Few studies have examined spontaneous remission from major depression. This study investigated the proportion of prevalent cases of untreated major depression that will remit without treatment in a year, and whether remission rates vary by disorder severity.

Wait-list controlled trials and observational cohort studies published up to 2010 with data describing remission from untreated depression at ⩽2-year follow-up were identified. Remission was defined as rescinded diagnoses or below threshold scores on standardized symptom measures. Nineteen studies were included in a regression model predicting the probability of 12-month remission from untreated depression, using logit transformed remission proportion as the dependent variable. Covariates included age, gender, study type and diagnostic measure.

Wait-listed compared to primary-care samples, studies with longer follow-up duration and older adult compared to adult samples were associated with lower probability of remission. Child and adolescent samples were associated with higher probability of remission. Based on adult samples recruited from primary-care settings, the model estimated that 23% of prevalent cases of untreated depression will remit within 3 months, 32% within 6 months and 53% within 12 months.

It is undesirable to expect 100% treatment coverage for depression, given many will remit before access to services is feasible. Data were drawn from consenting wait-list and primary-care samples, which potentially over-represented mild-to-moderate cases of depression. Considering reported rates of spontaneous remission, a short untreated period seems defensible for this subpopulation, where judged appropriate by the clinician. Conclusions may not apply to individuals with more severe depression.

Risk factors that are associated with depression in the mother also negatively affect the child. This research sought to extend current knowledge by examining the duration and timing of maternal depression as a moderator of: (1) the impact of dependent interpersonal stress (DIS), such as partner conflict or low social support, and contextual risk (e.g. poverty) on child dysregulation; and (2) continuity in early child dysregulation.

Mother–child pairs (n = 12 152) who participated in the Avon Longitudinal Study of Parents and Children (ALSPAC) were examined between pregnancy and age 4 years. Data on maternal depression were collected five times between pregnancy and 33 months postpartum; on DIS and contextual risk three times between pregnancy and 33 months; and on child dysregulation at age 2 and 4 years.

Longitudinal latent class analysis identified a class of mothers (10%) who evinced a chronic level of depression between pregnancy and 33 months. For chronic-depressed versus non-depressed mothers, the results indicate that: (1) DIS predicted higher child dysregulation if experienced between pregnancy and age 2; (2) contextual risk had a differential effect on child dysregulation if experienced during pregnancy; and (3) children had higher continuity in dysregulation between age 2 and age 4.

Assessing the impact of the timing and duration of maternal depression, and different types of co-occurring risk factors, on child well-being is important. Maternal depression and associated DIS, in comparison to contextual risk, may be more responsive to intervention.

Whether late-onset depression is a risk factor for or a prodrome of dementia remains unclear. We investigated the impact of depressive symptoms and early- v. late-onset depression on subsequent dementia in a cohort of elderly general-practitioner patients (n = 2663, mean age = 81.2 years).

Risk for subsequent dementia was estimated over three follow-ups (each 18 months apart) depending on history of depression, particularly age of depression onset, and current depressive symptoms using proportional hazard models. We also examined the additive prediction of incident dementia by depression beyond cognitive impairment.

An increase of dementia risk for higher age cut-offs of late-onset depression was found. In analyses controlling for age, sex, education, and apolipoprotein E4 genotype, we found that very late-onset depression (aged ⩾70 years) and current depressive symptoms separately predicted all-cause dementia. Combined very late-onset depression with current depressive symptoms was specifically predictive for later Alzheimer's disease (AD; adjusted hazard ratio 5.48, 95% confidence interval 2.41–12.46, p < 0.001). This association was still significant after controlling for cognitive measures, but further analyses suggested that it was mediated by subjective memory impairment with worries.

Depression might be a prodrome of AD but not of dementia of other aetiology as very late-onset depression in combination with current depressive symptoms, possibly emerging as a consequence of subjectively perceived worrisome cognitive deterioration, was most predictive. As depression parameters and subjective memory impairment predicted AD independently of objective cognition, clinicians should take this into account.

Clinical trials are typically designed to test the effect of a specific treatment on a single diagnostic entity. However, because common internalizing disorders are highly correlated (‘co-morbid’), we sought to establish a practical and parsimonious method to characterize and quantify changes in a broad spectrum of internalizing psychopathology targeted for treatment in a clinical trial contrasting two transdiagnostic psychosocial interventions.

Alcohol dependence treatment patients who had any of several common internalizing disorders were randomized to a six-session cognitive-behavioral therapy (CBT) experimental treatment condition or a progressive muscle relaxation training (PMRT) comparison treatment condition. Internalizing psychopathology was characterized at baseline and 4 months following treatment in terms of the latent structure of six distinct internalizing symptom domain surveys.

Exploratory structural equation modeling (ESEM) identified a two-factor solution at both baseline and the 4-month follow-up: Distress (measures of depression, trait anxiety and worry) and Fear (measures of panic anxiety, social anxiety and agoraphobia). Although confirmatory factor analysis (CFA) demonstrated measurement invariance between the time-points, structural models showed that the latent means of Fear and Distress decreased substantially from baseline to follow-up for both groups, with a small but statistically significant advantage for the CBT group in terms of Distress (but not Fear) reduction.

The approach demonstrated in this study provides a practical solution to modeling co-morbidity in a clinical trial and is consistent with converging evidence pointing to the dimensional structure of internalizing psychopathology.

Lack of coordination between screening studies for common mental disorders in primary care and community epidemiological samples impedes progress in clinical epidemiology. Short screening scales based on the World Health Organization (WHO) Composite International Diagnostic Interview (CIDI), the diagnostic interview used in community epidemiological surveys throughout the world, were developed to address this problem.

Expert reviews and cognitive interviews generated CIDI screening scale (CIDI-SC) item pools for 30-day DSM-IV-TR major depressive episode (MDE), generalized anxiety disorder (GAD), panic disorder (PD) and bipolar disorder (BPD). These items were administered to 3058 unselected patients in 29 US primary care offices. Blinded SCID clinical reinterviews were administered to 206 of these patients, oversampling screened positives.

Stepwise regression selected optimal screening items to predict clinical diagnoses. Excellent concordance [area under the receiver operating characteristic curve (AUC)] was found between continuous CIDI-SC and DSM-IV/SCID diagnoses of 30-day MDE (0.93), GAD (0.88), PD (0.90) and BPD (0.97), with only 9–38 questions needed to administer all scales. CIDI-SC versus SCID prevalence differences are insignificant at the optimal CIDI-SC diagnostic thresholds (χ21 = 0.0–2.9, p = 0.09–0.94). Individual-level diagnostic concordance at these thresholds is substantial (AUC 0.81–0.86, sensitivity 68.0–80.2%, specificity 90.1–98.8%). Likelihood ratio positive (LR+) exceeds 10 and LR− is 0.1 or less at informative thresholds for all diagnoses.

CIDI-SC operating characteristics are equivalent (MDE, GAD) or superior (PD, BPD) to those of the best alternative screening scales. CIDI-SC results can be compared directly to general population CIDI survey results or used to target and streamline second-stage CIDIs.

Prospective memory (PM) refers to the ability to remember to carry out an intended action in the future. PM is consistently found to be impaired in individuals with schizophrenia. Bipolar disorder and schizophrenia may represent conditions along a continuum, and share similar neurocognitive and genetic architecture. This study aimed to compare the nature and extent of PM impairment in individuals with schizophrenia and bipolar disorder.

Participants were 38 out-patients with schizophrenia and 40 out-patients with bipolar disorder in an early psychosis intervention programme, and 37 healthy controls. Time-, event- and activity-based PMs were assessed using a dual-task laboratory paradigm. Self-reported PM performance was gauged using the Prospective and Retrospective Memory Questionnaire. Analysis of covariance (ANCOVA), with intelligence quotient (IQ) and education included as covariates, was used to examine group difference on various types of PM. Repeated measures of ANCOVA were used to examine the group × PM type interaction effect. Correspondence between laboratory and self-reported PM measures was examined using correlational analysis.

The group × PM type interaction effect was not significant, but the main effect of group was significant. Patients with schizophrenia and patients with bipolar disorder both performed more poorly than healthy participants in PM. The two clinical groups did not significantly differ in PM. Laboratory and self-reported PM measures did not correlate significantly with each other.

Patients with bipolar disorder shared a similar PM impairment with those with schizophrenia. Findings of this study extended the similarity in neurocognitive impairments between the two psychiatric disorders to PM.

Although patients with chronic schizophrenia have substantially higher smoking rates than either the general population or patients with other mental illnesses, drug-naive patients with a first episode of schizophrenia have received little systemic study. This study examined smoking rates, the association between smoking and symptom severity and cognitive function in Chinese first-episode schizophrenia (FES) patients using cross-sectional and case-control designs.

Two hundred and forty-four drug-naive FES patients and 256 healthy controls matched for gender, age and education completed the Fagerström Test for Nicotine Dependence (FTND) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Patients were also rated on the Positive and Negative Symptom Scale (PANSS).

The rate and quantity of smoking were not significantly higher among FES patients compared to the general population. Among patients, smokers scored higher than non-smokers on the total PANSS and the positive symptom subscale scores. There were no significant associations between cognitive function and smoking in either FES patients or healthy controls.

In contrast to studies in patients with chronic schizophrenia, drug-naive FES patients did not smoke more frequently than the general population. Furthermore, patients with psychotic disorders who smoked did not exhibit significant cognitive differences compared with those who did not smoke. However, smoking may have other detrimental effects on physical and mental health, for example on positive symptoms.

Abnormalities in hippocampal–parahippocampal (H-PH) function are prominent features of schizophrenia and have been associated with deficits in episodic memory. However, it remains unclear whether these abnormalities represent a phenotype related to genetic risk for schizophrenia or whether they are related to disease state.

We investigated H-PH-mediated behavior and physiology, using blood oxygenation level-dependent functional magnetic resonance imaging (BOLD fMRI), during episodic memory in a sample of patients with schizophrenia, clinically unaffected siblings and healthy subjects.

Patients with schizophrenia and unaffected siblings displayed abnormalities in episodic memory performance. During an fMRI memory encoding task, both patients and siblings demonstrated a similar pattern of reduced H-PH engagement compared with healthy subjects.

Our findings suggest that the pathophysiological mechanism underlying the inability of patients with schizophrenia to properly engage the H-PH during episodic memory is related to genetic risk for the disorder. Therefore, H-PH dysfunction can be assumed as a schizophrenia susceptibility-related phenotype.

Dimensional models of co-morbidity have the potential to improve the conceptualization of mental disorders in research and clinical work, yet little is known about how relatively uncommon disorders may fit with more common disorders. The present study estimated the meta-structure of psychopathology in the US general population focusing on the placement of five under-studied disorders sharing features of thought disorder: paranoid, schizoid, avoidant and schizotypal personality disorders, and manic episodes as well as bipolar disorder.

Data were drawn from the National Epidemiologic Survey on Alcohol and Related Conditions, a face-to-face interview of 34 653 non-institutionalized adults in the US general population. The meta-structure of 16 DSM-IV Axis I and Axis II psychiatric disorders, as assessed by the Alcohol Use Disorder and Associated Disabilities Interview Schedule DSM-IV version (AUDADIS-IV), was examined using exploratory and confirmatory factor analysis.

We document an empirically derived thought disorder factor that is a subdomain of the internalizing dimension, characterized by schizoid, paranoid, schizotypal and avoidant personality disorders as well as manic episodes. Manic episodes exhibit notable associations with both the distress subdomain of the internalizing dimension as well as the thought disorder subdomain. The structure was replicated for bipolar disorder (I or II) in place of manic episodes.

As our understanding of psychopathological meta-structure expands, incorporation of disorders characterized by detachment and psychoticism grows increasingly important. Disorders characterized by detachment and psychoticism may be well conceptualized, organized and measured as a subdimension of the internalizing spectrum of disorders. Manic episodes and bipolar disorder exhibit substantial co-morbidity across both distress and thought disorder domains of the internalizing dimension. Clinically, these results underscore the potential utility of conceptualizing patient treatment needs using an approach targeting psychopathological systems underlying meta-structural classification rubrics.

Although auditory verbal hallucinations (AVH) are a core symptom of schizophrenia, they also occur in non-psychotic individuals, in the absence of other psychotic, affective, cognitive and negative symptoms. AVH have been hypothesized to result from deviant integration of inferior frontal, parahippocampal and superior temporal brain areas. However, a direct link between dysfunctional connectivity and AVH has not yet been established. To determine whether hallucinations are indeed related to aberrant connectivity, AVH should be studied in isolation, for example in non-psychotic individuals with AVH.

Resting-state connectivity was investigated in 25 non-psychotic subjects with AVH and 25 matched control subjects using seed regression analysis with the (1) left and (2) right inferior frontal, (3) left and (4) right superior temporal and (5) left parahippocampal areas as the seed regions. To correct for cardiorespiratory (CR) pulsatility rhythms in the functional magnetic resonance imaging (fMRI) data, heartbeat and respiration were monitored during scanning and the fMRI data were corrected for these rhythms using the image-based method for retrospective correction of physiological motion effects RETROICOR.

In comparison with the control group, non-psychotic individuals with AVH showed increased connectivity between the left and the right superior temporal regions and also between the left parahippocampal region and the left inferior frontal gyrus. Moreover, this group did not show a negative correlation between the left superior temporal region and the right inferior frontal region, as was observed in the healthy control group.

Aberrant connectivity of frontal, parahippocampal and superior temporal brain areas can be specifically related to the predisposition to hallucinate in the auditory domain.

Neuroticism has been consistently correlated with the post-traumatic stress disorder (PTSD) response to traumatic events. Interpretation of these findings is limited by the retrospective nature of these findings: neuroticism was measured after the trauma had occurred. The prospective association of neuroticism with PTSD has not been examined (the relationship of neuroticism with PTSD symptoms was examined in a few prospective studies). We evaluate prospectively the relationship of neuroticism, measured at baseline, with the cumulative occurrence of PTSD during the subsequent 10 years, using data from a longitudinal epidemiological study of young adults.

A sample of 1007 young adults randomly selected from the membership of a large health maintenance organization in southeast Michigan was assessed at baseline and followed up at 3, 5 and 10 years later. We conducted a series of multinomial logistic regressions to estimate the relative risk (RR) of exposure to trauma and PTSD by neuroticism at baseline, adjusting for history of major depression (n = 990).

During the 10-year follow-up, 50.2% of the sample experienced traumatic events and 5.2% developed PTSD. Neuroticism score at baseline increased significantly the RR of PTSD response to trauma. Additional analysis revealed that, among persons with history of major depression at baseline, RR for PTSD associated with neuroticism was equal to the null value of 1, but was increased significantly among those with no history of major depression.

The results confirm the role of neuroticism as diathesis in the PTSD response to traumatic experiences.

In previous studies an association between deployment to Iraq or Afghanistan and an overall increased risk for post-traumatic stress disorder (PTSD) in UK armed forces has not been found. The lack of a deployment effect might be explained by including, in the comparison group, personnel deployed on other operations or who have experienced traumatic stressors unrelated to deployment.

The sample comprised 8261 regular UK armed forces personnel who deployed to Iraq, Afghanistan or other operational areas or were not deployed. Participants completed the PTSD CheckList – Civilian Version (PCL-C) and provided information about deployment history, demographic and service factors, serious accidents and childhood experiences.

Deployment to Iraq or Afghanistan [odds ratio (OR) 1.2, 95% confidence interval (CI) 0.6–2.2] or elsewhere (OR 1.1, 95% CI 0.6–2.0) was unrelated to PTSD although holding a combat role was associated with PTSD if deployed to Iraq or Afghanistan (OR 2.7, 95% CI 1.9–3.9). Childhood adversity (OR 3.3, 95% CI 2.1–5.0), having left service (OR 2.7, 95% CI 1.9–4.0) and serious accident (OR 2.1, 95% CI 1.4–3.0) were associated with PTSD whereas higher rank was protective (OR 0.3, 95% CI 0.12–0.76).

For the majority of UK armed forces personnel, deployment whether to Iraq, Afghanistan or elsewhere confers no greater risk for PTSD than service in the armed forces per se but holding a combat role in those deployed to Iraq or Afghanistan is associated with PTSD. Vulnerability factors such as lower rank, childhood adversity and leaving service, and having had a serious accident, may be at least as important as holding a combat role in predicting PTSD in UK armed forces personnel.

Various studies support the inclusion of cannabis withdrawal in the diagnosis of cannabis use disorder (CUD) in the upcoming DSM-5. The aims of the current study were to (1) estimate the prevalence of DSM-5 cannabis withdrawal (criterion B), (2) estimate the role of genetic and environmental influences on individual differences in cannabis withdrawal and (3) determine the extent to which genetic and environmental influences on cannabis withdrawal overlap with those on DSM-IV-defined abuse/dependence.

The sample included 2276 lifetime cannabis-using adult Australian twins. Cannabis withdrawal was defined in accordance with criterion B of the proposed DSM-5 revisions. Cannabis abuse/dependence was defined as endorsing one or more DSM-IV criteria of abuse or three or more dependence criteria. The classical twin model was used to estimate the genetic and environmental influences on variation in cannabis withdrawal, along with its covariation with abuse/dependence.

Of all the cannabis users, 11.9% met criteria for cannabis withdrawal. Around 50% of between-individual variation in withdrawal could be attributed to additive genetic variation, and the rest of the variation was mostly due to non-shared environmental influences. Importantly, the genetic influences on cannabis withdrawal almost completely (99%) overlapped with those on abuse/dependence.

We have shown that cannabis withdrawal symptoms exist among cannabis users, and that cannabis withdrawal is moderately heritable. Genetic influences on cannabis withdrawal are the same as those affecting abuse/dependence. These results add to the wealth of literature that recommends the addition of cannabis withdrawal to the diagnosis of DSM-5 CUD.

We internally validated previously published rates of remission, continuation and incidence of broadly defined eating disorders during pregnancy in the Norwegian Mother and Child Cohort (MoBa) at the Norwegian Institute of Public Health.

A total of 77 267 pregnant women enrolled at 17 weeks gestation between 2001 and 2009 were split into a training sample (n = 41 243) from the version 2 dataset and a validation sample (n = 36 024) from the version 5 dataset who were not in the original study. Internal validation of original rate models involved fitting a calibration model to compare model parameters between the two samples and bootstrap estimates of bias in the entire version 5 dataset.

Remission, continuation and incidence estimates remained stable. Pre-pregnancy prevalence estimates in the validation sample were: anorexia nervosa (AN; 0.1%), bulimia nervosa (BN; 1.0%), binge eating disorder (BED; 3.3%) and eating disorder not otherwise specified-purging disorder (EDNOS-P; 0.1%). In early pregnancy, estimates were: BN (0.2%), BED (4.8%) and EDNOS-P (<0.01%). Incident BN and EDNOS-P during pregnancy were rare. The highest rates were for full or partial remission for BN and EDNOS-P and continuation for BED.

We validated previously estimated rates of remission, continuation and incidence of eating disorders during pregnancy. Eating disorders, especially BED, during pregnancy were relatively common, occurring in nearly one in every 20 women. Pregnancy was a window of remission from BN but a window of vulnerability for BED. Training to detect eating disorders by obstetricians/gynecologists and interventions to enhance pregnancy and neonatal outcomes warrant attention.

Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD), and associated subclinical traits, regularly co-occur with one another. However, the aetiology of their co-occurrence remains poorly understood. This paper provides the first genetically informative, longitudinal analysis of the interaction between traits of ASD and ADHD, and explores their genetic and environmental overlap.

Parents of approximately 5000 twin pairs completed questionnaires assessing traits of ASD and ADHD when twins were aged 8 and 12 years. Cross-lagged longitudinal modelling explored their developmental association, enabling a consideration of phenotypic-driven processes. Overlapping aetiological influences on traits at age 12 years were explored using bivariate twin modelling.

Traits of ADHD at age 8 years were more strongly predictive of traits of ASD at 12 years than traits of ASD at 8 years were of traits of ADHD at 12 years. Analysis of traits by subscales assessing specific symptom domains suggested that communication difficulties were most strongly associated with traits of ADHD. Bivariate modelling suggested moderate genetic overlap on traits in males (genetic correlation = 0.41), and a modest degree of overlap in females (genetic correlation = 0.23) at age 12 years.

Traits of ADHD at age 8 years significantly influence traits of ASD at age 12 years, after controlling for their initial relationship at age 8 years. In particular, early ADHD traits influenced later communication difficulties. These findings demonstrate the dynamic nature of co-occurring traits across development. In addition, these findings add to a growing body of literature suggesting that traits of ASD and ADHD may arise via similar aetiological processes.

The neuropeptide oxytocin (OT) has positive effects on the processing of emotional stimuli such as facial expressions. To date, research has focused primarily on conditions of overt visual attention.

We investigated whether a single intranasal dose of OT (24 IU) would modulate the allocation of attentional resources towards positive and negative facial expressions using a dot-probe paradigm in a sample of 69 healthy men. Attentional capacity for these facial cues was limited by presentation time (100 or 500 ms). In addition, we controlled for overt visual attention by recording eye movements using a remote eye tracker.

Reaction times (RTs) in the dot-probe paradigm revealed a pronounced shift of attention towards happy facial expressions presented for 100 ms after OT administration, whereas there were no OT-induced effects for longer presentation times (500 ms). The results could not be attributed to modulations of overt visual attention as no substance effects on gazes towards the facial target were observed.

The results suggest that OT increased covert attention to happy faces, thereby supporting the hypothesis that OT modulates early attentional processes that might promote prosocial behavior.

Long-term sickness absence (LTSA) is most commonly due to common mental disorders and symptom-based conditions. Relatively little research has examined individual, as opposed to occupational, risk factors for LTSA. Individual appraisal of the workplace has been considered in several studies but self-rated health has more often been examined as a consequence of, rather than as a risk factor for, sickness absence. We aimed to study the association between self-rated health and later LTSA.

We used data from the 1970 British Cohort Study (BCS70). LTSA was defined as being in receipt of Incapacity Benefit (IB)/Severe Disablement Allowance (SDA) at age 34. The mother rated the participant's overall health at age 16; the participants self-rated at age 30. Reports of psychological and somatic symptoms were available at age 16; data on major health conditions were available at age 30.

Analyses were restricted to those working, studying or caring for children at age 30 (n = 14 105). One hundred and fifty-six (1.1%) were receiving IB or SDA by age 34. After adjustment for social class at birth, educational attainment, health conditions at age 30 and psychological and somatic symptoms at age 16, those who reported their health as poor had more than five times the odds of being long-term sick at age 34.

The overall appraisal of an individual's health as poor, independent of any diagnosis, is a significant vulnerability factor for LTSA.

Employment is associated with health benefits over unemployment, but the psychosocial characteristics of work also influence health. There has, however, been little research contrasting the prevalence of psychiatric disorders among people who are unemployed with those in jobs of differing psychosocial quality.

Analysis of data from the English Adult Psychiatric Morbidity Survey (APMS) considered the prevalence of common mental disorders (CMDs) among 2603 respondents aged between 21 and 54 years who were either (i) employed or (ii) unemployed and looking for work at the time of interview in 2007. Quality of work was assessed by the number of adverse psychosocial job conditions reported (low control, high demands, insecurity and low job esteem).

The prevalence of CMDs was similar for those respondents who were unemployed and those in the poorest quality jobs. This pattern remained after controlling for relevant demographic and socio-economic covariates.

Although employment is thought to promote mental health and well-being, work of poor psychosocial quality is not associated with any better mental health than unemployment. Policy efforts to improve community mental health should consider psychosocial job quality in conjunction with efforts to increase employment rates.

Although basic research on neuroimmune interactions suggests that inflammatory processes may play a role in the development of fatigue, population-based evidence on this association is limited. This study examined whether plasma C-reactive protein (CRP) and interleukin-6 (IL-6), biomarkers of systemic inflammation, predict fatigue onset.

The Whitehall II study is a large-scale cohort study conducted in 20 civil service departments in London. Plasma CRP and IL-6 were measured in 4847 non-fatigued participants at phase 3 (1991–1993, aged 39–63 years). Fatigue was assessed using the Vitality subscale of the 36-item Short Form Health Survey (SF-36) at phase 3 and phase 4 (1995–1996).

During a mean follow-up of 3.1 years, 957 new fatigue cases (19.7%) were identified using the pre-established cut-off score of ⩽50 on the Vitality subscale. CRP values were dichotomized as low (<1.0 mg/l ) or high (⩾1.0 mg/l) using the Centers for Disease Control/American Heart Association recommendations. Similarly, IL-6 values were also dichotomized as low (<1.5 pg/ml) or high (⩾1.5 pg/ml). After full adjustment for sociodemographic and biobehavioral covariates, the odds ratios for new-onset fatigue were 1.28 [95% confidence interval (CI) 1.09–1.49, p = 0.003] for high CRP and 1.24 (95% CI 1.06–1.45, p = 0.008) for high IL-6. Similar results were found when CRP and IL-6 were treated as continuous variables.

Plasma CRP and IL-6 were prospectively associated with new-onset fatigue, supporting the hypothesis that low-grade inflammation has a role in the development of fatigue.