Over a century ago Beard referred to fatigue as the ‘Central Africa of medicine – an unexplored territory which few men enter’ (Beard, 1869). The last decade has seen major advances in our understanding of chronic fatigue syndrome (CFS). Much is now known of the epidemiology, clinical features and prognosis of the condition (Wessely et al. 1998), and a number of recent papers have reported randomized trials of successful treatments involving cognitive behaviour therapy (CBT) and graded exercise (Sharpe et al. 1996; Wearden et al. 1996; Deale et al. 1997; Fulcher & White, 1997). Despite these advances, which have defined some of the broad landmarks of the illness, and improved the care of patients, many areas remain uncharted. Several papers published in this issue of Psychological Medicine take us into such unexplored territory.

Background. Prolonged fatigue syndromes have been proposed as prevalent and disabling forms of distress that occur independently of conventional notions of anxiety and depression.

Methods. To investigate the genetic and environmental antecedents of common forms of psychological and somatic distress, we measured fatigue, anxiety, depression and psychological distress in 1004 normal adult twin pairs (533 monozygotic (MZ), 471 dizygotic (DZ)) over 50 years of age.

Results. Familial aggregation of psychological distress, anxiety and fatigue appeared to be due largely to additive genetic factors (MZ[ratio ]DZ ratios of 2·12–2·69). The phenotypic correlations between the psychological measures (distress, anxiety and depression) were moderate (0·67–0·79) and higher than that between fatigue and psychological distress (0·38). Multivariate genetic modelling revealed a common genetic factor contributing to the development of all the observed phenotypes (though most strongly for the psychological forms), a second independent genetic factor also influenced anxiety and depression and a third independent genetic factor made a major contribution to fatigue alone. In total, 44% (95% CI 25–60%) of the genetic variance for fatigue was not shared by the other forms of distress. Similarly, the environmental factor determining psychological distress made negligible contributions to fatigue, which was underpinned largely by its own independent environmental factor.

Conclusion. This study supports the aetiological independence of prolonged fatigue and, therefore, argues strongly for its inclusion in classification systems in psychiatry.

Background. Although there is considerable support for adverse relationships between states of psychological and somatic distress and immune response, there is little evidence in humans of the relative contribution of genetic and environmental factors.

Methods. This study utilized a twin methodology to examine the interplay between psychological distress, fatigue and immune function. We recorded a number of measures of distress, including conventional depression and anxiety as well as the somatic symptom of prolonged fatigue, and immune responsiveness (by delayed-type hypersensitivity skin response) in 124 normal adult twin pairs (79 monozygotic, 45 dizygotic).

Results. While there were strong genetic influences on the psychological distress and fatigue factors (only some of which are common to both), familial aggregation of immune responsiveness arose mainly from environmental factors shared by both members of a twin pair. Phenotypic correlations between psychological and immune measures were negligible, but multivariate genetic modelling revealed that these masked larger genetic and environmental correlations of opposite sign. Negative environmental effects of psychological distress and fatigue on immune responsiveness were countered by a positive genetic relationship between psychological distress and immune function.

Conclusions. Our study suggests that current psychoneuroimmunological hypotheses in humans need to be modified to place increasing importance on the individual's genotype. In this cohort immune responsiveness varied in response to a complex interplay of genetic and environmental factors. Additionally, although psychological distress and fatigue had some shared genetic determinants, independent genetic and environmental risk factors for fatigue were also identified.

Background. Medically unexplained chronic fatigue in childhood may cause considerable disability and (by definition) its cause remains unclear. A study of fatigue in healthy twins has been undertaken to examine whether or not genetic factors play a part.

Method. A questionnaire survey of the main carers of an epidemiological population-based sample of 670 twin pairs who were asked about periods of unexplained and disabling fatigue in their twins. Out of 1340 individuals a period of disabling fatigue was reported for 92 (6·9%). Thirty-three (2·5%) reported disabling fatigue for more than 1 month. Zygosity could be confidently assigned in 98% of the sample providing 278 monozygotic (MZ) and 378 dizygotic (DZ) pairs. These data were analysed using a structural equation modelling approach.

Results. The results showed that disabling fatigue in childhood is highly familial with an MZ tetrachoric correlation (rMZ) of 0·81 and a DZ tetrachoric correlation (rDZ) of 0·59, for fatigue lasting at least a week. The most acceptable model using Akaike's information criteria, was one containing additive genetic effects (A) and shared environment (C) plus residual (or non-shared) environment (E). For fatigue lasting at least a month rMZ was 0·75 and rDZ 0·47. The most acceptable model included just A and E. However, the role of shared environment could not be conclusively rejected.

Conclusions. Unexplained disabling fatigue in childhood is substantially familial. Both genetic and shared environmental factors are worth further exploration in a search for the causes.

Background. Chronic fatigue syndrome (CFS) patients often complain that they are more susceptible to acute mental fatigue. It is important to determine whether this is observed using objective tests of sustained attention and responding.

Methods. Sixty-seven patients who fulfilled the criteria for CFS proposed by Sharpe et al. (1991) were compared with 126 matched healthy controls. Acute fatigue was assessed by comparing performance at the start and end of a lengthy test session and by examining changes over the course of individual tasks.

Results. CFS patients showed impaired performance compared to the controls and these differences increased as the volunteers developed acute fatigue. In addition, differences between the two groups were larger at the end of the test session.

Conclusions. The present results show that CFS patients are more susceptible to acute fatigue than healthy controls. This could reflect motor fatigue or an inability to compensate for fatigue with increased effort. This profile is consistent with previous research on fatigue and suggests that interpretation of certain aspects of CFS may be helped by considering it as the end point of a continuum of fatigue rather than a distinct disease.

Background. Infectious diseases are accompanied by behavioural and psychological changes that suggest the implication of the central nervous system. Among them, cognitive alterations have been reported, but their specificity and implication in everyday life are still largely unclear. The purpose of the present study was to evaluate and specify the everyday memory disturbances in sick human subjects and to determinate the role of fever in the appearance of these alterations.

Methods. The study was carried out in a military training centre for naval recruits. Ninety-one volunteer subjects, healthy (N=30) or suffering from flu-like syndrome, with (N=29) or without fever (N=32), participated in this experiment and were administered a cognitive test (the ERBMT) according to a cross-sectional design for assessing various aspects of everyday memory.

Results. Sick subjects were specifically impaired in daily memory tasks that require the temporary management of a large amount of information. This impairment was similar for the feverish and apyretic sick subjects who both differed from the controls.

Conclusion. These findings suggest that infectious disease disturbs the complex cognitive processes that might be associated with attentional functions. Moreover, these results show that fever is not a necessary condition for the appearance of these cognitive disturbances.

Background. The development of drug dependence requires prior initiation. What is the relationship between the risk factors for initiation and dependence?

Methods. Using smoking as a model addiction, we assessed smoking initiation (SI) and nicotine dependence (ND) by personal interview in 1898 female twins from the population-based Virginia Twin Registry. We developed a twin structural equation model that estimates the correlation between the liability to SI and the liability to ND, given SI.

Results. The liabilities to SI and ND were substantially correlated but not identical. Heritable factors played an important aetiological role in SI and in ND. While the majority of genetic risk factors for ND were shared with SI, a distinct set of familial factors, which were probably partly genetic, solely influenced the risk for ND. SI was associated with low levels of education and religiosity, high levels of neuroticism and extroversion and a history of a wide range of psychiatric disorders. ND was associated with low levels of education, extroversion, mastery, and self-esteem, high levels of neuroticism and dependency and a history of mood and alcohol use disorders.

Conclusions. The aetiological factors that influence SI and ND, while overlapping, are not perfectly correlated. One set of genetic factors plays a significant aetiological role in both SI and ND, while another set of familial factors, probably in part genetic, solely influences ND. Some risk factors for SI and ND impact similarly on both stages, some act at only one stage and others impact differently and even in opposite directions at the two stages. The pathway to substance dependence is complex and involves multiple genetic and environmental risk factors.

Background. The paper describes prevalence, impairments, patterns of co-morbidity and other correlates of DSM-IV social phobia in adolescents and young adults, separating generalized and non-generalized social phobics.

Methods. Data are derived from the baseline investigation of the Early Developmental Stages of Psychopathology Study (EDSP), a prospective longitudinal community study of 3021 subjects, aged 14–24. Diagnoses were based on the DSM-IV algorithms of an expanded version of the Composite International Diagnostic Interview.

Results. Lifetime prevalence of DSM-IV/CIDI social phobia was 9·5% in females and 4·9% in males, with about one-third being classified as generalized social phobics. Twelve-month prevalence was only slightly lower, indicating considerable persistence. Respondents with generalized social phobia reported an earlier age of onset, higher symptom persistence, more co-morbidity, more severe impairments, higher treatment rates and indicated more frequently a parental history of mental disorders than respondents with non-generalized social phobia.

Conclusions. History of DSM-IV social phobia was found to be quite prevalent in 14–24 year-olds. The generalized subtype of social phobia was found to have different correlates and to be considerably more persistent, impairing and co-morbid than non-generalized social phobia. Although generalized social phobics are more likely than non-generalized social phobics to receive mental health treatments, the treatment rate in this sample was low despite the fact that mental health services are free in Germany.

Background. There is debate as to whether the elderly are really at lower risk for depressive disorders, or whether endorsement of symptoms is artefactually low. The present paper assesses the effects of age on anxiety and depression, and examines whether age has direct effects on self-report of individual symptoms independent of its effect on the underlying dimensions of anxiety and depression.

Methods. Structural equation modelling was used to assess the structure of the items and their associations with age and a number of demographic variables. The sample of 2622 participants aged between 18 and 79 years from Canberra (Australia) was drawn from the Electoral Roll. Two instruments were used: the anxiety and depression scales of Goldberg et al. (1988) and the Personal Disturbance Scale from the DSSI of Bedford et al. (1976).

Results. Both scales were found to fit satisfactorily to a two factor model. Age correlated negatively with depression. After controlling for the effects of gender, marital status, education and financial difficulty, direct effects of age were found on items from both instruments, indicating that certain depression items were associated with a differential probability of endorsement in older people, even when the level of depression was equal to that of younger people. Items with direct age effects reflected physical (feeling slowed down; waking early) and psychological (hopeless about the future) components of depression. Direct effects of age on items from both anxiety scales were also found.

Conclusions. The nature of the depression and anxiety experienced by younger and older people may differ qualitatively. Depression may be associated with an increase in somatic symptoms linked to physical changes and to an increase in endorsement of items which reflect the narrowing of opportunities in the long-term.

Background. Our prior psychometric work suggested that older adults interviewed in 1981 in a community survey were less likely than younger adults to report dysphoria. We hypothesized that this would also be true of older adults interviewed 13 years later.

Methods. This study is a population-based 13-year follow-up survey of community-dwelling adults living in East Baltimore in 1981. Subjects were the continuing participants of the Baltimore Epidemiologic Catchment Area Program. After excluding 269 adults who were 65 years of age and older at initial interview in 1981, 1651 adults remained (347 aged 65 years and older and 1304 who were 30–64 years-old at follow-up).

We applied structural equations with a measurement model for dichotomous data (the MIMIC – multiple indicators, multiple causes – model) to compare symptoms between adults who were 65 years and older at follow-up with younger adults, in relation to the nine symptom groups comprising the diagnostic criteria for major depression, adjusting for several potentially influential characteristics (namely, gender, self-reported ethnicity, educational attainment, cognitive impairment, marital status and employment).

Results. Older adults were less likely to endorse sadness as evidenced by a direct effect coefficient of −0·335 (95% Confidence Interval −0·643, −0·027). After adjusting for several potentially influential characteristics, the direct effect of age was substantially unchanged (−0·298 (95% CI −0·602, −0·006)).

Conclusions. Older adults in 1994, like older adults in 1981, were less likely to endorse sadness than younger persons. This finding suggests, but does not prove, that the observed age difference in reporting depression does not reflect a cohort effect.

Background. Evidence on the adult adaptation of individuals with mild mental retardation (MMR) is sparse, and knowledge of the factors associated with more and less successful functioning in MMR samples yet more limited.

Method. Prospective data from the National Child Development Study were used to examine social circumstances and psychosocial functioning in adulthood in individuals with MMR and in a non-retarded comparison group.

Results. For many individuals with MMR, living circumstances and social conditions in adulthood were poor and potential stressors high. Self-reports of psychological distress in adulthood were markedly elevated, but relative rates of psychiatric service use fell between childhood and adulthood, as reflected in attributable risks. Childhood family and social disadvantage accounted for some 20–30% of variations between MMR and non-retarded samples on a range of adult outcomes. Early social adversity also played a significant role in contributing to variations in functioning within the MMR sample.

Conclusions. MMR appears to be associated with substantial continuing impairment for many individuals.

Background. This study examined whether traumatic grief, depressive and anxiety symptoms formed three distinct factors for widows and widowers. In addition, we examined whether high symptom levels of traumatic grief, depression and anxiety predicted different mental and physical health outcomes for widows and widowers.

Method. Ninety-two future widows and 58 future widowers were interviewed at the time of their spouse's hospital admission and then at 6 weeks, 6, 13 and 25 month follow-ups. Principal axis factor analyses tested the distinctiveness of traumatic grief, depressive and anxiety symptoms, by gender. Repeated measures ANOVA tested for gender differences and changes over time in mean symptom levels of traumatic grief, depression and anxiety. Linear and logistic regression models estimated the effects of high symptom levels of traumatic grief, depression and anxiety at 6 months on health outcomes at 13 and 25 months post-intake by gender.

Results. Three distinct symptom clusters (i.e. traumatic grief, depressive and anxiety symptoms) were found to emerge for both widows and widowers. Widows had higher mean levels of traumatic grief, depressive and anxiety symptoms. High symptom levels of traumatic grief measured at 6 months predicted a physical health event (e.g. cancer, heart attack) at 25 months post-intake for widows. High symptom levels of anxiety measured at 6 months predicted suicidal ideation at 25 months for widowers.

Conclusions. The results suggest that there are gender differences in the levels of psychological symptoms resulting from bereavement and in their effects on subsequent mental and physical health for widows and widowers.

Background. Evidence is conflicting as to whether the association between marital status and psychological distress is due to selection (i.e. distress influences marital status) or causation (marital status influences distress). We investigate: (i) whether differences in psychological distress pre-date marital transitions; (ii) whether levels of distress change following transitions; and (iii) potential mediating and moderating factors.

Methods. Data on psychological distress (indicated by the Malaise Inventory) and marital status at ages 23 and 33 were analysed for 4514 men and 4842 women from the 1958 birth cohort.

Results. Higher levels of distress were found among the divorced and lower levels among the single and the married. Selection was seen in the lower initial mean symptoms of those who married (1·69 for men; 2·84 for women) compared to those remaining single (2·41 for men; 3·26 for women). Causation was indicated by the relative deterioration in distress of those who divorced compared to the continuously married (an increase of 0·31 and 0·03 respectively for men), especially in women (a decrease of 0·18 versus 0·71). This was most evident in women who were downwardly mobile and those with children. Recently separated men and women showed especially large increases in distress.

Conclusions. The relationship between marital status and psychological distress involves selection and causation. Findings failed to support ideas of marriage being protective (through social support), or detrimental (through family roles). Divorce increased distress, with both acute and longer-term components moderated by secondary factors such as childcare and declining socio-economic status.

Background. Perception of deficiencies in immunity are common in a number of patient complaints. However, little is known about the way in which individuals form perceptions about the competence of their immune system. In two studies we examined the relationship between subjects' perceptions of their immune functioning, physical symptoms, mood and measures of immunity.

Methods. In Study 1, 20 healthy volunteers completed global ratings of their immune system functioning, as well as mood and symptom reports, twice a week for 5 weeks. At the same time, blood samples were taken to assess serum IgA, IgG, and IgM antibodies. In Study 2, another sample of 58 subjects completed the same measures weekly for 5 weeks and their blood was tested for concentrations of CD3, CD4, CD8, and CD16 lymphocytes.

Results. We found perceptions of immune functioning to be unrelated to the concentrations of serum antibodies or blood lymphocytes. Immune perceptions were strongly related to mood and in particular, feelings of fatigue and vigour. The experience of recent physical symptoms, while not as strong as mood variables, was also important in perceptions of immune functioning.

Conclusions. Mood seems to be an important determinant in the perception of immune function, and complaints about immune dysfunction in clinical situation should be investigated with this possibility in mind.

Background. Physical symptoms are commonly presented for treatment in the absence of physical pathology. This study tests predictions arising from the theory that childhood sexual abuse leads to emotional distress, illness orientation and social dysfunction as adults and that one or more of these effects, in turn, leads to presentation of functional (i.e. unexplained) symptoms.

Methods. Two groups of patients with physical symptoms in the absence of organic disease (non-epileptic attack disorder or irritable bowel syndrome) were contrasted with organically diseased groups with comparable symptoms (epilepsy and Crohn's disease, respectively).

Results. Despite their contrasting clinical presentation, irritable bowel and non-epileptic attack groups were similar in recalling more sexual and physical abuse, as both children and adults, than their comparison groups. They were also similar in being more emotionally and socially disturbed and illness-orientated, but these putative mediating variables could not account for the relationship of abuse with presentation of functional symptoms.

Conclusions. Adults presenting functional neurological and abdominal symptoms are characterized by history of abuse. The current focus on childhood sexual abuse should be broadened to include sexual, and particularly physical, abuse in adulthood as well as childhood. The intervening processes that link abuse to somatization remain to be identified but are unlikely to include adult emotional and social disturbance or general illness-orientation.

Background. The purpose of this study was to assess clinical characteristics, including co-morbid personality disorders in patients with both anorexia nervosa (AN) and obsessive–compulsive disorder (OCD) in comparison with age- and sex-matched patients with OCD.

Methods. Fifty-three female patients with AN were divided into two groups based on the presence or absence of a current diagnosis of OCD, as assessed by the Structured Clinical Interview for DSM-III-R Patient version (SCID-P). Twenty-one women (40%) who met the DSM-III-R criteria for both AN and OCD were compared with 23 female patients with OCD, using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and the SCID Axis II disorders.

Results. There were no significant differences on the mean Y-BOCS severity scores between these groups. However, AN patients with OCD were significantly more likely than OCD patients to have obsessions with need for symmetry or exactness and ordering/arranging compulsions, whereas both aggressive obsessions and checking compulsions tended to be more frequently identified in OCD patients compared with AN patients with OCD. AN patients with OCD were significantly more likely than OCD patients to meet the criteria for obsessive–compulsive personality disorder (OCPD).

Conclusions. These results suggest that there are some differential characteristics of the OCD symptomatology between these disorders, although many patients with AN manifest significant impairment from primary OCD symptoms with similar magnitude in severity to that found in OCD patients.

Background. Investigators have used various experimental paradigms such as the Stroop colour naming test to study how adults with different emotional disorders process emotional information. However, to date, little research has been carried out on younger subjects.

Method. In the current experiment, children and adolescents with post-traumatic stress disorder (PTSD) and control subjects aged 9–17 years, participated in a modified Stroop colour naming task.

Results. The results indicated that the children and adolescents with PTSD showed increased Stroop interference for trauma-related material relative to neutral words and to the performance of the controls.

Conclusions. These findings indicate that attentional bias to trauma-congruent information is a function of PTSD in young age groups. The results are discussed with respect to the literature on information processing in PTSD.

Background. Numerous studies have shown that anxiety and depression are related to cognitive impairment, but the concomitant association between anxious symptoms, depressive symptoms and cognitive function has not been investigated, and, most studies have not considered psychotropic drug use as a possible confounding factor.

Methods. We assessed the independent association between depression, anxiety, psychotropic drug use and cognitive performance in 457 men and 659 women, aged 59–71 years living in the community. Data on demographic background, occupation, medical history, drug use and personal habits were obtained using a standardized questionnaire. The Spielberger Inventory Trait and the Center for Epidemiologic Study-Depression (CES-D) scales were used to evaluate anxious and depressive symptomatology respectively. Cognitive assessment included six traditional tests covering the main areas of cognitive functioning.

Results. In men, anxious and depressive symptomatologies had independent significant associations with most cognitive abilities, independent of psychotropic drug use. In women, the association between anxiety or depression and cognitive functioning was less strong and disappeared after adjustment for psychotropic drug use. Psychotropic drug use was associated with lower cognitive scores in both sexes. In men with high CES-D scores, we found positive correlations between anxiety level and cognitive scores.

Conclusions. The study showed that anxiety, depression and psychotropic drug use were significantly and independently associated with cognitive functioning in elderly men. The high prevalence of psychotropic drug use in women with or without psychological disorders may explain its major effect in women. Results suggested that anxiety may partly compensate for some negative effects of depression on cognitive functioning.

Background. The relationship between ethnicity and suicide risk is ill-understood. It is unclear whether, and if so, how, the ethnic mix of local areas affects risk in local individuals.

Methods. Coroners' records of 329 suicides were used to obtain ethnic (White, Afro-Caribbean, Asian) suicide rates in South London (population 902008) for 1991–3. Geographical variation and associations of ethnic suicide rates with small area (mean population 8274) ethnic densities (proportion of residents of given ethnic groups) and deprivation, were examined with random effects Poisson regression.

Results. Adjusted for deprivation, age and gender, suicide rates in wards with larger minority groups were higher among Whites (relative rate (RR) per standard deviation (S.D.) increase in minority density 1·18; 95% CI 1·02–1·37) but lower among minority groups (RR 0·75 (0·59–0·96)) (LR-test for interaction χ2=9·2 (df=1); P=0·003). Similar patterns were also apparent for Afro-Caribbeans and Asians separately. With White suicide rates as baseline, ethnic minority status is a risk factor for suicide in wards with small, but a protective factor in neighbourhoods with large minority populations. The RR of minority versus White suicide declines with a factor (relative RR) 0·67 (0·51–0·87) per S.D. increase in local minority density.

Conclusions. Minority suicide rates are higher in areas where minority groups are smaller. This effect is ethnic-specific and not due to confounding by gender, age, deprivation or unbalanced migration. Dependent on address, a suicide risk factor for a White individual may protect an ethnic minority individual and vice versa. This has implications for research and prevention.

Background. Assessment of capacity plays a pivotal role in determining when decisions need to be made on behalf of an individual. It therefore has major clinical management implications for health care professionals and civil liberties implications for the person concerned. In many countries, there is a presumption that adults have the capacity to make health care decisions. However, in persons with a mental disability, capacity may be temporarily or permanently impaired.

Methods. A selective review is presented which considers: (i) the broad approaches taken to determining capacity; (ii) the abilities commonly assessed in determining capacity; and (iii) the principles underlying health care decision-making for adults who are without capacity.

Results. Capacity is a functional concept, determined by the person's ability to understand, retain, and weigh up information relevant to the decision in order to arrive at a choice, and then to communicate that choice. We have reviewed the studies that examined decision-making abilities in people with dementia, chronic mental illness or intellectual disabilities. Approaches to decision-making in adults who lack capacity include: anticipatory decisions made through advance health care statements or decisions by proxy based on ‘best interests’ or ‘substituted judgement’.

Conclusions. The understanding of clinical and legal aspects of capacity is still developing. This paper examines current concepts of capacity and decision-making on behalf of those without capacity. We propose a framework, in line with current ethical and legal guidelines, as an aid to clinicians when they are seeking consent for a health care intervention.