title: 5HTT is associated with the phenotype psychological flexibility: results from a randomized clinical trial.
abstract: Adaption to changing environments is evolutionarily advantageous. Studies that link genetic and phenotypic expression of flexible adjustment to one's context are largely lacking. In this study, we tested the importance of psychological flexibility, or goal-related context sensitivity, in an interaction between psychotherapy outcome for panic disorder with agoraphobia (PD/AG) and a genetic polymorphism. Given the established role of the 5HTT-LPR polymorphism in behavioral flexibility, we tested whether this polymorphism (short group vs. long group) impacted therapy response as a function of various endophenotypes (i.e., psychological flexibility, panic, agoraphobic avoidance, and anxiety sensitivity). Patients with PD/AG were recruited from a large multicenter randomized controlled clinical trial on cognitive-behavioral therapy. Pre- to post-treatment changes by 5HTT polymorphism were analyzed. 5HTT polymorphism status differentiated pre- to post-treatment changes in the endophenotype psychological flexibility (effect size difference d = 0.4, p < 0.05), but none of the specific symptom-related endophenotypes consistently for both the intent-to-treat sample (n = 228) and the treatment completers (n = 194). Based on the consistency of these findings with existing theory on behavioral flexibility, the specificity of the results across phenotypes, and the consistency of results across analyses (i.e., completer and intent to treat), we conclude that 5HTT polymorphism and the endophenotype psychological flexibility are important variables for the treatment of PD/AG. The endophenotype psychological flexibility may help bridge genetic and psychological literatures. Despite the limitation of the post hoc nature of these analyses, further study is clearly warranted.
authors.affiliation: Division of Clinical Psychology and Epidemiology, Department of Psychology, University of Basel, Missionsstrasse 62A, 4055, Basel, Switzerland, andrew.gloster@unibas.ch.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Gloster
authors.forename: Alexander L
authors.initials: AL
authors.lastname: Gerlach
authors.forename: Alfons
authors.initials: A
authors.lastname: Hamm
authors.forename: Michael
authors.initials: M
authors.lastname: Höfler
authors.forename: Georg W
authors.initials: GW
authors.lastname: Alpers
authors.forename: Tilo
authors.initials: T
authors.lastname: Kircher
authors.forename: Andreas
authors.initials: A
authors.lastname: Ströhle
authors.forename: Thomas
authors.initials: T
authors.lastname: Lang
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Wittchen
authors.forename: Jürgen
authors.initials: J
authors.lastname: Deckert
authors.forename: Andreas
authors.initials: A
authors.lastname: Reif
mesh_terms: D000328:Adult; D000379:Agoraphobia / Q000235:genetics / Q000523:psychology / Q000534:rehabilitation; D000704:Analysis of Variance; D015928:Cognitive Behavioral Therapy / Q000379:methods*; D005260:Female; D005838:Genotype; D006801:Humans; D057194:Intention to Treat Analysis; D008297:Male; D008875:Middle Aged; D016584:Panic Disorder / Q000235:genetics / Q000523:psychology / Q000534:rehabilitation; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011569:Psychiatric Status Rating Scales; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D011795:Surveys and Questionnaires; D013997:Time Factors
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins