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Sex-dependent pathophysiology as predictors of comorbidity of major depressive disorder and cardiovascular disease

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Abstract

There is a strong and growing literature showing that key aspects of brain development may be critical antecedents of adult physiology and behavior or may lead to physiological and psychiatric disorders in adulthood. Many are significantly influenced by sex-dependent factors. Neurons of the paraventricular nucleus (PVN) of the hypothalamus occupy a key position in regulating homeostatic, neuroendocrine, and behavioral functions. This brain area is a critical link for our understanding of the etiology of a number of disorders with components ranging from mood to feeding and energy balance and to autonomic nervous system regulation. Thus, based on common brain circuitry, the PVN may be a critical anatomical intersection for understanding comorbidities among depression, obesity, and cardiovascular risk. Historically, the majority of approaches to brain development examine neuronal, glial, and vascular factors independently, with notably less emphasis on vascular contributions. The realization that the PVN undergoes a unique vascular developmental process places added value on discerning the cellular and molecular mechanisms that drive its late-onset angiogenesis and further implications for neuronal differentiation and function. This has ramifications in humans for understanding chronic, and sometimes fatal, comorbidities that share sex-dependent biological bases in development through functional and anatomical intersections with the hypothalamus.

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Acknowledgments

The ideas in this review emanated from research on a translational (human to animal) program project that was supported by the Office for Research on Women’s Health (ORWH) and National Institute of Mental Health (ORWH-NIMH P50 MH082679; principal investigators: Goldstein, Tobet, and Handa; http://mddscor.bwh.harvard.edu). Additionally, it was in part supported by NIMH-NHLBI R01 MH074679 (principal investigator: Goldstein). We are very grateful for the funding support and to our incredible research teams at Brigham and Women’s Hospital (Clinical Neuroscience Laboratory for Sex Differences in the Brain (http://cnl-sd.bwh.harvard.edu), Colorado State University, and University of Arizona College of Medicine.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Biomedical Sciences and School of Biomedical Engineering, Colorado State University, 1617 Campus Delivery, Fort Collins, CO, 80523, USA

    S. A. Tobet

  2. Department of Basic Medical Sciences, University of Arizona College of Medicine, 425 North 5th Street, Phoenix, AZ, 85004, USA

    R. J. Handa

  3. Department of Psychiatry, Harvard Medical School, Boston, MA, USA

    J. M. Goldstein

  4. Department of Medicine, Harvard Medical School, Boston, MA, USA

    J. M. Goldstein

  5. Connors Center for Women’s Health and Gender Biology, Brigham and Women’s Hospital (BWH), One Brigham Circle, 1620 Tremont Street BC-3-34, 3rd Floor, Boston, MA, 02120, USA

    J. M. Goldstein

  6. Department of Psychiatry, Brigham and Women’s Hospital (BWH), One Brigham Circle, 1620 Tremont Street BC-3-34, 3rd Floor, Boston, MA, 02120, USA

    J. M. Goldstein

  7. Department of Medicine, Brigham and Women’s Hospital (BWH), One Brigham Circle, 1620 Tremont Street BC-3-34, 3rd Floor, Boston, MA, 02120, USA

    J. M. Goldstein

Authors
  1. S. A. Tobet
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  2. R. J. Handa
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  3. J. M. Goldstein
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Correspondence to J. M. Goldstein.

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Tobet, S.A., Handa, R.J. & Goldstein, J.M. Sex-dependent pathophysiology as predictors of comorbidity of major depressive disorder and cardiovascular disease. Pflugers Arch - Eur J Physiol 465, 585–594 (2013). https://doi.org/10.1007/s00424-013-1248-6

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  • DOI: https://doi.org/10.1007/s00424-013-1248-6

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