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Atypical patterns of respiratory sinus arrhythmia index an endophenotype for depression

Published online by Cambridge University Press:  25 November 2014

Ilya Yaroslavsky*
Affiliation:
Cleveland State University
Jonathan Rottenberg
Affiliation:
University of South Florida
Maria Kovacs
Affiliation:
University of Pittsburgh School of Medicine
*
Address correspondence and reprint requests to: Ilya Yaroslavsky, Department of Psychology, Cleveland State University, 2121 Euclid Avenue, Cleveland, OH 44115; E-mail: i.yaroslavsky@csuohio.edu.

Abstract

Can atypical patterns of parasympathetic nervous system activity serve as endophenotypes for depression? Using respiratory sinus arrhythmia (RSA) as an index of parasympathetic nervous system function, we examined this question in two studies: one involving mothers with and without depression histories and their offspring (at high and low risk for depression, respectively), and a further study of adolescent sibling pairs concordant and discordant for major depression. In both studies, subjects were exposed to sad mood induction; subjects' RSA was monitored during rest periods and in response to the mood induction. We used Gottesman and Gould's (2003) criteria for an endophenotype and a priori defined “atypical” and “normative” RSA patterns (combinations of resting RSA and RSA reactivity). We found that atypical RSA patterns (a) predicted current depressive episodes and remission status among women with histories of juvenile onset depression and healthy controls, (b) predicted longitudinal trajectories of depressive symptoms among high- and low-risk young offspring, (c) were concordant across mothers and their juvenile offspring, (d) were more prevalent among never-depressed youth at high risk for depression than their low-risk peers, and (e) were more concordant across adolescent sibling pairs in which both versus only one had a history of major depression. Thus, the results support atypical RSA patterns as an endophenotype for depression. Possible mechanisms by which RSA patterns increase depression risk and their genetic contributors are discussed.

Type
Regular Articles
Copyright
Copyright © Cambridge University Press 2014 

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References

Achenbach, T. M. (1991). Integrative guide for the 1991 CBCL/4–18, YSR, and TRF Profiles. Burlington, VT: University of Vermont, Department of Psychiatry.Google Scholar
Agorastos, A., Kellner, M., Stiedl, O., Muhtz, C., Becktepe, J. S., Wiedemann, K., et al. (2013). The 5-HTTLPR genotype modulates heart rate variability and its adjustment by pharmacological panic challenge in healthy men. Journal of Psychiatric Research. Advance online publication.Google Scholar
Aiken, L. S., & West, S. G. (1991). Multiple regression: Testing and interpreting interactions. Newbury Park, CA: Sage.Google Scholar
Ashman, S. B., Dawson, G., & Panagiotides, H. (2008). Trajectories of maternal depression over 7 years: Relations with child psychophysiology and behavior and role of contextual risks. Development and Psychopathology, 20, 5577.Google Scholar
Baji, I., Lopez-Duran, N. L., Kovacs, M., George, C. J., Mayer, L., Kapornai, K., et al. (2009). Age and sex analyses of somatic complaints and symptom presentation of childhood depression in a Hungarian clinical sample. Journal of Clinical Psychiatry, 70, 14671472.Google Scholar
Beauchaine, T. P. (2001). Vagal tone, development, and Gray's motivational theory: Toward an integrated model of autonomic nervous system functioning in psychopathology. Development and Psychopathology, 13, 183214.CrossRefGoogle ScholarPubMed
Beauchaine, T. P., Gatzke-Kopp, L. M., & Mead, H. K. (2007). Polyvagal theory and developmental psychopathology: Emotion dysregulation and conduct problems from preschool to adolescence. Biological Psychology, 74, 174184.Google Scholar
Beck, A. T., Steer, R. A., & Carbin, M. G. (1988). Psychometric properties of the Beck Depression Inventory: Twenty-five years of evaluation. Clinical Psychology Review, 8, 77100.Google Scholar
Berntson, G. G., Bigger, J. T., Eckberg, D. L., Grossman, P., Kaufmann, P. G., Malik, M., et al. (1997). Heart rate variability: Origins, methods, and interpretive caveats. Psychophysiology, 34, 623648.CrossRefGoogle ScholarPubMed
Blom, E. H., Olsson, E. M., Serlachius, E., Ericson, M., & Ingvar, M. (2010). Heart rate variability (HRV) in adolescent females with anxiety disorders and major depressive disorder. Acta Paediatrica, 99, 604611.Google Scholar
Boomsma, D. I., Van Baal, G. C., & Orlebeke, J. F. (1990). Genetic influences on respiratory sinus arrhythmia across different task conditions. Acta Geneticae Medicae et Gemellologiae: Twin Research, 39, 181191.CrossRefGoogle ScholarPubMed
Bornstein, M. H., & Suess, P. E. (2000). Child and mother cardiac vagal tone: Continuity, stability, and concordance across the first 5 years. Developmental Psychology, 36, 5465.Google Scholar
Calkins, S. D. (1997). Cardiac vagal tone indices of temperamental reactivity and behavioral regulation in young children. Developmental Psychobiology, 31, 125135.3.0.CO;2-M>CrossRefGoogle ScholarPubMed
Caspi, A., Sugden, K., Moffitt, T. E., Taylor, A., Craig, I. W., Harrington, H., et al. (2003). Influence of life stress on depression: Moderation by a polymorphism in the 5-HTT gene. Science, 301, 386389.CrossRefGoogle ScholarPubMed
Chambers, A. S., & Allen, J. J. B. (2002). Vagal tone as an indicator of treatment response in major depression. Psychophysiology, 39, 861864.Google Scholar
Clarke, H., Flint, J., Attwood, A. S., & Munafò, M. R. (2010). Association of the 5 HTTLPR genotype and unipolar depression: A meta-analysis. Psychological Medicine, 40, 1767.Google Scholar
Connell, A. M., Hughes-Scalise, A., Klostermann, S., & Azem, T. (2011). Maternal depression and the heart of parenting: Respiratory sinus arrhythmia and affective dynamics during parent–adolescent interactions. Journal of Family Psychology, 25, 653662.Google Scholar
Conway, C. C., Hammen, C., Espejo, E. P., Wray, N. R., Najman, J. M., & Brennan, P. A. (2012). Appraisals of stressful life events as a genetically-linked mechanism in the stress–depression relationship. Cognitive Therapy and Research, 36, 338347.Google Scholar
Creaven, A., Skowron, E. A., Hughes, B. M., Howard, S., & Loken, E. (2014). Dyadic concordance in mother and preschooler resting cardiovascular function varies by risk status. Developmental Psychobiology, 56, 142152.CrossRefGoogle ScholarPubMed
Cribbet, M. R., Williams, P. G., Gunn, H. E., & Rau, H. K. (2011). Effects of tonic and phasic respiratory sinus arrhythmia on affective stress responses. Emotion, 11, 188193. doi:10.1037/a0021789 Google Scholar
Crişan, L. G., Pană, S., Vulturar, R., Heilman, R. M., Szekely, R., Drugă, B., et al. (2009). Genetic contributions of the serotonin transporter to social learning of fear and economic decision making. Social Cognitive and Affective Neuroscience, 4, 399408.CrossRefGoogle ScholarPubMed
Cuthbert, B. N., & Insel, T. R. (2013). Toward the future of psychiatric diagnosis: The seven pillars of RDoC. BMC Medicine, 11, 126.Google Scholar
Cyranowski, J. M., Hofkens, T. L., Swartz, H. A., Salomon, K., & Gianaros, P. J. (2011). Cardiac vagal control in nonmedicated depressed women and nondepressed controls: Impact of depression status, lifetime trauma history, and respiratory factors. Psychosomatic Medicine, 73, 336343.CrossRefGoogle ScholarPubMed
De Geus, E. J., Kupper, N., Boomsma, D. I., & Snieder, H. (2007). Bivariate genetic modeling of cardiovascular stress reactivity: Does stress uncover genetic variance? Psychosomatic Medicine, 69, 356364.Google Scholar
Del Giudice, M., Ellis, B. J., & Shirtcliff, E. A. (2011). The adaptive calibration model of stress responsivity. Neuroscience & Biobehavioral Reviews, 35, 15621592.Google Scholar
Dubin, M., Weissman, M., Xu, D., Bansal, R., Hao, X., Liu, J., et al. (2012). Identification of a circuit-based endophenotype for familial depression. Psychiatry Research: Neuroimaging, 201, 175181.Google Scholar
Dywan, J., Mathewson, K., Choma, B. L., Rosenfeld, B., & Segalowitz, S. (2008). Autonomic and electrophysiological correlates of emotional intensity in older and younger adults. Psychophysiology, 45, 389397.Google Scholar
Ellis, A. J., Beevers, C. G., Hixon, J. G., & McGeary, J. E. (2011). Serotonin transporter promoter region (5-HTTLPR) polymorphism predicts resting respiratory sinus arrhythmia. Psychophysiology, 48, 923926.Google Scholar
El-Sheikh, M., & Erath, S. A. (2011). Family conflict, autonomic nervous system functioning, and child adaptation: State of the science and future directions. Development and Psychopathology, 23, 703721.Google Scholar
El-Sheikh, M., Hinnant, J. B., & Erath, S. (2011). Developmental trajectories of delinquency symptoms in childhood: The role of marital conflict and autonomic nervous system activity. Journal of Abnormal Psychology, 120, 1632.Google Scholar
Fabes, R. A., & Eisenberg, N. (1997). Regulatory control and adults' stress-related responses to daily life events. Journal of Personality and Social Psychology, 73, 11071117.Google Scholar
First, M. B., Spitzer, R. L., Gibbon, M., & Williams, J. B. W. (1995). Structured Clinical Interview for DSM-IV Axis I disorders—Patient edition (SCID-I/P, Version 2.0). New York: New York State Psychiatric Institute, Biometrics Research Department.Google Scholar
Gentzler, A. L., Rottenberg, J., Kovacs, M. George, C. J., & Morey, J. N. (2012). Atypical development of resting respiratory sinus arrhythmia in children at high risk for depression. Developmental Psychobiology, 54, 556567. doi:10.1002/dev.20614 Google Scholar
Gentzler, A. L., Santucci, A. K., Kovacs, M., & Fox, N. (2009). Respiratory sinus arrhythmia reactivity predicts emotion regulation and depressive symptoms in at-risk and control children. Biological Psychology, 82, 156163.Google Scholar
Goodman, S. H. (2007). Depression in mothers. Annual Review of Clinical Psychology, 3, 107135.Google Scholar
Goodman, S. H., & Gotlib, I. H. (1999). Risk for psychopathology in the children of depressed mothers: A developmental model for understanding mechanisms of transmission. Psychological Review, 106, 458490.CrossRefGoogle ScholarPubMed
Gottesman, I. I., & Gould, T. D. (2003). The endophenotype concept in psychiatry: Etymology and strategic intentions. American Journal of Psychiatry, 160, 636645.Google Scholar
Graham, J. W. (2009). Missing data analysis: Making it work in the real world. Annual Review of Psychology, 60, 549576.Google Scholar
Gross, J. J., & Levenson, R. W. (1995). Emotion elicitation using films. Cognition and Emotion, 9, 87108.CrossRefGoogle Scholar
Hansen, A. L., Johnsen, B. H., & Thayer, J. F. (2003). Vagal influence on working memory and attention. International Journal of Psychophysiology, 48, 263274.CrossRefGoogle ScholarPubMed
Hinnant, J. B., & El-Sheikh, M. (2009). Children's externalizing and internalizing symptoms over time: The role of individual differences in patterns of RSA responding. Journal of Abnormal Child Psychology, 37, 10491061.Google Scholar
Hinnant, J. B., & El-Sheikh, M. (2013). Codevelopment of externalizing and internalizing symptoms in middle to late childhood: Sex, baseline respiratory sinus arrhythmia, and respiratory sinus arrhythmia reactivity as predictors. Development and Psychopathology, 25, 419436.Google Scholar
Hofmann, S. G., Schulz, S. M., Heering, S., Muench, F., & Bufka, L. F. (2010). Psychophysiological correlates of generalized anxiety disorder with or without comorbid depression. International Journal of Psychophysiology, 78, 3541.CrossRefGoogle ScholarPubMed
Jones, N. A., Field, T., Fox, N. A., Davalos, M., Lundy, B., & Hart, S. (1998). Newborns of mothers with depressive symptoms are physiologically less developed. Infant Behavior and Development, 21, 537541.Google Scholar
Kaufman, J., Birmaher, B., Brent, D., Rao, U. M. A., Flynn, C., Moreci, P., et al. (1997). Schedule for Affective Disorders and Schizophrenia for School-Age Children—Present and Lifetime Version (K-SADS-PL): Initial reliability and validity data. Journal of the American Academy of Child & Adolescent Psychiatry, 36, 980988.Google Scholar
Kemp, A. H., Quintana, D. S., Gray, M. A., Felmingham, K. L., Brown, K., & Gatt, J. M. (2010). Impact of depression and antidepressant treatment on heart rate variability: A review and meta-analysis. Biological Psychiatry, 67, 10671074.Google Scholar
Kiss, E., Gentzler, A. M., George, C., Kapornai, K., Tamas, Z., Kovacs, M., et al. (2007). Factors influencing mother–child reports of depressive symptoms and agreement among clinically referred depressed youngsters in Hungary. Journal of Affective Disorders, 100, 143151.Google Scholar
Kovacs, M. (1992). The Children's Depression Inventory (CDI) manual. North Tonawanda, NY: Multi-Health Systems.Google Scholar
Kovacs, M., & MHS Staff. (2011). Children's Depression Inventory (CDI 2): Technical manual (2nd ed.). North Tonawanda, NY: Multi-Health Systems.Google Scholar
Kovacs, M., Rottenberg, J., & George, C. (2009). Maladaptive mood repair responses distinguish young adults with early onset depressive disorders and predict future depressive outcomes. Psychological Medicine, 39, 18411854.Google Scholar
Kovacs, M., Yaroslavsky, I., Rottenberg, J., George, C. J., Baji, I., Benák, I., et al. (2014). Mood repair in adolescents with pediatric-onset major depression: The utility of attention refocusing and recall of positive memories for attenuating sadness. Manuscript submitted for publication.Google Scholar
Kreibig, S. D. (2010). Autonomic nervous system activity in emotion: A review. Biological Psychology, 84, 394421. doi:10.1016/j.biopsycho.2010.03.010 Google Scholar
Kupper, N., Willemsen, G., Posthuma, D., De Boer, D., Boomsma, D. I., & De Geus, E. J. C. (2005). A genetic analysis of ambulatory cardiorespiratory coupling. Psychophysiology, 42, 202212.Google Scholar
Lacey, J. I. (1959). Psychophysiological approaches to the evaluation of psychotherapeutic process and outcome. In Rubinstein, E. A. & Parloff, M. B. (Eds.), Research in psychotherapy (pp. 160208). Washington, DC: American Psychological Association.Google Scholar
Lehofer, M., Moser, M., Hoehn-Saric, R., McLeod, D., Liebmann, P., Drnorvsek, B., et al. (1997). Major depression and cardiac autonomic control. Biological Psychology, 42, 914919.Google ScholarPubMed
Lenzenweger, M. F. (2013). Endophenotype, intermediate phenotype, biomarker: Definitions, concept comparisons, clarifications. Depression and Anxiety, 30, 185189.Google Scholar
Licht, C. M. M., de Geus, E. J. C., Zitman, F. G., Hoogendijk, W. J. G., van Dyck, R., & Penninx, B. W. J. H. (2008). Association between major depressive disorder and heart rate variability in the Netherlands Study of Depression and Anxiety (NESDA). Archives of General Psychiatry, 65, 13581367.Google Scholar
López-León, S., Janssens, A. C. J. W., Ladd, A. G. Z., Del-Favero, J., Claes, S. J., Oostra, B. A., et al. (2008). Meta-analyses of genetic studies on major depressive disorder. Molecular Psychiatry, 13, 772785.Google Scholar
Maziade, M., Roy, M. A., Fournier, J. P., Cliche, D., Merette, C., Caron, C., et al. (1992). Reliability of best-estimate diagnosis in genetic linkage studies of major psychoses: Results from the Quebec Pedigree Studies. American Journal of Psychiatry, 149, 16741686.Google Scholar
Miller, A., Fox, N. A., Cohn, J. F., Forbes, E. E., Sherrill, J. T., & Kovacs, M. (2002). Regional patterns of brain activity in adults with a history of childhood-onset depression: Gender differences and clinical variability. American Journal of Psychiatry, 159, 934940. doi:10.1176/appi.ajp.159.6.934 CrossRefGoogle ScholarPubMed
Moser, M., Lehofer, M., Hoehn-Saric, R., McLeod, D. R., Hildebrandt, G., Steinbrenner, B., et al. (1998). Increased heart rate in depressed subjects in spite of unchanged autonomic balance? Journal of Affective Disorders, 48, 115124.Google Scholar
O'Connor, M. F., Allen, J. J., & Kaszniak, A. W. (2002). Autonomic and emotion regulation in bereavement and depression. Journal of Psychosomatic Research, 52, 183185.Google Scholar
Overbeek, T. J. M., van Boxtel, A., & Westerink, J. H. D. M. (2012). Respiratory sinus arrhythmia responses to induced emotional states: Effects of RSA indices, emotion induction method, age, and sex. Biological Psychology, 91, 128141.Google Scholar
Park, G., Van Bavel, J. J., Vasey, M. W., & Thayer, J. F. (2012). Cardiac vagal tone predicts inhibited attention to fearful faces. Emotion, 12, 12921302.CrossRefGoogle ScholarPubMed
Pickens, J. N., & Field, T. (1995), Facial expressions and vagal tone of infants of depressed and non-depressed mothers. Early Developmental Parenting, 4, 8389.Google Scholar
Porges, S. W. (2007). The polyvagal perspective. Biological Psychology, 74, 116143.Google Scholar
Porges, S. W., Doussard-Roosevelt, J., Portales, A. L., & Greenspan, S. I. (1996). Infant regulation of the vagal “brake” predicts child behavior problems: A psychobiological model of social behavior. Developmental Psychobiology, 29, 697712. doi:10.1002/(SICI)1098-2302(199612)29:8< 697::AID-DEV5>3.0.CO;2-O Google Scholar
Rechlin, T., Claus, D., Weis, M., & Kaschka, W. P. (1995). Depressed heart rate variability in amitryptyline treated depressed patients: Biological and clinical significance. European Psychiatry, 10, 189194.Google Scholar
Rottenberg, J. (2007). Cardiac vagal control in depression: A critical analysis. Biological Psychology, 74, 200211.Google Scholar
Rottenberg, J., Clift, A., Bolden, S., & Salomon, K. (2007). RSA fluctuation in major depressive disorder. Psychophysiology, 44, 450458.Google Scholar
Rottenberg, J., Gross, J. J., Wilhelm, F. H., Najmi, S., & Gotlib, I. H. (2002). Crying threshold and intensity in major depressive disorder. Journal of Abnormal Psychology, 111, 302312.Google Scholar
Rottenberg, J., Salomon, K., Gross, J. J., & Gotlib, I. H. (2005). Vagal withdrawal to a sad film predicts subsequent recovery from depression. Psychophysiology, 42, 277281. doi:10.1111/j.1469-8986.2005.00289.x Google Scholar
Rottenberg, J., Yaroslavsky, I., Carney, R. M., Freedland, K. E., George, C. J., Baji, I., et al. (2014). The association between major depressive disorder in childhood and risk factors for cardiovascular disease in adolescence. Psychosomatic Medicine. Advance online publication.Google Scholar
Santucci, A. K., Silk, J. S., Shaw, D. S., Gentzler, A., Fox, N. A., & Kovacs, M. (2008). Vagal tone and temperament as predictors of emotion regulation strategies in young children. Developmental Psychobiology, 50, 205216.Google Scholar
SAS Institute, Inc. (2013). SAS® 9.3: System options: Reference (2nd ed.) Cary, NC: Author.Google Scholar
Simmons, W. K., & Drevets, W. C. (2012). A “taste” of what is to come: Reward sensitivity as a potential endophenotype for major depressive disorder. Biological Psychiatry, 72, 526527.Google Scholar
Singh, J. P., Larson, M. G., O'Donnell, C. J., Tsuji, H., Evans, J. C., & Levy, D. (1999). Heritability of heart rate variability: The Framingham Heart Study. Circulation, 99, 22512254.Google Scholar
Sinnreich, R., Friedlander, Y., Luria, M. H., Sapoznikov, D., & Kark, J. D. (1999). Inheritance of heart rate variability: The Kibbutzim Family Study. Human Genetics, 105, 654661.Google Scholar
Stewart, J. L., Bismark, A. W., Towers, D. N., Coan, J. A., & Allen, J. J. B. (2010). Resting frontal EEG asymmetry as an endophenotype for depression risk: Sex-specific patterns of frontal brain asymmetry. Journal of Abnormal Psychology, 119, 502512. doi:10.1037/a0019196 Google Scholar
Tamás, Z., Kovacs, M., Gentzler, A. L., Tepper, P., Gádoros, J., Kiss, E., et al. (2007). The relations of temperament and emotion self-regulation with suicidal behaviors in a clinical sample of depressed children in Hungary. Journal of Abnormal Child Psychology, 35, 640652.Google Scholar
Thayer, J. F., Åhs, F., Fredrikson, M., Sollers, J. I., II, & Wager, T. D. (2012). A meta-analysis of heart rate variability and neuroimaging studies: Implications for heart rate variability as a marker of stress and health. Neuroscience & Biobehavioral Reviews, 36, 747756.Google Scholar
Thayer, J. F., Hansen, A. L., Saus-Rose, E., & Johnsen, B. H. (2009). Heart rate variability, prefrontal neural function, and cognitive performance: The neurovisceral integration perspective on self-regulation, adaptation, and health. Annals of Behavioral Medicine, 37, 141153.CrossRefGoogle ScholarPubMed
Thayer, J. F., & Lane, R. D. (2000). A model of neurovisceral integration in emotion regulation and dysregulation. Journal of Affective Disorders, 61, 201216.Google Scholar
Thayer, J. F., & Lane, R. D. (2009). Claude Bernard and the heart–brain connection: Further elaboration of a model of neurovisceral integration. Neuroscience & Biobehavioral Reviews, 33, 8188.Google Scholar
Tuvblad, C., Isen, J., Baker, L. A., Raine, A., Lozano, D., & Jacobson, K. C. (2010). The genetic and environmental etiology of sympathetic and parasympathetic activity in children. Behavior Genetics, 40, 452466.Google Scholar
von Leupoldt, A., Rohde, J., Beregova, A., Thordsen-Sörensen, I., Nieden, J. Z., & Dahme, B. (2007). Films for eliciting emotional states in children. Behavior Research Methods, 39, 606609.Google Scholar
Vulturar, R., Chiş, A., Ungureanu, L., & Miu, A. C. (2012). Respiratory sinus arrhythmia and serotonin transporter promoter gene polymorphisms: Taking a triallelic approach makes a difference. Psychophysiology, 49, 14121416.Google Scholar
Wichers, M., Myin-Germeys, I., Jacobs, N., Peeters, F., Kenis, G., Derom, C., et al. (2007). Genetic risk of depression and stress-induced negative affect in daily life. British Journal of Psychiatry, 191, 218223.Google Scholar
Yaroslavsky, I., Bylsma, L., Rottenberg, J., & Kovacs, M. (2013). Combinations of resting RSA and RSA reactivity impact maladaptive mood repair and depression symptoms. Biological Psychology, 94, 272281.Google Scholar
Yaroslavsky, I., Rottenberg, J., Bylsma, L., Jennings, J. R., George, G., Bajo, I., et al. (2014). Parasympathetic nervous system activity supports mood repair use and effectiveness among adolescents. Manuscript submitted for publication.Google Scholar
Yaroslavsky, I., Rottenberg, J., & Kovacs, M. (2013). The utility of combining RSA indices in depression prediction. Journal of Abnormal Psychology, 122, 314321.Google Scholar
Yeragani, V. K., Pohl, R., Balon, R., Ramesh, C., Glitz, D., Jung, I., et al. (1991). Heart rate variability in patients with major depression. Psychiatry Research, 37, 3546.Google Scholar