Brain Imaging and Behavior

, Volume 11, Issue 1, pp 62–75 | Cite as

FKBP5 modulates the hippocampal connectivity deficits in depression: a study in twins

  • Aldo Córdova-Palomera
  • Marcel A. de Reus
  • Mar Fatjó-Vilas
  • Carles Falcón
  • Nuria Bargalló
  • Martijn P. van den Heuvel
  • Lourdes Fañanás
Original Research


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.


FKBP5 Hippocampus Depression Brain network MZ twins DWI 



We are indebted to the Medical Image core facility of the Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) for the technical help. Supported by the Spanish SAF2008-05674-C03-01, European Twins Study Network on Schizophrenia Research Training Network (grant number EUTwinsS, MRTN-CT-2006-035987), the Catalan 2014SGR1636 and the Ministry of Science and Innovation (PIM2010ERN-00642) in frame of ERA-NET NEURON. MPvdH was supported by a VENI grant of the Dutch Council for Research (VENI: 451-12-001 NWO) and a Fellowship of the Brain Center Rudolf Magnus. The funders had no role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. Ximena Goldberg and Silvia Alemany contributed to sample collection. MRI technicians César Garrido and Santi Sotés also contributed to this work. Anna Valldeperas contributed to genotyping.

Compliance with ethical standards

Conflict of interest

Aldo Córdova-Palomera, Marcel A. de Reus, Mar Fatjó-Vilas, Carles Falcón, Nuria Bargalló, Martijn P. van den Heuvel, and Lourdes Fañanás declare that they have no conflict of interest.

Informed consent

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, and the applicable revisions at the time of the investigation. Informed consent was obtained from all subjects for being included in the study.

Supplementary material

11682_2015_9503_MOESM1_ESM.pdf (331 kb)
ESM 1 (PDF 331 kb)


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Aldo Córdova-Palomera
    • 1
    • 2
  • Marcel A. de Reus
    • 3
  • Mar Fatjó-Vilas
    • 1
    • 2
  • Carles Falcón
    • 4
    • 5
  • Nuria Bargalló
    • 2
    • 6
    • 7
  • Martijn P. van den Heuvel
    • 3
  • Lourdes Fañanás
    • 1
    • 2
  1. 1.Unidad de Antropología, Departamento de Biología Animal, Facultad de Biología and Instituto de Biomedicina (IBUB)Universitat de BarcelonaBarcelonaSpain
  2. 2.Centro de Investigaciones Biomédicas en Red de Salud Mental (CIBERSAM)MadridSpain
  3. 3.Brain Center Rudolf Magnus, Department of PsychiatryUniversity Medical Center UtrechtUtrechtthe Netherlands
  4. 4.BarcelonaBeta Brain Research CenterPasqual Maragall FoundationBarcelonaSpain
  5. 5.Centro de Investigación Biomédica en Red en BioingenieríaBiomedicina y Nanomedicina (CIBER-BBN)ZaragozaSpain
  6. 6.Centro de Diagnóstico por ImagenHospital ClínicoBarcelonaSpain
  7. 7.Medical Image core facilityInstitut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)BarcelonaSpain

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