Hostname: page-component-cd9895bd7-8ctnn Total loading time: 0 Render date: 2024-12-22T19:16:17.815Z Has data issue: false hasContentIssue false
  • English
  • Français

Trajectory of emotion dysregulation in positive and negative affect across childhood predicts adolescent emotion dysregulation and overall functioning

Published online by Cambridge University Press:  07 December 2021

Alecia C. Vogel Open the ORCID record for Alecia C. Vogel [Opens in a new window] ,
Rebecca Tillman ,
Nourhan M. El-Sayed ,
Joshua J. Jackson ,
Susan B. Perlman ,
Deanna M. Barch  and
Joan L. Luby
Alecia C. Vogel*
Affiliation:
Department of Psychiatry, Washington University in St. Louis School of Medicine, St Louis, MO, USA
Rebecca Tillman
Affiliation:
Department of Psychiatry, Washington University in St. Louis School of Medicine, St Louis, MO, USA
Nourhan M. El-Sayed
Affiliation:
Department of Psychological and Brain Sciences, Washington University in St. Louis, MO, USA
Joshua J. Jackson
Affiliation:
Department of Psychological and Brain Sciences, Washington University in St. Louis, MO, USA
Susan B. Perlman
Affiliation:
Department of Psychiatry, Washington University in St. Louis School of Medicine, St Louis, MO, USA
Deanna M. Barch
Affiliation:
Department of Psychiatry, Washington University in St. Louis School of Medicine, St Louis, MO, USA Department of Psychological and Brain Sciences, Washington University in St. Louis, MO, USA
Joan L. Luby
Affiliation:
Department of Psychiatry, Washington University in St. Louis School of Medicine, St Louis, MO, USA
*
Author for Correspondence: Alecia C. Vogel, Early Emotional Development Program, St Louis, Washington University School of Medicine, 4444 Forest Park Parkway, Suite 2100, St. Louis, Missouri 63108; E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Emotion dysregulation is cross-diagnostic and impairing. Most research has focused on dysregulated expressions of negative affect, often measured as irritability, which is associated with multiple forms of psychopathology and predicts negative outcomes. However, the Research Domain Criteria (RDoC) include both negative and positive valence systems. Emerging evidence suggests that dysregulated expressions of positive affect, or excitability, in early childhood predict later psychopathology and impairment above and beyond irritability. Typically, irritability declines from early through middle childhood; however, the developmental trajectory of excitability is unknown. The impact of excitability across childhood on later emotion dysregulation is also yet unknown. In a well-characterized, longitudinal sample of 129 children studied from ages 3 to 5.11 years through 14 to 19 years, enriched for early depression and disruptive symptoms, we assessed the trajectory of irritability and excitability using multilevel modeling and how components of these trajectories impact later emotion dysregulation. While irritability declines across childhood, excitability remains remarkably stable both within and across the group. Overall levels of excitability (excitability intercept) predict later emotion dysregulation as measured by parent and self-report and predict decreased functional magnetic resonance imaging activity in cognitive emotion regulation regions during an emotion regulation task. Irritability was not related to any dysregulation outcome above and beyond excitability.

Keywords

excitabilityirritabilityfMRIneuroimagingemotion lability
Type
Special Issue Article
Information
Development and Psychopathology , Volume 33 , Special Issue 5: Applying RDoC-Informed Approaches to the Study of Development and Psychopathology , December 2021 , pp. 1722 - 1733
Check for updates
Copyright
Copyright © The Author(s), 2021. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Angold, A., Prendergast, M., Cox, A., Harrington, R., Simonoff, E., & Rutter, M. (1995). The child and adolescent psychiatric assessment (CAPA). Psychological Medicine, 25, 739–753. doi:10.1017/S003329170003498XCrossRefGoogle Scholar
Avenevoli, S., Swendsen, J., He, J.-P., Burstein, M., & Merikangas, K. R. (2015). Major depression in the national comorbidity survey-adolescent supplement: Prevalence, correlates, and treatment. Journal of the American Academy of Child and Adolescent Psychiatry, 54, 37–44.e2. doi:10.1016/j.jaac.2014.10.010CrossRefGoogle ScholarPubMed
Barch, D. M., Burgess, G. C., Harms, M. P., Petersen, S. E., Schlaggar, B. L., Corbetta, M., … WU-Minn HCP Consortium (2013). Function in the human connectome: Task-fMRI and individual differences in behavior. NeuroImage, 80, 169–189. doi:10.1016/j.neuroimage.2013.05.033CrossRefGoogle ScholarPubMed
Beauchaine, T. P. (2015). Future directions in emotion dysregulation and youth psychopathology. Journal of Clinical Child & Adolescent Psychology, 44, 875–896. doi:10.1080/15374416.2015.1038827CrossRefGoogle ScholarPubMed
Beauchaine, T. P., & Zisner, A. (2017). Motivation, emotion regulation, and the latent structure of psychopathology: An integrative and convergent historical perspective. International Journal of Psychophysiology, 119, 108–118. doi:10.1016/j.ijpsycho.2016.12.014CrossRefGoogle ScholarPubMed
Belden, A. C., Pagliaccio, D., Murphy, E. R., Luby, J. L., & Barch, D. M. (2015). Neural activation during cognitive emotion regulation in previously depressed compared to healthy children: Evidence of specific alterations. Journal of the American Academy of Child & Adolescent Psychiatry, 54, 771–781. doi:10.1016/j.jaac.2015.06.014CrossRefGoogle ScholarPubMed
Belden, A. C., Thomson, N. R., & Luby, J. L. (2008). Temper tantrums in healthy versus depressed and disruptive preschoolers: Defining tantrum behaviors associated with clinical problems. The Journal of Pediatrics, 152, 117–122. doi:10.1016/j.jpeds.2007.06.030CrossRefGoogle ScholarPubMed
Benjamini, Y., & Hochberg, Y. (1995). Controlling the false discovery rate: A practical and powerful approach to multiple testing. Journal of the Royal Statistical Society: Series B (Methodological), 57, 289–300. doi:10.1111/j.2517-6161.1995.tb02031.xGoogle Scholar
Brotman, M. A., Kircanski, K., & Leibenluft, E. (2017). Irritability in children and adolescents. Annual Review of Clinical Psychology, 13, 317–341. doi:10.1146/annurev-clinpsy-032816-044941CrossRefGoogle ScholarPubMed
Brotman, M. A., Schmajuk, M., Rich, B. A., Dickstein, D. P., Guyer, A. E., Costello, E. J., … Leibenluft, E. (2006). Prevalence, clinical correlates, and longitudinal course of severe mood dysregulation in children. Biological Psychiatry, 60, 991–997. doi:10.1016/j.biopsych.2006.08.042CrossRefGoogle ScholarPubMed
Buhle, J. T., Silvers, J. A., Wager, T. D., Lopez, R., Onyemekwu, C., Kober, H., … Ochsner, K. N. (2014). Cognitive reappraisal of emotion: A meta-analysis of human neuroimaging studies. Cerebral Cortex, 24, 2981–2990. doi:10.1093/cercor/bht154CrossRefGoogle ScholarPubMed
Caprara, G. V., Paciello, M., Gerbino, M., & Cugini, C. (2007). Individual differences conducive to aggression and violence: Trajectories and correlates of irritability and hostile rumination through adolescence. Aggressive Behavior, 33, 359–374. doi:10.1002/ab.20192CrossRefGoogle ScholarPubMed
Cohen, P., Cohen, J., Aiken, L. S., & West, S. G. (1999). The problem of units and the circumstance for POMP. Multivariate Behavioral Research, 34, 315–346. doi:10.1207/S15327906MBR3403_2CrossRefGoogle Scholar
Copeland, W. E., Angold, A., Costello, E. J., & Egger, H. (2013). Prevalence, comorbidity, and correlates of DSM-5 proposed disruptive mood dysregulation disorder. American Journal of Psychiatry, 170, 173–179. doi:10.1176/appi.ajp.2012.12010132CrossRefGoogle ScholarPubMed
Copeland, W. E., Shanahan, L., Egger, H., Angold, A., & Costello, E. J. (2014). Adult diagnostic and functional outcomes of DSM-5 disruptive mood dysregulation disorder. American Journal of Psychiatry, 171, 668–674. doi:10.1176/appi.ajp.2014.13091213CrossRefGoogle ScholarPubMed
Cox, R. W. (1996). AFNI: Software for analysis and visualization of functional magnetic resonance neuroimages. Computers and Biomedical Research, 29, 162–173. doi:10.1006/cbmr.1996.0014CrossRefGoogle ScholarPubMed
Crick, N. R., Murray-Close, D., & Woods, K. (2005). Borderline personality features in childhood: A short-term longitudinal study. Development and Psychopathology, 17, 1051–1070. doi:10.1017/S0954579405050492CrossRefGoogle ScholarPubMed
Cuthbert, B. N., & Insel, T. R. (2013). Toward the future of psychiatric diagnosis: The seven pillars of RDoc. BMC Medicine, 11, 126. doi:10.1186/1741-7015-11-126CrossRefGoogle ScholarPubMed
Deater-Deckard, K., Beekman, C., Wang, Z., Kim, J., Petrill, S., Thompson, L., & DeThorne, L. (2010). Approach/positive anticipation, frustration/anger, and overt aggression in childhood: Approach and overt aggression in childhood. Journal of Personality, 78, 991–1010. doi:10.1111/j.1467-6494.2010.00640.xCrossRefGoogle ScholarPubMed
Diekhof, E. K., Geier, K., Falkai, P., & Gruber, O. (2011). Fear is only as deep as the mind allows. NeuroImage, 58, 275–285. doi:10.1016/j.neuroimage.2011.05.073CrossRefGoogle ScholarPubMed
Dougherty, L. R., Smith, V. C., Bufferd, S. J., Carlson, G. A., Stringaris, A., Leibenluft, E., & Klein, D. N. (2014). DSM-5 disruptive mood dysregulation disorder: Correlates and predictors in young children. Psychological Medicine, 44, 2339–2350. doi:10.1017/S0033291713003115CrossRefGoogle ScholarPubMed
Dougherty, L. R., Smith, V. C., Bufferd, S. J., Kessel, E. M., Carlson, G. A., & Klein, D. N. (2016). Disruptive mood dysregulation disorder at the age of 6 years and clinical and functional outcomes 3 years later. Psychological Medicine, 46, 1103–1114. doi:10.1017/S0033291715002809CrossRefGoogle ScholarPubMed
Egger, H. L., & Angold, A. (2004). The Preschool Age Psychiatric Assessment (PAPA): A Structured Parent Interview for diagnosis psychiatric disorders in preschool children. In Delcarmen-Wiggins, R. & Carter, A. (Eds.), A Handbook of infant, toddler, and preschool mental health assessment (pp. 224–243). New York: Oxford University Press.Google Scholar
Elsayed, N. M., Vogel, A. C., Luby, J. L., & Barch, D. M. (2021). Labeling emotional stimuli in early childhood predicts neural and behavioral indicators of emotion regulation in late adolescence. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 6, 89–98. doi:10.1016/j.bpsc.2020.08.018Google ScholarPubMed
Essex, M. J., Boyce, W. T., Goldstein, L. H., Armstrong, J. M., Kraemer, H. C., Kupfer, D. J., & MacArthur Assessment Battery Working Group (2002). The confluence of mental, physical, social, and academic difficulties in middle childhood. II: Developing the Macarthur health and behavior questionnaire. Journal of the American Academy of Child and Adolescent Psychiatry, 41, 588–603. doi:10.1097/00004583-200205000-00017CrossRefGoogle ScholarPubMed
Etkin, A., Büchel, C., & Gross, J. J. (2015). The neural bases of emotion regulation. Nature Reviews Neuroscience, 16, 693–700. doi:10.1038/nrn4044CrossRefGoogle ScholarPubMed
Ezpeleta, L., Granero, R., de la Osa, N., Trepat, E., & Domènech, J. M. (2016). Trajectories of oppositional defiant disorder irritability symptoms in preschool children. Journal of Abnormal Child Psychology, 44, 115–128. doi:10.1007/s10802-015-9972-3CrossRefGoogle ScholarPubMed
Felitti, V. J., Anda, R. F., Nordenberg, D., Williamson, D. F., Spitz, A. M., Edwards, V., … Marks, J. S. (1998). Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults. The adverse childhood experiences (ACE) study. American Journal of Preventive Medicine, 14, 245–258.CrossRefGoogle ScholarPubMed
Geselowitz, B., Whalen, D. J., Tillman, R., Barch, D. M., Luby, J. L., & Vogel, A. (2020). Preschool Age predictors of adolescent borderline personality symptoms. Journal of the American Academy of Child and Adolescent Psychiatry, doi:10.1016/j.jaac.2020.07.908CrossRefGoogle ScholarPubMed
Glasser, M. F., Sotiropoulos, S. N., Wilson, J. A., Coalson, T. S., Fischl, B., Andersson, J. L., … Jenkinson, M. (2013). The minimal preprocessing pipelines for the human connectome project. NeuroImage, 80, 105–124. doi:10.1016/j.neuroimage.2013.04.127CrossRefGoogle ScholarPubMed
Hawes, S. W., Perlman, S. B., Byrd, A. L., Raine, A., Loeber, R., & Pardini, D. A. (2016). Chronic anger as a precursor to adult antisocial personality features: The moderating influence of cognitive control. Journal of Abnormal Psychology, 125, 64–74. doi:10.1037/abn0000129CrossRefGoogle ScholarPubMed
He, J., Degnan, K. A., McDermott, J. M., Henderson, H. A., Hane, A. A., Xu, Q., & Fox, N. A. (2010). Anger and approach motivation in infancy: Relations to early childhood inhibitory control and behavior problems: APPROACH MOTIVATION IN INFANCY. Infancy, 15, 246–269. doi:10.1111/j.1532-7078.2009.00017.xCrossRefGoogle ScholarPubMed
Kaufman, J., Birmaher, B., Axelson, D., Pereplitchikova, F., Brent, D., & Ryan, N. (2016). The KSADS-PL DSM-5. Baltimore, MD: Kennedy Krieger Institute. Retrieved from https://www.kennedykrieger.org/sites/default/files/library/documents/faculty/ksads-dsm-5-screener.pdf.Google Scholar
Klein, D. N., Kotov, R., & Bufferd, S. J. (2011). Personality and depression: Explanatory models and review of the evidence. Annual Review of Clinical Psychology, 7, 269–295. doi:10.1146/annurev-clinpsy-032210-104540CrossRefGoogle Scholar
Kohn, N., Eickhoff, S. B., Scheller, M., Laird, A. R., Fox, P. T., & Habel, U. (2014). Neural network of cognitive emotion regulation – an ALE meta-analysis and MACM analysis. NeuroImage, 87, 345–355. doi:10.1016/j.neuroimage.2013.11.001CrossRefGoogle ScholarPubMed
Leibenluft, E., Cohen, P., Gorrindo, T., Brook, J. S., & Pine, D. S. (2006). Chronic versus episodic irritability in youth: A community-based, longitudinal study of clinical and diagnostic associations. Journal of Child and Adolescent Psychopharmacology, 16, 456–466. doi:10.1089/cap.2006.16.456CrossRefGoogle ScholarPubMed
Luby, J. L., Barch, D. M., Whalen, D., Tillman, R., & Freedland, K. E. (2018). A randomized controlled trial of parent-child psychotherapy targeting emotion development for early childhood depression. American Journal of Psychiatry, 175, 1102–1110. doi:10.1176/appi.ajp.2018.18030321CrossRefGoogle ScholarPubMed
Luby, J. L., Gaffrey, M. S., Tillman, R., April, L. M., & Belden, A. C. (2014). Trajectories of preschool disorders to full DSM depression at school Age and early adolescence: Continuity of preschool depression. American Journal of Psychiatry, 171, 768–776. doi:10.1176/appi.ajp.2014.13091198CrossRefGoogle ScholarPubMed
McNeil, C. B., & Hembree-Kigin, T. L. (2010). Parent-child interaction therapy (5th ed.). Boston, MA: Springer. doi:10.1007/978-0-387-88639-8CrossRefGoogle Scholar
Merikangas, K. R., He, J.-P., Burstein, M., Swanson, S. A., Avenevoli, S., Cui, L., … Swendsen, J. (2010). Lifetime prevalence of mental disorders in U.S. Adolescents: Results from the national comorbidity survey replication–adolescent supplement (NCS-A). Journal of the American Academy of Child and Adolescent Psychiatry, 49, 980–989. doi:10.1016/j.jaac.2010.05.017CrossRefGoogle Scholar
Nigg, J. T. (2006). Temperament and developmental psychopathology. Journal of Child Psychology and Psychiatry, 47, 395–422. doi:10.1111/j.1469-7610.2006.01612.xCrossRefGoogle ScholarPubMed
Pagliaccio, D., Pine, D. S., Barch, D. M., Luby, J. L., & Leibenluft, E. (2018). Irritability trajectories, cortical thickness, and clinical outcomes in a sample enriched for preschool depression. Journal of the American Academy of Child & Adolescent Psychiatry, 57, 336–342.e6. doi:10.1016/j.jaac.2018.02.010CrossRefGoogle Scholar
Perepletchikova, F., Nathanson, D., Axelrod, S. R., Merrill, C., Walker, A., Grossman, M., … Walkup, J. (2017). Randomized clinical trial of dialectical behavior therapy for preadolescent children with disruptive mood dysregulation disorder: Feasibility and outcomes. Journal of the American Academy of Child & Adolescent Psychiatry, 56, 832–840. doi:10.1016/j.jaac.2017.07.789CrossRefGoogle ScholarPubMed
Putnam, S. P., & Stifter, C. A. (2002). Development of approach and inhibition in the first year: Parallel findings from motor behavior, temperament ratings and directional cardiac response. Developmental Science, 5, 441–451. doi:10.1111/1467-7687.00239CrossRefGoogle Scholar
Rich, B. A., Schmajuk, M., Perez-Edgar, K. E., Fox, N. A., Pine, D. S., & Leibenluft, E. (2007). Different psychophysiological and behavioral responses elicited by frustration in pediatric bipolar disorder and severe mood dysregulation. American Journal of Psychiatry, 164, 309–317. doi:10.1176/ajp.2007.164.2.309CrossRefGoogle ScholarPubMed
Roy, A. K., Lopes, V., & Klein, R. G. (2014). Disruptive mood dysregulation disorder: A new diagnostic approach to chronic irritability in youth. American Journal of Psychiatry, 171, 918–924. doi:10.1176/appi.ajp.2014.13101301CrossRefGoogle ScholarPubMed
Rydell, A.-M., Berlin, L., & Bohlin, G. (2003). Emotionality, emotion regulation, and adaptation among 5- to 8-year-old children. Emotion, 3, 30–47. doi:10.1037/1528-3542.3.1.30CrossRefGoogle ScholarPubMed
Sallquist, J. V., Eisenberg, N., Spinrad, T. L., Reiser, M., Hofer, C., Zhou, Q., … Eggum, N. (2009). Positive and negative emotionality: Trajectories across six years and relations with social competence. Emotion, 9, 15–28. doi:10.1037/a0013970CrossRefGoogle ScholarPubMed
Shaffer, D., Fisher, P., Lucas, C. P., Dulcan, M. K., & Schwab-Stone, M. E. (2000). NIMH diagnostic interview schedule for children version IV (NIMH DISC-IV): Description, differences from previous versions, and reliability of some common diagnoses. Journal of the American Academy of Child & Adolescent Psychiatry, 39, 28–38. doi:10.1097/00004583-200001000-00014CrossRefGoogle ScholarPubMed
Sheppes, G., Suri, G., & Gross, J. J. (2015). Emotion regulation and psychopathology. Annual Review of Clinical Psychology, 11, 379–405. doi:10.1146/annurev-clinpsy-032814-112739CrossRefGoogle ScholarPubMed
Shields, A., & Cicchetti, D. (1997). Emotion regulation among school-age children: The development and validation of a new criterion Q-sort scale. Developmental Psychology, 33, 906–916. doi:10.1037/0012-1649.33.6.906CrossRefGoogle ScholarPubMed
Siever, L. J. (2008). Neurobiology of aggression and violence. American Journal of Psychiatry, 165, 429–442. doi:10.1176/appi.ajp.2008.07111774CrossRefGoogle ScholarPubMed
Silk, J. S., Steinberg, L., & Morris, A. S. (2003). Adolescents’ emotion regulation in daily life: Links to depressive symptoms and problem behavior. Child Development, 74, 1869–1880.CrossRefGoogle ScholarPubMed
Silvers, J. A., McRae, K., Gabrieli, J. D. E., Gross, J. J., Remy, K. A., & Ochsner, K. N. (2012). Age-related differences in emotional reactivity, regulation, and rejection sensitivity in adolescence. Emotion, 12, 1235–1247. doi:10.1037/a0028297CrossRefGoogle ScholarPubMed
Silvers, J. A., Shu, J., Hubbard, A. D., Weber, J., & Ochsner, K. N. (2015). Concurrent and lasting effects of emotion regulation on amygdala response in adolescence and young adulthood. Developmental Science, 18, 771–784. doi:10.1111/desc.12260CrossRefGoogle ScholarPubMed
Stringaris, A., & Goodman, R. (2009). Mood lability and psychopathology in youth. Psychological Medicine, 39, 1237–1245. doi:10.1017/S0033291708004662CrossRefGoogle ScholarPubMed
Vogel, A. C., Jackson, J. J., Barch, D. M., Tillman, R., & Luby, J. L. (2019). Excitability and irritability in preschoolers predicts later psychopathology: The importance of positive and negative emotion dysregulation. Development and Psychopathology, 31, 1067–1083. doi:10.1017/S0954579419000609CrossRefGoogle ScholarPubMed
Wakschlag, L. S., Choi, S. W., Carter, A. S., Hullsiek, H., Burns, J., McCarthy, K., … Briggs-Gowan, M. J. (2012). Defining the developmental parameters of temper loss in early childhood: Implications for developmental psychopathology: Early childhood parameters of temper loss. Journal of Child Psychology and Psychiatry, 53, 1099–1108. doi:10.1111/j.1469-7610.2012.02595.xCrossRefGoogle ScholarPubMed
Wakschlag, L. S., Estabrook, R., Petitclerc, A., Henry, D., Burns, J. L., Perlman, S. B., … Briggs-Gowan, M. L. (2015). Clinical implications of a dimensional approach: The normal:abnormal spectrum of early irritability. Journal of the American Academy of Child & Adolescent Psychiatry, 54, 626–634. doi:10.1016/j.jaac.2015.05.016CrossRefGoogle ScholarPubMed
Wakschlag, L. S., Perlman, S. B., Blair, R. J., Leibenluft, E., Briggs-Gowan, M. J., & Pine, D. S. (2018). The neurodevelopmental basis of early childhood disruptive behavior: Irritable and callous phenotypes as exemplars. American Journal of Psychiatry, 175, 114–130. doi:10.1176/appi.ajp.2017.17010045CrossRefGoogle ScholarPubMed
Whelan, Y. M., Stringaris, A., Maughan, B., & Barker, E. D. (2013). Developmental continuity of oppositional defiant disorder subdimensions at ages 8, 10, and 13 years and their distinct psychiatric outcomes at Age 16 years. Journal of the American Academy of Child & Adolescent Psychiatry, 52, 961–969. doi:10.1016/j.jaac.2013.06.013CrossRefGoogle ScholarPubMed
Wiggins, J. L., Brotman, M. A., Adleman, N. E., Kim, P., Oakes, A. H., Reynolds, R. C., … Leibenluft, E. (2016). Neural correlates of irritability in disruptive mood dysregulation and bipolar disorders. American Journal of Psychiatry, 173, 722–730. doi:10.1176/appi.ajp.2015.15060833CrossRefGoogle ScholarPubMed
Wiggins, J. L., Mitchell, C., Stringaris, A., & Leibenluft, E. (2014). Developmental trajectories of irritability and bidirectional associations with maternal depression. Journal of the American Academy of Child & Adolescent Psychiatry, 53, 1191–1205.e4. doi:10.1016/j.jaac.2014.08.005CrossRefGoogle ScholarPubMed
Young, K., Sandman, C., & Craske, M. (2019). Positive and negative emotion regulation in adolescence: Links to anxiety and depression. Brain Sciences, 9, 76. doi:10.3390/brainsci9040076CrossRefGoogle ScholarPubMed
Supplementary material: File

Vogel et al. supplementary material

Table S1

Download Vogel et al. supplementary material(File)
File 13.7 KB
Supplementary material: File

Vogel et al. supplementary material

Table S2

Download Vogel et al. supplementary material(File)
File 16.5 KB