title: The effect of allelic variation in CRHR1 on neural correlates of cognitive-behavioral therapy in female patients with panic disorder and agoraphobia - an explorative fMRI analysis of a multicenter study on fear conditioning
title: Die Auswirkung einer allelischen Variation von CRHR1 auf die neuronalen Korrelate der kognitiven Verhaltenstherapie bei weiblichen Patienten mit Panikstörung und Agoraphobie - eine explorative fMRI-Analyse einer multizentrischen Studie zur Furchtkonditionierung
titleType: AlternativeTitle
Creators: name: Cana, Denis
Publisher: name: Philipps-Universität Marburg
Year: 2023
Subjects: Furchtkonditionierung
Medical sciences Medicine
Medizin
fear conditioning
CRHR 1
Panikstörung
Panic disorder

description: The AA/AG-haplotype of the CRHR1 allele rs17689918 has been implicated in increasing the risk towards Panic Disorder in females. The female risk-allele carriers (AA/AG-Haplotype) that suffer from Panic Disorder/Agoraphobia (PD/A) exhibit impaired activation responses in the left dorsolateral prefrontal cortex for the conditioned response CS+&gt;CS- and increased activation in the left amygdala for safety signals (CS-), thus mirroring a phenotype that is characterized by fear generalization and dysfunctional safety signal processing. Therefore, this study is aimed at investigating the impact of the AA/AG-haplotype of rs17689918 regarding the effect of cognitive behavioral therapy (CBT) and the underlying neural activation changes in fear conditioning across time (pre/post comparison). For this, functional MRI (fMRI)-, clinical- and demographic data from 12 female PD/A-patients carrying the risk-allele and 13 female PD/A-controls (both medication free) were obtained from a subsample of a randomized, controlled multicenter clinical trial („PANIC-NET“). The neural correlates have been measured within a fear conditioning paradigm by fMRI and clinical data that have been ascertained respectively before and after 12 sessions of manualized CBT. Hence, clinical scores and fMRI data for both groups have been tested for between-group differences and correlations across time. Concerning the clinical response, minor differences were observed regarding CBT effects on depressive (stronger effects on risk-allele carriers) and maladaptive agoraphobic cognitions (stronger effect on control patients). Moreover, the risk-allele carriers reveal a different neuronal response in fear conditioning from baseline to prost-treatment: the PD/A-control group exhibit a normalized activation in the left inferior frontal gyrus (IFG), left anterior cingulate cortex and thalamus for the conditioned response CS+ &gt; CS-, which the risk-allele carriers however did not display. A post hoc analysis for risk allele carrier suggests a normalized activation in the left dorsomedial prefrontal cortex (dmPFC) and left precuneus for the conditioned response CS+ &gt; CS-, which however did not reach a significance when compared to the control patients. In conclusion, the AA/AG-haplotype of the CRHR1-risk allele rs17689918 suggests a distinct pathogenesis in PD/A and neural response to CBT in female patients suffering from PD/A, which does not interfere with the overal treatment response for CBT compared to control patients.