Autoimmunity Against Surfactant Protein B Is Associated with Pneumonitis During Checkpoint Blockade.

RATIONALE: Immune checkpoint inhibitor-related pneumonitis is a serious autoimmune event affecting up to 20% of patients with non-small cell lung cancer, yet the factors underpinning its development in some patients and not others are poorly understood. OBJECTIVES: To investigate the role of autoantibodies and autoreactive T cells against surfactant-related proteins in the development of pneumonitis. METHODS: The study cohort consisted of non-small cell lung cancer patients who gave blood samples before and during immune checkpoint inhibitor treatment. Serum was used for proteomics analyses and to detect autoantibodies present during pneumonitis. T cell stimulation assays and single-cell RNA sequencing were performed to investigate the specificity and functionality of peripheral autoreactive T cells. The findings were confirmed in a validation cohort comprising patients with non-small cell lung cancer and patients with melanoma. MEASUREMENTS AND MAIN RESULTS: Across both cohorts, patients who developed pneumonitis had higher pre-treatment levels of immunoglobulin G autoantibodies targeting surfactant protein-B. At the onset of pneumonitis, these patients also exhibited higher frequencies of CD4+ interferon-gamma-positive surfactant protein B-specific T cells, and expanding T cell clonotypes recognizing this protein, accompanied by a pro-inflammatory serum proteomic profile. CONCLUSIONS: Our data suggest that the co-occurrence of surfactant protein-B-specific immunoglobulin G autoantibodies and CD4+ T cells is associated with the development of pneumonitis during ICI therapy. Pre-treatment levels of these antibodies may represent a potential biomarker for elevated risk of developing pneumonitis and on-treatment levels may provide a diagnostic aid. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Domain-specific knowledge and domain-general abilities in children's science problem-solving.

BACKGROUND: Problem-solving in early and middle childhood is of high relevance for cognitive developmental research and educational support. Previous research on science problem-solving has focussed on the process and strategies of children handling challenging tasks, but less on providing insights into the cognitive network that enables science problem-solving. AIMS: In this study, we aimed to investigate whether performance in science problem-solving is mainly determined by domain-specific rule knowledge, by domain-general cognitive abilities or both. METHODS: In our study, 215 6- to 8-year-old children completed a set of three domain-specific rule knowledge tasks and three corresponding problem-solving tasks that were content-coherent, as well as a vocabulary task, and a reasoning task. RESULTS: Correlational and regression analyses revealed a negligible impact of domain-specific rule knowledge on corresponding problem-solving tasks. In contrast, the associations between problem-solving performance in different domains and the associations between problem-solving performance and domain-general abilities (vocabulary and reasoning) were comparably strong. CONCLUSIONS: The findings suggest that science problem-solving in primary school children primarily relies on domain-general cognitive abilities. Implications of these findings are discussed with regard to cognitive theories and early science education.

The effect of metacognitive executive function training on children's executive function, proactive control, and academic skills.

The current study investigated the effects of metacognitive and executive function (EF) training on childhood EF (inhibition, working memory [WM], cognitive flexibility, and proactive/reactive control) and academic skills (reading, reasoning, and math) among children from disadvantaged backgrounds. Children (N = 134, Mage = 8.70 years) were assigned randomly to the three training groups: (a) metacognitive training of basic EF processes (meta-EF), (b) training of basic EF processes (basic-EF), and (c) active controls (active control). They underwent 16 training sessions over the course of 2 months. No effects of EF and/or metacognitive training were found for academic outcomes. However, both meta-EF and basic-EF groups demonstrated greater gains than the active control group on proactive control engagement and WM, suggesting that EF training promotes a shift to more mature ways of engaging EF. Our findings suggest minimal near- and far-transfer effects of metacognitive training but highlight that proactive engagement of EF can be promoted through EF training in children. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Tumor-infiltrating lymphocytes mediate complete and durable remission in a patient with NY-ESO-1 expressing prostate cancer.

Adoptive transfer of autologous tumor-specific lymphocytes represents a viable treatment method for patients with advanced malignancies. Here, we report a patient's case with metastatic hormone-refractory New York esophageal squamous cell carcinoma 1 (NY-ESO-1) expressing prostate cancer treated with in vitro expanded tumor-infiltrating lymphocytes (TILs) in conjunction with IL-2 and immune-checkpoint blockade. Complete and durable tumor remission was observed after three TIL infusions consisting of 1.4×109, 2.0×109, and 8.0×109 T cells, respectively, lasting now for more than 3.5 years. Immunological correlates to the clinical development were the decrease of tumor-driven NY-ESO-1 serum antibody and the drop of prostate-specific antigen to <0.01 µg/L. TILs were reactive against cancer-testis antigen NY-ESO-1, individual tumor mutational proteins (eg, PRPF8, TRPS1), and the androgen receptor splice variant 12.

Immune signatures predict development of autoimmune toxicity in patients with cancer treated with immune checkpoint inhibitors.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are among the most promising treatment options for melanoma and non-small cell lung cancer (NSCLC). While ICIs can induce effective anti-tumor responses, they may also drive serious immune-related adverse events (irAEs). Identifying biomarkers to predict which patients will suffer from irAEs would enable more accurate clinical risk-benefit analysis for ICI treatment and may also shed light on common or distinct mechanisms underpinning treatment success and irAEs. METHODS: In this prospective multi-center study, we combined a multi-omics approach including unbiased single-cell profiling of over 300 peripheral blood mononuclear cell (PBMC) samples and high-throughput proteomics analysis of over 500 serum samples to characterize the systemic immune compartment of patients with melanoma or NSCLC before and during treatment with ICIs. FINDINGS: When we combined the parameters obtained from the multi-omics profiling of patient blood and serum, we identified potential predictive biomarkers for ICI-induced irAEs. Specifically, an early increase in CXCL9/CXCL10/CXCL11 and interferon-γ (IFN-γ) 1 to 2 weeks after the start of therapy are likely indicators of heightened risk of developing irAEs. In addition, an early expansion of Ki-67+ regulatory T cells (Tregs) and Ki-67+ CD8+ T cells is also likely to be associated with increased risk of irAEs. CONCLUSIONS: We suggest that the combination of these cellular and proteomic biomarkers may help to predict which patients are likely to benefit most from ICI therapy and those requiring intensive monitoring for irAEs. FUNDING: This work was primarily funded by the European Research Council, the Swiss National Science Foundation, the Swiss Cancer League, and the Forschungsförderung of the Kantonsspital St. Gallen.

Feeling lonely during the pandemic: Towards personality-tailored risk profiles.

This is the first study to disentangle associations of within- and between-person fluctuations in loneliness and their effect on evening mood during a nationwide lockdown due to COVID-19. To contribute to the development of personality-tailored risk profiles, we additionally explored the moderating role of trait neuroticism and extraversion on the association of within- and between-person loneliness and mood. We employed an ambulatory assessment design during 21 days of nationwide lockdown in Germany (13/04/2020-03/05/2020) with two interval-based assessments. The final sample comprised 322 participants (74.5% women) aged between 15 and 82 years (M = 30.7, SD = 14.9) providing 6,084 evening assessments. Linear mixed models were used to evaluate the effects of within- and between-person fluctuations in loneliness on evening mood while controlling for unspecific effects of time, sex, and age. Moderation analysis was used to investigate the influence of neuroticism and extraversion on the relation between loneliness and mood, respectively. Results indicate that especially higher between-person loneliness (i.e. participants felt lonelier compared to the average participant) but also higher within-person loneliness (i.e. participants felt lonelier compared to their individual mean) were associated with a more unpleasant mood. Neuroticism augmented the effect of within-person loneliness, while extraversion seemed to buffer the effect of between-person loneliness on mood. Our findings underline the importance of carefully monitoring loneliness during COVID-19. The findings contribute towards the development of personality-tailored risk profiles (e.g. among newly arising risk groups for loneliness due to COVID-19). We discuss how the differential consideration of within- and between-psychological processes might help to elucidate currently mixed findings on psychological coping during the COVID-19 pandemic.

Detecting subtle signs of depression with automated speech analysis in a non-clinical sample.

BACKGROUND: Automated speech analysis has gained increasing attention to help diagnosing depression. Most previous studies, however, focused on comparing speech in patients with major depressive disorder to that in healthy volunteers. An alternative may be to associate speech with depressive symptoms in a non-clinical sample as this may help to find early and sensitive markers in those at risk of depression. METHODS: We included n = 118 healthy young adults (mean age: 23.5 ± 3.7 years; 77% women) and asked them to talk about a positive and a negative event in their life. Then, we assessed the level of depressive symptoms with a self-report questionnaire, with scores ranging from 0-60. We transcribed speech data and extracted acoustic as well as linguistic features. Then, we tested whether individuals below or above the cut-off of clinically relevant depressive symptoms differed in speech features. Next, we predicted whether someone would be below or above that cut-off as well as the individual scores on the depression questionnaire. Since depression is associated with cognitive slowing or attentional deficits, we finally correlated depression scores with performance in the Trail Making Test. RESULTS: In our sample, n = 93 individuals scored below and n = 25 scored above cut-off for clinically relevant depressive symptoms. Most speech features did not differ significantly between both groups, but individuals above cut-off spoke more than those below that cut-off in the positive and the negative story. In addition, higher depression scores in that group were associated with slower completion time of the Trail Making Test. We were able to predict with 93% accuracy who would be below or above cut-off. In addition, we were able to predict the individual depression scores with low mean absolute error (3.90), with best performance achieved by a support vector machine. CONCLUSIONS: Our results indicate that even in a sample without a clinical diagnosis of depression, changes in speech relate to higher depression scores. This should be investigated in more detail in the future. In a longitudinal study, it may be tested whether speech features found in our study represent early and sensitive markers for subsequent depression in individuals at risk.

Durable spike-specific T cell responses after different COVID-19 vaccination regimens are not further enhanced by booster vaccination.

Several COVID-19 vaccines are approved to prevent severe disease outcome after SARS-CoV-2 infection. Whereas induction and functionality of antiviral antibody response are largely studied, the induction of T cells upon vaccination with the different approved COVID-19 vaccines is less studied. Here, we report on T cell immunity 4 weeks and 6 months after different vaccination regimens and 4 weeks after an additional booster vaccination in comparison with SARS-CoV-2 T cell responses in convalescents and prepandemic donors using interferon-gamma ELISpot assays and flow cytometry. Increased T cell responses and cross-recognition of B.1.1.529 Omicron variant-specific mutations were observed ex vivo in mRNA- and heterologous-vaccinated donors compared with vector-vaccinated donors. Nevertheless, potent expandability of T cells targeting the spike protein was observed for all vaccination regimens, with frequency, diversity, and the ability to produce several cytokines of vaccine-induced T cell responses comparable with those in convalescent donors. T cell responses for all vaccinated donors significantly exceeded preexisting cross-reactive T cell responses in prepandemic donors. Booster vaccination led to a significant increase in anti-spike IgG responses, which showed a marked decline 6 months after complete vaccination. In contrast, T cell responses remained stable over time after complete vaccination with no significant effect of booster vaccination on T cell responses and cross-recognition of Omicron BA.1 and BA.2 mutations. This suggested that booster vaccination is of particular relevance for the amelioration of antibody response. Together, our work shows that different vaccination regimens induce broad and long-lasting spike-specific CD4+ and CD8+ T cell immunity to SARS-CoV-2.

A Quantitative ELISA to Detect Anti-SARS-CoV-2 Spike IgG Antibodies in Infected Patients and Vaccinated Individuals.

There is an ongoing need for high-precision serological assays for the quantitation of anti-SARS-CoV-2 antibodies. Here, a trimeric SARS-CoV-2 spike (S) protein was used to develop an ELISA to quantify specific IgG antibodies present in serum, plasma, and dried blood spots (DBS) collected from infected patients or vaccine recipients. The quantitative S-ELISA was calibrated with international anti-SARS-CoV-2 immunoglobulin standards to provide test results in binding antibody units per mL (BAU/mL). The assay showed excellent linearity, precision, and accuracy. A sensitivity of 100% was shown for samples collected from 54 patients with confirmed SARS-CoV-2 infection more than 14 days after symptom onset or disease confirmation by RT-PCR and 58 vaccine recipients more than 14 days after vaccination. The assay specificity was 98.3%. Furthermore, antibody responses were measured in follow-up samples from vaccine recipients and infected patients. Most mRNA vaccine recipients had a similar response, with antibody generation starting 2-3 weeks after the first vaccination and maintaining positive for at least six months after a second vaccination. For most infected patients, the antibody titers increased during the second week after PCR confirmation. This S-ELISA can be used to quantify the seroprevalence of SARS-CoV-2 in the population exposed to the virus or vaccinated.

"Hot" executive functions are comparable across monolingual and bilingual elementary school children: Results from a study with the Iowa Gambling Task.

Past research found performance differences between monolingual and bilingual children in the domain of executive functions (EF). Furthermore, recent studies have reported advantages in processing efficiency or mental effort in bilingual adults and children. These studies mostly focused on the investigation of "cold" EF tasks. Studies including measures of "hot" EF, i.e., tasks operating in an emotionally significant setting, are limited and hence results are inconclusive. In the present study, we extend previous research by investigating performance in a task of the "hot" EF domain by both behavioral data and mental effort via pupillary changes during task performance. Seventy-three monolingual and bilingual school children (mean age = 107.23 months, SD = 10.26) solved the Iowa Gambling Task in two different conditions. In the standard task, characterized by constant gains and occasional losses, children did not learn to improve their decision-making behavior. In a reversed task version, characterized by constant losses and occasional gains, both monolinguals and bilinguals learned to improve their decision-making behavior over the course of the task. In both versions of the task, children switched choices more often after losses than after gains. Bilinguals switched their choices less often than monolinguals in the reversed task, indicating a slightly more mature decision-making strategy. Mental effort did not differ between monolinguals and bilinguals. Conclusions of these findings for the bilingual advantage assumption will be discussed.

Executive functions in mono- and bilingual children: Factor structure and relations with fluid intelligence.

The effects of bilingualism on executive functions (EFs) and intelligence are still controversially discussed. Most studies have focused on performance differences without considering the underlying structure of cognitive abilities. Thus, we examined whether the structure of EFs and the relations of EFs with intelligence differ between mono- and bilingual children. A total of 240 elementary school children (mean age = 8 years 6 months; 133 monolinguals and 95 bilinguals) performed two tasks measuring working memory, inhibition, cognitive flexibility, and fluid intelligence, respectively. Confirmatory factor analyses showed that one common EF factor provided the best fit to the data in both language groups, indicating that bilingualism is not associated with differences in the EF structure at this age. Moreover, there were no latent performance differences in either EFs or intelligence between mono- and bilingual children. However, we found a stronger relation between a common EF factor and fluid intelligence in bilingual children as compared with monolingual children, implying a closer coupling of EFs and intelligence abilities in bilingual children. This contributes to explaining the previous heterogeneous findings on the task level because more closely coupled cognitive functioning can be slightly beneficial for some tasks and irrelevant or even slightly obstructive for others.

Age-differences in network models of self-regulation and executive control functions.

Self-regulation (SR) and executive control functions (EF) are broad theoretical concepts that subsume various cognitive abilities supporting the regulation of behavior, thoughts, and emotions. However, many of these concepts stem from different psychological disciplines relying on distinct methodologies, such as self-reports (common in SR research) and performance-based tasks (common in EF research). Despite the striking overlap between SR and EF on the theoretical level, recent evidence suggests that correlations between self-report measures and behavioral tasks can be difficult to observe. In our study, participants from a life-span sample (14-82 years) completed self-report measures and behavioral tasks, which were selected to include a variety of different facets of SR (e.g., sensation seeking, mindfulness, grit, or eating behavior) and EF (working memory, inhibition, shifting). Using this broad approach, we systematically investigated connections and overlap of different aspects of SR and EF to improve their conceptual understanding. By comparing network models of a youth, middle-aged, and older-aged group, we identified key variables that are well connected in the SR and EF construct space. In general, we found connections to be stronger within the clusters of SR and EF than between them. However, older adults demonstrated more connections between SR and EF than younger individuals, likely because of declining cognitive resources.

Self-regulation in preschool: Are executive function and effortful control overlapping constructs?

The concepts of executive function (EF) and effortful control (EC) are strikingly similar. EF originate from neurocognitive research and are described as an accumulation of cognitive processes that serve the goal-oriented self-regulation (SR) of an individual. EC originates from temperament research and is defined as the efficiency of executive attention, including the ability to inhibit a dominant response, to activate a subdominant response, to proceed in a planned manner and to recognize conflicts or errors. The aim of this article was to examine the association between the constructs of EF and EC at the preschool-age. Eighty-eight children (49 female; M-age = 3.93 years, SD = .78) were tested with a computerized battery designed to assess EF at 3-6 years of age (EF Touch). Children's parents completed questionnaires assessing EF impairments (BRIEF-P) and EC (CBQ). Associations between the constructs and their conceptual overlap were analyzed using correlations and confirmatory factor analyses. We found significant correlations between EF and EC measures. A one-factor confirmatory model fitted the data very well and indicated that EF and EC are indeed overlapping and highly similar constructs. Therefore, our results show that measures of EC and EF have substantial overlap in preschoolers and suggest an integrated model of self-regulation.

Coping under a COVID-19 lockdown: patterns of daily coping and individual differences in coping repertoires.

BACKGROUND: Polyregulation-the concurrent or sequential use of multiple strategies to regulate affect or cope with stressors-is a frequent but understudied phenomenon. OBJECTIVES: We aimed to identify patterns of daily coping and individuals' coping repertoires (i.e., range of coping patterns employed across situations) during a COVID-19 pandemic lockdown. We investigated day-level covariates (appraisals, worrying, mood) of daily coping patterns and person-level covariates (psychopathology, average mood) of coping repertoires. Design: A non-representative community sample (n = 322, 15-82 years old) participated in a 21-day ambulatory assessment study. METHODS: We applied multilevel latent class analysis.. RESULTS: We identified seven daily coping patterns and ten classes of individuals differing in the size of their coping repertoire and their propensity for polyregulation. Daily coping patterns differed in daily perceived controllability and mood (but not in daily worrying or stress). At the person level, individuals with a higher level of average coronavirus-related worrying more frequently engaged in a high degree of polyregulation. The size of individuals' coping repertoire was unrelated to psychopathology and average mood. CONCLUSION: The findings provide insights into the composition of daily coping patterns and individuals' coping repertoires during crisis periods and contribute to a new polyregulation perspective on coping.

Differences in cognitive processing? The role of verbal processes and mental effort in bilingual and monolingual children's planning performance.

Past research documents a bilingual advantage in the domain of executive functions (EFs). However, controversial debates have questioned the robustness of those behavioral differences. The current study aimed to better understand the underlying cognitive prerequisites in bilingual students as compared with monolingual students and focused on two processes: the role of verbal processes, on the one hand, and mental effort during task execution, on the other. The use of self-regulatory speech has been found to be related to performance in tasks requiring EFs. For bilinguals who have grown up with two language systems from an early age, those relations are not fully understood. Furthermore, results from neuroimaging studies have shown that bilinguals might exhibit less mental effort in EF tasks. We investigated both processes in German-speaking monolingual elementary school students (n = 33; Mage = 8.78 years) and German-Russian bilingual elementary school students (n = 34; Mage = 8.88 years) solving a planning task. Results showed that monolinguals were impaired by a verbal secondary task in comparison with a motor control condition, whereas bilinguals performed in both tasks at an equal level, indicating a differential role of self-regulatory speech in both language groups. Analyses of changes in pupil diameter revealed less mental effort during task execution for bilingual children as compared with monolingual children. The current study adds to the existing literature by supplying further evidence for cognitive differences between monolingual and bilingual children.

A COVID-19 peptide vaccine for the induction of SARS-CoV-2 T cell immunity.

T cell immunity is central for the control of viral infections. CoVac-1 is a peptide-based vaccine candidate, composed of SARS-CoV-2 T cell epitopes derived from various viral proteins1,2, combined with the Toll-like receptor 1/2 agonist XS15 emulsified in Montanide ISA51 VG, aiming to induce profound SARS-CoV-2 T cell immunity to combat COVID-19. Here we conducted a phase I open-label trial, recruiting 36 participants aged 18-80 years, who received a single subcutaneous CoVac-1 vaccination. The primary end point was safety analysed until day 56. Immunogenicity in terms of CoVac-1-induced T cell response was analysed as the main secondary end point until day 28 and in the follow-up until month 3. No serious adverse events and no grade 4 adverse events were observed. Expected local granuloma formation was observed in all study participants, whereas systemic reactogenicity was absent or mild. SARS-CoV-2-specific T cell responses targeting multiple vaccine peptides were induced in all study participants, mediated by multifunctional T helper 1 CD4+ and CD8+ T cells. CoVac-1-induced IFNγ T cell responses persisted in the follow-up analyses and surpassed those detected after SARS-CoV-2 infection as well as after vaccination with approved vaccines. Furthermore, vaccine-induced T cell responses were unaffected by current SARS-CoV-2 variants of concern. Together, CoVac-1 showed a favourable safety profile and induced broad, potent and variant of concern-independent T cell responses, supporting the presently ongoing evaluation in a phase II trial for patients with B cell or antibody deficiency.

Validation of a digital, tablet-based version of the Trail Making Test in the ∆elta platform.

Using digital technology for neuropsychological assessment is gaining popularity in both clinical and research settings. Digital neuropsychology offers many benefits over the traditional paper-pencil assessments; however, their comparability requires further validation. The aim of this study was to compare a digital, tablet-based Trail Making Test to the standard paper version. In a within-subject design, 108 healthy adults completed both digital and paper Trail Making Test in a counterbalanced order. Each participant also performed other tasks measuring core executive abilities (inhibition, working memory, and flexibility) on the tablet. Our findings indicated that the Trail Making Test performance on the two different modalities correlated significantly. Furthermore, correlations of Trail Making Test performance with other cognitive tasks revealed that digital Trail Making Test is comparable with the paper version. However, the modality had a significant effect on Trail Making Test performance; that is, participants were generally faster on the digital platform. Taken together, our findings suggest that with new normative data, traditional Trail Making Test can be adapted successfully to a digital platform.

The relations between personality, components of executive functions, and intelligence in children and young adults.

Previous studies in adults showed heterogeneous results regarding the associations of personality with intelligence and executive functions (EF). In children, there is a lack of studies investigating the relations between personality and EF. Therefore, the aim of our study was to examine the relations between the Big Five personality traits, EF, and intelligence in a sample of children (Experiment 1) and young adults (Experiment 2). A total of 155 children (Experiment 1, mean age = 9.54 years) and 91 young adults (Experiment 2, mean age = 23.49 years) participated in the two studies. In both studies, participants performed tasks measuring working memory (WM), inhibitory control, cognitive flexibility, and fluid intelligence and completed a personality questionnaire. In Experiment 1, we found a negative relation between neuroticism and intelligence. In Experiment 2, we found a positive relation between conscientiousness and intelligence and a positive relation between conscientiousness and cognitive flexibility. Our results suggest a complex interplay between personality factors, EF, and intelligence both in children as well as in young adults.

Negative Emotion Differentiation Attenuates the Within-Person Indirect Effect of Daily Stress on Nightly Sleep Quality Through Calmness.

The ability to differentiate between negative emotional states [negative emotion differentiation (NED)] has been conceptualized as a trait that facilitates effective emotion regulation and buffers stress reactivity. In the present research, we investigated the role of NED in within-person processes of daily affect regulation and coping during times of stress (the first COVID-19-related pandemic lockdown in April 2020). Using intensive longitudinal data, we analyzed whether daily stress had an indirect effect on sleep quality through calmness in the evening, and we tested whether NED moderated this within-person indirect effect by buffering the link between daily stress and calmness in the evening. A non-representative community sample (n = 313, 15-82 years old) participated in a 21-day ambulatory assessment with twice-daily surveys. The results of multilevel mediation models showed that higher daily stress was related to within-day change in calmness from morning to evening, resulting in less calmness in the evening within persons. Less calmness in the evening, in turn, was related to poorer nightly sleep quality within persons. As expected, higher NED predicted a less negative within-person link between daily stress and calmness in the evening, thereby attenuating the indirect effect of daily stress on nightly sleep quality through calmness. This effect held when we controlled for mean negative emotions and depression. The results provide support for a diathesis-stress model of NED, and hence, for NED as a protective factor that helps to explain why some individuals remain more resilient during times of stress than others.

Changes in quality of life, depression, general anxiety, and heart-focused anxiety after defibrillator implantation.

AIMS: The Anxiety-CHF (Anxiety in patients with Chronic Heart Failure) study investigated heart-focused anxiety (HFA, with the dimensions fear, attention, and avoidance of physical activity), general anxiety, depression, and quality of life (QoL) in patients with heart failure. Psychological measures were assessed before and up to 2 years after the implantation of an implantable cardioverter defibrillator (ICD) with or without cardiac resynchronization therapy defibrillator (CRT-D). METHODS AND RESULTS: One hundred thirty-two patients were enrolled in this monocentric prospective study (44/88 CRT-D/ICD, mean age 61 ± 14 years, mean left ventricular ejection fraction 31 ± 9%, and 29% women). Psychological assessment was performed before device implantation as well as after 5, 12, and 24 months. After device implantation, mean total HFA, HFA-fear, HFA-attention, general anxiety, and QoL improved significantly. Depression and HFA-related avoidance of physical activity did not change. CRT-D patients compared with ICD recipients and women compared with men reported worse QoL at baseline. Younger patients (