Effect of Cognitive-Behavioral Therapy on Neural Correlates of Fear Conditioning in Panic Disorder

Kircher, Tilo; Arolt, Volker; Jansen, Andreas; Pyka, Martin; Reinhardt, Isabelle; Kellermann, Thilo; Konrad, Carsten; Lueken, Ulrike; Gloster, Andrew T.; Gerlach, Alexander L.; Ströhle, Andreas; Wittmann, André; Pfleiderer, Bettina; Wittchen, Hans‐Ulrich; Straube, Benjamin

doi:10.1016/j.biopsych.2012.07.026

Cited by 141 publications

(175 citation statements)

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“…An fMRI study investigating the effects of CBT on neuronal networks demonstrated the involvement of the inferior frontal gyrus (BA 45) in the pathology of panic disorders, and in the successful psychotherapy of such disorders (Kircher et al. 2013). Thus, we speculate that parts of the language system are involved in the cognitive processing occurring during symptom improvement in patients with panic disorders.…”

Section: Discussionmentioning

confidence: 99%

CBT reduces CBF: cognitive‐behavioral therapy reduces cerebral blood flow in fear‐relevant brain regions in spider phobia

et al. 2016

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BackgroundImaging studies have provided evidence that cognitive‐behavioral therapy (CBT) is able to change brain activation in phobic patients in response to threatening stimuli. The changes occurred in both emotion‐generating and modulatory regions. In this study, we use a data‐driven approach to explore resting state cerebral blood flow (CBF) measured by arterial spin labeling (ASL), before and after CBT.MethodsEight female patients with spider phobia were scanned before and 1 month after an exposure‐based group therapy for spider phobia. Each MRI session consisted of an ASL resting state measurement acquired before and after a symptom provocation task involving the showing of spider pictures in the scanner. The first ASL acquisition measured anticipatory anxiety and the second measured postprocessing of phobia‐relevant stimuli.ResultsCognitive‐behavioral therapy significantly reduced spider phobic symptoms in all patients. Symptom reduction during anticipatory anxiety was accompanied by reduced bilateral CBF in the parahippocampal gyrus, ventral anterior thalamus, Brodmann area 8, and the anterior cingulate cortex. During postprocessing of phobia‐relevant stimuli, patients showed reduced CBF in the bilateral insula, components of the motor cortex, and areas associated with language functions.ConclusionsLongitudinal CBF dynamics following CBT were in concordance with results from several studies using BOLD fMRI to investigate the effects of psychotherapy on brain activity. CBF can be quantified by ASL, with the principal advantage of sensitivity to slow variations in neural activity and task independence. Therefore, ASL may be a suitable method for monitoring and evaluating the efficacy of psychotherapy or pharmacotherapy approaches.

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Section: Discussionmentioning

confidence: 99%

CBT reduces CBF: cognitive‐behavioral therapy reduces cerebral blood flow in fear‐relevant brain regions in spider phobia

et al. 2016

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“…The task design and analyses has been described in detail elsewhere 51,52 . Briefly, we employed a differential fear conditioning task that consisted of three phases (familiarisation (F); acquisition (A) and extinction (E)), each subdivided into an early and a late phase.…”

Section: Functional Mrimentioning

confidence: 99%

“…In the acquisition phase, the US (white noise) was pseudo-randomly paired with one of the CS's (coloured spheres). MR images were analyzed using Statistical Parametric Mapping (SPM5; www.fil.ion.ucl.ac.uk) implemented in MATLAB 7.1 (Mathworks Inc., Sherborn, MA; see 51 ).…”

Section: Functional Mrimentioning

confidence: 99%

“…An fMRI centre variable was introduced as a covariate in order to account for scanner differences between sites. Contrasts of interest: We first tested for effects of genotype on differential conditioning processes in the early acquisition phase, since in this phase strongest effects for patients in contrast to healthy control subjects have been observed 51 . In a second step we tested for genotype effects on safety signal processing by focussing on activation differences during the processing of the CS-in contrast to resting baseline (fixation cross).…”

Section: Functional Mrimentioning

confidence: 99%

“…A Monte Carlo simulation was conducted to establish an appropriate voxel contiguity threshold 53 . Thus, for all analyses voxels with a significance level of p < 0.005 uncorrected belonging to clusters with at least 142 voxels are reported (see also 51,52,54,55 ). Whole-brain analysis was carried out first.…”

Section: Functional Mrimentioning

confidence: 99%

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Allelic variation in CRHR1 predisposes to panic disorder: evidence for biased fear processing

et al. 2015

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Corticotropin releasing hormone (CRH) is a major regulator of the hypothalamicpituitary-adrenal (HPA) axis. Binding to its receptor CRHR1 triggers the downstream release of cortisol, a hormone needed for regulation of stress responses. Biochemical, behavioral and genetic studies revealed CRHR1 as a possible candidate gene for mood and anxiety disorders. Here, we aimed to evaluate CRHR1 as a candidate molecule in panic disorder (PD).Allelic variation throughout the CRHR1 gene was captured by 9 selected single nucleotide polymorphisms (SNPs); these were genotyped in 531 matched case/control pairs (discovery sample (n=239); replication sample (n=292)). Four SNPs were found to be associated with PD, in at least one sub-sample. The minor alleles of rs17689918 and rs17689966 were found to significantly increase risk for PD in females of the discovery, the replication and the combined sample, both withstanding correction for multiple testing (p rs17689918 =1.3*10 -4 ; p rs17689966 =0.042). Expressional analysis demonstrated that both minor alleles of rs17689918 and rs17689966 significantly decreased CRHR1 mRNA in the forebrain and amygdala.Bioinformatical analysis revealed a high proportion of differential neuro-relevant transcription factor binding possibly underlying expression changes. When investigating the neural correlates underlying this association, risk allele carriers of rs17689918 and rs17689966 showed aberrant differential conditioning and safety signal processing arguing for predominant generalization of fear and hence anxious apprehension. Furthermore, the minor risk (A) allele of rs17689918 led to less flight behavior during fear provoking situations, but rather increased anxious apprehension and went along with increased anxiety sensitivity. Thus, reduced CRHR1 expression driven by CRHR1 risk allele leads to a phenotype characterized by a fear bias and hence sustained fear. These results strengthen the role of CRHR1 in PD and clarify the mechanisms by which genetic variation in CRHR1 is linked to this disorder.

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Predicting Treatment Response to Cognitive Behavioral Therapy in Panic Disorder With Agoraphobia by Integrating Local Neural Information

et al. 2015

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IMPORTANCE Although neuroimaging research has made substantial progress in identifying the large-scale neural substrate of anxiety disorders, its value for clinical application lags behind expectations. Machine-learning approaches have predictive potential for individual-patient prognostic purposes and might thus aid translational efforts in psychiatric research. OBJECTIVE To predict treatment response to cognitive behavioral therapy (CBT) on an individual-patient level based on functional magnetic resonance imaging data in patients with panic disorder with agoraphobia (PD/AG). DESIGN, SETTING, AND PARTICIPANTS We included 49 patients free of medication for at least 4 weeks and with a primary diagnosis of PD/AG in a longitudinal study performed at 8 clinical research institutes and outpatient centers across Germany. The functional magnetic resonance imaging study was conducted between July 2007 and March 2010. INTERVENTIONS Twelve CBT sessions conducted 2 times a week focusing on behavioral exposure. MAIN OUTCOMES AND MEASURES Treatment response was defined as exceeding a 50% reduction in Hamilton Anxiety Rating Scale scores. Blood oxygenation level-dependent signal was measured during a differential fear-conditioning task. Regional and whole-brain gaussian process classifiers using a nested leave-one-out cross-validation were used to predict the treatment response from data acquired before CBT. RESULTS Although no single brain region was predictive of treatment response, integrating regional classifiers based on data from the acquisition and the extinction phases of the fear-conditioning task for the whole brain yielded good predictive performance (accuracy, 82%; sensitivity, 92%; specificity, 72%; P < .001). Data from the acquisition phase enabled 73% correct individual-patient classifications (sensitivity, 80%; specificity, 67%; P < .001), whereas data from the extinction phase led to an accuracy of 74% (sensitivity, 64%; specificity, 83%; P < .001). Conservative reanalyses under consideration of potential confounders yielded nominally lower but comparable accuracy rates (acquisition phase, 70%; extinction phase, 71%; combined, 79%). CONCLUSIONS AND RELEVANCE Predicting treatment response to CBT based on functional neuroimaging data in PD/AG is possible with high accuracy on an individual-patient level. This novel machine-learning approach brings personalized medicine within reach, directly supporting clinical decisions for the selection of treatment options, thus helping to improve response rates.

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Effect of Cognitive-Behavioral Therapy on Neural Correlates of Fear Conditioning in Panic Disorder

Cited by 141 publications

References 61 publications

CBT reduces CBF: cognitive‐behavioral therapy reduces cerebral blood flow in fear‐relevant brain regions in spider phobia

CBT reduces CBF: cognitive‐behavioral therapy reduces cerebral blood flow in fear‐relevant brain regions in spider phobia

Allelic variation in CRHR1 predisposes to panic disorder: evidence for biased fear processing

Predicting Treatment Response to Cognitive Behavioral Therapy in Panic Disorder With Agoraphobia by Integrating Local Neural Information

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