TY - JOUR
T1 - Altered populations of natural killer cells, cytotoxic T lymphocytes, and regulatory T cells in major depressive disorder
T2 - Association with sleep disturbance
AU - Suzuki, Hideo
AU - Savitz, Jonathan
AU - Kent Teague, T.
AU - Gandhapudi, Siva K.
AU - Tan, Chibing
AU - Misaki, Masaya
AU - McKinney, Brett A.
AU - Irwin, Michael R.
AU - Drevets, Wayne C.
AU - Bodurka, Jerzy
N1 - Funding Information:
This study was supported by the 1R01MH0908099 award from National Institute of Mental Health, National Institutes of Health, United States. The authors thank all staff members at Laureate Institute for Brain Research, especially Brent Wurfel, M.D., Matthew Meyer, M.D., and William Yates, M.D. for conducting psychiatric interviews, Tim Collins for administering clinical interview and assessments, Megan Cole, Saman Aziz, and Cindy Bonebright for performing blood draws, and Julie Owen, Julie Crawford, Leslie Walker, and Tressia Lewis for working on all MRI technical issues. In addition, the authors acknowledge the contributions of Julie H. Marino, Ashlee Taylor, Brenda Davis, and Debbie Neal from the laboratory of TKT towards the transport, processing, and handling of the blood samples. WCD is an employee of Janssen Research & Development, LLC, of Johnson & Johnson, Inc. The other authors declare no financial interests in relation to the present work.
Funding Information:
This study was supported by the 1R01MH0908099 award from National Institute of Mental Health , National Institutes of Health, United States. The authors thank all staff members at Laureate Institute for Brain Research, especially Brent Wurfel, M.D., Matthew Meyer, M.D., and William Yates, M.D. for conducting psychiatric interviews, Tim Collins for administering clinical interview and assessments, Megan Cole, Saman Aziz, and Cindy Bonebright for performing blood draws, and Julie Owen, Julie Crawford, Leslie Walker, and Tressia Lewis for working on all MRI technical issues. In addition, the authors acknowledge the contributions of Julie H. Marino, Ashlee Taylor, Brenda Davis, and Debbie Neal from the laboratory of TKT towards the transport, processing, and handling of the blood samples. WCD is an employee of Janssen Research & Development , LLC, of Johnson & Johnson, Inc . The other authors declare no financial interests in relation to the present work. Appendix A
Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2017/11
Y1 - 2017/11
N2 - A subset of individuals with major depressive disorder (MDD) have impaired adaptive immunity characterized by a greater vulnerability to viral infection and a deficient response to vaccination along with a decrease in the number and/or activity of T cells and natural killer cells (NKC). Nevertheless, it remains unclear which specific subsets of lymphocytes are altered in MDD, a shortcoming we address here by utilizing an advanced fluorescence-activated cell sorting (FACS) method that allows for the differentiation of important functionally-distinct lymphocyte sub-populations. Furthermore, despite evidence that sleep disturbance, which is a core symptom of MDD, is itself associated with alterations in lymphocyte distributions, there is a paucity of studies examining the contribution of sleep disturbance on lymphocyte populations in MDD populations. Here, we measured differences in the percentages of 13 different lymphocytes and 6 different leukocytes in 54 unmedicated MDD patients (partially remitted to moderate) and 56 age and sex-matched healthy controls (HC). The relationship between self-reported sleep disturbance and cell counts was evaluated in the MDD group using the Pittsburgh Sleep Quality Index (PSQI). The MDD group showed a significantly increased percentage of CD127low/CCR4+ Treg cells, and memory Treg cells, as well as a reduction in CD56+CD16− (putative immunoregulatory) NKC counts, the latter, prior to correction for body mass index. There also was a trend for higher effector memory CD8+ cell counts in the MDD group versus the HC group. Further, within the MDD group, self-reported sleep disturbance was associated with an increased percentage of effector memory CD8+ cells but with a lower percentage of CD56+CD16− NKC. These results provide important new insights into the immune pathways involved in MDD, and provide novel evidence that MDD and associated sleep disturbance increase effector memory CD8+ and Treg pathways. Targeting sleep disturbance may have implications as a therapeutic strategy to normalize NKC and memory CD8+ cells in MDD.
AB - A subset of individuals with major depressive disorder (MDD) have impaired adaptive immunity characterized by a greater vulnerability to viral infection and a deficient response to vaccination along with a decrease in the number and/or activity of T cells and natural killer cells (NKC). Nevertheless, it remains unclear which specific subsets of lymphocytes are altered in MDD, a shortcoming we address here by utilizing an advanced fluorescence-activated cell sorting (FACS) method that allows for the differentiation of important functionally-distinct lymphocyte sub-populations. Furthermore, despite evidence that sleep disturbance, which is a core symptom of MDD, is itself associated with alterations in lymphocyte distributions, there is a paucity of studies examining the contribution of sleep disturbance on lymphocyte populations in MDD populations. Here, we measured differences in the percentages of 13 different lymphocytes and 6 different leukocytes in 54 unmedicated MDD patients (partially remitted to moderate) and 56 age and sex-matched healthy controls (HC). The relationship between self-reported sleep disturbance and cell counts was evaluated in the MDD group using the Pittsburgh Sleep Quality Index (PSQI). The MDD group showed a significantly increased percentage of CD127low/CCR4+ Treg cells, and memory Treg cells, as well as a reduction in CD56+CD16− (putative immunoregulatory) NKC counts, the latter, prior to correction for body mass index. There also was a trend for higher effector memory CD8+ cell counts in the MDD group versus the HC group. Further, within the MDD group, self-reported sleep disturbance was associated with an increased percentage of effector memory CD8+ cells but with a lower percentage of CD56+CD16− NKC. These results provide important new insights into the immune pathways involved in MDD, and provide novel evidence that MDD and associated sleep disturbance increase effector memory CD8+ and Treg pathways. Targeting sleep disturbance may have implications as a therapeutic strategy to normalize NKC and memory CD8+ cells in MDD.
KW - CD8 cells
KW - Depression
KW - Flow cytometry
KW - Natural killer cells
KW - Regulatory T cells
KW - Sleep
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UR - http://www.scopus.com/inward/citedby.url?scp=85021066782&partnerID=8YFLogxK
U2 - 10.1016/j.bbi.2017.06.011
DO - 10.1016/j.bbi.2017.06.011
M3 - Article
C2 - 28645775
AN - SCOPUS:85021066782
SN - 0889-1591
VL - 66
SP - 193
EP - 200
JO - Brain, Behavior, and Immunity
JF - Brain, Behavior, and Immunity
ER -