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Association of NPSR1 gene variation and neural activity in patients with panic disorder and agoraphobia and healthy controls.

ABSTRACT: INTRODUCTION:The neurobiological mechanisms behind panic disorder with agoraphobia (PD/AG) are not completely explored. The functional A/T single nucleotide polymorphism (SNP) rs324981 in the neuropeptide S receptor gene (NPSR1) has repeatedly been associated with panic disorder and might partly drive function respectively dysfunction of the neural "fear network". We aimed to investigate whether the NPSR1 T risk allele was associated with malfunctioning in a fronto-limbic network during the anticipation and perception of agoraphobia-specific stimuli. METHOD:121 patients with PD/AG and 77 healthy controls (HC) underwent functional magnetic resonance imaging (fMRI) using the disorder specific "Westphal-Paradigm". It consists of neutral and agoraphobia-specific pictures, half of the pictures were cued to induce anticipatory anxiety. RESULTS:Risk allele carriers showed significantly higher amygdala activation during the perception of agoraphobia-specific stimuli than A/A homozygotes. A linear group x genotype interaction during the perception of agoraphobia-specific stimuli showed a strong trend towards significance. Patients with the one or two T alleles displayed the highest and HC with the A/A genotype the lowest activation in the inferior orbitofrontal cortex (iOFC). DISCUSSION:The study demonstrates an association of the NPSR1rs324981 genotype and the perception of agoraphobia-specific stimuli. These results support the assumption of a fronto-limbic dysfunction as an intermediate phenotype of PD/AG.

SUBMITTER: Gechter J

PROVIDER: S-EPMC6854061 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Association of NPSR1 gene variation and neural activity in patients with panic disorder and agoraphobia and healthy controls.

Gechter Johanna J Liebscher Carolin C Geiger Maximilian J MJ Wittmann André A Schlagenhauf Florian F Lueken Ulrike U Wittchen Hans-Ulrich HU Pfleiderer Bettina B Arolt Volker V Kircher Tilo T Straube Benjamin B Deckert Jürgen J Weber Heike H Herrmann Martin J MJ Reif Andreas A Domschke Katharina K Ströhle Andreas A

NeuroImage. Clinical 20191021

<h4>Introduction</h4>The neurobiological mechanisms behind panic disorder with agoraphobia (PD/AG) are not completely explored. The functional A/T single nucleotide polymorphism (SNP) rs324981 in the neuropeptide S receptor gene (NPSR1) has repeatedly been associated with panic disorder and might partly drive function respectively dysfunction of the neural "fear network". We aimed to investigate whether the NPSR1 T risk allele was associated with malfunctioning in a fronto-limbic network during ...[more]

PMID: 31734525

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Project description:BACKGROUND:A relevant proportion of patients with panic disorder (PD) does not improve even though they receive state of the art treatment for anxiety disorders such as cognitive-behavioural therapy (CBT). At the same time, it is known, that from a neurobiological point of view, PD patients are often characterised by prefrontal hypoactivation. Intermittent Theta Burst Stimulation (iTBS) is a non-invasive type of neurostimulation which can modulate cortical activity and thus has the potential to normalise prefrontal hypoactivity found in PD. We therefore aimed at investigating the effects of iTBS as an innovative add-on to CBT in the treatment for PD. METHODS:In this double-blind, bicentric study, 44 PD patients, randomised to sham or verum stimulation, received 15 sessions of iTBS over the left prefrontal cortex (PFC) in addition to 9 weeks of group CBT. Cortical activity during a cognitive as well as an emotional (Emotional Stroop) paradigm was assessed both at baseline and post-iTBS treatment using functional near-infrared spectroscopy (fNIRS) and compared to healthy controls. RESULTS:In this manuscript we only report the results of the emotional paradigm; for the results of the cognitive paradigm please refer to Deppermann et al. (2014). During the Emotional Stroop test, PD patients showed significantly reduced activation to panic-related compared to neutral stimuli for the left PFC at baseline. Bilateral prefrontal activation for panic-related stimuli significantly increased after verum iTBS only. Clinical ratings significantly improved during CBT and remained stable at follow-up. However, no clinical differences between the verum- and sham-stimulated group were identified, except for a more stable reduction of agoraphobic avoidance during follow-up in the verum iTBS group. LIMITATIONS:Limitations include insufficient blinding, the missing control for possible state-dependent iTBS effects, and the timing of iTBS application during CBT. CONCLUSION:Prefrontal hypoactivity in PD patients was normalised by add-on iTBS. Clinical improvement of anxiety symptoms was not affected by iTBS.

Project description:BackgroundIn the context of the COVID-19 pandemic, legislations are being modified around the world to allow patients to receive mental health services through telehealth. Unfortunately, there are no large clinical trial available to reliably document the efficacy of delivering videoconferencing psychotherapy (VCP) for people with panic disorder and agoraphobia (PDA) and whether basic psychotherapeutic processes are altered.MethodsThis 2-arm intent-to-treat non-inferiority study reports on a clinical trial on VCP and documents how therapeutic working alliance and motivation toward psychotherapy are associated to treatment outcome. We hypothesized that VCP would not be inferior to standard face-to-face (FF) cognitive behavior therapy for PDA. No specific hypothesis was stated to address working alliance and treatment mechanisms. VCP was compared to a gold-standard psychotherapy treatment for PDA, which was delivered either in person or in videoconference, with a strict tolerance criterion of about 2 points on the primary outcome measure. Seventy one adult patients were recruited. Measures of working alliance were collected after the first, fifth, and last session. Motivation toward therapy at pre-treatment and working alliance after the fifth therapy session were used as predictors of treatment outcome and compared with change in dysfunctional beliefs toward bodily sensations.ResultsPanic disorder, agoraphobia, fear of sensations and depressed mood all showed significant improvements and large effect-sizes from pre to post-treatment. Gains were maintained at follow-up. No significant differences were found between VCP and FF, and effect sizes were trivial for three of the four outcome measures. Non-inferiority tests confirmed that VCP was no less effective than FF therapy on the primary outcome measure and two of the three secondary outcome measures. Working alliance was very strong in VCP and did not statistically differ from FF. Working alliance and motivation did not predict treatment outcome, which was significantly predicted by the reduction in dysfunctional beliefs. The strength of the therapeutic bond was correlated with change in dysfunctional beliefs.ConclusionMental health professionals can use VCP to provide services to patients with PDA. Building and maintaining a sound working alliance should not be a source concern. Practical recommendations are formulated.Isrctn trial registration numberISRCTN76456442.

Dataset Information

Association of NPSR1 gene variation and neural activity in patients with panic disorder and agoraphobia and healthy controls.

Publications

Association of NPSR1 gene variation and neural activity in patients with panic disorder and agoraphobia and healthy controls.

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