http://www.hindawi.comThe latest articles from Hindawi Publishing Corporation© 2012, Hindawi Publishing Corporation. All rights reserved.http://www.hindawi.com/journals/cpn/2011/649629/The literature emphasizes the risk of depression after a stroke. Less well known is the fact that depression may be as big a risk factor for strokes as hypertension, particularly in the older age group. This article reviews the risk for stroke and cognitive impairment consequent to depression, and describes the cardiovascular and immunological mechanisms that would appear to link depression to its cerebrovascular consequences. As well, the article refers to the brain imaging signatures that may allow prediction of impending brain injury. Finally, some questions that might be explored by future research are suggested, and some practical means to identify and help those at risk for the development of depression-associated vascular disease of the brain are suggested.Antoine M. HakimCopyright © 2011 Antoine M. Hakim. All rights reserved.http://www.hindawi.com/journals/cpn/2011/368324/Persons with heart failure (HF) frequently exhibit cognitive impairment with deficits in attention and memory. Depression is common in HF though its possible contribution to cognitive impairment is unknown. Cognitive dysfunction and depression may share common mechanisms in HF, as both are associated with similar abnormalities on neuroimaging. A total of 116 participants with HF (68.53±9.30 years) completed a neuropsychological battery and self-report measures of depression. Regression models showed depression incrementally and independently predicted test performance in all cognitive domains. Follow-up partial correlations revealed that greater depressive symptoms were associated with poorer performance on tests of attention, executive function, psychomotor speed, and language. These results indicate that depressive symptoms are associated with poorer cognitive performance in HF though further work is needed to clarify mechanisms for this association and possible cognitive benefits of treating depression in persons with HF.Sarah Garcia, Mary Beth Spitznagel, Ronald Cohen, Naftali Raz, Lawrence Sweet, Lisa Colbert, Richard Josephson, Joel Hughes, Jim Rosneck, and John GunstadCopyright © 2011 Sarah Garcia et al. All rights reserved.http://www.hindawi.com/journals/cpn/2011/315068/The Problem Areas in Diabetes (PAID) scale is a widely used self-report measure that can facilitate detection of diabetes-specific emotional distress in clinical practice. The aim of this study was to assess the factor structure and validity of the Turkish version of the PAID. A validation study was conducted among 154 patients with insulin-naïve type 2 diabetes. Participants completed the PAID, Centre for Epidemiological Studies Depression Scale (CES-D), Insulin Treatment Appraisal Scale (ITAS), and World Health Organization-Five Well-Being Index (WHO-5) questionnaires. Exploratory factor analyses yielded a 2-factor structure, identifying a 15-item “diabetes distress” factor and a 5-item “support-related issues” factor. The total PAID-score and the two dimensions were associated with higher levels of depression and poor emotional well-being. In the present study, the Turkish version of the PAID had satisfactory psychometric properties, however, the factorial structure was found to differ from factor solutions from other countries.Elisabeth M. J. Huis In ‘T Veld, Ceylan Makine, Arie Nouwen, Çağatay Karşıdağ, Pinar Kadıoğlu, Kubilay Karşıdağ, and François PouwerCopyright © 2011 Elisabeth M. J. Huis In ‘T Veld et al. All rights reserved.http://www.hindawi.com/journals/cpn/2011/723434/Peripheral microvascular complications in diabetes are associated with concurrent cerebrovascular disease. As detailed cognitive assessment is not routinely carried out among diabetic patients, the aim was to establish whether the presence of clinical “peripheral” microvascular disease can identify a subgroup of patients with early evidence of cognitive impairment. Detailed psychometric assessment was performed in 23 diabetic patients with no microvascular complications (Group D), 27 diabetic patients with at least one microvascular complication: retinopathy, neuropathy, and/or nephropathy (Group DC), and 25 healthy controls (Group H). Groups D and DC participants had significantly lower scores on reaction time (P=0.003 and 0.0001, resp.) compared to controls. Similarly, groups D and DC participants had significantly lower scores on rapid processing of visual information (P=0.034 and 0.001, resp.) compared to controls. In contrast, there was no significant difference between Groups D and DC on any of the cognitive areas examined. The results show that diabetes, in general, is associated with cognitive dysfunction, but the additional presence of peripheral microvascular disease does not add to cognitive decline. The study, however, indirectly supports the notion that the aetiology of cognitive impairment in diabetes may not be restricted to vascular pathology.Lorraine Ba-Tin, Paul Strike, and Naji TabetCopyright © 2011 Lorraine Ba-Tin et al. All rights reserved.http://www.hindawi.com/journals/cpn/2011/134040/Objective. We tested the association of specific psychological characteristics in patients having stable coronary disease with the reporting of anginal symptoms during daily activities, and positive exercise testing. Methods. One hundred and ninety-six patients with documented CAD enrolled in the Psychophysiological Investigations of Myocardial Ischemia (PIMI) Study completed an anginal history questionnaire and a battery of psychometric tests. They also underwent standardized exercise treadmill tests. Results. Patients with a recent history of angina were more likely to be female, and had higher Beck Depression (P=.002), State Anxiety (P=.001), Trait Anxiety (P=.03), Harm Avoidance (P=.04) and Muscle Tension (P=.004) scores than patients who had no recent history of angina. Along with several treadmill variables indicating more severe disease state and reduced exercise tolerance, patients who developed angina on a positive treadmill test also displayed higher scores on the Beck Depression Inventory (P=.003) and State Anxiety (P=.004) scales. Conclusions. Several psychological characteristics, and most notably anxiety and depression, are strong correlates of recent angina and angina in the presence of ischemia provoked by treadmill testing.Mark W. Ketterer, Nadine S. Bekkouche, A. David Goldberg, Robert P. McMahon, and David S. KrantzCopyright © 2011 Mark W. Ketterer et al. All rights reserved.http://www.hindawi.com/journals/cpn/2011/254569/While ischaemic stroke remains a leading cause of death and disability, there have been recent advancements in treatment modalities including thrombolysis and decompressive hemicraniectomy. A retrospective review of patients treated in our NHS teaching hospital, in Plymouth (UK), over a 2 year period identified 17 thrombolysed patients, of whom two had undergone subsequent decompressive hemicraniectomy. These were non-dominant hemisphere strokes in young patients, aged 51 and 57. Initial NIHSS scores were 16 and 17, and they received thrombolysis at 2 hrs 42 min and 5 hrs 10 min post onset of symptoms respectively. CT imaging demonstrated cerebral swelling with significant midline shift in both cases, and decompressive hemicraniectomy was undertaken at 29 hrs 8 min and 27 hrs 30 min post-thrombolysis. We found no significant intra-operative complications attributable to prior use of thrombolytics. Both patients have had acceptable psychological and physical outcomes, with Barthel Index scores of 40 and 25, and MMSE scores of 29/30 and 27/30. We conclude that the use of thrombolytic therapy does not contra-indicate subsequent decompressive hemicraniectomy in well selected patients with non-dominant hemisphere strokes. More research in this field is required to elucidate factors which would facilitate recognition of stroke patients who will benefit most from aggressive medical and neurosurgical intervention.A. Williams, M. Sittampalam, N. Barua, and A. Mohd NorCopyright © 2011 A. Williams et al. All rights reserved.http://www.hindawi.com/journals/cpn/2010/506952/The long-term consequences of forebrain ischemia include delayed Parkinson's syndrome. This study revealed delayed neurodegeneration in the substantia nigra 8 weeks after 12.5 minutes of global ischemia in rat brain. Following neuronal loss of 30–40% in central and dorsolateral striatum at day 3, neuronal damage in the substantia nigra (SN) was assessed at 4–8 weeks using immunohistochemistry for glutamate decarboxylase 67 (GAD67), vesicular GABA transporter (VGAT), and calretinin (CR). At day 56, the optical density of GAD67-, but not VGAT-, immunoreactivity in substantia nigra pars reticulata (SNR)—significantly decreased. CR-neurons concentrated in substantia nigra pars compacta (SNC) were reduced by 27% from day 3 (n=5) to day 56 (n=7, ANOVA, p<.01). Movement coordination was impaired at day 56, as evaluated using beam-walking test (time-to-traverse 5.6±1.2 sec versus 11.8±5.4 sec; sham versus ischemia, p<.05, n=5, and 7, resp.). Our results demonstrate delayed impairment of the GABAergic system components in SN and associated with movement deficits after global ischemia.B. Lin, S. Levy, A. P. Raval, M. A. Perez-Pinzon, and R. A. DeFazioCopyright © 2010 B. Lin et al. All rights reserved.http://www.hindawi.com/journals/cpn/2010/302102/Objective. Depression has been found to be an independent risk factor with cardiovascular diseases (CVDs) and also associated with increased mortality among these patients. Method. We used a comprehensive database of all suicides (n=2,283) committed in Northern Finland with information on all hospital-treated cardiovascular diseases and psychiatric disorders. Results. Coronary artery disease (CAD) had been present in 7.7% and other cardiovascular diseases (CVDs) in 11.6% of the suiciders. The likelihood of suicide for patients with hospital-treated CAD was estimated to be two-fold compared to the general population while likelihood for suicide was not elevated among those with other CVDs. Males with CAD and females with CAD or any CVD had been hospitalized significantly more often with depression compared to reference group. Conclusions. Suicidality among patients with cardiovascular diseases has been suggested to associate with depression. Psychiatric consultation is highly recommended in clinical practice for cardiac patients with depression or alcohol-related disorders.Arja Mainio, Helinä Hakko, Pirkko Räsänen, and Markku TimonenCopyright © 2010 Arja Mainio et al. All rights reserved.http://www.hindawi.com/journals/cpn/2010/838164/Phenomics is a systematic study of phenotypes on a genomewide scale that is expected to unravel, as of yet, unsuspected functional roles of the genome. It remains to be determined how to optimally approach and analyze the available phenomics databases to spearhead innovation in neuropsychiatry. By serendipitously connecting two unrelated phenotypes of increased blood levels of the adipokine leptin, a molecule that regulates appetite, in 5-lipoxygenase- (5-LOX) deficient mice and patients with a lower risk for Alzheimer's disease (AD), we postulated a leptin-mediated basis for beneficial effects of ALOX5 (a gene encoding 5-LOX) gene-deficiency in AD. We suggest that it might be possible to avoid relying on serendipity and develop data-mining tools capable of extracting from phenomics databases indications for such novel hypotheses. Hence, we provide an example of using a free-access Arrowsmith two-node search interface to identify ALOX5 as unsuspected putative mechanisms for the previously described clinical association between increased plasma levels of leptin and a lower risk of incident dementia and AD.Hari Manev and Radmila ManevCopyright © 2010 Hari Manev and Radmila Manev. All rights reserved.http://www.hindawi.com/journals/cpn/2010/396282/Serotonin transporter clustering is an important feature for regulation of this transporter activity. We used immunocytochemistry to analyze alterations in serotonin transporter clustering in blood lymphocytes of reeler mice. Serotonin transporter immunolabelling is observed mostly as a patchy staining in lymphocytes membranes. Comparison of the number and size of serotonin transporter clusters in wild-type mice, heterozygous reeler mice, and homozygous reeler mice showed an increase in the number and size of clusters in heterozygous reeler mice, but only an increase in clusters size in homozygous reeler mice. Reelin is down-regulated in the brain of schizophrenia, autism, and mood disorders, and is also expressed in blood plasma. There is the possibility therefore that alterations in serotonin transporter clustering in blood lymphocytes associated with a decrease in reelin expression may be operative in some cardiovascular or immune system alterations showing comorbidity with these mental disorders.Tania Rivera-Baltanas, Raquel Romay-Tallon, Iria G. Dopeso-Reyes, and Héctor J. CarunchoCopyright © 2010 Tania Rivera-Baltanas et al. All rights reserved.http://www.hindawi.com/journals/cpn/2010/501349/Depression is an independent risk factor for cardiovascular diseases and is associated with metabolic syndrome (MetS). Levels of plasminogen activator inhibitor-1 (PAI-1), an inhibitor of tissue-type and urokinase-type plasminogen activators, are associated with MetS. To clarify the role of PAI-1 in subjects with long-term adverse mental symptomatology (LMS; including depression) and MetS, we measured circulating PAI-1 levels in controls (n=111), in subjects with MetS and free of mental symptoms (n=42), and in subjects with both MetS and long-term mental symptoms (n=70). PAI-1 increased linearly across the three groups in men. In logistic regression analysis, men with PAI-1 levels above the median had a 3.4-fold increased likelihood of suffering from the comorbidity of long-term adverse mental symptoms and MetS, while no such associations were detected in women. In conclusion, our results suggest that in men high PAI-1 levels are independently associated with long-term mental symptomatology.Anne Huotari, Soili M. Lehto, Leo Niskanen, Karl-Heinz Herzig, Jukka Hintikka, Heli Koivumaa-Honkanen, Tommi Tolmunen, Kirsi Honkalampi, Noora Kaikkonen, and Heimo ViinamäkiCopyright © 2010 Anne Huotari et al. All rights reserved.http://www.hindawi.com/journals/cpn/2009/327360/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.Mark E. Obrenovich, Hector H. Palacios, Eldar Gasimov, Jerzy Leszek, and Gjumrakch AlievCopyright © 2009 Mark E. Obrenovich et al. All rights reserved.http://www.hindawi.com/journals/cpn/2010/318167/Hari ManevCopyright © 2010 Hari Manev. All rights reserved.http://www.hindawi.com/journals/cpn/2009/282059/There is a now a wealth of epidemiological, animal, and clinical data to suggest the benefits of uric acid reduction and xanthine 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.Peter Higgins, Jesse Dawson, and Matthew WaltersCopyright © 2009 Peter Higgins et al. All rights reserved.http://www.hindawi.com/journals/cpn/2009/618586/The phosphatidylinositol (PI) hydrolysis signaling system has been shown to be altered in platelets of depressed and schizophrenic subjects. Inositol (1,4,5) trisphosphate (Ins(1,4,5)P3), an integral component of the PI signaling system, mobilizes Ca2+ by activating Ins(1,4,5)P3 receptors. To eventually investigate the role of Ins(1,4,5)P3 receptors in depression and other mental disorders, we characterized [H3]Ins(1,4,5)P3 binding sites in crude platelet membranes prepared from small amounts of blood obtained from healthy human control subjects. We found a single, saturable binding site for [H3]Ins(1,4,5)P3 to crude platelet membranes, which is time dependent and modulated by pH, inositol phosphates, and heparin. Since cyclic adenosine monophosphate (cAMP) and Ca2+ have been shown to be important modulators in Ins(1,4,5)P3 receptors, in the present study we also determined the effects of various concentrations of CaCI2 and forskolin on Ins(1,4,5)P3 binding to platelet membranes. CaCI2 modulated [3H]Ins(1,4,5)P3 binding sites in a biphasic manner: at lower concentrations it inhibited [3H]Ins(1,4,5)P3 binding, whereas at higher concentrations, it stimulated [3H]Ins(1,4,5)P3 binding. On the other hand, forskolin inhibited [3H]Ins(1,4,5)P3 binding. Our results thus suggest that the pharmacological characteristics of [3H]Ins(1,4,5)P3 binding to crude platelet membranes are similar to that of Ins(1,4,5)P3 receptors; and that both Ca2+ and cAMP modulate [3H]Ins(1,4,5)P3 binding in crude platelet membranes.Yogesh Dwivedi and Ghanshyam N. PandeyCopyright © 2009 Yogesh Dwivedi and Ghanshyam N. Pandey. All rights reserved.http://www.hindawi.com/journals/cpn/2009/107286/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 Aβ and tau aggregation. We induced hypertension in APPswe Tg2576 and P301L-tauTg mouse models. In Tg2576 mice, experimental hypertension was associated with a significant increase of the accumulation of Amyloid-β (Aβ) peptides in brain tissue and a significant reduction of Aβ peptides in serum (P<.05). These results indicate that hypertension may promote AD-type Aβ 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 Aβ neuropathology and neurological disorders associated with abnormal tau metabolism.C. Díaz-Ruiz, J. Wang, H. Ksiezak-Reding, L. Ho, X. Qian, N. Humala, S. Thomas, P. Martínez-Martín, and G. M. PasinettiCopyright © 2009 C. Díaz-Ruiz et al. All rights reserved.http://www.hindawi.com/journals/cpn/2009/362795/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.Robert K. McNamaraCopyright © 2009 Robert K. McNamara. All rights reserved.http://www.hindawi.com/journals/cpn/2009/867041/Feeding mice, over 3 generations, an equicaloric diet in which α-linolenic acid, the dietary precursor of n-3 polyunsaturated fatty acids, was substituted by linoleic acid, the dietary precursor of n-6 polyunsaturated fatty acids, significantly increased body weight throughout life when compared with standard diet-fed mice. Adipogenesis observed in the low n-3 fatty acid mice was accompanied by a 6-fold upregulation of stearyl-coenzyme A desaturase 1 (Scd1), whose activity is correlated to plasma triglyceride levels. In total liver lipid and phospholipid extracts, the sum of n-3 fatty acids and the individual longer carbon chain acids, eicosapentaenoic acid (20:5n3), docosapentaenoic acid (22:5n3), and docosahexaenoic acid (22:6n3) were significantly decreased whereas arachidonic acid (20:4n6) was significantly increased. In addition, low n-3 fatty acid-fed mice had liver steatosis, heart, and kidney hypertrophy. Hence, reducing dietary α-linolenic acid, from 1.02 energy% to 0.16 energy% combined with raising linoleic acid intake resulted in obesity and had detrimental consequences on organ function.Ingeborg Hanbauer, Ignacio Rivero-Covelo, Ekrem Maloku, Adam Baca, Qiaoyan Hu, Joseph R. Hibbeln, and John M. DavisCopyright © 2009 Ingeborg Hanbauer et al. All rights reserved.http://www.hindawi.com/journals/cpn/2009/861324/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 P2X7, 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 P2X7 receptor was originally described in cells of hematopoietic origin, and mediates the influx of Ca2+ and Na+ and Ca2+ and Na+ ions as well as the release of proinflammatory cytokines. P2X7 receptors may affect neuronal cell death through their ability to regulate the processing and release of interleukin-1β, a key mediator in neurodegeneration, chronic inflammation, and chronic pain. Activation of P2X7, a key mediator in neurodegeneration, chronic inflammation, and chronic pain. Activation of P2X7 receptors provides an inflammatory stimulus, and P2X7 receptor-deficient mice have substantially attenuated inflammatory responses, including models of neuropathic and chronic inflammatory pain. Moreover, P2X7 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, P2X7 receptor activation, proinflammatory cytokine production, and endothelial cell apoptosis. In this context, the P2X7 receptor may be viewed as a gateway of communication between the nervous, immune, and cardiovascular systems.Stephen D. Skaper, Patrizia Debetto, and Pietro GiustiCopyright © 2009 Stephen D. Skaper et al. All rights reserved.http://www.hindawi.com/journals/cpn/2009/453786/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.Mladen I. Vidovich, Aneet Ahluwalia, and Radmila ManevCopyright © 2009 Mladen I. Vidovich et al. All rights reserved.http://www.hindawi.com/journals/cpn/2009/427840/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.Milos D. IkonomovicCopyright © 2009 Milos D. Ikonomovic. All rights reserved.http://www.hindawi.com/journals/cpn/2009/546737/Hari ManevCopyright © 2009 Hari Manev. All rights reserved.