This issue features groups of papers on genetic epidemiology, personality traits and associations with psychopathology, depression, social support and psychiatric disorder, schizophrenia, together with papers on other topics.

Background. Co-morbidity within anxiety disorders, and between anxiety disorders and depression, is common. According to the theory of Gray and McNaughton, this co-morbidity is caused by recursive interconnections linking the brain regions involved in fear, anxiety and panic and by heritable personality traits such as neuroticism. In other words, co-morbidity can be explained by one disorder being an epiphenomenon of the other and by a partly shared genetic etiology. The aim of this paper is to evaluate the theory of Gray and McNaughton using the results of genetic epidemiological studies.

Method. Twenty-three twin studies and 12 family studies on co-morbidity are reviewed. To compare the outcomes systematically, genetic and environmental correlations between disorders are calculated for the twin studies and the results from the family studies are summarized according to the method of Klein and Riso.

Results. Twin studies show that co-morbidity within anxiety disorders and between anxiety disorders and depression is explained by a shared genetic vulnerability for both disorders. Some family studies support this conclusion, but others suggest that co-morbidity is due to one disorder being an epiphenomenon of the other.

Conclusions. Discrepancies between the twin and family studies seem partly due to differences in used methodology. The theory of Gray and McNaughton that neuroticism is a shared risk factor for anxiety and depression is supported. Further research should reveal the role of recursive interconnections linking brain regions. A model is proposed to simultaneously investigate the influence of neuroticism and recursive interconnections on co-morbidity.

Background. Genetic influences have been shown to play a major role in determining the risk of attention-deficit hyperactivity disorder (ADHD). In addition, prenatal exposure to nicotine and/or alcohol has also been suggested to increase risk of the disorder. Little attention, however, has been directed to investigating the roles of genetic transmission and prenatal exposure simultaneously.

Method. Diagnostic telephone interview data from parents of Missouri adolescent female twin pairs born during 1975–1985 were analyzed. Logistic regression models were fitted to interview data from a total of 1936 twin pairs (1091 MZ and 845 DZ pairs) to determine the relative contributions of parental smoking and drinking behavior (both during and outside of pregnancy) as risk factors for DSM-IV ADHD. Structural equation models were fitted to determine the extent of residual genetic and environmental influences on ADHD risk while controlling for effects of prenatal and parental predictors on risk.

Results. ADHD was more likely to be diagnosed in girls whose mothers or fathers were alcohol dependent, whose mothers reported heavy alcohol use during pregnancy, and in those with low birth weight. Controlling for other risk factors, risk was not significantly increased in those whose mothers smoked during pregnancy. After allowing for effects of prenatal and childhood predictors, 86% of the residual variance in ADHD risk was attributable to genetic effects and 14% to non-shared environmental influences.

Conclusions. Prenatal and parental risk factors may not be important mediators of influences on risk with much of the association between these variables and ADHD appearing to be indirect.

Background. Little research has examined genetic and environmental contributions to psychopathic personality traits. Additionally, no studies have examined etiological connections between psychopathic traits and the broad psychopathological domains of internalizing (mood and anxiety) and externalizing (antisocial behavior, substance abuse). The current study was designed to fill these gaps in the literature.

Method. Participants were 626 pairs of 17-year-old male and female twins from the community. Psychopathic traits were indexed using scores on the Multidimensional Personality Questionnaire (MPQ). Symptoms of internalizing and externalizing psychopathology were obtained via structured clinical interviews. Structural equation modeling was used to estimate genetic and environmental influences on psychopathic personality traits as well as the degree of genetic overlap between these traits and composites of internalizing and externalizing.

Results. Twin analyses revealed significant genetic influence on distinct psychopathic traits (Fearless Dominance and Impulsive Antisociality). Moreover, Fearless Dominance was associated with reduced genetic risk for internalizing psychopathology, and Impulsive Antisociality was associated with increased genetic risk for externalizing psychopathology.

Conclusions. These results indicate that different psychopathic traits as measured by the MPQ show distinct genetically based relations with broad dimensions of DSM psychopathology.

Background. There is empirical evidence suggesting that individuals with bulimia nervosa vary considerably in terms of psychiatric co-morbidity and personality functioning. In this study, latent profile analysis was used to attempt to identify clusters of bulimic subjects based on psychiatric co-morbidity and personality.

Method. A total of 178 women with bulimia nervosa or a subclinical variant of bulimia nervosa completed a series of self-report inventories of co-morbid psychopathology and personality, and also provided a buccal smear sample for genetic analyses.

Results. Three clusters of bulimic women were identified: an affective-perfectionistic cluster, an impulsive cluster, and a low co-morbid psychopathology cluster. The clusters showed expected differences on external validation tests with both personality and eating-disorder measures. The impulsive cluster showed the highest elevations on dissocial behavior and the lowest scores on compulsivity, while the affective-perfectionistic cluster showed the highest levels of eating-disorder symptoms. The clusters did not differ on genetic variations of the serotonin transporter gene.

Conclusions. This study corroborates previous findings suggesting that the bulimia nervosa diagnostic category is comprised of three classes of individuals based on co-morbid psychopathology and personality. These differences may have significant etiological and treatment implications.

Background. Previous studies have suggested an association between personality traits and post-traumatic stress. These studies either focused exclusively on military veterans or assessed personality traits after the traumatic event. This study investigates to what extent personality traits as assessed before the traumatic experience predict post-traumatic stress in civilians experiencing air attacks at the end of the exposure to stressful events and 1 year later.

Method. The revised version of the NEO Personality Inventory was administered to 70 students in Belgrade, Yugoslavia. In 1999, 1 or 2 years after the assessment, all students were exposed to air attacks for 11 weeks. At the end of the attacks and 1 year later post-traumatic stress was measured on the Impact of Event Scale.

Results. Pre-trauma personality predicted 13% of the variance of intrusion scores 1 year after the attacks. There was no significant correlation between personality traits and subsequent avoidance scores at any point of time.

Conclusions. Personality traits that are assessed before a traumatic event can, to a limited extent, predict intrusive symptoms in a non-clinical sample of civilians. Pre-trauma assessments of personality might be less strongly associated with post-traumatic stress than personality traits obtained after the traumatic event.

Objective. To determine how often requests are made for euthanasia and physician-assisted suicide (EAS) in the absence of severe disease and how such requests are dealt with in medical practice in The Netherlands.

Method. Retrospective interview study. Participants: 125 general practitioners (GPs), 77 nursing home physicians (NHPs), and 208 clinical specialists.

Results. In The Netherlands, each year approximately 400 people request EAS, because they are ‘weary of life’. Thirty per cent of all physicians have at some time received an explicit request for EAS in the absence of severe disease; 3% of all physicians had granted a request for EAS in such a case. Most requests for EAS to GPs in the absence of severe disease (n=29) were made by single people aged 80 years and over. While their problems were most frequently of a social nature, 79% had one or more non-severe illnesses. Most GPs refused the request; half of them proposed an alternative treatment, which the patient often refused. Nineteen people who did not receive any treatment persisted in their wish to die; the request for EAS from 5 out of 10 patients who received one or more types of treatment was withdrawn or became less explicit.

Conclusions. Most physicians in The Netherlands refuse requests for EAS in the absence of severe disease. Most patients persist in their request. In an ageing population more research is needed to provide physicians with practical interventions to prevent suicide and to make life bearable and satisfactory for elderly people who wish to die.

Background. Preceding longitudinal course and current somatic and psychiatric co-morbidity of depression have been little investigated in primary care.

Method. Consecutive patients (n=1111) in primary care in the city of Vantaa, Finland, were screened for depression with the PRIME-MD, and positive cases interviewed by telephone. Cases with current depressive symptoms were diagnosed face-to-face with the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I/P). A cohort of 137 patients with unipolar depressive disorders, comprising all patients with at least two depressive symptoms and clinically significant distress or disability, was recruited. The Structured Clinical Interview for DSM-IV Axis II Disorders (SCID-II), medical records, rating scales, and a retrospective life-chart were used to obtain comprehensive cross-sectional and longitudinal information.

Results. Current major depressive disorder (MDD) was the most prevalent depressive disorder (66%); it was usually mild to moderate but recurrent. A quarter of cases (23%) had MDD in partial remission or prodromal phase, and only 10% had true minor depression. Axis I co-morbidity was present in 59%, Axis II in 52%, and chronic Axis III disorders in 47%; only 12% had no co-morbidity. One third of patients presented with a psychological complaint, predicted by higher depression severity and younger age.

Conclusion. From a lifetime perspective, the majority of primary-care patients with depressive disorders suffer from recurrent MDD, although they are currently often in prodromal or residual phase. Psychiatric and somatic co-morbidity are highly prevalent. Treatment of depression in primary care should not rely on an assumption of short-lived, uncomplicated mild disorders.

Background. Very little research has examined the frequency with which women with major depressive disorder experience premenstrual exacerbation (PME) of depression or the characteristics of those who report such worsening. The NIMH Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study provides a unique opportunity to evaluate PME in depressed women seeking treatment in primary care or psychiatric settings.

Method. This report presents data from the first 1500 participants enrolled in the STAR*D study. Premenopausal women with major depressive disorder were asked if they experienced a worsening of their depressive symptoms 5–10 days prior to menses. Those reporting PME were compared with those reporting no PME with regard to sociodemographic characteristics, course of illness features, symptom presentation, general medical co-morbidity, functional impairment, and quality of life.

Results. Of 433 premenopausal women not taking oral contraceptives, 64% reported a premenstrual worsening of their depression. Women who reported PME had a longer duration of their current major depressive episode [30·7 (S.D.=73·7) months versus 13·5 (S.D.=13·2) months; p=0·001], as well as greater general medical co-morbidity. Women reporting PME were also more likely to endorse symptoms of leaden paralysis, somatic complaints, gastrointestinal complaints, and psychomotor slowing, and were less likely to endorse blunted mood reactivity.

Conclusions. PME is endorsed by the majority of premenopausal women with major depressive disorder and appears to be associated with a longer duration of depressive episode. PME is a common and important clinical issue deserving of further attention in both research and practice.

Background. Researchers and clinicians use a variety of measures to assess depressive symptoms, including clinician reports [for example the 17-item Hamilton Rating Scale for Depression (HRSD-17) and the 30-item Inventory for Depressive Symptomatology – Clinician Report (IDS-C-30)]; and patient reports [for example, the Beck Depression Inventory (BDI) and the 30-item Inventory for Depressive Symptomatology – Self-Report (IDS-SR-30)]. Although their concurrent convergent validity is well established, the degree to which these measures reflect the same pattern and level of change during treatment is unclear.

Method. We assessed depressive symptoms with two clinician (HRSD-17, IDS-C-30) and two patient (BDI, IDS-SR-30) reports on 14–15 occasions in 127 out-patients with recurrent major depressive disorder treated with 20 sessions of acute-phase cognitive therapy.

Results. Factor analyses revealed that time was the major source of variation in depressive symptom severity and change, with distinct ‘early’ and ‘late’ assessment factors, regardless of measure or rater (patient v. clinician). Average symptom severity decreased rapidly on all measures until mid-treatment, after which gradual decreases continued through the end of treatment. Effect sizes for pre- to post-treatment change were large for all measures (d=1·9–2·2), although there were significant differences among measures at some time-points.

Conclusions. The HRSD-17, BDI, IDS-C-30 and IDS-SR-30 reflect essentially the same symptom severity and change constructs during acute-phase cognitive therapy. Clinicians and researchers using one of these measures may estimate scores on the others with the provided common-factor conversions.

Background. Structural characteristics of social networks such as primary group size have received less attention than measures of perceived social support. Previous research suggests that associations between social network size and later common mental disorder status may differ according to sex and initial mental state.

Method. Adults participating in the 2000 British National Household Survey of psychiatric morbidity were randomly selected for follow-up 18 months later. The revised Clinical Interview Schedule (CIS-R) and the Interview Measure of Social Relations (IMSR) were administered at baseline and follow-up. Primary group size was defined as the total number of close relatives and friends. A four-level scale of common mental disorder was modelled with ordinal logistic regression, based on weighted data (n=2413).

Findings. After adjusting for confounders, a primary group size of three or less at time 1 predicted worse mental health at time 2. This effect was greatest in men who were initially non-cases at baseline (averaged odds 4·5) and in women who were initially cases at baseline (average odds 2·9). Primary group size at time 2 was significantly predicted by level of common mental disorder at time 1 in women but not in men. Thus, confounding by baseline disorder does not explain risk of developing poor mental health in socially isolated men.

Conclusion. This study replicates the strong effects of primary group size on future mental health that emerge when men and women are studied separately and when subjects are categorized according to baseline mental health status.

Background. Previous studies suggest that separation is a major stressful life event that is linked with marked increases in depressive symptoms. Little is known, however, about the sources of variation in depressive symptoms following separation.

Method. This study examines factors moderating the effect of separation on depressive symptoms in women participating in the Avon Longitudinal Study of Parents and Children (ALSPAC), a prospective, longitudinal study of a large community sample in the west of England. Data on marital/partner status, depression, and hypothesized moderating factors were available on women (n=8264), assessed on two occasions approximately 12 months apart.

Results. Over this 1-year period, 2·7% of women experienced a separation. As expected, those who experienced a separation between assessment periods reported, on average, a significant increase in depressive symptoms, approximately 0·25 of a S.D. However, there were marked individual differences in response to separation, with 56·1% showing a increase of 0·5 S.D. or more and 21·0% showing an decrease of 0·5 S.D. or more in depressive symptoms following separation. Regression analyses identified several factors that moderated response to separation; specifically, the effect of separation on depressive symptoms was less for women who were in a cohabiting (non-marital) relationship and for women who experienced elevated marital conflict prior to separation.

Conclusion. The results underscore the wide variation in responses to separation and document the need to consider context in interpreting the effects of major life events on depressive symptoms.

Background. There are suggestions that mortality, especially that due to suicide, increases among schizophrenia patients during a period of declining psychiatric beds. We investigated the mortality of schizophrenia patients in the general population of Finland during the reduction of psychiatric beds during 1980–1996.

Method. Patients hospitalized for schizophrenia before 31 December 1996, and alive on 1 January 1980 (n=58761) were identified via the National Hospital Discharge Register. General population data came from the National Population Register, and mortality data from the National Causes of Death Register. We calculated relative risks (RR) for total mortality, mortality due to natural causes (cancer, ischaemic heart disease, respiratory disease), unnatural causes (accident, homicide, suicide), and suicide.

Results. Patients with schizophrenia had an increased mortality both from natural causes (RR 2·59, 95% CI 2·55–2·63) and from suicide (RR 9·9, 95% CI 9·43–10·30). The RR for both natural and unnatural deaths was highest among patients with <5 years since onset of schizophrenia. Among them all-cause mortality rose in the 1990s, but decreased among patients with >10 years from onset. Otherwise no major changes or linear trends were found in mortality during deinstitutionalization.

Conclusions. Reduction of psychiatric beds did not generally increase the mortality of patients with schizophrenia. However, patients in their early years of illness experienced increased mortality after the steepest bed reduction. Improved recognition and treatment of somatic illness would benefit patients with schizophrenia.

Background. Recent neurobiological models provide a possible mechanism of daily life stress directly affecting the intensity of psychotic experiences in vulnerable individuals. In order to validate such a mechanism, the impact of daily life stress on psychosis intensity was investigated in two groups at increased risk of onset (relatives) and relapse (patients) of psychosis.

Method. Patients with psychosis in a clinical state of remission (n=42), first-degree relatives (n=47), and control subjects (n=49) were studied with the Experiencing Sampling Method (ESM is a structured diary technique assessing current context and psychopathology in daily life) to assess (1) appraised subjective stress related to daily activities and events, and (2) intensity of subtle psychotic experiences in daily life.

Results. Multilevel regression analyses revealed significant increases in psychosis intensity associated with increases in subjective activity – and event-related stress in patients. First-degree relatives reported increases in psychosis intensity in relation to activity-related stress but not event-related stress. No association was found in control subjects.

Conclusions. Subjects at increased risk for psychosis show continuous variation in the intensity of subtle psychotic experiences associated with minor stresses in the flow of daily life. Behavioural sensitization to environmental stress may therefore be a vulnerability marker for schizophrenia, reflecting dopaminergic hyper-responsivity in response to environmental stimuli.

Background. Placebo response, drug response, and drug–placebo differences appear to vary among psychiatric conditions.

Method. We evaluated the Food and Drug Administration (FDA) Summary Basis of Approval (SBA) reports to compare the magnitude of placebo response, magnitude of psychotopic drug response, and drug–placebo differences among various diagnostic groups such as depression, anxiety, and psychotic disorders.

Results. Six diagnostic groups (psychosis, obsessive–compulsive disorder (OCD), generalized anxiety disorder (GAD), depression, post-traumatic stress disorder, panic) varied in response to both placebo and active drug treatments. Response to placebo was high among patients participating in GAD, depression, and panic disorder clinical trials. Conversely, patients participating in psychotic disorder and OCD trials experienced low response to placebo.

Conclusion. Our findings indicate that the magnitude of placebo response and drug response were heterogeneous and were statistically significantly different among various psychiatric disorders. Although a noticeable degree of heterogeneity was detected in the drug–placebo ratio among various disorders, the differences did not reach statistical significance. This finding suggests that placebo use should be continued for newer agents being tested for all of the psychiatric disorders. These findings may help in the development of psychopharmacology trial designs and in the deliberations of ethics committees.

Background. While general population studies indicate an increase in the rate of psychiatric disorder in adolescence, little is known about the course of mental health and behaviour problems between childhood and adolescence in young people with severe intellectual disabilities.

Method. From a sample of 111 children with severe intellectual disability who had been identified from the registers of six special schools at 4–11 years of age, 82 were traced and reassessed 5 years later at the age of 11–17 years. Behaviour problems were assessed by means of parental interviews conducted in the family home and parent and teacher questionnaires. Parental reports of psychiatric diagnoses were checked against health records.

Results. With most behaviour problems, including aggression, destructive behaviour and self-injury, there was little difference in rates between the two assessment occasions. However, in spite of this overall pattern of stability, the rates of some behaviour problems, including overactivity, showed significant reductions between childhood and early adolescence. Persistence rates for most behaviour problems appeared comparable to those reported for similar behaviours in general population studies of children. There was no significant difference in the proportion of cases with psychiatric diagnoses between the two assessment occasions, although brief psychotic episodes emerged in three cases in adolescence.

Conclusions. The findings suggest that the prevalence of mental health and behavioural problems in young people with severe learning disabilities remains relatively stable between childhood and adolescence, although some specific behaviour problems diminish. However, a small minority of children may develop severe psychiatric disorders in adolescence.