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https://www.readbyqxmd.com/read/27889704/pharmacogenetic-studies-a-tool-to-improve-antidepressant-therapy
#1
Marta Ramos, Cecilia Berrogain, Julia Concha, Laura Lomba, Cristina Belén García, Mª Pilar Ribate
The World Health Organization (WHO) predicts that major depressive disorder (MDD) will be the second leading cause of death and disability by 2020. Nowadays, approximately 60-70% of patients with this disorder have shown the lack of effectiveness and tolerability of the therapy with antidepressants. The US Food and Drug Administration (FDA) and the European Medicine Agency (EMA) are including pharmacogenetic information in the labeling of several antidepressants. The presence of this information represents the relevance of genetic polymorphisms in drug response...
December 1, 2016: Drug Metabolism and Personalized Therapy
https://www.readbyqxmd.com/read/27760575/the-interactive-effects-of-child-maltreatment-and-the-fk506-binding-protein-5-gene-fkbp5-on-dissociative-symptoms-in-adolescence
#2
Fatima Tuba Yaylaci, Dante Cicchetti, Fred A Rogosch, Okan Bulut, Susan R Hetzel
The FK506 binding protein 5 gene (FKBP5) has been associated with susceptibility to pathogenic effects of childhood trauma including dissociative symptoms. This study examines the impact of maltreatment on dissociative tendencies in adolescence as moderated by the FKBP5 gene. Dissociative symptoms and variation within FKBP5 were assessed in a high-risk, low socioeconomic status community sample of 279 maltreated and 171 nonmaltreated adolescents. Following the assignment of haplotypes across four single nucleotide polymorphisms (rs3800373, rs9296158, rs1360780, and rs9470080), individuals with one or more copies of the CATT haplotype (N = 230) were grouped together and compared to individuals with zero copies of this haplotype (N = 185)...
October 20, 2016: Development and Psychopathology
https://www.readbyqxmd.com/read/27754486/association-of-fkbp5-polymorphisms-and-resting-state-activity-in-a-frontotemporal-parietal-network
#3
R A Bryant, K L Felmingham, B Liddell, P Das, G S Malhi
The FKBP5 polymorphism is a key regulator of the glucocorticoid system underpinning stress responsivity, and risk alleles can increase vulnerability for developing posttraumatic stress disorder. To delineate the specific role of FKBP5 risk alleles unencumbered by the confounds of psychopathology, this study investigated whether high-risk alleles of the FKBP5 polymorphism are characterized by distinctive neural activity during resting state. Thirty-seven healthy participants were selected on the basis of four SNPs in the FKBP5 gene region (rs3800373, rs9296158, rs1360780 and rs9470080) to determine participants who were carriers of the FKBP5 high- and low-risk alleles...
October 18, 2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27752945/pharmacogenetics-and-imaging-pharmacogenetics-of-antidepressant-response-towards-translational-strategies
#4
Tristram A Lett, Henrik Walter, Eva J Brandl
Genetic variation underlies both the response to antidepressant treatment and the occurrence of side effects. Over the past two decades, a number of pharmacogenetic variants, among these the SCL6A4, BDNF, FKBP5, GNB3, GRIK4, and ABCB1 genes, have come to the forefront in this regard. However, small effects sizes, mixed results in independent samples, and conflicting meta-analyses results led to inherent difficulties in the field of pharmacogenetics translating these findings into clinical practice. Nearly all antidepressant pharmacogenetic variants have potentially pleiotropic effects in which they are associated with major depressive disorder, intermediate phenotypes involved in emotional processes, and brain areas affected by antidepressant treatment...
October 17, 2016: CNS Drugs
https://www.readbyqxmd.com/read/27709495/evidence-for-a-link-between-fkbp5-fkbp5-early-life-social-relations-and-alcohol-drinking-in-young-adult-rats-and-humans
#5
Ingrid Nylander, Aniruddha Todkar, Linnea Granholm, Maria Vrettou, Megha Bendre, Wout Boon, Henrik Andershed, Catherine Tuvblad, Kent W Nilsson, Erika Comasco
Alcohol misuse has been linked to dysregulation of stress, emotion, and reward brain circuitries. A candidate key mediator of this association is the FK506-binding protein (FKBP5), a negative regulator of the glucocorticoid receptor. The aim of the present study was to further understand the Fkbp5/FKBP5-related genetic underpinnings underlying the relationship between early life social relations and alcohol drinking. The effect of maternal separation and voluntary alcohol drinking on Fkbp5 expression was investigated in the brain of young adult rats, whereas the interaction effect of the functional FKBP5 single nucleotide polymorphism rs1360780 genotype and parent-child relationship on problematic drinking was examined in young adult humans...
October 5, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27691985/childhood-adversity-and-epigenetic-regulation-of-glucocorticoid-signaling-genes-associations-in-children-and-adults
#6
Audrey R Tyrka, Kathryn K Ridout, Stephanie H Parade
Early childhood experiences have lasting effects on development, including the risk for psychiatric disorders. Research examining the biologic underpinnings of these associations has revealed the impact of childhood maltreatment on the physiologic stress response and activity of the hypothalamus-pituitary-adrenal axis. A growing body of literature supports the hypothesis that environmental exposures mediate their biological effects via epigenetic mechanisms. Methylation, which is thought to be the most stable form of epigenetic change, is a likely mechanism by which early life exposures have lasting effects...
October 3, 2016: Development and Psychopathology
https://www.readbyqxmd.com/read/27690835/microrna-320a-predicts-chronic-axial-and-widespread-pain-development-following-motor-vehicle-collision-in-a-stress-dependent-manner
#7
Sarah D Linnstaedt, Kyle D Riker, Margaret G Walker, Jennifer E Nyland, Erin Zimny, Christopher Lewandowski, Phyllis L Hendry, Kathia Damiron, Claire Pearson, Marc-Anthony Velilla, Jeffrey Jones, Robert A Swor, Robert Domeier, Samuel A McLean
Study Design Prospective human cohort study combined with molecular studies. Background A microRNA is a small, noncoding RNA molecule that can play a role in disease onset. Recent studies found that circulating levels of microRNA 320a (miR-320a) are associated with musculoskeletal pain conditions and that miR-320a is stress responsive. Objectives To investigate whether circulating expression levels of miR-320a in the peritraumatic period predict persistent axial musculoskeletal pain 6 months after motor vehicle collision (MVC)...
October 2016: Journal of Orthopaedic and Sports Physical Therapy
https://www.readbyqxmd.com/read/27688096/the-mir-367-3p-increases-sorafenib-chemotherapy-efficacy-to-suppress-hepatocellular-carcinoma-metastasis-through-altering-the-androgen-receptor-signals
#8
Junjie Xu, Hui Lin, Gonghui Li, Yin Sun, Jiang Chen, Liang Shi, Xiujun Cai, Chawnshang Chang
The androgen receptor (AR) was found to suppress hepatocellular carcinoma (HCC) metastasis at late stages. Due to this discovery, we searched for some AR enhancers to increase the efficacy of Sorafenib chemotherapy, and identified the microRNA (miR)-367-3p, whose expression is positively correlated with AR expression in advanced HCC, as an HCC metastasis suppressor. Combining miR-367-3p with Sorafenib showed better efficacy to suppress HCC cell invasion in vitro and in vivo. Mechanism dissection revealed that miR-367-3p could increase AR expression via directly targeting the 3'UTR of MDM2 to decrease MDM2 protein expression...
July 14, 2016: EBioMedicine
https://www.readbyqxmd.com/read/27680313/novel-roles-of-fkbp5-in-muscle-alteration-induced-by-gravity-change-in-mice
#9
Takeshi Shimoide, Naoyuki Kawao, Yukinori Tamura, Hironobu Morita, Hiroshi Kaji
Skeletal muscle hypertrophy and wasting are induced by hypergravity and microgravity, respectively. However, the mechanisms by which gravity change regulates muscle mass still remain unclear. We previously reported that hypergravity increases muscle mass via the vestibular system in mice. In this study, we performed comparative DNA microarray analysis of the soleus muscle from mice kept in 1 or 3 g environments with or without vestibular lesions. Mice were kept in 1 g or 3 g environment for 4 weeks by using a centrifuge 14 days after surgical bilateral vestibular lesions...
October 21, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27664120/reduced-dna-methylation-of-fkbp5-in-cushing-s-syndrome
#10
Eugenia Resmini, Alicia Santos, Anna Aulinas, Susan M Webb, Yolanda Vives-Gilabert, Olivia Cox, Gary Wand, Richard S Lee
FKBP5 encodes a co-chaperone of HSP90 protein that regulates intracellular glucocorticoid receptor sensitivity. When it is bound to the glucocorticoid receptor complex, cortisol binds with lower affinity to glucocorticoid receptor. Cushing's syndrome is associated with memory deficits, smaller hippocampal volumes, and wide range of cognitive impairments. We aimed at evaluating blood DNA methylation of FKBP5 and its relationship with memory and hippocampal volumes in Cushing's syndrome patients. Polymorphism rs1360780 in FKBP5 has also been assessed to determine whether genetic variations can also govern CpG methylation...
September 23, 2016: Endocrine
https://www.readbyqxmd.com/read/27648526/the-influence-of-fkbp5-genotype-on-expression-of-fkbp5-and-other-glucocorticoid-regulated-genes-dependent-on-trauma-exposure
#11
S Yeo, M-A Enoch, E Gorodetsky, L Akhtar, K Schuebel, A Roy, D Goldman
The FK506 binding protein 51 (FKBP5), an intrinsic regulator of the glucocorticoid receptor, has been associated with pathological behaviors particularly in the context of childhood trauma (CT), via a putatively regulatory polymorphism, rs1360780. However, trans- and cis-acting effects of this locus and its interaction with CT are incompletely understood. To study its effects on the expression of glucocorticoid-regulated genes including FKBP5, we used lymphoblastoid cell lines (LCLs) derived from 16 CT-exposed patients with greater than two substance dependence/suicidal behavior diagnoses (casesCT+) and 13 non-CT-exposed controls (controlsCT-)...
September 20, 2016: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/27638035/association-between-fkbp5-and-crhr1-genes-with-suicidal-behavior-a-systematic-review
#12
Eduardo De la Cruz-Cano
Suicide is one of the leading causes of death around the world with approximately one million suicides per year. An increasing number of neurobiological studies implicate HPA system dysfunction in suicide behavior, stimulating genetic research to focus on genes related to this system. This systematic review was focused on searching a correlation between FKBP5 and CRHR1 genes with suicidal behavior. Therefore, an electronic search strategy, using PubMed, EBSCO and Cochrane Library databases, was conducted from the inception of the studies into the databases to July 2016...
September 13, 2016: Behavioural Brain Research
https://www.readbyqxmd.com/read/27603714/consensus-paper-of-the-wfsbp-task-force-on-genetics-genetics-epigenetics-and-gene-expression-markers-of-major-depressive-disorder-and-antidepressant-response
#13
Chiara Fabbri, Ladislav Hosak, Rainald Mössner, Ina Giegling, Laura Mandelli, Frank Bellivier, Stephan Claes, David A Collier, Alejo Corrales, Lynn E Delisi, Carla Gallo, Michael Gill, James L Kennedy, Marion Leboyer, Amanda Lisoway, Wolfgang Maier, Miguel Marquez, Isabelle Massat, Ole Mors, Pierandrea Muglia, Markus M Nöthen, Michael C O'Donovan, Jorge Ospina-Duque, Peter Propping, Yongyong Shi, David St Clair, Florence Thibaut, Sven Cichon, Julien Mendlewicz, Dan Rujescu, Alessandro Serretti
Major depressive disorder (MDD) is a heritable disease with a heavy personal and socio-economic burden. Antidepressants of different classes are prescribed to treat MDD, but reliable and reproducible markers of efficacy are not available for clinical use. Further complicating treatment, the diagnosis of MDD is not guided by objective criteria, resulting in the risk of under- or overtreatment. A number of markers of MDD and antidepressant response have been investigated at the genetic, epigenetic, gene expression and protein levels...
September 7, 2016: World Journal of Biological Psychiatry
https://www.readbyqxmd.com/read/27601205/common-variants-in-fkbp5-gene-and-major-depressive-disorder-mdd-susceptibility-a-comprehensive-meta-analysis
#14
Shuquan Rao, Yao Yao, Joanne Ryan, Tao Li, Duan Wang, Chuan Zheng, Yong Xu, Qi Xu
Previous studies have investigated the association between common variants in FKBP5 and MDD; however, the results remain inconsistent. In order to conduct a comprehensive meta-analysis of the association between FKBP5 variants and MDD risk, seven studies involving 26582 subjects, including 12491 cases with MDD and 14091 controls, were enrolled totally. Four common SNPs (rs1360780, rs4713916, rs3800373 and rs755658) with complete data from two or more studies were analyzed. In the total sample, there was no evidence of a significant association between MDD and any of the four SNPs using a random-effects model...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27562825/androgens-induce-a-distinct-response-of-epithelial-mesenchymal-transition-factors-in-human-prostate-cancer-cells
#15
Juliane Colditz, Benjamin Rupf, Caroline Maiwald, Aria Baniahmad
Inhibition of the androgen receptor (AR) is a major target of prostate cancer (PCa) therapy. However, prolonged androgen deprivation results eventually in castration-resistant PCa (CRPC) with metastasis and poor survival. Emerging evidence suggests that epithelial-mesenchymal transition (EMT) may facilitate castration-resistance and cancer metastasis in PCa. The human androgen-dependent, castration-sensitive prostate cancer (CSPC) cell line LNCaP and the CRPC cell line C4-2 are often used as a model system for human PCa...
October 2016: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/27552816/the-emerging-role-of-the-fkbp5-gene-polymorphisms-in-vulnerability-stress-model-of-schizophrenia-further-evidence-from-a-serbian-population
#16
Marina Mihaljevic, Katarina Zeljic, Ivan Soldatovic, Sanja Andric, Tijana Mirjanic, Alexander Richards, Kiran Mantripragada, Tatjana Pekmezovic, Ivana Novakovic, Nadja P Maric
Increased reactivity to stress is observed in patients with schizophrenia spectrum disorders and their healthy siblings in comparison with the general population. Additionally, higher levels of neuroticism, as a proposed psychological measure of stress sensitivity, increase the risk of schizophrenia. HPA axis dysregulation is one of the possible mechanisms related to the vulnerability-stress model of schizophrenia, and recent studies revealed a possible role of the functional genetic variants of FK506-binding protein 51 (FKBP5) gene which modulate activity of HPA axis...
August 23, 2016: European Archives of Psychiatry and Clinical Neuroscience
https://www.readbyqxmd.com/read/27549215/the-sex-dependent-role-of-the-glucocorticoid-receptor-in-depression-variations-in-the-nr3c1-gene-are-associated-with-major-depressive-disorder-in-women-but-not-in-men
#17
Nina Sarubin, Sven Hilbert, Felix Naumann, Peter Zill, Anna-Maria Wimmer, Caroline Nothdurfter, Rainer Rupprecht, Thomas C Baghai, Markus Bühner, Cornelius Schüle
Genetic variations in the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR) have been associated with maladaptive stress responses and major depressive disorder (MDD). In a case-control study design, we examined whether single nucleotide polymorphisms (SNPs) and haploid genotype (haplotype) associations of MR gene NR3C2, GR gene NR3C1 and genes of GR chaperone molecules FK506 binding protein 5 (FKBP5) and corticotrophin-releasing hormone receptor 1 (CRHR1) differed between healthy subjects (n = 634) and inpatients with major depressive disorder (n = 412)...
August 22, 2016: European Archives of Psychiatry and Clinical Neuroscience
https://www.readbyqxmd.com/read/27527158/the-fkbp5-gene-affects-alcohol-drinking-in-knockout-mice-and-is-implicated-in-alcohol-drinking-in-humans
#18
Bin Qiu, Susan E Luczak, Tamara L Wall, Aaron M Kirchhoff, Yuxue Xu, Mimy Y Eng, Robert B Stewart, Weinian Shou, Stephen L Boehm, Julia A Chester, Weidong Yong, Tiebing Liang
FKBP5 encodes FK506-binding protein 5, a glucocorticoid receptor (GR)-binding protein implicated in various psychiatric disorders and alcohol withdrawal severity. The purpose of this study is to characterize alcohol preference and related phenotypes in Fkbp5 knockout (KO) mice and to examine the role of FKBP5 in human alcohol consumption. The following experiments were performed to characterize Fkpb5 KO mice. (1) Fkbp5 KO and wild-type (WT) EtOH consumption was tested using a two-bottle choice paradigm; (2) The EtOH elimination rate was measured after intraperitoneal (IP) injection of 2...
2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27502757/baicalin-promotes-hippocampal-neurogenesis-via-sgk1-and-fkbp5-mediated-glucocorticoid-receptor-phosphorylation-in-a-neuroendocrine-mouse-model-of-anxiety-depression
#19
Kuo Zhang, Xing Pan, Fang Wang, Jie Ma, Guangyue Su, Yingxu Dong, Jingyu Yang, Chunfu Wu
Antidepressants increase hippocampal neurogenesis by activating the glucocorticoid receptor (GR), but excessive GR activation impairs hippocampal neurogenesis, suggesting that normal GR function is crucial for hippocampal neurogenesis. Baicalin was reported to regulate the expression of GR and facilitate hippocampal neurogenesis, but the underlying molecular mechanisms are still unknown. In this study, we used the chronic corticosterone (CORT)-induced mouse model of anxiety/depression to assess antidepressant-like effects of baicalin and illuminate possible molecular mechanisms by which baicalin affects GR-mediated hippocampal neurogenesis...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27485401/interactive-effects-of-attachment-and-genotype-on-school-aged-children-s-emotion-regulation-and-depressive-symptoms
#20
Jessica L Borelli, Patricia A Smiley, Hannah F Rasmussen, Anthony Gómez, Lauren C Seaman, Erika L Nurmi
Attachment insecurity is influenced by both environmental and genetic factors, but few studies have examined the effects of gene-environment interactions. In the context of environmental stress, a functional variant in the glucocorticoid receptor co-chaperone FKBP5 gene has been repeatedly shown to increase risk for psychiatric illness, including depression. We expand on prior work by exploring cross-sectional attachment by gene effects on both attachment insecurity and downstream physiological and behavioral measures in a diverse community sample of school-aged children (N=99, 49% girls, Mage=10...
July 30, 2016: Behavioural Brain Research
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