title: Effect of the interaction between childhood abuse and rs1360780 of the FKBP5 gene on gray matter volume in a general population sample.
abstract: 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.
  
  
  METHODS
  The hypothesis that abused TT genotype carriers show changes in gray matter (GM) volumes in affect-processing brain areas was investigated. About 1,826 Caucasian subjects (age ≤ 65 years) from the general population [Study of Health in Pomerania (SHIP)] in Germany were investigated. The interaction between rs1360780 and child abuse (Childhood Trauma Questionnaire) and its effect on GM were analyzed.
  
  
  RESULTS
  Voxel-based whole-brain interaction analysis revealed three large clusters (FWE-corrected) of reduced GM volumes comprising the bilateral insula, the superior and middle temporal gyrus, the bilateral hippocampus, the right amygdala, and the bilateral anterior cingulate cortex in abused TT carriers. These results were not confounded by major depressive disorders. In region of interest analyses, highly significant volume reductions in the right hippocampus/parahippocampus, the bilateral anterior and middle cingulate cortex, the insula, and the amygdala were confirmed in abused TT carriers compared with abused CT/CC carriers.
  
  
  CONCLUSIONS
  The results supported the hypothesis that the FKBP5 rs1360780 TT genotype predisposes subjects who have experienced childhood abuse to widespread structural brain changes in the subcortical and cortical emotion-processing brain areas. Those brain changes might contribute to an increased vulnerability of stress-related disorders in TT genotype carriers.
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.|German Center for Neurodegenerative Diseases (DZNE), Site Rostock/Greifswald, Germany.
authors.forename: Hans Jörgen
authors.initials: HJ
authors.lastname: Grabe
authors.affiliation: German Center for Neurodegenerative Diseases (DZNE), Site Rostock/Greifswald, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Wittfeld
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.|German Center for Neurodegenerative Diseases (DZNE), Site Rostock/Greifswald, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Van der Auwera
authors.affiliation: Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Deborah
authors.initials: D
authors.lastname: Janowitz
authors.affiliation: Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Hegenscheid
authors.affiliation: Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.|Center for Biomedical Image Computing and Analytics, University of Pennsylvania, Philadelphia, Pennsylvania.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Habes
authors.affiliation: Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, Greifswald, Germany.
authors.forename: Georg
authors.initials: G
authors.lastname: Homuth
authors.affiliation: Institute of Psychology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Barnow
authors.affiliation: Institute of Social Medicine and Prevention, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: John
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Nauck
authors.affiliation: Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Henry
authors.initials: H
authors.lastname: Völzke
authors.affiliation: Biopharmacy, Department Pharmaceutical Sciences, University of Basel, Basel, Switzerland.
authors.forename: Henriette
authors.initials: H
authors.lastname: Meyer zu Schwabedissen
authors.affiliation: Department of Psychiatry and Psychotherapy, Helios Hospital Stralsund, Stralsund, Germany.
authors.forename: Harald Jürgen
authors.initials: HJ
authors.lastname: Freyberger
authors.affiliation: Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Hosten
mesh_terms: D000328:Adult; D002648:Child; D002649:Child Abuse / Q000175:diagnosis*; D004843:Epistasis, Genetic / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D066128:Gray Matter / Q000000981:diagnostic imaging*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009929:Organ Size; D011159:Population Surveillance; D011897:Random Allocation; D012042:Registries; D022021:Tacrolimus Binding Proteins / Q000235:genetics*; D000099159:Tacrolimus Binding Protein 5
chemical_list: D022021:Tacrolimus Binding Proteins; D000099159:Tacrolimus Binding Protein 5
keywords: CTQ; FKBP5 gene; MRI; SPM8; VBM8; childhood abuse; gene-environment interaction; general population; major depression disorder; stress-related disorders
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