Cardiovascular psychiatry and neurology最新文献

P2X receptors are ATP-gated cation channels that mediate fast excitatory transmission in diverse regions of the brain and spinal cord. Several P2X receptor subtypes, including P2X(7), have the unusual property of changing their ion selectivity during prolonged exposure to ATP, which results in a channel pore permeable to molecules as large as 900 daltons. The P2X(7) receptor was originally described in cells of hematopoietic origin, and mediates the influx of Ca(2+) and Na(+) and Ca(2+) and Na(+) ions as well as the release of proinflammatory cytokines. P2X(7) receptors may affect neuronal cell death through their ability to regulate the processing and release of interleukin-1beta, a key mediator in neurodegeneration, chronic inflammation, and chronic pain. Activation of P2X(7), a key mediator in neurodegeneration, chronic inflammation, and chronic pain. Activation of P2X(7) receptors provides an inflammatory stimulus, and P2X(7) receptor-deficient mice have substantially attenuated inflammatory responses, including models of neuropathic and chronic inflammatory pain. Moreover, P2X(7) receptor activity, by regulating the release of proinflammatory cytokines, may be involved in the pathophysiology of depression. Apoptotic cell death occurs in a number of vascular diseases, including atherosclerosis, restenosis, and hypertension, and may be linked to the release of ATP from endothelial cells, P2X(7) receptor activation, proinflammatory cytokine production, and endothelial cell apoptosis. In this context, the P2X(7) receptor may be viewed as a gateway of communication between the nervous, immune, and cardiovascular systems.

Background. Based on epidemiological data, clinical trials, and meta-analytic reviews, omega-3 polyunsaturated fatty acids (n-3 PUFAs) seem to be a biological link between depression and cardiovascular diseases (CVDs). Presentation. Involvement of n-3 PUFAs in depression and CVDs may be associated with a chronic, low-grade, inflammation. We hypothesize that n-3 PUFAs link depression and CVDs via "PUFA-prostaglandin E2 (PGE2) cascade." Testing. To further support our hypothesis, case-control studies are needed to test the role of COX2 and PLA2 functions in depression and in CVDs. In addition, the effects of n-3 PUFAs on cardiovascular markers in depression and on depressive symptoms in CVDs should be investigated in clinical trials. Finally, the effects of manipulating COX2 and PLA2 functions on depression-like behaviors and cardiovascular functions could be explored in animal studies. Implications. n-3 PUFAs might be a promising treatment for both cardiovascular diseases and depression via its anti-inflammatory, cardioprotective, and neuroprotective effects.

An increasing body of evidence implicates proinflammatory cytokines in psychiatric disorders, namely, in depression. Of notice, recent studies showed that anti-inflammatory cytokines, such as IL-10, also modulate depressive-like behavior. In this article, we propose that the anti-inflammatory cytokine IL-10 is a putative link between two of the most widely reported phenomenon observed in depressed patients: the disruption of the hypothalamic-pituitary-adrenal axis and the imbalanced production of cytokines. If so, IL-10 might represent a novel target for antidepressant therapy.

Neurons, glial, cells, and brain tumor cells tissues release small vesicles (secretory exosomes and microvesicles), which may represent a novel mechanism by which neuronal activity could influence angiogenesis within the embryonic and mature brain. If CNS-derived vesicles can enter the bloodstream as well, they may communicate with endothelial cells in the peripheral circulation and with cells concerned with immune surveillance.

There is a now a wealth of epidemiological, animal, and clinical data to suggest the benefits of uric acid reduction and hxanthine oxidase inhibition in prevention of vascular disease. This review discusses the available epidemiological, preclinical, and clinical data and considers arguments for and against a role for serum uric acid in common cardiovascular disorders. It concludes that large scale trials with clinical endpoints are justified to address this important question and to define whether use of drugs such as allopurinol should be a routine part of preventative strategies.

Background. Studies have implicated abnormalities in epigenetic gene regulation in schizophrenia. Presentation. We hypothesize that identifying abnormalities in chromatin structure and the epigenetic machinery in peripheral blood mononuclear cells (PBMC) from schizophrenia patients could (a) help characterize a subset of schizophrenia patients and (b) lead to targeted pharmacological interventions. Testing. Investigate the relationship between clinical symptoms, demographics, hormonal fluctuations, substance abuse, disease characteristics across the major mental illnesses, and epigenetic parameters in PBMC. In addition, examine the effects of individual antipsychotics, mood stabilizers, as well as experimental agents both as clinically prescribed as well as in cultured PBMC to understand the effects of these agents on chromatin. Implications. If PBMC could serve as a reliable model of overall epigenetic mechanisms then this could lead to a "biomarker" approach to revealing pathological chromatin state in schizophrenia. This approach may provide an informed method for selecting chromatin modifying agents for psychiatric disorders.

Variant (Prinzmetal's) angina is an uncommon cause of precordial pain caused by coronary vasospasm and characterized by transient ST elevation and negative markers of myocardial necrosis. This is the case of a female patient with a prior history of depression and panic attacks who presented with recurrent symptoms including chest pain. A cardiac event monitor positively documented coronary vasospasm associated with anxiety-provoking chest pain, whereas the coronary arteries were angiographically normal. We noted that the frequency of angina attacks apparently increased during the period that coincided with the introduction of Bupropion SR for treatment of the patient's depression. Considering the possibility of bupropion-associated negative impact on coronary vasospasm, the antidepressant therapy was adjusted to exclude this drug. Although Prinzmetal's angina is relatively uncommon, we suspect that a routine use of cardiac event monitors in subjects with panic disorder might reveal a greater incidence of coronary vasospasm in this patient population.

Background. The conserved noncoding microRNAs (miRNAs) that function to regulate gene expression are essential for the development and function of the brain and heart. Changes in miRNA expression profiles are associated with an increased risk for developing neurodegenerative disorders as well as heart failure. Here, the hypothesis of how miRNA-regulated pathways could contribute to comorbid neurological and cardiovascular disorders will be discussed. Presentation. Changes in miRNA expression occurring in the brain and heart could have an impact on coexisting neurological and cardiovascular characteristics by (1) modulating organ function, (2) accentuating cellular stress, and (3) impinging on neuronal and/or heart cell survival. Testing. Evaluation of miRNA expression profiles in the brain and heart tissues from individuals with comorbid neurodegenerative and cardiovascular disorders will be of great importance and relevance. Implications. Careful experimental design will shed light to the deeper understanding of the molecular mechanisms tying up those different but yet somehow connected diseases.

Increasing evidence points to vascular damage as an early contributor to the development of two leading causes of age-associated dementia, namely Alzheimer disease (AD) and AD-like pathology such as stroke. This review focuses on the role of G protein-coupled receptor kinases (GRKs) as they relate to dementia and how the cardio and cerebrovasculature is involved in AD pathogenesis. The exploration of GRKs in AD pathogenesis may help bridge gaps in our understanding of the heart-brain connection in relation to neurovisceral damage and vascular complications of AD. The a priori basis for this inquiry stems from the fact that kinases of this family regulate numerous receptor functions in the brain, myocardium and elsewhere. The aim of this review is to discuss the finding of GRK2 overexpression in the context of early AD pathogenesis. Also, we consider the consequences for this overexpression as a loss of G-protein coupled receptor (GPCR) regulation, as well as suggest a potential role for GPCRs and GRKs in a unifying theory of AD pathogenesis through the cerebrovasculature. Finally, we synthesize this newer information in an attempt to put it into context with GRKs as regulators of cellular function, which makes these proteins potential diagnostic and therapeutic targets for future pharmacological intervention.

The saga of harmful levodopa (LD) in the treatment of Parkinson's disease (PD) resulted from outcomes of animal-and cell culture studies and the clinical observation of motor complication related to the short half life of LD. Further aspects of LD long term application, the LD associated homocysteine increase and its emerging consequences on progression, and onset of neuropsychiatric symptoms and of vascular disease are only partially considered. Therapeutic approaches for this LD-mediated neurotoxic homocysteine increase are vitamin supplementation or LD application with an inhibitor of catechol-O-methyltransferase (COMT). However, forcing central dopamine metabolism further down the methylation path by central blocking of COMT and MAO-B may reduce oxidative stress and homocysteine levels. But it may also increase N-methylation of tetrahydroisoquinolines to neurotoxic N-methylated tetrahydroisoquinolines. These compounds were observed in cerebrospinal fluid and plasma of long term LD-treated PD patients. Therefore LD application with peripheral COMT inhibition may be safer.