Stress Measurement in Primary Care: Conceptual Issues, Barriers, Resources, and Recommendations for Study.

OBJECTIVE: Exposure to stressors in daily life and dysregulated stress responses are associated with increased risk for a variety of chronic mental and physical health problems, including anxiety disorders, depression, asthma, heart disease, certain cancers, and autoimmune and neurodegenerative disorders. Despite this fact, stress exposure and responses are rarely assessed in the primary care setting and infrequently targeted for disease prevention or treatment. METHOD: In this narrative review, we describe the primary reasons for this striking disjoint between the centrality of stress for promoting disease and how rarely it is assessed by summarizing the main conceptual, measurement, practical, and reimbursement issues that have made stress difficult to routinely measure in primary care. The following issues will be reviewed: a) assessment of stress in primary care, b) biobehavioral pathways linking stress and illness, c) the value of stress measurements for improving outcomes in primary care, d) barriers to measuring and managing stress, and e) key research questions relevant to stress assessment and intervention in primary care. RESULTS: On the basis of our synthesis, we suggest several approaches that can be pursued to advance this work, including feasibility and acceptability studies, cost-benefit studies, and clinical improvement studies. CONCLUSIONS: Although stress is recognized as a key contributor to chronic disease risk and mortality, additional research is needed to determine how and when instruments for assessing life stress might be useful in the primary care setting, and how stress-related data could be integrated into disease prevention and treatment strategies to reduce chronic disease burden and improve human health and well-being.

Clinical and neural responses to cognitive behavioral therapy for functional tremor.

OBJECTIVES: To evaluate changes in tremor severity and motor/emotion-processing circuits in response to cognitive behavioral therapy (CBT) delivered as treatment for functional tremor (FT), the most common functional movement disorder in adults. METHODS: Fifteen patients with FT underwent fMRI with motor, basic-emotion, and intense-emotion tasks before and after 12 weeks of CBT. Baseline fMRI was compared to those of 25 healthy controls (HCs). The main clinical endpoint was the tremor score (sum of severity, duration, and incapacitation subscores) adapted from the Rating Scale for Psychogenic Movement Disorders (PMDRS) assessed by a blinded clinician. CBT responders were defined as those with PMDRS score reduction >75%. Anatomic and functional brain images were obtained with a 4T MRI system. Generalized linear model and region-of-interest analyses were used to evaluate before-versus-after treatment-related changes in brain activation. RESULTS: CBT markedly reduced tremor severity (p < 0.01) with remission/near remission achieved in 73.3% of the cohort. Compared to HCs, in those with FT, a functionally defined fMRI region of interest in the anterior cingulate/paracingulate cortex showed increased activation at baseline and decreased activation after CBT during basic-emotion processing (p = 0.012 for CBT responders). Among CBT responders, the change in anterior cingulate/paracingulate was more significant in those with more severe baseline depression (r = 0.75, p < 0.01). CONCLUSIONS: Tremor severity improved significantly after CBT. The improvement was associated with changes in the anterior cingulate/paracingulate activity, which may represent a marker of emotional dysregulation in FT and a predictor of treatment response. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that CBT significantly improves tremor severity in patients with functional tremor.

Another Step Toward Clarifying the Benefits and Burdens of Selective Serotonin Reuptake Inhibitors.

Selective serotonin reuptake inhibitors (SSRIs) have substantial beneficial effects for the treatment of major depressive mood disorders and other conditions but can also result in unwanted clinical outcomes. One of the reported disadvantages of SSRIs, based on cross-sectional studies, is their adverse effects on glycemic control. However, in this issue of Psychosomatic Medicine, Tharmaraja et al. report a meta-analysis of 16 randomized controlled trials, demonstrating beneficial effects of SSRIs on changes in glycemia. In this editorial, the advantages of meta-analysis in biobehavioral medicine are highlighted as well as the importance of the study designs (observational studies versus randomized controlled trials) on which the meta-analyses are based. This article concludes with an outline for future research directions in the area of SSRIs and glycemic control.

Cardiometabolic risks and omega-3 index in recent-onset bipolar I disorder.

OBJECTIVES: The aims of the present study were to characterize cardiometabolic risk factors in a cohort of bipolar disorder patients with limited exposure to psychotropic medications, and to evaluate their associations with mood symptoms and omega-3 polyunsaturated fatty acid (PUFA) blood levels. METHODS: Cardiometabolic risk assessments were compared in individuals with bipolar I disorder experiencing a first manic or mixed episode or an early depressive episode (n=117) and healthy subjects (n=56). Patients were medication free at assessment and had no or limited exposure to mood-stabilizer or antipsychotic medications prior to the current admission. Associations among cardiometabolic parameters and Clinical Global Impression-Severity scale (CGI-S), manic (Young Mania Rating Scale [YMRS]), and depressive (Hamilton Depression Rating Scale [HDRS]) symptom ratings were evaluated within the bipolar group. RESULTS: Following adjustment for demographic variables (i.e., age, gender, and parental education), significantly higher fasting triglyceride levels were observed in the bipolar group compared to the healthy group (121.7 mg/dL vs 87.0 mg/dL; P<.01). There were no clear trends for other metabolic indicators, including blood pressure, body mass index, and fasting glucose. Nineteen percent of the bipolar group and 6% of the healthy group met the criteria for metabolic syndrome (P=.23). The omega-3 index was lower in the bipolar group (3.4% vs 3.9%; P<.01). Within the bipolar group, no associations were found between the cardiometabolic parameters and CGI-S, YMRS, and HDRS symptom ratings. CONCLUSIONS: Recent-onset medication-free bipolar disorder is associated with higher triglyceride levels. These findings are suggestive of early metabolic dysregulation prior to long-term psychotropic medication exposure. Lower omega-3 PUFA levels in individuals with bipolar I disorder represent a potential therapeutic target for additional investigation.

The Contribution of Autonomic Imbalance to the Development of Metabolic Syndrome.

OBJECTIVES: Obesity, diabetes, and heart disease-the most costly epidemics of our time-share a common but rarely treated mechanism: autonomic imbalance. We examined the contribution of autonomic imbalance, relative to selected demographic and biobehavioral risk factors, to the development of metabolic syndrome in a community sample for 12 years. METHODS: We identified offspring cohort participants from the Framingham Heart Study who did not have metabolic syndrome at Examination 3 (1983-1987, baseline for this analysis) and whose metabolic syndrome status was assessed at the 4-, 8-, and 12-year follow-ups. We created logistic regression models, using baseline resting heart rate (RHR) and heart rate variability (HRV), to predict the odds of developing metabolic syndrome within 12 years, adjusting for age, sex, depressive symptoms, and smoking. HRV indices (standard deviation of the beat-to-beat interval [SDNN] and root mean square of the standard deviation) were calculated from 2-hour Holter monitor data. RESULTS: Our sample consisted of 1143 participants (mean [SD] age = 46.6 (9.9) years, 57% female). One standard deviation of a decrease in SDNN increased the odds of developing metabolic syndrome within 12 years by 43% (95% confidence interval = 1.302-1.572, p < .001). Without HRV in the model, each increase in RHR of 10 beats/min increased the odds of developing metabolic syndrome by 24% (95% confidence interval = 1.094-1.426, p < .001). CONCLUSIONS: In this community sample, low HRV by both measures (SDNN and root mean square of the standard deviation), high RHR, increased age, cigarette smoking, and being male significantly increased the odds of developing metabolic syndrome within 12 years of baseline.

Autonomic Imbalance as a Predictor of Metabolic Risks, Cardiovascular Disease, Diabetes, and Mortality.

CONTEXT: Identifying novel early predictors of metabolic disorders is essential to improving effective primary prevention. OBJECTIVES: The objectives were to examine the contribution of two measures of autonomic imbalance, resting heart rate (RHR) and heart rate variability (HRV), on the development of five metabolic risk outcomes, and on cardiovascular disease, diabetes, and early mortality. DESIGN: This study was a secondary analysis of prospective data from Offspring Cohort participants (N = 1882) in the Framingham Heart Study (FHS). PARTICIPANTS: Participants at FHS Exam 3 (1983-1987) with 1) age years 18 or older, and 2) data on RHR, HRV, and five measures of metabolic risk (blood pressure, fasting glucose, triglycerides, high-density lipoprotein [HDL] cholesterol, and body mass index [BMI]) at three follow-up visits over 12 years. We conducted a backward elimination variable selection procedure on a logistic regression model, using baseline RHR, HRV, age, sex, and smoking status to predict the odds of developing a specific metabolic risk. OUTCOMES: Measures included hyperglycemia, high blood pressure, high triglycerides, low HDL cholesterol, and high BMI over 12 years; incident diabetes, cardiovascular disease, and early mortality over 20 years. RESULTS: RHR and HRV, along with sex, age, and smoking were significant predictors of high blood pressure, hyperglycemia, and a diagnosis of diabetes within 12 years. RHR and HRV also predicted the development of cardiovascular disease and early mortality for most of the sample. CONCLUSIONS: In this community sample two measures of autonomic imbalance predicted multiple poor metabolic outcomes and mortality, making autonomic imbalance a potentially worthy target for intervention studies to reduce risks for cardiovascular disorders, diabetes, and early death.

Acute psychosis and type 2 diabetes mellitus:should screening guidelines be revised?

Although psychosis increases the risk for developing type 2 diabetes, the temporal relationship between the onset of psychosis and the onset of diabetes has not been studied. We present 6 cases of acute psychosis, which led to the new diagnosis of type 2 diabetes during inpatient psychiatric admission within days to weeks of the psychotic episode. The implications of these findings and the efficacy of current diabetes screening guidelines are discussed.

Depression and whole blood serotonin in patients with coronary heart disease from the Heart and Soul Study.

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.

Dimensionality reduction for knowledge discovery in medical claims database: application to antidepressant medication utilization study.

Data mining, through its capacity to discover knowledge embedded in large databases to improve organizational decision-making, has the potential to contribute to efficiencies and cost savings in the increasingly costly healthcare industry. One important aspect of the methods of mining medical databases includes reducing dimensionality through feature selection. Traditionally feature selection is accomplished through stepwise regression, which tends to produce an unnecessarily high number of "significant" variables. This paper applies a filter-based feature selection method using inconsistency rate measure and discretization, to a medical claims database to predict the adequacy of duration of antidepressant medication utilization. Compared to traditional stepwise logistic regression, which selected seven variables from a total of nine potential explanatory variables to characterize patients with inadequate antidepressant medication utilization, the filter-based method selected two variables (age and number of claims) to achieve a similar prediction accuracy. This comparison suggests it may be feasible and efficient to apply the filter-based feature selection method to reduce the dimensionality of healthcare databases.

Models of integrated care.

This article describes the range of options for integrating medicine and psychiatry, with a focus on the advantages and limitations of each model. The models were developed in different countries with specific health care cultures. This article illustrates the range of in- and outpatient options as currently practiced, with case reports from practitioners when possible, and describes qualifications for practicing in each model, the settings, the patient populations, the relevant financial issues, and the advantages and disadvantages of practicing in each model. It closes with comments on the next steps for advancing integrated care and the barriers to be overcome.

Treatment of depression in patients with coronary heart disease.

Depression and coronary heart disease are common conditions that often occur together. Evidence shows that the co-occurrence of these illnesses is not random but driven by depression as a risk factor for the occurrence and progression of coronary heart disease. This link is due, in part, to the impact that depression has on neuroendocrine pathways leading to increased platelet activation, cortisol and catecholamine excess, and altered autonomic nervous system function that influence the pathogenesis and progression of coronary atherosclerosis and subsequent heart disease. We know that treating depression in patients with coronary heart disease improves the symptoms and signs of depression. Evidence is less compelling that treating depression improves the morbidity and mortality of coronary heart disease. However, early findings suggest that some antidepressants may improve the course of coronary heart disease and improve patient compliance with various cardiac interventions. We outline a practical approach to the treatment of depression in patients with coronary heart disease. This approach includes education, counseling, antidepressant drugs, and referral when appropriate.

Depressive symptoms, coronary heart disease, and overall mortality in the Framingham Heart Study.

OBJECTIVE: Although a substantial number of studies have shown that depressive symptoms predict worse cardiac outcome for patients with existing coronary disease, relatively few methodologically rigorous studies have examined the relation of depressive symptoms to coronary disease incidence in individuals initially free of heart disease in the community. METHODS: Using multivariable-adjusted sex-stratified Cox proportional hazards regression, we examined the association between depressive symptoms and incident coronary disease and all-cause mortality in 3634 Framingham Heart Study original and offspring cohort participants (mean age 52 years, 55% women) attending a routine study examination between 1983 and 1994. RESULTS: Over 6 years of follow-up, 83 participants had a hard coronary heart disease event (myocardial infarction or coronary death), and 133 died. Depressive symptoms (Center for Epidemiologic Studies Depression Scale (CES-D) > or =16) did not predict hard coronary disease events. All-cause mortality, however, was directly associated with depressive symptoms. Compared with the lowest tertile of CES-D score, multivariable-adjusted risks of death in the second and third tertiles were 33% and 88% higher, respectively (hazards ratio per tertile increment = 1.37, 95% confidence interval 1.10-1.71, p for trend = 0.005). CONCLUSION: These findings underscore the importance of further research into the pathogenesis and prevention of excess mortality experienced with depressive symptoms.

Is depression a major risk factor for coronary disease? A systematic review of the epidemiologic evidence.

My objective is to examine systematically the status of the current evidence for and against depression as an independent major risk factor for coronary disease. From English-language reports on depression and coronary disease in MEDLINE (1966-2002) and PsycINFO (1967-2002), and from informal searches, I selected all studies that addressed the specific questions related to the established criteria for risk-factor status: (1) strength of association, (2) prediction, (3) specificity, (4) consistency, (5) dose-response effect, (6) biological plausibility, and (7) response to treatment. I find that the evidence for depression as a coronary disease risk factor is good for four criteria: strength of association, prediction, consistency, and dose-response effect. The evidence on specificity and biological plausibility is fair. Due to the lack of definitive studies, there is currently insufficient evidence for cardiac risk reduction in response to treatment for depression. My conclusion is that the evidence for depression's role as an independent major risk factor for coronary disease is good in four areas, but not yet conclusive in three, pointing to the need for three types of studies: (1) prospective, observational studies that address specificity questions, (2) studies of biological mechanisms linking depression and coronary disease, and (3) clinical trials of treatments for depression in people with coronary disease or at high risk for developing coronary disease.

An open-label pilot study of methylphenidate in the treatment of cocaine dependent patients with adult attention deficit/hyperactivity disorder.

A multi-site, open-label study of methylphenidate for treating patients with comorbid diagnoses of attention deficit/hyperactivity disorder and cocaine dependence was performed. Forty-one participants, who met DSM-IV criteria for adult attention deficit/hyperactivity disorder and cocaine dependence, were enrolled into this ten week outpatient study. The targeted total daily dose of methylphenidate was 60 mg (20 mg TID). Participants received individual substance abuse therapy throughout the trial. Safety measures included adverse events, vital signs, and electrocardiograms. Methylphenidate's efficacy was assessed by both objective and subjective measures. Seventy percent of the participants completed final study measures. Safety measures indicated that methylphenidate was well tolerated by the participants. Subjective efficacy measures suggested that participants evidenced improvement in both cocaine dependence and adult attention deficit/hyperactivity disorder symptoms. Quantitative benzoylecgonine indicated that only those participants categorized as being compliant showed improvement. A double-blind, placebo-controlled study of methylphenidate for this population may be warranted.

Do depressive symptoms increase the risk for the onset of coronary disease? A systematic quantitative review.

OBJECTIVE: The objectives of this study were to systematically review the recent studies of the contribution of depression to the onset of coronary disease and to estimate the magnitude of the risk posed by depression for onset of coronary disease. METHOD: We searched MEDLINE (1966-2000), PsychInfo (1967-2000), and cross references and conducted informal searches for all community studies of depression symptoms in samples with no clinically apparent heart disease at baseline. From these studies we selected all published cohort studies of 4 years or more follow-up that controlled for other major coronary disease risk factors and reported relative risks (or a comparable measure) of baseline depression for the onset of coronary disease. Following methods for the meta-analysis of epidemiologic studies, we used a random-effects model to estimate the combined overall relative risk. RESULTS: Ten studies met our inclusion criteria. Relative risks ranged from 0.98 to 3.5. Nine studies reported significantly increased risk, including two with mixed results; one study reported no increased risk. The combined overall relative risk of depression for the onset of coronary disease was 1.64 (95% CI = 1.41-1.90). CONCLUSIONS: This quantitative review suggests that depressive symptoms contribute a significant independent risk for the onset of coronary disease, a risk (1.64) that is greater than the risk conferred by passive smoking (1.25) but less than the risk conferred by active smoking (2.5). Future prospective community studies should examine the effect of severity and duration of depressive symptoms and disorders on the risk for the onset of coronary disease.