Maturation of the human striatal dopamine system revealed by PET and quantitative MRI.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
12 02 2020
Historique:
received: 13 07 2019
accepted: 28 01 2020
entrez: 14 2 2020
pubmed: 14 2 2020
medline: 24 4 2020
Statut: epublish

Résumé

The development of the striatum dopamine (DA) system through human adolescence, a time of increased sensation seeking and vulnerability to the emergence of psychopathology, has been difficult to study due to pediatric restrictions on direct in vivo assessments of DA. Here, we applied neuroimaging in a longitudinal sample of n = 146 participants aged 12-30. R2', an MR measure of tissue iron which co-localizes with DA vesicles and is necessary for DA synthesis, was assessed across the sample. In the 18-30 year-olds (n = 79) we also performed PET using [11C]dihydrotetrabenazine (DTBZ), a measure of presynaptic vesicular DA storage, and [11C]raclopride (RAC), an indicator of D2/D3 receptor availability. We observed decreases in D2/D3 receptor availability with age, while presynaptic vesicular DA storage (as measured by DTBZ), which was significantly associated with R2' (standardized coefficient = 0.29, 95% CI = [0.11, 0.48]), was developmentally stable by age 18. Our results provide new evidence for maturational specialization of the striatal DA system through adolescence.

Identifiants

pubmed: 32051403
doi: 10.1038/s41467-020-14693-3
pii: 10.1038/s41467-020-14693-3
pmc: PMC7015913
doi:

Substances chimiques

Receptors, Dopamine D2 0
Receptors, Dopamine D3 0
dihydrotetrabenazine 3466-75-9
Raclopride 430K3SOZ7G
Dopamine VTD58H1Z2X
Tetrabenazine Z9O08YRN8O

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

846

Subventions

Organisme : NIMH NIH HHS
ID : R01 MH080243
Pays : United States

Références

Harden, K. P. & Tucker-Drob, E. M. Individual differences in the development of sensation seeking and impulsivity during adolescence: further evidence for a dual systems model. Dev. Psychol. 47, 739–746 (2011).
pubmed: 21534657 doi: 10.1037/a0023279 pmcid: 21534657
Spear, L. P. The adolescent brain and age-related behavioral manifestations. Neurosci. Biobehav Rev. 24, 417–463 (2000).
pubmed: 10817843 doi: 10.1016/S0149-7634(00)00014-2 pmcid: 10817843
Steinberg, L. A dual systems model of adolescent risk-taking. Dev. Psychobiol. 52, 216–224 (2010).
pubmed: 20213754 pmcid: 20213754
Larsen, B. & Luna, B. Adolescence as a neurobiological critical period for the development of higher-order cognition. Neurosci. Biobehav. Rev. 94, 179–195 (2018).
pubmed: 30201220 pmcid: 6526538 doi: 10.1016/j.neubiorev.2018.09.005
Paus, T., Keshavan, M. & Giedd, J. N. Why do many psychiatric disorders emerge during adolescence? Nat. Rev. Neurosci. 9, 947–957 (2008).
pubmed: 19002191 pmcid: 2762785 doi: 10.1038/nrn2513
Dahl, R. E., Allen, N. B., Wilbrecht, L. & Suleiman, A. B. Importance of investing in adolescence from a developmental science perspective. Nature 554, 441–450 (2018).
pubmed: 29469094 doi: 10.1038/nature25770 pmcid: 29469094
Luna, B., Marek, S., Larsen, B., Tervo-Clemmens, B. & Chahal, R. An integrative model of the maturation of cognitive control. Annu Rev. Neurosci. 38, 151–170 (2015).
pubmed: 26154978 pmcid: 5661874 doi: 10.1146/annurev-neuro-071714-034054
Shulman, E. P. et al. The dual systems model: review, reappraisal, and reaffirmation. Dev. Cogn. Neurosci. 17, 103–117 (2016).
pubmed: 26774291 doi: 10.1016/j.dcn.2015.12.010 pmcid: 26774291
Andersen, S. L., Rutstein, M., Benzo, J. M., Hostetter, J. C. & Teicher, M. H. Sex differences in dopamine receptor overproduction and elimination. Neuroreport 8, 1495–1498 (1997).
pubmed: 9172161 doi: 10.1097/00001756-199704140-00034 pmcid: 9172161
Tarazi, F. I., Tomasini, E. C. & Baldessarini, R. J. Postnatal development of dopamine D4-like receptors in rat forebrain regions: comparison with D2-like receptors. Dev. Brain Res. 110, 227–233 (1998).
doi: 10.1016/S0165-3806(98)00111-4
Teicher, M. H., Andersen, S. L. & Hostetter, J. C. Evidence for dopamine receptor pruning between adolescence and adulthood in striatum but not nucleus accumbens. Dev. Brain Res. 89, 167–172 (1995).
doi: 10.1016/0165-3806(95)00109-Q
Giorgi, O. et al. Developmental and age-related changes in D1-dopamine receptors and dopamine content in the rat striatum. Brain Res. 432, 283–290 (1987).
pubmed: 2960426 doi: 10.1016/0165-3806(87)90053-8 pmcid: 2960426
Rao, P. A., Molinoff, P. B. & Joyce, J. N. Ontogeny of dopamine D1 and D2 receptor subtypes in rat basal ganglia: a quantitative autoradiographic study. Brain Res. Dev. Brain Res. 60, 161–177 (1991).
pubmed: 1832594 doi: 10.1016/0165-3806(91)90045-K pmcid: 1832594
Moll, G. H. et al. Age-associated changes in the densities of presynaptic monoamine transporters in different regions of the rat brain from early juvenile life to late adulthood. Dev. Brain Res. 119, 251–257 (2000).
doi: 10.1016/S0165-3806(99)00182-0
Tarazi, F. I., Tomasini, E. C. & Baldessarini, R. J. Postnatal development of dopamine and serotonin transporters in rat caudate-putamen and nucleus accumbens septi. Neurosci. Lett. 254, 21–24 (1998).
pubmed: 9780082 doi: 10.1016/S0304-3940(98)00644-2 pmcid: 9780082
Connor, J. R. & Menzies, S. L. Relationship of iron to oligodendrocytes and myelination. Glia 17, 83–93 (1996).
pubmed: 8776576 doi: 10.1002/(SICI)1098-1136(199606)17:2<83::AID-GLIA1>3.0.CO;2-7 pmcid: 8776576
Ward, R. J., Zucca, F. A., Duyn, J. H., Crichton, R. R. & Zecca, L. The role of iron in brain ageing and neurodegenerative disorders. Lancet Neurol. 13, 1045–1060 (2014).
pubmed: 25231526 pmcid: 5672917 doi: 10.1016/S1474-4422(14)70117-6
Ortega, R., Cloetens, P., Devès, G., Carmona, A. & Bohic, S. Iron storage within dopamine neurovesicles revealed by chemical nano-imaging. PloS ONE 2, e925 (2007).
pubmed: 17895967 pmcid: 1976597 doi: 10.1371/journal.pone.0000925
Zucca, F. A. et al. Interactions of iron, dopamine and neuromelanin pathways in brain aging and Parkinson’s disease. Prog. Neurobiol. 155, 96–119 (2017).
pubmed: 26455458 doi: 10.1016/j.pneurobio.2015.09.012 pmcid: 26455458
Adisetiyo, V. et al. Multimodal MR imaging of brain iron in attention deficit hyperactivity disorder: a noninvasive biomarker that responds to psychostimulant treatment? Radiology 272, 524–532 (2014).
pubmed: 24937545 pmcid: 4263268 doi: 10.1148/radiol.14140047
Khan, F. H., Ahlberg, C. D., Chow, C. A., Shah, D. R. & Koo, B. B. Iron, dopamine, genetics, and hormones in the pathophysiology of restless legs syndrome. J Neurol. 1–8 https://doi.org/10.1007/s00415-017-8431-1 (2017).
pubmed: 28236139 doi: 10.1007/s00415-017-8431-1 pmcid: 28236139
Ersche, K. D. et al. Disrupted iron regulation in the brain and periphery in cocaine addiction. Transl. Psychiatry 7, e1040 (2017).
pubmed: 28221362 pmcid: 5438021 doi: 10.1038/tp.2016.271
Larsen, B. & Luna, B. In vivo evidence of neurophysiological maturation of the human adolescent striatum. Dev. Cogn. Neurosci. 12C, 74–85 (2015).
doi: 10.1016/j.dcn.2014.12.003
Peterson, E. T. et al. Distribution of brain iron accrual in adolescence: evidence from cross-sectional and longitudinal analysis. Hum. Brain Mapp. 40, 1480–1495 (2019).
pubmed: 30496644 doi: 10.1002/hbm.24461 pmcid: 30496644
Haacke, E. M. et al. Imaging iron stores in the brain using magnetic resonance imaging. Magn. Reson. Imaging 23, 1–25 (2005).
pubmed: 15733784 doi: 10.1016/j.mri.2004.10.001 pmcid: 15733784
Haacke, E. M. et al. Correlation of change in R2* and phase with putative iron content in deep gray matter of healthy adults. J. Magn. Reson. Imaging 32, 561–576 (2010).
pubmed: 20815053 pmcid: 2936709 doi: 10.1002/jmri.22293
Sedlacik, J. et al. Reversible, irreversible and effective transverse relaxation rates in normal aging brain at 3 T. NeuroImage 84, 1032–1041 (2014).
pubmed: 24004692 doi: 10.1016/j.neuroimage.2013.08.051 pmcid: 24004692
Graham, J. M., Paley, M. N. J., Grünewald, R. A., Hoggard, N. & Griffiths, P. D. Brain iron deposition in Parkinson’s disease imaged using the PRIME magnetic resonance sequence. Brain 123, 2423–2431 (2000).
pubmed: 11099445 doi: 10.1093/brain/123.12.2423 pmcid: 11099445
Aquino, D. et al. Age-related iron deposition in the basal ganglia: quantitative analysis in healthy subjects1. Radiology 252, 165–172 (2009).
pubmed: 19561255 doi: 10.1148/radiol.2522081399 pmcid: 19561255
Kilbourn, M. R. in PET and SPECT of Neurobiological Systems 765–790 (Springer, Berlin, Heidelberg, 2014). https://doi.org/10.1007/978-3-642-42014-6_27 .
doi: 10.1007/978-3-642-42014-6_27
Hect, J. L., Daugherty, A. M., Hermez, K. M. & Thomason, M. E. Developmental variation in regional brain iron and its relation to cognitive functions in childhood. Dev. Cogn. Neurosci. 34, 18–26 (2018).
pubmed: 29894887 pmcid: 6250585 doi: 10.1016/j.dcn.2018.05.004
Wang, J. et al. Maturational and aging effects on human brain apparent transverse relaxation. PloS ONE 7, e31907 (2012).
pubmed: 22363767 pmcid: 3283700 doi: 10.1371/journal.pone.0031907
Seaman, K. L. et al. Differential regional decline in dopamine receptor availability across adulthood: Linear and nonlinear effects of age. Hum. Brain Mapp. 40, 3125–3138 (2019).
pubmed: 30932295 pmcid: 30932295
Karrer, T. M., Josef, A. K., Mata, R., Morris, E. D. & Samanez-Larkin, G. R. Reduced dopamine receptors and transporters but not synthesis capacity in normal aging adults: a meta-analysis. Neurobiol. Aging 57, 36–46 (2017).
pubmed: 28599217 pmcid: 5645072 doi: 10.1016/j.neurobiolaging.2017.05.006
Huttenlocher, P. R. Synapse elimination and plasticity in developing human cerebral cortex. Am. J. Ment. Defic. 88, 488–496 (1984).
pubmed: 6731486 pmcid: 6731486
Feinberg, I. Schizophrenia: caused by a fault in programmed synaptic elimination during adolescence? J. Psychiatr. Res 17, 319–334 (1983).
doi: 10.1016/0022-3956(82)90038-3
Eshel, N., Nelson, E. E., Blair, R. J., Pine, D. S. & Ernst, M. Neural substrates of choice selection in adults and adolescents: development of the ventrolateral prefrontal and anterior cingulate cortices. Neuropsychologia 45, 1270–1279 (2007).
pubmed: 17118409 doi: 10.1016/j.neuropsychologia.2006.10.004 pmcid: 17118409
Teslovich, T. et al. Adolescents let sufficient evidence accumulate before making a decision when large incentives are at stake. Dev. Sci. 17, 59–70 (2014).
pubmed: 24102682 doi: 10.1111/desc.12092
Tamnes, C. K. et al. Brain Maturation In Adolescence And Young Adulthood: Regional Age-related Changes In Cortical Thickness And White Matter Volume And Microstructure. Cereb. Cortex 20, 534–548 (2010).
pubmed: 19520764 doi: 10.1093/cercor/bhp118
Koikkalainen, J. et al. Shape variability of the human striatum—Effects of age and gender. NeuroImage 34, 85–93 (2007).
pubmed: 17056276 doi: 10.1016/j.neuroimage.2006.08.039 pmcid: 17056276
Dennison, M. et al. Mapping subcortical brain maturation during adolescence: evidence of hemisphere- and sex-specific longitudinal changes. Dev. Sci. 16, 772–791 (2013).
pubmed: 24033581 doi: 10.1111/desc.12057 pmcid: 24033581
Raznahan, A. et al. Longitudinal four-dimensional mapping of subcortical anatomy in human development. PNAS 111, 1592–1597 (2014).
pubmed: 24474784 doi: 10.1073/pnas.1316911111 pmcid: 24474784
Walhovd, K. B. et al. Maturation of cortico-subcortical structural networks—segregation and overlap of medial temporal and fronto-striatal systems in development. Cereb. Cortex. (2014) https://doi.org/10.1093/cercor/bht424 . (2014)
pubmed: 24436319 doi: 10.1093/cercor/bht424 pmcid: 24436319
Larsen, B., Verstynen, T. D., Yeh, F.-C. & Luna, B. Developmental changes in the integration of affective and cognitive corticostriatal pathways are associated with reward-driven behavior. Cereb. Cortex 28, 2834–2845 (2018).
pubmed: 29106535 doi: 10.1093/cercor/bhx162 pmcid: 29106535
van Duijvenvoorde, A. C. K., Achterberg, M., Braams, B. R., Peters, S. & Crone, E. A. Testing a dual-systems model of adolescent brain development using resting-state connectivity analyses. Neuroimage 124, 409–420 (2016).
pubmed: 25969399 doi: 10.1016/j.neuroimage.2015.04.069 pmcid: 25969399
Salvatore, M. F., Fisher, B., Surgener, S. P., Gerhardt, G. A. & Rouault, T. Neurochemical investigations of dopamine neuronal systems in iron-regulatory protein 2 (IRP-2) knockout mice. Mol. Brain Res. 139, 341–347 (2005).
pubmed: 16051392 doi: 10.1016/j.molbrainres.2005.06.002 pmcid: 16051392
Salvatore, M. F. & Pruett, B. S. Dichotomy of tyrosine hydroxylase and dopamine regulation between somatodendritic and terminal field areas of nigrostriatal and mesoaccumbens pathways. PloS ONE 7, e29867 (2012).
pubmed: 22242182 pmcid: 3252325 doi: 10.1371/journal.pone.0029867
Haber, S. N. & Knutson, B. The reward circuit: linking primate anatomy and human imaging. Neuropsychopharmacology 35, 4–26 (2010).
pubmed: 19812543 doi: 10.1038/npp.2009.129 pmcid: 19812543
Calipari, E. S., Huggins, K. N., Mathews, T. A. & Jones, S. R. Conserved dorsal-ventral gradient of dopamine release and uptake rate in mice, rats and rhesus macaques. Neurochem. Int. 61, 986–991 (2012).
pubmed: 22819794 pmcid: 3593229 doi: 10.1016/j.neuint.2012.07.008
Cragg, S. J., Hille, C. J. & Greenfield, S. A. Functional domains in dorsal striatum of the nonhuman primate are defined by the dynamic behavior of dopamine. J. Neurosci. 22, 5705–5712 (2002).
pubmed: 12097522 pmcid: 6758186 doi: 10.1523/JNEUROSCI.22-13-05705.2002
Leroux-Nicollet, I. & Costentin, J. Comparison of the subregional distributions of the monoamine vesicular transporter and dopamine uptake complex in the rat striatum and changes during aging. J. Neural Transm. Gen. Sect. 97, 93–106 (1994).
pubmed: 7873127 doi: 10.1007/BF01277946 pmcid: 7873127
Wu, Q., Reith, M. E., Kuhar, M. J., Carroll, F. I. & Garris, P. A. Preferential increases in nucleus accumbens dopamine after systemic cocaine administration are caused by unique characteristics of dopamine neurotransmission. J. Neurosci. 21, 6338–6347 (2001).
pubmed: 11487657 pmcid: 6763153 doi: 10.1523/JNEUROSCI.21-16-06338.2001
Funai, A. K., Fessler, J. A., Yeo, D. T. B., Olafsson, V. T. & Noll, D. C. Regularized field map estimation in MRI. IEEE Trans. Med Imaging 27, 1484–1494 (2008).
pubmed: 18815100 pmcid: 2856353 doi: 10.1109/TMI.2008.923956
Fessler, J. A. & Noll, D. C. model-based MR Image Reconstruction with Compensation for Through-plane Field Inhomogeneity. in Proc. 2007 4th IEEE International Symposium on Biomedical Imaging: From Nano to Macro 920–923 (IEEE, 2007). https://doi.org/10.1109/ISBI.2007.357003 .
Hager, W. & Zhang, H. The limited memory conjugate gradient method. SIAM J. Optim. 23, 2150–2168 (2013).
doi: 10.1137/120898097
Speck, O. & Hennig, J. Functional Imaging by I0- and T2* -parameter mapping using multi-image EPI. Magn. Reson. Med. 40, 243–248 (1998).
pubmed: 9702706 doi: 10.1002/mrm.1910400210 pmcid: 9702706
Cox, R. W. AFNI: software for analysis and visualization of functional magnetic resonance neuroimages. Computers Biomed. Res. 29, 162–173 (1996).
doi: 10.1006/cbmr.1996.0014
Martinez, D. et al. Imaging human mesolimbic dopamine transmission with positron emission tomography. Part II: amphetamine-induced dopamine release in the functional subdivisions of the striatum. J. Cereb. Blood Flow. Metab. 23, 285–300 (2003).
pubmed: 12621304 doi: 10.1097/01.WCB.0000048520.34839.1A pmcid: 12621304
Izquierdo-Garcia, D. et al. An SPM8-based approach for attenuation correction combining segmentation and nonrigid template formation: application to simultaneous PET/MR brain imaging. J. Nucl. Med. 55, 1825–1830 (2014).
pubmed: 25278515 pmcid: 4246705 doi: 10.2967/jnumed.113.136341
Ladefoged, C. N. et al. A multi-centre evaluation of eleven clinically feasible brain PET/MRI attenuation correction techniques using a large cohort of patients. Neuroimage 147, 346–359 (2017).
pubmed: 27988322 doi: 10.1016/j.neuroimage.2016.12.010 pmcid: 27988322
Fischl, B. FreeSurfer. Neuroimage 62, 774–781 (2012).
pubmed: 22248573 pmcid: 3685476 doi: 10.1016/j.neuroimage.2012.01.021
Normandin, M. D., Schiffer, W. K. & Morris, E. D. A linear model for estimation of neurotransmitter response profiles from dynamic PET data. Neuroimage 59, 2689–2699 (2012).
pubmed: 21767654 doi: 10.1016/j.neuroimage.2011.07.002 pmcid: 21767654
Gunn, R., Coello, C. & Searle, G. Molecular Imaging And Kinetic Analysis Toolbox (MIAKAT)—a quantitative software package for the analysis of PET neuroimaging data. J. Nucl. Med 57, 1928–1928 (2016).
Lammertsma, A. A. & Hume, S. P. Simplified reference tissue model for PET receptor studies. NeuroImage 4, 153–158 (1996).
pubmed: 9345505 doi: 10.1006/nimg.1996.0066 pmcid: 9345505
Nyberg, L. et al. Dopamine D2 receptor availability is linked to hippocampal–caudate functional connectivity and episodic memory. PNAS 113, 7918–7923 (2016).
pubmed: 27339132 doi: 10.1073/pnas.1606309113 pmcid: 27339132
Berry, A. S. et al. Dopamine synthesis capacity is associated with D2/3 receptor binding but not dopamine release. Neuropsychopharmacol 43, 1201–1211 (2018).
doi: 10.1038/npp.2017.180
Black, K. J. et al. Levodopa effects on [11C]raclopride binding in the resting human brain. F1000Res 4, 23 (2015).
pubmed: 26180632 pmcid: 4490799 doi: 10.12688/f1000research.5672.1
Alakurtti, K. et al. Long-term test–retest reliability of striatal and extrastriatal dopamine D2/3 receptor binding: Study with [11C]Raclopride and High-Resolution PET. J. Cereb. Blood Flow. Metab. 35, 1199–1205 (2015).
pubmed: 25853904 pmcid: 4640276 doi: 10.1038/jcbfm.2015.53
Yoder, K. K., Kareken, D. A. & Morris, E. D. What were they thinking?: cognitive states may influence [11C]raclopride binding potential in the striatum. Neurosci. Lett. 430, 38–42 (2008).
pubmed: 18060695 doi: 10.1016/j.neulet.2007.10.017 pmcid: 18060695
Yoder, K. K. et al. Test–retest variability of [11C]raclopride-binding potential in nontreatment-seeking alcoholics. Synapse 65, 553–561 (2011).
pubmed: 20963816 doi: 10.1002/syn.20874 pmcid: 20963816
Ichise, M. et al. Linearized reference tissue parametric imaging methods: application to [11C]DASB positron emission tomography studies of the serotonin transporter in human brain. J. Cereb. Blood Flow. Metab. 23, 1096–1112 (2003).
pubmed: 12973026 doi: 10.1097/01.WCB.0000085441.37552.CA pmcid: 12973026
Chan, G. L. et al. Reproducibility studies with 11C-DTBZ, a monoamine vesicular transporter inhibitor in healthy human subjects. J. Nucl. Med. 40, 283–289 (1999).
pubmed: 10025836 pmcid: 10025836
Tziortzi, A. C. et al. Imaging dopamine receptors in humans with [11C]-(+)-PHNO: dissection of D3 signal and anatomy. Neuroimage 54, 264–277 (2011).
pubmed: 20600980 doi: 10.1016/j.neuroimage.2010.06.044 pmcid: 20600980
Savalia, N. K. et al. Motion-related artifacts in structural brain images revealed with independent estimates of in-scanner head motion. Hum. Brain Mapp. 38, 472–492 (2017).
pubmed: 27634551 doi: 10.1002/hbm.23397 pmcid: 27634551
Kline, R. B. Principles and Practice of Structural Equation Modeling 4th edn. (Guilford Publications, 2015).

Auteurs

Bart Larsen (B)

Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, 15213, USA. bart.larsen@pennmedicine.upenn.edu.

Valur Olafsson (V)

NUBIC, Northeastern University, Boston, MA, 02115, USA.

Finnegan Calabro (F)

Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, 15213, USA.
Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, 15213, USA.

Charles Laymon (C)

Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, 15213, USA.
Department of Radiology, University of Pittsburgh, Pittsburgh, PA, 15213, USA.

Brenden Tervo-Clemmens (B)

Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, 15213, USA.

Elizabeth Campbell (E)

Department of Radiology, University of Pittsburgh, Pittsburgh, PA, 15213, USA.

Davneet Minhas (D)

Department of Radiology, University of Pittsburgh, Pittsburgh, PA, 15213, USA.

David Montez (D)

Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, 15213, USA.

Julie Price (J)

Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA.

Beatriz Luna (B)

Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, 15213, USA.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH