of another criterion has become compelling: medically related outcomes such as mortality, medical disability, or excessive healthcare utilization.^14–16

With the growing body of prospective-epidemiological, and treatment studies demonstrating that emotional distress is a complication, comorbidity, and/or risk factor for developing various medical illnesses such as coronary heart disease,^15–20 we believe the application of Diagnostic and Statistical Manual (DSM) diagnostic criteria to medical populations needs serious scrutiny. Comorbid emotional distress is the major determinant of dysfunction/disability in most medical populations.^15,16,21 For at least some medical conditions, emotional distress may be a major causal factor in initiating or aggravating disease progression.^19,22 The latter effect may be due to "psychobehavioral" (e.g., noncompliance, substance abuse) or "psychophysiological" (e.g., acute or chronic sympathetic arousal) mechanisms.²³ Of particular interest is coronary heart disease, where several dozen prospective studies indicate enhanced risk for increased symptoms, myocardial infarction, and mortality.^19,22 Strong circumstantial evidence now indicates that cognitive-behavioral therapy of emotional distress¹⁷ and psychopharmacological therapy of depression^18,20 may reduce the cause of death for most Americans—myocardial infarction—even for CHD patients with "subclinical" or "mild" depression or anxiety.

The present article examines the association of DSM Major Depressive Disorder (per Patient’s Health Questionnaire [PHQ]) and continuous measures of depression/distress (Symptom Checklist 90–Revised) with "age at initial diagnosis" (AAID) of CHD, a known marker of disease severity.^24,25 If MDD captures all relevant psychosocial variance in CHD onset, then MDD should be as potent a correlate of AAID as the continuous measures, and no residual predictive value should remain after removing patients meeting MDD criteria from the sample. However, if MDD misses a significant proportion of patients who remain at risk for CHD onset, then the continuous measures should be stronger correlates of early AAID and should retain significant predictive value even after removal of MDD patients.

METHOD

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This study was approved by the Henry Ford Hospital Institutional Review Board.

Subjects
The present study includes 77 patients with objectively-documented coronary artery disease (myocardial infarction or significant coronary artery disease by coronary angiography, defined as a 50%-or-greater lesion in the major epicardial arteries or any lesion in the left main branch), who were referred for "stress management" from a Cardiac Rehabilitation Program or Outpatient Cardiology Clinics at Henry Ford Hospital. Patients were excluded if they had significant cognitive deficits (N=3), were already on an antidepressant for longer than 1 week (N=1), or refused to have their data entered in a de-identified database (N=0). Mean age of the sample was 59.5 (standard deviation [SD]: 12.7). Mean years of education: 13.5 (SD: 2.1) years. When the patients meeting criteria for MDD were excluded (N=23; 29%), 54 patients remained in the sample. Another 21 patients (27%) received a T-score of 65 or higher on the SCL-90-R Depression Scale (e.g., 93rd percentile or greater against general-population norms) while not meeting PHQ criteria for MDD, and thus could be considered as having "minor" depression. Thirty of the subjects were women (39%), and 37 were non-Caucasian (48%).

Instruments
The patients were administered a semistructured interview to quantify demographic and risk-factor status, including: age at initial diagnosis of coronary artery disease (AAID), body mass index, hours of exercise per week, pack-years of smoking (number of years smoking x maximum packs per day), years of education, snoring (as a proxy for sleep apnea), sex (male versus female), family history of early CHD (none versus at least one first- or second-degree relative having onset of CHD before age 56), current smoking (Yes/No), history of diabetes (Yes/No), history of hypercholesterolemia (Yes/No), history of hypertension (Yes/No), history of myocardial infarction (Yes/No), history of coronary revascularization (Yes/No), race (Caucasian versus Other), and current marital status.(Married versus Not). Patients were administered the PHQ, which determines presence or absence of Major Depressive Disorder positive symptoms per DSM–IV criteria,²⁶ and the Symptom Checklist 90–Revised.²⁷ The PHQ Scale score was also scored and tested as a continuous measure of depression.

Procedures
During the course of a routine outpatient initial clinical evaluation, patients were administered the semistructured interview and the questionnaires.

Analyses
A p<0.05 level of significance was used, unless otherwise stated.

Both AAID and the SCL-90-R scales were compared across the MDD and non-MDD groups by use of two-sided, independent-sample t-tests.

The SCL-90-R scales, PHQ Scale, and demographic/cardiovascular risk factors were tested for their association with AAID for the sample as a whole by use of Pearson product-moment correlation coefficients and T-scores.

The SCL-90-R scales, and the PHQ Scale Score, were then tested for their association with AAID after removing patients who met DSM–IV (PHQ) criteria for MDD (residual N=54).

RESULTS

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AAID was negatively associated with snoring, male sex, family history of early CHD, being a current smoker, and having a history of MI, and positively associated with having a history of diabetes, and hypertension These results are summarized in Table 1.

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TABLE 1. Association of AAID With Demographic and Cardiovascular Risk Factors

The average AAID did not differ significantly between the MDD and non-MDD groups. However, all of the SCL-90-R scale scores were significantly correlated with MDD. These results are summarized in Table 2.

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TABLE 2. Association of Major Depressive Disorder With Age at Initial Diagnosis of CHD and the Scales of the SCL-90–R

Several of the SCL-90-R scale scores were significantly associated with AAID in the sample as a whole. These included Depression, Interpersonal Sensitivity, Anxiety, Paranoia, and Psychoticism.

Several SCL-90-R scale scores (Depression, Interpersonal Sensitivity, Anxiety, and Psychoticism) retained a significant association with AAID after removing the MDD patients from analysis.

The PHQ, scored as a continuous scale, trended in the same direction as the SCL-90-R scales, but did not reach significance. These results are also summarized in Table 3.

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TABLE 3. Correlation of the SCL-90–R Scales With AAID With, and Without, Major Depressive Disorder (MDD) Patients Included

DISCUSSION

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Present results indicate that current MDD is not a strong correlate of early-onset CHD. On the other hand, several scales of the SCL-90-R are associated with early onset of CHD, even after removing MDD patients from analysis. However, the fact that the PHQ Scale score, while trending in the expected direction, failed to achieve significance may mean that the SCL-90-R scales are more sensitive than the symptom cluster used for MDD. For example, the SCL 90–R Depression Scale does not ask about troubled sleep or trouble with concentration. On the other hand, it does ask about decreased sexual interest, crying easily, feeling caught/trapped, feeling lonely, and worry (Table 4). Might one or more of these symptoms contribute to greater sensitivity and therefore stronger association with early onset of CHD? For example, "worry," itself, has been demonstrated to be a prospective predictor of CHD onset.²⁸

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TABLE 4. Comparison of the Items in the PHQ–9 and the SCL-90–R Depression Scale

The fact that snoring, male sex, early family history of CHD, being a current smoker, and having a history of MI are associated with early CHD is not surprising. The fact that a history of diabetes and hypertension are associated with later-onset CHD replicates our findings in two previous samples.^29,30 Within a sample selected for presence of CHD, these variables apparently predict later-, rather than earlier-onset CHD. These findings may help explain why traditional risk factors lose their prospective predictive value in diagnosed as opposed to general population samples.^24,25

In the context of multiple previous prospective studies of depression/distress as a predictor of onset/aggravation of CHD,¹⁹ we interpret these results as indicating that continuous measures of emotional distress are more sensitive indicators of CHD relevant-risk-factor status than the categorical criteria of DSM MDD.^31,32 Even when MDD patients are excluded, several of these scales retained significant covariation with early onset of CHD. Thus, MDD criteria appear to exclude patients who are at risk for adverse outcomes from CHD. We find it difficult not to use the adjective "major" to describe depression that has predictive value for early onset of CHD, given that CHD is the cause of death for half of all Americans. Furthermore, many other investigators have found "minor" depression to be predictive of CHD morbidity and mortality.¹⁹ The most explicit comparison is Frasure-Smith’s comparison of MDD (per Diagnostic Interview Schedule) with Beck Depression Inventory scores (BDI) of 10.^33,34 At 6 months, no real difference was observed in predictive value for mortality (relative risks [RRs] of 4.8 versus 5.3), whereas, at 18 months, the BDI criterion was a much stronger predictor (RRs: 3.6 versus 7.8). This presumably occurs because of fewer false negatives and/or more true positives when the more liberal criterion is used. Such may also be the case for dysfunction, as well as disease progression.³⁵

Given that most patients with such conditions are not seen in mental health clinics, while appearing in medical settings (often for symptoms/noncompliance attributable to the psychiatric condition), it is not surprising that a system devised to serve practitioners who see a sample of patients skewed by clinical and self-selection is not well suited to serve the rest of the "iceberg"—the 80% of diagnosable patients never seen in mental health settings.³⁶ Stigma, denial, minimization, somatization, and nonrecognition are still major barriers to patients’ receiving appropriate care.^37–41 Rethinking the threshold, criteria, and methodology for detection of depression in such samples may help serve the goal of getting appropriate treatment to this population.

Present results must be interpreted in the context of any processes determining entry to the sample. Thus patients with clinically silent (and thus undiagnosed) CHD, death before diagnosis, and those refusing referral for stress management are all not represented here. A clinically unselected sample studied prospectively would be the ideal replication of our findings. Because CHD testing is expensive and often invasive (e.g., CT scanners, catheterization), justification for the costs/risks for purely research purposes is ethically and pragmatically problematic.

ACKNOWLEDGMENTS

 
A version of this study was presented at the American Psychosomatic Society meeting in Orlando, FL, March 2004.

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Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Email this article to a Colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My Articles & Searches Download to citation manager Citing Articles via Google Scholar Articles by Ketterer, M. W. Articles by Weaver, W. D. Search for Related Content PubMed Citation Articles by Ketterer, M. W. Articles by Weaver, W. D. Depression Syndromes Secondary to General Medical Disorders DSM Diagnostic Criteria Other Diagnostic Tools

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