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.

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.

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.

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.

Predictors of fatigue following the onset of infectious mononucleosis.

BACKGROUND: Infectious mononucleosis (IM) is a risk factor for chronic fatigue. Reduced activity is the most consistent factor found to be associated with poor outcome following the onset of infectious mononucleosis. However, little is known about the biological mechanisms involved in the pathogenesis of chronic fatigue following IM and no study, so far, has examined the relation between certain illness beliefs and poor outcome. This study explored immunological, endocrine, behavioural and cognitive responses to the acute illness and assessed which components of these groups of risk factors predicted a chronic course. METHOD: Using a prospective cohort design, 71 primary care patients with IM were enrolled onto the study and interviewed. Their recovery was explored by postal questionnaire up to 1 year later. RESULTS: In the univariate analysis, increased baseline levels of immune activation were associated with fatigue at baseline and 3 months. Cortisol levels were not associated with fatigue at any point. Using multivariate models of clinical and psychosocial baseline factors, severity of symptoms and illness perceptions were found to predict fatigue 3 months later. At 6 months, fatigue was best predicted by female gender and illness perceptions, and at 12 months by female gender and a symptoms-disability factor. CONCLUSIONS: In the multivariate analysis no factors were found to predict poor outcome at all time-points. Instead the pattern of predictors changed over time, partly but not completely consistent with our a priori predictions. Larger studies are needed to explore further the predictive nature of biopsychosocial factors in the pathogenesis of chronic fatigue related to IM. The psycho-behavioural predictors found in this study are amenable to intervention. Such interventions should be tested in randomized controlled trials.

Predictions and associations of fatigue syndromes and mood disorders that occur after infectious mononucleosis.

BACKGROUND: Certain infections can trigger chronic fatigue syndromes (CFS) in a minority of people infected, but the reason is unknown. We describe some factors that predict or are associated with prolonged fatigue after infectious mononucleosis and contrast these factors with those that predicted mood disorders after the same infection. METHODS: We prospectively studied a cohort of 250 primary-care patients with infectious mononucleosis or ordinary upper-respiratory-tract infections until 6 months after clinical onset. We sought predictors of both acute and chronic fatigue syndromes and mood disorders from clinical, laboratory, and psychosocial measures. FINDINGS: An empirically defined fatigue syndrome 6 months after onset, which excluded comorbid psychiatric disorders, was most reliably predicted by a positive Monospot test at onset (odds ratio 2.1 [95% CI 1.4-3.3]) and lower physical fitness (0.35 [0.15-0.8]). Cervical lymphadenopathy and initial bed rest were associated with, or predicted, a fatigue syndrome up to 2 months after onset. By contrast, mood disorders were predicted by a premorbid psychiatric history (2.3 [1.4-3.9]), an emotional personality score (1.21 [1.11-1.35]), and social adversity (1.7 [1.0-2.9]). Definitions of CFS that included comorbid mood disorders were predicted by a mixture of those factors that predicted either the empirically defined fatigue syndrome or mood disorders. INTERPRETATION: The predictors of a prolonged fatigue syndrome after an infection differ with both definition and time, depending particularly on the presence or absence of comorbid mood disorders. The particular infection and its consequent immune reaction may have an early role, but physical deconditioning may also be important. By contrast, mood disorders are predicted by factors that predict mood disorders in general.

[Diagnosis and approaches to therapy of emotional disorders in patients with infectious diseases]. / Diagnostika i podkhody k terapii émotsional'nykh narushenii u bol'nykh s infektsionnoi patologiei.

AIM: To examine psychological and emotional disorders in patients with infectious diseases, to specify indications for their pharmacological correction. MATERIAL AND METHODS: Clinicopsychological, clinicofunctional and laboratory tests were made to examine 30 patients with infectious mononucleosis (19 females and 11 males) and 30 patients with serous meningitis (16 females and 14 males) aged 16-35 admitted to hospital on the disease day 2-14. RESULTS: Shmishek's questionnaire revealed various types of personality accentuations with dominating hyperthymic (30%) and cyclothymic (20%). According to the data of the clinical scale SCL-90, the greatest number of cases with values over normal was in patients with serous meningitis. Beck's questionnaire revealed clinical depression in 12 patients (40%) with acute serous meningitis, subdepression in 14(46.7%) patients, severe depression in 6(20%) patients with infectious mononucleosis. In convalescence, emotional disorders persisted in 4 patients with serous meningitis. CONCLUSION: Affective disorders in the above patients require consultation of the psychiatrist to decide on psychopharmacotherapy inclusion in combined treatment of infectious diseases to prevent lingering course.

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.

[Emotional disturbances in patients with infectious mononucleosis and serous meningitis]. / Emotsional'nye narusheniia u bol'nykh infektsionnym mononukleozom i seroznymi meningitami.

30 patients with infectious mononucleosis (19 females and 11 males) and 30 ones with serous meningitis (16 females and 14 males) aged 16-35 years admitted to hospital on the disease day 2-14 were examined clinicopsychologically, clinicofunctionally and using laboratory tests. The examination has revealed emotional disturbances in 40% of patients with serous meningitis and 20% of those with infectious mononucleosis. Clinical manifestations were characterized by polymorphism, combination of somatovegetative and anxiodepressive disorders. Personality accentuations in the patients are described.

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.

The relationship between fatigue, psychological and immunological variables in acute infectious illness.

OBJECTIVE: The aim of this paper is to explore the longitudinal relationships between physical and psychological symptoms and immunological factors following acute infective illnesses. METHOD: Preliminary data from a prospective investigation of patients with serologically proven acute infectious illnesses due to Epstein-Barr virus (EBV), Ross River virus (RRV) or Q fever are reported. Patients were assessed within 4 weeks of onset of symptoms and then reviewed 2 and 4 weeks later. Physical illness data were collected at interview. Psychological and somatic symptom profiles were assessed by standardised self-report questionnaires. Cell-mediated immune (CMI) function was assessed by measurement of delayed-type hypersensitivity (DTH) skin responses. RESULTS: Thirty patients who had been assessed and followed over the 4-week period (including 17 patients with EBV, five with RRV and eight with Q fever) were included in this analysis. During the acute phase, profound fatigue and malaise were the most common symptoms. Classical depressive and anxiety symptoms were not prominent. Initially, 46% of cases had no DTH skin response (i.e. cutaneous anergy) indicative of impaired cellular immunity. Over the 4-week period, there was a marked improvement in both somatic and psychological symptoms, although fatigue remained a prominent feature in 63% of subjects. The reduction in reported fatigue was correlated with improvement in the DTH skin response (p = 0.001) and with improvement in General Health Questionnaire (GHQ) scores (p < 0.01). CONCLUSIONS: Acute infectious illnesses are accompanied by a range of nonspecific somatic and psychological symptoms, particularly fatigue and malaise rather than anxiety and depression. Although improvement in several symptoms occurs rapidly, fatigue commonly remains a prominent complaint at 4 weeks. Resolution of fatigue is associated with improvement in cell-mediated immunity.

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.

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.

Behavioural effects of infectious mononucleosis.

The aim of the present study was to provide preliminary information on the acute and chronic effects of infectious mononucleosis (IM) on memory, attention, psychomotor performance and mood. These issues were examined by comparing individuals with acute IM, those who had the initial illness some months before, and matched healthy controls. Objective measures of memory, attention, motor skills and visual functions were obtained, as were subjective reports of mood. The results showed selective effects of acute IM on performance and mood, with the profile of impairments being very similar to those observed in previous studies of influenza. Different impairments were observed in subjects who had the primary illness several months before, and the effects observed in this group were similar to those observed in recent studies of chronic fatigue syndrome patients. Both acute and chronic IM subjects reported similar levels of symptoms and psychopathology, with both groups having greater scores than the controls. However, the performance impairments did not reflect symptoms or psychopathology. One may conclude that the study of IM will provide important data on both the acute and longer lasting effects of viral infections on the brain and behaviour.