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Evidence of Antidepressive Effects of a Wakan-yaku, Hochuekkito, in Depression Model Mice with Learned-Helplessness Behavior  [PDF]
Michihisa Tohda,Salin Mingmalairak
Evidence-Based Complementary and Alternative Medicine , 2013, DOI: 10.1155/2013/319073
Abstract: Wakan-yaku is a type of Japanese and Sino traditional, systematized medical care that has been practiced for hundreds of years. This medicinal system includes many antidepressive prescriptions. One of the candidates is Hochuekkito, although experimental evidence has not yet been established clearly. To obtain evidence, a depression model of learned-helplessness (LH) mice was used. Based on the score of escape failure, an index of the depression degree, mice with a depressive condition were selected to assess Hochuekkito’s effects. This selection was significant and effective in the following two points: evaluation of the drug effect under disease conditions and minimization of the number of animals. Treatment with Hochuekkito (1 and 5?g/kg p.o.; estimated galenical amount) for 14 days significantly decreased the depression index, the number of escape failures, and desipramine (10?mg/kg p.o.) suggesting that Hochuekkito has an antidepressive effect. 1. Introduction Since the discovery of the antidepressive effect of imipramine in the 1950s, clinical antidepressants have been developed with monoamine transporters as the target molecules [1]. Meanwhile, many “Wakan-yaku prescriptions” have been traditionally used to treat depression. By studying the action mechanism of these Wakan-yaku prescriptions, elucidation of the generation mechanism of depression and the development of new antidepressants are expected; however, there is little experimental evidence for the antidepressive effects of Wakan-yaku. The learned-helplessness (LH) behavior of experimental animals caused by inescapable footshocks is one behavioral phenotype relevant to depression [1, 2]. Since this behavior can be ameliorated by antidepressants, LH animals have been used for studying the pathophysiology of depression and the actions of antidepressants [3, 4]. LH model animals can evaluate a drug effect under more pathological conditions than the forced swimming test and tail suspension test, which are evaluated by correlation. It has been also reported that the forced swimming itself is a strong and sustained stress [5]. Therefore, in this study, the effect of a Wakan-yaku prescription, Hochuekkito, was evaluated using LH mice. Hochuekkito has antidepressant-like effects in the forced swimming test [6]. A description of Hochuekkito (Bu Zhong Yi Qi Tang in Chinese) first appeared in Neiwaishang Bianhuolun, which was written by Dong Yuan Li in 1247. At that time, people living around Li had lost their physical strength because of malnutrition during war; therefore, Li developed Hochuekkito for
Xiangshao Granule Exerts Antidepressive Effects in a Depression Mouse Model by Ameliorating Deficits in Hippocampal BDNF and TrkB  [PDF]
Yi Chen,Jie Liu,Xiaoting Wu,Edouard Collins Nice
Evidence-Based Complementary and Alternative Medicine , 2013, DOI: 10.1155/2013/309262
Abstract: This study explores the therapeutic effects of Xiangshao granules in a mouse depression model and examines the potential molecular mechanisms involved. After 21 consecutive days of chronic stress challenge, all mice were divided into three groups: control group, depression group, and Xiangshao granule treatment group. On the 22nd day, rats in the Xiangshao granule treatment group received Xiangshao granules via gastrogavage for 3 consecutive weeks. Depression group mice showed a significant reduction of crossings ( ) but not rearings ( ). Serum CRH, CORT, and ACTH levels were significantly increased in depression mice compared with control ( ) and the expression levels of hippocampal BDNF and TrkB were reduced in the model group ( ). However, Xiangshao granule treatment remarkably rescued the decrease in the body weight ( ), increased crossings in the open field test ( ), upregulated the expression of hippocampal BDNF and TrkB expression, and reduced the serum CRH, CORT, and ACTH concentrations compared with the depression group ( ). Collectively, these results demonstrated that Xiangshao granule could effectively induce antidepressive effects in the depression mouse model by ameliorating the expression of hippocampal BDNF and TrkB. 1. Introduction Depression constitutes one of the major causes of disability and is the 4th leading cause of the global burden of disease, with a lifetime prevalence of up to 17% [1]. Although antidepressant medications represent the mainstay therapy for depression, almost one-quarter of the patients fail to respond to these therapeutics [2]. Attempts are therefore being made to seek alternative medication. Chinese traditional medicine treatment for patients suffering depression has more than a thousand years of history. It has proved efficacious and thus is attracting increasing attention from scientists working in this field. Xiangshao granule, which is made from the root of the herbaceous peony, Cyperus, and ligustrazine, and other natural products [3], has been demonstrated to exert therapeutic effects for premenstrual tension syndrome [4, 5]. Expression of μ-opioid receptor in brains of premenstrual tension syndrome Gan-qi invasion rats was regionally specific, and administration of Xiangshao granule showed corresponding regulatory effects [4]. It has been reported that the binding potential of the μ-opioid receptor is significantly lower in patients with major depressive disorders relative to nondepressed controls [5]. However, whether Xiangshao granule could also improve the outcome for depression patients and, if so,
Rhythmicity in Mice Selected for Extremes in Stress Reactivity: Behavioural, Endocrine and Sleep Changes Resembling Endophenotypes of Major Depression  [PDF]
Chadi Touma, Thomas Fenzl, J?rg Ruschel, Rupert Palme, Florian Holsboer, Mayumi Kimura, Rainer Landgraf
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0004325
Abstract: Background Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, including hyper- or hypo-activity of the stress hormone system, plays a critical role in the pathophysiology of mood disorders such as major depression (MD). Further biological hallmarks of MD are disturbances in circadian rhythms and sleep architecture. Applying a translational approach, an animal model has recently been developed, focusing on the deviation in sensitivity to stressful encounters. This so-called ‘stress reactivity’ (SR) mouse model consists of three separate breeding lines selected for either high (HR), intermediate (IR), or low (LR) corticosterone increase in response to stressors. Methodology/Principle Findings In order to contribute to the validation of the SR mouse model, our study combined the analysis of behavioural and HPA axis rhythmicity with sleep-EEG recordings in the HR/IR/LR mouse lines. We found that hyper-responsiveness to stressors was associated with psychomotor alterations (increased locomotor activity and exploration towards the end of the resting period), resembling symptoms like restlessness, sleep continuity disturbances and early awakenings that are commonly observed in melancholic depression. Additionally, HR mice also showed neuroendocrine abnormalities similar to symptoms of MD patients such as reduced amplitude of the circadian glucocorticoid rhythm and elevated trough levels. The sleep-EEG analyses, furthermore, revealed changes in rapid eye movement (REM) and non-REM sleep as well as slow wave activity, indicative of reduced sleep efficacy and REM sleep disinhibition in HR mice. Conclusion/Significance Thus, we could show that by selectively breeding mice for extremes in stress reactivity, clinically relevant endophenotypes of MD can be modelled. Given the importance of rhythmicity and sleep disturbances as biomarkers of MD, both animal and clinical studies on the interaction of behavioural, neuroendocrine and sleep parameters may reveal molecular pathways that ultimately lead to the discovery of new targets for antidepressant drugs tailored to match specific pathologies within MD.
The effects of depression and use of antidepressive medicines during pregnancy on the methylation status of the IGF2 imprinted control regions in the offspring
A Soubry, SK Murphy, Z Huang, A Murtha, JM Schildkraut, RL Jirtle, F Wang, J Kurtzberg, W Demark-Wahnefried, MR Forman, C Hoyo
Clinical Epigenetics , 2011, DOI: 10.1186/1868-7083-3-2
Abstract: Epigenetic mechanisms are important for regulating gene expression and differentiation during early life. Recent studies have highlighted the possible impact of environmental factors on epigenetic characteristics during development. In utero exposure to chemicals, nutrition, or social factors may change the methylation status at CpG-rich regions of gene promoter regions, causing permanent modification of gene expression patterns [1-3]. Such alterations may lead to increased risk of chronic diseases, including mental disorders, diabetes, cardiovascular diseases and cancer [4-6].Maternal depression, and associated drug use are common exposures to the developing fetus. The prevalence of depression in pregnant women is greater than ten percent [7], and the rate of prescriptions for mood regulators reported among pregnant women in the U.S. has increased threefold, from 1998 to 2005 [8]. Co-occuring adverse factors include: inadequate nutrition intake or insufficient weight gain, and cigarette smoking [9]. It has been shown that in utero exposure to maternal depression adversely affect fetal growth [10,11], fetal neurobehavioral development, or childhood behavior [12-15]. Exposure to SSRIs (Selective Serotonin Reuptake Inhibitors) has been associated with congenital malformations [16-20], respiratory distress, or neurobehavioral symptoms in newborns [21,22]. As a consequence, treatment of psychiatric disorders during pregnancy is controversial; the fetus is either exposed to the psychotropic drugs or to the disease itself.The biological mechanisms behind the adverse fetal developmental consequences of antidepressant use of the mother or exposure to maternal depression are unclear. Evidence suggests that mood disorders or antidepressant medicines are associated with modulation of epigenetic regulation [23]. Adverse social environments can induce altered DNA methylation at the promoter of the glucocorticoid receptor gene in the rat hippocampus [24,25,2]. Aberrant methylatio
Compliance to long-term treatment of cardiologic patients with mild to moderate depression: ineffectiveness of antidepressive therapy with pirlindol in randomized study  [cached]
E.V. Strokova,E.A. Naumova,J.G. Shvarts
Rational Pharmacotherapy in Cardiology , 2012,
Abstract: Aim. To evaluate the influence of antidepressant therapy with pirlindol on compliance to the long-term treatment and quality of life in patients with cardiovascular diseases and mild to moderate depression.Material and methods. 61 patients with cardiovascular diseases and mild to moderate depression (according to Beck depression scale) were randomized into two groups. Patients of intervention group received pirlindol, while patients of control group did not receive this drug. Compliance to cardiovascular and antidepressant treatment were estimated in 3 and 6 months. Adverse reactions and patients self-assessment of their well-being and global satisfaction in treatmen were also registered.Results. 24 (75%), 2 (6%) and 0 patients of intervention group continue pirlindol treatment in 1, 3 and 6 months, respectively. In 3 months of observation patients of intervention group took drugs for cardiovascular diseases more often than these in control group (81% vs 72%, respectively, р<0.05), they also less frequently showed adverse reactions (56% vs 72%, respectively, p=0.01) and more often — improvement of their well-being (65% vs 50%, respectively, р=0.03). Compliance to cardiovascular therapy did not differ significantly in patients of both groups by the end the study.Conclusion. Antidepressant therapy with pirlindol did not influence compliance to long-term cardiovascular treatment in patients with cardiovascular diseases and mild to moderate depression, apparently because of low compliance to pirlindol therapy.
Depression in acromegaly treated with escitalopram and cognitive therapy
De Sousa Avinash
Indian Journal of Psychological Medicine , 2009,
Abstract: Depression is one of the commonest disorders encountered in general hospital psychiatry. Acromegaly is a condition with excessive growth hormone secretion that may at times present with oversychopathology. We present the case of a 33-year-old lady with depression and acromegaly that successfully resolved after treatment with escitalopram and cognitive therapy.
Hypertension and depression
Scalco, Andréia Zavaloni;Scalco, M?nica Zavaloni;Azul, Jo?o Batista Serro;Lotufo Neto, Francisco;
Clinics , 2005, DOI: 10.1590/S1807-59322005000300010
Abstract: despite the high prevalence of depression and hypertension, the relationship between the two diseases has received little attention. this paper reviews the epidemiological, pathophysiological, and prognostic aspects of this association, as well as its implications for treatment. a medline search was conducted using the following key words: depression, blood pressure, blood pressure variability, physical morbidity, hypertension, mood, stress, hypertension, antidepressive agents, and genetics, from 1980 to 2004. we found descriptions of increased prevalence of hypertension in depressed patients, increased prevalence of depression in hypertensive patients, association between depressive symptomatology and hypotension, and alteration of the circadian variation of blood pressure in depressed patients. there is considerable evidence suggesting that hyperreactivity of the sympathetic nervous system and genetic influences are the underlying mechanisms in the relationship between depression and hypertension. depression can negatively affect the course of hypertensive illness. additionally, the use of antidepressive agents can interfere with blood pressure control of patients with hypertension by inducing changes in blood pressure and orthostatic hypotension.
Ethnopharmacokinetic- and Activity-Guided Isolation of a New Antidepressive Compound from Fructus Aurantii Found in the Traditional Chinese Medicine Chaihu-Shugan-San: A New Approach and Its Application
Rong Fan,Xi Huang,Yang Wang,Xiao Chen,Ping Ren,Hui Ji,Ying Xie,Yingjin Zhang,Wei Huang,Xinjian Qiu,Zhaoqian Liu,Honghao Zhou,Lan Fan,Lichen Gao
Evidence-Based Complementary and Alternative Medicine , 2012, DOI: 10.1155/2012/607584
Abstract: Aims. We aimed to identify an antidepressive compound found in traditional Chinese medicine (TCM) by a new approach called ethnopharmacokinetic- and activity-guided isolation (EAGI). Methods. The new approach targets an unknown chromatographic peak produced by an absorbed compound found in oral Chaihu-Shugan-San (CSS) taken by patients with depression. Once the compound was isolated from Fructus Aurantii (FA), spectral data was employed to identify the compound. The effects of this compound, FA, and CSS on depressive behaviors were investigated. Results. The identified compound was merazin hydrate (MH) according to the new approach. MH, FA, and CSS significantly reduced immobility time and increased locomotor activity. The effects of MH, FA and CSS were similar to Fluoxetine at high doses. Conclusion. MH, a compound whose antidepressive effect is similar to FA and CSS, was isolated for the first time from FA via targeting its corresponding unknown chromatographic peak, and its antidepressive effect was compared with FA or CSS. These findings highlight the potential for drug R&D and pharmacological research of ∼100,000 TCMs.
Identifying endophenotypes of autism: a multivariate approach  [PDF]
Fermín Segovia,Juan M. Górriz,Javier Ramírez,Christophe Phillips,Simon Baron-Cohen,John Suckling
Frontiers in Computational Neuroscience , 2014, DOI: 10.3389/fncom.2014.00060
Abstract: The existence of an endophenotype of autism spectrum condition (ASC) has been recently suggested by several commentators. It can be estimated by finding differences between controls and people with ASC that are also present when comparing controls and the unaffected siblings of ASC individuals. In this work, we used a multivariate methodology applied on magnetic resonance images to look for such differences. The proposed procedure consists of combining a searchlight approach and a support vector machine classifier to identify the differences between three groups of participants in pairwise comparisons: controls, people with ASC and their unaffected siblings. Then we compared those differences selecting spatially collocated as candidate endophenotypes of ASC.
Antidepressive Therapie bei depressiven St rungen im Gefolge von Schlaganf llen  [PDF]
Hofmann P,Ebner C,Kapfhammer HP
Journal für Neurologie, Neurochirurgie und Psychiatrie , 2011,
Abstract: Die Depression nach einem Schlaganfall ist ein sehr h ufiges Ph nomen, die Implikationen sind vielf ltig. Vor allem die Verschlechterung der Gesamtprognose, aber auch der Rehabilitierbarkeit steht neben pers nlichem Leid im Vordergrund. Eine genaue Diagnostik und eine konsequente Therapie sind daher gefragt. Im Vordergrund stehen eindeutig psychopharmakologische Strategien mit Antidepressiva. Hier gibt es eine gute Evidenz vor allem hinsichtlich der selektiven Serotonin-Wiederaufnahmehemmer (SSRI). Nicht nur die antidepressive Wirksamkeit ist hier attraktiv, sondern auch die Perspektive, dass mit SSRI-Therapie weitere positive Aspekte (Reduktion schwerer Komplikationen) m glich sind. Es gibt darüber hinaus eindeutige Belege, dass bereits im Vorfeld, also unmittelbar nach dem Schlaganfall, mit einer pharmakoprophylaktischen Therapie begonnen werden kann, um eine Symptombildung zu verhindern. Wichtig ist vor allem der Aspekt, dass eine antidepressive Therapie in aller Regel auch eine Verbesserung der Kognition bedeutet! Trotz des eindeutig hirnorganischen Bezugs des Krankheitsgeschehens erweist sich eine Kombinationstherapie aus Antidepressiva und psychotherapeutischen Strategien als wirksam. Psychotherapie alleine ist bisher zu wenig untersucht, es gibt aber bereits erste ermutigende Ergebnisse.
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