Does prior traumatization affect the treatment outcome of CBT for panic disorder? The potential role of the MAOA gene and depression symptoms
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Although cognitive behavioral therapy (CBT) is highly effective in the treatment of anxiety disorders, many patients still do not benefit. This study investigates whether a history of traumatic event experience is negatively associated with outcomes of CBT for panic disorder. The moderating role of the monoamine oxidase A (MAOA) gene and depression symptoms as well as the association between trauma history and fear reactivity as a potential mechanism are further analyzed. We conducted a post-hoc analysis of 172 male and 60 female patients with panic disorder treated with CBT in a multi-center study. Treatment outcome was assessed at post-treatment using self-report and clinician rating scales. Fear reactivity before treatment was assessed via heart rate and self-reported anxiety during a behavioral avoidance test. Among females, we did not find any differences in treatment response between traumatized and non-traumatized individuals or any two-way interaction trauma history × MAOA genotype. There was a significant three-way interaction trauma history × MAOA genotype × depression symptoms on all treatment outcomes indicating that in traumatized female patients carrying the low-activity allele, treatment effect sizes decreased with increasing depression symptoms at baseline. No such effects were observed for males. In conclusion, we found no evidence for a differential treatment response in traumatized and non-traumatized individuals. There is preliminary evidence for poorer treatment outcomes in a subgroup of female traumatized individuals carrying the low-active variant of the MAOA gene. These patients also report more symptoms of depression symptomatology and exhibit a dampened fear response before treatment which warrants further investigation.
KeywordsPanic disorder CBT Trauma MAOA Fear reactivity Depression
This work is part of the German multi-center trial ‘Mechanisms of Action in CBT’ (MAC). The MAC study was funded by the German Federal Ministry of Education and Research (BMBF; project no. 01GV0615) as part of the BMBF Psychotherapy Research Funding Initiative. The study was further supported by the DFG (Grant RE1632/5-1 to AR, DE357/4-1 to JD, RTG 1256 to JD and AR, and SFB TRR 58 Z02 to JD and AR). The principal investigators (PIs) of the centers with respective areas of responsibility in the MAC study were: V Arolt (Münster: Overall MAC Program Coordination), HU Wittchen (Dresden: PI for the Randomized Clinical Trial and Manual Development), A. Hamm (Greifswald: PI for Psychophysiology), A. L. Gerlach (Münster: PI for Psychophysiology and Panic subtypes), A. Ströhle (Berlin: PI for Experimental Pharmacology), T. Kircher (Marburg: PI for functional neuroimaging) and J. Deckert (Würzburg: PI for Genetics). Additional site directors in the RTC component of the program were GW Alpers (Würzburg), T. Fydrich and L. Fehm (Berlin-Adlershof) and T. Lang (Bremen). T. Töpner, N. Steigerwald, C. Gagel and J. Auer are credited for excellent technical assistance.
Compliance with ethical standards
All participants provided informed consent. The study protocol was approved by the Ethics Committee of the Medical Faculty of the Technische Universität Dresden (EK164082006).
Conflict of interest
HUW has served as a general consultant (non-product related) for Lundbeck.
- 6.James AC, James G, Cowdrey FA, Soler A, Choke A (2013) Cognitive behavioural therapy for anxiety disorders in children and adolescents. Cochrane Database Syst Rev. doi: 10.1002/14651858.CD004690.pub4
- 18.Berman MI, Hegel MT (2014) Predicting depression outcome in mental health treatment: a recursive partitioning analysis. Psychother Res J Soc Psychother Res 24(6):675–686Google Scholar
- 20.Alden LE, Taylor CT, Laposa JM, Mellings TMB (2006) Impact of social developmental experiences on cognitive-behavioral therapy for generalized social phobia. J Cogn Psychother 20(1):7–16Google Scholar
- 33.Maron E, Lang A, Tasa G et al (2005) Associations between serotonin-related gene polymorphisms and panic disorder. Int J Neuropsychopharmaco. 8(2):261–266Google Scholar
- 41.Gloster AT, Wittchen HU, Einsle F et al (2009) Mechanism of action in CBT (MAC): methods of a multi-center randomized controlled trial in 369 patients with panic disorder and agoraphobia. Eur Arch Psychiatry Clin Neurosc. 259(Suppl 2):S155–S166Google Scholar
- 42.Wittchen H-U, Pfister H (1997) DIA-X-Interviews: Manual Für Screening-Verfahren Und Interview; Interviewheft Längsschnittuntersuchung (DIA-X-Lifetime); Ergänzungsheft (DIA-X-Lifetime); Interviewheft Querschnittuntersuchung (DIA-X-Monate); Ergänzungsheft (DIA-X-Monate); PC-Programm Zur Durchführung Des Interviews (Längs- Und Querschnittuntersuchung); Auswertungsprogramm. Swets and Zeitlinger, FrankfurtGoogle Scholar
- 44.Guy W (1976) Clinical global impression scale. ECDEU Assess Man Psychopharmacol 338:218–222Google Scholar
- 45.Bandelow B (1999) Panic and Agoraphobia Scale (PAS), vol iii. Hogrefe & Huber, AshlandGoogle Scholar
- 47.Hautzinger M, Keller F, Kühner C (2006) BDI-II Beck-depressions-inventar. Franfurt Am Main: Harcourt Test ServicesGoogle Scholar
- 50.Royall R (1986) Model robust confidence-intervals using maximum-likelihood estimators. Int Stat Rev 54(2):221–226Google Scholar
- 51.Stata Corp (2012) Stata Statistical Software: Release 12.1. Stata CorporationGoogle Scholar
- 55.Homberg JR (2012) Serotonergic modulation of conditioned fear. Scientifica. doi: 10.6064/2012/821549
- 61.Merwin RM, Rosenthal MZ, Coffey KA (2008) Experiential avoidance mediates the relationship between sexual victimization and psychological symptoms: replicating findings with an ethnically diverse sample. Cogn Ther Res 33(5):537–542Google Scholar
- 65.Cribb G, Moulds ML, Carter S (2006) Rumination and experiential avoidance in depression. Behav Change 23(3):165–176Google Scholar
- 66.Brockmeyer T, Holtforth MG, Pfeiffer N, Backenstrass M, Friederich H-C, Bents H (2012) Mood regulation expectancies and emotion avoidance in depression vulnerability. Personal Individ Differ 53(3):351–354Google Scholar