title: FKBP5 modulates the hippocampal connectivity deficits in depression: a study in twins.
abstract: 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). Three main results were derived from the present analyses. First, graph-theoretical measures of hippocampal connectivity were altered in depression. Specifically, decreased connectivity strength and increased network centrality of the right hippocampus were found in depressed individuals. Second, these hippocampal alterations are potentially driven by familial factors (genes plus shared environment). Third, there is an additive interaction effect between FKBP5's rs1360780 variant and the graph-theoretical metrics of hippocampal connectivity to influence depression risk. Our data reveals alterations of the communication patterns between the hippocampus and the rest of the brain in depression, effects potentially driven by overall familial factors (genes plus shared twin environment) and modified by the FKBP5 gene.
authors.affiliation: Unidad de Antropología, Departamento de Biología Animal, Facultad de Biología and Instituto de Biomedicina (IBUB), Universitat de Barcelona, Av. Diagonal, 643, 08028, Barcelona, Spain.|Centro de Investigaciones Biomédicas en Red de Salud Mental (CIBERSAM), C/Doctor Esquerdo, 46, 28007, Madrid, Spain.
authors.forename: Aldo
authors.initials: A
authors.lastname: Córdova-Palomera
authors.affiliation: Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Heidelberglaan 100, 3508 GA, Utrecht, the Netherlands.
authors.forename: Marcel A
authors.initials: MA
authors.lastname: de Reus
authors.affiliation: Unidad de Antropología, Departamento de Biología Animal, Facultad de Biología and Instituto de Biomedicina (IBUB), Universitat de Barcelona, Av. Diagonal, 643, 08028, Barcelona, Spain.|Centro de Investigaciones Biomédicas en Red de Salud Mental (CIBERSAM), C/Doctor Esquerdo, 46, 28007, Madrid, Spain.
authors.forename: Mar
authors.initials: M
authors.lastname: Fatjó-Vilas
authors.affiliation: BarcelonaBeta Brain Research Center, Pasqual Maragall Foundation, C/Dr Aiguader, 88, 08003, Barcelona, Spain.|Centro de Investigación Biomédica en Red en Bioingeniería, Biomedicina y Nanomedicina (CIBER-BBN), C/Poeta Mariano Esquillor, s/n., 50018, Zaragoza, Spain.
authors.forename: Carles
authors.initials: C
authors.lastname: Falcón
authors.affiliation: Centro de Investigaciones Biomédicas en Red de Salud Mental (CIBERSAM), C/Doctor Esquerdo, 46, 28007, Madrid, Spain.|Centro de Diagnóstico por Imagen, Hospital Clínico, C/Villarroel, 170, 08036, Barcelona, Spain.|Medical Image core facility, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), C/Rosselló, 149-153, 08036, Barcelona, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Bargalló
authors.affiliation: Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Heidelberglaan 100, 3508 GA, Utrecht, the Netherlands.
authors.forename: Martijn P
authors.initials: MP
authors.lastname: van den Heuvel
authors.affiliation: Unidad de Antropología, Departamento de Biología Animal, Facultad de Biología and Instituto de Biomedicina (IBUB), Universitat de Barcelona, Av. Diagonal, 643, 08028, Barcelona, Spain. lfananas@ub.edu.|Centro de Investigaciones Biomédicas en Red de Salud Mental (CIBERSAM), C/Doctor Esquerdo, 46, 28007, Madrid, Spain. lfananas@ub.edu.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Fañanás
mesh_terms: D000328:Adult; D003866:Depressive Disorder / Q000000981:diagnostic imaging* / Q000235:genetics*; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D006624:Hippocampus / Q000000981:diagnostic imaging*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000000981:diagnostic imaging; D020641:Polymorphism, Single Nucleotide; D022021:Tacrolimus Binding Proteins / Q000235:genetics*; D014430:Twins, Monozygotic; D055815:Young Adult; D000099159:Tacrolimus Binding Protein 5
chemical_list: D022021:Tacrolimus Binding Proteins; D000099159:Tacrolimus Binding Protein 5
keywords: Brain network; DWI; Depression; FKBP5; Hippocampus; MZ twins