Sex-Specific Cardiac Remodeling in Aged Rats after Early-Life Chronic Stress: Associations with Endocrine and Metabolic Factors.

Background: Cardiovascular disease is a leading cause of death worldwide. Rates of cardiovascular disease vary both across the lifespan and between sexes. While multiple factors, including adverse life experiences, impact the development and progression of cardiovascular disease, the potential interactions of biological sex and stress history on the aged heart are unknown. To this end, we examined sex- and stress-specific impacts on left ventricular hypertrophy (VH) after aging. We hypothesized that early life chronic stress exposure impacts behavioral and physiologic responses that predict cardiac remodeling in a sex-specific manner. Methods: Histological analysis was conducted on hearts of male and female rats previously exposed to chronic variable stress during the late adolescent period (postnatal days 43-62). These animals were challenged with a forced swim test and a glucose tolerance test before aging to 15 months and again being challenged. Predictive analyses were then used to isolate factors that relate to cardiac remodeling among these groups. Results: Early-life chronic stress impacted cardiac remodeling in a sex-specific manner. Among rats with a history of chronic stress, females had increased inward VH. However, there were few associations within the female groups among individual behavioral and physiologic parameters and cardiac remodeling. While males as a group did not have VH after chronic stress, they exhibited multiple individual associations with cardiac susceptibility. Passive coping in young males and active coping in aged males related to VH in a stress history-dependent manner. Moreover, baseline corticosterone positively correlated with VH in unstressed males, while chronically-stressed males had positive correlations between VH and visceral adiposity. Conclusions: These results indicate that females as a group are uniquely susceptible to the effects of early-life stress on cardiac remodeling later in life. Conversely, males have more individual differences in vulnerability, where susceptibility to cardiac remodeling relates to endocrine, metabolic, and behavioral measures depending on stress history. These results ultimately support a framework for accessing cardiovascular risk based on biological sex and prior adverse experiences.

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.

Glucoregulation and coping behavior after chronic stress in rats: Sex differences across the lifespan.

The purpose of the current study was to determine how biological sex shapes behavioral coping and metabolic health across the lifespan after chronic stress. We hypothesized that examining chronic stress-induced behavioral and endocrine outcomes would reveal sex differences in the biological basis of susceptibility. During late adolescence, male and female Sprague-Dawley rats experienced chronic variable stress (CVS). Following completion of CVS, all rats experienced a forced swim test (FST) followed 3 days later by a fasted glucose tolerance test (GTT). The FST was used to determine coping in response to a stressor. Endocrine metabolic function was evaluated in the GTT by measuring glucose and corticosterone, the primary rodent glucocorticoid. Rats then aged to 15 months when the FST and GTT were repeated. In young rats, chronically stressed females exhibited more passive coping and corticosterone release in the FST. Additionally, chronically stressed females had elevated corticosterone and impaired glucose clearance in the GTT. Aging affected all measurements as behavioral and endocrine outcomes were sex specific. Furthermore, regression analysis between hormonal and behavioral responses identified associations depending on sex and stress. Collectively, these data indicate increased female susceptibility to the effects of chronic stress during adolescence. Further, translational investigation of coping style and glucose homeostasis may identify biomarkers for stress-related disorders.

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.

Innovations for integrated care: The Association of Medicine and Psychiatry recognizes new models.

This editorial looks at the current state of the integration of medicine and psychiatry in clinical practice. We note selected recent triumphs and barriers to implementing integrated care, highlighting some gaps and priorities for future innovations. In contrast to the relatively more orderly culture of health services research, where some notable innovations in integrated care were funded, tested, and published, the health care marketplace can be a difficult place to identify and track the innovations that could shape health care reform. Recognizing the need to find, describe, and disseminate the most innovative models in integrated care, the Association of Medicine and Psychiatry (AMP) launched in 2016 the Innovative Models for Integrated Care Awards. Although many service innovations solve local problems, some can also act as models to be adopted in multiple settings. The projects that win AMP Innovative Models for Integrated Care Awards are selected for their innovativeness, their clinical importance, their generalizability, and their effectiveness. We briefly describe here the four models that earned these awards at the 2017 AMP Annual Meeting. They demonstrate innovations across a range of settings and populations: inpatient general hospital patients under constant observation in New York, severely mentally ill patients in a federally qualified health center in San Francisco, outpatients in a VA women's health center in Chicago, and HIV patients in an academic infectious disease clinic in Charleston, south Carolina. These model descriptions aim to encourage the implementation of innovative models that advance the integration of medicine and psychiatry.

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.

Stress, autonomic imbalance, and the prediction of metabolic risk: A model and a proposal for research.

BACKGROUND: Devising novel prevention strategies for metabolic disorders will depend in part on the careful elucidation of the common pathways for developing metabolic risks. The neurovisceral integration model has proposed that autonomic imbalance plays an important role in the pathway from acute and chronic stress to cardiovascular disease. Though generally overlooked by clinicians, autonomic imbalance (sympathetic overactivity and/or parasympathetic underactivity) can be measured and modified by methods that are available in primary care. METHOD: This review applies the neurovisceral integration concept to the clinical setting by proposing that autonomic imbalance plays a primary role in the development of metabolic risks. We present a testable model, a systematic review of the evidence in support of autonomic imbalance as a predictor for metabolic risks, and specific approaches to test this model as a guide to future research on the role of stress in metabolic disorders. CONCLUSIONS: We propose that autonomic imbalance deserves consideration by researchers, clinicians, and policymakers as a target for early interventions to prevent metabolic disorders.

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.

Prevalence rates for depression by industry: a claims database analysis.

PURPOSE: To estimate and interpret differences in depression prevalence rates among industries, using a large, group medical claims database. METHODS: Depression cases were identified by ICD-9 diagnosis code in a population of 214,413 individuals employed during 2002-2005 by employers based in western Pennsylvania. Data were provided by Highmark, Inc. (Pittsburgh and Camp Hill, PA). Rates were adjusted for age, gender, and employee share of health care costs. National industry measures of psychological distress, work stress, and physical activity at work were also compiled from other data sources. RESULTS: Rates for clinical depression in 55 industries ranged from 6.9 to 16.2 %, (population rate = 10.45 %). Industries with the highest rates tended to be those which, on the national level, require frequent or difficult interactions with the public or clients, and have high levels of stress and low levels of physical activity. CONCLUSIONS: Additional research is needed to help identify industries with relatively high rates of depression in other regions and on the national level, and to determine whether these differences are due in part to specific work stress exposures and physical inactivity at work. CLINICAL SIGNIFICANCE: Claims database analyses may provide a cost-effective way to identify priorities for depression treatment and prevention in the workplace.

Depression as a risk factor for poor prognosis among patients with acute coronary syndrome: systematic review and recommendations: a scientific statement from the American Heart Association.

BACKGROUND: Although prospective studies, systematic reviews, and meta-analyses have documented an association between depression and increased morbidity and mortality in a variety of cardiac populations, depression has not yet achieved formal recognition as a risk factor for poor prognosis in patients with acute coronary syndrome by the American Heart Association and other health organizations. The purpose of this scientific statement is to review available evidence and recommend whether depression should be elevated to the status of a risk factor for patients with acute coronary syndrome. METHODS AND RESULTS: Writing group members were approved by the American Heart Association's Scientific Statement and Manuscript Oversight Committees. A systematic literature review on depression and adverse medical outcomes after acute coronary syndrome was conducted that included all-cause mortality, cardiac mortality, and composite outcomes for mortality and nonfatal events. The review assessed the strength, consistency, independence, and generalizability of the published studies. A total of 53 individual studies (32 reported on associations with all-cause mortality, 12 on cardiac mortality, and 22 on composite outcomes) and 4 meta-analyses met inclusion criteria. There was heterogeneity across studies in terms of the demographic composition of study samples, definition and measurement of depression, length of follow-up, and covariates included in the multivariable models. Despite limitations in some individual studies, our review identified generally consistent associations between depression and adverse outcomes. CONCLUSIONS: Despite the heterogeneity of published studies included in this review, the preponderance of evidence supports the recommendation that the American Heart Association should elevate depression to the status of a risk factor for adverse medical outcomes in patients with acute coronary syndrome.

Somatic symptom disorder: an important change in DSM.

This paper describes the rationale for the new diagnosis of somatic symptom disorder (SSD) within DSM5. SSD represents a consolidation of a number of previously listed diagnoses. It deemphasizes the centrality of medically unexplained symptoms and defines the disorder on the basis of persistent somatic symptoms associated with disproportionate thoughts, feelings, and behaviors related to these symptoms. Data are presented concerning reliability, validity, and prevalence of SSD, as well as tasks for future research, education, and clinical practice.

Psychiatry's integration with medicine: the role of DSM-5.

Mental disorders represent a significant global burden whose effects are exacerbated by gaps in diagnosis and service provision. A substantial number of individuals seek services not through specialty psychiatric clinics but through primary care. Thus, the interface between psychiatry and the rest of medicine represents an appropriate area of focus in which to improve the detection and treatment of mental disorders. Development of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) can play a key role in this process. DSM-5 is expected to include specific revisions in diagnostic criteria, chapter organization, text structure, and classification approach that are designed to improve use of DSM by nonpsychiatrist physicians. Furthermore, revisions to DSM-5 will inform development of the primary care version of DSM-5. The goal is to publish a manual that enhances clinical utility in a manner that is concise and more amenable to use in primary care.

Comparison of two depression measures for predicting stroke outcomes.

OBJECTIVES: Little is known about the effect of lifetime history of depression on ischemic stroke outcomes. This study compared a measure of current symptoms of depression at the time of the stroke and a measure of lifetime history of depression for their ability to predict quality of life and functioning at 3 and 12 months after stroke. METHODS: A cohort of 460 ischemic stroke patients from the 2005 Greater Cincinnati/North Kentucky Stroke Study was assessed within 2 weeks of the stroke, including the 10-item Center for Epidemiological Studies Depression Scale (CESD) for current symptoms of depression. Lifetime history of depression was also assessed by a 2-question measure at 3 and 12 months after stroke. Two outcome measures, Stroke Specific Quality of Life (SSQOL) and the modified Rankin Scale (mRS) to assess functional status, were also collected at 3 and 12 months. RESULTS: Of the 322 survivors included in the analysis, 52.2% reported depression on at least one measure. Both current symptoms and lifetime history of depression predicted poor functional outcomes and poor quality of life at 3 and 12 months, after adjustment for age, race, sex, prior stroke, baseline functional status, and stroke severity. The combination of depression measures was a better predictor of poor outcomes than either measure alone. CONCLUSION: Depression by either measure was a frequent, substantial, and independent predictor of poor outcomes at 3 and 12 months after stroke. Stroke outcomes studies should further examine the predictive value of assessing both depressive symptoms at the time of the stroke and lifetime history of depression.

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.

Prevalence of depression among mothers of young children in Honduras.

OBJECTIVE: Maternal depression is a substantial problem that has negative consequences on the health of both mother and child. Little research has been done on the prevalence of maternal depression in the developing world. This study aims to estimate the prevalence of current depression among mothers in Honduras and identify demographic predictors of depression in this sample. METHODS: A modified Spanish version of the PHQ-9 and a demographic questionnaire were administered by trained interviewers to 415 rural and urban women aged 15-66 who had children between 1 and 10 years old. RESULTS: Prevalence of current major depressive syndrome was 17.6%. Mild depressive symptoms were detected in 52% of the sample. The estimated prevalence of current major depressive syndrome in the urban sample (19%) was not significantly greater than in the rural sample (16%, p = 0.49). None of the demographic variables measured, including age, number of children, or marital status predicted major depression in this sample. CONCLUSIONS: Maternal depression occurred at a high rate in this sample of Honduran women. The estimated prevalence rates in this study are similar to rates of maternal depression in studies of mothers in other Latin American countries, as well as in samples of mothers on Medicaid in the United States. Further study is needed to confirm and extend these findings, and to identify predictors of maternal depression in this population.

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.