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1.
Clin Chim Acta ; 505: 148-159, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32145273

RESUMO

Glucocorticoid deficiency is the clinical state characterised by inadequate cortisol production. It may occur due to the primary failure of the adrenal cortex or to lack of stimulation of the adrenal cortex by adrenocorticotropic hormone. The aim of treatment of glucocorticoid deficiency is to mimic the normal physiological secretion of cortisol, in order to normalise quality of life and reverse pathological sequelae. However, the diurnal rhythm of cortisol secretion is difficult to reproduce with exogenous glucocorticoid therapy. There is wide inter- and intra-individual variability of in the dynamics of physiological glucocorticoid secretion, and glucocorticoid preparations that are currently available cannot reproduce physiological profiles. In addition, there are no reliable biomarkers to determine the adequacy of treatment. The treatment of acute glucocorticoid deficiency/ adrenal crisis involves prompt recognition and administration of parenteral hydrocortisone, rehydration, and management of electrolyte abnormalities. In the management of chronic glucocorticoid deficiency, the prevention of adrenal crisis must be balanced with avoidance of the long-term adverse effects of over-replacement. This requires close collaboration with the patient, for whom education and empowerment in the management of glucocorticoid deficiency, and the prevention of crises, are crucial.


Assuntos
Insuficiência Adrenal/terapia , Glucocorticoides/deficiência , Insuficiência Adrenal/mortalidade , Insuficiência Adrenal/fisiopatologia , Terapia de Reposição Hormonal , Humanos , Sistema Hipotálamo-Hipofisário/fisiopatologia , Sistema Hipófise-Suprarrenal/fisiopatologia
2.
Clin Chim Acta ; 505: 78-91, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32035851

RESUMO

Adrenal insufficiency (AI) is a serious condition, which can arise from pathology affecting the adrenal gland itself (primary adrenal insufficiency, PAI), hypothalamic or pituitary pathology (secondary adrenal insufficiency, SAI), or as a result of suppression of the hypothalamic-pituitaryadrenal (HPA) axis by exogenous glucocorticoid therapy (tertiary adrenal insufficiency, TAI). AI is associated with an increase in morbidity and mortality and a reduction in quality of life. In addition, the most common cause of PAI, autoimmune adrenalitis, may be associated with a variety of other autoimmune disorders. Untreated AI can present with chronic fatigue, weight loss and vulnerability to infection. The inability to cope with acute illness or infection can precipitate life-threatening adrenal crisis. It is therefore a critical diagnosis to make in a timely fashion, in order to institute appropriate management, aimed at reversing chronic ill health, preventing acute crises, and restoring quality of life. In this review, we will describe the normal physiology of the HPA axis and explain how knowledge of the physiology of this axis helps us understand the clinical presentation of AI, and forms the basis for the biochemical investigations which lead to the diagnosis of AI.


Assuntos
Insuficiência Adrenal/diagnóstico , Insuficiência Adrenal/fisiopatologia , Insuficiência Adrenal/complicações , Insuficiência Adrenal/terapia , Humanos , Sistema Hipotálamo-Hipofisário/fisiopatologia , Sistema Hipófise-Suprarrenal/fisiopatologia
3.
Adv Exp Med Biol ; 1191: 141-153, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32002927

RESUMO

Substantial evidence from various studies suggests a preeminent role for early adverse experiences in the development of psychopathology. The most recent studies reviewed here suggest that early life stressors are associated with an increased risk for anxiety disorders in adulthood. Early life stress predisposes individuals to develop a number of psychiatric syndromes, particularly affective disorders, including anxiety disorders, and is therefore a significant health problem.This review examines the emerging literature on the relationship between stress, hypothalamic-pituitary-adrenal (HPA) axis function, and generalized anxiety disorder (GAD), panic disorder, and phobias and the role of early life stress as an important risk factor for HPA axis dysfunction.The most consistent findings in the literature show increased activity of the HPA axis in depression associated with hypercortisolemia and reduced inhibitory feedback. In addition to melancholic depression, a spectrum of other conditions may be associated with increased and prolonged activation of the HPA axis, including panic, GAD, phobias and anxiety. Moreover, HPA axis changes appear to be state-dependent, tending to improve upon resolution of the anxiety syndrome. Interestingly, persistent HPA hyperactivity has been associated with higher rates of relapse. These studies suggest that an evaluation of the HPA axis during treatment may help identify patients who are at a higher risk for relapse. These findings suggest that this dysfunction of the HPA axis is partially attributable to an imbalance between glucocorticoid and mineralocorticoid receptors. Evidence has consistently demonstrated that glucocorticoid receptor function is impaired in anxiety disorders. Moreover, normal basal cortisol levels and hyper-responsiveness of the adrenal cortex during a psychosocial stressor are observed in social phobics. Finally, abnormal HPA axis activity has also been observed in generalized anxiety disordered patients. Early stressful life events may provoke alterations of the stress response and thus of the HPA axis that can endure during adulthood, predisposing individuals to develop psychopathology.


Assuntos
Experiências Adversas da Infância , Transtornos de Ansiedade/etiologia , Transtornos de Ansiedade/fisiopatologia , Ansiedade/etiologia , Ansiedade/fisiopatologia , Sistema Hipotálamo-Hipofisário/fisiopatologia , Sistema Hipófise-Suprarrenal/fisiopatologia , Estresse Psicológico/complicações , Ansiedade/psicologia , Transtornos de Ansiedade/psicologia , Humanos , Estresse Psicológico/psicologia
4.
Autoimmun Rev ; 19(2): 102454, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31838158

RESUMO

OBJECTIVE: Immune checkpoint inhibitors have introduced a new and heterogeneous class of immune-related adverse effects, with the endocrine system being a predominant target for autoimmunity. Autoimmune hypothalamic-pituitary-adrenal axis (HPA) diseases induced by checkpoint inhibitors are being increasingly recognized. We aimed to characterize the spectrum of checkpoint associated hypothalamic-pituitary-adrenal axis endocrinopathies. DESIGN: A retrospective cohort study of a tertiary cancer center. METHODS: Patients were characterized for HPA axis abnormalities based on clinical and pituitary axes evaluation. The risk for developing HPA endocrinopathies was compared by log- rank test, by the time since checkpoint inhibitors initiation. Additionally, the risk for developing HPA endocrinopathies after adjusting for covariates was assessed using multivariable logistic regression analysis. RESULTS: Among 1615 patients, fourteen (0.87%) patients developed isolated adrecocorticotrophic hormone deficiency (IAD), six (0.37%) - hypophysitis and no case of adrenalitis was identified. IAD presented with mild and non-specific symptoms, mainly asthenia. In multivariable analysis, exposure to both PD-1/PD-L1 and Ipilimumab and female gender were associated with an increased odds ratio (OR) for developing IAD (6.98 [95% CI 2.38-20.47, p < .001] and 3.67 [95% CI 1.13-11.84, p = .03]), respectively. CONCLUSIONS: IAD, a rare disease before the immunotherapy era, has become a predominant checkpoint related HPA axis autoimmune injury. Despite its life threatening potential, IAD may be missed due to its subtle presentation. Patients exposed to Ipilimumab and PD-1/PD-L1 in combination or sequentially and women have an increased risk for developing IAD.


Assuntos
Insuficiência Adrenal/induzido quimicamente , Ipilimumab/efeitos adversos , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Insuficiência Adrenal/patologia , Insuficiência Adrenal/fisiopatologia , Adulto , Idoso , Feminino , Humanos , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/patologia , Sistema Hipotálamo-Hipofisário/fisiopatologia , Masculino , Pessoa de Meia-Idade , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/patologia , Sistema Hipófise-Suprarrenal/fisiopatologia , Doenças Raras/induzido quimicamente , Doenças Raras/patologia , Doenças Raras/fisiopatologia , Estudos Retrospectivos
5.
Adv Exp Med Biol ; 1180: 147-178, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31784962

RESUMO

Stress is an adaptive response to environment aversive stimuli and a common life experience of one's daily life. Chronic or excessive stress especially that happened in early life is found to be deleterious to individual's physical and mental health, which is highly related to depressive disorders onset. Stressful life events are consistently considered to be the high-risk factors of environment for predisposing depressive disorders. In linking stressful life events with depressive disorder onset, dysregulated HPA axis activity is supposed to play an important role in mediating aversive impacts of life stress on brain structure and function. Increasing evidence have indicated the strong association of stress, especially the chronic stress and early life stress, with depressive disorders development, while the association of stress with depression is moderated by genetic risk factors, including polymorphism of SERT, BDNF, GR, FKBP5, MR, and CRHR1. Meanwhile, stressful life experience particularly early life stress will exert epigenetic modification in these risk genes via DNA methylation and miRNA regulation to generate long-lasting effects on these genes expression, which in turn cause brain structural and functional alteration, and finally increase the vulnerability to depressive disorders. Therefore, the interaction of environment with gene, in which stressful life exposure interplay with genetic risk factors and epigenetic modification, is essential in predicting depressive disorders development. As the mediator of environmental risk factors, stress will function together with genetic and epigenetic mechanism to influence brain structure and function, physiology and psychology, and finally the vulnerability to depressive disorders.


Assuntos
Transtorno Depressivo/genética , Epigênese Genética , Sistema Hipotálamo-Hipofisário/fisiopatologia , Sistema Hipófise-Suprarrenal/fisiopatologia , Estresse Psicológico , Transtorno Depressivo/fisiopatologia , Humanos , Fatores de Risco
6.
Br J Anaesth ; 123(5): 570-583, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31547969

RESUMO

The systemic stress response triggered by surgical trauma is characterised by sterile inflammation preceding metabolic and neuroendocrine dysregulation. However, the relevance of the classically described 'stress response' is now highly questionable in an era where profound physiological deconditioning is common in older, frail surgical patients. Commonly used assessment techniques do not accurately reflect hypothalamic-pituitary-adrenal axis integrity after major surgery. Clinical interpretation of plasma concentrations of cortisol, the prototypical stress hormone, is rarely accurate, because of study heterogeneity, the inherently dynamic characteristics of cortisol production, and assay variability. Before surgery, chronic psychosocial stress and common cardiorespiratory co-morbidities are clinically relevant modifiers of neuroendocrine activation to acute stress/inflammation. The frequent development of multi-morbidity after major surgery further clouds the compartmentalised, discrete model of neuroendocrine activation after initial tissue injury. Starvation, impaired mobility, and sepsis after surgery generate distinct neuroendocrine profiles that challenge the conventional model of neuroendocrine activation. Basic science studies suggest that high circulating levels of cortisol may directly cause organ injury. Conversely, randomised controlled clinical trials investigating glucocorticoid supplementation have delivered contrasting results, with some suggesting a protective effect in the perioperative period. Here, we consider many of the confounding factors that have emerged to challenge the conventional model of the surgical stress response, and suggest that a more nuanced understanding of changes in hypothalamic-pituitary-adrenal axis physiology is warranted to advance perioperative medicine. Re-examining the perioperative stress response presents opportunities for improving outcomes through enhancing the understanding of the neuroendocrine aspects of preparation for and recovery from surgery.


Assuntos
Sistema Hipotálamo-Hipofisário/fisiopatologia , Sistemas Neurossecretores/fisiopatologia , Período Perioperatório , Sistema Hipófise-Suprarrenal/fisiopatologia , Estresse Fisiológico/fisiologia , Idoso , Humanos
7.
Neurosurg Clin N Am ; 30(4): 491-498, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31471056

RESUMO

Although removal of pituitary tumors yields excellent surgical outcomes, perturbations in the hypothalamic-pituitary axis are not uncommon. Careful assessment of postoperative hormone status with supplementation or further medical therapy is critical to successful outcomes. Although many centers routinely use perioperative steroids, they can be associated with worse outcomes in the absence of intact preoperative adrenal function or damage to the pituitary gland or stalk during surgery. Postoperative assessment of prolactin, cortisol, and growth hormone can be prognostic of surgical cure. Hormonal axes should be reevaluated routinely several weeks after surgery, because longitudinal monitoring is important for surgical and medical outcomes.


Assuntos
Sistema Hipotálamo-Hipofisário/fisiopatologia , Doenças da Hipófise/cirurgia , Sistema Hipófise-Suprarrenal/fisiopatologia , Humanos , Doenças da Hipófise/fisiopatologia , Neoplasias Hipofisárias/fisiopatologia , Neoplasias Hipofisárias/cirurgia , Complicações Pós-Operatórias , Resultado do Tratamento
8.
Eur J Obstet Gynecol Reprod Biol ; 240: 139-143, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31284087

RESUMO

Pregnancy is characterized by marked alterations in the hypothalamic-pituitary-adrenal axis and in the function of the adrenal gland. Some of those alterations have clinical characteristics that are similar to those of adrenal gland disorders. While adrenal disorders are rare among pregnant women, they harbor the potential for significant morbidity if they remain unrecognized and untreated. As the majority of patients with adrenal disorders present with clinical features that are typical of normal pregnancy - diagnosis during pregnancy is not uncommonly delayed. A high index of suspicion must be practiced for these disorders as they might carry severe obstetrical negative outcomes. In this review we will survey the normal function of adrenal glands in pregnancy and the role of adrenal hormones in pregnancy. We will outline the adrenal disorders that commonly present during pregnancy and review the literature on treatment modalities.


Assuntos
Doenças do Córtex Suprarrenal/fisiopatologia , Córtex Suprarrenal/fisiopatologia , Complicações na Gravidez/fisiopatologia , Feminino , Humanos , Sistema Hipotálamo-Hipofisário/fisiopatologia , Sistema Hipófise-Suprarrenal/fisiopatologia , Gravidez
9.
J Clin Psychopharmacol ; 39(4): 367-371, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31211752

RESUMO

BACKGROUND: Insulin-like growth factor I (IGF-I) is a neurotrophic factor produced by the hypothalamic-pituitary-somatotropic axis and is considered a potential contributor to the pathology of major depressive disorder (MDD). Although it is known that the hypothalamic-pituitary-adrenal axis and cortisol are involved in the pathology of MDD, the association with dehydroepiandrosterone sulfate (DHEAS) remains unclear. The current study sought to clarify the relationship between these hormones and the pathology of MDD. METHODS: Subjects were 91 Japanese patients with a diagnosis of MDD. Serum IGF-I, cortisol, and DHEAS were measured. Samples were taken before breakfast after overnight fasting. Depressive symptoms were assessed using the Hamilton Rating Scale for Depression (HAM-D). RESULTS: Subjects included 59 men and 32 women with an average age of 44.1 ± 13.1 years (mean ± SD). The blood IGF-I level was 152.0 ± 50.0 ng/mL, the cortisol level was 10.1 ± 4.6, and the DHEAS level was 201.3 ± 112.7 µg/dL. The mean HAM-D score was 13.9 ± 9.0. Serum IGF-I levels were not correlated with cortisol. Higher IGF-I, cortisol, and cortisol/DHEAS ratios were associated with higher HAM-D scores (adjusted R = 0.240, P < 0.001), and higher IGF-I and cortisol were associated with higher melancholic or suicide subscores (adjusted R = 0.200, P < 0.001; adjusted R = 0.273, P < 0.001). CONCLUSIONS: Our findings suggest that hormonal dysregulation of the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-somatotropic axes may be related to the symptom severity of MDD, melancholia, and suicide-related factors.


Assuntos
Sulfato de Desidroepiandrosterona/sangue , Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/fisiopatologia , Hidrocortisona/sangue , Fator de Crescimento Insulin-Like I/análise , Adulto , Feminino , Humanos , Sistema Hipotálamo-Hipofisário/fisiopatologia , Hipotálamo/fisiopatologia , Masculino , Pessoa de Meia-Idade , Sistema Hipófise-Suprarrenal/fisiopatologia
10.
Transl Psychiatry ; 9(1): 158, 2019 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-31164628

RESUMO

A particular challenge in the development of a bipolar disorder (BD) model in animals is the complicated clinical course of the condition, characterized by manic, depressive and mixed mood episodes. Ouabain (OUA) is an inhibitor of Na+/K+-ATPase enzyme. Intracerebroventricular (ICV) injection of this drug in rats has been regarded a proper model to study BD by mimic specific manic symptoms, which are reversed by lithium (Li), an important mood stabilizer drug. However, further validation of this experimental approach is required to characterize it as an animal model of BD, including depressive-like behaviors. The present study aimed to assess manic- and depressive-like behaviors, potential alteration in the hypothalamic-pituitary-adrenal (HPA) system and oxidative stress parameters after a single OUA ICV administration in adult male Wistar rats. Moreover, we evaluated Li effects in this experimental setting. Data show that OUA ICV administration could constitute a suitable model for BD since the injection of the drug triggered manic- and depressive-like behaviors in the same animal. Additionally, the OUA model mimics significant physiological and neurochemical alterations detected in BD patients, including an increase in oxidative stress and change in HPA axis. Our findings suggest that decreased Na+/K+-ATPase activity detected in bipolar patients may be linked to increased secretion of glucocorticoid hormones and oxidative damage, leading to the marked behavioral swings. The Li administration mitigated these pathological changes in the rats. The proposed OUA model is regarded as suitable to simulate BD by complying with all validities required to a proper animal model of the psychiatric disorder.


Assuntos
Comportamento Animal/efeitos dos fármacos , Transtorno Bipolar/induzido quimicamente , Transtorno Bipolar/fisiopatologia , Modelos Animais de Doenças , Inibidores Enzimáticos/farmacologia , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Ouabaína/farmacologia , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Animais , Antimaníacos/farmacologia , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/fisiopatologia , Injeções Intraventriculares , Compostos de Lítio/farmacologia , Masculino , Sistema Hipófise-Suprarrenal/metabolismo , Sistema Hipófise-Suprarrenal/fisiopatologia , Ratos Wistar
11.
Cell Tissue Res ; 377(1): 95-106, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31165247

RESUMO

A theoretical framework is proposed to gain insight into the pathogenesis of major depressive disorder (MDD). Despite being a relatively weak argument, the neurogenesis theory is suggested to compensate for the limitations of the monoamine theory. In the adult hippocampus, neurogenesis is functionally related to regulation of the hypothalamic-pituitary-adrenal (HPA) axis, inflammatory processes, cognitive functions and other aspects that contribute to etiological factors that lead to MDD and promote recovery from MDD. Despite a lack of investigation into neurogenesis and antidepressant action, it is proposed that chronic administration of antidepressant(s) can induce the recruitment and integration of newborn neurons into the dentate gyrus and, ultimately, lead to the remission of MDD. The extant body of literature indicates that the suppression of neurogenesis per se may be associated with an impaired response to antidepressant treatment rather than with the induction of depressive-like behaviors. Moreover, recent studies have shown that increasing the survival rate and incorporation of new neurons can alleviate depressive-like behaviors and promote stress resilience. According to the neurogenic reserve hypothesis, hippocampal neurogenesis supports specific cortical functions, including executive functions, pattern separation and contextual information processing, control over the HPA axis and behavioral coping mechanisms in response to stressful situations. Therefore, hippocampal neurogenesis may be a promising biological indicator of stress resilience and antidepressant response in patients with MDD.


Assuntos
Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Hipocampo/embriologia , Neurogênese , Neurônios/fisiologia , Adulto , Animais , Antidepressivos/farmacologia , Transtorno Depressivo Maior/fisiopatologia , Modelos Animais de Doenças , Humanos , Sistema Hipotálamo-Hipofisário/embriologia , Camundongos , Neurônios/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/embriologia , Sistema Hipófise-Suprarrenal/fisiopatologia , Ratos
12.
Neuroimage ; 197: 493-501, 2019 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-31077842

RESUMO

High levels of negative, and low levels of positive parenting behaviors can increase the risk of internalizing symptoms in children, but the mechanisms underlying this association are still unclear. One possibility is that parenting behaviors affect the neural correlates of emotion processing in children. Further, genetic variants relevant to the function of the hypothalamic-pituitary-adrenal (HPA) axis are thought to moderate the effect of early experiences on the brain circuits underlying emotion processing, particularly those involving the amygdala. However, no studies have investigated the interactive effect of parenting behaviors and HPA axis-related genes on amygdala activity and connectivity during emotion processing, and in turn internalizing symptoms in children. Participants comprised 80 children (46 females, mean age = 10.0 years) from the community. Observational measures of maternal behavior were collected during mother-child interactions. Children underwent functional magnetic resonance imaging while performing an implicit emotion-processing task, and mothers and children completed measures of child internalizing symptoms. Genetic risk was calculated using an HPA genetic risk score. HPA genetic risk score was indirectly associated with greater child self-reported depressive symptoms via increased amygdala-precuneus connectivity during the emotion-processing task, and interacted with negative maternal parenting behavior to predict increased connectivity between amygdala and superior frontal gyrus, anterior cingulate cortex and parietal cortex. HPA-related genetic variation appears to moderate the effect of negative maternal parenting behavior on the neural underpinnings of emotion processing in children, and may confer risk for depressive symptoms via modulation of amygdala connectivity.


Assuntos
Tonsila do Cerebelo/fisiopatologia , Interação Gene-Ambiente , Comportamento Materno/psicologia , Relações Mãe-Filho/psicologia , Adulto , Criança , Depressão/etiologia , Depressão/fisiopatologia , Emoções , Feminino , Genótipo , Humanos , Sistema Hipotálamo-Hipofisário/fisiopatologia , Imagem por Ressonância Magnética , Masculino , Sistema Hipófise-Suprarrenal/fisiopatologia , Estresse Psicológico/fisiopatologia
13.
Ther Adv Cardiovasc Dis ; 13: 1753944719851950, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31144599

RESUMO

Women are at increased risk for developing depression and cardiovascular disease (CVD) across the lifespan and their comorbidity is associated with adverse outcomes that contribute significantly to rates of morbidity and mortality in women worldwide. Immune-system activity has been implicated in the etiology of both depression and CVD, but it is unclear how inflammation contributes to sex differences in this comorbidity. This narrative review provides an updated synthesis of research examining the association of inflammation with depression and CVD, and their comorbidity in women. Recent research provides evidence of pro-inflammatory states and sex differences associated with alterations in the hypothalamic-pituitary-adrenal axis, the renin-angiotensin-aldosterone system and the serotonin/kynurenine pathway, that likely contribute to the development of depression and CVD. Changes to inflammatory cytokines in relation to reproductive periods of hormonal fluctuation (i.e. the menstrual cycle, perinatal period and menopause) are highlighted and provide a greater understanding of the unique vulnerability women experience in developing both depressed mood and adverse cardiovascular events. Inflammatory biomarkers hold substantial promise when combined with a patient's reproductive and mental health history to aid in the prediction, identification and treatment of the women most at risk for CVD and depression. However, more research is needed to improve our understanding of the mechanisms underlying inflammation in relation to their comorbidity, and how these findings can be translated to improve women's health.


Assuntos
Doenças Cardiovasculares/imunologia , Depressão/imunologia , Sistema Imunitário/imunologia , Inflamação/imunologia , Reprodução/imunologia , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/fisiopatologia , Depressão/metabolismo , Depressão/fisiopatologia , Feminino , Humanos , Sistema Hipotálamo-Hipofisário/imunologia , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/fisiopatologia , Sistema Imunitário/metabolismo , Sistema Imunitário/fisiopatologia , Inflamação/metabolismo , Inflamação/fisiopatologia , Mediadores da Inflamação/imunologia , Mediadores da Inflamação/metabolismo , Cinurenina/imunologia , Cinurenina/metabolismo , Sistema Hipófise-Suprarrenal/imunologia , Sistema Hipófise-Suprarrenal/metabolismo , Sistema Hipófise-Suprarrenal/fisiopatologia , Sistema Renina-Angiotensina/imunologia , Serotonina/imunologia , Serotonina/metabolismo , Transdução de Sinais
14.
Dev Psychopathol ; 31(3): 1011-1022, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31064568

RESUMO

Early life stress (ELS) is a risk factor for the development of depression in adolescence; the mediating neurobiological mechanisms, however, are unknown. In this study, we examined in early pubertal youth the associations among ELS, cortisol stress responsivity, and white matter microstructure of the uncinate fasciculus and the fornix, two key frontolimbic tracts; we also tested whether and how these variables predicted depressive symptoms in later puberty. A total of 208 participants (117 females; M age = 11.37 years; M Tanner stage = 2.03) provided data across two or more assessment modalities: ELS; salivary cortisol levels during a psychosocial stress task; diffusion magnetic resonance imaging; and depressive symptoms. In early puberty there were significant associations between higher ELS and decreased cortisol production, and between decreased cortisol production and increased fractional anisotropy in the uncinate fasciculus. Further, increased fractional anisotropy in the uncinate fasciculus predicted higher depressive symptoms in later puberty, above and beyond earlier symptoms. In post hoc analyses, we found that sex moderated several additional associations. We discuss these findings within a broader conceptual model linking ELS, emotion dysregulation, and depression across the transition through puberty, and contend that brain circuits implicated in the control of hypothalamic-pituitary-adrenal axis function should be a focus of continued research.


Assuntos
Depressão/psicologia , Hidrocortisona/análise , Puberdade/psicologia , Estresse Psicológico/psicologia , Adolescente , Depressão/fisiopatologia , Emoções/fisiologia , Feminino , Lobo Frontal/diagnóstico por imagem , Humanos , Sistema Hipotálamo-Hipofisário/fisiopatologia , Sistema Límbico/diagnóstico por imagem , Masculino , Rede Nervosa/diagnóstico por imagem , Sistema Hipófise-Suprarrenal/fisiopatologia , Puberdade/fisiologia , Saliva/química , Estresse Psicológico/fisiopatologia , Substância Branca/diagnóstico por imagem
15.
Neurochem Res ; 44(7): 1517-1532, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31004261

RESUMO

Fibromyalgia is a chronic complex syndrome of non-articulate origin characterized by musculoskeletal pain, painful tender points, sleep problems and co-morbidities including depression, migraine. The etiopathogenesis of fibromyalgia is complex, variable and remains inconclusive. The etiological factors that have been defined include stress, genetic predisposition and environmental components. As per the reports of the American College of Rheumatology (ACR) the prevalence of fibromyalgia varies from 2 to 22% among the general population with poor diagnostic features primarily pain. Fibromyalgia encompasses a spectrum of co-morbid conditions with multifarious pathogenesis. The highly prevalent manifestations of fibromyalgia include heterogeneous pain and aches. Biochemical and neurobiological elements of fibromyalgia include neurotransmitters, hypothalamic pituitary adrenal axis (HPA axis), inflammatory cytokines, monoaminergic pathway, opioid peptides, sex hormones, nerve growth factor (NGF) and local free radical insult. An imbalance in the serotonergic system is the major underlying etiological factor that has been explored most widely. Owing to complex interplay of diverse pathophysiological pathways, overlapping co-morbidities such as depression have been clinically observed. Therapeutic management of fibromyalgia involves both non pharmacological and pharmacological measures. The current review presents various dysregulations and their association with symptoms of fibromyalgia along with their underlying neurobiological aspects.


Assuntos
Depressão/etiologia , Fibromialgia/etiologia , Hepatite C Crônica/etiologia , Doenças Inflamatórias Intestinais/etiologia , Transtornos de Enxaqueca/etiologia , Animais , Comorbidade , Citocinas/metabolismo , Depressão/metabolismo , Depressão/fisiopatologia , Fibromialgia/metabolismo , Fibromialgia/fisiopatologia , Hepatite C Crônica/metabolismo , Hepatite C Crônica/fisiopatologia , Humanos , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/fisiopatologia , Doenças Inflamatórias Intestinais/metabolismo , Doenças Inflamatórias Intestinais/fisiopatologia , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Transtornos de Enxaqueca/metabolismo , Transtornos de Enxaqueca/fisiopatologia , Neuropeptídeos/metabolismo , Estresse Oxidativo/fisiologia , Dor/metabolismo , Dor/fisiopatologia , Sistema Hipófise-Suprarrenal/metabolismo , Sistema Hipófise-Suprarrenal/fisiopatologia
16.
Biofactors ; 45(4): 495-506, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30937979

RESUMO

Environmental noise is a well-recognized health risk and part of the external exposome-the World Health Organization estimates that 1 million healthy life years are lost annually in Western Europe alone due to noise-related complications, including increased incidence of hypertension, heart failure, myocardial infarction, and stroke. Previous data suggest that noise works through two paired pathways in a proposed reaction model for noise exposure. As a nonspecific stressor, chronic low-level noise exposure can cause a disruption of sleep and communication leading to annoyance and subsequent sympathetic and endocrine stress responses leading to increased blood pressure, heart rate, stress hormone levels, and in particular more oxidative stress, being responsible for vascular dysfunction and representing changes of the internal exposome. Chronic stress generates cardiovascular risk factors on its own such as increased blood pressure, blood viscosity, blood glucose, and activation of blood coagulation. To this end, persistent chronic noise exposure increases cardiometabolic diseases, including arterial hypertension, coronary artery disease, arrhythmia, heart failure, diabetes mellitus type 2, and stroke. The present review discusses the mechanisms of the nonauditory noise-induced cardiovascular and metabolic consequences, focusing on mental stress signaling pathways, activation of the hypothalamic-pituitary-adrenocortical axis and sympathetic nervous system, the association of these activations with inflammation, and the subsequent onset of oxidative stress and vascular dysfunction. © 2019 BioFactors, 45 (4):495-506, 2019.


Assuntos
Arritmias Cardíacas/induzido quimicamente , Doença da Artéria Coronariana/induzido quimicamente , Diabetes Mellitus Tipo 2/induzido quimicamente , Poluentes Ambientais/efeitos adversos , Insuficiência Cardíaca/induzido quimicamente , Hipertensão/induzido quimicamente , Acidente Vascular Cerebral/induzido quimicamente , Arritmias Cardíacas/metabolismo , Arritmias Cardíacas/fisiopatologia , Coagulação Sanguínea/efeitos dos fármacos , Glicemia/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Viscosidade Sanguínea/efeitos dos fármacos , Doença da Artéria Coronariana/metabolismo , Doença da Artéria Coronariana/fisiopatologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/fisiopatologia , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/fisiopatologia , Humanos , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/fisiopatologia , Estresse Oxidativo/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/metabolismo , Sistema Hipófise-Suprarrenal/fisiopatologia , Acidente Vascular Cerebral/metabolismo , Acidente Vascular Cerebral/fisiopatologia , Sistema Nervoso Simpático/efeitos dos fármacos , Sistema Nervoso Simpático/metabolismo , Sistema Nervoso Simpático/fisiopatologia
17.
Int J Dev Neurosci ; 75: 27-35, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30954504

RESUMO

BACKGROUND: Maternal infection during pregnancy is known to adversely affect foetal development, but previous studies have rarely investigated the impact of gynaecological diseases during pregnancy on offspring during adulthood. Vaginitis is one of the most prevalent gynaecological diseases during pregnancy. METHODS: The effect of maternal vaginal inflammation on offspring was simulated by inducing maternal vaginal infection. We performed a transvaginal injection of lipopolysaccharide (LPS) in pregnant mice to induce vaginitis and investigated their offspring by means of behavioural tests and molecular and cellular measurements. RESULTS: Behavioural tests revealed that the offspring of mothers transvaginally injected with LPS exhibited sex-dependent differences. Male offspring showed increased anxiety-related behaviours, including reduced time exploring the open arm in the elevated plus maze test and light chamber in the light-dark box test. Serum levels of corticosterone were increased in LPS male offspring, indicating activation of the hypothalamic-pituitary-adrenal (HPA) axis. Corticotropin-releasing hormone (CRH) protein expression and c-Fos positive cells were increased in the hypothalamic paraventricular nucleus (PVN) in LPS male offspring, which presented with an increased number of microglia. CONCLUSION: This study suggests that prenatal vaginal infection increases anxiety-like behaviour in male offspring, possibly via activation of the HPA axis.


Assuntos
Ansiedade/fisiopatologia , Sistema Hipotálamo-Hipofisário/fisiopatologia , Inflamação/fisiopatologia , Sistema Hipófise-Suprarrenal/fisiopatologia , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Vagina/fisiopatologia , Animais , Ansiedade/psicologia , Comportamento Animal/fisiologia , Feminino , Inflamação/induzido quimicamente , Inflamação/psicologia , Lipopolissacarídeos , Masculino , Camundongos , Atividade Motora/fisiologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/psicologia
18.
Dev Psychobiol ; 61(4): 525-542, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30834520

RESUMO

Hair cortisol has the potential to provide insight into young children's long-term stress response to social adversity. This study investigated associations between children's exposure to adversity from pregnancy to 2 years of age and their hair cortisol at 2 years, using a longitudinal cohort of children enriched for adversity risk, whose mothers were recruited during pregnancy through the "right@home" trial. Exposures were 18 maternal socioeconomic and psychosocial indicators of adversity, examined as concurrent, cumulative, and longitudinal exposure from pregnancy to 2 years. Hair samples were analyzed from 319/603 (53%) children participating at 2 years. Multivariable regression analyses for concurrent exposure showed three indicators of adversity were associated with higher hair cortisol (housing tenure of public rental, paying board or living rent free; not living in a safe place; higher maternal stress symptoms), one with lower hair cortisol (housing problems), and 14 indicators with no evidence of association. There was no evidence of association for the cumulative adversity count. Longitudinal exposure showed "intermittent" and "persistent" high maternal stress symptoms were associated with higher hair cortisol. The small number of associations identified suggests that hair cortisol is limited as a measure of stress response to social adversity in children at 2 years.


Assuntos
Experiências Adversas da Infância , Cabelo/química , Hidrocortisona/análise , Estresse Psicológico/fisiopatologia , Pré-Escolar , Feminino , Humanos , Sistema Hipotálamo-Hipofisário/fisiopatologia , Estudos Longitudinais , Masculino , Sistema Hipófise-Suprarrenal/fisiopatologia
19.
Dev Psychobiol ; 61(4): 573-591, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30820941

RESUMO

Relations between maternal baseline cortisol and infant cortisol reactivity to an emotion induction procedure at child ages 7, 15, and 24 months were analyzed using data from the Family Life Project (N = 1,292). The emotion induction consisted of a series of standardized and validated tasks, including an arm restraint, toy removal, and mask presentation, intended to elicit responses of fear and frustration. Results revealed that at 7 and 15 months, maternal baseline cortisol was negatively related to child cortisol reactivity, such that children of mothers with lower cortisol exhibited steeper cortisol increases in response to the emotion induction. At 24 months, the association between mother and infant cortisol was moderated by socioeconomic risk, such that maternal baseline cortisol was associated with child cortisol reactivity only in dyads characterized by low socioeconomic risk. Furthermore, at 24 months, children of mothers with low baseline cortisol and low socioeconomic risk exhibited decreasing cortisol responses, whereas children of mothers with low baseline cortisol but high risk exhibited flat cortisol responses. Children in dyads characterized by high baseline maternal cortisol also exhibited flat cortisol responses regardless of socioeconomic risk. The role of caregiver physiology in the regulation of the child's stress response in the context of adversity is discussed.


Assuntos
Cuidadores , Emoções/fisiologia , Hidrocortisona/análise , Relações Mãe-Filho , Saliva/química , Feminino , Humanos , Sistema Hipotálamo-Hipofisário/fisiopatologia , Lactente , Masculino , Sistema Hipófise-Suprarrenal/fisiopatologia , Fatores de Risco , Fatores Socioeconômicos
20.
Mol Neurobiol ; 56(9): 6239-6250, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30741369

RESUMO

Depression is a common psychiatric disease which pharmacological treatment relieves symptoms, but still far from ideal. Tactile stimulation (TS) has shown beneficial influences in neuropsychiatric disorders, but the mechanism of action is not clear. Here, we evaluated the TS influence when applied on adult female rats previously exposed to a reserpine-induced depression-like animal model. Immediately after reserpine model (1 mg/kg/mL, 1×/day, for 3 days), female Wistar rats were submitted to TS (15 min, 3×/day, for 8 days) or not (unhandled). Imipramine (10 mg/kg/mL) was used as positive control. After behavioral assessments, animals were euthanized to collect plasma and prefrontal cortex (PFC). Behavioral observations in the forced swimming test, splash test, and sucrose preference confirmed the reserpine-induced depression-like behavior, which was reversed by TS. Our findings showed that reserpine increased plasma levels of adrenocorticotropic hormone and corticosterone, decreased brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B, and increased proBDNF immunoreactivity in the PFC, which were also reversed by TS. Moreover, TS reestablished glial fibrillary acidic protein and glucocorticoid receptor levels, decreased by reserpine in PFC, while glial cell line-derived neurotrophic factor was increased by TS per se. Our outcomes are showing that TS applied in adulthood exerts a beneficial influence in depression-like behaviors, modulating the HPA axis and regulating neurotrophic factors more effectively than imipramine. Based on this, our proposal is that TS, in the long term, could be considered a new therapeutic strategy for neuropsychiatric disorders improvement in adult life, which may represent an interesting contribution to conventional pharmacological treatment.


Assuntos
Envelhecimento/fisiologia , Comportamento Animal , Depressão/fisiopatologia , Sistema Hipotálamo-Hipofisário/fisiopatologia , Fatores de Crescimento Neural/metabolismo , Sistema Hipófise-Suprarrenal/fisiopatologia , Transdução de Sinais , Tato , Hormônio Adrenocorticotrópico/sangue , Animais , Peso Corporal/efeitos dos fármacos , Corticosterona/sangue , Depressão/sangue , Feminino , Proteína Glial Fibrilar Ácida/metabolismo , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Tamanho do Órgão/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Ratos Wistar , Reserpina/farmacologia , Transdução de Sinais/efeitos dos fármacos , Sacarose , Natação
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