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Liability to substance use disorder (SUD) is largely nonspecific to particular drugs and is related to behavior dysregulation, including reduced cognitive control. Recent data suggest that cognitive mechanisms may be influenced by exposure to neurotropic infections, such as human herpesviruses. In this study, serological evidence of exposure to human herpesvirus Herpes simplex virus Type 1 (HSV-1), cytomegalovirus (CMV), and Epstein-Barr virus (EBV) as well as Toxoplasma gondii was determined in childhood (age ~11 years) in 395 sons and 174 daughters of fathers with or without SUD. Its relationships with a cognitive characteristic (IQ) in childhood and with risk for SUD in adulthood were examined using correlation, regression, survival, and path analyses. Exposure to HSV-1, EBV, and T. gondii in males and females, and CMV in males, was associated with lower IQ. Independent of that relationship, EBV in females and possibly in males, and CMV and possibly HSV-1 in females were associated with elevated risk for SUD. Therefore, childhood neurotropic infections may influence cognitive development and risk for behavior disorders such as SUD. The results may point to new avenues for alleviating cognitive impairment and SUD risk.

Introduction: Persisting neurotropic viruses are proposed to increase the risk of dementia, but evidence of association from robust, adequately powered population studies is lacking. This is essential to inform clinical trials of targeted preventive interventions., Methods and Analysis: We will carry out a comprehensive systematic review of published and grey literature of the association between infection with, reactivation of, vaccination against or treatment of any of the eight human herpesviruses and dementia or mild cognitive impairment. We will search the Cochrane Library, Embase, Global Health, Medline, PsycINFO, Scopus, Web of Science, clinical trials registers, the New York Academy of Medicine Grey Literature Report, Electronic Theses Online Service through the British Library and the ISI Conference Proceedings Citation Index for randomised controlled trials, cohort, caseâ€"control, case crossover or self-controlled case series studies reported in any language up to January 2017. Titles, abstracts and full-text screening will be conducted by two researchers independently. Data will be extracted systematically from eligible studies using a piloted template. We will assess risk of bias of individual studies in line with the Cochrane Collaboration tool. We will conduct a narrative synthesis, grouping studies by exposure and outcome definitions, and will describe any differences by population subgroups and dementia subtypes. We will consider performing meta-analyses if there are adequate numbers of sufficiently homogeneous studies. The overall quality of cumulative evidence will be assessed using selected Grading of Recommendations, Assessment, Development and Evaluations criteria., Ethics and Dissemination: As this is a review of existing studies, no ethical approval is required. Results will be disseminated through a peer-reviewed publication and at national and international conferences. We anticipate the review will clarify the current extent and quality of evidence for a link between herpesviruses and dementia, identify gaps and inform the direction of future research., Prospero Registration Number: CRD42017054684., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Prior research has suggested an association between exposure to infectious disease and neurocognitive function in humans. While most of these studies have explored individual viral, bacterial, and even parasitic sources of infection, few have considered the potential neurocognitive burden associated with multiple infections. In this study, we utilized publically available data from a large dataset produced by the Centers for Disease Control and Prevention that included measures of neurocognitive function, sociodemographic variables, and serum antibody data for several infectious diseases. Specifically, immunoglobulin G antibodies for toxocariasis, toxoplasmosis, hepatitis A, hepatitis B, and hepatitis C, cytomegalovirus, and herpes 1 and 2 were available in 5662 subjects. We calculated an overall index of infectious-disease burden to determine if an aggregate measure of exposure to infectious disease would be associated with neurocognitive function in adults aged 20-59 years. The index predicted processing speed and learning and memory but not reaction time after controlling for age, sex, race-ethnicity, immigration status, education, and the poverty-to-income ratio. Interactions between the infectious-disease index and some sociodemographic variables were also associated with neurocognitive function. In summary, an index aggregating exposure to several infectious diseases was associated with neurocognitive function in young- to middle-aged adults., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Murine gammaherpesvirus (MuGHV) is a natural pathogen of wild rodents that has been studied extensively in terms of host immune responses to herpesviruses during acute infection, latency, and reactivation from latency. Although herpesvirus infections in people can be associated with fatigue and excessive sleepiness during both acute and latent infection, MuGHV has not been assessed extensively as a model for studying the behavioral consequences of chronic latent herpesvirus infections. To assess MuGHV infection as a model for evaluating fatigue and assessing potential mechanisms that underlie the exacerbation of fatigue during chronic viral disease, we evaluated sleep, temperature, and activity after exposure of healthy and latently MuGHV-infected mice to sleep fragmentation and social interaction. Neither treatment nor infection significantly affected temperature. However, at some time points, latently infected mice that underwent sleep fragmentation had less locomotor activity and more slow-wave sleep than did mice exposed to social interaction. In addition, delta-wave amplitude during slow-wave sleep was lower in infected mice exposed to sleep fragmentation compared with uninfected mice exposed to the same treatment. Both reduced locomotor activity and increased time asleep could indicate fatigue in infected mice after sleep fragmentation; reduced delta-wave amplitude during slow-wave sleep indicates a light plane of sleep from which subjects would be aroused easily. Identifying the mechanisms that underlie sleep responses of mice with chronic latent MuGHV infection may increase our understanding of fatigue during infec- tions and eventually contribute to improving the quality of life for people with chronic viral infections.

Purpose: To evaluate the role of counseling for patients undergoing screening for type 2 herpes simplex virus (HSV-2). Using pre- and post-screening questionnaires, we evaluated correlations between demographic factors, measures of self-efficacy and follow-through with the screening test, and willingness to take antiviral medication and share results with sexual partners., Data Sources: Subjects (N= 115) were recruited as part of usual care at a private, urban family practice. A total of 111 subjects completed pre-screening questionnaires, and 38 completed post-screening questionnaires., Conclusions: The overwhelming majority of participants were (a) willing to undergo screening; (b) take suppressive antiviral medication if necessary; (c) share their results with sexual partners; and (d) consider safer sexual practices as a consequence of screening. Older patients were less willing to consider daily antiviral medication. Men who have sex with men (MSM) had lower perceived susceptibility to HSV-2 but were more likely to undergo and report screening., Implications for Practice: Future research should include predictive models for determining the most appropriate patients to screen for HSV-2 and best practices for those who test positive. Shared decision making between patients and advanced practice nurses regarding the risks and benefits of screening for HSV-2 should be a component visits that include sexually transmitted disease screening. Particular attention should be paid to those at higher risk for contracting the virus, including patients with HIV and MSM., (©2012 The Author(s) Journal compilation ©2012 American Academy of Nurse Practitioners.)

Objective: To assess the expectations and perceptions of Nigerian patients regarding infectious diseases in dentistry., Methods: A questionnaire based cross-sectional survey of patients attending the dental centre of University of Benin Teaching Hospital, Nigeria was conducted in 2009., Results: Out of the 405 patients that responded, 75.6% expressed worry about contracting infection during the dental treatment. Respondents felt that they are at risk of contracting the following infection from the dental clinic, HIV (47.4%), hepatitis B and C (15.5%), herpes (3.5%) and tuberculosis (1.7%). One-quarter (25.4%) of the respondents would avoid dental treatment because of fear of contracting HIV. Ninety-two (22.7%) would switch from dental clinic with HIV infected personnel and 37.8% would allow HIV-infected dentist to treat them. Only 10.4% of the respondents would expect the dentist to refuse to render dental treatment to the HIV-infected patients., Conclusion: This survey revealed that a high proportion of Nigerian patients are worried about contracting infectious disease during dental treatment and this impacted negatively on how they seek dental care. Improved public education and communication on the risk involved with dental treatments is needed to allay the fear of Nigerian patients.

Objective: The authors evaluated procedures for recruiting college students for sexually transmitted disease (STD) testing as part of a research study examining the impact of HSV serologic testing., Participants: A convenience sample of 100 students was drawn from students aged 18 to 35 years enrolled at one university in a mid- Atlantic state between September 2004 and March 2006., Methods: Six strategies were used to recruit students for participation in the study. Upon enrollment, participants were asked where they heard about the study. Students were also asked about their motivations for participation., Results: Findings show that a significant recruitment strategy involves targeting places where students seek health care. Other effective strategies include those where information is directly provided to individuals. Most students were motivated to participate because of a possible past exposure to herpes simplex virus 2., Conclusions: Targeting places where students seek health care and educating students about STDs are important strategies for recruiting students for STD testing.

Herpes simplex virus (HSV) is a common office problem and may be trivialized as "just a cold sore." HSV infections may cause great concern to the otherwise healthy patient due to psychosocial issues and may lead to morbidity and mortality in certain populations. This article discusses clinical presentation, diagnosis, and management of orolabial/genital herpes and presents answers to questions frequently posed to primary care providers and specialists.

Historically, clinicians have suspected that both major and minor stressful events can have health implications. Observations and case reports link severely stressful life events with a sudden onset or worsening of a variety of illnesses. The immune system was quickly implicated as a means to help explain how stressful life events could produce this relationship. The field of psychoneuroimmunology (PNI) is a field of research that deals with the complex interactions between the central nervous system, endocrine and immune systems, and how behavior/stress can modify these interactions. In this review, I have selected some of our papers that represent our efforts to study the effects of stress on the immune response and also include selected papers that describe how our PNI program at The Ohio State University Medical Center has evolved; virtually all of this research has been performed in collaboration with Janice Kiecolt-Glaser and others in our research group.

Numerous herpesvirus infections are associated with clinically relevant outcomes as well as an accelerated HIV replication rate and subsequent disease progression. Stress management interventions may improve markers of cellular immune control over latent herpesvirus infections and these changes appear to be mediated by perceptions of increased social support availability. We examined the effects of a group-based cognitive behavioral stress management (CBSM) intervention on distress, dysphoria, perceived social support, and herpesvirus immunoglobulin G (IgG) antibody titers during the 6 to 12 months following the intervention. Of those who were initially randomized, 49 HIV-infected men were followed during the 6- to 12-month period after randomization to either a 10-week CBSM intervention (n = 31) or a modified wait-list control condition (n = 18). Measures of distress, dysphoria, social support, and blood samples for herpesvirus IgG titers were taken at baseline, immediately following CBSM and at 6- to 12-month follow-up. Men in CBSM displayed maintenance of previously observed intervention effects on dysphoria, reliable alliance support, and herpesvirus IgG antibody titers (i.e., Epstein-Barr virus capsid antigen; EBV-VCA). Intervention-related changes in EBV-VCA were unrelated to changes in lymphocyte subsets (i.e., CD4+, CD8+, and CD4+:CD8+) or changes in measures of dysphoria and social support during the investigation period. Data indicate that HIV-infected men participating in a CBSM intervention maintain better psychosocial status and immunologic control of latent EBV infection up to 1 year after its conclusion.

Background: Herpes simplex encephalitis is one of the most common and serious sporadic encephalitides of immunocompetent adults. Herpes simplex virus 2 (HSV-2) infections of the central nervous system usually manifest as subacute encephalitis, recurrent meningitis, myelitis, and forms resembling psychiatric syndromes., Objectives: To report and discuss magnetic resonance imaging (MRI) findings and clinical features in atypical brainstem encephalitis and facial palsy associated with HSV-2., Setting: Neurology department of a tertiary referral center., Patient: A 37-year-old woman was admitted to the hospital with fever, diplopia, left hemiparesis, sensory change in the face and limbs, personality changes, frontal dysexecutive syndrome, and a stiff neck. Brain MRI showed multifocal high-signal intensities in the pons, midbrain, and frontal lobe white matter on T2-weighted and fluid-attenuated inversion recovery images. Cerebrospinal fluid (CSF) polymerase chain reaction (PCR) amplification analysis was positive for HSV-2. Acyclovir therapy was started, and the encephalitic symptoms disappeared with a negative conversion of HSV-2 PCR in the CSF. However, after the discontinuation of acyclovir therapy, peripheral facial palsy occurred on the left side. A possible relapse or delayed manifestation of the HSV-2 infection was suspected, and the acyclovir therapy was restarted. A complete remission was achieved 3 days after the treatment. She was discharged without any neurologic sequelae., Conclusions: We describe a patient who developed atypical encephalitis due to HSV-2 and peripheral facial palsy, which could also be related to the HSV-2. This case suggests that HSV-2 should be considered among the possible causes of atypical or brainstem encephalitis and that the PCR amplification method of the CSF can help reveal the possible cause of HSV-2.

Background: Numerous case reports and studies have suggested that psychological stress may have a role in the onset or exacerbation of a variety of skin diseases., Objective: We review the literature pertaining to the role of psychological stress in the exacerbation of psoriasis, urticaria, eczematous dermatitis, herpesvirus infections, and other skin diseases; discuss potential mechanisms of stress-induced skin disease; and review studies and case reports of psychotherapeutic interventions that have been found helpful in the therapy of skin diseases., Conclusions: There is evidence linking psychological stress to exacerbation of certain skin diseases. Both the clinical and the basic science evidence, however, can be hard to interpret in light of the difficulty of defining and quantifying psychological stress as well as the questions regarding the etiologic significance of neuroimmunologic findings in skin diseases.

Two patients with severe global amnesia are described who differ in the extent to which they have acquired new semantic information. Patient SS, who has extensive medial temporal lobe damage including the hippocampus as well as surrounding cortical areas, has failed to acquire virtually any new information regarding vocabulary or famous faces that entered the public domain since the onset of his amnesia. In contrast, patient PS, who has a selective lesion of the hippocampus proper, has gained a sense of familiarity of novel vocabulary and famous people, even though her effortful retrieval of this new semantic knowledge remains impaired. These findings extend to amnesia of adult onset, the proposal of Vargha-Khadem and colleagues that in patients with selective hippocampal injury, cortical areas surrounding the hippocampus may play an important role in new semantic learning [Vargha-Khadem, F., Gadian, D.G., Watkins, K. E., Connelly, A., Van Paesschen, W. and Mishkin, M., regarding the importance of the subhippocampal cortices in the mediation of new semantic learning in children with hippocampal lesions, Science, 1997, 277, 376-380].

In this study, we searched for evidence for reactivation of three latent herpesviruses, Epstein-Barr virus (EBV), herpes simplex virus type-1 (HSV-1), and human herpesvirus 6 (HHV-6), in West Point cadets experiencing two different stressors. Blood samples were obtained from cadets before and after a 6-week training period known as "Cadet Basic Training" (CBT), at a baseline prior to final examinations, and then once again during the week of final examinations. Antibody titers to latent HSV-1, EBV, and HHV-6 were determined as a measure of the steady-state expression of latent virus. EBV virus capsid antigen (VCA) IgG antibody titers were unchanged in blood samples obtained prior to and immediately after CBT. However, EBV antibody titers were significantly higher in the blood sample obtained during examination week than in the baseline period before examination; they were also higher than antibody titers before/after CBT. None of the serum samples were positive for EBV VCA IgM antibodies, indicating that the changes in antibody titers to EBV were not associated with recent EBV infections in the class. No significant changes in antibody titers to HSV-1 or HSV-6 were found over the identical time periods, including examination week. Academic stress but not CBT modulated the steady-state expression of latent EBV, resulting in the reactivation of latent virus. The same stressors, however, did not affect the steady-state expression of latent HSV-1 or HSV-6, at least as measured by changes in antibody titers. The data provide additional evidence of the impact of different psychological stressors on the steady-state expression of latent herpesviruses., (Copyright 1999 Academic Press.)

The role of the hippocampus in retrograde amnesia remains controversial and poorly understood. Two cases are reported of discrete bilateral hippocampal damage, one of which was a rare case of limbic encephalitis secondary to the human herpes virus 6. Detailed memory testing showed marked anterograde memory impairment, but only mild, temporally-limited retrograde amnesia that covered a period of several years in both autobiographical and factual knowledge domains. The absence of extensive retrograde amnesia in these two cases points to a time-limited role for the hippocampus in the retrieval of retrograde memories, and suggests that entorhinal, perirhinal, parahippocampal, or neocortical areas of the temporal lobe may be more critical than the hippocampus proper for long-term retrograde memory functioning. Our findings offer general support to theories of memory consolidation that propose a gradual transfer of memory from hippocampal to neocortical dependency.

We report the naming performances of a 25 year-old woman with a left internal and inferior temporal lesion caused by herpes encephalitis who showed a preferential impairment for naming man-made objects. Evidence for category-specific effect was provided by a stepwise logistic regression using 171 pictures characterized by several parameters (words frequency, diversity of responses, length, name agreement, majoritary response, familiarity, visual complexity and canonicity). Analyses were realized over a 5 month period. Methodological considerations, anatomic correlations and arguments suggesting lexical access or semantic storage disturbance are discussed.

The psychiatric manifestations of hematological diseases are interesting because of their diverse presentations, complex treatment, pharmacological interactions, and frequent infectious complications. A patient with acute myeloblastic leukemia (AML) presented psychiatric manifestations of sudden onset and psychotic characteristics. The absence of organic lesions in routine neuroimaging studies suggested an added schizophreniform disorder. Further neurological study using more sensitive methods disclosed herpetic encephalitis as the origin of delirium. This case illustrates how early diagnosis, although not always possible, is important if major sequelae are to be avoided. Likewise, it is important to make a through search for organic factors in psychotic pictures that appear in the context of systemic disease.

We tested the hypothesis that partial forms of retrograde amnesia were associated with highly asymmetric lesions to the inferior and anterior-medial temporal lobe. Postencephalitic subjects EK and DR were both impaired on standardized retrograde memory tests, but showed strikingly different profiles in cognitive tasks of name stem completion, name:face matching, temporal ordering, forced choice recognition, and occupational judgments of famous names and faces from the past 3 decades. EK sustained left inferior and anterior-medial temporal lobe lesion with a small right temporal polar lesion, and showed near-complete loss of retrieval, knowledge, and familiarity associated with famous names but minimal deficiencies with famous faces. DR sustained right inferior and anterior-medial temporal lobe lesion and showed a milder retrograde loss limited to utilizing famous face prompts in name stem completion, name:face matching, occupational judgments, and forced choice recognition. These impairments were also different from the memory retrieval deficit, but intact recognition shown by a case of ruptured anterior communicating artery aneurysm with presumed basal forebrain damage. We hypothesize that EK's extensive loss of famous name knowledge was related to left inferior temporal lobe damage, particularly in the lateral and medial occipitotemporal gyri. This region in the left temporal lobe may serve as a critical processing area for retrograde memory that permits activation of established semantic, temporal, and visual (i.e., facial) associations biographically dependent on the category of proper names. On the basis of connectional anatomy patterns in the nonhuman primate, this region receives extensive hippocampal output and is interconnected with the temporal polar region and cortical association areas, which have been implicated in retrieval and storage aspects of retrograde memory. In the right hemisphere, the occipitotemporal gyri may serve an important role in famous face processing as part of a bilateral neural network.

In this paper the cognitive and psychiatric impairments associated with chronic fatigue syndrome (CFS) and related disorders are reviewed. It is concluded that while acute mononucleosis and infection with Epstein-Barr virus occasionally result in impaired cognition, such changes have not yet been objectively verified in patients with CFS. However, when patients with CFS are carefully studied, concurrent or premorbid psychiatric disorders are revealed at a greater than chance level. Finally, some suggestions are offered regarding improved neuropsychological assessment of fatigue, concentration, and attention for patients with CFS. The findings to date, while suggesting that psychological predisposition may play a role in the expression of CFS, are still inconclusive regarding the etiology of CFS.

Clinical, serologic, virologic, and immunologic evaluations for 31 adults with chronic illness and fatigue suggested that 23 had persisting Epstein-Barr virus infection. Among these 23 patients, cellular immune mechanisms were generally normal, but 4 had mild immunoglobulin deficiencies. However, 20 patients had abnormal serologic profiles specific for Epstein-Barr virus shown by significantly elevated titers of antibodies to the viral capsid antigen or early antigen, or by a deficiency of late-appearing antibodies. In 11 of 15 patients tested, circulating immune complexes were found. Circulating interferon was not found in 18 patients tested, but the activity of 2-5 oligoadenylate synthetase, an interferon-induced enzyme, was increased in 5 patients studied. Of 19 patients, 18 had persisting suppressor T-cell activity typically found in patients recovering from acute infectious mononucleosis. We believe that the Epstein-Barr virus may be associated with chronic illness in adults.

EBV has both physiological and psychological implications. Few medical/nursing interventions are available to alleviate the physical stressors and fatigue. The primary nursing intervention, therefore, becomes one of providing emotional support and psychosocial interventions. Providing measures to ensure adequate sleep will assist the patient in more positive feelings about self. Although causation and diagnosis of this syndrome may be debated in the medical literature, the nursing role is to provide support and guidance for these patients. Longitudinal studies could be done to facilitate the understanding of the long-term effects of EBV and the outcome measures of mental health interventions.

Forty-four patients, including 26 adults and 18 children under 15 years of age, were referred for evaluation of recurrent or persistent illnesses, with symptoms including pharyngitis, lymphadenopathy, fever, headaches, arthralgia, fatigue, depression, dyslogia, and myalgia. Thirty-nine patients were positive for Epstein-Barr virus antibody with antibody levels compatible with active infection for at least 1 year. Antiviral capsid antigen and anti-early antigen titers of patients were significantly greater (p less than 0.001) than age-group-matched controls. The frequency, number, duration, and patterns of symptoms, as well as patient sex, were compared by age in study patients seropositive and seronegative for Epstein-Barr virus. Illness patterns were not associated with changes in specific antibody titers or clinical findings. Lymphocyte phenotype and function analyses were done in 11 of the 39 patients positive for Epstein-Barr virus antibody; no consistent differences from normal were found. Only 1 of 32 patients had circulating interferon, in contrast to 7 of 7 patients with acute infectious mononucleosis. There were many adverse consequences of the illness. Epstein-Barr virus infection may not be self-limiting, and the virus may be associated with clinically recognizable illness other than infectious mononucleosis in children as well as in adults.

Patients with persistent fatigue are often suspected of having psychiatric illnesses, particularly depression. The authors used the Diagnostic Interview Schedule to assess the lifetime prevalence of psychiatric disorders in 28 patients who met Centers for Disease Control case definition criteria for chronic fatigue syndrome. Compared with studies of the general population and studies of chronically medically ill patients who received the same structured interview, the rates of psychiatric illness in patients with the chronic fatigue syndrome appeared high. An examination of the medical histories of the 28 patients indicated that psychiatric disorders more often preceded the chronic fatigue than followed it.

This study used a prospective design to examine the influence of examination stress and loneliness on herpesvirus latency as measured by changes in antibody levels to three herpesviruses, Epstein-Barr virus (EBV), Herpes simplex type I (HSV-1), and cytomegalovirus (CMV). Three blood samples were obtained from 49 first-year medical students, with the first sample drawn 1 month before final examinations, the second on the first day of final examinations, and the third during the first week after their return from summer vacation. A median split on the UCLA Loneliness Scale divided subjects into high- and low-scoring loneliness groups. There were significant changes in the antibody titers to all three herpesviruses across the sample points, with the lowest levels found in the third (low stress) sample. High-loneliness subjects had significantly higher EBV antibody titers than low-loneliness subjects. These data suggest that stress-related immunosuppression can significantly modulate herpesvirus latency.