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rTMS treatment for depression in Parkinson`s disease increases BOLD responses in the left prefrontal cortex

CARDOSO, Ellison Fernando; FREGNI, Felipe; MAIA, Fernanda Martins; BOGGIO, Paulo S.; MYCZKOWSKI, Martin Luis; CORACINI, Karen; VIEIRA, Adriana Lopes; MELO, Luciano M.; SATO, Joao R.; MARCOLIN, Marco Antonio; RIGONATTI, Sergio P.; CRUZ JR., Antonio Cesario
Fonte: CAMBRIDGE UNIV PRESS Publicador: CAMBRIDGE UNIV PRESS
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
56.26%
The mechanisms underlying the effects of antidepressant treatment in patients with Parkinson`s disease (PD) are unclear. The neural changes after successful therapy investigated by neuroimaging methods can give insights into the mechanisms of action related to a specific treatment choice. To study the mechanisms of neural modulation of repetitive transcranial magnetic Stimulation (rTMS) and fluoxetine, 21 PD depressed patients were randomized into only two active treatment groups for 4 wk: active rTMS over left dorsolateral prefrontal cortex (DLPFC) (5 Hz rTMS; 120% motor threshold) with placebo pill and sham rTMS with fluoxetine 20mg/d. Event-related functional magnetic resonance imaging (fMRI) with emotional stimuli was performed before and after treatment - in two sessions (test and re-test) at each time-point. The two groups of treatment had a significant, similar mood improvement. After rTMS treatment, there were brain activity decreases in left fusiform gyrus, cerebellum and right DLPFC and brain activity increases in left DLPFC and anterior cingulate gyrus compared to baseline. In contrast, after fluoxetine treatment, there were brain activity increases in right premotor and right medial prefrontal cortex. There was a significant interaction effect between groups vs. time in the left medial prefrontal cortex...

Variation in the Gene Encoding the Serotonin 2A Receptor Is Associated with Outcome of Antidepressant Treatment

McMahon, Francis J.; Buervenich, Silvia; Charney, Dennis; Lipsky, Robert; Rush, A. John; Wilson, Alexander F.; Sorant, Alexa J. M.; Papanicolaou, George J.; Laje, Gonzalo; Fava, Maurizio; Trivedi, Madhukar H.; Wisniewski, Stephen R.; Manji, Husseini
Fonte: The American Society of Human Genetics Publicador: The American Society of Human Genetics
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
46.37%
Depressive disorders account for a large and increasing global burden of disease. Although the condition of many patients improves with medication, only a minority experience full remission, and patients whose condition responds to one medication may not have a response to others. Individual variation in antidepressant treatment outcome is, at present, unpredictable but may have a partial genetic basis. We searched for genetic predictors of treatment outcome in 1,953 patients with major depressive disorder who were treated with the antidepressant citalopram in the Sequenced Treatment Alternatives for Depression (STAR*D) study and were prospectively assessed. In a split-sample design, a selection of 68 candidate genes was genotyped, with 768 single-nucleotide–polymorphism markers chosen to detect common genetic variation. We detected significant and reproducible association between treatment outcome and a marker in HTR2A (P range 1×10-6 to 3.7×10-5 in the total sample). Other markers in HTR2A also showed evidence of association with treatment outcome in the total sample. HTR2A encodes the serotonin 2A receptor, which is downregulated by citalopram. Participants who were homozygous for the A allele had an 18% reduction in absolute risk of having no response to treatment...

Regional Alterations in the Endocannabinoid System in an Animal Model of Depression: Effects of Concurrent Antidepressant Treatment

Hill, Matthew N.; Carrier, Erica J.; McLaughlin, Ryan J.; Morrish, Anna C.; Meier, Sarah E.; Hillard, Cecilia J.; Gorzalka, Boris B.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
46.33%
It has been suggested that disturbances in endocannabinoid signaling contribute to the development of depressive illness; however, at present there is insufficient evidence to allow for a full understanding of this role. To further this understanding, we performed an analysis of the endocannabinoid system in an animal model of depression. Male rats exposed to chronic, unpredictable stress (CUS) for 21 days exhibited a reduction in sexual motivation, consistent with the hypothesis that CUS in rats induces depression-like symptoms. We determined the effects of CUS, with or without concurrent treatment with the antidepressant imipramine (10 mg/kg), on CP55940 binding to the cannabinoid CB1 receptor; whole tissue endocannabinoid content; and fatty acid amide hydrolase (FAAH) activity in the prefrontal cortex, hippocampus, hypothalamus, amygdala, midbrain and ventral striatum. Exposure to CUS resulted in a significant increase in CB1 receptor binding site density in the prefrontal cortex and a decrease in CB1 receptor binding site density in the hippocampus, hypothalamus and ventral striatum. Except in the hippocampus, these CUS-induced alterations in CB1 receptor binding site density were attenuated by concurrent antidepressant treatment. CUS alone produced a significant reduction in N-arachidonylethanolamine (anandamide) content in every brain region examined...

The Effects of Antidepressant Treatment on Serum Cytokines and Nutritional Status in Hemodialysis Patients

Lee, Sang-Kyu; Lee, Hong-Seock; Lee, Tae-Byeong; Kim, Do-Hoon; Koo, Ja-Ryong; Kim, Yong-Ku; Son, Bong-Ki
Fonte: The Korean Academy of Medical Sciences Publicador: The Korean Academy of Medical Sciences
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
46.35%
The aim of this study was to investigate the effects of antidepressant treatment on serum cytokines and nutritional status in hemodialysis patients. Twenty-eight hemodialysis patients with a depressed mood were given 20 mg of fluoxetine for 8 weeks. The degree of depressive symptoms, the serum levels of interleukin-1β, interleukin-2, interleukin-6, tumor necrosis factor-α, c-reactive protein, and markers of nutritional status were assessed at baseline and after treatment. The outcome was assessed in terms of response to treatment (>50% reduction in the score of the Hamilton depression rating scale). Antidepressant treatment decreased the serum level of interleukin-1β in both response and nonresponse groups, and increased the serum level of interleukin-6 only in the response group. At baseline, the level of interleukin-6 in the response group was lower than in the nonresponse group. Antidepressant treatment also increased fat distribution significantly in the response group which might have slightly improved the nutritional status. This study suggests that antidepressant treatment improve depressive symptoms and may affect immunological functions and nutritional status in chronic hemodialysis patients with depression.

The Roles of BDNF in the Pathophysiology of Major Depression and in Antidepressant Treatment

Lee, Bun-Hee; Kim, Yong-Ku
Fonte: Korean Neuropsychiatric Association Publicador: Korean Neuropsychiatric Association
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
46.33%
Neurotrophic factors are critical regulators of the formation and plasticity of neuronal networks. Brain-derived neurotrophic factor (BDNF) is abundant in the brain and periphery, and is found in both human serum and plasma. Animal studies have demonstrated that stress reduces BDNF expression or activity in the hippocampus and that this reduction can be prevented by treatment with antidepressant drugs. A similar change in BDNF activity occurs in the brain of patients with major depression disorder (MDD). Recently, clinical studies have indicated that serum or plasma BDNF levels are decreased in untreated MDD patients. Antidepressant treatment for at least four weeks can restore the decreased BDNF function up to the normal value. Therefore, MDD is associated with impaired neuronal plasticity. Suicidal behavior can be a consequence of severe impaired neuronal plasticity in the brain. Antidepressant treatment promotes increased BDNF activity as well as several forms of neuronal plasticity, including neurogenesis, synaptogenesis and neuronal maturation. BDNF could also play an important role in the modulation of neuronal networks. Such a neuronal plastic change can positively influence mood or recover depressed mood. These alterations of BDNF levels or neuronal plasticity in MDD patients before and after antidepressant treatment can be measured through the examination of serum or plasma BDNF concentrations. BDNF levels can therefore be useful markers for clinical response or improvement of depressive symptoms...

Differential Effects of Chronic Antidepressant Treatment on Swim Stress- and Fluoxetine-Induced Secretion of Corticosterone and Progesterone1

DUNCAN, GARY E.; KNAPP, DARIN J.; CARSON, STANLEY W.; BREESE, GEORGE R.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /05/1998 Português
Relevância na Pesquisa
46.46%
Hypersecretion of cortisol occurs in numerous patients with major depression and normalizes with clinical recovery during the course of chronic antidepressant treatment. These clinical data suggest that investigation of the effects of antidepressant treatments on the regulation of the brain-pituitary-adrenal axis may assist in elucidating the therapeutic basis of antidepressant actions. In the present investigation, both swim stress and acute fluoxetine challenge increased release of corticosterone and progesterone to reflect an activation of the brain pituitary-adrenal axis. The effects of chronic antidepressant treatment (21 days) on corticosterone and progesterone secretion induced by these challenges were investigated. Chronic fluoxetine treatment (5 mg/kg/day) completely blocked the increased secretion of corticosterone and progesterone in response to the acute fluoxetine challenge. Chronic treatment with desipramine, imipramine or amytriptyline (15 mg/kg/day) also markedly attenuated fluoxetine-induced corticosterone and progesterone secretion. However, chronic treatment with the monoamine oxidase inhibitors, phenelzine (5 mg/kg) and tranylcypromine (5 mg/kg), did not affect this hormonal response to acute fluoxetine challenge. Plasma levels of fluoxetine after acute challenge were not significantly different for the various chronic antidepressant treatment conditions from the chronic saline controls; therefore...

The Expression of VGF is Reduced in Leukocytes of Depressed Patients and it is Restored by Effective Antidepressant Treatment

Cattaneo, Annamaria; Sesta, Antonella; Calabrese, Francesca; Nielsen, Gabriela; Riva, Marco Andrea; Gennarelli, Massimo
Fonte: Nature Publishing Group Publicador: Nature Publishing Group
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
46.36%
Major depression is a disease characterized by an inability of neuronal systems to show appropriate adaptive plasticity especially under challenging conditions, such as stress. Conversely, pharmacological intervention may normalize such defects through the modulation of factors that might act in concert for the functional recovery of depressed patients, like the neuropeptide VGF, which has previously shown to possess antidepressant like activity. We analyzed VGF mRNA levels in the brain of rodents exposed to stress or treated with antidepressant drugs. In addition, we assessed VGF expression in leukocytes obtained from 25 drug-free depressed patients before and during antidepressant treatment. We found a persistent reduction of VGF expression after exposure to prenatal stress and an upregulation of its levels following chronic treatment with different antidepressant drugs. Moreover, VGF mRNA levels were significantly reduced in drug-free depressed patients, as compared with controls, and were modulated in response to effective antidepressant treatment. Our data provide further support to the role of VGF in mood disorders and suggest that VGF could be a more specific biomarker for treatment responsiveness.

Benzodiazepines and adequacy of initial antidepressant treatment for depression

Pfeiffer, Paul N.; Ganoczy, Dara; Zivin, Kara; Valenstein, Marcia
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /06/2011 Português
Relevância na Pesquisa
46.46%
In short term efficacy studies, co-prescription of a benzodiazepine improves first-month adherence and response to antidepressant treatment. We used Veterans Health Administration (VHA) data to examine the impact of co-prescribed benzodiazepines on initial antidepressant adherence in routine clinical practice and the risks of long-term benzodiazepine use, abuse, and dependence. Our study population was 43,915 VHA patients diagnosed with depression and started on an antidepressant between October 2006 and September 2007. Using logistic regression adjusting for demographic and clinical covariates, we predicted the likelihood that patients received antidepressant treatment for an adequate duration (90 days) with our primary independent variable of interest being receipt of a benzodiazepine on the same day as the antidepressant start. We also assessed the frequency and characteristics of patients whose benzodiazepine use persisted for one year or who were diagnosed with anxiolytic abuse or dependence after receiving combined treatment. The adjusted probability of receiving antidepressant treatment of adequate duration was 42.4% for patients who received a benzodiazepine with their initial antidepressant compared to 39.3% for patients initially treated with an antidepressant alone (p < 0.001). Among patients who received combined treatment...

Genome-wide approaches to antidepressant treatment: working towards understanding and predicting response

Hodgson, Karen; Mufti, Shaista Jeelani; Uher, Rudolf; McGuffin, Peter
Fonte: BioMed Central Publicador: BioMed Central
Tipo: Artigo de Revista Científica
Publicado em 27/06/2012 Português
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46.37%
Antidepressants are among the most commonly prescribed drugs, and a range of medications are available. However, treatment response to a particular drug varies greatly between patients, with only 30% of patients responding well to the first treatment administered. Given evidence that antidepressant treatment response is a heritable trait, together with technological advances in genetic research, three recently published genome-wide investigations into antidepressant responses have examined the determinants of variability in treatment outcomes between depressed patients. Here, we review these studies within the context of wider research efforts to identify treatment response predictors. Some interesting genes have been implicated, but no variants have yet been robustly and reliably linked to response. This may suggest that genetic effect sizes are smaller than originally anticipated. Candidate gene approaches in these samples have lent support to the involvement of serotonergic, glutamatergic and stress-response systems in treatment response, although corroborative evidence from genome-wide analyses indicates these results should be interpreted cautiously. Closer examination of antidepressant response, considering it as a complex trait...

Does prophylactic antidepressant treatment boost interferon-alpha treatment completion in HCV?

Rowan, Paul J
Fonte: Baishideng Publishing Group Co., Limited Publicador: Baishideng Publishing Group Co., Limited
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
46.45%
Depression is often a side effect of interferon-alpha treatment for hepatitis C, and is recognized as a cause for treatment discontinuation. When detected, antidepressant treatment begins promptly. In contrast to this rescue approach, prophylactic antidepressant treatment has been considered as a superior approach. While studies indicate that depression is lower with prophylaxis, no study has prospectively evaluated the degree that treatment completion might be boosted by the prophylactic strategy. A structured literature search was conducted to discover all trials of antidepressant prophylaxis for patients undergoing antiviral treatment for chronic hepatitis C. Selection criteria included: antidepressant prophylaxis study; report of depression treatment outcome; report of numbers discontinuing and reason for discontinuation (including any of the following: discontinuation data for medical side effects (i.e., thrombocytopenia); discontinuation due to lack of antiviral response; discontinuation due to lack of antidepressant effect; discontinuation due to antidepressant side effects; discontinuation due to patient preference; discontinuation due to loss to follow-up; or unspecified discontinuation). Across the studies, total enrollees were determined for the prophylaxis arms and the rescue arms...

Resistance to antidepressant treatment is associated with polymorphisms in the leptin gene, decreased leptin mRNA expression, and decreased leptin serum levels

Kloiber, Stefan; Ripke, Stephan; Kohli, Martin A.; Reppermund, Simone; Salyakina, Daria; Uher, Rudolf; McGuffin, Peter; Perlis, Roy H.; Hamilton, Steven P.; Pütz, Benno; Hennings, Johannes; Brückl, Tanja; Klengel, Torsten; Bettecken, Thomas; Ising, Marc
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
46.41%
Leptin, a peptide hormone from adipose tissue and key player in weight regulation, has been suggested to be involved in sleep and cognition and to exert antidepressant-like effects, presumably via its action on the HPA-axis and hippocampal function. This led us to investigate whether genetic variants in the leptin gene, the level of leptin mRNA-expression and leptin serum concentrations are associated with response to antidepressant treatment. Our sample consisted of inpatients from the Munich Antidepressant Response Signature (MARS) project with weekly Hamilton Depression ratings, divided into two subsamples. In the exploratory sample (n=251) 17 single nucleotide polymorphisms (SNPs) covering the leptin gene region were genotyped. We found significant associations of several SNPs with impaired antidepressant treatment outcome and impaired cognitive performance after correction for multiple testing. The SNP (rs10487506) showing the highest association with treatment response (p=3.9 × 10−5) was analyzed in the replication sample (n=358) and the association could be verified (p=0.021) with response to tricyclic antidepressants. In an additional meta-analysis combining results from the MARS study with data from the Genome-based Therapeutic Drugs for Depression (GENDEP) and the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) studies...

The effects of antenatal depression and antidepressant treatment on placental gene expression

Olivier, Jocelien D. A.; Åkerud, Helena; Skalkidou, Alkistis; Kaihola, Helena; Sundström-Poromaa, Inger
Fonte: Frontiers Media S.A. Publicador: Frontiers Media S.A.
Tipo: Artigo de Revista Científica
Publicado em 13/01/2015 Português
Relevância na Pesquisa
46.36%
The effects of antenatal depression and antidepressant treatment during pregnancy on both mother and child are vigorously studied, but the underlying biology for these effects is largely unknown. The placenta plays a crucial role in the growth and development of the fetus. We performed a gene expression study on the fetal side of the placenta to investigate gene expression patterns in mothers with antenatal depression and in mothers using antidepressant treatment during pregnancy. Placental samples from mothers with normal pregnancies, from mothers with antenatal depression, and from mothers using antidepressants were collected. We performed a pilot microarray study to investigate alterations in the gene expression and selected several genes from the microarray for biological validation with qPCR in a larger sample. In mothers with antenatal depression 108 genes were differentially expressed, whereas 109 genes were differentially expressed in those using antidepressants. Validation of the microarray revealed more robust gene expression differences in the seven genes picked for confirmation in antidepressant-treated women than in depressed women. Among the genes that were validated ROCK2 and C12orf39 were differentially expressed in both depressed and antidepressant-treated women...

A Longitudinal Functional Neuroimaging Study in Medication-Naïve Depression after Antidepressant Treatment

Tomioka, Hiroi; Yamagata, Bun; Kawasaki, Shingo; Pu, Shenghong; Iwanami, Akira; Hirano, Jinichi; Nakagome, Kazuyuki; Mimura, Masaru
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 18/03/2015 Português
Relevância na Pesquisa
46.37%
Recent studies have indicated the potential clinical use of near infrared spectroscopy (NIRS) as a tool in assisting the diagnosis of major depressive disorder (MDD); however, it is still unclear whether NIRS signal changes during cognitive task are state- or trait-dependent, and whether NIRS could be a neural predictor of treatment response. Therefore, we conducted a longitudinal study to explore frontal haemodynamic changes following antidepressant treatment in medication-naïve MDD using 52-channel NIRS. This study included 25 medication-naïve individuals with MDD and 62 healthy controls (HC). We performed NIRS scans before and after antidepressant treatment and measured changes of [oxy-Hb] activation during a verbal fluency task (VFT) following treatment. Individuals with MDD showed significantly decreased [oxy-Hb] values during a VFT compared with HC in the bilateral frontal and temporal cortices at baseline. There were no [oxy-Hb] changes between pre- and post-antidepressant treatment time points in the MDD cohort despite significant improvement in depressive symptoms. There was a significant association between mean [oxy-Hb] values during a VFT at baseline and improvement in depressive symptoms following treatment in the bilateral inferior frontal and middle temporal gyri in MDD. These findings suggest that hypofrontality response to a VFT may represent a potential trait marker for depression rather than a state marker. Moreover...

Association of the COMT val158met Variant with Antidepressant Treatment Response in Major Depression

Baune, B.; Hohoff, C.; Berger, K.; Neumann, A.; Mortensen, S.; Roehrs, T.; Deckert, J.; Arolt, V.; Domschke, K.
Fonte: Elsevier Science Inc Publicador: Elsevier Science Inc
Tipo: Artigo de Revista Científica
Publicado em //2008 Português
Relevância na Pesquisa
56.24%
In several previous biochemical, pharmacological, and genetic studies, the catechol-O-methyltransferase (COMT) has been suggested to be involved in the pathogenesis as well as the pharmacological treatment of affective disorders. In the present study, 256 patients with major depression (DSM-IV) of Caucasian descent were genotyped for the functional COMT val158met polymorphism and characterized for clinical response to antidepressive pharmacological treatment as measured by intra-individual changes of Hamilton Depression (HAM-D-21) scores over 6 weeks. The COMT 158val/val genotype conferred a significant risk of worse response after 4–6 weeks of antidepressant treatment in patients with major depression (week 4: p=0.003; week 5: p<0.0001; week 6: p<0.0001) after Bonferroni correction for multiple comparisons. The present results strongly point toward a negative influence of the higher activity COMT 158val/val genotype on antidepressant treatment response during the first 6 weeks of pharmacological treatment in major depression, possibly conferred by consecutively decreased dopamine availability. This finding suggests a potentially beneficial effect of an antidepressive add-on therapy with substances increasing dopamine availability individually tailored according to COMT val158met genotype.; Bernhard T Baune...

The Interleukin 1 Beta (IL1B) Gene Is Associated with Failure to Achieve Remission and Impaired Emotion Processing in Major Depression

Baune, B.; Dannlowski, U.; Domschke, K.; Janssen, D.; Jordan, M.; Ohrmann, P.; Bauer, J.; Biros, E.; Arolt, V.; Kugel, H.; Baxter, A.; Suslow, T.
Fonte: Elsevier Science Inc Publicador: Elsevier Science Inc
Tipo: Artigo de Revista Científica
Publicado em //2010 Português
Relevância na Pesquisa
46.34%
Background: Accumulating evidence suggests the involvement of inflammatory processes and cytokines in particular in the pathophysiology of major depression (MDD) and resistance to antidepressant treatment. Furthermore, amygdala and anterior cingulate cortex (ACC) responsiveness to emotional stimuli has been suggested as a predictor of treatment response. This study investigated the association between genetic variants of the interleukin 1 beta (IL1B) gene and amygdala and ACC responsiveness to emotional stimuli and response to antidepressant treatment. Methods: In this analysis, 256 Caucasian patients with MDD (145 women, 111 men) were genotyped for variants rs16944, rs1143643, and rs1143634 in the IL1B gene (2q14). Response to antidepressant treatment over 6 weeks was defined as remission (≤ 7 on the Hamilton Rating Scale for Depression–21-question) and response (>50% decrease on Hamilton Rating Scale for Depression–21-question). Brain activity under visual presentation of emotional faces was assessed in a subsample of 32 depressed patients by means of functional magnetic resonance imaging at 3 T. Results: Pharmacogenetic analyses show significant associations of the GG genotypes of single nucleotide polymorphisms (SNPs) rs16944 (odds ratio = 1.74; 95% confidence interval 1.2–4.3) and rs1143643 (odds ratio = 3.1; 95% confidence interval 1.3–7.8) (compared with the AA genotype) with nonremission after 6 weeks. The imaging analyses show that the number of G-alleles in both SNPs (rs16944 and rs1143643) was associated with reduced responsiveness of the amygdala and ACC to emotional stimulation. Conclusions: The present study suggests a negative effect of the IL1B gene on pharmacological response and amygdala and ACC function involving the same genotypes of two SNPs (rs16944...

Brain-derived neurotrophic factor (BDNF) gene: no major impact on antidepressant treatment response

Domschke, K.; Lawford, B.; Laje, G.; Berger, K.; Young, R.; Morris, P.; Deckert, J.; Arolt, V.; McMahon, F.; Baune, B.
Fonte: Cambridge Univ Press Publicador: Cambridge Univ Press
Tipo: Artigo de Revista Científica
Publicado em //2010 Português
Relevância na Pesquisa
56.42%
The brain-derived neurotrophic factor (BDNF) has been suggested to play a pivotal role in the aetiology of affective disorders. In order to further clarify the impact of BDNF gene variation on major depression as well as antidepressant treatment response, association of three BDNF polymorphisms [rs7103411, Val66Met (rs6265) and rs7124442] with major depression and antidepressant treatment response was investigated in an overall sample of 268 German patients with major depression and 424 healthy controls. False discovery rate (FDR) was applied to control for multiple testing. Additionally, ten markers in BDNF were tested for association with citalopram outcome in the STAR*D sample. While BDNF was not associated with major depression as a categorical diagnosis, the BDNF rs7124442 TT genotype was significantly related to worse treatment outcome over 6 wk in major depression (p=0.01) particularly in anxious depression (p=0.003) in the German sample. However, BDNF rs7103411 and rs6265 similarly predicted worse treatment response over 6 wk in clinical subtypes of depression such as melancholic depression only (rs7103411: TT

Possible associations of NTRK2 polymorphisms with antidepressant treatment outcome: findings from an extended tag SNP approach

Hennings, J.; Kohli, M.; Czamara, D.; Geise, M.; Eckert, A.; Wolf, C.; Heck, A.; Domschke, K.; Arolt, V.; Baune, B.; Horstmann, S.; Bruckl, T.; Klengel, T.; Menke, A.; Muller-Myhsok, B.; Ising, M.; Uhr, M.; Lucae, S.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em //2013 Português
Relevância na Pesquisa
56.39%
BACKGROUND Data from clinical studies and results from animal models suggest an involvement of the neurotrophin system in the pathology of depression and antidepressant treatment response. Genetic variations within the genes coding for the brain-derived neurotrophic factor (BDNF) and its key receptor Trkb (NTRK2) may therefore influence the response to antidepressant treatment. METHODS We performed a single and multi-marker association study with antidepressant treatment outcome in 398 depressed Caucasian inpatients participating in the Munich Antidepressant Response Signature (MARS) project. Two Caucasian replication samples (N = 249 and N = 247) were investigated, resulting in a total number of 894 patients. 18 tagging SNPs in the BDNF gene region and 64 tagging SNPs in the NTRK2 gene region were genotyped in the discovery sample; 16 nominally associated SNPs were tested in two replication samples. RESULTS In the discovery analysis, 7 BDNF SNPs and 9 NTRK2 SNPs were nominally associated with treatment response. Three NTRK2 SNPs (rs10868223, rs1659412 and rs11140778) also showed associations in at least one replication sample and in the combined sample with the same direction of effects (P(corr) = .018, P(corr) = .015 and P(corr) = .004...

Serotonin transporter gene hypomethylation predicts impaired antidepressant treatment response

Domschke, K.; Tidow, N.; Schwarte, K.; Deckert, J.; Lesch, K.P.; Arolt, V.; Zwanzger, P.; Baune, B.T.
Fonte: Cambridge University Press Publicador: Cambridge University Press
Tipo: Artigo de Revista Científica
Publicado em //2014 Português
Relevância na Pesquisa
46.37%
Variation in the serotonin transporter gene (5-HTT; SERT; SLC6A4) has been suggested to pharmacogenetically drive interindividual differences in antidepressant treatment response. In the present analysis, a 'pharmaco-epigenetic' approach was applied by investigating the influence of DNA methylation patterns in the 5-HTT transcriptional control region on antidepressant treatment response. Ninety-four patients of Caucasian descent with major depressive disorder (MDD) (f = 61) were analysed for DNA methylation status at nine CpG sites in the 5-HTT transcriptional control region upstream of exon 1A via direct sequencing of sodium bisulfite treated DNA extracted from blood cells. Patients were also genotyped for the functional 5-HTTLPR/rs25531 polymorphisms. Clinical response to treatment with escitalopram was assessed by intra-individual changes of HAM-D-21 scores after 6 wk of treatment. Lower average 5-HTT methylation across all nine CpGs was found to be associated with impaired antidepressant treatment response after 6 wk (p = 0.005). This effect was particularly conferred by one individual 5-HTT CpG site (CpG2 (GRCh37 build, NC_000017.10 28.563.102; p = 0.002). 5-HTTLPR/rs25531 haplotype was neither associated with 5-HTT DNA methylation nor treatment response. This analysis suggests that DNA hypomethylation of the 5-HTT transcriptional control region - possibly via increased serotonin transporter expression and consecutively decreased serotonin availability - might impair antidepressant treatment response in Caucasian patients with MDD. This pharmaco-epigenetic approach could eventually aid in establishing epigenetic biomarkers of treatment response and thereby a more personalized treatment of MDD.; Katharina Domschke...

The pattern of melatonin receptor expression in the brain may influence antidepressant treatment

Hirsch-Rodriguez, Eric; Imbesi, Marta; Manev, Radmila; Uz, Tolga; Manev, Hari
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
46.37%
The pineal hormone melatonin produces most of its biological effects via G protein-coupled receptors MT1 and MT2. In mammals, these receptors are expressed in various tissues and organs including in the brain. Recent research points to a putative role of MT1/MT2 dimerization as a mechanism that could determine the receptor-mediated biological effects of melatonin. Brain content and the ratios between MT1 and MT2 receptors are affected by illness, e.g., Alzheimer's disease, and by prolonged drug treatment, e.g., antidepressants. New drugs with antidepressant properties that bind and activate melatonin receptors have been discovered. We hypothesize that endogenous, i.e., low, levels of melatonin could contribute to antidepressant effects depending on the expression pattern of melatonin receptors in the brain. Hence, we propose that a prolonged treatment with classical antidepressant drugs alters the brain ratio of MT1/MT2 receptors to enable the endogenous melatonin, which is secreted during the night, to further improve the antidepressant effects. A corollary of this hypothesis is that antidepressants would be less effective in conditions of pathologically altered brain melatonin receptors, e.g., in Alzheimer's patients or due to genetic polymorphisms. If our hypothesis is confirmed...

A preliminary analysis of association between plasma microRNA expression alteration and symptomatology improvement in Major Depressive Disorder (MDD) patients before and after antidepressant treatment

Qiao-li,Zhang; Jim,Lu; Xin-yang,Sun; Wei,Guo; Lin,Zhao; Hui-min,Fan; Ai-fang,Zhong; Wei,Niu; Yun-hua,Dai; Li-yi,Zhang; Hong-tao,Song; Liang,Zhang
Fonte: The European Journal of Psychiatry Publicador: The European Journal of Psychiatry
Tipo: info:eu-repo/semantics/article; journal article; info:eu-repo/semantics/publishedVersion Formato: text/html; application/pdf
Publicado em 01/12/2014 Português
Relevância na Pesquisa
56.2%
Background and Objectives: Currently, there is a serious need to find practical biomarker(s) for Major Depressive Disorder (MDD) therapeutic target(s). This study aimed to investigate the association between microRNA (miRNA, miR) expression level in Peripheral Blood Mononuclear Cells (PBMCs) and symptomatology improvement in MDD patients before and after six-week antidepressant treatment. Methods: By using an Affymetrix array that covers 723 human miRNAs, 26 miRNAs were identified with significantly altered expression in PBMCs in MDD patients, of which 10 miRNAs were selected for quantitative real-time Reverse Transcription Polymerase Chain Reaction (RT-PCR) study. Twenty out of all the 81 MDD patients were selected for miRNA expression levels testing and symptomatology assessments before and after six-week treatment. Results: Compared with the control group, the expression levels of miR-26b, miR-4743, miR-4498, miR-4485 and miR-1972 of the MDD group were significantly higher (P < 0.05); the changes of expression levels of miR-4743, miR-4498, miR-4485 and miR-1972 were positively related to retardation improvement (P < 0.05), and the change of expression level of miR-26b negatively to the improvement of day and night change (P < 0.05); regression analysis result demonstrated that the alteration of miR-4485 expression accounted for 28.8% of retardation improvement (P < 0.05). Conclusions: These five miRNAs (miR-4743...