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)

The objective of the study is to determine the effects of motivational interviewing (MI), a novel technique of behavioral counseling to promote exercise, on pain and physical function in patients with fibromyalgia (FMS). Patients who met the American College of Rheumatology criteria for FMS and had a visual analog pain score of > or =6 were enrolled in a single group intervention pilot study. Participants received two supervised exercise sessions and an exercise prescription. Thereafter, six exercise-based MI phone calls were made over a 10-week period. Assessments were done at baseline, week 12 (immediate postintervention) and week 30 (follow-up). The primary endpoints were changes from baseline in the fibromyalgia impact questionnaire (FIQ)-pain and physical impairment at week 30. Secondary measures were brief pain inventory (BPI)-pain severity and BPI-pain interference, the number of exercise minutes (NEM) per week, and the arthritis impact measurement scale (AIMS)-depression. The 19 enrolled female participants had a mean age of 52.2 +/- 9.1 years, mean disease duration of 7.5 +/- 5.0 years, and a mean FIQ-pain score of 7.7 +/- 1.4. By week 30, there was significant improvement in both FIQ-pain (-2.6 +/- 2.6, p < 0.001) and FIQ-physical impairment (-1.3 +/- 2.1, p = 0.01). Likewise, BPI-pain severity and pain interference were reduced by -2.4 +/- 2.1 (p < 0.001) and -2.4 +/- 2.0 (p < 0.001), respectively. While the median NEM per week increased from 0 to 32 min (p = 0.001) at week 30, AIMS-depression score was unchanged. In this pilot study, we conclude that telephone-delivered MI to promote exercise was associated with an improvement in patient's level of pain and physical impairment.
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PMID:Exercise-based motivational interviewing for female patients with fibromyalgia: a case series. 1731 Feb 68

Subtotal lesion of the inferior olive (IO) achieved by treating experimental animals with 3-acetylpyridine (3AP) induces partial Purkinje cells (PCs) deafferentation that leads to PC hyperactivity and new spine formation. Coincidentally, the olivary terminals belonging to the few survived olivary neurons undergo an extensive collateral sprouting resulting in reinnervation of the neighboring denervated PCs. We obtained chemical deafferentation of PCs in adult rats (body weight, 120-170 g; age, 35-40 days) by a single intraperitoneal injection of 3AP (65 mg/kg body weight), and as early as 3 days after 3AP treatment, important morphological changes could be observed on PCs. Mitogen-activated protein kinase (MAPK) cascades and more specifically extracellular signal-regulated kinases 1/2 (ERK1/2) play a critical role in the signaling events underlying synaptic plasticity. For instance, long-term depression (LTD) in the adult hippocampus and long-term potentiation (LTP) in cerebellum both involve ERK activation. Since PCs deprived of their climbing fibers (CFs) afferents initiate an intensive remodeling of the spines and rapid recall of the remaining CFs, it prompted us to see whether the observed phenomena correlated with MAPK and Akt activation. Immunohistochemistry and Western blotting were done at various time points after 3AP application (from 24 h to 6 days), as the exact dynamics of CF loss is not precisely known. As judged by Western blotting, there was no increase of activated ERK in the cerebellum. However, immunohistochemistry revealed increased ERK phosphorylation in the "pinceaux" of basket cells in 3AP animals. Similarly, stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK), p38 MAPK, and Akt activation were also studied by means of Western blotting and immunohistochemistry. Upon 3AP treatment no changes in phosphorylation status could be seen in the different kinases subjected to analysis. Our results suggest that activation of MAPK and Akt cascades is not essential in this model of neuronal plasticity.
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PMID:Intensive remodeling of Purkinje cell spines after climbing fibers deafferentation does not involve MAPK and Akt activation. 1740 34

The receptor tyrosine kinase product of the anaplastic lymphoma kinase (ALK) gene has been implicated in oncogenesis as a product of several chromosomal translocations, although its endogeneous role in the hematopoietic and neural systems has remained poorly understood. We describe that the generation of animals homozygous for a deletion of the ALK tyrosine kinase domain leads to alterations in adult brain function. Evaluation of adult ALK homozygotes (HOs) revealed an age-dependent increase in basal hippocampal progenitor proliferation and alterations in behavioral tests consistent with a role for this receptor in the adult brain. ALK HO animals displayed an increased struggle time in the tail suspension test and the Porsolt swim test and enhanced performance in a novel object-recognition test. Neurochemical analysis demonstrates an increase in basal dopaminergic signalling selectively within the frontal cortex. Altogether, these results suggest that ALK functions in the adult brain to regulate the function of the frontal cortex and hippocampus and identifies ALK as a new target for psychiatric indications, such as schizophrenia and depression, with an underlying deregulated monoaminergic signalling.
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PMID:Behavioral and neurochemical alterations in mice deficient in anaplastic lymphoma kinase suggest therapeutic potential for psychiatric indications. 1748 25

Desipramine (DP) is a tricyclic antidepressant used for treating depression and numerous other psychiatric disorders. Recent studies have shown that DP can promote neurogenesis and improve the survival rate of hippocampal neurons. However, whether DP induces neuroprotection or promotes the differentiation of neural stem cells (NSCs) needs to be elucidated. In this study, we cultured NSCs derived from the hippocampal tissues of adult rats as an in vitro model to evaluate the modulation effect of DP on NSCs. First, we demonstrated that the expression of Bcl-2 mRNA and nestin in 2 microM DP-treated NSCs were up-regulated and detected by real-time reverse transcriptase polymerase chain reaction (RT-PCR). The results of Western blotting and immunofluorescent study confirmed that Bcl-2 protein expression was significantly increased in Day 3 DP-treated NSCs. Using the Bcl-2 small interfering RNA (siRNA) method, our results further showed that DP protects the lipopolysaccharide (LPS)-induced apoptosis in NSCs, in part by activating the expression of Bcl-2. Furthermore, DP treatment significantly inhibited the induction of proinflammatory factor interleukin (IL)-1beta, IL-6, and tumor necrosis factor-alpha in the culture medium of LPS-treated NSCs mediated by Bcl-2 modulation. The results of high performance liquid chromatography coupled to electrochemical detection further confirmed that DP significantly increased the functional production of serotonin (26+/-3.5 microM, DP-treated 96 h) and noradrenaline (50+/-8.9 microM, DP-treated 96 h) in NSCs through activation of the MAPK/ERK pathway and partially mediated by Bcl-2. In conclusion, the present results indicate that DP can increase neuroprotection ability by inhibiting the LPS-induced inflammatory process in NSCs via the modulation of Bcl-2 expression, as confirmed by the siRNA method.
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PMID:Desipramine activated Bcl-2 expression and inhibited lipopolysaccharide-induced apoptosis in hippocampus-derived adult neural stem cells. 1751 May 25

Cytokines are involved both in various immune reactions and in controlling certain events in the central nervous system (CNS). In our earlier studies, it was shown that monoamine neurotransmitters, released in stress situations, represent a tonic sympathetic control on cytokine production and on the balance of proinflammatory/anti-inflammatory cytokines. Basic and clinical studies have provided evidence that the biophase level of monoamines, determined by the balance of their release and uptake, is involved in the pathophysiology and treatment of depression, while inflammatory mediators might also have a role in its etiology. In this work, we studied the role of changes in norepinephrine (NE) level on the lipopolysaccharide (LPS) evoked tumor necrosis factor (TNF)-alpha and interleukin (IL)-10 response both in the plasma and in the hippocampus of mice. We demonstrated that the LPS induced TNF-alpha response is in direct correlation with the biophase level of NE, as it is significantly higher when the release of NE of vesicular origin was completely inhibited in an animal model of depression (reserpine treatment) and it is significantly lower in the case of increasing biophase levels of NE by genetic (NET-KO) or chemical (desipramine) disruption of NE reuptake. IL-10 was changed inversely to TNF-alpha levels only in the desipramine-treated animals. Our results showed that depression is related both to changes in peripheral and in hippocampal inflammatory cytokine production and to monoamine neurotransmitter levels. Since several anti-inflammatory drugs also have antidepressant effects, we hypothesized that antidepressants are also able to modulate the LPS-induced inflammatory response, which might contribute to their antidepressant effect.
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PMID:The catecholamine cytokine balance: interaction between the brain and the immune system. 1758 82

Current therapies to treat skeletal fracture pain are extremely limited. Some non-steroidal anti-inflammatory drugs have been shown to inhibit bone healing and opiates induce cognitive dysfunction and respiratory depression which are especially problematic in the elderly suffering from osteoporotic fractures. In the present report, we developed a closed femur fracture pain model in the mouse where skeletal pain behaviors such as flinching and guarding of the fractured limb are reversed by 10mg/kg morphine. Using this model we showed that the administration of a monoclonal antibody against nerve growth factor (anti-NGF) reduced fracture-induced pain-related behaviors by over 50%. Treatment with anti-NGF reduced c-Fos and dynorphin up-regulation in the spinal cord at day 2 post-fracture. However, anti-NGF treatment did not reduce p-ERK and c-Fos expression at 20 and 90 min, respectively, following fracture. This suggests NGF is involved in maintenance but not the acute generation of fracture pain. Anti-NGF therapy did not inhibit bone healing as measured by callus formation, bridging of the fracture site or mechanical strength of the bone. As the anti-NGF antibody does not appreciably cross the blood-brain barrier, the present data suggest that the anti-hyperalgesic action of anti-NGF therapy results from blockade of activation and/or sensitization of the CGRP/trkA positive fibers that normally constitute the majority of sensory fibers that innervate the bone. These results demonstrate that NGF plays a significant role in driving fracture pain and that NGF sequestering therapies may be efficacious in attenuating this pain.
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PMID:Nerve growth factor sequestering therapy attenuates non-malignant skeletal pain following fracture. 1769 23

Neuronal monoamine transporters (MATs) are involved in the pathophysiology and treatment of mental health conditions such as depression, attention deficit hyperactivity disorder, substance abuse and neurodegenerative disorders including Alzheimer's disease and Parkinson's disease. Various structural classes of compounds have been synthesized and tested in vitro for activity against transporters of three monoamine signaling molecules: noradrenaline (NET); serotonin (SERT) and dopamine (DAT). We have developed and validated a number of pharmacophore models describing the interaction of two classes of compounds with each of these three MATs. These pharmacophores explain the selectivity of binding to the MATs for various compound classes and have been used to search in silico databases for novel, potentially selective ligands. These ligands, after confirmation of their activities, will provide tools for investigating the function of MATs as well as the potential for new therapeutic agents in mental health applications. The database searches also retrieved close analogues of known MAT ligands, further validating the approach.
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PMID:Pharmacophore design and database searching for selective monoamine neurotransmitter transporter ligands. 1802 78

Opioid-like medications (OLM) are commonly used by patients with various types of chronic pain, but their long-term benefit is questionable. Electroacupuncture (EA) has been previously shown beneficial in reducing post-operative acute OLM consumption. In this pilot randomized controlled trial, the effect of EA on OLM usage and associated side effects in chronic pain patients was evaluated. After a two-week baseline assessment, participants using OLM for their non-malignant chronic pain were randomly assigned to receive either real EA (REA, n=17) or sham EA (SEA, n=18) treatment twice weekly for 6 weeks before entering a 12-week follow-up. Pain, OLM consumption and their side effects were recorded daily. Participants also completed the McGill Pain Questionnaire (MPQ), SF-36 and Beck Depression Inventory (BDI) at baseline, and at the 5th, 8th, 12th, 16th and 20th week. Nine participants withdrew during the treatment period with another three during the follow-up period. Intention to treat analysis was applied. At the end of treatment period, reductions of OLM consumption in REA and SEA were 39% and 25%, respectively (p=0.056), but this effect did not last more than 8 weeks after treatment. There was no difference between the two groups with respect to reduction of side effects and pain and the improvement of depression and quality of life. In conclusion, REA demonstrates promising short-term reduction of OLM for participants with chronic non-malignant pain, but such effect needs to be confirmed by trials with adequate sample sizes.
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PMID:The effect of electroacupuncture on opioid-like medication consumption by chronic pain patients: a pilot randomized controlled clinical trial. 1803 66

The fibroblast growth factor (FGF) system has previously been found to be altered in post-mortem brains of individuals with major depressive disorder (MDD). The present study tested whether the FGF system is altered following acute social defeat. Rats were exposed to four consecutive days of either a social defeat paradigm or novel cages. Animals were sacrificed after the last social defeat session and gene expression was assessed in the hippocampus by mRNA in situ hybridization. Molecular components of the FGF system were significantly downregulated following social defeat. Specifically, FGF2 and FGFR1 mRNA expression was decreased in various subfields of the hippocampus. Decreased tone of the FGF system following an acute social stressor is congruent with human post-mortem results of FGF system downregulation in depression. These findings suggest that modulating the FGF system may have therapeutic value in the treatment of MDD.
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PMID:The fibroblast growth factor system is downregulated following social defeat. 1806 49

Unipolar major depressive disorder (MDD) is a prevalent, disabling condition with multiple genetic and environmental factors impacting disease risk. The diagnosis of MDD relies on a cumulative measure derived from multiple trait dimensions and alone is limited in elucidating MDD genetic determinants. We and others have proposed that MDD may be better dissected using paradigms that assess how specific genes associate with component features of MDD. This within-disease design requires both a well-phenotyped cohort and a robust statistical approach that retains power with multiple tests of genetic association. In the present study, common polymorphic variants of genes related to central monoaminergic and cholinergic pathways that previous studies align with functional change in vitro or depression associations in vivo were genotyped in 110 individuals with unipolar MDD. Subphenotypic characteristics were examined using responses to individual items assessed with the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (DSM IV), the 17-item Hamilton Rating Scale for Depression (HAM-D) and the NEO Five Factor Inventory. Multivariate Permutation Testing (MPT) was used to infer genotype-phenotype relationships underlying dimensional findings within clinical categories. MPT analyses show significant associations of the norepinephrine transporter (NET, SLC6A2) -182 T/C (rs2242446) with recurrent depression [odds ratio, OR = 4.15 (1.91-9.02)], NET -3081 A/T (rs28386840) with increase in appetite [OR = 3.58 (1.53-8.39)] and the presynaptic choline transporter (CHT, SLC5A7) Ile89Val (rs1013940) with HAM-D-17 total score {i.e. overall depression severity [OR = 2.74 (1.05-7.18)]}. These relationships illustrate an approach to the elucidation of gene influences on trait components of MDD and with replication, may help identify MDD subpopulations that can benefit from more targeted pharmacotherapy.
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PMID:Multivariate permutation analysis associates multiple polymorphisms with subphenotypes of major depression. 1808 10


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