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.

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. 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. We aimed to provide prevalence data on depression and other current mental disorders, impairment, need of psychiatric care and use of mental health services among young adults.

Methods. Based on a semi-structured clinical interview, current DSM-IV disorders, impairment, need of psychiatric care and use of mental health services were evaluated in a sample of 20–24-year-old young urban adults (N = 245), mean age 21·8, screened from a baseline population of 706. One-month prevalence estimates for disorders were calculated by the double sampling method, using various additional criteria to identify cases.

Results. One in four young adults (23·8%) suffered from a current mental disorder, the most prevalent being depressive (10·8%), anxiety (6·9%), substance use (6·2%) and personality disorders (6·0%). Prevalence estimates varied substantially according to the use of additional diagnostic criteria. Impairment (GAF < 61) together with DSM-IV symptom criteria produced an overall disorder prevalence of 10·3%, and 5·5% for depression. Prevalences were higher for females than males, except for alcohol abuse and personality disorders. Current co-morbidity was found in 39% of subjects with any disorder, and in more than half of those with depression. One-third of subjects with a current disorder reported an associated contact with psychiatric services and 16% had an ongoing contact.

Conclusions. Our findings support the use of additional criteria to produce clinically relevant prevalence data. Co-morbidity should receive special attention due to its amplification of both need for psychiatric care and severity of impairment. Finally, our results show disturbed young adults to be severely undertreated.

Background. The protective effects of religion against late life depression may depend on the broader sociocultural environment. This paper examines whether the prevailing religious climate is related to cross-cultural differences of depression in elderly Europeans.

Methods. Two approaches were employed, using data from the EURODEP collaboration. First, associations were studied between church-attendance, religious denomination and depression at the syndrome level for six EURODEP study centres (five countries, N = 8398). Secondly, ecological associations were computed by multi-level analysis between national estimates of religious climate, derived from the European Value Survey and depressive symptoms, for the pooled dataset of 13 EURODEP study centres (11 countries, N = 17739).

Results. In the first study, depression rates were lower among regular church-attenders, most prominently among Roman Catholics. In the second study, fewer depressive symptoms were found among the female elderly in countries, generally Roman Catholic, with high rates of regular church-attendance. Higher levels of depressive symptoms were found among the male elderly in Protestant countries.

Conclusions. Religious practice is associated with less depression in elderly Europeans, both on the individual and the national level. Religious practice, especially when it is embedded within a traditional value-orientation, may facilitate coping with adversity in later life.

Background. Culture influences symptom presentation and help-seeking and may influence the general practitioner's assessment.

Methods. We recruited Punjabi and English GP attenders to a two-phase survey in London (UK) using the Amritsar Depression Inventory and the General Health Questionnaire as screening instruments. The Clinical Interview Schedule was the criterion measure. General practitioners completed Likert assessments.

Results. The second phase was completed by 209 Punjabi and 180 English subjects. The prevalence of common mental disorders was not influenced by culture. Punjabi cases more often had ‘poor concentration and memory’ and ‘depressive ideas’ but were not more likely to have somatic symptoms. General practitioners were more likely to assess Punjabis with common mental disorder as having ‘physical and somatic’ symptoms or ‘sub-clinical disorders’. Punjabi cases with depressive ideas were less likely to be detected compared with English ones. In comparison to English men, English women were under-detected by Asian general practitioners. Help-seeking English subjects were more likely to be correctly identified as cases.

Conclusions. The prevalence of common mental disorders and somatic symptoms does not differ across cultures. Among English subjects, general practitioners were more likely to identify correctly pure psychiatric illness and mixed pathology; but Punjabi subjects with common mental disorders were more often assessed as having ‘sub-clinical disorders’ and ‘physical and somatic’ disorders. English women were less well detected than English men. English help-seeking cases were more likely to be detected.

Background. Geographic variations in the incidence of deliberate self-harm (DSH) and suicide have been shown to be associated with area-based measures of socio-economic deprivation and social fragmentation. Previous studies have been subject to methodological limitations. None has investigated whether ecological associations are reflected in characteristics of individuals involved in suicidal behaviour.

Methods. DSH patients presenting to a general hospital between 1985 and 1995 and suicides (including open verdicts) from the same catchment area were studied. Mean annual rates of DSH and suicide by gender were calculated for electoral wards. The wards were amalgamated into 20 groups according to their ranking for socio-economic deprivation (Townsend) and social fragmentation scores. Associations of these variables with DSH and suicide rates were investigated. Characteristics of DSH patients living in ward groups with the highest and lowest socio-economic deprivation and social fragmentation scores were compared.

Results. Socio-economic deprivation was associated with DSH rates among males (r = 0·89) and females (r = 0·87). After controlling for social fragmentation the associations remained relatively strong, particularly in young males. Associations with social fragmentation in both genders (males, r = 0·83; females, r = 0·86) were attenuated after controlling for socio-economic deprivation. For suicide, the only significant association was with socio-economic deprivation in males (r = 0·79), but this was attenuated after controlling for social fragmentation. The characteristics of individual DSH patients reflected those of the areas where they lived.

Conclusions. Reducing socio-economic deprivation and its associated problems may be an important strategy in the prevention of suicidal behaviour, especially in young men.

Background. Few studies have examined the extent to which populations of suicides and attempted suicides are similar, or different. This paper compares suicides and serious suicide attempts in terms of known risk factors for suicidal behaviour.

Methods. Using case–control methodology, risk factors for suicidal behaviour were examined in 202 individuals who died by suicide, 275 individuals who made medically serious suicide attempts and 984 randomly selected control subjects. Based on data from significant others, measures used spanned sociodemographic factors, childhood experiences, psychiatric morbidity and psychiatric history, exposure to recent stressful life events and social interaction.

Results. Multiple logistic regression identified the following risk factors that were common to suicide and serious suicide attempts: current mood disorder; previous suicide attempts; prior out-patient psychiatric treatment; admission to psychiatric hospital within the previous year; low income; a lack of formal educational qualifications; exposure to recent stressful interpersonal, legal and work-related life events. Suicides and suicide attempts were distinguished in the following ways: suicides were more likely to be male (OR = 1·9, 95% CI 1·1, 3·2); older (OR = 1·03, 95% CI 1·02, 1·04); and to have a current diagnosis of non-affective psychosis (OR = 8·5, 95% CI 2·0, 35·9). Suicide attempts were more likely than suicides to have a current diagnosis of anxiety disorder (OR = 3·5, 95% CI 1·6, 7·8) and to be socially isolated (OR = 2·0, 95% CI 1·2, 3·5). These findings were confirmed by discriminant function analysis, which identified two functions that described the three subject groups: the first function discriminated the two suicide groups from control subjects on a dimension corresponding to risk factors for suicide; the second function discriminated suicide from suicide attempt subjects on a series of factors including gender, non-affective psychosis and anxiety disorder.

Conclusions. Suicides and medically serious suicide attempts are two overlapping populations that share common psychiatric diagnostic and history features, but are distinguished by gender and patterning of psychiatric disorder.

Background. There is now evidence that the availability of plasma tryptophan is decreased during pregnancy and the puerperium and also in patients with major depression and inflammation. The aims of the present study were to examine: (i) the effects of pregnancy and delivery on plasma tryptophan and the amino acids known to compete for the same cerebral uptake mechanism (CAAs), valine, leucine, tyrosine, phenylalanine and isoleucine; (ii) the relationships between the availability of plasma tryptophan and postpartum depression or anxiety; and (iii) the relationships between the availability of plasma tryptophan to the brain and inflammatory markers, such as serum interleukin-6 (IL-6), interleukin-1 receptor-antagonist (IL-1RA) and the leukaemia inhibitory factor receptor (LIF-R).

Methods. The above variables were measured in 13 healthy non-pregnant and in 98 pregnant women 3 to 6 days before delivery and 1 and 3 days after delivery. On each occasion the parturient women completed the state version of Spielberger State–Trait Anxiety Inventory (STAI) and the Zung Depression Rating Scale (ZDS).

Results. Plasma tryptophan and the tryptophan/CAA ratio were significantly lower at the end of term and after delivery than in the plasma of non-pregnant, healthy women. The tryptophan/CAA ratio was significantly lower in the early puerperium than at the end of term. There were no significant relationships between the availability of plasma tryptophan and either post-partum depression or changes in the STAI or ZDS scores in the early puerperium. The changes in the tryptophan/CAA ratio from the end of term to the early puerperium were significantly and inversely related to serum IL-6, IL-1RA and LIF-R.

Conclusions. The results show that the reduction in the availability of plasma tryptophan from the end of term to the early puerperium is related to immune activation; and that the lowered availability of plasma tryptophan is not related either to depressive or anxiety symptoms in the early puerperium or to post-partum depression ensuing some months later.

Background. The importance of stressful life events and long-term difficulties in the onset of episodes of unipolar depression is well established for young and middle-aged persons, but less so for older people.

Method. A prospective case–control study was nested in a large community survey of older people. We recruited 83 onset cases during a 2-year period starting 2½ years after the survey, via screening (N = 59) and GP monitoring (N = 24), and 83 controls, a random sample from the same survey population. We assessed depression with the PSE-10 and life stress exposure with the LEDS.

Results. Risk of onset was increased 22-fold by severe events and three-fold by ongoing difficulties of at least moderate severity. Severe events accounted for 21% of all episodes but ongoing difficulties for 45%. The association of onset with life stress, often health-related such as death, major disability and hospitalization of subject or someone close, was most pronounced in the cases identified by screening. While a clear risk threshold for events was found between threat 2 and 3 (on a scale of 1–4), the risk associated with difficulties increased more gradually with severity of difficulty. Compared with controls, severe events involved a larger risk for cases without a prior history of depression (OR = 39·48) than for cases with (OR = 8·86). The opposite was found for mild events (OR = 2·94 in recurrent episodes; OR = 1·09 in first episodes). The impact of ongoing difficulties was independent of severity of episode and history of depression.

Conclusion. Although the nature of life stress in later life, in particular health-related disability and loss of (close) social contacts, is rather different from that in younger persons, it is a potent risk factor for onset of a depressive episode in old age. Severe events show the largest relative risk, but ongoing difficulties account for most episodes. The association of severe events with onset tends to be stronger in first than in recurrent episodes. Mild events can trigger a recurrent episode but not a first one.

Background. This study compared the effectiveness of cognitive therapy (CT), nutritional therapy (NT), the combination of cognitive and nutritional therapy (CNT), against a control condition of support group (SG) in the treatment of bulimia nervosa.

Methods. One hundred female out-patients who fulfilled DSM-III-R criteria for bulimia nervosa were randomized to the four treatment groups. NT and CT were designed to cover different areas with minimal overlap, and CNT provided all of the features of both of these treatments. The control condition was conducted in a group self-help format. Each of the treatments lasted 14 weeks.

Results. All three active treatments as well as SG produced significant decreases in binge/vomit episodes. Intent-to-treat analysis found CNT and CT to be significantly more effective than SG in retaining subjects in treatment and completion of study, as well as in producing greater improvements in dysfunctional attitudes and self-control. CNT was superior to SG in achieving abstinence from bulimic behaviour. NT was superior to SG only in increase of self-control. Logistic regression found that the cognitive component, whether given alone or in conjunction with NT, and higher pre-treatment self-control scores were significant predictors for both completion of study and abstinence.

Conclusion. CT (either alone, or in combination with nutritional therapy) remains the treatment of choice for bulimia nervosa. A treatment escalation approach should be tested for the treatment of bulimia with the more intensive and less widely available CT (with or without nutritional counselling) offered after patients have failed the less intensive and more widely available support group treatment.

Background. Given our poor understanding of the very long-term course of anorexia nervosa, many questions remain regarding the potential for recovery and relapse. The purpose of the present study was to investigate long-term outcome and prognosis in an anorexic sample 21 years after the initial treatment.

Method. A multidimensional and prospective design was used to assess outcome in 84 patients 9 years after a previous follow-up and 21 years after admission. Among the 70 living patients, the follow-up rate was 90%. Causes of death for the deceased patients were obtained through the attending physician. Predictors of a poor outcome at the 21-year follow-up were selected based on the results of a previous 12-year follow-up of these patients.

Results. Fifty-one per cent of the patients were found to be fully recovered at follow-up, 21% were partially recovered and 10% still met full diagnostic criteria for anorexia nervosa. Sixteen per cent were deceased, due to causes related to anorexia nervosa. The standardized mortality rate was 9·8. The three groups also showed significant differences in psychosocial outcome. A low body mass index and a greater severity of social and psychological problems were identified as predictors of a poor outcome.

Conclusions. Recovery is still possible for anorexic patients after a period of 21 years. On the other hand, patients can relapse, becoming symptomatic again despite previously achieving recovery status. Only a few patients classified as having a poor outcome were found to seek any form of treatment, therefore, it is recommended that these patients should be monitored regularly and offered treatment whenever possible.

Background. There is a paucity of long-term outcome studies of panic disorder that exceed a 2-year follow-up. The aim of the study was to evaluate the long-term follow-up of patients with panic disorder with agoraphobia treated according to a standardized protocol.

Methods. A consecutive series of 200 patients satisfying the DSM-IV criteria for panic disorder with agoraphobia was treated in an out-patient clinic with behavioural methods based on exposure homework. One hundred and thirty-six patients became panic free after 12 sessions of psychotherapy and 132 were available for follow-up. A 2- to 14-year (median = 8 years) follow-up was performed. Survival analysis was employed to characterize the clinical course of patients.

Results. Thirty-one of the 132 patients (23%) had a relapse of panic disorder at some time during follow-up. The estimated cumulative percentage of patients remaining in remission was 93·1 after 2 years, 82·4 after 5 years, 78·8 after 7 years and 62·1 after 10 years. Such probabilities increased with younger age, and in the absence of a personality disorder, of high pre-treatment levels of depressed mood, of residual agoraphobic avoidance after exposure, and of concurrent use of benzodiazepines and antidepressant drugs.

Conclusions. The findings suggest that exposure treatment can provide lasting relief to the majority of patients with panic disorder and agoraphobia. Disappearance of residual and subclinical agoraphobic avoidance, and not simply of panic attacks, should be the aim of exposure therapy.

Background. There is very little information on long-term follow-up of social phobia.

Methods. A consecutive series of 70 patients satisfying the DSM-IV criteria for social phobia was treated in an out-patient clinic with behavioural methods based on exposure homework. Forty-five patients were judged to be remitted after eight individual sessions of psychotherapy. A 2 to 12 year (median = 6 years) follow-up was performed. Survival analysis was selected to characterize the clinical course of patients. Assessments were performed before treatment, at the end of therapy, after 1 year, and subsequently on a yearly basis, and utilized selected items of Paykel's Clinical Interview for Depression.

Results. Six of the 45 patients (13%) had a relapse of social phobia at some time during follow-up. The estimated cumulative percentage of patients remaining in remission was 98 after 2 years, 85 after 5 years and 85 after 10 years. Such probabilities increased in the absence of a personality disorder, of residual social phobic avoidance after exposure, and of concurrent use of benzodiazepines.

Conclusions. The findings suggest that, even though one patient out of three is unable to complete treatment or does not benefit sufficiently from it, exposure treatment can provide lasting effects to the majority of patients with social phobia. Disappearance of residual, subclinical social phobic avoidance appears to be the target of treatment.

Background. Many previous studies have shown that individuals who develop schizophrenia in adult life are more likely than normal controls to have a history of obstetric complications (OCs) at birth. However, little attention has been paid to the involvement of OCs in the risk of developing childhood-onset schizophrenia (COS). In our earlier report, we found an association between OCs and the development of COS. In this study, we determined whether the association could be replicated in another, independent set of patients with COS.

Methods. OCs, birth weight and gestational age were retrospectively assessed in 35 children, aged between 14 and 15 years old (average 15·4 years), who met the DSM-III-R criteria for schizophrenia, and in age- and gender-matched controls (children with anxiety disorders).

Results. The COS patients showed significantly greater scores in all of the three measures of OCs according to the Parnas et al. scale compared to controls. Moreover, individuals exposed to OCs were about 3·2 times (odds ratio = 3·22; 95% confidence interval, 1·1–9·8) more likely to develop schizophrenia than those without a history of OCs. The mean birth weight was significantly lower in schizophrenics than in controls (P < 0·05). The frequency of prematurity signs with weight < 2500 g was significantly higher in schizophrenics than in controls (P < 0·05).

Conclusion. Repeatedly reported association between OCs and adult-onset schizophrenia have also been demonstrated in patients with COS. This suggests that there may be a continuity between childhood- and adult-onset schizophrenia.

Background. The aim of this study was to assess visual information processing and cognitive functions in unaffected siblings of patients with schizophrenia, bipolar disorder and control subjects with a negative family history.

Methods. The siblings of patients with schizophrenia (N = 25), bipolar disorder (N = 20) and the controls subjects (N = 20) were matched for age, education, IQ, and psychosocial functioning, as indexed by the Global Assessment of Functioning scale. Visual information processing was measured using two visual backward masking (VBM) tests (target location and target identification). The evaluation of higher cognitive functions included spatial and verbal working memory, Wisconsin Card Sorting Test, letter fluency, short/long delay verbal recall and recognition.

Results. The relatives of schizophrenia patients were impaired in the VBM procedure, more pronouncedly at short interstimulus intervals (14, 28, 42 ms) and in the target location task. Marked dysfunctions were also found in the spatial working memory task and in the long delay verbal recall test. In contrast, the siblings of patients with bipolar disorder exhibited spared performances with the exception of a deficit in the long delay recall task.

Conclusions. Dysfunctions of sensory-perceptual analysis (VBM) and working memory for spatial information distinguished the siblings of schizophrenia patients from the siblings of individuals with bipolar disorder. Verbal recall deficit was present in both groups, suggesting a common impairment of the fronto-hippocampal system.

Objective. Although family, twin and adoption studies have suggested that lifetime major depression (MD) is a heritable condition, nearly all these studies have relied for the diagnosis on long-term human memory, which is fallible and potentially biased. Could the estimates of heritability of MD be biased by the well-demonstrated genetic influences on memory?

Methods. Both members of 858 female–female twin pairs from a population-based registry were personally interviewed at least three times over 9 years. The interview assessed a history of depressive onsets and recoveries in the last year to the nearest month. We examine heritability of MD using four recall intervals: last year, last 6 months, last 3 months and current month.

Results. Examining the occurrence of one or more depressive episodes across all three interviews, heritabilities of MD (95% CI) for the four time periods were: 0·41 (0·27–0·54), 0·41 (0·26–0·55), 0·35 (0·16–0·52) and 0·34 (0·11–0·55). These heritability estimates did not differ significantly from one another. A similar pattern was found if heritability was assessed for the number of interviews in which criteria for MD were met.

Conclusion. Modelling results suggest that the heritability of MD was not influenced by the duration of the required recall. Genetic influences on human recall do not appear to contribute substantially to estimated heritability of MD.

Background. Controlled studies have demonstrated that variations in electro-convulsive therapy (ECT) technique impacts on efficacy and cognitive side effects. However, there is little information on the extent of variation in how ECT is practiced in community settings in the United States.

Methods. A survey of practice patterns was conducted at ECT facilities in the greater New York City metropolitan area.

Results. The 59 facilities varied considerably in many aspects of ECT practice, often clearly departing from the standards in the field. The more intensive the form of ECT used at facilities, the less likely was cognitive status assessed following the treatment course.

Conclusion. There is marked variability in the nature of ECT practices in community settings. The extent to which this variability impacts on the benefits and risks of ECT needs to be examined.

Background. Self-asphyxiation using car exhaust gas is a common method of suicide in England and Wales, particularly in young males. The introduction of catalytic converters has reduced the toxicity of car exhausts. The main aims of the study were: to seek evidence of a fall in car exhaust suicides in the general population and in age and gender groups; to relate any fall to changes in car exhaust systems, particularly since legislation on car exhaust emissions in 1993; and to examine rates of suicide by other methods for evidence of method substitution.

Methods. Population study in England and Wales using national suicide statistics for 1987 to 1998.

Results. There was a fall in suicide by car exhaust asphyxiation in all age and gender groups. This change was most marked after 1993. The overall population suicide rate (all methods) also fell but there was no overall change in suicides by young males or females. In these groups suicide by hanging increased.

Conclusions. Legislation on catalytic converters appears to have contributed to a fall in car exhaust suicides. However, the effect on overall suicide rates in young people has been reduced by method substitution.