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Neurobiology of the major psychoses: a translational perspective on brain structure and function—the FOR2107 consortium

  • Tilo Kircher
  • Markus Wöhr
  • Igor Nenadic
  • Rainer Schwarting
  • Gerhard Schratt
  • Judith Alferink
  • Carsten Culmsee
  • Holger Garn
  • Tim Hahn
  • Bertram Müller-Myhsok
  • Astrid Dempfle
  • Maik Hahmann
  • Andreas Jansen
  • Petra Pfefferle
  • Harald Renz
  • Marcella Rietschel
  • Stephanie H. Witt
  • Markus Nöthen
  • Axel Krug
  • Udo Dannlowski
Original Paper

Abstract

Genetic (G) and environmental (E) factors are involved in the etiology and course of the major psychoses (MP), i.e. major depressive disorder (MDD), bipolar disorder (BD), schizoaffective disorder (SZA) and schizophrenia (SZ). The neurobiological correlates by which these predispositions exert their influence on brain structure, function and course of illness are poorly understood. In the FOR2107 consortium, animal models and humans are investigated. A human cohort of MP patients, healthy subjects at genetic and/or environmental risk, and control subjects (N = 2500) has been established. Participants are followed up after 2 years and twice underwent extensive deep phenotyping (MR imaging, clinical course, neuropsychology, personality, risk/protective factors, biomaterials: blood, stool, urine, hair, saliva). Methods for data reduction, quality assurance for longitudinal MRI data, and (deep) machine learning techniques are employed. In the parallelised animal cluster, genetic risk was introduced by a rodent model (Cacna1c deficiency) and its interactions with environmental risk and protective factors are studied. The animals are deeply phenotyped regarding cognition, emotion, and social function, paralleling the variables assessed in humans. A set of innovative experimental projects connect and integrate data from the human and animal parts, investigating the role of microRNA, neuroplasticity, immune signatures, (epi-)genetics and gene expression. Biomaterial from humans and animals are analyzed in parallel. The FOR2107 consortium will delineate pathophysiological entities with common neurobiological underpinnings (“biotypes”) and pave the way for an etiologic understanding of the MP, potentially leading to their prevention, the prediction of individual disease courses, and novel therapies in the future.

Keywords

Cohort study Animal model Mental disorder Etiology Course of illness 

Notes

Acknowledgements

The FOR 2107 consortium is supported by the German Research Council (Deutsche Forschungsgemeinschaft, DFG, Grant nos. KI 588/14-1, KI 588/14-2, KR 3822/7-1, KR 3822/7-2, NE 2254/1-2, DA 1151/5-1, DA 1151/5-2, SCHW 559/14-1, SCHW 559/14-2, WO 1732/4-1, WO 1732/4-2, AL 1145/5-2, CU 43/9-2, GA 545/7-2, RI 908/11-2, WI 3439/3-2, NO 246/10-2, DE 1614/3-2, HA 7070/2-2, JA 1890/7-1, JA 1890/7-2, MU 1315/8-2, RE 737/20-2, PF 784/1-2, KI 588/17-1, CU 43/9-1). We are deeply indebted to all participants of this study, the recruitment sites and their staff.

Compliance with ethical standards

Conflict of interest

On behalf of all authors, the corresponding author states that there is no conflict of interest.

Supplementary material

406_2018_943_MOESM1_ESM.docx (20 kb)
Supplementary material 1 (DOCX 19 KB)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Tilo Kircher
    • 1
    • 2
  • Markus Wöhr
    • 2
    • 3
  • Igor Nenadic
    • 1
    • 2
  • Rainer Schwarting
    • 2
    • 3
  • Gerhard Schratt
    • 4
  • Judith Alferink
    • 5
  • Carsten Culmsee
    • 2
    • 6
  • Holger Garn
    • 7
  • Tim Hahn
    • 5
  • Bertram Müller-Myhsok
    • 8
  • Astrid Dempfle
    • 9
  • Maik Hahmann
    • 10
  • Andreas Jansen
    • 1
    • 2
    • 11
  • Petra Pfefferle
    • 12
  • Harald Renz
    • 7
  • Marcella Rietschel
    • 13
  • Stephanie H. Witt
    • 13
  • Markus Nöthen
    • 14
  • Axel Krug
    • 1
    • 2
  • Udo Dannlowski
    • 5
  1. 1.Department of Psychiatry and PsychotherapyUniversity of MarburgMarburgGermany
  2. 2.Centre for Mind, Brain and BehaviourUniversity of MarburgMarburgGermany
  3. 3.Department of Experimental and Biological PsychologyUniversity of MarburgMarburgGermany
  4. 4.Department of NeuroscienceETH ZürichZurichGermany
  5. 5.Department of Psychiatry and PsychotherapyUniversity of MünsterMunichGermany
  6. 6.Institute for Pharmacology and Clinical PharmacyUniversity of MarburgMarburgGermany
  7. 7.Institute of Laboratory Medicine and PathobiochemistryUniversity of MarburgMarburgGermany
  8. 8.Max Planck Institute of PsychiatryMunichGermany
  9. 9.Institute of Medical Informatics and StatisticsUniversity of KielKielGermany
  10. 10.Coordinating Centre for Clinical TrialsUniversity of MarburgMarburgGermany
  11. 11.Core-Facility Brainimaging, Faculty of MedicineUniversity of MarburgMarburgGermany
  12. 12.Comprehensive Biomaterial Bank MarburgUniversity of MarburgMarburgGermany
  13. 13.Department of Genetic Epidemiology in Psychiatry, Medical Faculty Mannheim, Central Institute of Mental HealthUniversity of HeidelbergMannheimGermany
  14. 14.Department of Genomics, Life and Brain CentreUniversity of BonnBonnGermany

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