title: Therapygenetics: anterior cingulate cortex-amygdala coupling is associated with 5-HTTLPR and treatment response in panic disorder with agoraphobia.
abstract: Variation in the 5'-flanking promoter region of the serotonin transporter gene SLC6A4, the 5-HTT-linked polymorphic region (5-HTTLPR) has been inconclusively associated with response to cognitive-behavioural therapy (CBT). As genomic functions are stronger related to neural than to behavioural markers, we investigated the association of treatment response, 5-HTTLPR and functional brain connectivity in patients with panic disorder with agoraphobia (PD/AG). Within the national research network PANIC-NET 231 PD/AG patients who provided genetic information underwent a manualized exposure-based CBT. A subset of 41 patients participated in a functional magnetic resonance imaging (fMRI) add-on study prior to treatment applying a differential fear conditioning task. Neither the treatment nor the reduced fMRI sample showed a direct effect of 5-HTTLPR on treatment response as defined by a reduction in the Hamilton Anxiety Scale score ≥50 % from baseline to post assessment. On a neural level, inhibitory anterior cingulate cortex (ACC)-amygdala coupling during fear conditioning that had previously been shown to characterize treatment response in this sample was driven by responders with the L/L genotype. Building upon conclusive evidence from basic and preclinical findings on the association of the 5-HTTLPR polymorphism with emotion regulation and related brain connectivity patterns, present findings translate these to a clinical sample of PD/AG patients and point towards a potential intermediate connectivity phenotype modulating response to exposure-based CBT.
authors.affiliation: Department of Psychology, Institute of Clinical Psychology and Psychotherapy, Technische Universität Dresden, Chemnitzer Straße 46, 01187, Dresden, Germany, ulrike.lueken@tu-dresden.de.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Lueken
authors.forename: Benjamin
authors.initials: B
authors.lastname: Straube
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Wittchen
authors.forename: Carsten
authors.initials: C
authors.lastname: Konrad
authors.forename: Andreas
authors.initials: A
authors.lastname: Ströhle
authors.forename: André
authors.initials: A
authors.lastname: Wittmann
authors.forename: Bettina
authors.initials: B
authors.lastname: Pfleiderer
authors.forename: Volker
authors.initials: V
authors.lastname: Arolt
authors.forename: Tilo
authors.initials: T
authors.lastname: Kircher
authors.forename: Jürgen
authors.initials: J
authors.lastname: Deckert
authors.forename: Andreas
authors.initials: A
authors.lastname: Reif
mesh_terms: D000328:Adult; D000379:Agoraphobia / Q000150:complications / Q000235:genetics* / Q000534:rehabilitation*; D000679:Amygdala / Q000098:blood supply / Q000473:pathology*; D015928:Cognitive Behavioral Therapy; D005260:Female; D005838:Genotype; D006179:Gyrus Cinguli / Q000098:blood supply / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010100:Oxygen / Q000097:blood; D016584:Panic Disorder / Q000150:complications / Q000235:genetics* / Q000534:rehabilitation*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D010100:Oxygen