Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Metabotropic glutamate receptors (mGluRs) belong to a family of G-protein coupled receptors involved in the modulation of fast excitatory transmission. In particular, the subtype-5 receptor (mGluR5) was found to be an attractive target for the treatment and diagnosis of variety of psychiatric and neurological disease including anxiety, depression, epilepsy, drug addiction, and Parkinson's disease. Positron emission tomography (PET) is a highly sensitive imaging technique that holds great potential for the diagnosis of a brain disorder. In the study published in the American Journal of Nuclear Medicine and Molecular Imaging, a (18)F labelled PET probe was developed targeting mGluR5. This paper represents the efforts and challenges on the design and development of novel PET tracers for mGluR5 imaging.
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PMID:PET imaging of metabotropic glutamate receptor subtype 5 (mGluR5). 2313

Schizophrenia is a chronic brain disorder comprising a range of clinical features, including positive and negative symptoms, cognitive dysfunction and mood symptoms (particularly depression and anxiety). The management of schizophrenia requires effective short- and long-term treatment with antipsychotic medication that is effective across these symptom domains, while being well tolerated over the long term. Asenapine is the first tetracyclic atypical antipsychotic to be licensed in the USA and several other countries outside Europe for the acute and maintenance treatment of schizophrenia in adults. It has a unique receptor-binding profile and a broad range of therapeutic effects. Since clinical trials are conducted under strict conditions in tightly defined patient populations, evidence of an agent's efficacy and tolerability under 'real-world' clinical practice conditions is also required. As in clinical trials, real-life case reports demonstrate that asenapine is effective in treating the positive symptoms of schizophrenia, both in the acute setting and for relapse prevention. It is also effective in treating negative symptoms and shows promise in the treatment of depressive symptoms associated with schizophrenia. Asenapine has a favourable tolerability profile, having a minimal impact on weight and metabolic parameters. As such, asenapine is valuable option for the treatment of schizophrenia in adults.
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PMID:Management of schizophrenia: clinical experience with asenapine. 2353 51

Neuroimaging data support the idea that schizophrenia is a brain disorder with altered brain structure and function. New resting-state functional connectivity techniques allow us to highlight synchronization of large-scale networks, such as the default-mode network (DMN) and salience network (SN). A large body of work suggests that disruption of these networks could give rise to specific schizophrenia symptoms. We examined the intra-network connectivity strength and gray matter content (GMC) of DMN and SN in 26 schizophrenia patients using resting-state functional magnetic resonance imaging and voxel-based morphometry. Resting-state data were analyzed with independent component analysis and dual-regression techniques. We reported reduced functional connectivity within both DMN and SN in patients with schizophrenia. Concerning the DMN, patients showed weaker connectivity in a cluster located in the right paracingulate cortex. Moreover, patients showed decreased GMC in this cluster. With regard to the SN, patients showed reduced connectivity in the left and right striatum. Decreased connectivity in the paracingulate cortex was correlated with difficulties in abstract thinking. The connectivity decrease in the left striatum was correlated with delusion and depression scores. Correlation between the connectivity of DMN frontal regions and difficulties in abstract thinking emphasizes the link between negative symptoms and the likely alteration of the frontal medial cortex in schizophrenia. Correlation between the connectivity of SN striatal regions and delusions supports the aberrant salience hypothesis. This work provides new insights into dysfunctional brain organization in schizophrenia and its contribution to specific schizophrenia symptoms.
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PMID:Links among resting-state default-mode network, salience network, and symptomatology in schizophrenia. 2372 17

Depression is a common brain disorder affecting about 350 million people worldwide. Although the pharmacological treatment currently available can produce benefits in the majority of cases, residual depressive symptoms, cognitive deficits, functional impairment, and increase in frequency of relapses are frequently present in unipolar and bipolar depressed patients correctly treated. In the last years, numerous evidences have demonstrated the involvement of endocannabinoid system in the pathophysiology of mood disorders. Considering the recent findings about the antidepressant effect of palmitoylethanolamide in animal model, we have hypothesized the potential antidepressant effect of this fatty acid amide in unipolar and bipolar depressed patients.
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PMID:Is there a role for palmitoylethanolamide in the treatment of depression? 2463 Aug 55

Alcohol dependence has traditionally been considered a brain disorder. Alteration in the composition of the gut microbiota has recently been shown to be present in psychiatric disorders, which suggests the possibility of gut-to-brain interactions in the development of alcohol dependence. The aim of the present study was to explore whether changes in gut permeability are linked to gut-microbiota composition and activity in alcohol-dependent subjects. We also investigated whether gut dysfunction is associated with the psychological symptoms of alcohol dependence. Finally, we tested the reversibility of the biological and behavioral parameters after a short-term detoxification program. We found that some, but not all, alcohol-dependent subjects developed gut leakiness, which was associated with higher scores of depression, anxiety, and alcohol craving after 3 wk of abstinence, which may be important psychological factors of relapse. Moreover, subjects with increased gut permeability also had altered composition and activity of the gut microbiota. These results suggest the existence of a gut-brain axis in alcohol dependence, which implicates the gut microbiota as an actor in the gut barrier and in behavioral disorders. Thus, the gut microbiota seems to be a previously unidentified target in the management of alcohol dependence.
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PMID:Intestinal permeability, gut-bacterial dysbiosis, and behavioral markers of alcohol-dependence severity. 2528 60

Depression is one of the most frequent causes of disability in the 21st century. Despite the many preclinical and clinical studies that have addressed this brain disorder, the pathophysiology of depression is not well understood and the available antidepressant drugs are therapeutically inadequate in many patients. In recent years, the potential role of lipid-derived molecules, particularly endocannabinoids (eCBs) and endovanilloids, has been highlighted in the pathogenesis of depression and in the action of antidepressants. There are many indications that the eCB/endovanilloid system is involved in the pathogenesis of depression, including the localization of receptors, modulation of monoaminergic transmission, inhibition of the stress axis and promotion of neuroplasticity in the brain. Preclinical pharmacological and genetic studies of eCBs in depression also suggest that facilitating the eCB system exerts antidepressant-like behavioral responses in rodents. In this article, we review the current knowledge of the role of the eCB/endovanilloid system in depression, as well as the effects of its ligands, models of depression and antidepressant drugs in preclinical and clinical settings.
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PMID:The endocannabinoid/endovanilloid system and depression. 2542 13

Migraine is a common, disabling, and undertreated episodic brain disorder that is more common in women than in men. Unbiased genome-wide association studies have identified 13 migraine-associated variants pointing at genes that cluster in pathways for glutamatergic neurotransmission, synaptic function, pain sensing, metalloproteinases, and the vasculature. The individual pathogenetic contribution of each gene variant is difficult to assess because of small effect sizes and complex interactions. Six genes with large effect sizes were identified in patients with rare monogenic migraine syndromes, in which hemiplegic migraine and non-hemiplegic migraine with or without aura are part of a wider clinical spectrum. Transgenic mouse models with human monogenic-migraine-syndrome gene mutations showed migraine-like features, increased glutamatergic neurotransmission, cerebral hyperexcitability, and enhanced susceptibility to cortical spreading depression, which is the electrophysiological correlate of aura and a putative trigger for migraine. Enhanced susceptibility to cortical spreading depression increased sensitivity to focal cerebral ischaemia, and blocking of cortical spreading depression improved stroke outcome in these mice. Changes in female hormone levels in these mice modulated cortical spreading depression susceptibility in much the same way that hormonal fluctuations affect migraine activity in patients. These findings confirm the multifactorial basis of migraine and might allow new prophylactic options to be developed, not only for migraine but potentially also for migraine-comorbid disorders such as epilepsy, depression, and stroke.
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PMID:Migraine pathophysiology: lessons from mouse models and human genetics. 2549 98

Computational neuroanatomical techniques that are used to evaluate the structural correlates of disorders in the brain typically measure regional differences in gray matter or white matter, or measure regional differences in the deformation fields required to warp individual datasets to a standard space. Our aim in this study was to combine measurements of regional tissue composition and of deformations in order to characterize a particular brain disorder (here, major depressive disorder). We use structural Magnetic Resonance Imaging (MRI) data from young adults in a first episode of depression, and from an age- and sex-matched group of non-depressed individuals, and create population gray matter (GM) and white matter (WM) tissue average templates using DARTEL groupwise registration. We obtained GM and WM tissue maps in the template space, along with the deformation fields required to co-register the DARTEL template and the GM and WM maps in the population. These three features, reflecting tissue composition and shape of the brain, were used within a joint independent-components analysis (jICA) to extract spatially independent joint sources and their corresponding modulation profiles. Coefficients of the modulation profiles were used to capture differences between depressed and non-depressed groups. The combination of hippocampal shape deformations and local composition of tissue (but neither shape nor local composition of tissue alone) was shown to discriminate reliably between individuals in a first episode of depression and healthy controls, suggesting that brain structural differences between depressed and non-depressed individuals do not simply reflect chronicity of the disorder but are there from the very outset.
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PMID:Fusion analysis of first episode depression: where brain shape deformations meet local composition of tissue. 2561 Jul 73

Migraine is a common brain disorder characterized by recurrent attacks of severe headaches and other neurological symptoms. In one-third of patients headaches are accompanied by auras, which consist of transient visual and sensory disturbances, believed to be caused by cortical spreading depression (CSD). CSD is characterized by a wave of neuronal and glial depolarization with concomitant changes in metabolite concentrations in the brain and cerebrospinal fluid. It remains unknown whether CSD-induced brain metabolic changes can be captured outside the central nervous system, i.e., in peripheral fluids. This study investigated plasma metabolic changes in transgenic mice that harbor a gene mutation in voltage-gated CaV2.1 Ca(2+) channels previously identified in patients with familial hemiplegic migraine, a subtype of migraine with auras. The use of a mouse model allows investigation of molecular changes occurring shortly after CSD, which is notoriously difficult in patients. Capillary electrophoresis - mass spectrometry was used for the analysis of plasma samples to obtain, for the first time, a comprehensive view of molecular changes immediately after experimentally induced CSD. Multivariate data analysis showed a clear distinction between profiles of transgenic and wild-type animals after CSD. Two metabolites considered important for this discrimination were tentatively identified as being lysine and its by-product pipecolic acid with additional evidence provided by hydrophilic interaction chromatography combined with tandem mass spectrometry. The changed metabolites suggest a compensatory increase in GABAergic neurotransmission upon enhanced excitatory neurotransmission. These results show that CSD induces metabolic remodeling in transgenic migraine mice that can be captured and measured in plasma.
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PMID:Plasma metabolic profiling after cortical spreading depression in a transgenic mouse model of hemiplegic migraine by capillary electrophoresis--mass spectrometry. 2585 90

Depression is a brain disorder characterized by severe emotional, cognitive, neuroendocrine and somatic dysfunction. Although the latest generation of antidepressant drugs has improved clinical efficacy and safety, the onset of their clinical effect is significantly delayed after treatment commencement, and a large number of patients exhibit inadequate response to these drugs and/or depression relapse even following initially successful treatment. It is therefore essential to develop new antidepressant drugs and/or adjuncts to existing ones. Recent studies suggest that the beneficial effect of antidepressant drugs is mediated, at least in part, via stimulation of adult hippocampal neurogenesis and subsequent increase in hippocampal plasticity. Since the stimulatory effect of antidepressant drugs on hippocampal neurogenesis involves G-protein coupled receptors (GPCR) and voltage-dependent calcium channels (VDCC), greater efficacy may be available if future antidepressant drugs directly target these specific GPCR and VDCC. The potential advantages and limitations of these treatment strategies are discussed in the article.
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PMID:Cellular and molecular mechanisms underlying the treatment of depression: focusing on hippocampal G-protein-coupled receptors and voltage-dependent calcium channels. 2592 50


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