Tracey A. Davenport

Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study.

Abstract Objective To delineate the risk factors, symptom patterns, and longitudinal course of prolonged illnesses after a variety of acute infections. Design Prospective cohort study following patients from the time of acute infection with Epstein-Barr virus (glandular fever), Coxiella burnetii (Q fever), or Ross River virus (epidemic polyarthritis). Setting The region surrounding the township of Dubbo in rural Australia, encompassing a 200 km geographical radius and 104 400 residents. Participants 253 patients enrolled and followed at regular intervals over 12 months by self report, structured interview, and clinical assessment. Outcome measures Detailed medical, psychiatric, and laboratory evaluations at six months to apply diagnostic criteria for chronic fatigue syndrome. Premorbid and intercurrent illness characteristics recorded to define risk factors for chronic fatigue syndrome. Self reported illness phenotypes compared between infective groups. Results Prolonged illness characterised by disabling fatigue, musculoskeletal pain, neurocognitive difficulties, and mood disturbance was evident in 29 (12%) of 253 participants at six months, of whom 28 (11%) met the diagnostic criteria for chronic fatigue syndrome. This post-infective fatigue syndrome phenotype was stereotyped and occurred at a similar incidence after each infection. The syndrome was predicted largely by the severity of the acute illness rather than by demographic, psychological, or microbiological factors. Conclusions A relatively uniform post-infective fatigue syndrome persists in a significant minority of patients for six months or more after clinical infection with several different viral and non-viral micro-organisms. Post-infective fatigue syndrome is a valid illness model for investigating one pathophysiological pathway to chronic fatigue syndrome.

Young men's attitudes and behaviour in relation to mental health and technology: Implications for the development of online mental health services

BackgroundThis mixed-methods study was designed to explore young Australian men’s attitudes and behaviour in relation to mental health and technology use to inform the development of online mental health services for young men.MethodsNational online survey of 486 males (aged 16 to 24) and 17 focus groups involving 118 males (aged 16 to 24).ResultsYoung men are heavy users of technology, particularly when it comes to entertainment and connecting with friends, but they are also using technology for finding information and support. The focus group data suggested that young men would be less likely to seek professional help for themselves, citing a preference for self-help and action-oriented strategies instead. Most survey participants reported that they have sought help for a problem online and were satisfied with the help they received. Focus group participants identified potential strategies for how technology could be used to overcome the barriers to help-seeking for young men.ConclusionsThe key challenge for online mental health services is to design interventions specifically for young men that are action-based, focus on shifting behaviour and stigma, and are not simply about increasing mental health knowledge. Furthermore, such interventions should be user-driven, informed by young men’s views and everyday technology practices, and leverage the influence of peers.

Production of pro-inflammatory cytokines correlates with the symptoms of acute sickness behaviour in humans.

BACKGROUND Elaboration of the concept of cytokine-induced sickness behaviour in recent years has opened new avenues for understanding brain involvement in sickness and recovery processes. Additionally, this has led to much speculation about the role of the immune system in neuropsychiatric syndromes, including depression and chronic fatigue. However, few studies have examined this phenomenon as it naturally occurs in sick humans, and none has attempted to document the quantitative relationships between cytokine levels and non-specific symptoms. The aim of this research was to examine human sickness behaviour and its immunological correlates in documented Epstein-Barr virus (EBV), Q fever or Ross River virus (RRV) infections. METHOD We studied two separate samples. The first consisted of 21 patients with acute Q fever. The second included 48 patients with acute RRV or EBV infection. Psychological and somatic symptom profiles were derived from self-report measures completed at enrolment. Quantification of proinflammatory cytokines [interleukin (IL)-1beta and IL-6] in sera and supernatants of peripheral blood mononuclear cell (PBMC) cultures was undertaken by specific ELISAs. RESULTS Levels of IL-1beta and IL-6 spontaneously released from PBMC cultures were consistently correlated with reported manifestations of acute sickness behaviour including fever, malaise, pain, fatigue, mood and poor concentration. CONCLUSIONS IL-1beta and IL-6 produced as part of the host response represent sensitive markers of sickness behaviour in humans with acute infection. Further work is needed to systematically characterize the spectrum and natural history of sickness behaviour in humans and to elucidate its biological basis.

The effect of oxytocin nasal spray on social interaction deficits observed in young children with autism: a randomized clinical crossover trial

Interventions for autism are limited. The synthetic hormone oxytocin may provide a potential treatment to improve core social and behavioral difficulties in autism, but its efficacy has yet to be evaluated in young children who potentially may benefit to a greater extent. We investigated the efficacy, tolerability and safety of oxytocin treatment in young children with autism using a double-blind, randomized, placebo-controlled, crossover, clinical trial. Thirty-one children with autism received 12 International Units (IU) of oxytocin and placebo nasal spray morning and night (24 IU per day) for 5 weeks, with a 4-week washout period between each treatment. Compared with placebo, oxytocin led to significant improvements on the primary outcome of caregiver-rated social responsiveness. Overall, nasal spray was well tolerated, and the most common reported adverse events were thirst, urination and constipation. This study is the first clinical trial to support the potential of oxytocin as an early intervention for young children with autism to help improve social interaction deficits.

Fatigue states after cancer treatment occur both in association with, and independent of, mood disorder: a longitudinal study

BackgroundPersistent fatigue is recognised as one of the most common, ongoing symptoms reported by patients following cancer treatment and may have profound effects on the quality of life. However, recent cross-sectional studies also highlight the close relationship between cancer related fatigue (CRF) and diagnoses of depression or anxiety disorder. There is currently limited information about the relationships between these conditions over time. We sought to examine the longitudinal relationships between fatigue and mood disorder in women treated with adjuvant therapy for early stage breast cancer.MethodsWomen who had recently completed adjuvant therapy for Stage I or II breast cancer (n = 212) were sent a questionnaire with established case thresholds for clinically-significant fatigue and psychological disorder, as well as a questionnaire assessing disability. Potentially relevant variables linked to fatigue states, including age, treatment modality, menopausal status, and hematological indices were recorded. The illness outcomes were assessed over 48 months of follow-up.ResultsThe 176 women who responded to the questionnaire (84%) had a mean age of 55 (range 24–83) years and had completed adjuvant treatment on average 10 (range 4.7 – 16.3) months previously. Radiotherapy had been administered, either alone (50% of women) or in combination with chemotherapy (36%). Responses from 87 women (48%) indicated a significant fatigue state (termed here post-cancer fatigue; PCF), and from 59 women (33%) responses indicated significant psychological distress. Thirty-four women (19%) were cases of fatigue alone (i.e. unaccompanied by psychological disorder), whereas 52 (30%) were cases of both disorders. Multivariate analysis did not reveal any association between demographic, clinical or laboratory variables, and caseness for PCF. Self-reported functional disability was significantly associated with fatigue. Follow-up at 24, 36 and 48 months revealed high rates of ongoing PCF in conjunction with psychological distress, despite falling rates of psychological distress alone and fatigue alone.ConclusionPost-cancer fatigue was prevalent and sustained on follow-up. Concurrent psychological disorder was evident in the majority, but not all, cases of PCF and tended to be sustained over time. Further prospective cohort studies to define the longitudinal co-morbid relationships between fatigue, mood disorder, and ongoing disability after cancer treatment are indicated.

Sphere: A National Depression Project: Common Psychiatric Disorders Remain Untreated

Although 18% of Australians suffered a psychiatric disorder in the last 12 months, only 38% presented to health services. Of these, the vast majority (76%) consulted their general practitioner [1]. While two-thirds of those who present to primary care have significant psychological symptoms, at least 30% have psychological disorders that result in disability, long-term morbidity and/or mortality [2–4]. These disorders are often co-morbid with other medical disorders and/or substance abuse [1]. Despite the advances in pharmacological and non-pharmacological therapies available [5,6] less than half of the patients who present receive a psychiatric diagnosis and less than half of these receive any specific treatment [7]. Recommendations under the National Mental Health Strategy [8] recognise the urgent need for educational programs and practice support mechanisms to correct these major public health deficits.

Applying clinical staging to young people who present for mental health care

Aim: The study aims to apply clinical staging to young people who present for mental health care; to describe the demographic features, patterns of psychological symptoms, disability correlates and clinical stages of those young people; and to report longitudinal estimates of progression from less to more severe stages.

Screening for prolonged fatigue syndromes: validation of the SOFA scale

Abstract  Background: The identification of syndromes characterised by persistent and disabling mental and/or physical fatigue is of renewed interest in psychiatric epidemiology. This report details the development of two specific instruments: the SOFA/CFS for identification of patients with chronic fatigue syndrome (CFS) in specialist clinics and the SOFA/GP for identification of prolonged fatigue syndromes (PFS) in community and primary care settings. Methods: Patients with clinical diagnoses of CFS (n = 770) and consecutive attenders at primary care (n = 1593) completed various self-report questionnaires to assess severity of current fatigue-related symptoms and other common somatic and psychological symptoms. Quality receiver operating characteristic curves were used to derive appropriate cut-off scores for each of the instruments. Comparisons with other self-report measures of anxiety, depression and somatic distress are noted. Various multivariate statistical modelling techniques [latent class analysis (LCA), longitudinal LCA] were utilised to define the key features of PFS and describe its longitudinal characteristics. Results: The SOFA/CFS instrument performs well in specialist samples likely to contain a high proportion of patients with CFS disorders. Cut-off scores of either 1/2 or 2/3 can be used, depending on whether the investigators wish to preferentially emphasise false-negatives or false-positives. Patients from these settings can be thought of as consisting not only of those with a large number of unexplained medical symptoms, but also those with rather specific musculoskeletal and pain syndromes. The SOFA/GP instrument has potential cut-off scores of 1/2 or 2/3, with the latter preferred as it actively excludes all non-PFS cases (sensitivity = 81%, specificity = 100%). Patients with these syndromes in the community represent broader sets of underlying classes, with the emergence of not only musculoskeletal and multisymptomatic disorders, but also persons characterised by significant cognitive subjective impairment. Twelve-month longitudinal analyses of the primary care sample indicated that the underlying class structure was preserved over time. Comparisons with other measures of psychopathology indicated the relative independence of these constructs from conventional notions of anxiety and depression. Conclusions: The SOFA/GP instrument (which is considerably modified from the SOFA/CFS in terms of anchor points for severity and chronicity) is preferred for screening in primary care and community settings. Patients with PFS and CFS present a range of psychopathology that differs in its underlying structure, cross-sectionally and longitudinally, from coventional notions of anxiety and depression.

Positive relationships between public awareness activity and recognition of the impacts of depression in Australia

OBJECTIVE This report records the level of exposure to depression-related information across the Australian community and explores associations with recognition of depression and relevant sociodemographic factors. METHOD A cross-sectional telephone survey was conducted with a representative community sample. Participants consisted of 3200 respondents (400 respondents across each Australian State/Territory). RESULTS Sixty-five point four per cent (n=2089/3193) of respondents indicated that they or someone close to them had experienced depression, of whom 18.7% (n=391/2089) reported a personal experience of this illness. Various measures of recent exposure to depression-related information were high with 69.0% (n=2207/3200) reporting that they had seen, read or heard something in the media in the last 12 months. Recognition of beyondblue: the national depression initiative was also surprisingly high (61.9%, 1982/3200). Those with greater understanding that depression is common and debilitating were more likely to recall recent media stories, spontaneously recall relevant organizations such as beyondblue, to have had direct or family experiences, to be younger and to have achieved higher levels of education. Depression, however, is rarely mentioned (1.3%, 47/3720) as a major general health as distinct from a mental health problem. CONCLUSION The active promotion of depression-related material to the community appears to have contributed to recognition of the commonality and impacts of this illness. Although depression is commonly recognized as a mental health problem, it is not yet considered a major general health problem. Further, like many public health campaigns, those initially reached appear more likely to be female, younger, better educated and residing in metropolitan areas.

Cytokine Polymorphisms Have a Synergistic Effect on Severity of the Acute Sickness Response to Infection

BACKGROUND Functional polymorphisms in immune response genes are increasingly recognized as important contributors to the marked individual differences in susceptibility to and outcomes of infectious disease. The acute sickness response is a stereotypical set of illness manifestations mediated by the proinflammatory cytokines induced by many different pathogens. The genetic determinants of severity of the acute sickness response have not previously been explored. METHODS We examined the impact of functional polymorphisms in cytokine genes with critical roles in the early immune response (tumor necrosis factor-alpha, interleukin-6, interleukin-10, and interferon-gamma) on the severity and duration of illness following acute infection with Epstein-Barr virus, Coxiella burnetii (the causative agent of Q fever), or Ross River virus. RESULTS We found that the interferon-gamma +874T/A and the interleukin-10 -592C/A polymorphisms significantly affected illness severity, cytokine protein levels, and the duration of illness. These cytokine genotypes acted in synergy to potentiate their influence on disease outcomes. CONCLUSIONS These findings suggest that genetically determined variations in the intensity of the inflammatory response underpin the severity of the acute sickness response and predict the recovery time across varied infections.