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Background: Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9., Methods: We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy., Results: 16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (-0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01)., Conclusions: PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.

Background: Screening for major depression with the Patient Health Questionnaire-9 (PHQ-9) can be done using a cutoff or the PHQ-9 diagnostic algorithm. Many primary studies publish results for only one approach, and previous meta-analyses of the algorithm approach included only a subset of primary studies that collected data and could have published results., Objective: To use an individual participant data meta-analysis to evaluate the accuracy of two PHQ-9 diagnostic algorithms for detecting major depression and compare accuracy between the algorithms and the standard PHQ-9 cutoff score of ≥10., Methods: Medline, Medline In-Process and Other Non-Indexed Citations, PsycINFO, Web of Science (January 1, 2000, to February 7, 2015). Eligible studies that classified current major depression status using a validated diagnostic interview., Results: Data were included for 54 of 72 identified eligible studies (n participants = 16,688, n cases = 2,091). Among studies that used a semi-structured interview, pooled sensitivity and specificity (95% confidence interval) were 0.57 (0.49, 0.64) and 0.95 (0.94, 0.97) for the original algorithm and 0.61 (0.54, 0.68) and 0.95 (0.93, 0.96) for a modified algorithm. Algorithm sensitivity was 0.22-0.24 lower compared to fully structured interviews and 0.06-0.07 lower compared to the Mini International Neuropsychiatric Interview. Specificity was similar across reference standards. For PHQ-9 cutoff of ≥10 compared to semi-structured interviews, sensitivity and specificity (95% confidence interval) were 0.88 (0.82-0.92) and 0.86 (0.82-0.88)., Conclusions: The cutoff score approach appears to be a better option than a PHQ-9 algorithm for detecting major depression., (© 2019 S. Karger AG, Basel.)

Background: Different diagnostic interviews are used as reference standards for major depression classification in research. Semi-structured interviews involve clinical judgement, whereas fully structured interviews are completely scripted. The Mini International Neuropsychiatric Interview (MINI), a brief fully structured interview, is also sometimes used. It is not known whether interview method is associated with probability of major depression classification.AimsTo evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics., Method: Data collected for an individual participant data meta-analysis of Patient Health Questionnaire-9 (PHQ-9) diagnostic accuracy were analysed and binomial generalised linear mixed models were fit., Results: A total of 17 158 participants (2287 with major depression) from 57 primary studies were analysed. Among fully structured interviews, odds of major depression were higher for the MINI compared with the Composite International Diagnostic Interview (CIDI) (odds ratio (OR) = 2.10; 95% CI = 1.15-3.87). Compared with semi-structured interviews, fully structured interviews (MINI excluded) were non-significantly more likely to classify participants with low-level depressive symptoms (PHQ-9 scores ≤6) as having major depression (OR = 3.13; 95% CI = 0.98-10.00), similarly likely for moderate-level symptoms (PHQ-9 scores 7-15) (OR = 0.96; 95% CI = 0.56-1.66) and significantly less likely for high-level symptoms (PHQ-9 scores ≥16) (OR = 0.50; 95% CI = 0.26-0.97)., Conclusions: The MINI may identify more people as depressed than the CIDI, and semi-structured and fully structured interviews may not be interchangeable methods, but these results should be replicated.Declaration of interestDrs Jetté and Patten declare that they received a grant, outside the submitted work, from the Hotchkiss Brain Institute, which was jointly funded by the Institute and Pfizer. Pfizer was the original sponsor of the development of the PHQ-9, which is now in the public domain. Dr Chan is a steering committee member or consultant of Astra Zeneca, Bayer, Lilly, MSD and Pfizer. She has received sponsorships and honorarium for giving lectures and providing consultancy and her affiliated institution has received research grants from these companies. Dr Hegerl declares that within the past 3 years, he was an advisory board member for Lundbeck, Servier and Otsuka Pharma; a consultant for Bayer Pharma; and a speaker for Medice Arzneimittel, Novartis, and Roche Pharma, all outside the submitted work. Dr Inagaki declares that he has received grants from Novartis Pharma, lecture fees from Pfizer, Mochida, Shionogi, Sumitomo Dainippon Pharma, Daiichi-Sankyo, Meiji Seika and Takeda, and royalties from Nippon Hyoron Sha, Nanzando, Seiwa Shoten, Igaku-shoin and Technomics, all outside of the submitted work. Dr Yamada reports personal fees from Meiji Seika Pharma Co., Ltd., MSD K.K., Asahi Kasei Pharma Corporation, Seishin Shobo, Seiwa Shoten Co., Ltd., Igaku-shoin Ltd., Chugai Igakusha and Sentan Igakusha, all outside the submitted work. All other authors declare no competing interests. No funder had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.

Major depressive disorder (MDD) has been associated with reduced leukocyte telomere length (LTL). It is not known, however, whether psychosocial and behavioral protective factors moderate this association. In the current study, we examine whether multisystem resiliency--defined by healthy emotion regulation, strong social connections, and health behaviors (sleep and exercise)--predicts LTL and mitigates previously demonstrated associations between depression diagnosis and LTL. LTL was measured, using a quantitative PCR assay, in 954 patients with stable cardiovascular disease in the Heart and Soul Study. In a fully adjusted model, high multisystem resiliency predicted longer LTL (b=80.00, SE=27.17, p=.003), whereas each individual factor did not. Multisystem resiliency significantly moderated the MDD-LTL association (p=.02). Specifically, MDD was significantly related to LTL at 1 SD below the mean of multisystem resiliency (b=-142.86, SE=56.46, p=.01), but not at 1 SD above the mean (b=49.07, SE=74.51, p=.51). This study suggests that MDD associations with biological outcomes should be examined within a psychosocial-behavioral context, because this context shapes the nature of the direct relationship. Further research should explore the cognitive, neural, and other physiological pathways through which multisystem resiliency may confer biological benefit., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Approximately one out of every five patients with cardiovascular disease (CVD) suffers from major depressive disorder (MDD). Both MDD and depressive symptoms are risk factors for CVD incidence, severity and outcomes. Great progress has been made in understanding potential mediators between MDD and CVD, particularly focusing on health behaviors. Investigators have also made considerable strides in the diagnosis and treatment of depression among patients with CVD. At the same time, many research questions remain. In what settings is depression screening most effective for patients with CVD? What is the optimal screening frequency? Which therapies are safe and effective? How can we better integrate the care of mental health conditions with that of CVD? How do we motivate depressed patients to change health behaviors? What technological tools can we use to improve care for depression? Gaining a more thorough understanding of the links between MDD and heart disease, and how best to diagnose and treat depression among these patients, has the potential to substantially reduce morbidity and mortality from CVD., (Published by Elsevier Inc.)

BACKGROUND- In 2008, the American Heart Association (AHA) recommended a 2-step screening method, consisting of the 2-item Patient Health Questionnaire (PHQ-2) followed by the 9-item Patient Health Questionnaire (PHQ-9), for identifying depression in cardiovascular patients. The accuracy and prognostic value of this screening method have not been evaluated. METHODS AND RESULTS- We administered the 2-step AHA-recommended screening algorithm to 1024 patients with stable coronary heart disease and calculated sensitivity and specificity against a gold standard interview for major depressive disorder. Subsequent cardiovascular events (myocardial infarction, stroke, transient ischemic attack, heart failure, or death) were determined during a mean of 6.27 ± 2.11 years of follow-up. The AHA-recommended screening method had high specificity (0.91; 95% confidence interval, 0.89 to 0.93) but low sensitivity (0.52; 95% confidence interval, 0.46 to 0.59) for a diagnosis of major depressive disorder. Participants who screened positive on the AHA depression protocol had a 55% greater risk of events than those who screened negative (age-adjusted hazard ratio, 1.55; 95% confidence interval, 1.21 to 1.97; P=0.0005). After adjustment for age, sex, body mass index, history of myocardial infarction, hypertension, diabetes, heart failure, and high-density lipoprotein levels, screening positive remained associated with a 41% greater rate of cardiovascular events (hazard ratio, 1.41; 95% confidence interval, 1.10 to 1.81; P=0.008). CONCLUSIONS- Among outpatients with stable coronary heart disease, the AHA-recommended depression screening protocol is highly specific for depression and identifies patients at risk for adverse cardiovascular outcomes.

Objective: Shortened telomere length has been associated with mortality in patients with coronary heart disease (CHD) and is considered as an emerging marker of biologic age. Whether depression is associated with telomere length or trajectory has not been evaluated in patients with CHD., Methods: In a prospective cohort study, we measured leukocyte telomere length in 952 participants with stable CHD at baseline and in 608 of these participants after 5 years of follow-up. The presence of major depressive disorder in the past month was assessed using the computerized diagnostic interview schedule at baseline. We used linear and logistic regression models to evaluate the association of depression with baseline and 5-year change in leukocyte telomere length., Results: Of the 952 participants, 206 (22%) had major depression at baseline. After the adjustment for age and sex, the patients with current major depressive disorder had shorter baseline telomere length than those without depression (mean [standard error] = 0.86 [0.02] versus 0.90 [0.01]; p = .02). This association was similar (but no longer statistically significant) after adjustment for body mass index, smoking, diabetes, left ventricular ejection fraction, statin use, antidepressant use, physical inactivity, and anxiety (0.85 [0.02] versus 0.89 [0.01], p = .06). Depression was not predictive of 5-year change in telomere length after adjustment for the mentioned covariates and baseline telomere length., Conclusions: Depression is associated with reduced leukocyte telomere length in patients with CHD but does not predict 5-year change in telomere length. Future research is necessary to elucidate the potential mechanisms underlying the association between depression and telomere length.

Objective: To evaluate whether depression is associated with whole blood serotonin in outpatients with stable coronary heart disease (CHD). Depression is associated with incident CHD and with adverse cardiovascular outcomes. Dysregulation of peripheral serotonin, common to both depression and CHD, may contribute to this association., Methods: We performed a cross-sectional study of 791 participants with stable CHD enrolled in the Heart and Soul Study and not taking antidepressant medication. We assessed major depression using the Computerized Diagnostic Interview Schedule (CDIS-IV) and measured whole blood serotonin (WBS) from fasting venous samples., Results: Of the 791 participants, 114 (14%) had current (past month) major depression, 186 (24%) had past (but not current) major depression, and 491 (62%) had no history of depression. Age-adjusted mean WBS was higher in participants with current major depression (139 +/- 6.5 ng/ml) than in those with past depression (120 +/- 5.0 ng/ml) or no history of depression (119 +/- 3.1 ng/ml) (p = .02). This association was unchanged after adjustment for demographic characteristics, medical comorbidities, medication use, and cardiac disease severity (p = .02). When serotonin was analyzed as a dichotomous variable, current depression was associated with a 70% greater odds of having WBS in the highest quartile (adjusted odds ratio = 1.71; 95% Confidence Interval = 1.03-2.83; p = .04)., Conclusions: In this sample of patients with stable CHD, current major depression was independently associated with higher mean WBS levels. Future studies should examine whether elevated WBS may contribute to adverse outcomes in patients with depression and CHD.

Background: Clinical guidelines recommend depression screening in patients with coronary artery disease (CAD), but how to accomplish this is unclear., Objective: We evaluated the test characteristics of the two-item Patient Health Questionnaire (PHQ-2), the nine-item Patient Health Questionnaire (PHQ-9), and a two-step screening approach (PHQ-2 then PHQ-9 if positive on PHQ-2), compared with the Computerized Diagnostic Interview Schedule (C-DIS) for major depression. We also evaluated a "PHQ diagnosis" of depression, requiring five of nine symptoms "more than half the days," compared with the C-DIS., Design: Cross-sectional study of 1,024 outpatients with CAD., Main Results: Two hundred twenty-four patients (22%) had current major depression. Optimal cutpoints were >or=2 for the PHQ-2 (82% sensitive, 79% specific) and >or=6 for the PHQ-9 (83% sensitive, 76% specific). The two-step screening approach was less sensitive (75%), but more specific (84%), than the PHQ-2 or PHQ-9 alone. The "PHQ diagnosis" had low sensitivity (28%), but high specificity (96%)., Conclusions: Cutpoints of >or=2 on the PHQ-2 and >or=6 on the PHQ-9 had similar test characteristics. A two-step approach using the PHQ-2 followed by the PHQ-9 was no better than either instrument alone. A "PHQ diagnosis" of depression had high specificity, but poor sensitivity.

Context: Depressive symptoms predict adverse cardiovascular outcomes in patients with coronary heart disease, but the mechanisms responsible for this association are unknown., Objective: To determine why depressive symptoms are associated with an increased risk of cardiovascular events., Design and Participants: The Heart and Soul Study is a prospective cohort study of 1017 outpatients with stable coronary heart disease followed up for a mean (SD) of 4.8 (1.4) years., Setting: Participants were recruited between September 11, 2000, and December 20, 2002, from 12 outpatient clinics in the San Francisco Bay Area and were followed up to January 12, 2008., Main Outcome Measures: Baseline depressive symptoms were assessed using the Patient Health Questionnaire (PHQ). We used proportional hazards models to evaluate the extent to which the association of depressive symptoms with subsequent cardiovascular events (heart failure, myocardial infarction, stroke, transient ischemic attack, or death) was explained by baseline disease severity and potential biological or behavioral mediators., Results: A total of 341 cardiovascular events occurred during 4876 person-years of follow-up. The age-adjusted annual rate of cardiovascular events was 10.0% among the 199 participants with depressive symptoms (PHQ score > or = 10) and 6.7% among the 818 participants without depressive symptoms (hazard ratio [HR], 1.50; 95% confidence interval, [CI], 1.16-1.95; P = .002). After adjustment for comorbid conditions and disease severity, depressive symptoms were associated with a 31% higher rate of cardiovascular events (HR, 1.31; 95% CI, 1.00-1.71; P = .04). Additional adjustment for potential biological mediators attenuated this association (HR, 1.24; 95% CI, 0.94-1.63; P = .12). After further adjustment for potential behavioral mediators, including physical inactivity, there was no significant association (HR, 1.05; 95% CI, 0.79-1.40; P = .75)., Conclusion: In this sample of outpatients with coronary heart disease, the association between depressive symptoms and adverse cardiovascular events was largely explained by behavioral factors, particularly physical inactivity.

Context: Several practice guidelines recommend that depression be evaluated and treated in patients with cardiovascular disease, but the potential benefits of this are unclear., Objective: To evaluate the potential benefits of depression screening in patients with cardiovascular disease by assessing (1) the accuracy of depression screening instruments; (2) the effect of depression treatment on depression and cardiac outcomes; and (3) the effect of screening on depression and cardiac outcomes in patients in cardiovascular care settings., Data Sources: MEDLINE, PsycINFO, CINAHL, EMBASE, ISI, SCOPUS, and Cochrane databases from inception to May 1, 2008; manual journal searches; reference list reviews; and citation tracking of included articles., Study Selection: We included articles in any language about patients in cardiovascular care settings that (1) compared a screening instrument to a valid major depressive disorder criterion standard; (2) compared depression treatment with placebo or usual care in a randomized controlled trial; or (3) assessed the effect of screening on depression identification and treatment rates, depression, or cardiac outcomes., Data Extraction: Methodological characteristics and outcomes were extracted by 2 investigators., Results: We identified 11 studies about screening accuracy, 6 depression treatment trials, but no studies that evaluated the effects of screening on depression or cardiovascular outcomes. In studies that tested depression screening instruments using a priori-defined cutoff scores, sensitivity ranged from 39% to 100% (median, 84%) and specificity ranged from 58% to 94% (median, 79%). Depression treatment with medication or cognitive behavioral therapy resulted in modest reductions in depressive symptoms (effect size, 0.20-0.38; r(2), 1%-4%). There was no evidence that depression treatment improved cardiac outcomes. Among patients with depression and history of myocardial infarction in the ENRICHD trial, there was no difference in event-free survival between participants treated with cognitive behavioral therapy supplemented by an antidepressant vs usual care (75.5% vs 74.7%, respectively)., Conclusions: Depression treatment with medication or cognitive behavioral therapy in patients with cardiovascular disease is associated with modest improvement in depressive symptoms but no improvement in cardiac outcomes. No clinical trials have assessed whether screening for depression improves depressive symptoms or cardiac outcomes in patients with cardiovascular disease.

Objective: The short allele of a functional polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) has been shown to interact with stressful life events to predict depression in otherwise healthy individuals. Whether the short allele increases risk for depression associated with the stress of a chronic illness has not been established., Method: In a cross-sectional genetic association study, the authors examined the association of 5-HTTLPR with current depression (measured by the Computerized Diagnostic Interview Schedule), perceived stress (measured by the Perceived Stress Scale), and 24-hour urinary norepinephrine excretion in 557 outpatients with chronic coronary disease., Results: Among individuals carrying an s allele, 25% (97 of 383) had current depression, compared with 17% (29 of 174) of l/l homozygotes. The unadjusted odds ratio was 1.6, with a 95% confidence interval (CI) of 1.0-2.6; the age- and gender-adjusted odds ratio was also 1.6 (95% CI=1.0-2.5). Participants carrying an s allele had a higher mean score for perceived stress than l/l homozygotes (5.4 versus 4.7) and a higher rate of moderate or high perceived stress (adjusted odds ratio=1.6, 95% CI=1.1-2.3). Mean 24-hour norepinephrine excretion was higher in s allele carriers (55.6 versus 50.2 mg/day), who were more likely to have norepinephrine values in the highest quartile (adjusted odds ratio=1.7, 95% CI=1.0-3.0)., Conclusions: Among patients with chronic illness, carriers of the s allele of 5-HTTLPR are more vulnerable to depression, perceived stress, and high norepinephrine secretion. These factors may contribute to worse cardiovascular outcomes in these patients.

Background: Depression and inflammation independently predict adverse cardiovascular outcomes in patients with coronary heart disease (CHD). Depression has been associated with elevated levels of inflammation in otherwise healthy patients without known CHD. However, studies investigating the link between depression and inflammation in patients with established CHD have produced inconclusive results., Methods: We sought to examine the association of major depression with inflammation in 984 outpatients with established CHD from the Heart and Soul Study. We assessed current major depression with the Computerized Diagnostic Interview Schedule and collected venous blood samples for measurement of five inflammatory biomarkers (white blood cell count, CD40 ligand, C-reactive protein [CRP], fibrinogen, and interleukin-6 [IL-6]). We used multivariate analysis of variance to examine the association of current depression with inflammatory markers, adjusted for potential confounding variables., Results: Of the 984 participants, 217 (22%) had current major depression. Depression was not associated with increased levels of any inflammatory marker. Contrary to our hypothesis, depression was associated with lower levels of CRP (p = .09), fibrinogen (p = .006), and IL-6 (p = .007) in both unadjusted and adjusted models., Conclusions: We found no evidence that current depression is associated with greater inflammation in outpatients with CHD. Inflammation is unlikely to explain the adverse cardiovascular outcomes associated with depression in patients with established CHD.

Major depressive disorder is a risk factor for the development of incident coronary heart disease events in healthy patients and for adverse cardiovascular outcomes in patients with established heart disease. Depression is present in 1 of 5 outpatients with coronary heart disease and in 1 of 3 outpatients with congestive heart failure, yet the majority of cases are not recognized or appropriately treated. It is not known whether treating depression improves cardiovascular outcomes, but antidepressant treatment with selective serotonin reuptake inhibitors is generally safe, alleviates depression, and improves quality of life. This article evaluates the importance of major depression in patients with cardiovascular disease, and provides practical guidance for identifying and treating this disorder.

Context: Depression is associated with low heart rate variability (HRV) in patients following myocardial infarction, suggesting that alterations in the autonomic nervous system may contribute to the adverse cardiac outcomes associated with depression. Whether depression is associated with low HRV in patients with stable coronary heart disease (CHD) is not known., Objective: To examine the association between major depression and 24-hour HRV in patients with stable CHD., Design, Setting, and Participants: Cross-sectional study of 873 outpatients with stable CHD recruited from outpatient clinics in the San Francisco Bay Area, California., Main Outcome Measures: Major depression was assessed using the Computerized National Institute of Mental Health Diagnostic Interview Schedule. Heart rate variability was measured by 24-hour ambulatory electrocardiography., Results: A total of 195 participants (22%) had major depression. Overall, we observed no association between depression and HRV as measured by time domain or frequency domain variables. Mean HRV was similar in participants with and without depression (all P values >.10), and participants with depression were no more likely than those without depression to have low HRV (all P values >.10)., Conclusions: We found no evidence of an association between depression and HRV in 873 outpatients with stable CHD. These findings raise questions about the potential role of HRV in the association between depression and cardiovascular disease.

Background: In patients with coronary heart disease (CHD), depression leads to worse cardiovascular outcomes. Depression has been associated with increased cortisol in medically healthy patients, suggesting that cortisol may act as a mediator in the pathway between depression and cardiovascular events. However, it is not known whether depression is associated with elevated cortisol levels in patients with CHD., Methods: We examined the association between depression (assessed by the Computerized Diagnostic Interview Schedule) and 24-hour urinary cortisol in 693 medical outpatients with known CHD., Results: Of 693 participants, 138 (20%) had current depression. Depressed participants had greater mean cortisol levels than those without depression (42 +/- 25 vs. 36 +/- 20 microg/day, p <.01). With each increasing quartile of cortisol concentration the frequency of depression increased (p <.01). Participants in the highest quartile of cortisol had a twofold increased odds of having depression, compared with those in the lowest quartile (odds ratio [OR] 2.1, 95% confidence interval [CR] 1.2-3.6, p =.01). This association remained strong after adjusting for potential confounding variables (OR 2.4, 95% CI 1.3-4.4, p <.01). In this cross-sectional analysis, elevated cortisol was not associated with worse cardiac function., Conclusions: In patients with CHD,depression is associated with elevated cortisol levels.