PROJECT I. Sweat Patch Biomarkers: Clinical Studies. This is currently the main focus of the SNIB. We previously showed that neural and immune biomarkers are detectable in sweat and strongly correlate with plasma levels in a group of women with major depressive disorder (MDD) in clinical remission (Marques-Deak, 2006, J Immunol Methods;Cizza 2008, Biol Psych). Specifically, pro-inflammatory cytokines were elevated, as was the sympathetic neuropeptide neuropeptide Y (NPY) and the sensory/pain-related neuropeptides, substance P (SP) and CGRP (calcitonin gene-related peptide), while the parasympathetic neuropeptide vasoactive intestinal polypeptide (VIP) was significantly decreased. This pattern is consistent with a shift in MDD from parasympathetic to sympathetic tone, and an underlying pro-inflammatory state that could account for enhanced susceptibility to conditions known to be co-morbidly expressed with MDD, including cardiovascular disease, osteoporosis and diabetes. Moreover, biomarker levels strongly correlated with symptoms of depression and anxiety, indicating functional significance of these biomarker profiles. In order to determine the extent to which particular biomarker profiles reflect specific diseases or a state of health, in FY11 we are continuing to apply sweat patches in five ongoing IRB approved clinical protocols in collaboration with other NIH institutes and extramural institutions, including: (i) Emory University TRD-Infliximab Study. (Emory University IRB 00011734, NIMH OHSR Exemption #4025);(ii) Brazil - OCD Study (NIH protocol IRB 3737);(iii) Emory/CDC CFS Study (Emory University IRB 000551-2005, NIMH OHSR Exemption #4026);(iv) NCCAM - Tai Chi/Cancer Survivor Study (NCI protocol #06-AT-0016);(v) GSA - Work Environment Study (NIA IRB 2003-142). Results of study (v), (GSA Workplace Study) indicate that physical features of the workplace environment are associated with altered measures of the physiological stress response, as indicated by a greater rise in salivary cortisol upon awakening and flatter circadian variation of heart rate variability in subjects occupying old office space compared to those in new office space (Thayer et al. 2010 Eur J Cardiovasc Prev Rehabil). Our current studies focus on transitioning to a more high-throughput static antibody glass chip microarray platform and developing a better patch using nanotechnology. In FY10-11 the SNIB obtained funding support for this project through an NIH Directors Challenge Award in partnership with the NCCAM Director;NCCAM;the Center for Neuroscience and Regenerative Medicine (CNRM)/USUHS/DoD/NIH);and NIMH IRP funds.

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National Center for Complementary & Alternative Medicine
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Thayer, Julian F; Sternberg, Esther M (2010) Neural aspects of immunomodulation: focus on the vagus nerve. Brain Behav Immun 24:1223-8
Butts, C L; Candando, K M; Warfel, J et al. (2010) Progesterone regulation of uterine dendritic cell function in rodents is dependent on the stage of estrous cycle. Mucosal Immunol 3:496-505
Thayer, Julian F; Verkuil, Bart; Brosschot, Jos F et al. (2010) Effects of the physical work environment on physiological measures of stress. Eur J Cardiovasc Prev Rehabil 17:431-9
Silverman, Marni N; Sternberg, Esther M (2010) Matching therapy to body rhythms: an endocrine approach to treating rheumatoid arthritis. J Rheumatol 37:1981-2
Marques, Andrea H; Silverman, Marni N; Sternberg, Esther M (2010) Evaluation of stress systems by applying noninvasive methodologies: measurements of neuroimmune biomarkers in the sweat, heart rate variability and salivary cortisol. Neuroimmunomodulation 17:205-8