TY - JOUR
T1 - Association of depressive symptoms and heart rate variability in Vietnam war-era twins
T2 - A longitudinal twin difference study
AU - Huang, Minxuan
AU - Shah, Amit
AU - Su, Shaoyong
AU - Goldberg, Jack
AU - Lampert, Rachel J.
AU - Levantsevych, Oleksiy M.
AU - Shallenberger, Lucy
AU - Pimple, Pratik
AU - Bremner, J. Douglas
AU - Vaccarino, Viola
N1 - Funding Information:
Funding/Support: This work was supported by the National Institutes of Health (grants R01 HL68630, R01 AG026255, R01 HL125246, 2K24 HL077506, R01 HL109413, and R01HL136205). The US Department of Veterans Affairs has provided financial support for the development and maintenance of the Vietnam Era Twin Registry.
Publisher Copyright:
© 2018 American Medical Association. All rights reserved.
PY - 2018/7
Y1 - 2018/7
N2 - IMPORTANCE: Depressive symptoms are associated with lower heart rate variability (HRV), an index of autonomic dysregulation, but the direction of the association remains unclear. OBJECTIVE :To investigate the temporal association between depression and HRV. DESIGN, SETTINGS, AND PARTICIPANTS: A longitudinal, cross-lagged twin difference study, with baseline assessments from March 2002 to March 2006 (visit 1) and a 7-year follow-up (visit 2) at an academic research center with participants recruited from a national twin registry. Twins (n = 166) from the Vietnam Era Twin Registry, who served in the US military during the VietnamWar, and were discordant for depression at baseline were recruited. MAIN OUTCOMES AND MEASURES: At both visits, depressive symptomswere measured using the Beck Depression Inventory-II (BDI-II), and HRV was measured through 24-hour electrocardiogram monitoring. To assess the direction of the association, within-pair differences in multivariable mixed-effects regression models were examined, and standardized β coefficients for both pathways were calculated. The associations were evaluated separately in monozygotic and dizygotic twins. RESULTS: In the final analytic sample (N = 146), all participants were men, 138 (95%) were white, and the mean (SD) age was 54 (3) years at baseline. Results showed consistent associations between visit 1 HRV and visit 2 BDI score across all HRV domains and models (β coefficients ranging from -0.14 to -0.29), which were not explained by antidepressants or other participant characteristics. Themagnitude of the association was similar in the opposite pathway linking visit 1 BDI score to visit 2 HRV, with β coefficients ranging from 0.05 to -0.30, but it was largely explained by antidepressant use. In stratified analysis by zygosity, significant associations were observed in monozygotic and dizygotic twins for the path linking visit 1 HRV to visit 2 BDI score, although the associations were slightly stronger in dizygotic twins. CONCLUSIONS AND RELEVANCE: The association between depression and autonomic dysregulation, indexed by HRV, is bidirectional, with stronger evidence suggesting that autonomic function affects depression risk rather than vice versa. The opposite causal pathway from depression to lower HRV is mostly driven by antidepressant use. These findings highlight an important role of autonomic nervous system in the risk of depression and contribute new understanding of the mechanisms underlying the comorbidity of depression and cardiovascular disease.
AB - IMPORTANCE: Depressive symptoms are associated with lower heart rate variability (HRV), an index of autonomic dysregulation, but the direction of the association remains unclear. OBJECTIVE :To investigate the temporal association between depression and HRV. DESIGN, SETTINGS, AND PARTICIPANTS: A longitudinal, cross-lagged twin difference study, with baseline assessments from March 2002 to March 2006 (visit 1) and a 7-year follow-up (visit 2) at an academic research center with participants recruited from a national twin registry. Twins (n = 166) from the Vietnam Era Twin Registry, who served in the US military during the VietnamWar, and were discordant for depression at baseline were recruited. MAIN OUTCOMES AND MEASURES: At both visits, depressive symptomswere measured using the Beck Depression Inventory-II (BDI-II), and HRV was measured through 24-hour electrocardiogram monitoring. To assess the direction of the association, within-pair differences in multivariable mixed-effects regression models were examined, and standardized β coefficients for both pathways were calculated. The associations were evaluated separately in monozygotic and dizygotic twins. RESULTS: In the final analytic sample (N = 146), all participants were men, 138 (95%) were white, and the mean (SD) age was 54 (3) years at baseline. Results showed consistent associations between visit 1 HRV and visit 2 BDI score across all HRV domains and models (β coefficients ranging from -0.14 to -0.29), which were not explained by antidepressants or other participant characteristics. Themagnitude of the association was similar in the opposite pathway linking visit 1 BDI score to visit 2 HRV, with β coefficients ranging from 0.05 to -0.30, but it was largely explained by antidepressant use. In stratified analysis by zygosity, significant associations were observed in monozygotic and dizygotic twins for the path linking visit 1 HRV to visit 2 BDI score, although the associations were slightly stronger in dizygotic twins. CONCLUSIONS AND RELEVANCE: The association between depression and autonomic dysregulation, indexed by HRV, is bidirectional, with stronger evidence suggesting that autonomic function affects depression risk rather than vice versa. The opposite causal pathway from depression to lower HRV is mostly driven by antidepressant use. These findings highlight an important role of autonomic nervous system in the risk of depression and contribute new understanding of the mechanisms underlying the comorbidity of depression and cardiovascular disease.
UR - http://www.scopus.com/inward/record.url?scp=85049571569&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85049571569&partnerID=8YFLogxK
U2 - 10.1001/jamapsychiatry.2018.0747
DO - 10.1001/jamapsychiatry.2018.0747
M3 - Article
C2 - 29799951
AN - SCOPUS:85049571569
SN - 2168-622X
VL - 75
SP - 705
EP - 712
JO - JAMA Psychiatry
JF - JAMA Psychiatry
IS - 7
ER -