Harm as a Necessary Component of the Concept of Medical Disorder: Reply to Muckler and Taylor.

Wakefield's harmful dysfunction analysis asserts that the concept of medical disorder includes a naturalistic component of dysfunction (failure of biologically designed functioning) and a value (harm) component, both of which are required for disorder attributions. Muckler and Taylor, defending a purely naturalist, value-free understanding of disorder, argue that harm is not necessary for disorder. They provide three examples of dysfunctions that, they claim, are considered disorders but are entirely harmless: mild mononucleosis, cowpox that prevents smallpox, and minor perceptual deficits. They also reject the proposal that dysfunctions need only be typically harmful to qualify as disorders. We argue that the proposed counterexamples are, in fact, considered harmful; thus, they fail to disconfirm the harm requirement: incapacity for exertion is inherently harmful, whether or not exertion occurs, cowpox is directly harmful irrespective of indirect benefits, and colorblindness and anosmia are considered harmful by those who consider them disorders. We also defend the typicality qualifier as viably addressing some apparently harmless disorders and argue that a dysfunction's harmfulness is best understood in dispositional terms.

High trait shame undermines the protective effects of prevalence knowledge on state shame following HPV/CIN diagnosis in women.

Human papillomavirus (HPV), and the related, cervical intraepithelial neoplasia (CIN), are common yet poorly understood physical conditions. The diagnosis of HPV often elicits shame and guilt, which in turn may undermine psychological and physical health. The current study compared shame and guilt responses to diagnosis among two groups: women diagnosed with HPV/CIN and women diagnosed with Epstein-Barr Virus (EBV/IM). Eighty women recently diagnosed with HPV/CIN or EBV/IM completed measures of shame- and guilt-proneness, shame and guilt following diagnosis, and disease knowledge including prevalence estimates (HPV and EBV, respectively). HPV/CIN (vs. EBV/IM) predicted more diagnosis-related shame and guilt. Estimates of high prevalence interacted with diagnosis and shame-proneness to predict diagnosis-related shame. Simple slope analyses indicated that in women with HPV/CIN reporting low-to-average shame-proneness, high prevalence estimates reduced diagnosis-related shame; however, women high in shame-proneness experienced high diagnosis-related shame regardless of more accurate prevalence estimates. Women high in shame-proneness appear to be particularly vulnerable to HPV-related shame even when they are aware that it is very common.

IFN-gamma mediated pathways in patients with fatigue and chronic active Epstein Barr virus-infection.

BACKGROUND: Chronic active Epstein Barr virus (EBV)-infection is characterized by mononucleosis like symptoms including fatigue, lymphadenopathy and/or hepatosplenomegaly and serologic evidence for ongoing EBV replication. Interferon-gamma (IFN-gamma) triggers several antiviral mechanisms in target cells including the induction of indoleamine-2,3-dioxygenase (IDO), which degrades the essential amino acid tryptophan to kynurenine. Because tryptophan is a precursor of the neurotransmitter 5-hydroxytryptamine (serotonin), tryptophan depletion by IDO can cause mood disturbances in patients with chronic immune activation. METHODS: This study investigated the tryptophan metabolism in 20 patients with chronic active EBV-infection, who were followed up for 4 to 8 months and in 10 healthy age-matched controls. The clinical suspicion of chronic active EBV infection was verified by the presence of circulating antibodies against EBV early antigen (EA) and virus capsid antigen (VCA). RESULTS: Patients with detectable EBV-DNA had higher serum neopterin (p<0.01) and lower tryptophan concentrations (p=0.01) than EBV-DNA negative patients. Serum concentrations of neopterin, indicating Th-1 mediated immune activation via IFN-gamma, were positively correlated to enhanced tryptophan degradation (rs=0.650, p<0.001) in patients, but not in healthy individuals. Patients suffering from more severe symptoms (as assessed by questionnaires) tended to have aggravated tryptophan degradation. CONCLUSION: Our data show that EBV viremia is associated with cell-mediated immune activation and increased tryptophan degradation, which may partly account for the symptoms found in this disorder.

Stereotypes, prejudice and discrimination of women with anorexia nervosa.

Limited research indicates that public attitudes toward individuals with eating disorders are moderately negative. The present study examined specific forms of stigmatisation attributed to individuals with anorexia nervosa (AN). Eighty female participants recruited from an undergraduate institution completed questionnaires assessing stereotypes, prejudice and discrimination of four target individuals: a woman with AN, depression, schizophrenia and mononucleosis. AN was considered to result more from lack of social support and biological factors than poor living habits. Characteristics attributed to targets were less positive for AN than the targets with schizophrenia and mononucleosis; participants reported greater discomfort interacting with the target with AN compared to the targets with depression and mononucleosis. Having actual contact with an individual with AN related to a positive predicted outcome of and comfort in interacting with the target with AN. Findings support the existence of stigma toward individuals with AN. Future research should examine means of reducing stigma.

Correlation of psycho-neuroendocrine-immune (PNI) gene expression with symptoms of acute infectious mononucleosis.

Acute infection is known to perturb psycho-neuroendocrine-immune (PNI) gene expression. Oligonucleotide microarrays were used to examine PNI gene expression in the peripheral blood of 13 subjects with infectious mononucleosis (IM). Novel peripheral blood gene expression activity was correlated with central-nervous-system-mediated symptoms including fatigue and sleep disturbance. Of note, expression of the MADS box transcription enhancer factor 2 polypeptide C (MEF2C) gene, previously implicated in skeletal muscle myogenesis, correlated with symptoms of musculo-skeletal pain and fatigue. Expression of the hypocretin/orexin receptor HCRTR2, which has been implicated in narcolepsy, correlated with sleep disturbance. And, VACHT, the vesicular acetylcholine transporter, was highly correlated with neurocognitive disturbance. The expression of both HCRTR2 and MEF2C in the peripheral blood was validated by reverse transcription PCR. Thus, investigation of the PNI response in peripheral blood may provide novel insights into the complex pathophysiology of centrally mediated disease states.

Psychiatric and neurologic sequelae of infectious mononucleosis.

Infectious mononucleosis is usually thought to be a benign disease with occasional neurologic sequelae. Depression, incoordination, a reduction in intellectual ability, and altered EEG patterns were found in two patients; one recovered and the other seemed to have permanent residual effects. The possibility of tranylcypromine as a treatment for the depression and appropriate counselling of patient and family are discussed.

Acute infectious mononucleosis: characteristics of patients who report failure to recover.

PURPOSE: We sought to determine how often acute mononucleosis precipitates chronic illness, and to describe the demographic, clinical, and psychosocial features that characterize patients who report failure to recover. SUBJECTS AND METHODS: We enrolled 150 patients with infectious mononucleosis during the acute illness and asked them to assess their recovery at 2 and 6 months. At baseline, we performed physical and laboratory examinations; obtained measures of psychological and somatic functioning, social support, and life events; and administered a structured psychiatric interview. RESULTS: Self-assessed failure to recover was reported by 38% of patients (55 of 144) at 2 months and by 12% (17 of 142) at 6 months. Those who had not recovered reported a persistent illness characterized by fatigue and poor functional status. No objective measures of disease, including physical examination findings or serologic or laboratory markers, distinguished patients who failed to recover from those who reported recovery. Baseline predictors for failure to recover at 2 months were older age (odds ratio [OR] = 1.4, 95% confidence interval [CI]: 1.1 to 1.8, per 5-year increase), higher temperature (OR = 1.5, 95% CI: 1.1 to 2.2, per 0.5 degrees C increase), and greater role limitation due to physical functioning (OR = 1.5, 95% CI: 1.2 to 1.9, per 20-point decrease in Short Form-36 score). At 6 months, baseline predictors for failure to recover included female sex (OR = 3.3, 95% CI: 1.0 to 12), a greater number of life events more than 6 months before the disease began (OR = 1.7, 95% CI: 1.1 to 2.5, per each additional life event), and greater family support (OR = 1.9, 95% CI: 1.1 to 4.2, per 7-point increase in social support score). CONCLUSIONS: We were not able to identify objective measures that characterized self-reported failure to recover from acute infectious mononucleosis. The baseline factors associated with self-reported failure to recover at 2 months differed from those associated with failure to recover at 6 months. Future studies should assess the generalizability of these findings and determine whether interventions can hasten recovery.

Plasma cortisol levels and reactivation of latent Epstein-Barr virus in response to examination stress.

In this study, we explored the possibility that glucocorticoid hormones, known to increase under stress, might be one component of the mechanism involved in induction of latent Epstein Barr virus (EBV). We obtained blood samples from 45 male medical students during examinations and approximately 3-4 weeks before the examinations (baseline) and measured antibody titers to EBV and plasma cortisol levels. We found reproducible changes in EBV, virus capsid antigen (VCA) antibody titers, with higher antibody titers observed in the examination blood samples consistent with the reactivation of latent virus. However, we found no evidence that day and night plasma cortisol values across the sampling points changed significantly from baseline to examinations. Therefore, academic stress did not elevate cortisol levels, but increases in EBV VCA antibody titers were still observed. The data suggest in these subjects that other neuropeptides or hormones were involved in the induction of latent EBV.

Case report: manic depressive psychosis following infectious mononucleosis.

The onset of manic depressive psychosis following infectious mononucleosis is reported. The patient appeared to be predisposed to develop such an illness, and it is postulated that the initial hypomanic episode may have been precipitated by an alteration in cerebral biogenic amines due to the infectious mononucleosis.

Psychiatric diagnoses in patients who have chronic fatigue syndrome.

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.

Acute psychosis in a patient with Epstein-Barr virus infection.

A case study is presented of an adolescent female who became psychotic and attempted suicide during an acute Epstein-Barr Virus infection. Resolution of the infection resulted in the patient returning to her previous normal mental status. The adolescent's ingestion of acetaminophen masked the signs and symptoms of infection and delayed proper diagnosis.

Defensiveness, trait anxiety, and Epstein-Barr viral capsid antigen antibody titers in healthy college students.

The relationship of individual differences in repressive coping styles with differences in antibody titer to Epstein-Barr viral capsid antigen (EBV-VCA) were investigated in a normal, healthy college population made up of people previously exposed to EBV. Each of 54 1st-year undergraduates completed a battery of physical-status questions and items pertaining to potential behavioral immunomodulatory confounds, along with the Taylor Manifest Anxiety Scale (T-MAS) and the Marlowe-Crowne Social Desirability Scale (MC-SDS). Ss reporting high and middle levels of anxiety had higher antibody titers to EBV, suggesting poorer immune control over the latent virus, as compared with the low-anxious group. Similarly, high-defensive Ss had higher antibody titers than their low-defensive counterparts, and neither group differed from the middle group.

Stress and the memory T-cell response to the Epstein-Barr virus in healthy medical students.

This study investigated the memory T-cell proliferative response to several early and late Epstein-Barr virus (EBV) polypeptides. Blood samples were collected twice, 1 month before a 3-day block of examinations and again on the last day of the exam series. Ss were 25 healthy, EBV seropositive medical students. The proliferative response to 5 of the 6 EBV polypeptides significantly decreased during examinations. In addition, Ss high (above the median) in seeking support, as measured by the COPE, had lower proliferative responses to 3 EBV polypeptides (p17, p52/50, and p85), as well as higher levels of antibody to EBV virus capsid antigen. The data provide further evidence that psychological stress can modulate the cellular immune response to latent EBV.

Illness representations and matching labels with symptoms.

Three studies are reported that show that health-relevant information (e.g., blood pressure [BP] or symptoms) initiates an active cognitive search process that results in the construction of an illness representation. Study 1 showed that informing subjects that their BP was elevated affected two attributes of illness representation: identity (label and symptoms), and time line or expected chronology of the health threat. Subjects given a high-BP reading reported symptoms commonly associated with high BP, especially if they attributed the high-BP reading to stress. Study 2 showed that the active search process uses causal information (a third attribute of representations) to give meaning to symptoms. Specifically, subjects used environmental cues to interpret whether familiar, unfamiliar, and ambiguous symptoms were due to illness or to stress. In Study 3 we showed that the constructive process, initiated by a high-BP reading, is directed by prior beliefs about the time line for developing high BP and by the presence of external cues about the stressfulness of the subject's daily life. Subjects who believed BP was labile and that they were under high daily stress or who believed BP was stable and that they were under low daily stress reported more symptoms. The significance of these findings for understanding how people process diagnostic labels and symptom information involved in the construction of illness representations is discussed.

Alice in Wonderland syndrome as an initial manifestation of Epstein-Barr virus infection.

We present a patient with serologically confirmed Epstein-Barr virus (EBV) infection who had illusions of size, shape, and colour of objects but none of the typical symptoms and signs peculiar to infectious mononucleosis (IM) except sore throat which developed 2 weeks after the initial visual disturbances. The bizarre feelings about the images of body and objects are called the 'Alice in Wonderland syndrome' due to the similarity with Alice's dreams. The same symptomatology including visual metamorphosia is defined in patients with migraine, epilepsy, intoxication due to hallucinogenic drugs, schizophrenia, hyperpyrexia, and cerebral lesions. Alice in Wonderland syndrome has also been reported in the course of IM.

A neuroimmune hypothesis for the aetiopathology of viral illness and manic depression: a case report of an adolescent.

This paper explores the unifying aetiopathology between disorders of the immune system and the CNS, using a case example. An adolescent had a 2-year history of chronic-active Epstein-Barr virus infection and recurrent acute pancreatitis that resolved following a course of immunotherapy. Subsequently, she redeveloped acute symptoms of infectious mononucleosis and pancreatitis, along with manic depression, and then made a complete recovery with combination of lithium carbonate and electroconvulsive therapy. On follow-up, lithium carbonate effectively controlled the previous neuroimmune dysfunction.

Infectious mononucleosis: psychological symptoms during acute and subacute phases of illness.

Although anecdotal reports suggest that anxiety and depressive disorders may be precipitated by acute infectious mononucleosis (AIM), there are few population-based studies measuring distress and psychiatric disorder during and after infection. The purpose of this research was to study the prevalence of psychiatric disorders and psychological distress in patients with AIM at initial infection and over the subsequent 6 months. In addition, we examined the correlation of baseline biopsychosocial factors with distress at 2 and 6 months postillness. A population-based cohort with AIM was surveyed at initial infection and at 2- and 6-month follow-up visits. Measures included physical and laboratory examinations, trait and state measures of psychological and somatic distress, locus of control, social support, and functioning. Patients also received a structured psychiatric interview during the initial infection. Although transient psychological distress was common during acute infection, few patients met criteria for DSM-III-R psychiatric illness. Greater distress at 2 months was associated with significantly lower social functioning in the month prior to diagnosis and higher aspartate aminotransferase (SGOT/AST) levels, less confidence in the physician and health care system (locus of control), and less severe physical symptoms of AIM at baseline. Greater distress at 6 months was associated with an increased number of adverse life events in the 6 months after developing AIM and more days of reduced activity in the 2 weeks prior to the onset of AIM. This population-based study suggests that few subjects develop DSM-III-R psychiatric disorders with AIM. Both biological and psychosocial factors are highly correlated with psychosocial distress at 2 months, whereas psychosocial factors are more important at 6-month follow-up.

Acute psychosis in a 45-year-old man with bipolar disorder and primary Epstein-Barr virus infection: a case report.

A 45-year-old physician with bipolar disorder presented with an acute organic psychosis, fever, and hematologic and serologic findings of a primary Epstein-Barr virus infection. Pathogenesis was complicated by the history of discontinued lithium therapy prior to the psychosis. The patient recovered completely. Literature concerning psychosis and infectious mononucleosis is reviewed.

Stress, adaptation, and immunity: studies in humans.

The notion that some combination of excessive "stress" and inadequate coping may increase susceptibility to illness has long been part of our conventional wisdom. Yet, until recently, there have been few data to support this contention. During the past decade, the relationship between stress, adaptation, and human immunity has come under closer scrutiny. There is now considerable evidence that certain types of experimental and naturally-occurring stress are associated with alterations of human cellular immune function. Furthermore, these observed changes generally are immunosuppressive. However, the mediating mechanisms underlying this relationship remain poorly understood. Critical factors in the stress-adaptation-immunity relationship are: the duration and proximity of the stressor, the adaptive capacity of the individual, and the differential effects of certain stressors on immunologic components.

Poor concentration and the ability to process information after glandular fever.

The symptom of poor concentration and the ability to process information were measured prospectively in 245 subjects three times in the 6 months after glandular fever or an ordinary upper respiratory tract infection. The effects of the different infections, having a fatigue state, a psychiatric disorder, sleep disturbance, and estimates of premorbid intelligence were also assessed. The most frequent complaint of poor concentration and the worst information processing occurred at the onset of the infection, but these problems decreased over time, and were not related to each other. Multiple regression modeling showed that higher socioeconomic class and vocabulary IQ were associated with information processing ability at all three interviews. In contrast, logistic regression modeling showed that the symptom of poor concentration was associated with the severity of general psychiatric morbidity (CIS score) followed by suffering from a fatigue state. These results suggest that the ability to process information after these particular infections is related to estimates of premorbid IQ, whereas poor concentration is related independently to both psychiatric morbidity and a fatigue state, but not the particular infection itself.