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.

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. 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. While there is a growing body of epidemiological evidence on the prevalence of mental illnesses in late-life in developing countries, there is limited data on cultural perceptions of mental illnesses and care arrangement for older people.

Method. This qualitative study used focus group discussions with older people and key informants to investigate the status of older people and concepts of late-life mental health conditions, particularly dementia and depression, in Goa, India.

Results. Vignettes of depression and dementia were widely recognized. However, neither condition was thought to constitute a health condition. Dementia was construed as a normal part of ageing and was not perceived as requiring medical care. Thus, primary health physicians rarely saw this condition in their clinical work, but community health workers frequently recognized individuals with dementia. Depression was a common presentation in primary care, but infrequently diagnosed. Both late-life mental disorders were attributed to abuse, neglect, or lack of love on the part of children towards a parent. There was evidence that the system of family care and support for older persons was less reliable than has been claimed. Care was often conditional upon the child's expectation of inheriting the parent's property. Care for those with dependency needs was almost entirely family-based with little or no formal services. Unsurprisingly, fear for the future, and in particular ‘dependency anxiety’ was commonplace among older Goans.

Conclusions. There is a need to raise awareness about mental disorders in late-life in the community and among health professionals, and to improve access to appropriate health care for the elderly with mental illness. The study suggests directions for the future development of locally appropriate support services, such as involving the comprehensive network of community health workers.

Background. Hospital-based studies report that depression in the elderly is associated with brain atrophy. This notion could not be confirmed in a population study on 85-year-olds. We aimed to assess depression in relation to brain atrophy and cognition in 70- and 74-year-old women.

Methods. A representative sample of 70- and 74-year-old women (N = 501) was examined with a psychiatric examination including the Mini-Mental State Examination (MMSE), measuring global cognitive function, and computerized tomography (CT) of the brain (N = 268). Depression was diagnosed according to DSM-III-R. Previous depression was diagnosed by history and by information from previous examinations in this 24-year longitudinal study.

Results. The prevalence of depression was 11·6%, including 8·4% with major depression (MDD). Among those who were currently mentally healthy, 43·0% had a history of previous depression. Women with current MDD had lower scores on the MMSE than the mentally healthy women. This association was only found in women with a lower level of education. Current depressives, previous depressives and mentally healthy women without a history of depression did not differ on CT with regard to brain atrophy or white matter lesions. The association between MDD and lower cognitive performance was independent of the association of cognitive performance with structural brain changes on CT.

Conclusions. Brain atrophy on CT is not associated with depression in the general population, despite the fact that individuals with depression have a worse cognitive performance. The finding that cognitive performance was not decreased in individuals with previous depression suggests that cognitive dysfunction is a state phenomenon in depression.

Background. Depressive syndromes not fulfilling the criteria for specified disorders (subthreshold depression, SD) may be clinically important. We aimed to study SD in old and very old age, in comparison with subjects with no depressive symptoms (NDS) and subjects with major depression (MD).

Methods. A community-based random sample of 516 subjects, age 70 to 100 years and over, stratified by age and sex, was examined. All participants were investigated by psychiatrists and by geriatricians independently.

Results. In 16·5% (N = 85) of the study subjects SD was identified. Study subjects with SD had, similarly to the subjects with MD, significantly more somatic diagnoses and used more somatic as well as psychotropic medications than the subjects with NDS. Self-ratings and observer ratings of depression indicated that SD was a milder depressive state than MD.

Conclusions. Compared with MD, SD is probably a milder form of depression. The increased use of psychotropic medications indicates that at least a portion of these individuals have a disorder requiring treatment. One of the characteristics of SD is co-morbidity with somatic illnesses and physical disability.

Background. Depression is a common problem in patients with Parkinson's disease, but its mechanism is poorly understood. It is thought that neurochemical changes contribute to its occurrence, but it is unclear why some patients develop depression and others do not. Using a community-based sample of patients with Parkinson's disease, we investigated the contributions of impairment, disability and handicap to depression in Parkinson's disease.

Methods. Ninety-seven patients seen in a population-based study on the prevalence of Parkinson's disease completed the Beck Depression Inventory (BDI). Clinical and historical information on symptoms and complications of Parkinson's disease were obtained from the patients by a neurologist. In addition, clinician and patient ratings of disability on the Schwab and England scale were obtained and a quality of life questionnaire was completed.

Results. Moderate to severe depression (BDI [ges ] 18) was reported by 19·6% of the patients. Higher depression scores were associated with advancing disease severity, recent self-reported deterioration, higher akinesia scores, a mini-mental score of < 25 and occurrence of falls. Disability as rated by the neurologist accounted for 34% of the variance of depression scores. Self-reported impairment of cognitive function and the feeling of stigmatization accounted for > 50% of the variance of depression scores.

Conclusions. Depression in patients with Parkinson's disease is associated with advancing disease severity, recent disease deterioration and occurrence of falls. Regression analysis suggests that depression in Parkinson's disease is more strongly influenced by the patients' perceptions of handicap than by actual disability. The treatment of depression should therefore be targeted independently of treatment of the motor symptoms of Parkinson's disease, and consider the patients' own perception of their disease.

Background. Brain 5-hydroxytryptamine (5-HT) function is implicated in the pathophysiology of schizophrenia and the action of new generation antipsychotic drugs. By the method of acute tryptophan depletion (ATD) 5-HT can be selectively manipulated. The aim of this study was to examine the effects of ATD on symptoms, mood and cognition in schizophrenic patients.

Methods. Twenty-eight schizophrenic patients participated in a within subject, double-blind, placebo-controlled counterbalanced cross-over study. Patients with a concurrent DSM-IV axis I diagnosis were excluded. Symptoms, mood and cognitive function were evaluated following ATD or ingestion of a control drink.

Results. The depleting drink significantly reduced plasma total and free tryptophan. Tryptophan/LNAA ratios did not alter with the administration of the control drink, but differed significantly with ATD; however there was no significant change in tyrosine/LNAA ratio. ATD led to impairment in executive function that was dependent upon the order of administration. Tests of sustained attention, speed of processing, and everyday memory were not affected. No effects were observed on subjective mood ratings, movement disorders or PANSS scores.

Conclusions. Acute tryptophan depletion selectively alters cognition in schizophrenia, but has no effect on symptoms, mood ratings or movement disorders.

Background. Bulimic, impulsive and depressive syndromes have all been associated with abnormalities in brain serotonin (5-hydroxytryptamine; 5-HT) mechanisms.

Methods. We had 26 bulimic women and 22 normal-eater women report impulsive, affective, self-destructive and bulimic symptoms, and then provide serial blood samples for measurement of: [3H]-paroxetine binding in platelets; and, prolactin (PRL) responses following oral meta-chlorophenyl-piperazine (m-CPP).

Results. Bulimic status was associated with markedly reduced density of paroxetine-binding sites, modest blunting of m-CPP stimulated PRL response, and greater nausea following m-CPP. Biological variables did not co-vary with most psychopathological or eating-symptom indices. However, there were inverse associations (in bulimic women only) between scores indicating impulsivity (largely ‘unreflectiveness’) and density of platelet 5-HT uptake sites.

Conclusions. Our observations link bulimia nervosa to altered 5-HT functioning, and suggest that there may be a relatively symptom-specific association between impulsivity and reduced 5-HT reuptake.

Background. Patients with chronic fatigue syndrome (CFS) often make somatic attributions for their illness which has been associated with poor outcome. A tendency to make somatic attributions in general may be a vulnerability factor for the development of CFS.

Methods. This cross-sectional study based on self-report questionnaire data aimed to investigate the type of attributions for symptoms made by patients with CFS and to compare this to attributions made by their partners. It was hypothesized that patients with CFS would make more somatic attributions for their own symptoms than control subjects and that partners of patients with CFS would make more somatic attributions for their ill relative's symptoms but would be similar to controls regarding their own symptoms. Fifty patients with CFS were compared to 50 controls from a fracture clinic in the same hospital and 46 relatives living with the patients with CFS. A modified Symptom Interpretation Questionnaire was used to assess causal attributions.

Results. CFS patients were more likely to make somatic attributions for their symptoms. The relatives of patients with CFS made significantly more somatic attributions for symptoms in their ill relative. However, they were like the fracture clinic controls in terms of making predominantly normalizing attributions for their own symptoms.

Conclusions. The data support modification of existing cognitive behavioural treatments for CFS to investigate whether addressing partners' attributions for patients' symptoms improves recovery in the patient. Furthermore, a tendency to make somatic attributions for symptoms may be a vulnerability factor for the development of CFS.

Background. Chronic fatigue syndrome (CFS) patients often complain that physical exertion produces an increase of complaints, leading to a greater need for rest and more time spent in bed. It has been suggested that this is due to a bad physical fitness and that physical deconditioning is a perpetuating factor in CFS. Until now, studies on physical deconditioning in CFS have shown inconsistent results.

Methods. Twenty CFS patients and 20 matched neighbourhood controls performed a maximal exercise test with incremental load. Heart rate, blood pressure, respiratory tidal volume, O2 saturation, O2 consumption, CO2 production, and blood-gas values of arterialized capillary blood were measured. Physical fitness was quantified as the difference between the actual and predicted ratios of maximal workload versus increase of heart rate. Fatigue, impairment and physical activity were assessed to study its relationship with physical fitness.

Results. There were no statistically significant differences in physical fitness between CFS patients and their controls. Nine CFS patients had a better fitness than their control. A negative relationship between physical fitness and fatigue was found in both groups. For CFS patients a negative correlation between fitness and impairment and a positive correlation between fitness and physical activity was found as well. Finally, it was found that more CFS patients than controls did not achieve a physiological limitation at maximal exercise.

Conclusions. Physical deconditioning does not seem a perpetuating factor in CFS.

Background. A previous study of women 9 months after discharge from in-patient treatment for depression found that low self-esteem as measured by a self-report questionnaire at admission was associated with a worse prognosis. This study investigates the womens' outcome more than 4 years after discharge and the continued prognostic relevance of self-esteem and other variables.

Method. Fifty-six women who had been admitted to hospital with major depression and studied in detail during their admission and 9 months following discharge were traced 4–5 years later. Possible prognostic factors were investigated in relation to time to recovery and recurrence, and to a global outcome measure.

Results. In keeping with other published work only 16 out of 52 (31%) women had recovered and remained well. Fifteen out of 52 (29%) subjects had experienced depressive symptoms for more than 70% of the follow-up time or died from unnatural causes. Low self-esteem scores recorded at the initial admission correlated with slow recovery but not subsequent recurrence of depression. The occurrence of one or more life events in the year preceding admission was associated with a better prognosis.

Conclusions. The poor long-term prognosis of many women with severe depression was confirmed. Social factors, such as social support and marital relationships were less important for prognosis than in previous studies of less severely ill subjects. The prognostic value of self-esteem warrants further investigation and appears to have therapeutic implications.

Background. The purpose of the study was to examine the effect of employment status measured at baseline on the risk of suicide by years of follow-up, using a large nationally representative sample of the US population.

Methods. Cox regression models were applied to data from the National Longitudinal Mortality Study, based on the 1979–1989 follow-up. In estimating the effect of baseline employment status on suicide, adjustments were made for baseline demographic and socio-economic variables.

Results. After 3 years of follow-up, unemployed men were a little over twice as likely to commit suicide as their employed counterparts. Among men, the lower the socio-economic status, the higher the suicide risk. Among women, in each year of follow-up, the unemployed had a much higher suicide risk than the employed. After 9 years of follow-up unemployed women were over three times more likely to kill themselves than their employed counterparts.

Conclusions. Unemployment is strongly related to suicide, but this relationship is more enduring and stronger among women. For men, the unemployment effect is stronger at earlier years of follow-up. In women, unemployment increases the risk of suicide regardless of the number of follow-up years. The finding with regard to women disconfirms earlier research reports suggesting that unemployment affects suicide only in men.

Background. Psychiatrists are asked to give opinions as to fitness to plead, a legal concept. There is a dearth of research into fitness to plead in the UK, with no prospective studies and no studies involving the comparison of fit and unfit subjects. In particular, there have been no investigations into the meaning of ‘unfit to plead’ in terms of psychiatric symptomatology, or as to the relative importance of each legal fitness criterion in psychiatrists' conclusions as to fitness.

Method. The study comprised a prospective evaluation of 479 consecutive referrals to psychiatrists at court. Individual legal fitness criteria were examined as predictors of unfitness. Associations of unfitness, and of individual legal fitness criteria, were examined with Brief Psychiatric Rating Scale (BPRS) symptom scores.

Results. The two most important of the legal criteria in clinical decisions as to unfitness were whether the person could follow the proceedings of the trial or give adequate instructions to their solicitor. The legal criteria concerning trial were more predictive of unfitness than those concerning plea. Unfitness was significantly associated with the presence of positive psychotic symptomatology, in particular conceptual disorganization and delusional thinking, but not with symptoms of anxiety, depression or withdrawal.

Conclusion. Unfitness is most significantly associated with symptoms affecting comprehension and communication. The fitness criteria could be simplified without loss of power. These results, predominantly concerned with mental illness, may not generalize to the mentally impaired.

Background. Although studies investigating changes in diagnosis between psychotic episodes have differed in design, some consistent findings have emerged. This study seeks to clarify and extend these findings by describing and comparing clinical and operationally defined diagnostic stability in a group of subjects with multiple episodes of functional psychotic illness.

Methods. The OPCRIT programme was applied to case notes of 204 subjects with multiple admissions for psychotic illness. Clinical and operationally defined diagnoses were compared and the spread and stability of diagnoses determined.

Results. An increase in the frequency of diagnosis of schizophrenia from initial to subsequent episodes was demonstrated. High levels of stability were found for schizophrenia (58 to 98%), moderate levels for affective disorders (24 to 83%), low levels for other non-organic psychotic conditions (27 to 54%) and atypical psychosis (27 to 53%), and very low levels for schizoaffective disorder (5 to 39%) and other conditions (0 to 4%).

Conclusions. The stability levels for schizophrenia and affective disorders are adequate, but the low levels for a range of other psychotic conditions raise questions regarding their predictive validity.

Background. Despite more than 100 years of study, there remains no definitive diagnostic validation of the functional psychoses. Factor analysis suggests the presence of three or more psychopathological syndromes in functional psychoses as a whole. The relationship between these factors and cerebral anatomy has been investigated in schizophrenia only. This study aimed to address the relationship of symptom factors to clinically important variables and cerebral anatomy in a sample of psychotic patients with a spread of diagnoses.

Methods. In a sample of patients with functional psychoses, symptom data was obtained on four consecutive admissions using the OPCRIT symptom checklist. OPCRIT data was used to generate operational diagnoses in accordance with pre-set criteria and a principle components analysis was performed on symptom data. Factor loadings were compared between each admission to examine factor stability over time. Factor scores at first admission were also correlated with clinical variables obtained from patients' case notes. From the sample of 204 patients, 64 subjects were recruited and underwent an MRI scan of the brain. Regional anatomical volumes were compared with diagnosis and factor loadings at first admission.

Results. A principal components analysis gave a four-factor solution of ‘manic’, ‘depressive’, ‘disorganization’ and ‘reality distortion’ factors at each admission. Factors showed a high degree of stability over the four admissions studied. The factors were significantly associated with several clinical variables. Three of the four factors were associated with a specific pattern of cerebral anatomy.

Conclusions. This study suggests that factors may correspond to relatively specific disease processes underlying functional psychotic illness. We propose that the use of symptom factors may facilitate the investigation of the underlying mechanisms of psychotic illness.