Adults with putative attention deficit hyperactivity disorder (ADHD) are increasingly being referred to psychiatric clinics, often following a self-diagnosis, and demanding a prescription for stimulant medication. This has disconcerted many clinicians and started a debate on the appropriateness of this diagnosis in adults (Shaffer, 1994; Lomas, 1995; Diller, 1996) that is reminiscent of the controversies of the childhood diagnosis in previous years (Lancet, 1986). At issue is not only concern about the widespread use of stimulant medication, but also a neurobiological understanding of impulsivity, hyperactivity and antisocial behaviour and the genesis of some psychiatric disorders in adults. How is the validity of this disorder in adults then to be established?

The recent and pending introduction of new antipsychotic medications carries the hope of a significant advance in the treatment of schizophrenia. Although the propensity of these agents to cause fewer motor side-effects than conventional neuroleptics may lead to improved compliance and clinical effectiveness, the promise of a significant impact upon the lives of patients may primarily reside in the evidence that the atypicals alleviate negative features such as emotional flattening, social withdrawal and impoverished speech. Auditory hallucinations and delusional thinking are the more dramatic expressions of illness, but these negative symptoms, along with neuropsychological deficits, are arguably more responsible for the persisting debilitation exhibited by schizophrenics (McKay, 1980; Pogue-Geile & Harrow, 1985; Breier et al. 1991; Crow, 1991; Mukherjee et al. 1991; Kane & Freeman, 1994; Perlick et al. 1992; Green, 1996; Green et al. 1997). Negative symptoms and neuropsychological deficits are minimally responsive to conventional neuroleptics (Goldberg et al. 1991; Meltzer, 1992; Lee et al. 1994; Meltzer et al. 1994), leaving schizophrenics ill-equipped to deal with the demands of normal living.

The claim is often made that clozapine alleviates both negative symptoms and neurocognitive deficits (e.g. Meltzer, 1995a). Although there is hope that the newer antipsychotics will do likewise, the evidence for neurocognitive gains in particular is, so far, limited. Only a few studies of the effects of novel antipsychotics (such as risperidone, olanzapine, sertindole and related in-trial agents) on neuropsychological functioning have been undertaken. When effects have been demonstrated, their significance has remained unclear.

This state of affairs is unsatisfactory, as a positive impact upon neuropsychological functioning would be of interest for more than just clinical reasons. An amelioration of cognitive deficiencies would suggest that these features are not inexorably tied to an irreversible pathology, such as gross neurodevelopmental aberrations or loss of neural tissue. Rather, such gains would suggest a treatable underlying pathophysiology, lending hope to other treatments, including cognitive rehabilitation. Since these deficits are increasingly viewed as fundamental to our conceptions of severe psychiatric illness (Goldberg et al. 1991; Green, 1996; Nuechterlein & Subotnik, 1996), neurocognitive changes might reciprocally shed light on these medications and schizophrenia. Finally, differential effects on cognition across medications should be factored into cost–benefit analyses, particularly when these effects are accompanied by broader adaptive functioning gains.

Is there any reason to believe that the novel antipsychotics will significantly improve the functional capacities of schizophrenics? Several considerations are relevant, including purported action mechanisms, animal behaviour findings, neurological effects, negative symptoms effects and existing cognitive outcome data.

Psychiatric case-identification in general populations allows us to study both individuals with functional psychiatric disorders and the populations from which they come. The individual level of analysis permits disorders to be related to factors of potential aetiological significance and the study of attributes of the disorders that need to be assessed in non-referred populations (an initially scientific endeavour). At the population level valid case identification can be used to evaluate needs for treatment and the utilization of service resources (a public health project). Thus, prevalence is of interest both to scientists and to those responsible for commissioning and planning services (Brugha et al. 1997; Regier et al. 1998). The quality of case identification techniques and of estimates of prevalence is thus of general concern (Bartlett & Coles, 1998).

Structured diagnostic interviews were introduced into general population surveys in the 1970s as a method ‘to enable interviewers to obtain psychiatric diagnoses comparable to those a psychiatrist would obtain’ (Robins et al. 1981). The need to develop reliable standardized measures was partly driven by an earlier generation of prevalence surveys showing rates ranging widely from 10·9% (Pasamanick et al. 1956) to 55% (Leighton et al. 1963) in urban and rural North American communities respectively. If the success of large scale psychiatric epidemiological enquiries using structured diagnostic interviews and standardized classifications is measured in terms of citation rates it would seem difficult to question. But the development of standardized interviews of functional psychiatric disorders has not solved this problem of variability: the current generation of large scale surveys, using structured diagnostic interviews and serving strictly defined classification rules, have generated, for example, 12-month prevalence rates of major depression in the US of 4·2% (Robins & Regier, 1991) and 10·1% (Kessler et al. 1994). This calls into question the validity of the assessments, such that we must reopen the question of what they should be measuring and how they should do it.

Psychiatric epidemiology is becalmed. Since mid-century, there has been substantial progress in finding risk factors for the common mental disorders of anxiety and depression. This has been almost entirely within a social paradigm. Much has been learned about the effects of interpersonal and other social exposures across the lifespan in contributing to these disorders (Brown & Harris, 1978, 1989; Paykel, 1992; Blazer, 1995; Henderson, 1988, 1999). But the range of possibly causal variables has been narrow: demography, socio-economic status, childhood experiences, recent exposure to adversity and the availability of social support. The dominant paradigm has been environmental exposure, examining how experiences that arise outside the individual may have an enduring impact on mental health. The environment in question has been interpersonal or social. Within this paradigm, no new hypotheses of major significance have emerged in recent years.

Epidemiologists have known that the biological domain might be important in aetiology, but for the common mental disorders it has been largely passed over. Properties of the adult brain, whether innate or moulded by environmental exposures, have only rarely been accessible. With the advances in molecular genetics, this is changing (Rutter & Plomin, 1997). For epidemiology, there is now the possibility of bringing molecular genetics into studies of aetiology. Because of the significance of this development, we present a critical assessment of the prospects for population-based research using molecular genetics, the work already reaching publication and the methodological issues that are arising.

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. Mental health service research continues to use only outcome measures that are available rather than develop measures that are important. This paper argues that it is necessary to select and then define a set of ethical principles that can be operationalized and validated as outcome measures to provide a wider balance of information for health policy and clinical service decisions.

Methods. The method used is to adopt a five stage procedure: (i) to select ethical principles most directly relevant for mental health services and their evaluation at the local level; (ii) to propose definitions of these principles; (iii) to validate these definitions; (iv) to translate the defined principles into operationalized outcome measures; and (v) to use these outcome measures in mental health services research, within the context of evidence-based medicine.

Results. We address steps (i) and (ii) of this five-stage procedure. Nine principles are selected and defined: autonomy, continuity, effectiveness, accessibility, comprehensiveness, equity, accountability, coordination and efficiency. These principles can together be referred to as the three ACEs.

Conclusions. Of these nine principles, only two (effectiveness and efficiency) have so far been fully translated into quantitative outcome measures, upon which the evidence-based medicine approach depends. We propose that further concepts also be developed into a more complete multi- dimensional range of fully operationalized outcome measures.

Background. There are few cross-national comparisons of the rates of suicide ideation and attempts across diverse countries. Nine independently conducted epidemiological surveys using similar diagnostic assessment and criteria provided an opportunity to obtain that data.

Methods. Suicide ideation and attempts were assessed on the Diagnostic Interview Schedule in over 40000 subjects drawn from the United States, Canada, Puerto Rico, France, West Germany, Lebanon, Taiwan, Korea and New Zealand.

Results. The lifetime prevalence rates/100 for suicide ideation ranged from 2·09 (Beirut) to 18·51 (Christchurch, New Zealand). Lifetime prevalence rates/100 for suicide attempts ranged from 0·72 (Beirut) to 5·93 (Puerto Rico). Females as compared to males had only marginally higher rates of suicidal ideation in most countries, reaching a two-fold increase in Taiwan. Females as compared to males had more consistently higher rates for suicide attempts, reaching a two- to three-fold increase in most countries. Suicide ideation and attempts in most countries were associated with being currently divorced/separated as compared to currently married.

Conclusions. While the rates of suicide ideation varied widely by country, the rates of suicide attempts were more consistent across most countries. The variations were only partly explained by variation in rates of psychiatric disorders, divorce or separation among countries and are probably due to cultural features that we do not, as yet, understand.

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.

Brugha and his colleagues in this issue raise important questions about the validity of standardized diagnostic interviews of mental disorders, such as the Composite International Diagnostic Interview (CIDI) (WHO, 1990). Although their concerns refer predominantly to the use of such instruments in epidemiological research, the authors' conclusions also have significant implications for diagnostic assessments in clinical practice and research. We agree with Brugha et al. that the inflexible approach to questioning used in standardized interviews can lead to an increased risk of invalidity with regard to some diagnoses. We also agree that the use of more semi-structured clinical questions has the potential to address this problem. However, we disagree with Brugha et al. in several other respects.

First, we disagree with the authors' initial exclusive emphasis on diagnosis with regard to need assessment and consequences for the allocation of service resources. It is becoming increasingly clear that knowledge about diagnosis does not, in itself, whether assessed by clinical or non-clinical diagnostic interviews, provide sufficient information we need for policy purposes and the determination of societal costs, or to judge clinical management guidelines and treatment needs (Regier et al. 1998). Additional, preferably dimensional, data on associated disabilities and distress as well as a focused need evaluation for those psychosocial, psychological and drug interventions that characterize modern treatment strategies are also important. It also has become evident that a great many people in the general population carry more than one diagnosis. This ‘co-morbidity’ complicates further such simple equation of diagnosis prevalence with need assessment and policy decisions. Secondly, we disagree with the conclusion of Brugha et al. that the use of a semi-structured clinical interview, like the most current version of the Structured Clinical Assessment for Neuropsychiatry (SCAN), whether in the hands of clinical or non-clinical interviewers, is most closely approximating the ‘clinical gold standard’ and is the most feasible way to correct the problem of disagreement between semi-structured clinical diagnostic interviews and standardized diagnostic interviews. We believe that the practical reliability and validity problems associated with using such a clinical interviewing approach especially in large-scale community surveys as well as in cross-national research more than cancel out any theoretical advantage this approach might have in clarifying meaning. Thirdly, we disagree with the suggestion of Brugha et al. that the problem of validity is inherent in standardized non-clinician interviews. Indeed, as detailed below, there is no evidence that across all diagnoses clinical semi-structured interviews reveal more promising psychometric properties than standardized interviews. Also methodological research shows quite clearly that a substantial number of potential validity problems in standardized interviews can be overcome.

Background. Previous research has reported co-morbidity between attention deficit hyperactivity disorder (ADHD) and anxiety disorders. Interpretation of these findings is complicated by symptom overlap in the clinical presentation of the disorders. We estimate the prevalence of ADHD in both the current and childhood histories of adults with anxiety disorders, while taking symptom overlap into account. We also evaluate the utility of the Wender Utah Rating Scale (WURS) for retrospective reporting of ADHD.

Methods. Consecutive admissions (N=149) to an anxiety disorders clinic were given a diagnostic and psychometric assessment. The WURS was administered to obtain a retrospective diagnosis of childhood ADHD. Twenty-nine of the 35 people surpassing the cut-off score on the WURS were given a structured interview of adult ADHD symptoms.

Results. The WURS contains many ‘internalizing’ items that may inflate retrospective accounts of ADHD. After taking this into account, there is still a significantly higher prevalence of ADHD in the retrospective reports of adults with anxiety disorders (15%) than would be expected by chance (4%). Furthermore, of those who meet retrospective criteria for ADHD, 45% (13 of 29) continue to meet diagnostic criteria for ADHD as adults.

Conclusions. The WURS may require considerable revision for use with clinical populations. In spite of these difficulties with retrospective assessment, available evidence indicates that ADHD is more prevalent in the histories of anxiety disordered patients than would be expected from base rates.

Background. There is some uncertainty about the rate and correlates of autism.

Method. Twenty-three epidemiological surveys of autism published in the English language between 1966 and 1998 were reviewed.

Results. Over 4 million subjects were surveyed; 1533 subjects with autism were identified. The methodological characteristics of each study are summarized, including case definition, case-finding procedures, participation rates and precision achieved. Across surveys, the median prevalence estimate was 5·2/10000. Half the surveys had 95% confidence intervals consistent with population estimates of 5·4–5·5/10000. Prevalence rates significantly increased with publication year, reflecting changes in case definition and improved recognition; the median rate was 7·2/10000 for 11 surveys conducted since 1989. The average male/female ratio was 3·8[ratio ]1, varying according to the absence or presence of mental retardation. Intellectual functioning within the normal range was reported in about 20% of subjects. On average, medical conditions of potential causal significance were found in 6% of subjects with autism, with tuberous sclerosis having a consistently strong association with autism. Social class and immigrant status did not appear to be associated with autism. There was no evidence for a secular increase in the incidence of autism. In eight surveys, rates for other forms of pervasive developmental disorders were two to three times higher than the rate for autism.

Conclusion. Based on recent surveys, a minimum estimate of 18·7/10000 for all forms of pervasive developmental disorders was derived, which outlines the needs in special services for a large group of children.

Background. Dysthymia is a common mental disorder, associated with considerable disability and high co-morbidity. This review assessed the role of pharmacological treatment.

Methods. All randomized-controlled trials that compared active drug versus placebo for dysthymic patients were included. Pooled relative risks (RR) and 95% confidence intervals (CI) were calculated with the Random Effect Model method. Where possible, number needed to treat and number needed to harm were estimated.

Results. Fifteen trials were included for the main comparisons. Similar results were obtained in terms of efficacy for different groups of drugs, such as tricyclic (TCA), selective serotonin reuptake inhibitors (SSRI), monoamine oxidase inhibitors (MAOI) and other drugs (sulpiride, amineptine, and ritanserin). The pooled RR treatment response was 0·68 (95% CI 0·59–0·78) for TCA, 0·64 (95% CI 0·55–0·74) for SSRIs, 0·59 (95% CI 0·48–0·71) for MAOIs. Other drugs (amisulpride, amineptine and ritanserin) showed similar results. Patients treated on TCA were more likely to report adverse events, compared with placebo. There were no differences in response to active treatment when dysthymia was compared to either dysthymia plus major depression or briefer non-major depressive states.

Conclusions. Drug treatment appears to be effective in the short-term management of dysthymic disorder. The choice of drug should take into account specific side-effects profile of each drug.

Background. Executive function deficits have been reported repeatedly in children with Attention Deficit Hyperactivity Disorder (ADHD). Stimulant medication has been shown to be effective in improving cognitive performance on most executive function tasks, but neuropsychological tests of executive function in this population have yielded inconsistent results. Methodological limitations may explain these inconsistencies. This study aimed to measure executive function in medicated and non-medicated children with ADHD by using a computerized battery, the Cambridge Neuropsychological Test Automated Battery (CANTAB), which is sensitive to executive function deficits in older patients with frontostriatal neurological impairments.

Methods. Executive function was assessed in 30 children with ADHD: 15 were stimulant medication naïve and 15 were treated with stimulant medication. These two groups were compared to 15 age, sex and IQ matched controls.

Results. The unmedicated children with ADHD displayed specific cognitive impairments on executive function tasks of spatial short-term memory, spatial working memory, set-shifting ability and planning ability. Impairments were also seen on spatial recognition memory and delayed matching to sample, while pattern recognition memory remained intact. The medicated children with ADHD were not impaired on any of the above executive function tasks except for deficits in spatial recognition memory.

Conclusions. ADHD is associated with deficits in executive function. Stimulant medication is associated with better executive function performance. Prospective follow-up studies are required to examine these effects.

Background. Comparisons of structured diagnostic interviews with clinical assessments in general population samples show marked discrepancies. In order to validate the CIS-R, a fully structured diagnostic interview used for the National Survey of Psychiatric Morbidity in Great Britain, it was compared with SCAN, a standard, semi-structured, clinical assessment.

Methods. A random sample of 1882 Leicestershire addresses from the Postcode Address File yielded 1157 eligible adults: of these 860 completed the CIS-R; 387 adults scores [ges ]8 on the CIS-R and 205 of these completed a SCAN reference examination. Neurotic symptoms, in the previous week and month only, were enquired about. Concordance was estimated for ICD-10 neurotic and depressive disorders, F32 to F42 and for depression symptom score.

Results. Sociodemographic characteristics closely resembled National Survey and 1991 census profiles. Concordance was poor for any ICD-10 neurotic disorder (kappa = 0·25 (95% CI, 0·1–0·4)) and for depressive disorder (kappa = 0·23 (95% CI, 0–0·46)). Sensitivity to the SCAN reference classification was also poor. Specificity ranged from 0·8 to 0·9. Rank order correlation for total depression symptoms was 0·43 (Kendall's tau b; P<0·001; N=205).

Discussion. High specificity indicates that the CIS-R and SCAN agree that prevalence rates for specific disorders are low compared with estimates in some community surveys. We have revealed substantial discrepancies in case finding. Therefore, published data on service utilization designed to estimate unmet need in populations requires re-interpretation. The value of large-scale CIS-R survey data can be enhanced considerably by the incorporation of concurrent semi-structured clinical assessments.

Background. A unique way of determining patterns of parent–offspring transmission of risk to affective disorders is to focus on aggregation within sibling pairs. We attempt to extend our previous finding that sibling aggregation is notable for anxiety disorders in a 10-year follow-up of siblings at high and low risk for depression, by virtue of parental diagnosis.

Methods. The sample, which included 173 unique sibling pairs in the high risk cohort, and 83 pairs in the low risk cohort, had been assessed using semi-structured clinical interviews three times over a 10-year period, spanning from childhood to adulthood. Sibling aggregation was quantified using pairwise odds ratios.

Results. Sibling aggregation in the high risk cohort was greater than aggregation in the low risk cohort for anxiety disorders, especially those that emerged in childhood, and later co-morbid disorders, especially major depressive disorder and suicide attempts.

Conclusions. Familial liability to affective disorders may be reflected most strongly by a developmental sequence of anxiety disorders in childhood followed by later depressive and suicidal behaviour in adolescence and adulthood.

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. The treatment of deliberate self-harm (parasuicide) remains limited in efficacy. Despite a range of psychosocial, educational and pharmacological interventions only one approach, dialectical behaviour therapy, a form of cognitive-behaviour therapy (CBT), has been shown to reduce repeat episodes, but this is lengthy and intensive and difficult to extrapolate to busy clinical practice. We investigated the effectiveness of a new manual-based treatment varying from bibliotherapy (six self-help booklets) alone to six sessions of cognitive therapy linked to the booklets, which contained elements of dialectical behaviour therapy.

Methods. Thirty-four patients, aged between 16 and 50, seen after an episode of deliberate self-harm, with personality disturbance within the flamboyant cluster and a previous parasuicide episode within the past 12 months, were randomly assigned to treatment with manual-assisted cognitive-behaviour therapy (MACT N=18) or treatment as usual (TAU N=16). Assessment of clinical symptoms and social function were made at baseline and repeated by an independent assessor masked to treatment allocation at 6 months. The number and rate of all parasuicide attempts, time to next episode and costs of care were also determined.

Results. Thirty-two patients (18 MACT; 14 TAU) were seen at follow-up and 10 patients in each group (56% MACT and 71% TAU) had a suicidal act during the 6 months. The rate of suicidal acts per month was lower with MACT (median 0·17/month MACT; 0·37/month TAU; P=0·11) and self-rated depressive symptoms also improved (P=0·03). The treatment involved a mean of 2·7 sessions and the observed average cost of care was 46% less with MACT (P=0·22).

Conclusions. Although limited by the small sample, the results of this pilot study suggest that this new form of cognitive-behaviour therapy is promising in its efficacy and feasible in clinical practice.

Background. Lifetime rates of depression reported in epidemiological surveys are generally only twice the 12 month rates. Either people forget the symptoms of depression or many people who have a depressive episode remain depressed for many years. Both may be true. There is a need to examine the long-term clinical validity of interviews that are used to make lifetime diagnoses.

Methods. Forty-five patients who were part of a long-term follow-up study of depression were interviewed 25 years after the index episode. The diagnoses from the original, fully structured interviews were compared with the responses people made for that period when interviewed using the CIDI 25 years later.

Results. Twenty-seven patients met CIDI DSM-III-R criteria for depression at index episode. At the 25 year follow-up, 19 of the 27 reported the essential symptoms of ‘depression or loss of interest’ being present at the index time, and in 14 of the 27 the depressive symptoms recalled met criteria for DSM-III-R major depressive episode at that time.

Conclusions. Seventy per cent of people who were hospitalized for a major depressive episode can recall being depressed but only half can recall sufficient detail to satisfy the diagnostic criteria when interviewed 25 years later. As depressive episodes, especially those severe enough to warrant admission, are recalled better than many other diagnoses, one must be cautious about the lifetime rates for mental disorders reported in retrospective epidemiological surveys.

Background. Throughout their reproductive years, women suffer from a higher prevalence of depression than men. Before puberty, however, this is not the case. In an earlier study, we found that reaching Tanner Stage III of puberty was associated with increased levels of depression in girls. This paper examines whether the morphological changes associated with puberty (as measured by Tanner stage) or the hormonal changes underlying them are more strongly associated with increased rates of depression in adolescent girls.

Methods. Data from three annual waves of interviews with 9 to 15-year-olds from the Great Smoky Mountains study were analysed.

Results. Models including the effects of testosterone and oestradiol eliminated the apparent effect of Tanner stage. The effect of testosterone was non-linear. FSH and LH had no effects on the probability of being depressed.

Conclusions. These findings argue against theories that explain the emergence of the female excess of depression in adulthood in terms of changes in body morphology and their resultant psychosocial effects on social interactions and self-perception. They suggest that causal explanations of the increase in depression in females need to focus on factors associated with changes in androgen and oestrogen levels rather than the morphological changes of puberty.

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.