The cornerstone of evidence-based medicine is the belief that good quality research should form the basis of clinical practice and decision-making (Muir Gray, 1997). Psychiatry has kept abreast of this movement (Geddes et al. 1997) and claims have been made that randomized-controlled trials (the highest quality primary evaluative research) can be used to justify 65% of routine clinical decisions (Geddes et al. 1996). However, it is largely published research that forms the ‘knowledge base’ of the evidence movement. A fundamental difficulty arises when published research results are a biased sample of all research results – published and unpublished. Publication bias presents one such threat and has been much discussed in wider healthcare (Easterbrook et al. 1991; Dickersin & Min, 1993; Dickersin, 1997), but has been little discussed or researched in psychiatry, despite the fact that psychiatry is likely to be at least as prone to publication bias as other specialities.

Background. Interferons are a class of cytokines profoundly affecting immune function. Several interferons are now synthesized and used clinically, notably for viral diseases and cancer. In addition to their desired immune effects, interferons cause a number of toxicities, including prominent effects on the nervous system.

Methods. This literature review focused on the incidence of depression associated with interferon treatment. Possible neurochemical mechanisms and remedial strategies were also considered.

Results. Interferon treatment, particularly with the alpha subtype, is unquestionably linked with depression, but the strength of association is uncertain because of erratic ascertainment and pre- treatment co-morbidity. A likely pathogenic mechanism has been described, involving interferon suppression of serotonin synthesis. Controlled treatment trials of interferon-induced depression are not yet available.

Conclusions. Neurotoxicity substantially limits the use of interferons. At least some of the risk of depression appears to derive from their anti-serotonergic effects, consistent with the large body of evidence pointing to a general link between serotonin and affective illness. Vigilant detection and aggressive treatment of depression is necessary to optimize interferon treatment of many patients.

Background. Studies of urban–rural differences in prevalence of non-psychotic mental disorder have not given consistent findings. Such differences have received relatively little study in Great Britain.

Methods. Data from 9777 subjects in the Household Survey of the National Morbidity Survey of Great Britain were analysed for differences between urban, semi-rural and rural areas. Psychiatric morbidity was assessed by scores on the Revised Clinical Interview Schedule (CIS-R), together with alcohol dependence, drug dependence, receipt of treatment from general practitioners. Associations with other characteristics were examined by logistic regression.

Results. Urban subjects had higher rates than rural of CIS-R morbidity, alcohol dependence and drug dependence, with semi-rural subjects intermediate. Urban subjects also tended to be members of more deprived social groups, with more adverse living circumstances and greater life stress, factors themselves associated with disorder. Urban–rural differences in alcohol and drug dependence were no longer significant after adjustment for these factors by logistic regression, and differences on CIS-R morbidity were considerably reduced. There were no differences in treatment.

Conclusions. There are considerable British urban–rural differences in mental health, which may largely be attributable to more adverse urban social environments.

Background. Although parenting has long been considered an important risk factor for subsequent psychopathology, most investigations of this question have studied a single informant, clinical populations, one or a few disorders and did not consider relevant covariates.

Methods. Three dimensions of parenting (coldness, protectiveness and authoritarianism) were measured by combining the retrospective reports from adult female twins, their co-twins, and their mothers and fathers. We assessed by personal interview, lifetime history in the twins of eight common psychiatric and substance abuse disorders and a range of predictors of parenting. Analyses were performed using logistic regression.

Results. Examined individually, high levels of coldness and authoritarianism were modestly but significantly associated with increased risk for nearly all disorders, while the impact of protectiveness was more variable. These associations declined modestly when putative predictors of parenting were added as covariates. Maternal and paternal parenting were equally associated with outcomes in adult daughters. When coldness, protectiveness and authoritarianism were examined together, nearly all significant associations were seen solely with coldness. Few significant interactions were found between maternal and paternal parenting or between coldness, protectiveness and authoritarianism. The shared experience of these three dimensions of parenting predicts a quite small correlation in liability to these disorders in dizygotic twin pairs (e.g. r < 0·04).

Conclusion. In women, parenting behaviour, especially levels of coldness, is probably causally related to risk for a broad range of adult psychiatric disorders. The impact of parenting on substance use disorders may be largely mediated through their co-morbidity with major depression, phobias and generalized anxiety disorder. In general population samples, the association of poor parenting with psychiatric illness is modest, largely non-specific and explains little of the observed aggregation of these disorders in families.

Background. Based on the developing clinical and legal literature, and using the framework adopted in draft legislation, capacity to make a valid decision about a clinically required blood test was investigated in three groups of people with a ‘mental disability’ (i.e. mental illness (chronic schizophrenia), ‘learning disability’ (‘mental retardation’, or intellectual or developmental disability), or, dementia) and a fourth, comparison group.

Methods. The three ‘mental disability’ groups (N = 20 in the ‘learning disability’ group, N = 21 in each of the other two groups) were recruited through the relevant local clinical services; and through a phlebotomy clinic for the ‘general population’ comparison group (N = 20). The decision-making task was progressively simplified by presenting the relevant information as separate elements and modifying the assessment of capacity so that responding became gradually less dependent on expressive verbal ability.

Results. Compared with the ‘general population’ group, capacity to make the particular decision was significantly more impaired in the ‘learning disability’ and ‘dementia’ groups. Importantly, however, it was not more impaired among the ‘mental illness’ group. All the groups benefited as the decision-making task was simplified, but at different stages. In each of the ‘mental disability’ groups, one participant benefited only when responding did not require any expensive verbal ability.

Conclusions. Consistent with current views, capacity reflected an interaction between the decision-maker and the demands of the decision-making task. The findings have implications for the way in which decisions about health care interventions are sought from people with a ‘mental disability’. The methodology may be extended to assess capacity to make other legally-significant decisions.

Background. People with intellectual disabilities who have been victims or other witnesses of crime have had limited access to the criminal justice system, often on the basis of assumptions about their incapacity to be interviewed by the police and to give evidence in court. The aim of this study was to assess their capacity to be witnesses in court.

Methods. Forty-nine men and women with intellectual disabilities, all of whom were potential witnesses of ill-treatment, were assessed in order to provide advice, initially to the police, about their capacity to be interviewed for judicial purposes. The assessments included evaluations of each person's intellectual ability, memory, acquiescence, suggestibility, and their ability to explain concepts relating to the oath.

Results. Only 37 (76%) were able to complete the assessments. Most of those with a Full Scale IQ score of [ges ] 60 had a basic understanding of the oath, compared with only a third of those with IQ scores between 50 and 59, and none of those with IQ scores < 50. Nevertheless, some of the people who were unable to demonstrate an understanding of the oath did understand the words ‘truth’ and ‘lie’, especially when asked about these concepts in relation to concrete examples.

Conclusions. While intellectual ability appears to be the best overall predictor of the capacity of people with intellectual disabilities to act as witnesses, confining witnesses to those who could explain the meaning of the oath would mean that a number of persons who might be interviewed by the police and subsequently appear in court could be excluded from the judicial process.

Background. Patients with schizophrenia have a winter–spring excess of births compared with the general population, the cause of which is unresolved. Fluctuations in the magnitude of the seasonal variation may provide clues to its aetiology.

Methods. All Finnish patients with schizophrenia born between 1950 and 1969 (N = 15892) were identified from two nationwide health-care registers. Their background demographic information was obtained from the Population Register Centre, which also provided monthly numbers of births in each municipality of Finland as multidimensional tables, with sex and year, month and place of birth as marginals. The incidence of schizophrenia was modelled using Poisson regression analysis, with sex, onset age, birth cohort, place of birth (urban/rural), trend and seasonal variation as explanatory variables. We also constructed a monthly time series and decomposed it into three components – seasonal, trend and remainder.

Results. Seasonal variation of births among patients born in the 1950s, especially between 1955 and 1959, was marked, but decreased among patients born in the 1960s. No interaction between place of birth or sex and seasonal variation was observed. The incidence was higher among the rural-born than the urban-born, but declined more slowly among the urban-born than the rural-born.

Conclusions. The intensity of the factor causing the seasonal variation of births in schizophrenia may be decreasing. Urban birth may be emerging as a risk factor for schizophrenia in Finland, as elsewhere.

Background. The schizophrenia-like psychoses of epilepsy (SLPE) might represent a secondary form of schizophrenia in which the pathology is relatively confined to the temporal lobe. To test this possibility we have compared the neuropsychological profile of schizophrenia and SLPE. Our main hypothesis was that both psychotic groups would show deficits of temporal lobe function but that prefrontal impairment, as measured by tests of executive function, would be found only in the primary schizophrenic group.

Methods. Four groups were studied: (1) patients with SLPE (N = 25); (2) patients with epilepsy but not psychiatric history (N = 24); (3) patients with schizophrenia (N = 22); and (4) healthy volunteers (N = 24). Neuropsychological testing comprised measures of pre-morbid IQ, current verbal and performance IQ, information processing, digit span, motor speed, verbal and visual learning and memory, verbal fluency, the Wisconsin Card Sorting Task, the Stroop test and the trail making task.

Results. Patients with schizophrenia and those with SLPE had almost identical neuropsychological profiles, with impairments of attention, episodic memory (verbal > visual) and executive function. The epileptic controls showed similar though less severe impairments of memory and of some tests of executive function.

Conclusions. Our results do not support the hypothesis that the pathophysiology of SLPE and schizophrenia are distinct. While our findings suggest an important role for dominant temporal lobe abnormality in schizophrenia, both in its primary form and in that occurring in patients with epilepsy, they also implicate generalized cognitive impairment, manifest in particular as attentional deficits, in both forms of the disorder.

Background. Cognitive therapy for psychotic symptoms often embraces self-evaluative beliefs (e.g. self-worth) but whether and how such beliefs are related to delusions remains uncertain. In previous research we demonstrated that distress arising from voices was linked to beliefs about voices and not voice content alone. In this study we examine whether the relationship with the voice is a paradigm of social relationships in general, using a new framework of social cognition, ‘ranking’ theory.

Method. In a sample of 59 voice hearers, measures of power and social rank difference between voice and voice hearer are taken in addition to parallel measures of power and rank in wider social relationships.

Results. As predicted, subordination to voices was closely linked to subordination and marginalization in other social relationships. This was not the result of a mood-linked appraisal. Distress arising from voices was linked not to voice characteristics but social and interpersonal cognition.

Conclusion. This study suggests that the power imbalance between the individual and his persecutor(s) may have origins in an appraisal by the individual of his social rank and sense of group identification and belonging. The results also raise the possibility that the appraisal of voice frequency and volume are the result of the appraisal of voices' rank and power. Theoretical and novel treatment implications are discussed.

Background. As a group, positively thought-disordered (TD) schizophrenic patients are relatively impaired in their ability to use linguistic context to process sentences online (Kuperberg et al. 1998). This study investigates the heterogeneity in the use of linguistic context both between individual TD patients and within the individual patients as severity of thought disorder changes over time.

Methods. Seventeen TD schizophrenics performed an online word-monitoring task on four separate occasions. In each patient, baseline reaction time (RTs) to target words in normal sentences were subtracted from RTs to target words in pragmatically-, semantically- and syntactically-violated sentences to obtain a measure of online sensitivity to each type of linguistic violation, and these were compared with normative data of a healthy volunteer and a non-TD schizophrenic control group. In addition, the co-variation of severity of thought disorder and sensitivity to linguistic context within all individual TD patients over the four testing sessions, was examined.

Results. There was marked heterogeneity between individual TD patients in their sensitivity to different types of linguistic violations: some were selectively insensitive to pragmatic violations, while others were insensitive to semantic and syntactic (subcategorization) violations. There was also an inverse relationship between severity of thought disorder and sensitivity to linguistic violations within individual patients over the four sessions.

Conclusions. It is likely that a single cognitive deficit does not account for all types of schizophrenic thought disorder, but rather that there are multiple deficits affecting specific levels of linguistic processing. In these schizophrenic patients, impairment in the use of linguistic context was related to the state, rather than the trait, of thought disorder.

Background. We have recently reported a two-phase study on psychiatric morbidity in a sample of general hospital patients. This paper reports the results of the 6-month and 12-month follow-up of these patients.

Methods. The screening questionnaire was the GHQ-12. The main diagnostic instrument used in the second phase was the CIDI-PHC. All patients who had been interviewed with CIDI-PHC (N = 363) were followed-up and the baseline assessment was compared with the scoring on questionnaires administered in the 6-month postal enquiry and with the psychopathological status at 12-month, elicited with a telephone structured interview.

Results. Sixty-two and 87% of patients completed the 6- and 12-month follow-up assessment respectively. The first follow-up indicated no significant decrease in the level of symptoms. The 12-month follow-up interview showed that 23% of males and 40% of females had poor/mostly poor mental health. The logistic model showed that females with a definite ICD-10 diagnosis, admitted to a medical department, who had consumed psychotropic drugs in the previous year, had the most unfavourable outcome. The risk of a poor/mostly poor outcome steadily increased with the severity of the psychopathology during hospitalization.

Conclusion. In medical and surgical general hospital patients the risk factors associated with a poor mental health outcome are similar to those found in primary care patients. Greater attention should be paid in assessing routinely mental health status of general hospital patients during hospitalization.

Background. Poor physical health has long been recognized to be one of the most important risk factors for depression in older adults. Since many aspects of physical health can be targeted for improvement in primary care, it is important to know whether physical health problems predict the onset and/or the persistence of depression.

Methods. The study is based on a sample which at the outset consisted of 327 depressed and 325 non-depressed older adults (55–85) drawn from a larger random community-based sample in the Netherlands. Depression was measured using the Center for Epidemiologic Studies Depression scale (CES-D) at eight successive waves.

Results. From all incident episodes, the majority (57%) was short-lived. These short episodes could generally not be predicted by physical health problems. The remaining incident episodes (43%) were not short-lived and could be predicted by poor physical health. Chronicity (34%) was also predicted by physical health problems.

Conclusions. The study design with its frequent measurements recognized more incident cases than previous studies; these cases however did have a better prognosis than is often assumed. The prognosis of prevalent cases was rather poor. Physical health problems were demonstrated to be a predictor of both the onset and the persistence of depression. This may well have implications for prevention and intervention.

Background. We examined whether the relationships between hostility and physiological coronary heart disease (CHD) risk factors differ as a function of depressive tendencies (DT).

Methods. The participants were 672 randomly selected healthy young adults who self-reported their hostility (anger, cynicism, and paranoia) and DT. The physiological CHD risk factors studied were systolic blood pressure, diastolic blood pressure, body-mass index, serum high-density lipoprotein cholesterol, serum low-density lipoprotein cholesterol and serum triglycerides.

Results. We found that hostility was negatively associated with the physiological CHD risk factors among individuals exhibiting high DT while hostility was positively associated with, or unrelated to, the physiological risk factors among individuals showing low DT. The Hostility × DT interaction explained 2 to 5% of the variance in the physiological parameters.

Conclusion. The findings suggest that DT have a moderating influence on the relationships between hostility and CHD risk. Despite the established risk factor status of hostility, lack of anger and hostility, when combined with high DT, may represent the most severe exhaustion where the individual has given up. Disregard of this fact may explain some null findings in the research on hostility and CHD risk.

Background. The high prevalence of depression in developing countries is not well understood. This study aimed to replicate the previous finding of a high prevalence of depression in Pakistan and assess in detail the associated social difficulties.

Method. A two-phase survey of a general population sample in a Pakistani village was performed. The first-phase screen used the Personal Health Questionnaire (PHQ) and the self-rating questionnaire (SRQ). A one in two sample of high scorers and a one in three sample of the low scorers were interviewed using the Psychiatric Assessment Schedule (PAS) and Life Events and Difficulties Schedule (LEDS).

Results. A total of 259 people were screened (96% response rate). The second stage yielded 55 cases, of whom 54 had depressive disorder, and 48 non-cases. The adjusted prevalence of depressive disorders was 44·4% (95% CI 35·3 to 53·6): 25·5% in males and 57·5% in females. Nearly all cases had lasted longer than 1 year. Comparison of the cases and non-cases indicated that cases were less well educated, had more children and experienced more marked, independent chronic difficulties. Multivariate analysis indicated that severe financial and housing difficulties, large number of children and low educational level were particularly closely associated with depression.

Conclusion. This study confirms the high prevalence of depressive disorders in Pakistan and suggests that this may be higher than other developing countries because of the high proportion of the population who experience social adversity.

Background. There is not yet consensus on the best diagnostic definition of mixed bipolar episodes. Many have suggested the DSM-III-R/-IV definition is too rigid. We propose alternative criteria using data from a large patient cohort.

Methods. We evaluated 237 manic in-patients using DSM-III-R criteria and the Scale for Manic States (SMS). A bimodally distributed factor of dysphoric mood has been reported from the SMS data. We used both the factor and the DSM-III-R classifications to identify candidate depressive symptoms and then developed three candidate depressive symptom sets. Using ROC analysis we determined the optimal threshold number of symptoms in each set and compared the three ROC solutions. The optimal solution was tested against the DSM-III-R classification for cross-validation.

Results. The optimal ROC solution was a set, derived from both the DSM-III-R and the SMS, and the optimal threshold for diagnosis was two or more symptoms. Applying this set iteratively to the DSM-III-R classification produced the identical ROC solution. The prevalence of mixed episodes in the cohort was 13·9% by DSM-III-R, 20·2% by the dysphoria factor and 27·4% by the new ROC solution.

Conclusions. A diagnostic set of six dysphoric symptoms (depressed mood, anhedonia, guilt, suicide, fatigue and anxiety), with a threshold of two symptoms, is proposed for a mixed episode. This new definition has a foundation in clinical data, in the proved diagnostic performance of the qualifying symptoms, and in ROC validation against two previous definitions that each have face validity.

Background. GPs' attitudes towards depression vary, as do their abilities to detect and manage it effectively. Associations between attitudes and clinical behaviour have not yet been demonstrated directly. We tested two hypotheses: (1) that questionnaire measures of GPs' confidence in identifying depression predict their ability to identify depression in their patients; and (2) that GPs who prefer antidepressants prescribe more than those who prefer psychotherapy.

Methods. Forty GPs in Liverpool and Manchester completed the Depression Attitude Questionnaire (DAQ) and were asked for prescribing (PACT) information. Attender surveys using the General Health Questionnaire (GHQ-12), in combination with GP ratings of patients' psychological status, generated indices for GPs' case identification, bias and accuracy. We tested associations between these indices and the four DAQ components, in particular GPs' confidence in diagnosis, across a total of 1436 patients. We also compared the DAQ component on attitudes to treatment with relevant PACT data.

Results. The DAQ assessment of GPs' ability to identify cases of depression bore no relationship to their observed ability, as measured by accuracy, bias, or identification indices. However, there were significant associations between observed diagnostic ability and: preference for psychotherapy; ease in managing depression; and, belief in successful treatment. PACT data were available for 26 (65%) GPs. There was an association between preference for antidepressants and prescription of SSRIs (rs 0·3981, P < 0·044), but not for overall antidepressant or tricyclic prescribing, or for dose of dothiepin.

Conclusions. The DAQ measure of ease of identification is not valid when compared to actual clinical practice. The ability of GPs to identify depression may not be an independent variable, but may rather reflect other beliefs, attitudes and skills. This has considerable implications for educational interventions in primary care.

Background. Many studies have demonstrated co-morbidity of alcohol abuse/dependence with mood and anxiety disorders but relatively little is known about anxiety and depression across the full continua of alcohol consumption and problems associated with drinking.

Methods. Participants from a general population sample (N = 2725) aged 18–80 years completed the Alcohol Use Disorders Identification Test (AUDIT) and four measures of negative affect (two depression and two anxiety symptom scales) included in a self-completion questionnaire.

Results. High consumption, AUDIT total score, and AUDIT problems score were associated with high negative affect scores in participants under 60 years old (ORs in the range 1·80–2·83). Graphical and statistical analyses using continuous measures of alcohol use/problems and negative affect identified non-linear relationships where abstainers and occasional drinkers, as well as heavy and problem drinkers, were at risk of high anxiety and depression levels. This pattern, however, was not found in those aged [ges ] 60 years. The U-shaped relationship was not an artefact of abstainers being typical of the general population in their distribution of negative affect.

Conclusions. Studies of co-morbidity should acknowledge the possibility of non-linear associations and employ both continuous and discrete measures. Abstainers, as well as heavy drinkers, are at increased risk of symptoms of depression and anxiety disorders. Psychosocial factors may play a role in the U-shaped relationship between alcohol consumption and mortality.

Background. Chronic fatigue syndrome (CFS) and major depressive disorder (MDD) share many symptoms and aetiological factors but may have different neurobiological underpinnings. We wished to determine the profile of the biological variables disturbed in CFS and MDD, and identify any critical factors that differentiate the disorders.

Methods. Thirty patients with CFS, 20 with MDD and 15 healthy controls – matched group-wise for age and sex – were recruited. Subjects were given a detailed battery of motor and cognitive tests, including measures of psychomotor speed, memory and maximal voluntary muscle contraction in both the morning and evening that were balanced to avoid order effects.

Results. CFS patients generally performed worse on cognitive tests than healthy controls, but better than patients with MDD. Both patient groups had markedly impaired motor function compared with healthy controls. MDD subjects showed a significantly greater diurnal improvement in maximal voluntary contraction than healthy controls.

Conclusions. Patients with CFS and MDD show similarly substantial motor impairment, but cognitive deficits are generally more marked in MDD. Diurnal changes in some functions in MDD may differentiate the disorder from CFS.

Background. Many reports have appeared on associations between platelet monoamine oxidase (MAO) activity and susceptibility to psychiatric conditions; principally alcohol dependence but also conduct disorder, other drug use and depression. Recently, it has become apparent that MAO activity is inhibited by some component of cigarette smoke, and smokers have low platelet MAO activity. Since the prevalence of smoking is higher in many of the conditions in which MAO has been implicated, the MAO susceptibility associations may be partly, or entirely, false.

Methods. We have measured platelet MAO in 1551 subjects, recruited from the Australian NHMRC Twin Registry, who have provided information on alcohol use and dependence, smoking, conduct disorder, depression, attempted suicide, panic disorder and social phobia.

Results. Current smoking reduced platelet MAO activity in a significant and dose-related manner, with no evidence of lower MAO in ex-smokers or in non-smoking subjects with co-twins who smoked. Alcohol use and lifetime DSM-III-R alcohol dependence history were not associated with MAO activity when smoking was taken into account. Depression, panic disorder and social phobia showed no significant associations with platelet MAO activity. Subjects with a history of serious attempts at suicide had low platelet MAO activity; but although the difference from controls was as great as the reduction associated with smoking it was not significant after correction for smoking effects.

Conclusions. Although synaptic MAO activity undoubtedly plays a role in psychopathology, the concept that platelet MAO activity is a direct genetic marker of vulnerability to alcohol dependence cannot be sustained.

Background. The Well-being Questionnaire (W-BQ) has been designed to measure psychological well-being in people with a chronic somatic illness and is recommended by the World Health Organization for widespread use. However, studies into the factor structure of this instrument are still limited and their findings are inconsistent. This study aimed to investigate the factor structure of the Dutch version of the W-BQ.

Methods. A cross-validation design was used. A total of 1472 people with diabetes completed the W-BQ and were randomly assigned to group A or B. In group A (N = 736), exploratory factor analyses were conducted. Group B (N = 736) was split up into four subgroups of male or female patients with type 1 or type 2 diabetes. In these subgroups, confirmatory factor analyses were employed to test the model(s) developed in group A and the two models described in the literature (four-factor model with 22 items and a three-factor model with 12 items).

Results. Exploratory factor analyses yielded a three-factor model with 21 items (negative well-being, energy and positive well-being). In the subgroups of group B confirmatory factor analyses only accepted the three-factor model with 12 items. This factor solution was stable across gender, type of diabetes and level of education.

Conclusions. The best description of the factor structure of the Dutch translation of the W-BQ was given by a three-factor solution with 12 items (W-BQ12), measuring positive well-being (four items), negative well-being (four items) and energy (four items).