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Modeling and treating internalizing psychopathology in a clinical trial: a latent variable structural equation modeling approach

  • M. G. Kushner (a1), R. F. Krueger (a2), M. M. Wall (a3), E. W. Maurer (a1), J. S. Menk (a4) and K. R. Menary (a1)...

Clinical trials are typically designed to test the effect of a specific treatment on a single diagnostic entity. However, because common internalizing disorders are highly correlated (‘co-morbid’), we sought to establish a practical and parsimonious method to characterize and quantify changes in a broad spectrum of internalizing psychopathology targeted for treatment in a clinical trial contrasting two transdiagnostic psychosocial interventions.


Alcohol dependence treatment patients who had any of several common internalizing disorders were randomized to a six-session cognitive-behavioral therapy (CBT) experimental treatment condition or a progressive muscle relaxation training (PMRT) comparison treatment condition. Internalizing psychopathology was characterized at baseline and 4 months following treatment in terms of the latent structure of six distinct internalizing symptom domain surveys.


Exploratory structural equation modeling (ESEM) identified a two-factor solution at both baseline and the 4-month follow-up: Distress (measures of depression, trait anxiety and worry) and Fear (measures of panic anxiety, social anxiety and agoraphobia). Although confirmatory factor analysis (CFA) demonstrated measurement invariance between the time-points, structural models showed that the latent means of Fear and Distress decreased substantially from baseline to follow-up for both groups, with a small but statistically significant advantage for the CBT group in terms of Distress (but not Fear) reduction.


The approach demonstrated in this study provides a practical solution to modeling co-morbidity in a clinical trial and is consistent with converging evidence pointing to the dimensional structure of internalizing psychopathology.

Corresponding author
*Address for correspondence: M. G. Kushner, Ph.D., 282-2A West, 2450 Riverside Avenue, Minneapolis, MN 55454, USA. (Email:
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Andrews G, Goldberg DP, Krueger RF, Carpenter WT, Hyman SE, Sachdev P, Pine DS (2009). Exploring the feasibility of a meta-structure for DSM-V and ICD-11: could it improve utility and validity? Psychological Medicine 39, 19932000.
Andrews G, Slade T, Issakidis C (2002). Deconstructing current comorbidity: data from the Australian National Survey of Mental Health and Well-Being. British Journal of Psychiatry 181, 306314.
APA (1980). Diagnostic and Statistical Manual of Mental Disorders, 3rd edn.American Psychiatric Association: Washington, DC.
Barlow DH, Allen LB, Choate ML (2004). Toward a unified treatment for emotional disorders. Behavior Therapy 35, 205230.
Barlow DH, Craske MG, Cerny JA, Klosko JS (1989). Behavioral treatment of panic disorder. Behavior Therapy 20, 261282.
Beck AT (1976). Cognitive Therapy and the Emotional Disorders. International Universities Press: New York.
Beck AT, Rush AJ, Shaw BF, Emery G (1979). Cognitive Therapy of Depression. Guilford Press: New York.
Beck AT, Ward CH, Mendelson M, Mock J, Erbaugh J (1961). An inventory for measuring depression. Archives of General Psychiatry 4, 5363.
Beekman AT, de Beurs E, van Balkom AJ, Deeg DJ, van Dyck R, van Tilburg W (2000). Anxiety and depression in later life: co-occurrence and communality of risk factors. American Journal of Psychiatry 157, 8995.
Bernstein DA, Borkovec TD (1973). Progressive Relaxation Training. A Manual for the Helping Professions. Research Press: Champaign, IL.
Borsboom D, Mellenbergh G, van Heerden J (2003). The theoretical status of latent variables. Psychological Review 110, 203219.
Brown EJ, Turovsky J, Heimberg RG, Juster HR, Brown TA, Barlow DH (1997). Validation of the Social Interaction Anxiety Scale and the Social Phobia Scale across the anxiety disorders. Psychological Assessment 9, 2127.
Brown SA, Irwin M, Schuckit MA (1991). Changes in anxiety among abstinent male alcoholics. Journal of Studies on Alcohol 52, 5561.
Brown TA, Campbell LA, Lehman CL, Grisham JR, Mancill RB (2001). Current and lifetime comorbidity of the DSM-IV anxiety and mood disorders in a large clinical sample. Journal of Abnormal Psychology 110, 585599.
Chambless DL, Caputo GC, Jasin SE, Gracely EJ, Williams C (1985). The Mobility Inventory for Agoraphobia. Behaviour Research and Therapy 23, 3544.
Eaton NR, Krueger RF, Oltmanns TF (2011). Aging and the structure and the long-term stability of the internalizing spectrum of personality and psychopathology. Psychology and Aging 26, 987993.
Ellard KK, Fairholme CP, Boisseau CL, Farchione TJ, Barlow DH (2010). Unified protocol for the transdiagnostic treatment of emotional disorders: protocol development and initial outcome data. Cognitive Behavioral Practice 17, 88101.
Ellis A, Harper RO (1975). A New Guide to Rational Living. Prentice-Hall: Oxford, UK.
Foa EB, Kozak MJ (1986). Emotional processing of fear: exposure to corrective information. Psychological Bulletin 99, 2035.
First MB, Spitzer R, Gibbon M, Williams J (1989). Structural Clinical Interview for Axis-I DSM-IV Disorders Patient Edition (SCID-I/P Version 2.0). New York State Psychiatric Institution: New York, NY.
Heimberg RG, Dodge CS, Hope DA, Kennedy CR, Zollo LJ, Becker RE (1990). Cognitive behavioral group treatment for social phobia: comparison with a credible placebo control. Cognitive Therapy and Research 14, 123.
Houck PR, Spiegel DA, Shear MK, Rucci P (2002). Reliability of the self-report version of the Panic Disorder Severity Scale. Depression and Anxiety 15, 183185.
Hu L, Bentler PM (1999). Cutoff criteria for fit indexes in covariance structure analysis: conventional criteria versus new alternatives. Structural Equation Modeling 6, 155.
Jacobson E (1938). Progressive Relaxation, 2nd edn.University of Chicago Press: Oxford, UK.
Kendler KS, Prescott CA, Myers J, Neale MC (2003). The structure of genetic and environmental risk factors for common psychiatric and substance use disorders in men and women. Archives of General Psychiatry 60, 929937.
Kessler RC, Chiu W, Demler O, Walters E (2005). Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Archives of General Psychiatry 62, 617627.
Kessler RC, Ormel J, Petukhova M, McLaughlin KA, Green JG, Russo LJ, Stein DJ, Zaslavsky AM, Aguilar-Gaxiola S, Alonso J, Andrade L, Benjet C, de Girolamo G, de Graaf R, Demyttenaere K, Fayyad J, Haro JM, Hu CY, Karam A, Lee S, Lepine J, Matchsinger H, Mihaescu-Pintia C, Posada-Villa J, Sagar R, Üstün TB (2011). Development of lifetime comorbidity in the World Health Organization World Mental Health Surveys. Archives of General Psychiatry 68, 90100.
Kline RB (2010). Principles and Practice of Structural Equation Modeling. Guilford Press: New York.
Krueger RF (1999). The structure of common mental disorders. Archives of General Psychiatry 56, 921926.
Krueger RF, Finger MS (2001). Using item response theory to understand comorbidity among anxiety and unipolar mood disorders. Psychological Assessment 13, 140151.
Krueger RF, Goldman D (2010). The need for dimensional approaches in discerning the origins of psychopathology. In Causality and Psychopathology: Finding the Determinants of Disorders and their Cures (ed. Shrout P., Keyes K. and Ornstein K.), pp. 338351. Oxford University Press: New York.
Krueger RF, Markon KE (2006). Reinterpreting comorbidity: a model-based approach to understanding and classifying psychopathology. Annual Review of Clinical Psychology 2, 111133.
Kushner MG, Abrams K, Thuras P, Hanson KL, Brekke M, Sletten S (2005). Follow-up study of anxiety disorder and alcohol dependence in comorbid alcoholism treatment patients. Alcoholism: Clinical and Experimental Research 29, 14321443.
Kushner MG, Maurer EW, Thuras P, Donahue C, Frye B, Menary KR, Hobbs J, Haeny AM, Van Demark J (in press). Hybrid cognitive-behavioral therapy versus relaxation training for co-occurring anxiety and alcohol disorder: a randomized clinical trial. Journal of Consulting and Clinical Psychology.
Kushner MG, Wall MM, Krueger RF, Sher KJ, Maurer E, Thuras P, Lee S (2012). Alcohol dependence is related to overall internalizing psychopathology load rather than to particular internalizing disorders: evidence from a national sample. Alcoholism: Clinical and Experimental Research 36, 325331.
Little RJA, Rubin DB (2002). Statistical Analysis with Missing Data, 2nd edn.John Wiley & Sons: New York.
Mansell W, Harvey A, Watkins ER, Shafran R (2008). Cognitive behavioral processes across psychological disorders: a review of the utility and validity of the transdiagnostic approach. International Journal of Cognitive Therapy 1, 181191.
Mansell W, Harvey A, Watkins E, Shafran R (2009). Conceptual foundations of the transdiagnostic approach to CBT. Journal of Cognitive Psychotherapy 23, 619.
Markon KE (2010). Modeling psychopathology structure: a symptom-level analysis of Axis I and II disorders. Psychological Medicine 40, 273288.
Marsh HW, Muthén B, Asparouhov T, Lüdtke O, Robitzsch A, Morin AJS, Trautwein U (2009). Exploratory structural equation modeling, integrating CFA and EFA: application to students' evaluations of university teaching. Structural Equation Modeling 16, 439476.
McGlinchey JB, Zimmerman M (2007). Examining a dimensional representation of depression and anxiety disorders' comorbidity in psychiatric outpatients with item response modeling. Journal of Abnormal Psychology 116, 464474.
Meredith W (1993). Measurement invariance, factor analysis and factorial invariance. Psychometrika 58, 525543.
Meyer TJ, Miller ML, Metzger RL, Borkovec TD (1990). Development and validation of the Penn State Worry Questionnaire. Behaviour Research and Therapy 28, 487495.
Millsap RE, Hartog SB (1988). Alpha, beta and gamma change in evaluation research: a structural equation approach. Journal of Applied Psychology 73, 574584.
Mineka S, Watson D, Clark LA (1998). Comorbidity of anxiety and unipolar mood disorders. Annual Review of Psychology 49, 377412.
Moffitt TE, Harrington H, Caspi A, Kim-Cohen J, Goldberg D, Gregory AM, Poulton R (2007). Depression and generalized anxiety disorder: cumulative and sequential comorbidity in a birth cohort followed prospectively to age 32 years. Archives of General Psychiatry 64, 651660.
Muthén LK, Muthén BO (2011). Mplus User's Guide, 6th edn.Muthén & Muthén: Los Angeles, CA.
Simms LJ, Prisciandaro JJ, Kruger RF, Goldberg DP (2012). The structure of depression, anxiety and somatic symptoms in primary care. Psychological Medicine 42, 1528.
Spielberger CD, Sydeman SJ, Owen AE, Marsh BJ (1999). Measuring anxiety and anger with the State-Trait Anxiety Inventory (STAI) and State-Trait Anger Expression Inventory (STAXI). In The Use of Psychological Testing for Treatment Planning and Outcome Assessment, 2nd edn (ed. Maruish M. E.), pp. 295300. Lawrence Erlbaum Associates: Mahwah, NJ.
Vrieze SI (2012). Model selection and psychological theory: a discussion of the differences between the Akaike information criterion (AIC) and the Bayesian information criterion (BIC). Psychological Methods 17, 228243.
Watson D (2009). Differentiating the mood and anxiety disorders: a quadripartite model. Annual Review of Clinical Psychology 5, 221247.
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Psychological Medicine
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