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The Twin Study of Negative Valence Emotional Constructs

  • Dever M. Carney (a1), Elizabeth Moroney (a2), Laura Machlin (a2), Shannon Hahn (a1), Jeanne E. Savage (a1), Minyoung Lee (a1), Kenneth A. Towbin (a2), Melissa A. Brotman (a2), Daniel S. Pine (a2), Ellen Leibenluft (a2), Roxann Roberson-Nay (a1) and John M. Hettema (a1)...


The Twin Study of Negative Valence Emotional Constructs is a multi-site study designed to examine the relationship between a broad selection of potential measures designed to assess putative endophenotypes for negative valence systems (NVS) and early symptoms of internalizing disorders (IDs). In this article, we describe the sample characteristics, data collection protocols, and measures used. Pre-adolescent Caucasian twin pairs were recruited through the Mid-Atlantic Twin Registry; data collection began in February of 2013. Enrolled twins completed various dimensional self-report measures along with cognitive, emotional, and psychophysiological tasks designed to assess NVS function. Parents also completed surveys about their twins and themselves. In addition, a subset of the twins also participated in a neuroimaging protocols. Data collection is in the final stages, and preliminary analyses are underway. The findings will potentially expand our understanding of the mechanisms by which genetic and environmental factors contribute to individual differences in NVS phenotypes and provide new insights into underlying risk factors for IDs.

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Corresponding author

address for correspondence: John M. Hettema, MD, PhD, VCU Department of Psychiatry, PO Box 980126, Richmond, VA 23298-0126, USA. E-mail:


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Achenbach, T. M. (1991). Manual for the child behavior checklist/4-18 and 1991 profile. Burlington, VT: University of Vermont, Department of Psychiatry.
Angold, A., Costello, E. J., Messer, S. C., Pickles, A., Winder, F., & Silver, D. (1995). The development of a short questionnaire for use in epidemiological studies of depression in children and adolescents. International Journal of Methods in Psychiatric Research, 5, 112.
Bailey, J. E., Argyropoulos, S. V., Kendrick, A. H., & Nutt, D. J. (2005). Behavioral and cardiovascular effects of 7.5% CO2 in human volunteers. Depression and Anxiety, 21, 1825.
Birmaher, B., Khetarpal, S., Brent, D., Cully, M., Balach, L., Kaufman, J. A., & Neer, S. M. (1997). The screen for child anxiety related emotional disorders (SCARED): Scale construction and psychometric characteristics. Journal of the American Academy of Child & Adolescent Psychiatry, 36, 545553.
Britton, J. C., Grillon, C., Lissek, S., Norcross, M. A., Szuhany, K. L., Chen, G., . . . Pine, D. S. (2013). Response to learned threat: An FMRI study in adolescent and adult anxiety. American Journal of Psychiatry, 170, 11951204.
Britton, J. C., Lissek, S., Grillon, C., Norcross, M. A., & Pine, D. S. (2011). Development of anxiety: The role of threat appraisal and fear learning. Depression and Anxiety, 28, 517.
Carver, C. S., & White, T. L. (1994). Behavioral inhibition, behavioral activation, and affective responses to impending reward and punishment: The BIS/BAS scales. Journal of Personality and Social Psychology, 67, 319333.
Dalgleish, T., Taghavi, R., Neshat-Doost, H., Moradi, A., Canterbury, R., & Yule, W. (2003). Patterns of processing bias for emotional information across clinical disorders: A comparison of attention, memory, and prospective cognition in children and adolescents with depression, generalized anxiety, and posttraumatic stress disorder. Journal of Clinical Child & Adolescent Psychology, 32, 1021.
Davis, M. (1986). Pharmacological and anatomical analysis of fear conditioning using the fear-potentiated startle paradigm. Behavioral Neuroscience, 100, 814824.
Deveney, C. M., Connolly, M. E., Haring, C. T., Bones, B. L., Reynolds, R. C., Kim, P., . . . Leibenluft, E. (2013). Neural mechanisms of frustration in chronically irritable children. American Journal of Psychiatry, 170, 11861194.
Eysenck, H. J., & Eysenck, S. B. G. (1975). Manual of the eysenck personality questionnaire. London: Hodder and Stoughton.
Eysenck, S. B. (1965). A new scale for personality measurements in children. British Journal of Educational Psychology, 35, 362367.
Geller, B., Bolhofner, K., Craney, J. L., Williams, M., DelBello, M. P., & Gundersen, K. (2000). Psychosocial functioning in a prepubertal and early adolescent bipolar disorder phenotype. Journal of the American Academy of Child & Adolescent Psychiatry, 39, 15431548.
Gottesman, I. I., & Gould, T. D. (2003). The endophenotype concept in psychiatry: Etymology and strategic intentions. American Journal of Psychiatry, 160, 636645.
Grillon, C., & Baas, J. (2003). A review of the modulation of the startle reflex by affective states and its application in psychiatry. Clinical Neurophysiology, 114, 15571579.
Grillon, C., Lissek, S., Rabin, S., McDowell, D., Dvir, S., & Pine, D. S. (2008). Increased anxiety during anticipation of unpredictable but not predictable aversive stimuli as a psychophysiologic marker of panic disorder. American Journal of Psychiatry, 165, 898904.
Guyer, A. E., Choate, V. R., Grimm, K. J., Pine, D. S., & Keenan, K. (2011). Emerging depression is associated with face memory deficits in adolescent girls. Journal of the American Academy of Child & Adolescent Psychiatry, 50, 180190.
Hariri, A. R., Bookheimer, S. Y., & Mazziotta, J. C. (2000). Modulating emotional responses: Effects of a neocortical network on the limbic system. Neuroreport, 11, 4348.
Harris, P. A., Taylor, R., Thielke, R., Payne, J., Gonzalez, N., & Conde, J. G. (2009). Research electronic data capture (REDCap) - A metadata-driven methodology and workflow process for providing translational research informatics support. Journal of Biomedical Informatics, 42, 377381.
Haxby, J. V., Hoffman, E. A., & Gobbini, M. I. (2002). Human neural systems for face recognition and social communication. Biological Psychiatry, 51, 5967.
Insel, T., Cuthbert, B., Garvey, M., Heinssen, R., Pine, D. S., Quinn, K., . . . Wang, P. (2010). Research domain criteria (RDoC): Toward a new classification framework for research on mental disorders. American Journal of Psychiatry, 167, 748751.
Kaufman, J., Birmaher, B., Brent, D., Rao, U., Flynn, C., Moreci, P., . . . Ryan, N. (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.
Kendler, K. S. (2001). Twin studies of psychiatric illness: An update. Archives of General Psychiatry, 58, 10051014.
Kendler, K. S., Karkowski, L. M., & Prescott, C. A. (1998). Stressful life events and major depression: Risk period, long-term contextual threat, and diagnostic specificity. Journal of Nervous and Mental Disease, 186, 661669.
Kessler, R. C., Andrews, G., Mroczek, D. K., Ustun, B., & Wittchen, H.-U. (1998). The World health organization composite international diagnostic interview short form (CIDI-SF). International Journal of Methods in Psychiatric Research, 7, 171185.
Kessler, R. C., Berglund, P., Demler, O., Jin, R., Merikangas, K. R., & Walters, E. E. (2005). Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the national comorbidity survey replication. Archives of General Psychiatry, 62, 593602.
Kimonis, E. R., Frick, P. J., Skeem, J. L., Marsee, M. A., Cruise, K., Munoz, L. C., . . . Morris, A. (2008). Assessing callous-unemotional traits in adolescent offenders: Validation of the Inventory of Callous-Unemotional Traits. International Journal of Law and Psychiatry, 31, 241252.
Kramer, M. D., Patrick, C. J., Krueger, R. F., & Gasperi, M. (2012). Delineating physiologic defensive reactivity in the domain of self-report: Phenotypic and etiologic structure of dispositional fear. Psychological Medicine, 42, 13051320.
Landis, C. W. (1939). The startle pattern. Oxford: Farrah & Rinehart.
Lilley, E. C., & Silberg, J. L. (2013). The mid-atlantic twin registry, revisited. Twin Research and Human Genetics, 16, 424428.
Marsh, A. A., Yu, H. H., Pine, D. S., & Blair, R. J. (2010). Oxytocin improves specific recognition of positive facial expressions. Psychopharmacology (Berl), 209, 225232.
Mynard, H., & Joseph, S. (2000). Development of the multidimensional peer-victimization scale. Aggressive Behavior, 26, 169178.
Nichols, R. C., & Bilbro, W. C. Jr. (1966). The diagnosis of twin zygosity. Acta Genetica et Statistica Medica, 16, 265275.
Ollendick, T. H. (1983). Reliability and validity of the revised fear surgery schedule for children (FSSC-R). Behaviour Research and Therapy, 21, 685692.
Otowa, T., Hek, K., Lee, M., Byrne, E. M., Mirza, S. S., Nivard, M. G., . . . Hettema, J. M. (2016). Meta-analysis of genome-wide association studies of anxiety disorders. Molecular Psychiatry. Advance online publication.
Papp, L. A., Klein, D. F., & Gorman, J. M. (1993). Carbon dioxide hypersensitivity, hyperventilation, and panic disorder. American Journal of Psychiatry, 150, 11491157.
Parker, G., Tupling, H., & Brown, L. (1979). A parental bonding instrument. British Journal of Medical Psychology, 52, 110.
Peeters, H., Van, G. S., Vlietinck, R., Derom, C., & Derom, R. (1998). Validation of a telephone zygosity questionnaire in twins of known zygosity. Behavior Genetics, 28, 159163.
Philippot, P., & Feldman, R. S. (1990). Age and social competence in preschoolers' decoding of facial expression. British Journal of Social Psychology, 29, 4354.
Pine, D. S., Klein, R. G., Coplan, J. D., Papp, L. A., Hoven, C. W., Martinez, J., . . . Gorman, J. M. (2000). Differential carbon dioxide sensitivity in childhood anxiety disorders and nonill comparison group. Archives of General Psychiatry, 57, 960967.
Pine, D. S., Klein, R. G., Mannuzza, S., Moulton, J. L. III, Lissek, S., Guardino, M., & Woldehawariat, G. (2005). Face-emotion processing in offspring at risk for panic disorder. Journal of the American Academy of Child & Adolescent Psychiatry, 44, 664672.
Reznick, J. S., Hegeman, I. N., Kaufman, E. R., Woods, S. W., & Jacobs, M. (1992). Retrospective and concurrent self-report of behavioral inhibition and their relation to adult mental health development and psychopathology. Development and Psychopathology, 4, 301321.
Rich, B. A., Grimley, M. E., Schmajuk, M., Blair, K. S., Blair, R. J., & Leibenluft, E. (2008). Face emotion labeling deficits in children with bipolar disorder and severe mood dysregulation. Development and Psychopathology, 20, 529546.
Rich, B. A., Holroyd, T., Carver, F. W., Onelio, L. M., Mendoza, J. K., Cornwell, B. R., . . . Leibenluft, E. (2010). A preliminary study of the neural mechanisms of frustration in pediatric bipolar disorder using magnetoencephalography. Depression and Anxiety, 27, 276286.
Ripke, S., Wray, N. R., Lewis, C. M., Hamilton, S. P., Weissman, M. M., Breen, G., . . . Sullivan, P. F. (2013). A mega-analysis of genome-wide association studies for major depressive disorder. Molecular Psychiatry, 18, 497511.
Savage, J. E., Sawyers, C., Roberson-Nay, R., Hettema, J. M. (2016). The genetics of anxiety-related negative valence system traits. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics. Advance online publication.
Schmitz, A., Merikangas, K., Swendsen, H., Cui, L., Heaton, L., & Grillon, C. (2011). Measuring anxious responses to predictable and unpredictable threat in children and adolescents. Journal of Experimental Child Psychology, 110, 159170.
Silverman, W. K., Fleisig, W., Rabian, B., & Peterson, R. A. (1991). Childhood anxiety sensitivity index. Journal of Clinical Child Psychology, 20, 162168.
Stringaris, A., Goodman, R., Ferdinando, S., Razdan, V., Muhrer, E., Leibenluft, E., & Brotman, M. A. (2012). The Affective Reactivity Index: A concise irritability scale for clinical and research settings. Journal of Child Psychology and Psychiatry, 53, 11091117.
Swartz, J. R., Phan, K. L., Angstadt, M., Fitzgerald, K. D., & Monk, C. S. (2014). Dynamic changes in amygdala activation and functional connectivity in children and adolescents with anxiety disorders. Development and Psychopathology, 26, 13051319.
Visscher, P. M. (2004). Power of the classical twin design revisited. Twin Research, 7, 505512.



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