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Richard Lieberman, Henry R Kranzler, Eric S Levine, Jonathan Covault
In peripheral blood leukocytes, FKBP5 mRNA expression is upregulated following glucocorticoid receptor activation. The single nucleotide polymorphism rs1360780 in FKBP5 is associated with psychiatric illness and has functional molecular effects. However, examination of FKBP5 regulation has largely been limited to peripheral cells, which may not reflect regulation in neural cells. We used 27 human induced pluripotent stem cell lines (iPSCs) derived from 20 subjects to examine FKBP5 mRNA expression following GR activation...
November 24, 2016: Psychiatry Research
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
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
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
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
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
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
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
Johan Isaksson, Erika Comasco, Cecilia Åslund, Mattias Rehn, Catherine Tuvblad, Henrik Andershed, Kent W Nilsson
The gene that encodes the FK506-binding protein 5 (FKBP5) is regarded as a candidate for investigating how negative life events interact with a genetic predisposition to stress-related disorders, such as depression and anxiety. Given the role of FKBP5 as an important regulator of stress responses, we aimed to investigate if single-nucleotide polymorphisms (SNPs) in FKBP5-in the presence/absence of exposure to violence-are associated with symptoms of depression and anxiety. Data from two community-based samples of adolescents (n=1705) and young adults (n=1800) regarding ratings on depression, anxiety, exposure to violence and FKBP5 genotype were collected...
October 2016: Psychoneuroendocrinology
Ingrid Borba Hartmann, Gabriel Rodrigo Fries, Joana Bücker, Ellen Scotton, Lisia von Diemen, Marcia Kauer-Sant'Anna
BACKGROUND: Bariatric surgery is the most effective treatment choice for severe obesity. Recent literature indicates that FK506-binding protein 51 (FKBP51) could play a role in energy homeostasis, influencing adipogenesis and weight. OBJECTIVE: To evaluate if the presence of the T allele of the FKBP5 SNP rs1360780, associated with increased FKBP51 expression, could influence weight loss after bariatric surgery. SETTING: Hospital de Clínicas de Porto Alegre, Brazil...
April 20, 2016: Surgery for Obesity and related Diseases: Official Journal of the American Society for Bariatric Surgery
Paula Cristóbal-Narváez, Tamara Sheinbaum, Araceli Rosa, Sergi Ballespí, Marta de Castro-Catala, Elionora Peña, Thomas R Kwapil, Neus Barrantes-Vidal
AIM: The present study employed Experience Sampling Methodology to examine whether the interaction between childhood bullying and FKBP5 variability (i) is associated with the expression of psychotic-like experiences, paranoia, and negative affect, and (ii) moderates psychotic-like, paranoid, and affective reactivity to different forms of momentary stress (situational and social) in daily life. METHODS: A total of 206 nonclinical young adults were interviewed for bullying with the Childhood Experience of Care and Abuse and were prompted randomly eight times daily for one week to complete assessments of their current experiences, affect, and stress appraisals...
2016: PloS One
Richard Lieberman, Stephen Armeli, Denise M Scott, Henry R Kranzler, Howard Tennen, Jonathan Covault
Alcohol use disorder (AUD) is debilitating and costly. Identification and better understanding of risk factors influencing the development of AUD remain a research priority. Although early life exposure to trauma increases the risk of adulthood psychiatric disorders, including AUD, many individuals exposed to early life trauma do not develop psychopathology. Underlying genetic factors may contribute to differential sensitivity to trauma experienced in childhood. The hypothalamic-pituitary-adrenal (HPA) axis is susceptible to long-lasting changes in function following childhood trauma...
September 2016: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
Mary-Anne Enoch, Harriet Kitzman, Joyce A Smith, Elizabeth Anson, Colin A Hodgkinson, David Goldman, David L Olds
OBJECTIVE: This study investigated genetic and environmental influences on behavior in a cohort of 600 children followed prenatally to 18 years. METHOD: A randomized controlled trial of prenatal/infancy nurse home visits (NHV) was conducted in 600 predominantly African American mothers and their firstborn children from Memphis, TN. Mothers were assessed in pregnancy for mental health (MH), self-efficacy, and mastery. Mothers reported longitudinally on smoking and alcohol/drug use...
May 2016: Journal of the American Academy of Child and Adolescent Psychiatry
Laura E Watkins, Shizhong Han, Ilan Harpaz-Rotem, Natalie P Mota, Steven M Southwick, John H Krystal, Joel Gelernter, Robert H Pietrzak
Polymorphisms in the FK506 Binding Protein 5 (FKBP5) gene may interact with childhood abuse to increase risk of developing posttraumatic stress disorder (PTSD) symptoms. The objective of this study was to examine the relationship of four previously identified FKBP5 putative risk SNPs (rs9296158, rs3800373, rs1360780, rs947008), childhood abuse, and lifetime PTSD symptoms, including contemporary phenotypic models of PTSD symptoms, in two nationally representative samples of European-American (EA) U.S. military veterans...
July 2016: Psychoneuroendocrinology
Anne Koopmann, Jennifer Bez, Tagrid Lemenager, Derik Hermann, Christina Dinter, Iris Reinhard, Rilana Schuster, Klaus Wiedemann, Georg Winterer, Falk Kiefer
Tobacco smoking modulates activity in the hypothalamic-pituitary-adrenal (HPA) axis and is used to cope with stress, especially by females. The single nucleotide polymorphism (SNP) rs1360780, linked to FK506-binding protein 51 (FKBP5), has been shown to affect HPA axis functioning, and has thus been suggested as a promising candidate for indicating vulnerability to stress-related disorders. The aim of this study was to investigate the interaction between nicotine consumption and rs1360780 on cortisol plasma levels in females...
May 2016: Annals of Human Genetics
Negar Fani, Tricia Z King, Jaemin Shin, Amita Srivastava, Ryan C Brewster, Tanja Jovanovic, Bekh Bradley, Kerry J Ressler
BACKGROUND: The integrity of connections between the hippocampus and the anterior cingulate cortex (ACC) is critical for adaptive cognitive and emotional processing; these connections may be compromised in posttraumatic stress disorder (PTSD). However, there is a lack of PTSD research that combines structural and functional connectivity data, and no studies have examined whether abnormal ACC-hippocampal connectivity is associated with genetic variability, particularly for polymorphisms of a gene that has been previously associated with PTSD, FKBP5...
April 2016: Depression and Anxiety
Hirofumi Hirakawa, Jotaro Akiyoshi, Masaaki Muronaga, Yoshihiro Tanaka, Yoshinobu Ishitobi, Ayako Inoue, Harumi Oshita, Saeko Aizawa, Koji Masuda, Haruka Higuma, Masayuki Kanehisa, Taiga Ninomiya, Yoshihisa Kawano
The present study was to investigate the effects of 6 FK506 binding protein 51 (FKBP5) single nucleotide polymorphisms (SNPs) on brain structure using voxel-based morphometry (VBM) and the psychological tests to psychological stress. We genotyped 112 healthy controls with respect to 6 SNPs (rs) of FKBP5. We examined the Beck Depression Inventory and the State (STAI-S) and Trait (STAI-T) versions of the Spielberger Anxiety Inventory and the Profile of Mood States (POMS) to evaluate mood. The right amygdala was larger in subjects with the minor allele (C) of rs3800373 and rs992105 and the minor allele (T) of rs1360780...
2016: International Journal of Psychiatry in Clinical Practice
Hans Jörgen Grabe, Katharina Wittfeld, Sandra Van der Auwera, Deborah Janowitz, Katrin Hegenscheid, Mohamad Habes, Georg Homuth, Sven Barnow, Ulrich John, Matthias Nauck, Henry Völzke, Henriette Meyer zu Schwabedissen, Harald Jürgen Freyberger, Norbert Hosten
OBJECTIVE: The FKBP5 gene codes for a co-chaperone that regulates glucocorticoid receptor sensitivity and thereby impacts the reactivity of the hypothalamic-pituitary-adrenal (HPA)-axis. Evidence suggested that subjects exposed to childhood abuse and carrying the TT genotype of the FKBP5 gene single nucleotide polymorphism (SNP) rs1360780 have an increased susceptibility to stress-related disorders. METHOD: The hypothesis that abused TT genotype carriers show changes in gray matter (GM) volumes in affect-processing brain areas was investigated...
April 2016: Human Brain Mapping
Aldo Córdova-Palomera, Marcel A de Reus, Mar Fatjó-Vilas, Carles Falcón, Nuria Bargalló, Martijn P van den Heuvel, Lourdes Fañanás
The hippocampus is a key modulator of stress responses underlying depressive behavior. While FKBP5 has been found associated with a large number of stress-related outcomes and hippocampal features, its potential role in modifying the hippocampal communication transfer mechanisms with other brain regions remains largely unexplored. The putative genetic or environmental roots of the association between depression and structural connectivity alterations of the hippocampus were evaluated combining diffusion weighted imaging with both a quantitative genetics approach and molecular information on the rs1360780 single nucleotide polymorphism, in a sample of 54 informative monozygotic twins (27 pairs)...
January 22, 2016: Brain Imaging and Behavior
Jari Lahti, Heidi Ala-Mikkula, Eero Kajantie, Kadri Haljas, Johan G Eriksson, Katri Räikkönen
BACKGROUND: FK506-binding protein 51 is involved in hypothalamic-pituitary-adrenal axis regulation. Single nucleotide polymorphisms (SNPs) in the FKBP5 gene have been shown to interact with retrospectively self-reported early life stress (ELS) in patients with psychiatric disorders. We examined interactions between three selected FKBP5 SNPs and self-reported and objectively recorded ELS in relation to depressive symptoms in midlife. METHODS: This study comprised 1431 Helsinki Birth Cohort Study participants genotyped for FKBP5 SNPs shown to alter cortisol metabolism (rs1360780, rs9470080, and rs9394309)...
November 10, 2015: Biological Psychiatry
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