The aetiology of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is still unknown. The identification of risk factors for CFS/ME is of great importance to practitioners.

A systematic scoping review was conducted to locate studies that analysed risk factors for CFS/ME using multiple predictors. We searched for published and unpublished literature in 11 electronic databases, reference lists of retrieved articles and guideline stakeholder submissions in conjunction with the development of a forthcoming national UK guideline. Risk factors and findings were extracted in a concise tabular overview and studies synthesized narratively.

Eleven studies were identified that met inclusion criteria: two case-control studies, four cohort studies, three studies combining a cohort with a case-control study design, one case-control and twin study and one cross-sectional survey. The studies looked at a variety of demographic, medical, psychological, social and environmental factors to predict the development of CFS/ME. The existing body of evidence is characterized by factors that were analysed in several studies but without replication of a significant association in more than two studies, and by studies demonstrating significant associations of specific factors that were not assessed in other studies. None of the identified factors appear suitable for the timely identification of patients at risk of developing CFS/ME within clinical practice.

Various potential risk factors for the development of CFS/ME have been assessed but definitive evidence that appears meaningful for clinicians is lacking.

Increased rates of psychiatric disorder have previously been reported in those diagnosed with chronic fatigue syndrome (CFS) or myalgic encephalomyelitis (ME), although the direction of causation in this relationship has not been established. We aimed to test the hypothesis that individuals with self-reported CFS/ME have increased levels of psychiatric disorder prior to the onset of their fatigue symptoms.

A total of 5362 participants were prospectively followed with various measures of personality, psychiatric disorder and fatigue levels collected over the first 43 years of their life. CFS/ME was identified through self-report during a semi-structured interview at age 53 years.

Thirty-four (1.1%) of the 3035 subjects assessed at age 53 years reported a diagnosis of CFS/ME. CFS/ME was more common among females, but there was no association between CFS/ME and either social class, social mobility or educational level. Those with psychiatric illness between the ages of 15 and 36 years were more likely to report CFS/ME later in life with an odds ratio (OR, adjusted for sex) of 2.65 [95% confidence interval (CI) 1.26–5.57, p=0.01]. Increased levels of psychiatric illness, in particular depression and anxiety, were present prior to the occurrence of fatigue symptoms. There was a dose–response relationship between the severity of psychiatric symptoms and the likelihood of later CFS/ME. Personality factors were not associated with a self-reported diagnosis of CFS/ME.

This temporal, dose–response relationship suggests that psychiatric disorders, or shared risk factors for psychiatric disorders, are likely to have an aetiological role in some cases of CFS/ME.

Fatigue is the central symptom in chronic fatigue syndrome (CFS) and yet very little is known about its neural correlates. The aim of this study was to explore the functional brain response, using functional magnetic resonance imaging (fMRI), to the imaginal experience of fatigue in CFS patients and controls.

We compared the blood oxygen level dependent (BOLD) responses of 12 CFS patients and 11 healthy controls to a novel fatigue provocation procedure designed to mimic real-life situations. A non-fatiguing anxiety-provoking condition was also included to control for the non-specific effects of negative affect.

During the provocation of fatigue, CFS patients reported feelings of both fatigue and anxiety and, compared to controls, they showed increased activation in the occipito-parietal cortex, posterior cingulate gyrus and parahippocampal gyrus, and decreased activation in dorsolateral and dorsomedial prefrontal cortices. The reverse pattern of findings was observed during the anxiety-provoking scenarios.

The results may suggest that, in CFS patients, the provocation of fatigue is associated with exaggerated emotional responses that patients may have difficulty suppressing. These findings are discussed in relation to the cognitive-behavioural model of CFS.

The aim was to determine the prevalence of chronic fatigue syndrome (CFS), chronic fatigue and fibromyalgia in UK military personnel after the Gulf War 1990–1991.

A two-phase cohort study was used. Three randomly selected subsamples identified from a population-based cross-sectional postal survey of over 10 000 current and ex-service UK military personnel (Gulf veterans were those deployed to the Gulf War 1990–1991; non-Gulf veterans were Bosnia peacekeepers 1992–1997 and those on active duty during the Gulf War 1990–1991 but not deployed) were recruited. Their disability status was assessed using the Short Form 36 physical functioning scale; Gulf veterans who reported physical disability (n=111) were compared with non-Gulf (n=133) veterans who reported similar levels of physical disability. Screening for known medical and psychiatric conditions was conducted to exclude medical explanations for disability and symptomatic distress. Standardised criteria for CFS, chronic fatigue and fibromyalgia were used.

Disabled Gulf veterans were more likely to be overweight, have elevated γ-glutamyl transferase levels and screen positive for hypertension. There were no other clinically significant differences in clinical markers for medically explainable conditions. Disabled Gulf veterans were more likely than similarly disabled Bosnia and Era veterans (adjusted odds ratio 7.8, 95% confidence interval 2.5–24.5) to meet the criteria for CFS. Rates for other medically unexplained conditions were not significantly increased.

Symptoms in keeping with CFS account for a significant part of the symptomatic distress in Gulf veterans.

Studies of hypothalamic–pituitary–adrenal (HPA) axis function in chronic fatigue syndrome (CFS) point to hypofunction, although there are negative reports. Suggested mechanisms include a reduced hypothalamic or supra-hypothalamic stimulus to the HPA axis and enhanced sensitivity to the negative feedback of glucocorticoids. The aim of the current study was to investigate HPA axis function in CFS with the dexamethasone/corticotropin-releasing factor (Dex/CRF) test, in analogy with research in affective disorders.

Thirty-four well-characterized female CFS patients and 25 healthy control subjects participated in the low-dose Dex/CRF test. Current major depressive episode was an exclusion criterion. History of early-life stress (ELS) was assessed with the Structured Trauma Interview.

Salivary cortisol responses after 0.5 mg Dex were lower in CFS patients than in controls (before 100 μg CRF, p=0.038; after 100 μg CRF, p=0.015). A secondary analysis revealed an influence of early-life stress and of oestrogen intake. After removal of the 10 participants who were taking an oral oestrogen, patients without a history of ELS showed lower cortisol responses than patients with ELS and controls (before CRF, p=0.005; after CRF, p=0.008).

CFS is globally associated with reduced cortisol responses in the combined low-dose Dex/CRF test, but this effect is only clearly present in CFS patients without a history of ELS. This study provides further support for an enhanced glucocorticoid negative feedback and/or a reduced central HPA axis drive in CFS. Furthermore, it demonstrates that ELS is an important variable to consider in CFS research.

Conduct disorder (CD) prior to age 15 has been associated with an increased risk of aggressive behaviour and crime among men with schizophrenia. The present study aimed to replicate and extend this finding in a clinical sample of severely mentally ill men and women.

We examined a cohort of in-patients with severe mental illness in one mental health trust. A total of 205 men and women participated, average age 38.5 years. CD was diagnosed using a structured diagnostic tool. Alcohol and illicit drug use, aggressive behaviour and victimization were self-reported. Information on convictions was extracted from official criminal records. Analyses controlled for age and sex.

CD prior to age 15 was associated with an increased risk of assault over the lifespan [odds ratio (OR) 3.98, 95% confidence interval (CI) 1.87–8.44)], aggressive behaviour in the 6 months prior to interview (OR 2.66, 95% CI 1.24–5.68), and convictions for violent crimes (OR 3.19, 95% CI 1.46–6.97) after controlling for alcohol and illicit drug use. The number of CD symptoms present prior to age 15 significantly increased the risk of serious assaults over the lifespan, aggressive behaviour in the past 6 months, and violent crime after controlling for alcohol and illicit drug use.

Men and women with severe mental illness who have a history of CD by mid-adolescence are at increased risk for aggressive behaviour and violent crime. These patients are easily identifiable and may benefit from learning-based treatments aimed at reducing antisocial behaviour. Longitudinal, prospective investigations are needed to understand why CD is more common among people with than without schizophrenia.

The long-term consequences of child and adolescent externalizing problems often involve a wide spectrum of social maladaptation in adult life. The purpose of this study was to describe the predictive link of child and adolescent externalizing developmental trajectories to social functioning in adulthood.

Social functioning was predicted from developmental trajectories of parent-reported aggression, opposition, property violations and status violations that were defined in a longitudinal multiple birth cohort study of 2076 males and females aged 4–18 years. Social functioning was assessed using self-reports by young adults aged 18–30 years. Linear and logistic regression analyses were used to describe the extent to which developmental trajectories are prospectively related to social functioning.

Children with high-level trajectories of opposition and status violations reported more impaired social functioning as young adults than children with high-level trajectories of aggression and property violations. Young adults who showed onset of problems in adolescence reported overall less impaired social functioning than individuals with high-level externalizing problems starting in childhood. Overall, males reported more impaired social functioning in adulthood than females. However, females with persistent high-level externalizing behaviour reported more impairment in relationships than males with persistent high-level externalizing behaviour.

The long-term consequences of high levels of opposition and status violations in childhood to serious social problems during adulthood are much stronger than for individuals who show only high levels of aggressive antisocial behaviours.

Conduct disorder (CD) and peer deviance (PD) both powerfully predict future externalizing behaviors. Although levels of CD and PD are strongly correlated, the causal relationship between them has remained controversial and has not been examined by a genetically informative study.

Levels of CD and PD were assessed in 746 adult male–male twin pairs at personal interview for ages 8–11, 12–14 and 15–17 years using a life history calendar. Model fitting was performed using the Mx program.

The best-fit model indicated an active developmental relationship between CD and PD including forward transmission of both traits over time and strong causal relationships between CD and PD within time periods. The best-fit model indicated that the causal relationship for genetic risk factors was from CD to PD and was constant over time. For common environmental factors, the causal pathways ran from PD to CD and were stronger in earlier than later age periods.

A genetically informative model revealed causal pathways difficult to elucidate by other methods. Genes influence risk for CD, which, through social selection, impacts on the deviance of peers. Shared environment, through family and community processes, encourages or discourages adolescent deviant behavior, which, via social influence, alters risk for CD. Social influence is more important than social selection in childhood, but by late adolescence social selection becomes predominant. These findings have implications for prevention efforts for CD and associated externalizing disorders.

Conduct disorder (CD) is a relatively common disorder of childhood and adolescence in the USA with substantial associated morbidity, yet little has been published on CD among Asians and Native Hawaiian/Pacific Islanders (NH/PI) in the USA.

We used the National Epidemiological Survey on Alcohol and Related Conditions (NESARC) to examine the prevalence and correlates of retrospectively reported CD within Asians and NH/PI (18 years and older). We also completed logistic regressions to explore factors associated with CD within Asians (n=1093) and, separately, NH/PI (n=139) and to explain racial differences in CD prevalence.

Asians were about a third as likely [odds ratio (OR) 0.4, 95% confidence interval (CI) 0.22–0.58] whereas NH/PI were about two and half times more likely (OR 2.6, 95% CI 1.31–5.06) to have had CD compared with Caucasian respondents. Within Asians and NH/PI, CD was strongly associated with adult antisocial behavior, substance use and affective disorders. Demographic factors, the age that subjects came to the USA, measures of family environment and family history could not explain the observed differences in prevalence of CD for NH/PI relative to Caucasians.

Asian and NH/PI youth with CD represent a subgroup of Asian youth at very high risk for a number of serious psychiatric disorders. Further investigation is needed to explain the high CD prevalence among NH/PI.

A better understanding of the long-term scope and impact of the co-morbidity with oppositional defiant disorder (ODD) and conduct disorder (CD) in attention deficit hyperactivity disorder (ADHD) youth has important clinical and public health implications.

Subjects were assessed blindly at baseline (mean age=10.7 years), 1-year (mean age=11.9 years), 4-year (mean age=14.7 years) and 10-year follow-up (mean age=21.7 years). The subjects' lifetime diagnostic status of ADHD, ODD and CD by the 4-year follow-up were used to define four groups (Controls, ADHD, ADHD plus ODD, and ADHD plus ODD and CD). Diagnostic outcomes at the 10-year follow-up were considered positive if full criteria were met any time after the 4-year assessment (interval diagnosis). Outcomes were examined using a Kaplan–Meier survival function (persistence of ODD), logistic regression (for binary outcomes) and negative binomial regression (for count outcomes) controlling for age.

ODD persisted in a substantial minority of subjects at the 10-year follow-up. Independent of co-morbid CD, ODD was associated with major depression in the interval between the 4-year and the 10-year follow-up. Although ODD significantly increased the risk for CD and antisocial personality disorder, CD conferred a much larger risk for these outcomes. Furthermore, only CD was associated with significantly increased risk for psychoactive substance use disorders, smoking, and bipolar disorder.

These longitudinal findings support and extend previously reported findings from this sample at the 4-year follow-up indicating that ODD and CD follow a divergent course. They also support previous findings that ODD heralds a compromised outcome for ADHD youth grown up independently of the co-morbidity with CD.

Interrogative suggestibility and compliance are important psychological vulnerabilities during interrogation. The aim of the study was to investigate the relationship of suggestibility and compliance with childhood and current symptoms of attention deficit hyperactivity disorder (ADHD). Compliance has not been studied previously in relation to ADHD. A further aim was to investigate the relationship between ADHD and the reporting of having made a false confession to the police.

The participants were 90 male prisoners, all of whom had completed the Gudjonsson Suggestibility and Compliance Scales (GSS and GCS) within 10 days of admission to the prison. Childhood ADHD symptoms were screened by the Wender Utah Rating Scale (WURS) and current adult symptoms by the DSM-IV Checklist criteria for ADHD.

Half of the prisoners (50%) were found on screening to meet criteria for ADHD in childhood and, of those, over half (60%) were either fully symptomatic or in partial remission of their symptoms. ADHD symptoms were found to be significantly associated with compliance, but not with suggestibility. The relationship with compliance was stronger (effect size) in relation to current than childhood symptoms. The ADHD symptomatic groups were significantly more likely to claim that they had made a false confession to the police in the past.

The findings raise important questions about the potential vulnerability of adults with ADHD symptoms in terms of their ability to cope with interrogation.

Although attention deficit hyperactivity disorder (ADHD) and bipolar disorder (BPD) co-occur frequently and represent a particularly morbid clinical form of both disorders, neuroimaging research addressing this co-morbidity is scarce. Our aim was to evaluate the morphometric magnetic resonance imaging (MRI) underpinnings of the co-morbidity of ADHD with BPD, testing the hypothesis that subjects with this co-morbidity would have neuroanatomical correlates of both disorders.

Morphometric MRI findings were compared between 31 adults with ADHD and BPD and with those of 18 with BPD, 26 with ADHD, and 23 healthy controls. The volumes (cm3) of our regions of interest (ROIs) were estimated as a function of ADHD status, BPD status, age, sex, and omnibus brain volume using linear regression models.

When BPD was associated with a significantly smaller orbital prefrontal cortex and larger right thalamus, this pattern was found in co-morbid subjects with ADHD plus BPD. Likewise, when ADHD was associated with significantly less neocortical gray matter, less overall frontal lobe and superior prefrontal cortex volumes, a smaller right anterior cingulate cortex and less cerebellar gray matter, so did co-morbid ADHD plus BPD subjects.

Our results support the hypothesis that ADHD and BPD independently contribute to volumetric alterations of selective and distinct brain structures. In the co-morbid state of ADHD plus BPD, the profile of brain volumetric abnormalities consists of structures that are altered in both disorders individually. Attention to co-morbidity is necessary to help clarify the heterogeneous neuroanatomy of both BPD and ADHD.

A variety of methodologies and techniques converge on the notion that adults and children with attention deficit hyperactivity disorder (ADHD) have similar deficits, but there is limited knowledge about whether adult retrospective reports reflect similar genetic and environmental influences implicated in childhood ADHD.

DSM-IV ADHD symptoms were collected retrospectively from 3896 young adults participating in the National Longitudinal Study of Adolescent Health. Responses from this genetically informative sample of same- and opposite-sex twins and siblings were used to determine the magnitude of genetic and environmental influences. Possible gender differences in these effects were also examined. The degree of familial specificity of the genetic and environmental influences on the Inattentive and Hyperactive-Impulsive symptom dimensions was also determined.

Additive genetic effects contributed moderately to DSM-IV Inattentive, Hyperactive-Impulsive and Combined ADHD subtypes (heritability estimates of 0.30–0.38). Individual-specific influences accounted for the remaining proportion of the variance. Both genetic and individual-specific environmental effects contributed to the covariation of Inattentive and Hyperactive-Impulsive symptomologies.

Results from our genetic analyses agree with previous findings based on self-assessment of current and retrospectively reported ADHD symptoms in adolescents and adults. Large individual-specific environmental influences as identified here suggest that current questionnaires used for retrospective diagnoses may not provide the most accurate reconstruction of the etiological influences on childhood ADHD in general population samples.