Tag: Hickie

Predictors of Chronic Fatigue Syndrome and Mood Disturbance After Acute Infection

Abstract:

Prospective cohort studies following individuals from acute infections have documented a prevalent post-infective fatigue state meeting diagnostic criteria for chronic fatigue syndrome (CFS) – that is, a post-infective fatigue syndrome (PIFS). The Dubbo Infection Outcomes Study (DIOS) was a prospective cohort following individuals from acute infection with Epstein-Barr virus (EBV), Ross River virus (RRV), or Q fever through to assessment of caseness for CFS designated by physician and psychiatrist assessments at 6 months. Previous studies in DIOS have revealed that functional genetic polymorphisms in both immunological (pro- and anti-inflammatory cytokines) and neurological (the purinergic receptor, P2X7) genes are associated with both the severity of the acute infection and subsequent prolonged illness.

Principal components analysis was applied to self-report data from DIOS to describe the severity and course of both the overall illness and concurrent mood disturbance. Associations between demographics and acute infection characteristics, with prolonged illness course as well as the PIFS outcome were examined using multivariable statistics. Genetic haplotype-driven functional variations in the neuropeptide Y (NPY) gene previously shown to be associated with brain responses to stress, and to trait anxiety were also examined as predictors.

The sample included 484 subjects (51% female, median age 32, IQR 19-44), of whom 90 (19%) met diagnostic criteria for CFS at 6 months. Participants with greater overall illness severity and concurrent mood disturbance in the acute illness had a more prolonged illness severity (HR = 0.39, 95% CI: 0.34-0.46, p < 0.001) and mood disturbance (HR = 0.36, 95% CI: 0.30-0.42, p < 0.001), respectively. Baseline illness severity and RRV infection were associated with delayed recovery.

Female gender and mood disturbance in the acute illness were associated with prolonged mood disturbance. Logistic regression showed that the odds of an individual being diagnosed with PIFS increased with greater baseline illness severity (OR = 2.24, 95% CI: 1.71-2.94, p < 0.001). There was no association between the NPY haplotypes with overall illness severity or mood disturbance either during the acute illness phase or with prolonged illness (p > 0.05). Severe acute infective illnesses predicted prolonged illness, prolonged mood disturbance and PIFS. These factors may facilitate early intervention to manage both PIFS and mood disturbances.

Source: Sandler CX, Cvejic E, Valencia BM, Li H, Hickie IB, Lloyd AR. Predictors of Chronic Fatigue Syndrome and Mood Disturbance After Acute Infection. Front Neurol. 2022 Jul 25;13:935442. doi: 10.3389/fneur.2022.935442. PMID: 35959390; PMCID: PMC9359311. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9359311/ (Full text)

Characterization of fatigue states in medicine and psychiatry by structured interview

Abstract:

CONTEXT: Unexplained fatigue states are prevalent, with uncertain diagnostic boundaries.

OBJECTIVE: Patients with fatigue-related illnesses were investigated by questionnaire and a novel semistructured interview to identify discriminatory features.

METHODS: Cross-sectional samples of women from specialist practices with chronic fatigue syndrome (n = 20), postcancer fatigue (PCF; n = 20), or major depression (n = 16) were recruited. Additionally, two longitudinal samples were studied: women with fatigue associated with acute infection who subsequently developed postinfective fatigue syndrome (n = 20) or recovered uneventfully (n = 21), and women undergoing adjuvant therapy for breast cancer experiencing treatment-related fatigue who subsequently developed PCF (n = 16) or recovered uneventfully (n = 16). Patients completed self-report questionnaires, and trained interviewers applied the Semi-structured Clinical Interview for Neurasthenia. The receiver operating characteristics curves of the interview were measured against clinician-designated diagnoses. Cluster analyses were performed to empirically partition participants by symptom characteristics.

RESULTS: The interview had good internal consistency (Cronbach alpha “fatigue” = .83), and diagnostic sensitivity and specificity for chronic fatigue syndrome (100% and 83%) and major depression (100% and 72%), with reasonable parameters for PCF (72% and 58%). Empirical clustering by “fatigue” or “neurocognitive difficulties” items allocated most patients to one group, whereas “mood disturbance” items correctly classified patients with depression only.

CONCLUSIONS: The Semi-structured Clinical Interview for Neurasthenia offers reliable diagnostic use in assessing fatigue-related conditions. The symptom domains of fatigue and neurocognitive difficulties are shared across medical and psychiatric boundaries, whereas symptoms of depression such as anhedonia are distinguishing.

 

Source: Bennett BK, Goldstein D, Chen M, Davenport TA, Vollmer-Conna U, Scott EM, Hickie IB, Lloyd AR. Characterization of fatigue states in medicine and psychiatry by structured interview. Psychosom Med. 2014 Jun;76(5):379-88. https://www.ncbi.nlm.nih.gov/pubmed/25076512

 

Are chronic fatigue and chronic fatigue syndrome valid clinical entities across countries and health-care settings?

Abstract:

OBJECTIVE: The validity of the diagnosis of chronic fatigue syndrome and related chronic fatigue states remains controversial, particularly in psychiatry. This project utilized international epidemiological and clinical research data to test construct validity across diagnostic categories, health-care settings and countries. Relevant demographic, symptom and diagnostic data were obtained from 33 studies in 21 countries. The subjects had fatigue lasting 1-6 months (prolonged fatigue), or >6 months (chronic fatigue), or met diagnostic criteria for chronic fatigue syndrome.

METHOD: Common symptom domains were derived by factor analytic techniques. Mean scores on each symptom factor were compared across diagnostic categories, health-care settings and countries.

RESULTS: Data were obtained on 37,724 subjects (n = 20,845 female, 57%), including from population-based studies (n = 15,749, 42%), studies in primary care (n = 19 472, 52%), and secondary or specialist tertiary referral clinics (n = 2503, 7%). The sample included 2013 subjects with chronic fatigue, and 1958 with chronic fatigue syndrome. A five-factor model of the key symptom domains was preferred (‘musculoskeletal pain/fatigue’, ‘neurocognitive difficulties’, ‘inflammation’, ‘sleep disturbance/fatigue’ and ‘mood disturbance’) and was comparable across subject groups and settings. Although the core symptom profiles were similar, some differences in symptoms were observed across diagnostic categories, health-care settings and between countries.

CONCLUSIONS: The construct validity of chronic fatigue and chronic fatigue syndrome is supported by an empirically derived factor structure from existing international datasets.

 

 

Source: Hickie I, Davenport T, Vernon SD, Nisenbaum R, Reeves WC, Hadzi-Pavlovic D, Lloyd A; International Chronic Fatigue Syndrome Study Group. Collaborators (28) Are chronic fatigue and chronic fatigue syndrome valid clinical entities across countries and health-care settings? Aust N Z J Psychiatry. 2009 Jan;43(1):25-35. Doi: 10.1080/00048670802534432. https://www.ncbi.nlm.nih.gov/pubmed/19085525

 

The experience of cancer-related fatigue and chronic fatigue syndrome: a qualitative and comparative study

Abstract:

Cancer-related fatigue (CRF) is a common and disabling symptom complex reported by survivors. This study aimed to better understand the manifestations of CRF in women treated for breast cancer, and to compare them with those of women diagnosed with chronic fatigue syndrome (CFS).

Women with CRF persisting 6 months after treatment for early stage breast cancer, and women with CFS participated in separate, audiotaped focus groups. Transcripts of the sessions were analyzed using the NUD*IST software, and interpreted using grounded theory. Twenty-eight women participated, 16 with CRF and 12 with CFS. Analysis of transcripts from both groups revealed a similar core set of symptoms, featuring fatigue, neurocognitive difficulties, and mood disturbances.

Women with CFS reported additional symptoms including musculoskeletal pain and influenza-like manifestations. Both groups suffered disabling behavioral consequences of the symptom complex. Qualitatively, CRF appears closely related to CFS. These findings raise the emergent hypothesis of a conserved neurobehavioral symptom complex, which results from diverse triggering insults.

 

Source: Bennett B, Goldstein D, Friedlander M, Hickie I, Lloyd A. The experience of cancer-related fatigue and chronic fatigue syndrome: a qualitative and comparative study. J Pain Symptom Manage. 2007 Aug;34(2):126-35. Epub 2007 Jun 4. https://www.ncbi.nlm.nih.gov/pubmed/17544246

 

Gene expression correlates of postinfective fatigue syndrome after infectious mononucleosis

Abstract:

BACKGROUND: Infectious mononucleosis (IM) commonly triggers a protracted postinfective fatigue syndrome (PIFS) of unknown pathogenesis.

METHODS: Seven subjects with PIFS with 6 or more months of disabling symptoms and 8 matched control subjects who had recovered promptly from documented IM were studied. The expression of 30,000 genes was examined in the peripheral blood by microarray analysis in 65 longitudinally collected samples. Gene expression patterns associated with PIFS were sought by correlation with symptom factor scores.

RESULTS: Differential expression of 733 genes was identified when samples collected early during the illness and at the late (recovered) time point were compared. Of these genes, 234 were found to be significantly correlated with the reported severity of the fatigue symptom factor, and 180 were found to be correlated with the musculoskeletal pain symptom factor. Validation by analysis of the longitudinal expression pattern revealed 35 genes for which changes in expression were consistent with the illness course. These genes included several that are involved in signal transduction pathways, metal ion binding, and ion channel activity.

CONCLUSIONS: Gene expression correlates of the cardinal symptoms of PIFS after IM have been identified. Further studies of these gene products may help to elucidate the pathogenesis of PIFS.

Comment in: What causes prolonged fatigue after infectious mononucleosis: and does it tell us anything about chronic fatigue syndrome? [J Infect Dis. 2007]

 

Source: Cameron B, Galbraith S, Zhang Y, Davenport T, Vollmer-Conna U, Wakefield D, Hickie I, Dunsmuir W, Whistler T, Vernon S, Reeves WC, Lloyd AR; Dubbo Infection Outcomes Study. Gene expression correlates of postinfective fatigue syndrome after infectious mononucleosis. J Infect Dis. 2007 Jul 1;196(1):56-66. Epub 2007 May 24. http://jid.oxfordjournals.org/content/196/1/56.long (Full article)

 

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.

 

Source: Hickie I, Davenport T, Wakefield D, Vollmer-Conna U, Cameron B, Vernon SD, Reeves WC, Lloyd A; Dubbo Infection Outcomes Study Group. Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study. BMJ. 2006 Sep 16;333(7568):575. Epub 2006 Sep 1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1569956/ (Full article)

 

The genetic aetiology of somatic distress

Abstract:

BACKGROUND: Somatoform disorders such as neurasthenia and chronic fatigue syndrome are characterized by a combination of prolonged mental and physical fatigue. This study aimed to investigate the heritability of somatic distress and determine whether this dimension is aetiologically distinct from measures of depression and anxiety.

METHOD: Measures of anxiety, depression, phobic anxiety, somatic distress and sleep difficulty were administered in a self-report questionnaire to a community-based sample of 3469 Australian twin individuals aged 18 to 28 years. Factor analysis using a Promax rotation, produced four factors: depression, phobic anxiety, somatic distress and sleep disturbance. Multivariate and univariate genetic analyses of the raw categorical data scores for depression, phobic anxiety and depression were then analysed in Mx1.47.

RESULTS: Univariate genetic analysis revealed that an additive genetic and non-shared environmental (AE) model best explained individual differences in depression and phobic anxiety scores, for male and female twins alike, but could not resolve whether additive genes or shared environment were responsible for significant familial aggregation in somatic distress. However, multivariate genetic analysis showed that an additive genetic and non-shared environment (AE) model best explained the covariation between the three factors. Furthermore, 33 % of the genetic variance in somatic distress was due to specific gene action unrelated to depression or phobic anxiety. In addition, 74% of the individual environmental influence on somatic distress was also unrelated to depression or phobic anxiety.

CONCLUSION: These results support previous findings that somatic symptoms are relatively aetiologically distinct both genetically and environmentally from symptoms of anxiety and depression.

 

Source: Gillespie NA, Zhu G, Heath AC, Hickie IB, Martin NG. The genetic aetiology of somatic distress. Psychol Med. 2000 Sep;30(5):1051-61. http://www.ncbi.nlm.nih.gov/pubmed/12027042

 

A twin study of the etiology of prolonged fatigue and immune activation

Abstract:

Risk factors to prolonged fatigue syndromes (PFS) are controversial. Pre-morbid and/or current psychiatric disturbance, and/or disturbed cell-mediated immunity (CMI), have been proposed as etiologic factors.

Self-report measures of fatigue and psychologic distress and three in vitro measures of CMI were collected from 124 twin pairs. Crosstwin-crosstrait correlations were estimated for the complete monozygotic (MZ; 79 pairs) and dizygotic (DZ; 45 pairs) twin groups. Multivariate genetic and environmental models were fitted to explore the patterns of covariation between etiologic factors. For fatigue, the MZ correlation was more than double the DZ correlation (0.49 versus 0.16) indicating strong genetic control of familial aggregation.

By contrast, for in vitro immune activation measures MZ and DZ correlations were similar (0.49-0.69 versus 0.42-0.53) indicating the etiologic role of shared environments. As small univariate associations were noted between prolonged fatigue and the in vitro immune measures (r = -0.07 to -0.12), multivariate models were fitted. Relevant etiologic factors included: a common genetic factor accounting for 48% of the variance in fatigue which also accounted for 4%, 6% and 8% reductions in immune activation; specific genetic factors for each of the in vitro immune measures; a shared environment factor influencing the three immune activation measures; and, most interestingly, unique environmental influences which increased fatigue but also increased markers of immune activation.

PFS that are associated with in vitro measures of immune activation are most likely to be the consequence of current environmental rather than genetic factors. Such environmental factors could include physical agents such as infection and/or psychologic stress.

 

Source: Hickie IB, Bansal AS, Kirk KM, Lloyd AR, Martin NG. A twin study of the etiology of prolonged fatigue and immune activation. Twin Res. 2001 Apr;4(2):94-102. http://www.ncbi.nlm.nih.gov/pubmed/11665341

 

What is chronic fatigue syndrome? Heterogeneity within an international multicentre study

Abstract:

OBJECTIVE: We sought to compare the characteristics of patients presenting with chronic fatigue (CF) and related syndromes in eight international centres and to subclassify these subjects based on symptom profiles. The validity of the subclasses was then tested against clinical data.

METHOD: Subjects with a clinical diagnosis of CF completed a 119-item self-report questionnaire to provide clinical symptom data and other information such as illness course and functional impairment. Subclasses were generated using a principal components-like analysis followed by latent profile analysis (LPA).

RESULTS: 744 subjects returned complete data sets (mean age 40.8 years, mean length of illness 7.9 years, female to male ratio 3:1). Overall, the subjects had a high rate of reporting typical CF symptoms (fatigue, neuropsychological dysfunction, sleep disturbance). Using LPA, two subclasses were generated. Class one (68% sample) was characterized by: younger age, lower female to male ratio; shorter episode duration; less premorbid, current and familial psychiatric morbidity; and, less functional disability. Class two subjects (32%) had features more consistent with a somatoform illness. There was substantial variation in subclass prevalences between the study centres (Class two range 6-48%).

CONCLUSIONS: Criteria-based approaches to the diagnosis of CF and related syndromes do not select a homogeneous patient group. While substratification of patients is essential for further aetiological and treatment research, the basis for allocating such subcategories remains controversial.

 

Source: Wilson A, Hickie I, Hadzi-Pavlovic D, Wakefield D, Parker G, Straus SE, Dale J, McCluskey D, Hinds G, Brickman A, Goldenberg D, Demitrack M, Blakely T,Wessely S, Sharpe M, Lloyd A. What is chronic fatigue syndrome? Heterogeneity within an international multicentre study. Aust N Z J Psychiatry. 2001 Aug;35(4):520-7. http://www.ncbi.nlm.nih.gov/pubmed/11531735

 

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.

 

Source: Hadzi-Pavlovic D, Hickie IB, Wilson AJ, Davenport TA, Lloyd AR, Wakefield D. Screening for prolonged fatigue syndromes: validation of the SOFA scale. Soc Psychiatry Psychiatr Epidemiol. 2000 Oct;35(10):471-9. http://www.ncbi.nlm.nih.gov/pubmed/11127722