Cardiovascular psychiatry and neurology最新文献

Epidemiological evidence suggests that hypertension may accelerate the onset and progression of Alzheimer's disease (AD). In this study, we explored the role of hypertension in the neurodegenerative changes associated with Abeta and tau aggregation. We induced hypertension in APP(swe) Tg2576 and P301L-tauTg mouse models. In Tg2576 mice, experimental hypertension was associated with a significant increase of the accumulation of Amyloid-beta (Abeta) peptides in brain tissue and a significant reduction of Abeta peptides in serum (P < .05). These results indicate that hypertension may promote AD-type Abeta neuropathology in Tg2576. In P301L-tauTg mice we found that the presence of hypertension was significantly associated with aggravated motor function assessed by hindlimb extension test (P = .01). These results suggest that hypertension may play a role in accelerating the progression of motor dysfunction associated with tau-related alterations. Our studies suggest that the management of blood pressure (BP) may alleviate AD-type Abeta neuropathology and neurological disorders associated with abnormal tau metabolism.

Epidemiological studies indicate age as a strong risk factor for developing cardiovascular and neurodegenerative diseases. During the aging process, changes in the expression of particular genes can influence the susceptibility to these diseases. 5-Lipoxygenase (5-LO) by oxidizing fatty acids forms leukotrienes, potent mediators of oxidative and inflammatory reactions, two key pathogenic events in both clinical settings. This enzyme is widely distributed in the cardiovascular as well as in the central nervous system, where its expression levels increase with age, suggesting that it may be involved in their diseases of aging. The central theme of this article is that during aging, 5-LO acts as biologic link between different stressors and the development of cardiovascular and neurodegenerative diseases. We hypothesize that the age-dependent upregulation of 5-LO represents a "priming" factor in the vasculature as well as in the brain, where a subsequent exposure to triggering stimuli (i.e., infections) leads to an abnormal chronic inflammatory reaction, and ultimately results in increased organ vulnerability and functional deficits.

Epidemiological studies point to a strong and possibly causal association of psychiatric and neurological disorders with cardiovascular disease (CVD). Mechanistic links between these co-occurring illnesses are not well understood. Better insight into their relationship could help identify novel diagnostic markers and therapeutic targets. For successful translation of basic biomedical research into clinical practice, analyses of postmortem human tissues are essential. However, current tissue banks dedicated to psychiatric and neurological research collect only brain tissue samples deemed most important to the institution's participating investigators. While this practice is often dictated by budget constraints, restricted tissue storage space and other practical reasons, it limits the ability of the biological research community to access and study multiple organ systems relevant to cardiovascular and neuronal systems dysfunction. This problem is worsened when clinical records pertaining to coexistent systemic pathology are not available. To promote further understanding of co-occurring CVD and psychiatric/neurological disorders, efforts should be made to support tissue banks that harvest heart, coronary arteries, and aorta samples as well as brain tissue, from the same subjects.

Matrix metalloproteinase-9 (MMP9) has been implicated in numerous somatic illnesses, including cardiovascular disorders and cancer. Recently, MMP9 has been shown to be increasingly important in several aspects of central nervous system activity. Furthermore, a pathogenic role for this enzyme has been suggested in such neuropsychiatric disorders as schizophrenia, bipolar illness, and multiple sclerosis. In this paper, the results of biochemical and molecular-genetic studies on MMP9 that have been performed in these pathological conditions will be summarized. Furthermore, I hypothesize that the MMP9 gene, as shown by functional -1562 C/T polymorphism studies, may be mediating the relationship of neuropsychiatric illnesses (schizophrenia, bipolar mood disorder, multiple sclerosis) that are comorbid with cardiovascular disease and cancer.

Major depression disorder (MDD) significantly increases the risk for coronary heart disease (CHD) which is a leading cause of mortality in patients with MDD. Moreover, depression is frequently observed in a subset of patients following acute coronary syndrome (ACS) and increases risk for mortality. Here evidence implicating omega-3 (n-3) fatty acid deficiency in the pathoaetiology of CHD and MDD is reviewed, and the hypothesis that n-3 fatty acid deficiency is a preventable risk factor for CHD comorbidity in MDD patients is evaluated. This hypothesis is supported by cross-national and cross-sectional epidemiological surveys finding an inverse correlation between n-3 fatty acid status and prevalence rates of both CHD and MDD, prospective studies finding that lower dietary or membrane EPA+DHA levels increase risk for both MDD and CHD, case-control studies finding that the n-3 fatty acid status of MDD patients places them at high risk for emergent CHD morbidity and mortality, meta-analyses of controlled n-3 fatty acid intervention studies finding significant advantage over placebo for reducing depression symptom severity in MDD patients, and for secondary prevention of cardiac events in CHD patients, findings that n-3 fatty acid status is inversely correlated with other documented CHD risk factors, and patients diagnosed with MDD after ACS exhibit significantly lower n-3 fatty acid status compared with nondepressed ACS patients. This body of evidence provides strong support for future studies to evaluate the effects of increasing dietary n-3 fatty acid status on CHD comorbidity and mortality in MDD patients.

There are high levels of comorbidity between neuropsychiatric and cardiovascular disorders. A key molecule central to both cognitive and cardiovascular function is the molecule serotonin. In the brain, serotonin modulates neuronal activity and is actively involved in mediating many cognitive functions and behaviors. In the periphery, serotonin is involved in vasoconstriction, inflammation, and cell growth, among other processes. It is hypothesized that one component of the serotonin system, the 5-HT(2A) receptor, is a common and contributing factor underlying aspects of the comorbidity between neuropsychiatric and cardiovascular disorders. Within the brain this receptor participates in processes such as cognition and working memory, been implicated in effective disorders such as schizophrenia, and mediate the primary effects of hallucinogenic drugs. In the periphery, 5-HT(2A) receptors have been linked to vasoconstriction and hypertension, and to inflammatory processes that can lead to atherosclerosis.

The exact nature of the comorbidity between cardiovascular disease (CVD) and major depressive disorder (MDD) is poorly understood. The proposed mechanisms include various biochemical and molecular pathways as well as health behaviors such as physical inactivity. One possible link between MDD and CVD is increased platelet activity and blood viscosity. Recently, it was discovered that platelets express functional subtype of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, for example, glutamate receptor 1 (GluR1). Here, I propose that this type of AMPA receptor could play a role in comorbid MDD and CVD, and antidepressants may interfere with platelet activation via direct or indirect effects on platelet GluR1 phosphorylation. Testing this hypothesis could provide a novel view on the pathobiological mechanisms of comorbid MDD and CVD. With respect to the recently discovered role of AMPA receptors in regulating platelet activation and thrombosis, it appears that the information about the putative effects of psychoactive AMPA-modifying drugs on platelet AMPA receptors would be critical in evaluating the putative effects of such drugs on CVD.

Background. Over-stimulation of the purinergic P2X(7) receptor may bring about cellular dysfunction and injury in settings of neurodegeneration, chronic inflammation, as well as in psychiatric and cardiovascular diseases. Here we speculate how P2X(7) receptor over-activation may lead to the co-occurrence of neurological and psychiatric disorders with cardiovascular disorders. Presentation. We hypothesize that proinflammatory cytokines, in particular interleukin-1beta, are key players in the pathophysiology of neurological, psychiatric, and cardiovascular diseases. Critically, this premise is based on a role for the P2X(7) receptor in triggering a rise in these cytokines. Given the broad distribution of P2X(7) receptors in nervous, immune, and vascular tissue cells, this receptor is proposed as central in linking the nervous, immune, and cardiovascular systems. Testing. Investigate, retrospectively, whether a bidirectional link can be established between illnesses with a proinflammatory component (e.g., inflammatory and chronic neuropathic pain) and cardiovascular disease, for example, hypertension, and whether patients treated with anti-inflammatory drugs have a lower incidence of disease complications. Positive outcome would indicate a prospective study to evaluate therapeutic efficacy of P2X(7) receptor antagonists. Implications. It should be stressed that sufficient direct evidence does not exist at present supporting our hypothesis. However, a positive outcome would encourage the further development of P2X(7) receptor antagonists and their application to limit the co-occurrence of neurological, psychiatric, and cardiovascular disorders.