Depression, Contraception, and Ambivalence Concerning Fertility.

Individuals suffering from depression exhibit a higher rate of unintended pregnancies, which are associated with negative outcomes for both parents and children. Often, unintended pregnancies result from contraceptive mistakes. Here, we examine the relationship between depression and the consistency of contraceptive behavior, testing ambivalence as a possible mediator. The analyses were based on cross-sectional data from the second and third waves of the German Relationship and Family Panel Pairfam. A German-speaking sample without children (N = 190; 117 female, 73 male), who reported not attempting to conceive or become pregnant during the last 12 months, was analyzed in comparison with a propensity score matched sample. Ambivalence was operationalized as the difference between the ideal and realistic number of children in wave 2. Data from wave 3 were used to assess contraceptive behavior. Depressed mood in wave 2 and consistency of contraceptive behavior in wave 3 were negatively correlated. After including ambivalence in wave 2 as a mediator in the model, the direct path between depressed mood and consistency of contraceptive behavior remained significant, with no significant mediation found. For men only, we observed a significant negative association of ambivalence with the consistency of contraceptive behavior in the last 3 months. No significant relationship was found between depressed mood and ambivalence. We conclude that future research aiming to better understand the consistency of contraceptive behavior should incorporate measures of ambivalence.

Respiratory Interoception and Pathological Illness Anxiety: Disentangling Bias.

OBJECTIVE: Biased interoception decoupled from physiology might be relevant in the etiology of pathological illness anxiety (PIA). Empirical evidence for interoceptive deviations in illness anxiety is scarce but potentially informative to optimize treatments. We hypothesized that persons with PIA differ fundamentally in the classification of bodily sensations from those without PIA. METHODS: In a respiratory categorization task, participants breathed into a pulmonary training device. Inspiration effort was varied by eight resistive loads. The lower/higher four loads were introduced as belonging to arbitrary categories "A"/"B," respectively. Participants memorized respiratory sensations in a first experimental block and were asked to label the resistances in a second block. We calculated the sensitivity of resistance classification according to category and response bias in terms of categorical misclassification. Data of 39 participants with PIA and 35 controls were compared with regard to sensitivity and response bias by group, resistive load, and their interaction in a multiple regression. RESULTS: With similar sensitivity, patients more often labeled loads above the categorical border erroneously as belonging to category A, thus underestimating their resistance ( ß = -0.06, p = .001; η2 = 0.02). CONCLUSIONS: Individuals with PIA showed a systematic "wait and see" approach. Altered respiroception in PIA might stem from biased perception during training phase, the recognition phase, biased memory, or a combination of these. Its exact characteristics remain unknown, and future research must address the challenge of developing reliable and valid paradigms accounting for the variability of interoceptive biases. REGISTRATION: This work was preregistered on OSF ( https://osf.io/9shcw ).

Symptom Perception in Pathological Illness Anxiety: Tactile Sensitivity and Bias.

OBJECTIVE: Symptom perception in pathological illness anxiety (PIA) might be biased so that somatic signals are overreported. In the somatic signal detection task (SSDT), performance in detecting weak tactile stimuli gives information on overreporting or underreporting of stimuli. This task has not yet been applied in PIA. METHODS: Participants with PIA (n = 44) and healthy controls (n = 40) underwent two versions of the SSDT in randomized order. In the original version, tactile and auxiliary light-emitting diode (LED) stimuli were each presented in half of the trials. In the adapted version, illness or neutral words were presented alongside tactile stimuli. Participants also conducted a heartbeat mental tracking task. RESULTS: We found significantly higher sensitivity and a more liberal response bias in LED versus no-LED trials, but no significant differences between word types. An interaction effect showed a more pronounced increase of sensitivity from no LED to LED trials in participants with PIA when compared with the adapted SSDT and control group (F(1,76) = 5.34, p = .024, η2 = 0.066). Heartbeat perception scores did not differ between groups (BF01 of 3.63). CONCLUSIONS: The increase in sensitivity from no LED to LED trials in participants with PIA suggests stronger multisensory integration. Low sensitivity in the adapted SSDT indicates that attentional resources were exhausted by processing word stimuli. Word effects on response bias might have carried over to the original SSDT when the word version was presented first, compromising group effects regarding bias. TRIAL REGISTRATION: The study was preregistered on OSF (https://osf.io/sna5v/).

Behavioural and functional evidence revealing the role of RBFOX1 variation in multiple psychiatric disorders and traits.

Common variation in the gene encoding the neuron-specific RNA splicing factor RNA Binding Fox-1 Homolog 1 (RBFOX1) has been identified as a risk factor for several psychiatric conditions, and rare genetic variants have been found causal for autism spectrum disorder (ASD). Here, we explored the genetic landscape of RBFOX1 more deeply, integrating evidence from existing and new human studies as well as studies in Rbfox1 knockout mice. Mining existing data from large-scale studies of human common genetic variants, we confirmed gene-based and genome-wide association of RBFOX1 with risk tolerance, major depressive disorder and schizophrenia. Data on six mental disorders revealed copy number losses and gains to be more frequent in ASD cases than in controls. Consistently, RBFOX1 expression appeared decreased in post-mortem frontal and temporal cortices of individuals with ASD and prefrontal cortex of individuals with schizophrenia. Brain-functional MRI studies demonstrated that carriers of a common RBFOX1 variant, rs6500744, displayed increased neural reactivity to emotional stimuli, reduced prefrontal processing during cognitive control, and enhanced fear expression after fear conditioning, going along with increased avoidance behaviour. Investigating Rbfox1 neuron-specific knockout mice allowed us to further specify the role of this gene in behaviour. The model was characterised by pronounced hyperactivity, stereotyped behaviour, impairments in fear acquisition and extinction, reduced social interest, and lack of aggression; it provides excellent construct and face validity as an animal model of ASD. In conclusion, convergent translational evidence shows that common variants in RBFOX1 are associated with a broad spectrum of psychiatric traits and disorders, while rare genetic variation seems to expose to early-onset neurodevelopmental psychiatric disorders with and without developmental delay like ASD, in particular. Studying the pleiotropic nature of RBFOX1 can profoundly enhance our understanding of mental disorder vulnerability.

[Metacognitions and interoceptive sensibility in the perception of premonitory urges in tic disorders across the lifespan]. / Metakognitionen und interozeptive Sensibilität bei der Wahrnehmung des Vorgefühls bei Tic-Störungen über die Lebensspanne.

Metacognitions and interoceptive sensibility in the perception of premonitory urges in tic disorders across the lifespan Abstract. Objective: Depending on contextual factors, the prevalence of premonitory urges (PU) in patients with tic disorders (TD) increases with age and varies both intra- and interindividually. In youth, PUs correlate with metacognitions. In both youth and adults, interoceptive sensibility is altered compared to healthy controls. We examined the relationship between PUs, tics, metacognitions, and interoceptive sensibility across the lifespan regarding tic severity. Method: In an online survey, 53 participants reported their PUs on the Premonitory Urge for Tics Scale (PUTS) and tic severity on the Symptom Checklist for Tic Disorders (SBB-TIC). We assessed interoceptive sensibility via the Body Perception Questionnaire (BPQ-A) and metacognitions regarding tics with the Belief About Tics Scale (BATS). Results: Adults scored higher on the PUTS than youth. In youth, interoceptive sensibility increased with age; interoceptive sensibility correlated with PUTS. Metacognitions and interoceptive sensibility explained a significant amount of variance in premonitory urges, even after controlling for tic severity and age. Conclusions: The presumed cause of age-dependent development of PUs in youth lies in their neurophysiological maturing processes. However, negative metacognitions and interoceptive abilities also play an important role in the development and maintenance of PU and might be of therapeutic use in the treatment of TD.

Genome-wide association study of panic disorder reveals genetic overlap with neuroticism and depression.

Panic disorder (PD) has a lifetime prevalence of 2-4% and heritability estimates of 40%. The contributory genetic variants remain largely unknown, with few and inconsistent loci having been reported. The present report describes the largest genome-wide association study (GWAS) of PD to date comprising genome-wide genotype data of 2248 clinically well-characterized PD patients and 7992 ethnically matched controls. The samples originated from four European countries (Denmark, Estonia, Germany, and Sweden). Standard GWAS quality control procedures were conducted on each individual dataset, and imputation was performed using the 1000 Genomes Project reference panel. A meta-analysis was then performed using the Ricopili pipeline. No genome-wide significant locus was identified. Leave-one-out analyses generated highly significant polygenic risk scores (PRS) (explained variance of up to 2.6%). Linkage disequilibrium (LD) score regression analysis of the GWAS data showed that the estimated heritability for PD was 28.0-34.2%. After correction for multiple testing, a significant genetic correlation was found between PD and major depressive disorder, depressive symptoms, and neuroticism. A total of 255 single-nucleotide polymorphisms (SNPs) with p < 1 × 10-4 were followed up in an independent sample of 2408 PD patients and 228,470 controls from Denmark, Iceland and the Netherlands. In the combined analysis, SNP rs144783209 showed the strongest association with PD (pcomb = 3.10 × 10-7). Sign tests revealed a significant enrichment of SNPs with a discovery p-value of <0.0001 in the combined follow up cohort (p = 0.048). The present integrative analysis represents a major step towards the elucidation of the genetic susceptibility to PD.

Psychometric evaluation of the Positive Mental Health (PMH) scale using item response theory.

BACKGROUND: The investigation of patient-reported outcomes and psycho-oncological interventions mainly focuses on psychological distress or psychopathology. However, the recognition of the equal importance of positive mental health (PMH) has increased lately. The PMH-scale is a brief questionnaire allowing to assess well-being in individuals in the general population and in patients. Previous studies evaluated the psychometric properties of the PMH-scale using classical test theory (CTT). This study is the first to investigate the PMH-scale in patients with cancer using item analysis according to the Rasch model. METHODS: In total, N = 357 cancer patients participated in the study. A Rasch analysis of the PMH-scale was conducted including testing of unidimensionality, local independence, homogeneity and differential item functioning (DIF) with regard to age, gender, type of cancer, the presence of metastases, psycho-oncological support, and duration of disease. Additionally, the ordering of the item thresholds as well as the targeting of the scale were investigated. RESULTS: After excluding one misfitting item and accounting for local dependence by forming superitems, a satisfactory overall fit to the Rasch model was established (χ2 = 30.34, p = 0.21). The new PMH-8 scale proved to be unidimensional, and homogeneity of the scale could be inferred. All items showed ordered thresholds, there was no further item misfit. DIF was found for age, but as the impact of DIF was not substantial, no adjustment related to the age-DIF had to be made. The Person Separation Index (PSI = 0.89) was excellent, indicating excellent discriminatory power between different levels of positive mental health. Overall, the targeting of the PMH-8 was good for the majority of the present sample. However, at both ends of the scale item thresholds are missing as indicated by a slight floor effect (1.4%) and a considerable ceiling effect (9.8%). CONCLUSIONS: Overall, the results of the analysis according to the Rasch model support the use of the revised PMH-scale in a psycho-oncological context.

Integrated, cross-sectoral psycho-oncology (isPO): a new form of care for newly diagnosed cancer patients in Germany.

BACKGROUND: The annual incidence of new cancer cases has been increasing worldwide for many years, and is likely to continue to rise. In Germany, the number of new cancer cases is expected to increase by 20% until 2030. Half of all cancer patients experience significant emotional and psychosocial distress along the continuum of their disease, treatment, and aftercare, and also as long-term survivors. Consequently, in many countries, psycho-oncological programs have been developed to address this added burden at both the individual and population level. These programs promote the active engagement of patients in their cancer therapy, aftercare and survivorship planning and aim to improve the patients' quality of life. In Germany, the "new form of care isPO" ("nFC-isPO"; integrated, cross-sectoral psycho-oncology/integrierte, sektorenübergreifende Psycho-Onkologie) is currently being developed, implemented and evaluated. This approach strives to accomplish the goals devised in the National Cancer Plan by providing psycho-oncological care to all cancer patients according to their individual healthcare needs. The term "new form of care" is defined by the Innovation Fund (IF) of Germany's Federal Joint Committee as "a structured and legally binding cooperation between different professional groups and/or institutions in medical and non-medical care". The nFC-isPO is part of the isPO project funded by the IF. It is implemented in four local cancer centres and is currently undergoing a continuous quality improvement process. As part of the isPO project the nFC-isPO is being evaluated by an independent institution: the Institute for Medical Sociology, Health Services Research, and Rehabilitation Science (IMVR), University of Cologne, Germany. The four-year isPO project was selected by the IF to be eligible for funding because it meets the requirements of the federal government's National Cancer Plan (NCP), in particular, the "further development of the oncological care structures and quality assurance" in the psycho-oncological domain. An independent evaluation is required by the IF to verify if the new form of care leads to an improvement in cross-sectoral care and to explore its potential for permanent integration into the German health care system. METHODS: The nFC-isPO consists of six components: a concept of care (C1), care pathways (C2), a psycho-oncological care network (C3), a care process organization plan (C4), an IT-supported documentation and assistance system (C5) and a quality management system (C6). The two components concept of care (C1) and care pathways (C2) represent the isPO clinical care program, according to which the individual cancer patients are offered psycho-oncological services within a period of 12 months after program enrolment following the diagnosis of cancer. The remaining components (C3-C6) represent the formal-administrative aspects of the nFC-isPO that are intended to meet the legally binding requirements of patient care in the German health care system. With the aim of systematic development of the nFC-isPO while at the same time enabling the external evaluators to examine its quality, effectiveness and efficiency under conditions of routine care, the project partners took into consideration approaches from translational psycho-oncology, practice-based health care research and program theory. In order to develop a structured, population-based isPO care program, reference was made to a specific program theory, to the stepped-care approach, and also to evidence-based guideline recommendations. RESULTS: The basic version, nFC-isPO, was created over the first year after the start of the isPO project in October 2017, and has since been subject to a continuous quality improvement process. In 2019, the nFC-isPO was implemented at four local psycho-oncological care networks in the federal state North Rhine-Westphalia, in Germany. The legal basis of the implementation is a contract for "special care" with the German statutory health insurance funds according to state law (§ 140a SCB V; Social Code Book V for the statutory health insurance funds). Besides the accompanying external evaluation by the IMVR, the nFC-isPO is subjected to quarterly internal and cross-network quality assurance and improvement measures (internal evaluation) in order to ensure continuous quality improvement process. These quality management measures are developed and tested in the isPO project and are to be retained in order to ensure the sustainability of the quality of nFC-isPO for later dissemination into the German health care system. DISCUSSION: Demands on quality, effectiveness and cost-effectiveness of in the German health care system are increasing, whereas financial resources are declining, especially for psychosocial services. At the same time, knowledge about evidence-based screening, assessment and intervention in cancer patients and about the provision of psychosocial oncological services is growing continuously. Due to the legal framework of the statutory health insurance in Germany, it has taken years to put sound psycho-oncological findings from research into practice. Ensuring the adequate and sustainable financing of a needs-oriented, psycho-oncological care approach for all newly diagnosed cancer patients, as required by the NCP, may still require many additional years. The aim of the isPO project is to develop a new form of psycho-oncological care for the individual and the population suffering from cancer, and to provide those responsible for German health policy with a sound basis for decision-making on the timely dissemination of psycho-oncological services in the German health care system. TRIAL REGISTRATION: The study was pre-registered at the German Clinical Trials Register (https://www.drks.de/DRKS00015326) under the following trial registration number: DRKS00015326 ; Date of registration: October 30, 2018.

Linking Depression with Negative Alcohol-Related Consequences: A Structural Equation Model Among a Clinically Depressed Population.

Background and Objectives: Previous research suggests that rumination acts as a mediating mechanism in the association between depression and drinking motives, particularly drinking to cope, as well as negative alcohol-related consequences. In this study, we tested the connections between depressive symptoms, rumination, drinking motives, alcohol consumption, and alcohol-related problems in a clinically depressed population (N = 209). Methods: Structural equation modeling was used to test the models. Specifications were based on the results of a previously evaluated model in a sample of college students. Results: The complex model showed a significant positive association between depressive symptoms and rumination. Drinking motives (enhancement and coping) were linked to more negative alcohol-related consequences. In a simplified model, pronounced depressive symptoms were associated with both increased ruminative thinking and more negative alcohol-related problems. Rumination was connected with stronger drinking motives (combined in one general factor), which were again associated with alcohol consumption and alcohol-related problems. Limitations: The use of self-report measures to determine diagnostic validity. Conclusions: In a clinically depressed sample, depressive symptoms were linked to increased negative alcohol-related consequences. This association was partially explained by rumination and drinking motives. However, rumination was less relevant than previous studies suggested.

Somatosensory Illusions Elicited by Sham Electromagnetic Field Exposure: Experimental Evidence for a Predictive Processing Account of Somatic Symptom Perception.

OBJECTIVE: According to the predictive processing theory of somatic symptom generation, body sensations are determined by somatosensory input and central nervous predictions about this input. We examined how expectations shape predictions and consequently bodily perceptions in a task eliciting illusory sensations as laboratory analogue of medically unexplained symptoms. METHODS: Using the framework of signal detection theory, the influence of sham Wi-Fi on response bias (c) and somatosensory sensitivity (d') for tactile stimuli was examined using the somatic signal detection task (SSDT). A healthy student sample (n = 83) completed the SSDT twice (sham Wi-Fi on/off) in a randomized order after watching a film that promoted adverse health effects of electromagnetic fields. RESULTS: When expecting a Wi-Fi signal to be present, participants showed a significantly more liberal response bias c (p = .010, ηp2 = 0.08) for tactile stimuli in the SSDT as evidence of a higher propensity to experience somatosensory illusions. No significant alteration of somatosensory sensitivity d' (p = .76, ηp2 < 0.002) was observed. CONCLUSIONS: Negative expectations about the harmfulness of electromagnetic fields may foster the occurrence of illusory symptom perceptions via alterations in the somatosensory decision criterion. The findings are in line with central tenets of the predictive processing account of somatic symptom generation. This account proposes a decoupling of percept and somatosensory input so that perception becomes increasingly dependent on predictions. This biased perception is regarded as a risk factor for somatic symptom disorders.

An item analysis according to the Rasch model of the German 12-item WHO Disability Assessment Schedule (WHODAS 2.0).

PURPOSE: The World Health Organization Disability Assessent Schedule 2.0 (WHODAS 2.0) assesses disability in individuals irrespective of their health condition. Previous studies validated the usefulness of the WHODAS 2.0 using classical test theory. This study is the first investigating the psychometric properties of the 12-items WHODAS 2.0 in patients with cancer using item analysis according to the Rasch model. METHODS: In total, 350 cancer patients participated in the study. Rasch analysis of the 12-items version of the WHODAS 2.0 was conducted and included testing unidimensionality, local independence, and testing for differential item functioning (DIF) with regard to age, gender, type of cancer, presence of metastases, psycho-oncological support, and duration of disease. RESULTS: After accounting for local dependence, which was mainly found across items of the same WHODAS domain, satisfactory overall fit to the Rasch model was established (χ2 = 36.14, p = 0.07) with good reliability (PSI = 0.82) and unidimensionality of the scale. DIF was found for gender (testlet 'Life activities') and age (testlet 'Getting around/Self-care'), but the size of DIF was not substantial. CONCLUSION: Overall, the analysis results according to the Rasch model support the use of the WHODAS 2.0 12-item version as a measure of disability in cancer patients.

The significance of the Interpersonal-Psychological Theory of Suicide in an oncological context-A scoping review.

OBJECTIVES: Since individuals afflicted with cancer are at an elevated risk of dying by suicide, understanding suicide-related ideation and behaviours is critical in identifying vulnerable patients. The interpersonal theory of suicide (IPTS) provides a framework to research risk factors for suicide and has been validated in different samples. The aim of this scoping review is to study literature related to IPTS and cancer patients. METHODS: This scoping review was registered with the OPEN Science Framework (osf.io/92465). The databases PsycINFO, Web of Science, PubMed and PubMed Central were searched. Eligible research needed to use a minimum of one psychometric element to measure at least one of the factors of the IPTS in individuals with cancer. RESULTS: Ninety-six studies were identified and screened. Eligible research included individuals with cancer and the use of at least one measurement of at least one of the factors of the IPTS. Overall, four articles met the inclusion criteria and three studies found significant associations of components of the IPTS and suicidal ideation/behaviour. CONCLUSION: While these initial findings support the notion that the IPTS is relevant for individuals with cancer as well, a direct validation of the IPTS in cancer patients is needed.

Interoceptive Sensibility, Alexithymia, and Emotion Regulation in Individuals Suffering from Fibromyalgia.

INTRODUCTION: People suffering from fibromyalgia syndrome report various difficulties in emotional processing, possibly resulting from changes in bodily perception (interoception). In our study, we investigated the relationships between interoceptive sensibility (IS) and two disease-relevant emotional components (alexithymia and emotion regulation) in fibromyalgia sufferers compared to healthy individuals. METHODS: Fifty-five fibromyalgia sufferers and 55 healthy individuals, matched with regard to age and gender, participated in our cross-sectional study. All participants completed the following self-report measures: the Multidimensional Assessment of Interoceptive Awareness, the Toronto Alexithymia Scale, and the Emotion Regulation Skills Questionnaire. Depression and anxiety scores served as confounding variables. RESULTS: Fibromyalgia sufferers reported a stronger tendency to note as well as to avoid (unpleasant) body sensations. IS and psychopathology each explained about thirty percent of the variance in emotion regulation in fibromyalgia sufferers. Alexithymia was related to IS and emotion regulation in controls but not in fibromyalgia sufferers. CONCLUSION: Disturbances in interoception could be seen as the starting point of emotional difficulties in people with fibromyalgia. Following the fear-avoidance-model, experiential avoidance may restrict patients' ability to adaptively regulate emotional states, possibly initiating a vicious cycle of psychological distress and pain.

An investigation of genetic variability of DNA methyltransferases DNMT3A and 3B does not provide evidence for a major role in the pathogenesis of panic disorder and dimensional anxiety phenotypes.

While DNA methylation patterns have been studied for a role in the pathogenesis of anxiety disorders, the role of the enzymes establishing DNA methylation-DNA methyltransferases (DNMTs)-has yet to be investigated. In an effort to investigate DNMT genotype-specific effects on dimensional anxiety traits in addition to the categorical phenotype of panic disorder, 506 panic disorder patients and 3112 healthy participants were assessed for anxiety related cognition [Agoraphobic Cognitions Questionnaire (ACQ)], anxiety sensitivity [Anxiety Sensitivity Index (ASI)] as well as pathological worry [Penn State Worry Questionnaire (PSWQ)] and genotyped for five single nucleotide polymorphisms (SNPs) in the DNMT3A (rs11683424, rs1465764, rs1465825) and DNMT3B (rs2424932, rs4911259) genes, which have previously been found associated with clinical and trait-related phenotypes. There was no association with the categorical phenotype panic disorder. However, a significant association was discerned between DNMT3A rs1465764 and PSWQ scores in healthy participants, with the minor allele conveying a protective effect. In addition, a marginally significant association between questionnaire scores (PSWQ, ASI) in healthy participants and DNMT3B rs2424932 was detected, again with the minor allele conveying a protective effect. The present results suggest a possible minor role of DNMT3A and DNMT3B gene variation in conveying resilience towards anxiety disorders. As the observed associations indicated a protective effect of two SNPs particularly with pathological worry, future studies are proposed to explore these variants in generalized anxiety disorder rather than panic disorder.

Does prior traumatization affect the treatment outcome of CBT for panic disorder? The potential role of the MAOA gene and depression symptoms.

Although cognitive behavioral therapy (CBT) is highly effective in the treatment of anxiety disorders, many patients still do not benefit. This study investigates whether a history of traumatic event experience is negatively associated with outcomes of CBT for panic disorder. The moderating role of the monoamine oxidase A (MAOA) gene and depression symptoms as well as the association between trauma history and fear reactivity as a potential mechanism are further analyzed. We conducted a post-hoc analysis of 172 male and 60 female patients with panic disorder treated with CBT in a multi-center study. Treatment outcome was assessed at post-treatment using self-report and clinician rating scales. Fear reactivity before treatment was assessed via heart rate and self-reported anxiety during a behavioral avoidance test. Among females, we did not find any differences in treatment response between traumatized and non-traumatized individuals or any two-way interaction trauma history × MAOA genotype. There was a significant three-way interaction trauma history × MAOA genotype × depression symptoms on all treatment outcomes indicating that in traumatized female patients carrying the low-activity allele, treatment effect sizes decreased with increasing depression symptoms at baseline. No such effects were observed for males. In conclusion, we found no evidence for a differential treatment response in traumatized and non-traumatized individuals. There is preliminary evidence for poorer treatment outcomes in a subgroup of female traumatized individuals carrying the low-active variant of the MAOA gene. These patients also report more symptoms of depression symptomatology and exhibit a dampened fear response before treatment which warrants further investigation.

Effects of Cognitive Behavioral Therapy on Neural Processing of Agoraphobia-Specific Stimuli in Panic Disorder and Agoraphobia.

BACKGROUND: Patients suffering from panic disorder and agoraphobia are significantly impaired in daily life due to anxiety about getting into a situation due to apprehension about experiencing a panic attack, especially if escape may be difficult. Dysfunctional beliefs and behavior can be changed with cognitive behavioral therapy; however, the neurobiological effects of such an intervention on the anticipation and observation of agoraphobia-specific stimuli are unknown. METHODS: We compared changes in neural activation by measuring the blood oxygen level-dependent signal of 51 patients and 51 healthy controls between scans before and those after treatment (group by time interaction) during anticipation and observation of agoraphobia-specific compared to neutral pictures using 3-T fMRI. RESULTS: A significant group by time interaction was observed in the ventral striatum during anticipation and in the right amygdala during observation of agoraphobia-specific pictures; the patients displayed a decrease in ventral striatal activation during anticipation from pre- to posttreatment scans, which correlated with clinical improvement measured with the Mobility Inventory. During observation, the patients displayed decreased activation in the amygdala. These activational changes were not observed in the matched healthy controls. CONCLUSIONS: For the first time, neural effects of cognitive behavioral therapy were shown in patients suffering from panic disorder and agoraphobia using disorder-specific stimuli. The decrease in activation in the ventral striatum indicates that cognitive behavioral therapy modifies anticipatory anxiety and may ameliorate abnormally heightened salience attribution to expected threatening stimuli. The decreased amygdala activation in response to agoraphobia-specific stimuli indicates that cognitive behavioral therapy can alter the basal processing of agoraphobia-specific stimuli in a core region of the fear network.

5HTT is associated with the phenotype psychological flexibility: results from a randomized clinical trial.

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.

The relevance of accuracy of heartbeat perception in noncardiac and cardiac chest pain.

BACKGROUND: The development and course of noncardiac chest pain are assumed to be influenced by interoceptive processes. PURPOSE: It was investigated whether heartbeat perception was enhanced in patients suffering from noncardiac chest pain and to what degree it was associated with self-reported cognitive-perceptual features and chest pain characteristics. METHODS: A total of 42 patients with noncardiac chest pain (NCCP), 35 patients with cardiac chest pain, and 52 healthy controls were recruited. Heartbeat perception was assessed using the Schandry task and a modified Brener-Kluvitse task. Self-report measures assessed anxiety sensitivity, somatosensory amplification, heart-focused anxiety, and chest pain characteristics. RESULTS: Heartbeat perception was not more accurate in patients with NCCP, compared to patients with cardiac chest pain and healthy controls. However, in patients with NCCP, the error score (Schandry task) was significantly associated with stronger chest pain impairment, and the response bias (Brener-Kluvitse task) was associated with lower chest pain intensity. CONCLUSION: Against assumptions of current etiological models, heartbeat perception was not enhanced in patients with NCCP. Chest pain characteristics and particularly their appraisal as threatening might be more relevant to NCCP than the perceptional accuracy of cardiac sensations and should be focused in psychological interventions. However, associations with chest pain impairment suggest cardiac interoception to influence the course of NCCP.

RGS2 ggenetic variation: association analysis with panic disorder and dimensional as well as intermediate phenotypes of anxiety.

Accumulating evidence from mouse models points to the G protein-coupled receptor RGS2 (regulator of G-protein signaling 2) as a promising candidate gene for anxiety in humans. Recently, RGS2 polymorphisms were found to be associated with various anxiety disorders, e.g., rs4606 with panic disorder (PD), but other findings have been negative or inconsistent concerning the respective risk allele. To further examine the role of RGS2 polymorphisms in the pathogenesis of PD, we genotyped rs4606 and five additional RGS2 tag single nucleotide polymorphisms (SNPs; rs16834831, rs10801153, rs16829458, rs1342809, rs1890397) in two independent PD samples, comprising 531 matched case/control pairs. The functional SNP rs4606 was nominally associated with PD when both samples were combined. The upstream SNP rs10801153 displayed a Bonferroni-resistant significant association with PD in the second and the combined sample (P = 0.006 and P = 0.017). We furthermore investigated the effect of rs10801153 on dimensional anxiety traits, a behavioral avoidance test (BAT), and an index for emotional processing in the respective subsets of the total sample. In line with categorical results, homozygous risk (G) allele carriers displayed higher scores on the Agoraphobic Cognitions Questionnaire (ACQ; P = 0.015) and showed significantly more defensive behavior during fear provoking situations (P = 0.001). Furthermore, significant effects on brain activation in response to angry (P = 0.013), happy (P = 0.042) and neutral faces (P = 0.032) were detected. Taken together, these findings provide further evidence for the potential role of RGS2 as a candidate gene for PD.

Internal focus of attention in anxiety-sensitive females up-regulates amygdale activity: an fMRI study.

Cognitive behavioral models of panic disorder (PD) stress the importance of an increased attentional focus towards bodily symptoms in the onset and maintenance of this debilitating anxiety disorder. In this fMRI mental tracking paradigm, we looked at the effects of focusing one's attention internally (interoception) vs. externally (exteroception) in a well-studied group at risk for PD-that is anxiety-sensitive females (AS-high). We hypothesized that AS-high subjects compared to control subjects will present higher arousal and decreased valence scores during interoception and parallel higher activity in brain areas which are associated with fear and interoception. 24 healthy female students with high levels of anxiety sensitivity and 24 healthy female students with normal levels of anxiety sensitivity serving as control group were investigated by 3 T fMRI. Subjects either focused their attention on their heartbeats (internal condition) or on neutral tones (external condition). Task performance was monitored by reporting the number of heartbeats or tones after each block. State of arousal and emotional valence were also assessed. The high anxiety-sensitive group reported higher arousal scores compared to controls during the course of the experiment. Simultaneously, fMRI results indicated higher activation in anxiety-sensitive participants than in controls during interoception in a network of cortical and subcortical brain regions (thalamus, amygdala, parahippocampus) that overlaps with known fear circuitry structures. In particular, the activity of the right amygdala was up-regulated. Future prospective-longitudinal studies are needed to validate the role of the amygdala for transition to disorder. Attention to internal body functions up-regulates the activity of interoceptive and fear-relevant brain regions in anxiety-sensitive females, a high-risk group for the development of anxiety disorders.