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.

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.

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.

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.

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.

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.

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.

Incomplete childhood vaccination and associated factors among children aged 12-23 months in Gondar city administration, Northwest, Ethiopia 2018.

OBJECTIVE: Despite the fact that immunization services are offered free of charge in Ethiopia but the coverage of complete vaccination is still low. The aim of the study is to determine incomplete vaccination and associated factors among children aged 12-23 months in Gondar city administration, Northwest Ethiopia, 2018. RESULT: The proportion of incomplete vaccination among children aged 12-23 months in Gondar city adminstration was 24.3% (95% CI 19.3, 29.2). Knowledge about the benefits of vaccination (AOR = 6.1 (95% CI 1.3, 28.9), the age at which the child begins vaccination (AOR = 2.4 (95% CI 1.09, 8.4) time taken to reach nearby health facility and means of transportation to nearby health facility (AOR = 0.22 95% CI 0.06, 0.9) have statistically significant association with incomplete vaccination. In the current study the proportion of incomplete vaccination was found to be high. Increasing the awareness about vaccination for child care givers and further improve caregiver's knowledge towards the benefit of vaccination is important.

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.

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.

Preliminary investigation of the STBBI Stigma Scale: Description and pilot results.

OBJECTIVES: Sexually transmitted and blood-borne infections (STBBIs) are associated with stigmatizing attitudes and beliefs, which can affect the quality of and access to health care, as well as mental health and quality of life. The current study describes the adaptation from an HIV-related stigma scale and pilot testing of a new STBBI Stigma Scale, assessing the stigmatizing attitudes and beliefs of health and social service providers in Canada. METHODS: 144 health and social service providers from across Canada completed the newly adapted scale assessing stigma associated with HIV, hepatitis C, other viral STBBIs and bacterial STBBIs, as well as demographic information, a scale of social desirability and measures of convergent and divergent validity. Participants were recruited through listservs and completed the scale online. RESULTS: The new scale, consisting of 21 items for each category, demonstrated excellent internal consistency, reliability, and convergent and divergent validity. The factor structure of the scale supports a tripartite model of stigma consisting of stereotyping, prejudice and discrimination. Stereotyping had the highest relative scores on the subscales, and attitudes regarding other viral STBBIs differed significantly from the other STBBI categories. CONCLUSION: The new scale provides a contextually relevant and applicable psychometrically valid tool to assess STBBI-related stigma among health and social service providers in Canada. The tool can be used to assess attitudes and beliefs, as well as guide self-assessment and possible trainings for providers.

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.

Vaccine hesitancy in Austria : A cross-sectional survey.

BACKGROUND: Vaccine hesitancy is an emerging phenomenon particularly in industrialized nations. It has led to repeated epidemic outbreaks of otherwise vaccine-preventable, infectious diseases. Compared to other countries very low rates of influenza and measles vaccination rates have been reported in Austria. METHODS: We performed a single-center cross-sectional, questionnaire-based survey. A total of 350 adult patients attending our emergency room participated in this survey. We assessed knowledge and attitudes towards vaccination and the associated infectious diseases. RESULTS: Out of 350 participants 40 (11.4 %) declared that they deliberately refused vaccinations. Most common reasons for non-vaccination were fear of adverse effects (35.9 %), doubt of effectiveness of vaccines (35.9 %) and distrust towards the pharmaceutical industry (23.1 %). Of all 350 participants only 148 (42.3 %) thought themselves to be sufficiently informed about national vaccination recommendations as stated in the Austrian National Vaccination Program (ANVP). General practitioners (GP) were the primary source of healthcare-related information for 256 (73.1 %) participants. Furthermore, GPs as well as hospital-based physicians achieved the highest level of trust in this study population. CONCLUSIONS: The results of our study underline the necessity of comprehensive informational campaigns on the merits of vaccination. A lack of knowledge about the benefits of vaccination, uncertainty and unfounded fears seem to prevent the achievement of recommended vaccination rates. Family GPs enjoyed the highest levels of trust in our study population. We believe that additional information communicated by GPs could help boost the low vaccination rates. This study underlines the important role of primary care practitioners in informing patients about vaccines and healthcare topics.

[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.

The Association between Infections and General Cognitive Ability in Young Men - A Nationwide Study.

BACKGROUND: Infections and activated immune responses can affect the brain through several pathways that might also affect cognition. However, no large-scale study has previously investigated the effect of infections on the general cognitive ability in the general population. METHODS: Danish nationwide registers were linked to establish a cohort of all 161,696 male conscripts during the years 2006-2012 who were tested for cognitive ability, which was based on logical, verbal, numerical and spatial reasoning at a mean age of 19.4 years. Test scores were converted to a mean of 100.00 and with a standard deviation (SD) of 15. Data were analyzed as a cohort study with severe infections requiring hospitalization as exposure using linear regression. RESULTS: Adjusted effect sizes were calculated with non-exposure to severe infections as reference, ranging from 0.12 SD to 0.63 SD on general cognitive ability. A prior infection was associated with significantly lower cognitive ability by a mean of 1.76 (95%CI: -1.92 to -1.61; corresponding to 0.12 SD). The cognitive ability was affected the most by the temporal proximity of the last infection (P<0.001) and by the severity of infection measured by days of admission (P<0.001). The number of infections were associated with decreased cognitive ability in a dose-response relationship, and highest mean differences were found for ≥10 hospital contacts for infections (Mean: -5.54; 95%CI: -7.20 to -3.89; corresponding to 0.37 SD), and for ≥5 different types of infections (Mean: -9.44; 95%CI: -13.2 to -5.69; corresponding to 0.63 SD). Hospital contacts with infections had occurred in 35% of the individuals prior to conscription. CONCLUSIONS: Independent of a wide range of possible confounders, significant associations between infections and cognitive ability were observed. Infections or related immune responses might directly affect the cognitive ability; however, associated heritable and environmental factors might also account for the lowered cognitive ability.

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.

Guns, germs, and stealing: exploring the link between infectious disease and crime.

Can variation in crime rates be traced to the threat of infectious disease? Pathogens pose an ongoing challenge to survival, leading humans to adapt defenses to manage this threat. In addition to the biological immune system, humans have psychological and behavioral responses designed to protect against disease. Under persistent disease threat, xenophobia increases and people constrict social interactions to known in-group members. Though these responses reduce disease transmission, they can generate favorable crime conditions in two ways. First, xenophobia reduces inhibitions against harming and exploiting out-group members. Second, segregation into in-group factions erodes people's concern for the welfare of their community and weakens the collective ability to prevent crime. The present study examined the effects of infection incidence on crime rates across the United States. Infection rates predicted violent and property crime more strongly than other crime covariates. Infections also predicted homicides against strangers but not family or acquaintances, supporting the hypothesis that in-group-out-group discrimination was responsible for the infections-crime link. Overall, the results add to evidence that disease threat shapes interpersonal behavior and structural characteristics of groups.