Distress, anxiety, and depression in persons with hereditary cancer syndromes: Results from a nationwide cross-sectional study in Germany.

BACKGROUND: Persons with hereditary cancer syndromes (carriers) have a higher risk of developing cancer early. They are confronted with decisions regarding prophylactic surgeries, communication within their families, and childbearing. The present study aims to assess distress, anxiety, and depression in adult carriers and identify risk groups and predictors; clinicians can use to screen for particularly distressed persons. METHODS: N = 223 participants (n = 200 women, n = 23 men) with different hereditary cancer syndromes affected and unaffected by cancer answered questionnaires measuring their distress, anxiety, and depression levels. The sample was compared to the general population using one-sample t-tests. The n = 200 women with (n = 111) and without cancer (n = 89) were then compared and predictors for increased levels of anxiety and depression were identified using stepwise linear regression analyses. RESULTS: 66% reported clinical relevant distress, 47% reported clinical relevant anxiety, and 37% reported clinical relevant depression. Compared to the general population, carriers experienced increased distress, anxiety, and depression. Additionally, women with cancer suffered from more depressive symptoms than those without cancer. Past psychotherapy for a mental disorder and high distress were identified as predictors for increased anxiety and depression in female carriers. CONCLUSIONS: The results suggest that the psychosocial consequences of hereditary cancer syndromes are serious. Clinicians could regularly screen carriers regarding anxiety and depression. The NCCN Distress Thermometer can be combined with questions about past psychotherapy to identify especially vulnerable persons. Further studies are needed to develop psychosocial interventions.

Desire for Children and Distress in Women with Hereditary Cancer Syndromes.

The diagnosis of a hereditary cancer syndrome can be psychologically stressful and influence family planning. This study aimed to gain insights into the relationship between the desire for children and the distress of female carriers. Women (N = 255) with different hereditary cancer syndromes were assessed from November 2019 to July 2021 at genetic counseling centers, the centers of the German HBOC-Consortium and the centers of the German HNPCC-Consortium regarding their distress levels with the NCCN Distress Thermometer (DT). The desire for children was measured by self-developed questions. Levels of distress and desire for children were evaluated descriptively. Factors influencing the desire for children and distress were calculated using binary logistic regression: 56% (n = 51) of 18- to 39-year-old participants reported a desire to have children; 70.6% of the carriers with a desire for children indicated a need for advice from their physicians regarding family planning. The diagnosis led 61.5% to postpone the timing of family planning, and the majority (68.8%) opted for an earlier birth. Carriers had higher levels of distress. Younger carriers (p = 0.037) and those living in poorer economic circumstances (p = 0.011) were more distressed. The diagnosis of hereditary cancer syndrome affects family planning. The results emphasize the importance of physicians addressing family planning in their counseling sessions.

Vectored antibody gene delivery restores host B and T cell control of persistent viral infection.

Passive antibody therapy and vectored antibody gene delivery (VAGD) in particular offer an innovative approach to combat persistent viral diseases. Here, we exploit a small animal model to investigate synergies of VAGD with the host's endogenous immune defense for treating chronic viral infection. An adeno-associated virus (AAV) vector delivering the lymphocytic choriomeningitis virus (LCMV)-neutralizing antibody KL25 (AAV-KL25) establishes protective antibody titers for >200 days. When therapeutically administered to chronically infected immunocompetent wild-type mice, AAV-KL25 affords sustained viral load control. In contrast, viral mutational escape thwarts therapeutic AAV-KL25 effects when mice are unable to mount LCMV-specific antibody responses or lack CD8+ T cells. VAGD augments antiviral germinal center B cell and antibody-secreting cell responses and reduces inhibitory receptor expression on antiviral CD8+ T cells. These results indicate that VAGD fortifies host immune defense and synergizes with B cell and CD8 T cell responses to restore immune control of chronic viral infection.

Chasing Intracellular Zika Virus Using Proteomics.

Flaviviruses are the most medically relevant group of arboviruses causing a wide range of diseases in humans and are associated with high mortality and morbidity, as such posing a major health concern. Viruses belonging to this family can be endemic (e.g., dengue virus), but can also cause fulminant outbreaks (e.g., West Nile virus, Japanese encephalitis virus and Zika virus). Intense research efforts in the past decades uncovered shared fundamental strategies used by flaviviruses to successfully replicate in their respective hosts. However, the distinct features contributing to the specific host and tissue tropism as well as the pathological outcomes unique to each individual flavivirus are still largely elusive. The profound footprint of individual viruses on their respective hosts can be investigated using novel technologies in the field of proteomics that have rapidly developed over the last decade. An unprecedented sensitivity and throughput of mass spectrometers, combined with the development of new sample preparation and bioinformatics analysis methods, have made the systematic investigation of virus-host interactions possible. Furthermore, the ability to assess dynamic alterations in protein abundances, protein turnover rates and post-translational modifications occurring in infected cells now offer the unique possibility to unravel complex viral perturbations induced in the infected host. In this review, we discuss the most recent contributions of mass spectrometry-based proteomic approaches in flavivirus biology with a special focus on Zika virus, and their basic and translational potential and implications in understanding and characterizing host responses to arboviral infections.

A Scent of Anxiety: Olfactory Context Conditioning and its Influence on Social Cues.

Perception and evaluation of objects are highly dependent on surrounding contexts. Threatening contexts enhance processing of faces. Because odors are assumed to deliver strong contextual information, the present study aimed at demonstrating 1) that odors can constitute threat and safety contexts, and 2) consequently modulate the processing of faces presented in these contexts. Therefore, previously neutral odors were used as contextual stimuli in a context conditioning paradigm, resulting in an olfactory anxiety and a safety context. Then, faces showing angry, neutral, or fearful expressions were presented within both contexts during a test phase to investigate the effects of threat versus safety contexts on face perception. The late positive potential (LPP) from the EEG, skin conductance level, and subjective ratings were recorded. Results reveal successful olfactory context conditioning as reflected in enhanced processing of the anxiety context, indicated by enhanced LPP after conditioning, increased skin conductance level, and marginally respectively increased ratings. Moreover, faces presented within the threat context were rated as more unpleasant and marginally more arousing than faces presented in the safety context. Thus, olfactory stimuli can serve as context in fear conditioning, and a threatening olfactory context seems to enhance processing of stimuli perceived within this context.

Sustained attention in context conditioning: Evidence from steady-state VEPs.

In classical fear conditioning an aversive event is paired repeatedly with a predictive stimulus, which later elicits fear. Repeated presentation of an aversive event in the absence of a predictive cue however may induce anxiety, and the context may gain a threatening value. As such conditioned anxiety can be considered a sustained reaction compared to phasic fear, it would be interesting to track continuous cortical responses during context conditioning. The present study realized a differential context conditioning paradigm and assessed sustained cortical activations to the threatening and the safe context and how neutral cues are processed within both contexts. Two pictures of different office rooms presented for 20s served as contexts. One room became associated with an unpleasant noise that was presented unpredictably (CTX+) while the other office (CTX-) was never associated with this unpleasant noise. After acquisition, a social agent or an object was presented as a distractor in both contexts. Cortical activations in response to contexts and distractors were assessed separately by steady-state visually evoked potentials (ssVEPs) using frequency tagging. Results revealed enhanced ssVEP-amplitudes for CTX+ compared to CTX- in a lateral occipital cluster during acquisition. Similarly, CTX+ elicited higher ssVEP-amplitudes during the test phase, and these context conditioning effects were not reduced by the simultaneous presentation of novel distractors. These results indicate that context conditioning was successfully implemented and that the anxiety context received facilitated cortical processing across the whole viewing time. We conclude that threatening contexts capture attention over a longer period of time, and are immune to distraction by new objects.

Affective engagement for facial expressions and emotional scenes: the influence of social anxiety.

Pictures of emotional facial expressions or natural scenes are often used as cues in emotion research. We examined the extent to which these different stimuli engage emotion and attention, and whether the presence of social anxiety symptoms influences responding to facial cues. Sixty participants reporting high or low social anxiety viewed pictures of angry, neutral, and happy faces, as well as violent, neutral, and erotic scenes, while skin conductance and event-related potentials were recorded. Acoustic startle probes were presented throughout picture viewing, and blink magnitude, probe P3 and reaction time to the startle probe also were measured. Results indicated that viewing emotional scenes prompted strong reactions in autonomic, central, and reflex measures, whereas pictures of faces were generally weak elicitors of measurable emotional response. However, higher social anxiety was associated with modest electrodermal changes when viewing angry faces and mild startle potentiation when viewing either angry or smiling faces, compared to neutral. Taken together, pictures of facial expressions do not strongly engage fundamental affective reactions, but these cues appeared to be effective in distinguishing between high and low social anxiety participants, supporting their use in anxiety research.