Serum methylarginines and incident depression in a cohort of older adults

Mark A. McEvoy, Peter Schofield, Wayne Smith, Kingsley Agho, Arduino A. Mangoni, Roy L Soiza, Roseanne Peel, Stephen Hancock, Brian Kelly, Kerry Inder, Ciriaco Carru, Angelo Zinellu, John Attia

Research output: Contribution to journalArticle

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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 languageEnglish
Pages (from-to)493-499
Number of pages7
JournalJournal of Affective Disorders
Volume151
Issue number2
Early online date7 Sep 2013
DOIs
Publication statusPublished - Nov 2013

Fingerprint

Depression
Serum
Arginine
Antidepressive Agents
Demography
Independent Living
Proxy
Nitric Oxide Synthase
Population
Life Style
Epidemiologic Studies
Nitric Oxide
Asthma
Pharmacology

Keywords

  • Methylarginines
  • Depression
  • Cohort study

Cite this

McEvoy, M. A., Schofield, P., Smith, W., Agho, K., Mangoni, A. A., Soiza, R. L., ... Attia, J. (2013). Serum methylarginines and incident depression in a cohort of older adults. Journal of Affective Disorders, 151(2), 493-499. https://doi.org/10.1016/j.jad.2013.06.033

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 journalArticle

McEvoy, MA, Schofield, P, Smith, W, Agho, K, Mangoni, AA, Soiza, RL, Peel, R, Hancock, S, Kelly, B, Inder, K, Carru, C, Zinellu, A & Attia, J 2013, 'Serum methylarginines and incident depression in a cohort of older adults', Journal of Affective Disorders, vol. 151, no. 2, pp. 493-499. https://doi.org/10.1016/j.jad.2013.06.033
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. / Serum methylarginines and incident depression in a cohort of older adults. In: Journal of Affective Disorders. 2013 ; Vol. 151, No. 2. pp. 493-499.
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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.",
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author = "McEvoy, {Mark A.} and Peter Schofield and Wayne Smith and Kingsley Agho and Mangoni, {Arduino A.} and Soiza, {Roy L} and Roseanne Peel and Stephen Hancock and Brian Kelly and Kerry Inder and Ciriaco Carru and Angelo Zinellu and John Attia",
note = "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.",
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AU - Schofield, Peter

AU - Smith, Wayne

AU - Agho, Kingsley

AU - Mangoni, Arduino A.

AU - Soiza, Roy L

AU - Peel, Roseanne

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AU - Zinellu, Angelo

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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.

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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.

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KW - Depression

KW - Cohort study

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