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

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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.

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Acknowledgments

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.

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Authors and Affiliations

  1. Unidad de Antropología, Departamento de Biología Animal, Facultad de Biología and Instituto de Biomedicina (IBUB), Universitat de Barcelona, Av. Diagonal, 643, 08028, Barcelona, Spain

    Aldo Córdova-Palomera, Mar Fatjó-Vilas & Lourdes Fañanás

  2. Centro de Investigaciones Biomédicas en Red de Salud Mental (CIBERSAM), C/Doctor Esquerdo, 46, 28007, Madrid, Spain

    Aldo Córdova-Palomera, Mar Fatjó-Vilas, Nuria Bargalló & Lourdes Fañanás

  3. Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Heidelberglaan 100, 3508 GA, Utrecht, the Netherlands

    Marcel A. de Reus & Martijn P. van den Heuvel

  4. BarcelonaBeta Brain Research Center, Pasqual Maragall Foundation, C/Dr Aiguader, 88, 08003, Barcelona, Spain

    Carles Falcón

  5. Centro de Investigación Biomédica en Red en Bioingeniería, Biomedicina y Nanomedicina (CIBER-BBN), C/Poeta Mariano Esquillor, s/n., 50018, Zaragoza, Spain

    Carles Falcón

  6. Centro de Diagnóstico por Imagen, Hospital Clínico, C/Villarroel, 170, 08036, Barcelona, Spain

    Nuria Bargalló

  7. Medical Image core facility, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), C/Rosselló, 149-153, 08036, Barcelona, Spain

    Nuria Bargalló

Authors
  1. Aldo Córdova-Palomera
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  2. Marcel A. de Reus
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  3. Mar Fatjó-Vilas
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  4. Carles Falcón
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  5. Nuria Bargalló
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  6. Martijn P. van den Heuvel
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  7. Lourdes Fañanás
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Corresponding author

Correspondence to Lourdes Fañanás.

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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.

Additional information

Martijn P. van den Heuvel and Lourdes Fañanás contributed equally to this work.

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Córdova-Palomera, A., de Reus, M.A., Fatjó-Vilas, M. et al. FKBP5 modulates the hippocampal connectivity deficits in depression: a study in twins. Brain Imaging and Behavior 11, 62–75 (2017). https://doi.org/10.1007/s11682-015-9503-4

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  • DOI: https://doi.org/10.1007/s11682-015-9503-4

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