Spineless Behavior of CX3CR1+ Monocytes in Response to Infection.

Sickness in mammals can lead to cognition deficits, although the underlying mechanisms remain elusive. In a recent Nature Medicine article, Garré et al. (2017) report that sickness-induced cortical dendritic spine loss and impaired memory formation is mediated by CX3CR1+ monocyte-derived TNF-α.

Social history and exposure to pathogen signals modulate social status effects on gene regulation in rhesus macaques.

Social experience is an important predictor of disease susceptibility and survival in humans and other social mammals. Chronic social stress is thought to generate a proinflammatory state characterized by elevated antibacterial defenses and reduced investment in antiviral defense. Here we manipulated long-term social status in female rhesus macaques to show that social subordination alters the gene expression response to ex vivo bacterial and viral challenge. As predicted by current models, bacterial lipopolysaccharide polarizes the immune response such that low status corresponds to higher expression of genes in NF-κB-dependent proinflammatory pathways and lower expression of genes involved in the antiviral response and type I IFN signaling. Counter to predictions, however, low status drives more exaggerated expression of both NF-κB- and IFN-associated genes after cells are exposed to the viral mimic Gardiquimod. Status-driven gene expression patterns are linked not only to social status at the time of sampling, but also to social history (i.e., past social status), especially in unstimulated cells. However, for a subset of genes, we observed interaction effects in which females who fell in rank were more strongly affected by current social status than those who climbed the social hierarchy. Taken together, our results indicate that the effects of social status on immune cell gene expression depend on pathogen exposure, pathogen type, and social history-in support of social experience-mediated biological embedding in adulthood, even in the conventionally memory-less innate immune system.

Understanding the genetic contribution of the human leukocyte antigen system to common major psychiatric disorders in a world pandemic context.

The human leukocyte antigen (HLA) is a complex genetic system that encodes proteins which predominantly regulate immune/inflammatory processes. It can be involved in a variety of immuno-inflammatory disorders ranging from infections to autoimmunity and cancers. The HLA system is also suggested to be involved in neurodevelopment and neuroplasticity, especially through microglia regulation and synaptic pruning. Consequently, this highly polymorphic gene region has recently emerged as a major player in the etiology of several major psychiatric disorders, such as schizophrenia, autism spectrum disorder and bipolar disorder and with less evidence for major depressive disorders and attention deficit hyperactivity disorder. We thus review here the role of HLA genes in particular subgroups of psychiatric disorders and foresee their potential implication in future research. In particular, given the prominent role that the HLA system plays in the regulation of viral infection, this review is particularly timely in the context of the Covid-19 pandemic.

Suicidal behaviors and ideation during emerging viral disease outbreaks before the COVID-19 pandemic: A systematic rapid review.

The current COVID-19 pandemic is the most severe pandemic of the 21st century, on track to having a rising death toll. Beyond causing respiratory distress, COVID-19 may also cause mortality by way of suicide. The pathways by which emerging viral disease outbreaks (EVDOs) and suicide are related are complex and not entirely understood. We aimed to systematically review the evidence on the association between EVDOs and suicidal behaviors and/or ideation. An electronic search was conducted using five databases: Medline, Embase, Web of Science, PsycINFO and Scopus in April 2020. A rapid systematic review was carried out, which involved separately and independently extracting quantitative data of selected articles. The electronic search yielded 2480 articles, of which 9 met the inclusion criteria. Most of the data were collected in Hong Kong (n = 3) and the USA (n = 3). Four studies reported a slight but significant increase in deaths by suicide during EVDOs. The increase in deaths by suicide was mainly reported during the peak epidemic and in older adults. Psychosocial factors such as the fear of being infected by the virus or social isolation related to quarantine measures were the most prominent factors associated with deaths by suicide during EVDOs. Overall, we found scarce and weak evidence for an increased risk of deaths by suicide during EVDOs. Our results inform the need to orient public health policies toward suicide prevention strategies targeting the psychosocial effects of EVDOs. High-quality research on suicide risk and prevention are warranted during the current pandemic.

Two Distinct Immune Pathways Linking Social Relationships With Health: Inflammatory and Antiviral Processes.

OBJECTIVE: Social relationships can both influence and be influenced by immune processes. Past work implicates two distinct pathways along which this interaction may occur: inflammatory processes and antiviral processes. This article reviews how social behavior is modulated by these two immune processes and how such processes may in turn regulate social behavior. METHODS: This narrative review outlines existing work on social behavior and both inflammatory and antiviral processes. We propose an evolutionary framework that aims to integrate these findings. Specifically, social isolation has evolutionarily increased the likelihood of wounding and therefore increased the need for inflammation, which works to promote healing. Conversely, broader social networks provide protection from physical threats but also lead to increased pathogen exposure, necessitating a more robust antiviral response. RESULTS: This review highlights that social adversity, such as social exclusion or loneliness, is associated with increased inflammation, whereas social contact is associated with increased antiviral immunity. Furthermore, increased inflammation leads to sensitivity to social stimuli, presumably to avoid hostile conspecifics and approach allies who may provide care while vulnerable. Individuals with inadequate antiviral immunity engage in behaviors that minimize pathogen exposure, such as reduced affiliative behavior. CONCLUSIONS: This review suggests that adverse social experiences (social isolation, perceived social threat) may induce inflammatory responses while suppressing antiviral immunity, whereas positive experiences of social connection may reduce inflammation and bolster antiviral responses. Although acutely elevated inflammation would be adaptive under conditions where wounding is likely, chronic inflammation related to continued social adversity may have detrimental health consequences.

Psychological distress and infectious disease mortality in the general population.

There is a paucity of studies examining the relation between high psychological distress and infectious disease in the general population. We examined this association in a large multi-cohort study drawn from the general population. The analytic sample comprised 104,923 men and women (age, 47.3 ±â€¯17.4 year; 45.7% men) in which psychological distress symptoms was assessed using the 12-item version of the General Health Questionnaire. There were 1535 deaths attributed to infectious diseases during 971,220 person-years of follow up (mean 9.3; range 0.1-17.1 years). A dose-response association between GHQ-12 score and all infectious disease mortality was observed after adjusting for age, sex, survey year, occupational social class, longstanding illness, smoking, alcohol, and physical activity (per SD increase, hazard ratio = 1.24; 95% CI, 1.20-1.28). A similar pattern was apparent for viral infections (1.23; 1.14, 1.33) and pneumonia (1.20; 1.13, 1.28), but weaker for bacterial infections (1.09; 1.00, 1.19). In conclusion, psychological distress is associated with higher risk of infectious disease.

Expert-novice differences in mental models of viruses, vaccines, and the causes of infectious disease.

Humans are exposed to viruses everywhere they live, play, and work. Yet people's beliefs about viruses may be confused or inaccurate, potentially impairing their understanding of scientific information. This study used semi-structured interviews to examine people's beliefs about viruses, vaccines, and the causes of infectious disease. We compared people at different levels of science expertise: middle school students, teachers, and professional virologists. The virologists described more entities involved in microbiological processes, how these entities behaved, and why. Quantitative and qualitative analyses revealed distinctions in the cognitive organization of several concepts, including infection and vaccination. For example, some students and teachers described viral replication in terms of cell division, independent of a host. Interestingly, most students held a mental model for vaccination in which the vaccine directly attacks a virus that is present in the body. Our findings have immediate implications for how to communicate about infectious disease to young people.

[Topical preparations for therapy of tonsillar pathology].

This paper highlights clinical and diagnostic aspects of tonsillar pathology with special reference to modern methods for the treatment of pharyngeal diseases of different etiology. A detailed characteristic of local symptomatic therapy is presented including the use of NSAIDs (non-steroidal anti-inflammatory drugs). These agents have advantages over other medications for local therapy due to high anti-inflammatory and analgesic activities. Also, they significantly improve the patients' quality of life. The use of a local anti-inflammatory drug is a major component of the treatment of inflammatory pharyngeal pathology. Regardless of the nature of the disease, either bacterial or viral.

[High level of efficacy and safety of antiviral vaccines and unsubstantiated critique].

To counterbalance the unsubstantial declarations of some vaccinologists that vaccines and vaccination are not only useless, but also injurious to the health, this work represents the evidence that vaccines and vaccination not only reduce the morbidity of viral infection, but also allow some viral diseases to be eradicated and eliminated. The work also adduces the data about reducing economic impact of viral infections with the help of vaccination, as well as the data, which clearly show that serious reactions to vaccination are thousands of times less frequent than reactions and complications caused by infectious diseases.

Learning from the past: young Indigenous people's accounts of blood-borne viral and sexually transmitted infections as resilience narratives.

The Indigenous Resilience Project is an Australian community-based participatory research project using qualitative methods to explore young Aboriginal and Torres Strait Islander people's views of blood-borne viral and sexually transmitted infections (BBV/STI) affecting their communities. In this paper we present an analysis of narratives from young people who had a previous BBV/STI diagnosis to explore how they actively negotiate the experience of BBV/STI infection to construct a classic resilience narrative. We examine two overarching themes: first, the context of infection and diagnosis, including ignorance of STI/BBV prior to infection/diagnosis and, second, turning points and transformations in the form of insights, behaviours, roles and agency. Responding to critical writing on resilience theory, we argue that providing situated accounts of adversity from the perspectives of young Indigenous people prioritises their subjective understandings and challenges normative definitions of resilience.

Factors associated with acute fatigue in primary care.

BACKGROUND: To examine the role of psychological distress, negative life events, social support and lack of fitness (using breathlessness on exertion as a proxy) in the development of new onset fatigue in a primary care population. METHOD: Adults between the ages of 18 and 45 years who were registered with five general practices in South East England were asked to complete a fatigue questionnaire and the 12-item General Health Questionnaire. Between 1 and 12 months later, subjects who visited the general practitioner (GP) with a suspected viral infection were recruited to the study and asked to complete measures of fatigue, psychological distress, life events, social support and allergies (stage 2). The next person to present to the GP with a complaint other than a viral illness was recruited as a control. Factors assessed at stage 2 that were associated with the development of fatigue were examined with stepwise logistic regression. RESULTS: Acute fatigue was not associated with a viral illness. Negative life events and breathlessness on exertion (interpreted as lack of fitness) were associated with incident cases of fatigue. However, when controlling for concurrent psychological distress, the independent association of negative life events disappeared. CONCLUSIONS: Psychological distress was strongly associated with new onset fatigue and hence emphasizes the significance of psychological distress as a concomitant complaint in fatigue. Further, the salient association between breathlessness and fatigue may indicate the need to recommend exercise as a therapeutic strategy to improve physical fitness in the primary care setting.

Applying the transtheoretical model to the readiness to change blood-borne virus transmission behaviors among drug-dependent inmates.

Our study set out to assess readiness to change blood-borne virus transmission behaviors using the Transtheoretical Model among inmates in a court-ordered detention center. A cross-sectional descriptive study was conducted in southern Taiwan. All men convicted of illicit drug use and sentenced to undergo the 6-month detoxification program were invited to participate. Half of the 172 participating inmates described themselves as being in the contemplation stage of change. The length of residency in the detoxification program was not associated with self-reported readiness to change, chi(2)= 6.53, p = .16. Inmates in the precontemplation stage had increased rates for high-risk behaviors than those in the contemplation and action stages (p < .001). The efficacy of forced-abstinence detention programs on readiness to change risky behaviors needs to be reevaluated.

Stigmatising attitudes towards people who inject drugs, and people living with blood borne viruses or sexually transmissible infections in a representative sample of the Australian population.

Stigma has significant detrimental health outcomes for those affected. This study examined socio-demographic characteristics that were associated with stigmatising attitudes among the general population towards people who inject drugs, and people living with blood borne viruses or sexually transmissible infections. Questions were included in the Australian Survey of Social Attitudes (total sample = 1,001). Attitudes towards each of the target populations were measured by 5-item stigma scales. Bivariate analyses and multiple regression analyses were conducted to identify socio-demographic characteristics associated with stigmatising attitudes. Knowing a person affected by a stigmatised attribute was associated with reduced stigmatising attitudes, while voting for a conservative political party was associated with increased stigmatising attitudes. Age, gender, education, income, and marital status were each related to some stigmatising attitudes. Results also highlight differences between attitudes towards a stigmatised behaviour (i.e., injecting drug use) and stigmatised conditions (i.e., blood borne viruses and sexually transmissible infections). Identifying socio-demographic characteristics that are associated with stigmatising attitudes may have global implications for informing stigma reduction interventions, in order to promote positive health outcomes for affected communities.

Maternal host responses to poly(I:C) during pregnancy leads to both dysfunctional immune profiles and altered behaviour in the offspring.

PROBLEM: Autism spectrum disorder (ASD)-like phenotypes in murine models are linked to elevated pro-inflammatory cytokine profiles caused by maternal immune activation (MIA), but whether MIA alters the immune response in the offspring remains unclear. METHOD OF STUDY: Polyinosinic:polycytidylic acid (poly:[IC]) was used to induce MIA in immunocompetent and control TLR3-deficient pregnant mice, and cytokine levels were measured in maternal and foetal organs. Furthermore, cytokines and behaviour responses were tested after challenge with lipopolysaccharide in 7-day-old and adult mice. RESULTS: MIA induced on E12 resulted in changes in the cytokine expression profile in maternal and foetal organs and correlated with TNFα and IL-18 dysregulation in immune organs and brains from neonatal mice born to MIA-induced dams. Such changes further correlated with altered behavioural responses in adulthood. CONCLUSION: MIA induced by pathogens during pregnancy can interfere with the development of the foetal immune and nervous systems leading to dysfunctional immune responses and behaviour in offspring.

Risk markers for both chronic fatigue and irritable bowel syndromes: a prospective case-control study in primary care.

BACKGROUND: Fatigue syndromes and irritable bowel syndrome (IBS) often occur together. Explanations include being different manifestations of the same condition and simply sharing some symptoms. METHOD: A matched case-control study in UK primary care, using data collected prospectively in the General Practice Research Database (GPRD). The main outcome measures were: health-care utilization, specific symptoms and diagnoses. Risk markers were divided into distant (from 3 years to 1 year before diagnosis) and recent (1 year before diagnosis). RESULTS: A total of 4388 patients with any fatigue syndrome were matched to two groups of patients: those attending for IBS and those attending for another reason. Infections were specific risk markers for both syndromes, with viral infections being a risk marker for a fatigue syndrome [odds ratios (ORs) 2.3-6.3], with a higher risk closer to onset, and gastroenteritis a risk for IBS (OR 1.47, compared to a fatigue syndrome). Chronic fatigue syndrome (CFS) shared more distant risk markers with IBS than other fatigue syndromes, particularly other symptom-based disorders (OR 3.8) and depressive disorders (OR 2.3), but depressive disorders were a greater risk for CFS than IBS (OR 2.4). Viral infections were more of a recent risk marker for CFS compared to IBS (OR 2.8), with gastroenteritis a greater risk for IBS (OR 2.4). CONCLUSIONS: Both fatigue and irritable bowel syndromes share predisposing risk markers, but triggering risk markers differ. Fatigue syndromes are heterogeneous, with CFS sharing predisposing risks with IBS, suggesting a common predisposing pathophysiology.

Dyadic Adjustment in HPV-Infected Women One Year After Diagnosis.

Objective: This study examined the contribution of age, type of human papillomavirus (HPV), attachment, sexual satisfaction, and spirituality in dyadic adjustment in women with HPV from diagnosis to one year later. Method: This is a longitudinal study with three assessment moments: (T1) at the diagnosis appointment, (T2) six months after, and (T3) 12 months after the diagnosis. Participants answered a sociodemographic questionnaire as well as several other measures: HPV Knowledge Questionnaire (HPVQ), Papanicolaou Exam Knowledge Questionnaire (PEK-Q), Hospital Anxiety and Depression Scale (HADS), Courtauld Emotional Control Scale (CECS), Index of Sexual Satisfaction (ISS), Experiences in Close Relationship Scale-Short Form (ECR-S), Spiritual and Religious Attitudes in Dealing With Illness (SpREUK), and the Revised Dyadic Adjustment Scale (RDAS). Results: Age showed a positive impact on sexual dissatisfaction at T2. Sexual dissatisfaction at T1 predicted sexual dissatisfaction at T2 and dyadic adjustment at T3. Spirituality and insecure attachment at T1 negatively predicted insecure attachment at T2, and the latter predicted dyadic adjustment at T3. Conclusions: The results corroborate the need to assess the dyad when women are diagnosed with HPV. Only then it will be possible to design differentiated intervention programs that take into consideration women's age, attachment style, and sexual satisfaction. Interventions should also include women's partners to promote dyadic adjustment in this population.

The embodied relationality of blood-borne viruses: How families matter in the context of a stigmatised viral infection.

This paper argues that blood-borne viruses are relationally embodied, providing an alternative ontology to the individualising tendencies in medical science, and a more inclusive analysis of serodiscordance (mixed infection status) than the literature's focus on transmission risk in couples. We know little about the wider world of significant relationships in the lives of those with blood-borne viruses. People with HIV and hepatitis C are in a mixed-status relationship not just with intimate partners, but with other family members too. Drawing on qualitative interviews and phenomenological theory, we make the case that families (broadly defined) matter in the context of stigmatised, transmissible infections in ways that extend beyond individual bodies and beyond the usual preoccupation with risk. Despite recent advances in the treatment of blood-borne viruses, our study shows that these infections continue to be experienced and negotiated through embodied connections to significant others, made meaningful through culturally situated understandings and expectations regarding kinship, affinity, love, shared history and obligations. Our findings encourage broader recognition of these viral infections as intercorporeal phenomena, with families intimately entangled in co-creating the meanings and experiences of disease.

A model of human endogenous retrovirus (HERV) activation in mental health and illness.

Despite strong evidence for the heritability of major depressive disorder (MDD), efforts to identify causal genes have been disappointing. Furthermore, although there is strong support for life stress as a major predictor of MDD, there are also considerable individual differences in susceptibility and resilience that remain poorly understood. Efforts to identify specific gene-by-environment risk factors produced results that were initially encouraging, but that were not supported by later large-scale studies. Here I propose a novel mechanism that could address the "missing heritability" of MDD, the role of environmental risk factors, and individual differences in susceptibility and resilience. This mechanism focuses on a class of transposable elements, Human Endogenous Retroviruses (HERVs), which make up approximately 8% of the human genome as the result of ancient retroviral infections that entered mammalian germ lines throughout the course of evolution. My primary hypothesis is that exposure to either exogenous viruses or traumatic experiences can activate HERVs in the brain to cause depressive (and possibly other psychiatric) symptoms. My secondary hypothesis is that individual differences in vulnerability or resilience result from the balance of activated HERVs with pathogenic versus protective functions in the brain. Future research can test these hypotheses by analysis of postmortem human brain tissue from donors with known viral or trauma histories; animal studies manipulating HERV expression; cell culture studies examining regulatory mechanisms of HERV expression; and from brain imaging studies of individuals with known HERV-expression. Such research may reveal novel functions of HERVs in neural tissue and may lead to a new generation of psychiatric interventions designed to target aberrant HERV activation.