Benjamin C Nephew1, Marcelo Febo2, Wei Huang3, Luis M Colon-Perez2, Laurellee Payne3, Guillaume L Poirier3, Owen Greene4, Jean A King3. 1. Department of Biomedical Sciences, Tufts University Cummings School of Veterinary Medicine, 200 Westborough Road, North Grafton, MA 01536, USA. Electronic address: bcnephew@aol.com. 2. Department of Psychiatry, McKnight Brain Institute, University of Florida College of Medicine, Gainesville, FL, 32611, USA. 3. Center for Comparative NeuroImaging, Department of Psychiatry, University of Massachusetts Medical School, Worcester, MA, 01655, USA. 4. Department of Biomedical Sciences, Tufts University Cummings School of Veterinary Medicine, 200 Westborough Road, North Grafton, MA 01536, USA.
Abstract
INTRODUCTION: Continued development and refinement of resting state functional connectivity (RSFC) fMRI techniques in both animal and clinical studies has enhanced our comprehension of the adverse effects of stress on psychiatric health. The objective of the current study was to assess both maternal behavior and resting state functional connectivity (RSFC) changes in these animals when they were dams caring for their own young. It was hypothesized that ECSS exposed dams would express depressed maternal care and exhibit similar (same networks), yet different specific changes in RSFC (different individual nuclei) than reported when they were adult females. METHODS: We have developed an ethologically relevant transgenerational model of the role of chronic social stress (CSS) in the etiology of postpartum depression and anxiety. Initial fMRI investigation of the CSS model indicates that early life exposure to CSS (ECSS) induces long term changes in functional connectivity in adult nulliparous female F1 offspring. RESULTS: ECSS in F1 dams resulted in depressed maternal care specifically during early lactation, consistent with previous CSS studies, and induced changes in functional connectivity in regions associated with sensory processing, maternal and emotional responsiveness, memory, and the reward pathway, with robust changes in anterior cingulate circuits. LIMITATIONS: The sample sizes for the fMRI groups were low, limiting statistical power. CONCLUSION: This behavioral and functional neuroanatomical foundation can now be used to enhance our understanding of the neural etiology of early life stress associated disorders and test preventative measures and treatments for stress related disorders.
INTRODUCTION: Continued development and refinement of resting state functional connectivity (RSFC) fMRI techniques in both animal and clinical studies has enhanced our comprehension of the adverse effects of stress on psychiatric health. The objective of the current study was to assess both maternal behavior and resting state functional connectivity (RSFC) changes in these animals when they were dams caring for their own young. It was hypothesized that ECSS exposed dams would express depressed maternal care and exhibit similar (same networks), yet different specific changes in RSFC (different individual nuclei) than reported when they were adult females. METHODS: We have developed an ethologically relevant transgenerational model of the role of chronic social stress (CSS) in the etiology of postpartum depression and anxiety. Initial fMRI investigation of the CSS model indicates that early life exposure to CSS (ECSS) induces long term changes in functional connectivity in adult nulliparous female F1 offspring. RESULTS: ECSS in F1 dams resulted in depressed maternal care specifically during early lactation, consistent with previous CSS studies, and induced changes in functional connectivity in regions associated with sensory processing, maternal and emotional responsiveness, memory, and the reward pathway, with robust changes in anterior cingulate circuits. LIMITATIONS: The sample sizes for the fMRI groups were low, limiting statistical power. CONCLUSION: This behavioral and functional neuroanatomical foundation can now be used to enhance our understanding of the neural etiology of early life stress associated disorders and test preventative measures and treatments for stress related disorders.
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