Background. We reported previously that the socio-economic status (SES) of individuals predicts variation in brain serotonergic responsivity, as assessed by neuropharmacological challenge in an adult community sample, and that this association is qualified by allelic variation in the serotonin transporter gene-linked polymorphic region (5-HTTLPR). Here we examine whether serotonergic responsivity covaries similarly with the SES of communities, as indexed by US Census data in the same study sample.

Method. Community SES was defined by levels of income, economic disadvantage, housing costs, and educational attainment of census tracts in which 249 locally recruited study participants (54% male) resided. Serotonergic responsivity was assessed as the baseline-adjusted, peak plasma prolactin (Prl) concentration following acute administration of the serotonin-releasing agent, fenfluramine; tissue for DNA extraction and 5-HTTLPR genotyping was available on 131 participants.

Results. Subjects residing in census tracts of lower SES showed a blunted Prl response to fenfluramine (diminished serotonergic responsivity) relative to individuals living in more affluent neighborhoods. When adjusted for personal income and education, SES at the community level continued to predict fenfluramine-stimulated Prl responses and did so independently of 5-HTTLPR genotype.

Conclusions. Area-level indices of relative social and economic disadvantage covary with individual differences in brain serotonergic responsivity, and this association is, in part, independent of individually defined SES. These findings may be relevant to reported effects of low community SES on the prevalence of psychiatric disorders or behaviors associated with dysregulation of central serotonergic function, such as depression, impulsive aggression, and suicide.

Background. This paper sought to examine the relationship between sexual orientation and mental health in a New Zealand birth cohort studied to age 25 years.

Method. The analysis is based on a sample of 967 participants (469 males; 498 females) in the Christchurch Health and Development Study. As part of this study information was gathered on: (a) measures of sexual orientation, same-sex behaviour and sexual attraction obtained at ages 21 and 25 years; (b) measures of mental disorders and suicidal behaviours over the interval 21–25 years; (c) measures of childhood and family background.

Results. Latent class analysis was used to combine indicators of sexual orientation, same sex behaviour and attraction to form an empirically based classification of sexual orientation. The best-fitting model classified the sample into three groups: exclusively heterosexual orientation (87·6%); predominantly heterosexual but with same-sex inclinations or experience (9·6%); predominantly homosexual (2·8%). Proportionately more women than men were classified as predominantly heterosexual (14·2% v. 4·8% respectively) or predominantly homosexual (3·9% v. 1·5% respectively). Cohort members with a predominantly homosexual orientation had rates of mental disorder and suicidal behaviours that were between 1·5 and 12 times higher than for those with an exclusively heterosexual orientation. These associations persisted after adjustment for confounding. The associations between sexual orientation and mental health were more marked for males than females.

Conclusions. The findings suggest a continuum of sexual preferences amongst young adults. Variations in sexual orientation were clearly associated with mental health. These associations tended to be stronger for males.

Background. Several small-N, uncontrolled reports have demonstrated that the behavioral technique of attention shaping has significantly increased attention span among severely ill schizophrenia patients.

Method. In this study, we evaluated the effectiveness of using an individually administered intervention for improving sustained attention, Attention Process Training (APT), followed by an attention-shaping procedure within the context of an ongoing skills training group. Patients were randomly assigned to receive either the APT and attention-shaping sequence (n=18) or equivalent hours of treatment in the same intensive behavioral rehabilitation program (n=13).

Results. Results indicated dramatic improvements in attentiveness in the cognitive rehabilitation condition compared with the control condition, which demonstrated essentially no change in attentiveness over the 12 weeks of treatment. The attention-shaping intervention appeared to account for the majority of the effect. In contrast to the observational data, performance on neuropsychological tests was unaffected by the cognitive interventions.

Conclusions. This two-phase intervention demonstrated effectiveness in promoting attentive behavior among chronic schizophrenia patients with severe attentional impairment.

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. Individual genome-wide linkage scans and meta-analyses support that one or more susceptibility genes for schizophrenia are located in chromosome 8p. A gene from this region, neuregulin 1 (NRG1), known to be involved with glutamatergic function, has been found to be associated in some studied samples.

Method. We have examined a new combined schizophrenia sample with 136 schizophrenia families largely of European ancestry (EA) and 646 subjects with DNA. We genotyped 14 single nucleotide polymorphisms (SNPs) in NRG1 including those reported to comprise schizophrenia-associated haplotypes in Icelandic, Scottish, Irish, and Chinese Han populations.

Results. We found no evidence of association at a single-marker or a haplotypic level. We review methodological aspects of previous studies to enable us to put our findings into context.

Conclusions. Our failure to find an association between NRG1 and schizophrenia might reflect different linkage disequilibrium (LD) patterns found in different populations, disease allelic heterogeneity, clinical heterogeneity of schizophrenia, or inadequate statistical power deriving from moderate sample size. NRG1, if a true gene for schizophrenia, accounts for a small fraction of the disease in most populations. The confirmation of NRG1 as a schizophrenia susceptibility gene will require studies with a comprehensive set of markers and in larger samples. The possibility remains that reports of NRG1 association might reflect false positives.

Background. Case control studies have supported a relationship between low folic acid and vitamin B12 and high homocysteine levels as possible predictors of depression. The results from epidemiological studies are mixed and largely from elderly populations.

Method. A random subsample of 412 persons aged 60–64 years from a larger community sample underwent psychiatric and physical assessments, and brain MRI scans. Subjects were assessed using the PRIME-MD Patient Health Questionnaire for syndromal depression and severity of depressive symptoms. Blood measures included serum folic acid, vitamin B12, homocysteine and creatinine levels, and total antioxidant capacity. MRI scans were quantified for brain atrophy, subcortical atrophy, and periventricular and deep white-matter hyperintensity on T2-weighted imaging.

Results. Being in the lowest quartile of homocysteine was associated with fewer depressive symptoms, after adjusting for sex, physical health, smoking, creatinine, folic acid and B12 levels. Being in the lowest quartile of folic acid was associated with increased depressive symptoms, after adjusting for confounding factors, but adjustment for homocysteine reduced the incidence rate ratio for folic acid to a marginal level. Vitamin B12 levels did not have a significant association with depressive symptoms. While white-matter hyperintensities had significant correlations with both homocysteine and depressive symptoms, the brain measures and total antioxidant capacity did not emerge as significant mediating variables.

Conclusions. Low folic acid and high homocysteine, but not low vitamin B12 levels, are correlates of depressive symptoms in community-dwelling middle-aged individuals. The effects of folic acid and homocysteine are overlapping but distinct.

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. Despite their impact on outcomes, the effect of patient treatment attitudes on the cost-effectiveness of health-care interventions is not widely studied. This study estimated the impact of patient receptivity to antidepressant medication on the cost-effectiveness of an evidence-based primary-care depression intervention.

Method. Twelve community primary-care practices were stratified and then randomized to enhanced (intervention) or usual care. Subjects included 211 patients beginning a new treatment episode for major depression. At baseline, 111 (52·6%) and 145 (68·7%) reported receptivity to antidepressant medication and counseling respectively. The intervention trained the primary-care teams to assess, educate, and monitor depressed patients. Twelve-month incremental (enhanced minus usual care) total costs and quality-adjusted life years (QALYs) were calculated.

Results. Among patients receptive to antidepressants, the mean incremental cost-effectiveness ratio was $5864 per QALY (sensitivity analyses up to $14689 per QALY). For patients not receptive to antidepressants, the mean incremental QALY score was negative (for both main and sensitivity analyses), or the intervention was at least no more effective than usual care.

Conclusions. These findings suggest a re-thinking of the ‘one size fits all’ depression intervention, given that half of depressed primary-care patients may be non-receptive to antidepressant medication treatment. A brief assessment of treatment receptivity should occur early in the treatment process to identify patients most likely to benefit from primary-care quality improvement efforts for depression treatment. Patient treatment preferences are also important for the development, design, and analysis of depression interventions.

Background. There is good evidence now that cognitive behaviour therapy (CBT) is effective in the treatment of people suffering from schizophrenia. There is also some evidence that the benefits of CBT persist after the end of treatment and that the direct costs of providing CBT as an adjunct to standard care are no higher than the direct costs of standard care alone. The aims of the present study were to discover if the benefits of CBT for acute schizophrenia which were found 1 year after index admission persist for another year, and to evaluate the comparative costs of providing CBT.

Method. Consecutive admissions meeting criteria were recruited. After screening, 43 were assigned at random to a treatment-as-usual (TAU) control group and 47 were assigned to TAU plus CBT. Patients (73% of original) were rated on symptoms and social functioning 2 years after index admission. An evaluation of the direct costs of services was also completed.

Results. The CBT group had maintained its advantage over the TAU group on negative symptoms and social functioning but had lost the advantage it previously enjoyed in positive symptoms. The difference between groups in total direct costs over the 2 years was not statistically significant despite the cost of providing CBT.

Conclusions. Some of the benefits of CBT for patients suffering acute psychotic episodes persist for 2 years. After the end of regular treatment, CBT should probably be targeted on the appearance of early signs of relapse to forestall the re-emergence of positive symptoms.

Background. The aim of this study was to examine the linkages between suicidal ideation and attempt in adolescence and subsequent suicidal behaviours and mental health in young adulthood.

Method. Data were gathered during the course of a 25-year longitudinal study of a birth cohort of 1265 New Zealand children. The information collected included: (a) measures of suicidal thoughts and attempts in adolescence (<18 years); (b) measures of suicidal ideation, suicide attempt, major depression, anxiety disorders, and substance use disorders in young adulthood (18–25 years); and (c) measures of childhood and family background, individual characteristics, and mental disorders in adolescence.

Results. After statistical adjustment for confounding factors, suicide attempt in adolescence was associated with increased risks of subsequent suicidal ideation (OR 5·7) suicide attempt (OR 17·8) and major depression (OR 1·5). Those reporting suicidal ideation without suicide attempt showed moderate increases in risks of later suicidal ideation (OR 2·5), suicide attempt (OR 2·0) and major depression (OR 1·6). In addition, there was evidence of an interactive relationship in which suicidal behaviour in adolescence was associated with increased risks of later substance use disorders in females but not males.

Conclusions. Young people reporting suicidal ideation or making a suicide attempt are an at-risk population for subsequent suicidal behaviour and depression. Further research is needed into the reasons for suicidal adolescent females being at greater risk of later substance use disorder.

Background. The objectives were to assess thoughts about suicide, plans to commit suicide and suicide attempts in the community, to investigate the use of health services following a suicide attempt, and to describe basic socio-cultural indices of the community.

Method. The community survey was one component of the larger WHO multisite intervention study on suicidal behaviours (SUPRE-MISS). In each site, it aimed at randomly selecting and interviewing at least 500 subjects of the general population living in the catchment area of the emergency department where the intervention component of the study was conducted. Communities of eight SUPRE-MISS sites (in Brazil, China, Estonia, India, Iran, South Africa, Sri Lanka, and Viet Nam) participated plus two additional sites from Australia and Sweden conducting similar surveys.

Results. Suicide attempts (0·4–4·2%), plans (1·1–15·6%), and ideation (2·6–25·4%) varied by a factor of 10–14 across sites, but remained mostly within the ranges of previously published data. Depending on the site, the ratios between attempts, plans, and thoughts of suicide differed substantially. Medical attention following a suicide attempt varied between 22% and 88% of the attempts.

Conclusions. The idea of the suicidal process as a continuous and smooth evolution from thoughts to plans and attempts of suicide needs to be further investigated as it seems to be dependent on the cultural setting. There are indications, that the burden of undetected attempted suicide is high in different cultures; an improved response from the health sector on how to identify and support these individuals is needed.

Objective. The goal of this study is to determine the association between panic attacks in adolescence and the risk of personality disorders during young adulthood.

Method. Data were drawn from the Children in the Community Study, a longitudinal epidemiological study of psychopathology across the life-course in 717 individuals in the community. Multiple logistic regression analyses were used to determine the association between panic attacks during adolescence in 1983 and the risk of personality disorders during young adulthood in 1993, adjusting for differences in sociodemographic characteristics, adolescent personality disorders, and co-morbid depressive and substance use disorders.

Results. Panic attacks during adolescence (in 1983) were associated with an increased risk of any DSM-IV personality disorder (in 1993) during young adulthood, which persisted after adjusting for differences in sociodemographic characteristics, adolescent personality disorders, and co-morbid depressive and substance use disorders. Panic attacks were associated with a statistically significantly increased risk of Cluster A, B, and C personality disorders.

Conclusions. These data provide initial evidence that panic attacks early in life are a marker or risk factor for the development of personality disorders in young adulthood. Replication of these findings is needed, as is more in-depth investigation into the mechanism of this link. If replicated in future research, these results may reveal a novel potential pathway for identifying youth at high risk for personality disorders.

Background. Evidence has mounted that some patients with schizophrenia experience remission of symptoms and restoration of social and vocational functioning. The purpose of this study was to identify neurocognitive variables associated with recovery from schizophrenia.

Method. Twenty-eight patients diagnosed with DSM-IV schizophrenia or schizoaffective disorder and who met our operational definition of recovery from schizophrenia underwent a battery of neurocognitive tests. These subjects were matched with schizophrenia patients who did not meet recovery criteria (‘non-recovered’) and with normal controls.

Results. On tests of executive functioning, verbal fluency and verbal working memory, recovered subjects performed significantly better than non-recovered subjects and were comparable to normal controls. Patient groups did not differ on a test that assessed early visual processing, but both groups performed significantly worse than normal controls.

Conclusions. Three measures of frontal lobe functioning appear to be neurocognitive domains associated with recovery from schizophrenia. These findings help narrow the search for targets for cognitive remediation that may have implications for improving community functioning.

Background. Although there is good evidence that cognitive therapy (CBT) lessens relapse and recurrence in unipolar depression, the duration of this effect is not known.

Method. One hundred and fifty-eight subjects, from a randomized controlled trial of CBT plus medication and clinical management versus medication and clinical management alone, were followed 6 years after randomization (4½ years after completion of CBT) and the longitudinal course assessed.

Results. Effects in prevention of relapse and recurrence were found to persist, with weakening, and were not fully lost until 3½ years after the end of CBT. Residual symptoms were also lessened.

Conclusions. The effect of CBT in reduction of relapse and recurrence persists for several years. The potential value of subsequent additional CBT some time after cessation should be explored.

Background. Few studies of physical activity in patients with anorexia nervosa (AN) have included a suitable control group. Nor has such research considered the influence of parents' activity on that of their children. Our first prediction was that adolescents with AN would be significantly more active than healthy controls both prior to, and during, the progression of their disorder. We also expected that the activity levels of parents and their daughters would be correlated, and that this relationship would be stronger in patient than control families. Finally, we expected that the AN parents would be more active and report a greater commitment to exercise than the control parents.

Method. In a case-control design, we employed multiple indicators of physical activity from adolescent females and their parents, using longitudinal, retrospective, self-report measurements.

Results. AN patients were significantly more active than controls both during the course of their disorder and prior to its onset. Parents' activity related to their daughter's activity, but this relationship was not stronger in the parents of the patients.

Conclusions. Future research is needed to determine whether the relationship between parents' and children's activity levels reflects environmental or genetic influences, or a combination of both factors. The important observation of a significant increase in patients' activity levels at least a year prior to diagnosis of the disorder suggests that enhanced physical activity may play a role in the development of the disorder. This may also serve as an early warning sign of a subclinical eating disorder in adolescent girls.

Background. This study addressed the prevalences, correlates, co-morbidity and disability of DSM-IV generalized anxiety disorder (GAD) and other psychiatric disorders in a large national survey of the general population, the National Institute on Alcohol Abuse and Alcoholism's (NIAAA) National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). The study presents nationally representative data, for the first time, on prevalence, correlates, co-morbidity, and comparative disability of DSM-IV GAD.

Method. Data are taken from a large (n=43093) representative sample of the adult USA population.

Results. Prevalences of 12-month and lifetime GAD were 2·1% and 4·1%. Being female, middle-aged, widowed/separated/divorced, and low income increased risk, while being Asian, Hispanic, or Black decreased risk. GAD was highly co-morbid with substance use, and other anxiety, mood, and personality disorders. Co-morbidity in GAD was not substantially greater than for most other Axis I and II disorders. Disability and impairment in pure GAD were equivalent to pure mood disorders, but significantly greater than in pure substance use, and other anxiety and personality disorders. Individuals co-morbid for GAD and each mood disorder were more disabled than those with pure forms of GAD or each mood disorder. When co-morbid with GAD, nicotine dependence and other anxiety and personality disorders were not associated with increased disability over that associated with pure GAD, but GAD did show increased disability over that due to each of these disorders in pure form.

Conclusions. Associations between GAD and Axis I and II disorders were strong and significant, with variation among specific disorders. Results strongly support GAD as an independent disorder with significant impairment and disability.

Background. The objective was to describe patients presenting themselves at emergency-care settings following a suicide attempt in eight culturally different sites [Campinas (Brazil), Chennai (India), Colombo (Sri Lanka), Durban (South Africa), Hanoi (Viet Nam), Karaj (Iran), Tallinn (Estonia), and Yuncheng, (China)].

Method. Subjects seen for suicide attempts, as identified by the medical staff in the emergency units of 18 collaborating hospitals were asked to participate in a 45-minute structured interview administered by trained health personnel after the patient was medically stable.

Results. Self-poisoning was the main method of attempting suicide in all eight sites. Self-poisoning by pesticides played a particularly important role in Yuncheng (71·6% females, 61·5% males), in Colombo (43·2% males, 19·6% females), and in Chennai (33·8% males, 23·8% females). The suicide attempt resulted in danger to life in the majority of patients in Yuncheng and in Chennai (over 65%). In four of the eight sites less than one-third of subjects received any type of referral for follow-up evaluation or care.

Conclusions. Action for the prevention of suicide attempts can be started immediately in the sites investigated by addressing the one most important method of attempted suicide, namely self-poisoning. Regulations for the access to drugs, medicaments, pesticides, and other toxic substances need to be improved and revised regulations must be implemented by integrating the efforts of different sectors, such as health, agriculture, education, and justice. The care of patients who attempt suicide needs to include routine psychiatric and psychosocial assessment and systematic referral to professional services after discharge.

Background. Excessive worry is required by DSM-IV, but not ICD-10, for a diagnosis of generalized anxiety disorder (GAD). No large-scale epidemiological study has ever examined the implications of this requirement for estimates of prevalence, severity, or correlates of GAD.

Method. Data were analyzed from the US National Comorbidity Survey Replication, a nationally representative, face-to-face survey of adults in the USA household population that was fielded in 2001–2003. DSM-IV GAD was assessed with Version 3.0 of the WHO Composite International Diagnostic Interview. Non-excessive worriers meeting all other DSM-IV criteria for GAD were compared with respondents who met full GAD criteria as well as with other survey respondents to consider the implications of removing the excessiveness requirement.

Results. The estimated lifetime prevalence of GAD increases by ~40% when the excessiveness requirement is removed. Excessive GAD begins earlier in life, has a more chronic course, and is associated with greater symptom severity and psychiatric co-morbidity than non-excessive GAD. However, non-excessive cases nonetheless evidence substantial persistence and impairment of GAD, high rates of treatment-seeking, and significantly elevated co-morbidity compared with respondents without GAD. Non-excessive cases also have sociodemographic characteristics and familial aggregation of GAD comparable to excessive cases.

Conclusions. Individuals who meet all criteria for GAD other than excessiveness have a somewhat milder presentation than those with excessive worry, yet resemble excessive worriers in a number of important ways. These findings challenge the validity of the excessiveness requirement and highlight the need for further research into the optimal definition of GAD.

Background. Few epidemiological studies have investigated incidence by age or age at onset distributions for mania or bipolar disorder. The current study aimed to determine these in a defined area in south-east London, over a 35-year period.

Method. All cases of first-episode mania presenting to psychiatric services in Camberwell, south-east London, between 1965 and 1999 were identified. Incidence rates by age, using 5-year age-at-onset bands, were estimated and the structure of the age-at-onset distribution for first-episode mania was investigated using finite mixture distributions (admixture analysis).

Results. The incidence of DSM-IV bipolar I disorder (BP I), first manic episode peaked in early adult life (16·38/100000 population per year in the 21–25 years band) with a much smaller peak in mid-life. A two-component normal mixture distribution fitted age at onset better than either a single normal distribution or a three-component mixture, implying the existence of early and later onset subgroups. The early onset group had a stronger family history of bipolar disorder, and showed more acute, severe and atypical symptoms during their first manic episode.

Conclusions. The incidence of mania peaks in early adult life but there is clear evidence of early and later onset subgroups which may represent different forms of disorder.

Background. While several personality characteristics are implicated in the etiology and phenotypic expression of schizophrenia, little is known about their trait status or clinical correlates during the early course of this disorder.

Method. The stability of five personality characteristics derived from the MMPI-168 was examined in recent-onset schizophrenia patients (n=59) during a psychotic period at study entry and at two out-patient assessments over the following 15 months and in non-patient controls (n=39) at similar time intervals. Among patients, associations between personality characteristics and clinical symptoms and exposure to stressful life events during the study period were also examined.

Results. Multilevel modeling analyses indicated that the between-subjects or trait-like variance components for these characteristics among patients were substantial, albeit smaller than those found for controls. Patients reported higher mean levels of Neuroticism, Cynicism, and Psychotic Ideation and lower mean levels of Psychopathic Tendencies and Denial of Somatic Complaints than controls. Among patients, several personality characteristics were systematically related to mean clinical symptom levels as well as frequency of exposure to dependent, but not independent, life events.

Conclusions. Stable individual differences in personality are detectable during the early course of schizophrenia and may help account for heterogeneity in clinical symptoms and functional outcome.