title: Brain network reorganization differs in response to stress in rats genetically predisposed to depression and stress-resilient rats.
abstract: Treatment-resistant depression (TRD) remains a pressing clinical problem. Optimizing treatment requires better definition of the specificity of the involved brain circuits. The rat strain bred for negative cognitive state (NC) represents a genetic animal model of TRD with high face, construct and predictive validity. Vice versa, the positive cognitive state (PC) strain represents a stress-resilient phenotype. Although NC rats show depressive-like behavior, some symptoms such as anhedonia require an external trigger, i.e. a stressful event, which is similar to humans when stressful event induces a depressive episode in genetically predisposed individuals (gene-environment interaction). We aimed to distinguish neurobiological predisposition from the depressogenic pathology at the level of brain-network reorganization. For this purpose, resting-state functional magnetic resonance imaging time series were acquired at 9.4 Tesla scanner in NC (N=11) and PC (N=7) rats before and after stressful event. We used a graph theory analytical approach to calculate the brain-network global and local properties. There was no difference in the global characteristics between the strains. At the local level, the response in the risk strain was characterized with an increased internodal role and reduced local clustering and efficiency of the anterior cingulate cortex (ACC) and prelimbic cortex compared to the stress-resilient strain. We suggest that the increased internodal role of these prefrontal regions could be due to the enhancement of some of their long-range connections, given their connectivity with the amygdala and other default-mode-like network hubs, which could create a bias to attend to negative information characteristic for depression.
authors.affiliation: Department of Neuroimaging, Research Group Translational Imaging, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Gass
authors.affiliation: Department of Neuroimaging, Research Group Translational Imaging, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Becker
authors.affiliation: Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, USA.|Department of Radiology and Imaging Sciences, Indiana University, Indianapolis, IN, USA.
authors.forename: A J
authors.initials: AJ
authors.lastname: Schwarz
authors.affiliation: Department of Neuroimaging, Research Group Translational Imaging, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Weber-Fahr
authors.affiliation: Department of Neuroimaging, Research Group Translational Imaging, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.|Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Clemm von Hohenberg
authors.affiliation: Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Vollmayr
authors.affiliation: Department of Neuroimaging, Research Group Translational Imaging, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.|Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Sartorius
mesh_terms: D000223:Adaptation, Psychological / Q000502:physiology; D000818:Animals; D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping; D003863:Depression / Q000235:genetics* / Q000503:physiopathology*; D004195:Disease Models, Animal; D004924:Escape Reaction / Q000502:physiology; D006179:Gyrus Cinguli / Q000503:physiopathology; D007090:Image Interpretation, Computer-Assisted; D008032:Limbic System / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D009415:Nerve Net / Q000503:physiopathology*; D010641:Phenotype; D051381:Rats; D017207:Rats, Sprague-Dawley; D055500:Resilience, Psychological; D013315:Stress, Psychological / Q000235:genetics / Q000503:physiopathology