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      Depressão e comorbidades clínicas Translated title: Depression and medical comorbidity

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          Abstract

          A associação entre depressão e doenças clínicas é muito freqüente, levando a pior evolução tanto do quadro psiquiátrico como da doença clínica, com menor aderência às orientações terapêuticas, além de maior morbidade e mortalidade. A depressão muitas vezes é subdiagnosticada e subtratada, principalmente pela presença de sintomas depressivos, que também podem ocorrer em doenças crônicas, como fadiga e anorexia. Diversas doenças estão claramente associadas à depressão, com maior destaque para as doenças cardiovasculares, endocrinológicas, neurológicas, renais, oncológicas e outras síndromes dolorosas crônicas. Os autores discutem as evidências na literatura que demonstram essa associação, com enfoque nos avanços em fisiopatologia e terapêutica psiquiátrica.

          Translated abstract

          The association between major depression and other clinical conditions is frequently observed, leading to worse prognosis both on the psychiatric and clinical conditions, poorer compliance with therapy and increased rates of morbidity and mortality. Depression is often under diagnosed and under treated, mainly when depressive symptoms may be attributed to chronic diseases, such as fatigue and anorexia. Several diseases are clearly linked to depression, typical examples are cardiovascular disease, endocrinological conditions, kidney diseases, neoplasias, and chronic pain. The authors review and discuss the evidence in the literature that suggest such associations, with focus on the advances on the physiopathology and the psychiatric management.

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          Most cited references160

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          Diagnostic and statistical manual of mental disorders.

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            Impact of Psychological Factors on the Pathogenesis of Cardiovascular Disease and Implications for Therapy

            Recent studies provide clear and convincing evidence that psychosocial factors contribute significantly to the pathogenesis and expression of coronary artery disease (CAD). This evidence is composed largely of data relating CAD risk to 5 specific psychosocial domains: (1) depression, (2) anxiety, (3) personality factors and character traits, (4) social isolation, and (5) chronic life stress. Pathophysiological mechanisms underlying the relationship between these entities and CAD can be divided into behavioral mechanisms, whereby psychosocial conditions contribute to a higher frequency of adverse health behaviors, such as poor diet and smoking, and direct pathophysiological mechanisms, such as neuroendocrine and platelet activation. An extensive body of evidence from animal models (especially the cynomolgus monkey, Macaca fascicularis) reveals that chronic psychosocial stress can lead, probably via a mechanism involving excessive sympathetic nervous system activation, to exacerbation of coronary artery atherosclerosis as well as to transient endothelial dysfunction and even necrosis. Evidence from monkeys also indicates that psychosocial stress reliably induces ovarian dysfunction, hypercortisolemia, and excessive adrenergic activation in premenopausal females, leading to accelerated atherosclerosis. Also reviewed are data relating CAD to acute stress and individual differences in sympathetic nervous system responsivity. New technologies and research from animal models demonstrate that acute stress triggers myocardial ischemia, promotes arrhythmogenesis, stimulates platelet function, and increases blood viscosity through hemoconcentration. In the presence of underlying atherosclerosis (eg, in CAD patients), acute stress also causes coronary vasoconstriction. Recent data indicate that the foregoing effects result, at least in part, from the endothelial dysfunction and injury induced by acute stress. Hyperresponsivity of the sympathetic nervous system, manifested by exaggerated heart rate and blood pressure responses to psychological stimuli, is an intrinsic characteristic among some individuals. Current data link sympathetic nervous system hyperresponsivity to accelerated development of carotid atherosclerosis in human subjects and to exacerbated coronary and carotid atherosclerosis in monkeys. Thus far, intervention trials designed to reduce psychosocial stress have been limited in size and number. Specific suggestions to improve the assessment of behavioral interventions include more complete delineation of the physiological mechanisms by which such interventions might work; increased use of new, more convenient "alternative" end points for behavioral intervention trials; development of specifically targeted behavioral interventions (based on profiling of patient factors); and evaluation of previously developed models of predicting behavioral change. The importance of maximizing the efficacy of behavioral interventions is underscored by the recognition that psychosocial stresses tend to cluster together. When they do so, the resultant risk for cardiac events is often substantially elevated, equaling that associated with previously established risk factors for CAD, such as hypertension and hypercholesterolemia.
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              Hypothalamic-pituitary-adrenal axis, neuroendocrine factors and stress.

              The stress system coordinates the adaptive responses of the organism to stressors of any kind.(1). The main components of the stress system are the corticotropin-releasing hormone (CRH) and locus ceruleus-norepinephrine (LC/NE)-autonomic systems and their peripheral effectors, the pituitary-adrenal axis, and the limbs of the autonomic system. Activation of the stress system leads to behavioral and peripheral changes that improve the ability of the organism to adjust homeostasis and increase its chances for survival. The CRH and LC/NE systems stimulate arousal and attention, as well as the mesocorticolimbic dopaminergic system, which is involved in anticipatory and reward phenomena, and the hypothalamic beta-endorphin system, which suppresses pain sensation and, hence, increases analgesia. CRH inhibits appetite and activates thermogenesis via the catecholaminergic system. Also, reciprocal interactions exist between the amygdala and the hippocampus and the stress system, which stimulates these elements and is regulated by them. CRH plays an important role in inhibiting GnRH secretion during stress, while, via somatostatin, it also inhibits GH, TRH and TSH secretion, suppressing, thus, the reproductive, growth and thyroid functions. Interestingly, all three of these functions receive and depend on positive catecholaminergic input. The end-hormones of the hypothalamic-pituitary-adrenal (HPA) axis, glucocorticoids, on the other hand, have multiple roles. They simultaneously inhibit the CRH, LC/NE and beta-endorphin systems and stimulate the mesocorticolimbic dopaminergic system and the CRH peptidergic central nucleus of the amygdala. In addition, they directly inhibit pituitary gonadotropin, GH and TSH secretion, render the target tissues of sex steroids and growth factors resistant to these substances and suppress the 5' deiodinase, which converts the relatively inactive tetraiodothyronine (T(4)) to triiodothyronine (T(3)), contributing further to the suppression of reproductive, growth and thyroid functions. They also have direct as well as insulin-mediated effects on adipose tissue, ultimately promoting visceral adiposity, insulin resistance, dyslipidemia and hypertension (metabolic syndrome X) and direct effects on the bone, causing "low turnover" osteoporosis. Central CRH, via glucocorticoids and catecholamines, inhibits the inflammatory reaction, while directly secreted by peripheral nerves CRH stimulates local inflammation (immune CRH). CRH antagonists may be useful in human pathologic states, such as melancholic depression and chronic anxiety, associated with chronic hyperactivity of the stress system, along with predictable behavioral, neuroendocrine, metabolic and immune changes, based on the interrelations outlined above. Conversely, potentiators of CRH secretion/action may be useful to treat atypical depression, postpartum depression and the fibromyalgia/chronic fatigue syndromes, all characterized by low HPA axis and LC/NE activity, fatigue, depressive symptomatology, hyperalgesia and increased immune/inflammatory responses to stimuli.
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                Author and article information

                Journal
                rpc
                Archives of Clinical Psychiatry (São Paulo)
                Arch. Clin. Psychiatry (São Paulo)
                Faculdade de Medicina da Universidade de São Paulo (São Paulo, SP, Brazil )
                0101-6083
                1806-938X
                June 2005
                : 32
                : 3
                : 149-159
                Affiliations
                [02] orgnameUniversidade de São Paulo orgdiv1Faculdade de Medicina orgdiv2Departamento de Psiquiatria
                [01] orgnameUniversidade de São Paulo orgdiv1Faculdade de Medicina orgdiv2Instituto de Psiquiatria do Hospital das Clínicas
                Article
                S0101-60832005000300007 S0101-6083(05)03200307
                10.1590/S0101-60832005000300007
                256b9b6e-53c1-4cd8-b264-84c9b61380ad

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                History
                : 28 March 2005
                : 19 February 2005
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 92, Pages: 11
                Product

                SciELO Brazil

                Self URI: Texto completo somente em PDF (PT)
                Categories
                Artigos Originais

                mood disorders,mortality and morbidity,Depressão,comorbidade médica,medical comorbidity,transtornos afetivos,mortalidade,morbidade,Depression

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