Background. The concept of duration of untreated psychosis (DUP) has recently attracted much interest because of its possible relationship to treatment outcome and implications for preventive efforts with reference to psychotic disorders, especially schizophrenia. In this paper we review critically the literature concerning the concept and its importance.

Methods. Articles concerned with measuring DUP and those that have been suggested to provide indirect or direct evidence of the effect of DUP on treatment outcome are reviewed.

Results. Evidence thus far suggests that DUP may be related to ease of reducing psychotic symptoms once treatment begins for first episode patients, but there is no evidence of a relationship to likelihood of relapse. There has been little investigation of the relationship of DUP to other long-term outcomes such as negative symptoms and cognitive functioning neither have the possible confounds of DUP been widely investigated or controlled.

Conclusions. It is important that there should be more thorough investigations of DUP, its correlates, and the extent to which it does mediate any advantages of earlier intervention.

Somatic distress syndromes, which include somatoform disorders and syndromes of chronic fatigue such as neurasthenia but not somatic presentations of anxiety and depression, are one of the common expressions of distress in primary care (Ormel et al. 1994) and general hospital settings (Hemert et al. 1993). They are of considerable importance cross-culturally (Ono et al. 1999), and often lie at the interface of psychiatry and medicine (Hickie, 1999). They are associated with significant disability (Ormel et al. 1994; Andrews, 2000) and health-care utilization (Escobar et al. 1991).

In the last 10 years a consensus has developed that the symptoms of psychosis may be better understood by linking the steps between the phenomenological experiences and social, psychological and neurobiological levels of explanation. Cognitive models of psychosis are an important link in this chain. They provide a psychological description of the phenomena from which hypotheses concerning causal processes can be derived and tested; social, individual, and neurobiological factors can then be integrated via their impact on these cognitive processes. In this paper, we set out the cognitive processes that we think lead to the formation and maintenance of the positive symptoms of psychosis and we attempt to integrate into our model research in social factors. If this model proves useful, a fuller integration with the findings of biological research will be required (Frith, 1992).

Background. Full-spectrum fluorescent lighting (FSFL) has been credited with causing dramatic beneficial effects on a wide variety of behaviours, mental health outcomes and physical health effects, as compared to other fluorescent lamp types. These effects are hypothesized to occur because of similarity between FSFL emissions and daylight, which is said to have evolutionary superiority over other light sources.

Method. This review, covering the period 1941–1999, critically considers the evidence for direct effects of FSFL through skin absorption as well as indirect effects on hormonal and neural processes.

Conclusions. Overall, the evidence does not show dramatic effects of fluorescent lamp type on behaviour or health, neither does it support the evolutionary hypothesis.

Background. Disturbance of the HPA axis may be important in the pathophysiology of chronic fatigue syndrome (CFS) and fibromyalgia. Symptoms may be due to: (1) low circulating cortisol; (2) disturbance of central neurotransmitters; or (3) disturbance of the relationship between cortisol and central neurotransmitter function. Accumulating evidence of the complex relationship between cortisol and 5-HT function, make some form of hypothesis (3) most likely. We review the methodology and results of studies of the HPA and other neuroendocrine axes in CFS.

Method. Medline, Embase and Psychlit were searched using the Cochrane Collaboration strategy. A search was also performed on the King's College CFS database, which includes over 3000 relevant references, and a citation analysis was run on the key paper (Demitrack et al. 1991).

Results. One-third of the studies reporting baseline cortisol found it to be significantly low, usually in one-third of patients. Methodological differences may account for some of the varying results. More consistent is the finding of reduced HPA function, and enhanced 5-HT function on neuroendocrine challenge tests. The opioid system, and arginine vasopressin (AVP) may also be abnormal, though the growth hormone (GH) axis appears to be intact, in CFS.

Conclusions. The significance of these changes, remains unclear. We have little understanding of how neuroendocrine changes relate to the experience of symptoms, and it is unclear whether these changes are primary, or secondary to behavioural changes in sleep or exercise. Longitudinal studies of populations at risk for CFS will help to resolve these issues.

Psychological Medicine is proud to announce a major step forward. With this issue Dr Kenneth S. Kendler joins as American Editor. Dr Kendler will be well known to the readership of Psychological Medicine. One of the most distinguished of psychiatric genetic epidemiologists, he is Rachel Brown Banks Distinguished Professor of Psychiatry, Professor of Human Genetics, and Co-Director of Virginia Institute for Psychiatric and Behavioral Genetics at the Medical College of Virginia, Virginia Commonwealth University. He has been a contributor of papers to Psychological Medicine for many years, and a member of the Editorial Board since 1995.

The proportion of papers which we publish from the Americas has been gradually increasing. They are now nearly one-third of all papers, mostly from the USA. There will be an additional editorial office in Richmond, Virginia and Dr Kendler will deal with submissions from the Americas, together with all submissions in psychiatric genetics, whatever their origin. Revised submission instructions are included in this issue. Our high standards for publication will continue.

We also announce an additional smaller change. From now on each volume will include eight rather than six issues. The total number of pages per year will be unchanged, with issues slightly slimmer and a little more frequent. This will allow us to expedite publication of major papers, has advantages for the printers, and is similar to the pattern of eight issues per year adopted by what is now our sister Cambridge University Press publication, the Journal of Child Psychology and Psychiatry.

With this issue also a loss: after seven years Simon Wessely relinquishes the role of associate editor and book review editor. We are grateful to him for his many contributions and pleased that he has agreed to remain as a member of the Editorial Board.

Over the past 20 years, psychoneuroimmunological research has produced a large body of evidence that challenges the historically dominant view that the immune system operates in an autonomous manner independent of other physiological systems. Today, there is little doubt that the brain and the immune system are intimately linked and capable of reciprocal communication (Ader et al. 1991). Despite the acknowledged bi-directional nature of the brain–immune system connection, the predominant focus of study has been on the effects of psychological and behavioural events (e.g. stress) on immune responses and disease processes, and the mechanisms underlying such effects (see Kusnekov & Rabin, 1994; Maier et al. 1994; Rozlog et al. 1999). However, considerable interest in the possibilities of immune-system-to-brain communication was initiated by a seminal paper considering the biological basis of behaviour in sick animals (Hart, 1988). Subsequently, the immunological determinants of the behavioural, cognitive and emotional changes associated with acute illness, as well as with more chronic psychopathological states (e.g. depression) have become the subject of rapidly expanding areas of research (e.g. Kent et al. 1992; Lloyd et al. 1992; Hickie & Lloyd, 1995; Maes et al. 1995a; Rothwell & Hopkins, 1995; Dantzer et al. 1996; Maier & Watkins, 1998; Vollmer-Conna et al. 1998; Maes, 1999).

The main objective of this editorial is to provide a succinct overview of current knowledge of the normal behavioural correlates of acute infective illness, their adaptive function and underlying mechanisms. Elucidation of the processes involved in the appearance, maintenance and inhibition of ‘normal’ sickness behaviour is important if extrapolations from this phenomenon to more chronic psychopathological conditions are to provide more than a new label for poorly understood non-specific symptom clusters.

Introduction. Repetitive transcranial magnetic stimulation (rTMS) has been proposed as a possible alternative to electroconvulsive therapy for the treatment of selected patients with depression, bipolar affective disorder and schizophrenia. The aim of this study was to evaluate the evidence for the effectiveness of rTMS in mood disorders and schizophrenia.

Methods. Studies were identified using MEDLINE (1966 to January 2000), EMBASE/Excerpta Medica (1980 to January 2000), Biological Abstracts and Index to Scientific and Technical Proceedings. A number of biomedical and TMS related websites were also searched. We estimated the number needed to treat to show beneficial effect of rTMS when compared with the placebo controlled group.

Results. Seven controlled trials of rTMS depression were identified. Five of these were suitable for meta-analysis and show a beneficial effect of rTMS compared to placebo, with a number needed to treat of 2·3 with a 95% confidence interval 1·6 to 4·0, total; 81 patients. A single trial of rTMS has also been performed in mania, which shows a beneficial effect of right hemisphere stimulation when compared with left hemisphere stimulation. A controlled trial in schizophrenia failed to show any benefit of rTMS.

Discussion. rTMS has demonstrable beneficial effects in depression. The extent and the duration of the anti-depressant effect of rTMS has yet to be defined. There now needs to be randomized controlled trials to compare rTMS directly with standardized electroconvulsive therapy in order to take this subject forward. With regard to the treatment of other mood disorders and schizophrenia, we are at an early stage in the assessment of further studies that are needed to examine any potential role for rTMS.

Background. Although poor language test performance has been documented in schizophrenia, its relationship to formal thought disorder remains unclear.

Method. Forty schizophrenic patients were administered eight language tests and, under blind conditions, rated for formal thought disorder. Measures of general intellectual function were also obtained.

Results. Performance on all language tests was significantly correlated with the general intellectual measures. Three language test scores also showed significant correlations with formal thought disorder scores. Multiple regression and analysis of intellectually preserved patients suggested particular associations of formal thought disorder with semantic comprehension and picture description.

Conclusions. General intellectual impairment is an important determinant of poor language test performance in schizophrenia, but presence of formal thought disorder may also contribute. A higher-order semantic deficit may be particularly relevant to both linguistic impairment and formal thought disorder.

Background. The overall aim of the GENESiS project is to identify quantitative trait loci (QTLs) for anxiety/depression, and to examine the interaction between these loci and psychosocial adversity. Here we present life-events data with the aim of clarifying: (i) the aetiology of life events as inferred from sibling correlations; (ii) the relationship between life events and measures of anxiety and depression, as well as neuroticism; and (iii) the interaction between life events and neuroticism on anxiety/depression indices.

Methods. We assessed the occurrence of one network and three personal life-event categories and multiple indices of anxiety/depression including General Health Questionnaire, Anhedonic Depression, Anxious Arousal and Neuroticism in a large community-based sample of 2150 sib pairs, 410 trios and 81 quads. Liability threshold models and raw ordinal maximum likelihood were used to estimate within-individual and between-sibling correlations of life events. The relationship between life events and indices of emotional states and personality were assessed by multiple linear regression and canonical correlations.

Results. Life events showed sibling correlations of 0·37 for network events and between 0·10 and 0·19 for personal events. Adverse life events were related to anxiety and depression and, to a less extent, neuroticism. Trait-vulnerability (as indexed by co-sib's neuroticism, anxiety and depression) accounted for 11% and life events for 3% of the variance in emotional states. There were no interaction effects.

Conclusions. Life events show moderate familiality and are significantly related to symptoms of anxiety and depression in the community. Appropriate modelling of life events in linkage and association analyses should help to identify QTLs for depression and anxiety.

Background. Huntington's disease (HD) is a fatal neurodegenerative disorder with an autosomal dominant mode of inheritance. It leads to progressive dementia, psychiatric symptoms and an incapacitating choreiform movement disorder, culminating in premature death. HD is caused by an increased CAG repeat number in a gene coding for a protein with unknown function, called huntingtin. The trinucleotide CAG codes for the amino acid glutamine and the expanded CAG repeats are translated into a series of uninterrupted glutamine residues (a polyglutamine tract).

Methods. This review describes the epidemiology, clinical symptomatology, neuropathological features and genetics of HD. The main aim is to examine important findings from animal and cellular models and evaluate how they have enriched our understanding of the pathogenesis of HD and other diseases caused by expanded polyglutamine tracts.

Results. Selective death of striatal and cortical neurons occurs. It is likely that the HD mutation confers a deleterious gain of function on the protein. Neuronal intranuclear inclusions containing huntingtin and ubiquitin develop in patients and transgenic mouse models of HD. Other proposed mechanisms contributing to neuropathology include excitotoxicity, oxidative stress, impaired energy metabolism, abnormal protein interactions and apoptosis.

Conclusions. Although many interesting findings have accumulated from studies of HD and other polyglutamine diseases, there remain many unresolved issues pertaining to the exact roles of intranuclear inclusions and protein aggregates, the mechanisms of selective neuronal death and delayed onset of illness. Further knowledge in these areas will inspire the development of novel therapeutic strategies.

Background. Hypochondriasis is recognized as an important disorder in clinical populations, associated with increased health care utilization, disability and psychiatric co-morbidity. Few studies have investigated hypochondriasis in the community. We report on the broader concept of illness worry in a community population.

Methods. Five hundred and seventy-six subjects from an ethnically diverse urban setting were surveyed. Information was gathered on sociodemographic variables, medical and psychiatric status, health care utilization and disability. Bivariate and multivariate regression analyses were used to compare groups with illness worry (with and without the medical condition) to those without illness worry.

Results. Only one subject of 533 (0·2 %) met criteria for hypochondriasis and seven (1·3 %) fulfilled abridged criteria. However, 33 (6 %) of the sample had illness worry. Of these, 17 had the illness about which they worried. Compared with controls, both illness worry groups had elevated levels of medical illness, psychiatric symptoms, help-seeking, health care use and disability. In multiple regression analyses, illness worry was an independent predictor of somatic symptoms, help-seeking, and disability, when sociodemographic and medical variables were controlled.

Conclusions. Hypochondriasis appears to be a rare disorder in the community while illness worry is relatively common. Illness worry was present in equal numbers of subjects with the illness of concern, as those without. Illness worry was an independent factor contributing to increased levels of distress, health care utilization, and disability, even when medical status was controlled, suggesting that it is an important issue for further research.

Background. It is hypothesized from previous positron emission tomography (PET) studies of patients with major depression that dysfunction of regions of the limbic system and the frontal lobes in close connection with the basal ganglia is involved in the pathophysiology of major depression.

Methods. By means of PET and 15O labelled radioactive water we determined an index of the neuronal activity by mapping the cerebral blood flow distribution of 42 unselected in-patients suffering from moderate to severe depression and 47 healthy controls controlling for age and gender. The PET maps were co-registered to magnetic resonance images of the anatomy of the brain.

Results. The functions-of-interest analysis revealed significant gender differences in cerebral blood flow and changes in the relative distribution of the blood with increasing age. The patients had increased activity of the hippocampus and the cerebellum compared to the healthy controls when corrected for these confounders and the influence of antidepressant medication. Furthermore, data in the Danish Psychiatric Central Register showed that the patients studied were representative of the population of depressed patients admitted to the hospital during the study period.

Conclusion. Our main finding is increased blood flow to the hippocampus, even when controlling for a number of confounders. This is in accordance with a rapidly expanding literature suggesting an important role for this structure in major depression.

Background. Research shows that psychopathology, child sexual abuse and other childhood adversities are risk factors for suicide. However, few have investigated their joint and independent roles in the pursuit of a reliable, predictive model of suicidal behaviour.

Methods. Data are from the National Comorbidity Survey (N = 5877), a nationally representative study of prevalence, risk factors, and social consequences of psychiatric disorders in the US. Discrete time survival analysis and population attributable risk methodologies were utilized.

Results. Among those sexually abused as children, odds of suicide attempts were 2–4 times higher among women and 4–11 times higher among men, compared with those not abused, controlling for other adversities. Odds ratios were reduced but most remained statistically significant after adjusting for lifetime psychiatric illnesses preceding suicide attempts. In the same predictive equation, 79% of serious suicide attempts among women could be attributed to psychiatric disorders while 12% was attributable to rape and 7% to molestation. The highest probability of a first attempt was during early adolescence for those who were sexually abused and had a lifetime disorder, but it was 8–12 years older for those sexually abused without any disorders.

Conclusions. In the US, a strong association exists between child sexual abuse and suicidal behaviour, mediated by psychopathology. There is a substantial proportion of suicide risk attributable to child sexual abuse beyond the presence of psychopathology and other adversities. From a clinical standpoint, abuse survivors represent a high-risk population for suicidal behaviour. Further research into this preventable antecedent of suicide attempts is necessary.

Background. Lifetime and 12-month prevalence estimates of mental disorders consistently reported in large-scale community surveys have met with deserved scepticism. A crucial variable is the extent to which people who are considered cases are also disabled by their symptoms. In a national population survey, we hypothesized that an administratively significant proportion of persons with anxiety or depressive disorders according to ICD-10 and DSM-IV would report no disability.

Methods. Interviews were sought on a nationally representative sample of people aged 18 and over across Australia. The Composite International Diagnostic Interview on laptop (CIDI-A) was used by professional survey interviewers to identify persons meeting ICD-10 or DSM-IV criteria for anxiety or depressive disorders in the previous 4 weeks, together with self-reported data on associated disability and medical consultations for the same period.

Results. In an achieved sample of 10641 persons (response rate = 78%), no disability in daily life was reported by 28% of persons with an anxiety disorder and 15% with a depressive disorder by ICD-10 criteria; and by 20·4% and 13·9% respectively by DSM-IV. Non-disabled respondents had lower scores on two measures of psychological distress and markedly lower rates for having consulted a doctor for their symptoms.

Conclusion. The ICD-10 and DSM-IV criteria for anxiety and depressive disorders, when applied to the information on symptoms elicited by the CIDI-A, inadequately discriminate between people who are and are not disabled by their symptoms. There may be a group of highly symptomatic people in the general population who tolerate their symptoms and are not disabled by them.

Background. There is still a relative paucity of information about the long-term course of depression.

Methods. Consecutive patients admitted to a teaching hospital psychiatry unit with symptoms of depression, previously assessed at 6 months and 2, 5 and 15 years after index admission, were reviewed at 25 years (N = 49, including eight informants of deceased probands, of an original 145 with major depression (DEPs)). Prospective psychiatric (N = 22) and retrospective surgical (N = 50) control groups assessed after 25 years were used for comparison.

Results. A further decade of follow-up confirmed the chronicity of depression. Of depressed patients (DEPs) followed for the full 25-year-period only 12% of the 49 original DEPs recovered and remained continuously well, 84% experienced recurrences, 2% experienced an unremitting course and another 2% died by suicide. Note that in the first 15-year-period 6% (9/145 DEPs) committed suicide, a further 38 died and 32 were lost to follow-up. They experienced an average of three episodes of depression over the 25 years. In the decade since the 15-year follow-up, 27% improved in clinical outcome (including four of five previously chronically depressed patients), 55% remained unchanged and 18% worsened; and the number of episodes per year declined. Patients initially diagnosed with neurotic or endogenous depression had similar long-term outcomes. The criteria for a current DSM-III-R disorder were met by 37% of DEPs, including 11% with depression or dysthymia. On the global assessment of functioning scale 78% of the DEPs had some impairment compared to 62% of psychiatric controls and 40% of surgical controls.

Conclusion. Even after 25 years, severe depressive disorders appear to have poor long-term outcomes. Patients with chronic outcomes over 15 years can improve when followed over longer periods.

Background. The 1896 and 1996 populations of North West Wales are similar in number, ethnic and social mix and rurality, enabling a study of the comparative incidence and prevalence of service utilization over the course of a century.

Methods. We collected records on all psychiatric admissions from North-West Wales in 1894–1896 and 1996. These were assessed and diagnosed by the responsible sector area consultant.

Results. The data reveal substantially more patients admitted for all diagnoses in 1996, even when comparisons are restricted to detained patients. The incidence of hospitalization by detention for schizophrenia is slightly lower 1996 than in 1896 but the incidence of hospitalization is higher now than in 1996. The incidence of hospitalization by detention for non-affective disorder psychoses is the same in both 1896 and 1996 but there is a doubling of incidence of hospitalization. The incidence of hospitalization for bipolar disorders is similar in the two periods. Modern mental health services admit large numbers of personality disordered patients, where none were admitted 100 years ago.

Conclusions. Factors general to changing health care and expectations and others specific to mental health would appear to have led to the increase in rates of admissions observed in the modern period.

Background. Higher education has been posited to protect against cognitive decline, either because the rate of decline is slower in the more highly educated or the start of decline is delayed. Latent growth models provide improved methodology to examine this issue.

Methods. The sample consisted of 887 participants aged 70–93 years in 1991 and followed up in 1994 and 1998. Latent growth models and standard regression techniques were used to examine the rate of cognitive decline in four cognitive measures while controlling for health status and sex. A delayed start model was examined by incorporating interaction effects in a regression model.

Results. Neither the latent growth models nor the regression techniques revealed a slower rate of decline for the more highly educated. The proportion of the highly educated showing no change was no larger than the proportion of the less well educated. There were no significant age by education interaction effects, no chronologically later accelerations in the rate of change as a function of education, and no differences in rate of decline between the first measurement interval and the second.

Conclusions. Education may not protect against cognitive decline although it is associated with long-term individual differences in level of functioning. The discrepancy between our study and others may be attributable to attrition effects, follow-up length, sample age, scaling artefacts and negative publication bias. Most importantly, practice effects may favour the better educated and hence account for the supposed protective effect in many longitudinal studies of cognitive change.

Background. Due to the limited data available, it is not clear whether the incidence of first-onset depression varies with age in the elderly.

Methods. A representative sample of individuals born 1901–2 (N = 392) was examined at the ages of 70, 75, 79, 81, 83 and 85 years by psychiatrists using a semi-structured schedule. Information on depressive episodes was also collected from self-report and examination of case records. Depression was diagnosed according to the DSM-III-R criteria.

Results. The incidence of depression was 12 per 1000 person-years in men and 30 per 1000 person-years in women between the ages of 70 and 85 (sex difference P = 0·001). The incidence increased from 17 per 1000 person-years (men 8·7, women 23·2, P = 0·007) between the ages of 70 and 79 to 44 per 1000 person years (men 27·0, women 52·8, P = 0·166) between 79 and 85 (age difference: RR 2·6, P < 0·001; men RR 3·1, P = 0·036; women RR 2·3, P = 0·003) . A diagnosis of depression was associated with increased mortality and refusal rate during the 15-year follow-up. Previous episodes of depression were associated with an increased risk of further episodes. The prevalence of depression increased from 5·6% at the age of 70 to 13·0% at the age of 85. The lifetime prevalence of depression was 23% in men and 45% in women.

Conclusions. Both the incidence and prevalence of depression increased with age in this longitudinally followed birth cohort, and the incidence was higher in women than in men.

Background. Several studies have examined the ability of schizophrenic patients to represent mental states (‘theory of mind'; ToM). There is consensus that some patients have impaired ToM, but there is disagreement about the relation between ToM and symptomatology, and about the severity and specificity of the deficit.

Methods. Two first-order and one second-order false belief tests of ToM were given to groups of schizophrenic patients and psychiatric and normal controls. The relation between ToM and symptomatology was explored using regression and symptom subgroup analyses. Severity was investigated by using the same task methodology as in autism research, to enable direct comparison with that disorder. Specificity was investigated using matched control tasks which were as difficult as the ToM tasks, but did not require ToM.

Results. Symptom subgroup analysis showed that schizophrenic patients with behavioural signs were impaired relative to controls on ToM, and that remitted patients and a single case with passivity symptoms performed as well as controls. Regression analysis showed that ratings of behavioural signs predicted impaired ToM in schizophrenia. There was weak evidence that a subgroup with paranoid symptoms had ToM impairments, although these were associated with low IQ. Schizophrenic patients only showed ToM deficits on the second-order task. No impairments appeared on the matched control tasks which did not require ToM.

Conclusions. There is a clear association between ToM impairment and behavioural signs in schizophrenia. Deficits in paranoid patients are harder to detect with current tasks and may be compensated for by IQ-dependent problem-solving skills. ToM impairments in schizophrenia are less severe than in autism, but are specific and not a reflection of general cognitive deficits.