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Neural Mechanisms of Early-Life Social Stress as a Developmental Risk Factor for Severe Psychiatric Disorders.
Reinwald, Jonathan Rochus; Becker, Robert; Mallien, Anne Stephanie; Falfan-Melgoza, Claudia; Sack, Markus; Clemm von Hohenberg, Christian; Braun, Urs; Cosa Linan, Alejandro; Gass, Natalia; Vasilescu, Andrei-Nicolae; Tollens, Fabian; Lebhardt, Philipp; Pfeiffer, Natascha; Inta, Dragos; Meyer-Lindenberg, Andreas; Gass, Peter; Sartorius, Alexander; Weber-Fahr, Wolfgang.
Affiliation
  • Reinwald JR; Research Group Translational Imaging, Department of Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany; Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heide
  • Becker R; Research Group Translational Imaging, Department of Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.
  • Mallien AS; Research Group Animal Models in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.
  • Falfan-Melgoza C; Research Group Translational Imaging, Department of Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.
  • Sack M; Research Group Translational Imaging, Department of Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.
  • Clemm von Hohenberg C; Research Group Translational Imaging, Department of Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany; Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heide
  • Braun U; Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany; Research Group Systems Neuroscience in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelbe
  • Cosa Linan A; Research Group In Silico Psychopharmacology, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.
  • Gass N; Research Group Translational Imaging, Department of Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.
  • Vasilescu AN; Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany; Research Group Animal Models in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Ger
  • Tollens F; Research Group Translational Imaging, Department of Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.
  • Lebhardt P; Research Group Translational Imaging, Department of Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.
  • Pfeiffer N; Research Group Animal Models in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.
  • Inta D; Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany; Research Group Animal Models in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Ger
  • Meyer-Lindenberg A; Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.
  • Gass P; Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany; Research Group Animal Models in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Ger
  • Sartorius A; Research Group Translational Imaging, Department of Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany; Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heide
  • Weber-Fahr W; Research Group Translational Imaging, Department of Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Heidelberg, Germany.
Biol Psychiatry ; 84(2): 116-128, 2018 07 15.
Article in En | MEDLINE | ID: mdl-29397900
ABSTRACT

BACKGROUND:

To explore the domain-general risk factor of early-life social stress in mental illness, rearing rodents in persistent postweaning social isolation has been established as a widely used animal model with translational relevance for neurodevelopmental psychiatric disorders such as schizophrenia. Although changes in resting-state brain connectivity are a transdiagnostic key finding in neurodevelopmental diseases, a characterization of imaging correlates elicited by early-life social stress is lacking.

METHODS:

We performed resting-state functional magnetic resonance imaging of postweaning social isolation rats (N = 23) 9 weeks after isolation. Addressing well-established transdiagnostic connectivity changes of psychiatric disorders, we focused on altered frontal and posterior connectivity using a seed-based approach. Then, we examined changes in regional network architecture and global topology using graph theoretical analysis.

RESULTS:

Seed-based analyses demonstrated reduced functional connectivity in frontal brain regions and increased functional connectivity in posterior brain regions of postweaning social isolation rats. Graph analyses revealed a shift of the regional architecture, characterized by loss of dominance of frontal regions and emergence of nonfrontal regions, correlating to our behavioral results, and a reduced modularity in isolation-reared rats.

CONCLUSIONS:

Our result of functional connectivity alterations in the frontal brain supports previous investigations postulating social neural circuits, including prefrontal brain regions, as key pathways for risk for mental disorders arising through social stressors. We extend this knowledge by demonstrating more widespread changes of brain network organization elicited by early-life social stress, namely a shift of hubness and dysmodularity. Our results highly resemble core alterations in neurodevelopmental psychiatric disorders such as schizophrenia, autism, and attention-deficit/hyperactivity disorder in humans.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Social Isolation / Brain / Conditioning, Psychological / Mental Disorders / Neural Pathways Type of study: Diagnostic_studies / Etiology_studies / Prognostic_studies / Risk_factors_studies Limits: Animals Language: En Journal: Biol Psychiatry Year: 2018 Type: Article
Fulltext
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PubMed Links
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Social Isolation / Brain / Conditioning, Psychological / Mental Disorders / Neural Pathways Type of study: Diagnostic_studies / Etiology_studies / Prognostic_studies / Risk_factors_studies Limits: Animals Language: En Journal: Biol Psychiatry Year: 2018 Type: Article