Abstract
BACKGROUND: Methylarginines are endogenous nitric oxide synthase inhibitors that have been implicated in depression. This study measured serum concentrations of l-arginine, asymmetric (ADMA) and symmetric (SDMA) dimethylarginine in a representative sample of older community-dwelling adults and determined their association with incident depression over 6-years of follow-up.
METHODS: Data on clinical, lifestyle, and demographic characteristics, methylated arginines, and l-arginine (measured using LC-MS/MS) were collected from a population-based sample of older Australian adults (Median age=64 years; IQR=60-70) from the Hunter Community Study. Clinical depression was defined as a Centre for Epidemiological Studies Depression Scale (CES-D) score ≥16 or use of antidepressant medications.
RESULTS: In adjusted analyses ADMA (Q3), SDMA (Q2), l-arginine (Q2), gender, and asthma remained statistically significant predictors of incident depression at follow-up. Quartile 3 of ADMA concentration was associated with 3.5 times the odds of developing depression compared with Q1 (OR=3.54; 95% CI: 1.25-9.99).
LIMITATIONS: Limitations of our study include the use of a subjective self-reported questionnaire tool using a dichotomous cut-off, together with use of antidepressant medications, as proxies for clinical depression. Moreover, similarly to most population studies on methylated arginines, the measurement of ADMA and SDMA from blood does not necessarily reflect intracellular concentrations of these compounds. Finally, there were no measures of nitric oxide metabolites to determine if these levels were altered in the presence of elevated methylarginines and depression.
CONCLUSIONS: After adjusting for clinical, demographic, biochemical, and pharmacological confounders, higher serum ADMA was independently associated with incident depression at 6-years follow-up.
| Original language | English |
|---|---|
| Pages (from-to) | 493-499 |
| Number of pages | 7 |
| Journal | Journal of Affective Disorders |
| Volume | 151 |
| Issue number | 2 |
| Early online date | 7 Sep 2013 |
| DOIs | |
| Publication status | Published - Nov 2013 |
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Keywords
- Methylarginines
- Depression
- Cohort study
Cite this
Serum methylarginines and incident depression in a cohort of older adults. / McEvoy, Mark A.; Schofield, Peter; Smith, Wayne; Agho, Kingsley; Mangoni, Arduino A.; Soiza, Roy L; Peel, Roseanne; Hancock, Stephen; Kelly, Brian; Inder, Kerry; Carru, Ciriaco; Zinellu, Angelo; Attia, John.
In: Journal of Affective Disorders, Vol. 151, No. 2, 11.2013, p. 493-499.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Serum methylarginines and incident depression in a cohort of older adults
AU - McEvoy, Mark A.
AU - Schofield, Peter
AU - Smith, Wayne
AU - Agho, Kingsley
AU - Mangoni, Arduino A.
AU - Soiza, Roy L
AU - Peel, Roseanne
AU - Hancock, Stephen
AU - Kelly, Brian
AU - Inder, Kerry
AU - Carru, Ciriaco
AU - Zinellu, Angelo
AU - Attia, John
N1 - Role of funding source The research on which this paper is based was conducted as part of the Hunter Community Study, funded by the University of Newcastle Strategic Initiative Fund, the Vincent Family Foundation, and the Brawn Fellowship, and the Extending Treatments, Education and Networks study, funded by the Hunter Medical Research Institute, beyondblue, the national depression initiative, and Xstrata Coal. Conflict of interest None. Acknowledgements The research on which this paper is based was conducted as part of the Hunter Community Study, funded by the University of Newcastle and the Extending Treatments, Education and Networks study, funded by the Hunter Medical Research Institute, beyondblue, the national depression initiative and Xstrata Coal. The authors wish to thank the funding bodies, the chief investigators, research staff and participants of the parent studies: The Hunter Community Study (Mcevoy et al., 2010) and the Australian Rural Mental Health Study for their contribution to this project. We are grateful to the men and women of the Hunter region who provided the information recorded.
PY - 2013/11
Y1 - 2013/11
N2 - BACKGROUND: Methylarginines are endogenous nitric oxide synthase inhibitors that have been implicated in depression. This study measured serum concentrations of l-arginine, asymmetric (ADMA) and symmetric (SDMA) dimethylarginine in a representative sample of older community-dwelling adults and determined their association with incident depression over 6-years of follow-up.METHODS: Data on clinical, lifestyle, and demographic characteristics, methylated arginines, and l-arginine (measured using LC-MS/MS) were collected from a population-based sample of older Australian adults (Median age=64 years; IQR=60-70) from the Hunter Community Study. Clinical depression was defined as a Centre for Epidemiological Studies Depression Scale (CES-D) score ≥16 or use of antidepressant medications.RESULTS: In adjusted analyses ADMA (Q3), SDMA (Q2), l-arginine (Q2), gender, and asthma remained statistically significant predictors of incident depression at follow-up. Quartile 3 of ADMA concentration was associated with 3.5 times the odds of developing depression compared with Q1 (OR=3.54; 95% CI: 1.25-9.99).LIMITATIONS: Limitations of our study include the use of a subjective self-reported questionnaire tool using a dichotomous cut-off, together with use of antidepressant medications, as proxies for clinical depression. Moreover, similarly to most population studies on methylated arginines, the measurement of ADMA and SDMA from blood does not necessarily reflect intracellular concentrations of these compounds. Finally, there were no measures of nitric oxide metabolites to determine if these levels were altered in the presence of elevated methylarginines and depression.CONCLUSIONS: After adjusting for clinical, demographic, biochemical, and pharmacological confounders, higher serum ADMA was independently associated with incident depression at 6-years follow-up.
AB - BACKGROUND: Methylarginines are endogenous nitric oxide synthase inhibitors that have been implicated in depression. This study measured serum concentrations of l-arginine, asymmetric (ADMA) and symmetric (SDMA) dimethylarginine in a representative sample of older community-dwelling adults and determined their association with incident depression over 6-years of follow-up.METHODS: Data on clinical, lifestyle, and demographic characteristics, methylated arginines, and l-arginine (measured using LC-MS/MS) were collected from a population-based sample of older Australian adults (Median age=64 years; IQR=60-70) from the Hunter Community Study. Clinical depression was defined as a Centre for Epidemiological Studies Depression Scale (CES-D) score ≥16 or use of antidepressant medications.RESULTS: In adjusted analyses ADMA (Q3), SDMA (Q2), l-arginine (Q2), gender, and asthma remained statistically significant predictors of incident depression at follow-up. Quartile 3 of ADMA concentration was associated with 3.5 times the odds of developing depression compared with Q1 (OR=3.54; 95% CI: 1.25-9.99).LIMITATIONS: Limitations of our study include the use of a subjective self-reported questionnaire tool using a dichotomous cut-off, together with use of antidepressant medications, as proxies for clinical depression. Moreover, similarly to most population studies on methylated arginines, the measurement of ADMA and SDMA from blood does not necessarily reflect intracellular concentrations of these compounds. Finally, there were no measures of nitric oxide metabolites to determine if these levels were altered in the presence of elevated methylarginines and depression.CONCLUSIONS: After adjusting for clinical, demographic, biochemical, and pharmacological confounders, higher serum ADMA was independently associated with incident depression at 6-years follow-up.
KW - Methylarginines
KW - Depression
KW - Cohort study
U2 - 10.1016/j.jad.2013.06.033
DO - 10.1016/j.jad.2013.06.033
M3 - Article
C2 - 23931830
VL - 151
SP - 493
EP - 499
JO - Journal of Affective Disorders
JF - Journal of Affective Disorders
SN - 0165-0327
IS - 2
ER -