This issue contains two reviews, one on the aetiology of depression and one on outcome studies of first-episode psychosis. Other sets of papers examine further aspects of depression and psychosis, and four individual papers examine a variety of topics.

This review will start by considering studies of the genetic contribution to the liability to depression, and go on to consider some of the ways in which environmental factors can modify gene expression. This will lead on to the pathways by which the genetic factors also appear to control stressful life events in adolescence and adult life, and then to a consideration of causes that are entirely environmental. We will conclude by considering the causes of the gender differences in the prevalence of depression during adult life.

Background. Existing outcome literature has had an over-representation of chronic patients and suggested a progressive course and poor outcome for schizophrenia. The current study aimed to recombine data of samples from longitudinal studies of first-episode psychosis (FEP) to describe outcome and its predictors.

Method. A literature search (1966–2003) was conducted for prospective studies examining outcome in first-episode non-affective psychosis using the following key words: early, first, incident, episode, admission, contact, psychosis, schizophrenia, psychotic disorders, course, outcome, follow-up, longitudinal, cohort. These were pooled and analyzed using descriptive and regression analyses.

Results. Thirty-seven studies met the inclusion criteria, representing 4100 patients with a mean follow-up of 35·1±6·0 months. Studies varied in the categories of outcome used, the most common being ‘good’ (54% of studies) and ‘poor’ (34% of studies), variably defined. In studies reporting these categories, good outcomes were reported in 42·2% (3·5%) and poor outcomes in 27·1% (2·8%) of cases. Predictors associated with better outcome domains were: combination of pharmacotherapy and psychosocial therapy, lack of epidemiologic representativeness of the sample, and a developing country of origin. Use of typical neuroleptics was associated with worse outcome. Stratification analyses suggested that populations with schizophrenia only, and those with prospective design, were associated with worse outcome domains.

Conclusions. Outcome from FEP may be more favorable than previously reported, and treatment and methodological variables may be important contributors to outcome. Significant heterogeneity in definitions and methodology limited the comparison and pooling of data. A multi-dimensional, globally used definition of outcome is required for future research.

Background. Social rhythm disruption life events are significant predictors of mood relapse in bipolar patients. However, no research has examined the relationship between these events and their hypothesized mechanism of action: disrupted sleep-wake patterns. The goal of this study was to test whether participants with major depressive disorder have a greater disruption of daily sleep and motor activity following disrupting life events when compared to normal controls.

Method. Over the course of 2 weeks, 39 normal controls and 39 individuals with major depressive disorder completed life events interviews and wore actigraphs to obtain estimates of sleep/wake activity.

Results. Statistically significant interactions indicated that the presence of at least one disrupting life event in the previous 4 months correlated with elevations in the amount of time spent awake after sleep onset [β=0·45, ΔF(1,73)=4·80, p<0·05], and decreases in the percentage of time spent asleep [β=−0·53, ΔF(1,73)=6·57, p<0·05], in depressed individuals but not in normal controls.

Conclusions. The results indicated that depressed individuals may be more susceptible to the effects of life events on sleep than normal controls. This is the first study to date to correlate life events with objective measures of sleep. However, prospective longitudinal research is necessary to clarify the temporal relationship among these variables.

Background. Research suggests high levels of depression and low levels of service use among older adults from UK minority ethnic groups. This study aimed to explore older adults' attitudes and beliefs regarding what would help someone with depression, and to consider how these may facilitate or deter older people from accessing treatment.

Method. In-depth individual qualitative interviews were conducted with older adults with depression (treated and untreated) and the non-depressed older population. A multi-cultural approach was used that incorporated the perspectives of 32 black Caribbean, 33 South Asian and 45 white British older adults.

Results. Participants felt that the responsibility for combating depression was an internal and individual task with support considered secondary. However, the majority expressed a willingness and desire to discuss psychosocial problems. Within the black Caribbean group, conversing with God through prayer was seen as an effective means of overcoming depression, while a large proportion of South Asian and white British participants identified families as an important source of help. There was wide variation in how older adults construed the role of the general practitioner (GP) and many expressed acute awareness of the demands on GPs' time.

Conclusions. Efforts to socialize and remain active may provide a useful and acceptable adjunct to clinical interventions. However, there is a need to communicate that depression often necessitates formal help, and that it is acceptable to voice concerns regarding emotional states in a GP consultation. The findings suggest that older adults would welcome the opportunity to discuss their feelings with health-care professionals.

Background. We report here a study examining the relationships between insight and psychopathology, cognitive performance, brain volume and co-morbid depression in 251 patients experiencing a first episode of psychosis, who were then randomly assigned to 2 years of double-blind treatment with either olanzapine or haloperidol.

Method. Repeated measures of insight were obtained at baseline and 12, 24, 52 and 104 weeks by the Insight and Treatment Attitudes Questionnaire (ITAQ).

Results. Older age, female gender and white ethnicity were associated with more insight. Higher total, positive, negative and general psychopathology scores on the Positive and Negative Syndromes Scale (PANSS) were associated with less insight. Higher depression scores were associated with more insight. Better neurocognitive function and large brain volumes were associated with more insight. More insight throughout the study was associated with longer time to medication non-adherence. However, baseline insight was not significantly related to the probability of discontinuing the study before 2 years. Insight improved significantly over the course of the study, but the improvement in insight was not significantly different between the two antipsychotic treatment groups.

Conclusions. Multiple factors contribute to insight. Patients experiencing a first episode of psychosis who have little insight are at increased risk of discontinuing their medication.

Background. There have been recent advances in the ability to identify people at high risk of developing psychosis. This has led to interest in the possibility of preventing the development of psychosis and provides the opportunity to investigate psychological mechanisms that may confer vulnerability to psychosis.

Method. Fifty-eight patients at ultra-high risk of developing a first episode of psychosis were compared with 56 non-patients matched for age and occupational status on measures of meta-cognition, schizotypal traits, dysfunctional attitudes and distress.

Results. Analyses of covariance revealed that people at high risk of developing psychosis scored higher on measures of cognitive vulnerability, including negative meta-cognitive beliefs, beliefs about rejection and criticism from others, and discrepancies in self-perception, schizotypal traits and general mental distress. Correlational analyses revealed that negative meta-cognitive beliefs, dysfunctional attitudes and beliefs about rejection and criticism from others were positively associated with several dimensions of symptomatology in at-risk mental states (ARMS) patients.

Conclusions. Cognitive and personality factors appear to characterize people at high-risk of developing psychosis and are associated with their distressing experiences. The clinical implications of these findings are discussed.

Background. Military samples provide an excellent context to systematically ascertain hospitalization for severe psychiatric disorders. The National Collaborative Study of Early Psychosis and Suicide (NCSEPS), a collaborative study of psychiatric disorders in the US Armed Forces, estimated rates of first hospitalization in the military for three psychiatric disorders: bipolar disorder (BD), major depressive disorder (MDD) and schizophrenia.

Method. First hospitalizations for BD, MDD and schizophrenia were ascertained from military records for active duty personnel between 1992 and 1996. Rates were estimated as dynamic incidence (using all military personnel on active duty at the midpoint of each year as the denominator) and cohort incidence (using all military personnel aged 18–25 entering active duty between 1992 and 1996 to estimate person-years at risk).

Results. For all three disorders, 8723 hospitalizations were observed in 8120136 person-years for a rate of 10·7/10000 [95% confidence interval (CI) 10·5–11·0]. The rate for BD was 2·0 (95% CI 1·9–2·1), for MDD, 7·2 (95% CI 7·0–7·3), and for schizophrenia, 1·6 (95% CI 1·5–1·7). Rates for BD and MDD were greater in females than in males [for BD, rate ratio (RR) 2·0, 95% CI 1·7–2·2; for MDD, RR 2·9, 95% CI 2·7–3·1], but no sex difference was found for schizophrenia. Blacks had lower rates than whites of BD (RR 0·8, 95% CI 0·7–0·9) and MDD (RR 0·8, 95% CI 0·8–0·9), but a higher rate of schizophrenia (RR 1·5, 95% CI 1·3–1·7).

Conclusions. This study underscores the human and financial burden that psychiatric disorders place on the US Armed Forces.

Objective. Recurrence risk estimates for schizophrenia are fundamental to our understanding of this complex disease. Widely cited estimates are from small/older samples. If these estimates are biased upwards, then the rationale for molecular genetic studies of schizophrenia may not be as solid.

Method. We created a population-based, Swedish national cohort by linking two Swedish national registers into a relational database (the Swedish Hospital Discharge Register and the Multi-Generation Register). Affection was defined as the lifetime presence of at least two in-patient hospitalizations with a core schizophrenia diagnosis.

Results. Merging the Swedish national registers created a population-based cohort of 7739202 individuals of known parentage. The lifetime prevalence of the narrow definition of schizophrenia was 0·407% and we estimated that one in every 79 extended Swedish families had been impacted by schizophrenia. The proportion of affected families with multiple affected members was 3·81%. Recurrence risk estimates for all relative types were strikingly similar to those reported in smaller and older studies. For example, we estimated λsibs at 8·55 [95% confidence interval (CI) 7·86–9·57] compared with a literature estimate of 8·6.

Conclusions. In the largest and most comprehensive sample yet studied, we confirm the accepted estimates of recurrence risks for schizophrenia, and provide more accurate estimates of recurrence risks of schizophrenia in relatives, an estimate of the familial impact of schizophrenia, and the multiplex proportion (essential for gauging the generalizability of findings from multiplex pedigrees). These data may be valuable for planning and interpreting genetic studies of schizophrenia.

Background. Verbal declarative memory is a core deficit in schizophrenia patients, seen to a lesser extent in unaffected biological relatives. Neuroimaging studies suggest volumetric differences and aberrant function in prefrontal and temporal regions in schizophrenia patients compared to controls. These deficits are also reflected in the small number of similar investigations in unaffected biological relatives. However, it is unclear the extent to which dysfunction is genetically mediated or a feature of the established illness.

Method. Event-related blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) was used to measure brain activation in 68 biological relatives of schizophrenia patients (of whom 27 experienced transient or isolated psychotic symptoms) and 21 controls during verbal classification and recognition.

Results. During word classification, the high-risk group showed a greater response relative to controls in the right inferior frontal gyrus. During correct recognition (relative to correct rejection), the high-risk group showed significantly greater response relative to controls in the right cerebellum. When the high-risk group was split into those with (HR+) and without (HR−) psychotic symptoms, the increased response in the right inferior frontal gyrus was only seen when the HR+ were compared to controls. The greater cerebellar response was seen when both HR groups were compared to controls.

Conclusions. Activation increases in the right inferior frontal gyrus and cerebellum in high-risk subjects compared to controls during a relatively low-load memory task are likely to represent compensation for genetically mediated abnormalities. This is consistent with a leftward shift of the inverted ‘U’ load–response model of cognitive function in schizophrenia.

Background. There is evidence that cannabis use might be relevant to the aetiology of schizophrenia. We aimed to measure any change in cannabis use over time in those first presenting with schizophrenia in South-East London from 1965 to 1999, and compare this with change in use in those presenting with non-psychotic psychiatric disorders.

Method. The rate of cannabis use in the year prior to first ever presentation was measured over seven time periods. Logistic regression modelling was used to determine (a) whether cannabis use changed over time, after controlling for age, sex and ethnicity, and (b) whether there was an interaction between diagnosis and time.

Results. Cannabis use increased over time in both the schizophrenia group [odds ratio per time period (OR) 2·03, 95% confidence interval (CI) 1·74–2·38, p<0·0001] and the non-psychotic disorders group (OR 1·24, 95% CI 1·05–1·47, p=0·012), after controlling for age, sex and ethnicity. However, the effect of time was significantly greater in the schizophrenia group than in the non-schizophrenia group (χ2=17, p<0·0001).

Conclusion. Cannabis use in the year prior to presentation with schizophrenia increased markedly between 1965 and 1999, and disproportionately so compared to increase in cannabis use in other psychiatric disorders.

Background. The purpose of this study was to present 12-month and lifetime estimates of the prevalence, sociodemographic and clinical correlates, and psychiatric co-morbidity of DSM-IV cannabis abuse and dependence.

Method. Data were derived from a large nationally representative survey (n=43093) of US adults.

Results. The prevalence of 12-month and lifetime DSM-IV cannabis abuse (1·1% and 7·2%) exceeded the corresponding rates of cannabis dependence (0·3% and 1·3%). Being male, Native American, widowed/separated/divorced, and residing in the West increased the odds whereas being Black, Asian or Hispanic decreased the odds of cannabis abuse and dependence. Cannabis dependence was significantly associated with low income. Ages of onset for both cannabis use disorders occurred in adolescence and the majority of individuals with these disorders remained untreated. Co-morbidity was high between cannabis use disorders and other Axis I and II disorders.

Conclusions. Cannabis use disorders continue to present a widespread and serious personal and public health problem. Native Americans were found to have high rates of cannabis use disorders, warranting closer attention to the mental health needs of this subgroup. Associations between cannabis abuse and dependence and Axis I and II disorders were strong, signaling the need for more comprehensive assessment of individuals with cannabis use disorders. Further controlled treatment studies are needed, especially among co-morbid individuals, in view of growing evidence of the adverse personal, medical and societal impacts of cannabis use disorders in the USA.

Background. Children of alcoholics are significantly more likely to experience high-risk environmental exposures, including prenatal substance exposure, and are more likely to exhibit externalizing problems [e.g. attention deficit hyperactivity disorder (ADHD)]. While there is evidence that genetic influences and prenatal nicotine and/or alcohol exposure play separate roles in determining risk of ADHD, little has been done on determining the joint roles that genetic risk associated with maternal alcohol use disorder (AUD) and prenatal risk factors play in determining risk of ADHD.

Method. Using a children-of-twins design, diagnostic telephone interview data from high-risk families (female monozygotic and dizygotic twins concordant or discordant for AUD as parents) and control families targeted from a large Australian twin cohort were analyzed using logistic regression models.

Results. Offspring of twins with a history of AUD, as well as offspring of non-AUD monozygotic twins whose co-twin had AUD, were significantly more likely to exhibit ADHD than offspring of controls. This pattern is consistent with a genetic explanation for the association between maternal AUD and increased offspring risk of ADHD. Adjustment for prenatal smoking, which remained significantly predictive, did not remove the significant genetic association between maternal AUD and offspring ADHD.

Conclusions. While maternal smoking during pregnancy probably contributes to the association between maternal AUD and offspring ADHD risk, the evidence for a significant genetic correlation suggests: (i) pleiotropic genetic effects, with some genes that influence risk of AUD also influencing vulnerability to ADHD; or (ii) ADHD is a direct risk-factor for AUD.

Background. This study examined the relationships between self-reported childhood sexual abuse (CSA) and drug-related outcomes in an Australian twin panel.

Method. A semi-structured psychiatric interview was conducted in 1996–2000 by telephone with young adult Australian twins (mean age 29·9 years). Data reported here are from 6050 twins who responded to both CSA and drug-related items.

Results. A history of CSA was associated with significant risk for subsequently occurring regular smoking and use of each illicit drug class. Further CSA-associated risk was found among regular users, for nicotine and alcohol dependence, and among illicit drug users, for abuse/dependence of most drug classes. In same-sex discordant pairs, significant risk for regular smoking and illicit drug use was found in twins with a history of CSA compared to their non-abused co-twins. Similar analyses for abuse/dependence found significant risk for opioids, any illicit drug, and any non-cannabis illicit drug. CSA was associated with significantly earlier drug use. Despite the association of CSA with risk for early-onset cannabis use and regular smoking, risks for illicit drug outcomes associated with CSA and with either form of early-onset use combine in near-additive fashion.

Conclusions. CSA is associated with risk for subsequently occurring regular smoking and illicit drug use and abuse/dependence. Risks for drug use are mildly attenuated with control for familial contributions; similar risks for abuse/dependence remain significant for opioids and for illicit drugs combined across classes. Although we found evidence of earlier onset drug use with CSA, risks associated with CSA and with early-onset use combine in a largely additive manner.

Background. Psychiatric in-patients are at particularly high risk of suicide but few studies have investigated trends in in-patient suicide over time.

Method. We conducted a prospective study of all patients admitted to National Health Service (NHS) in-patient psychiatric care in England (1997–2003). The study was carried out as part of the National Confidential Inquiry into Suicide. The main outcome measure was death by suicide. Suicide rates were determined using Hospital Episode Statistics (HES) as the denominator.

Results. Between the first 2 years of the study (1997 and 1998) and the last 2 years of the study (2002 and 2003) the annual number of in-patient deaths from suicide fell from 187 to 156 (a 17% reduction). The rate of in-patient suicide fell by between 9% and 28% depending on which denominator was used. This fall was observed for both males and females, and was most marked for those aged 15–44 years. Reductions were also observed for the three most common methods of death (hanging, jumping, poisoning), but the trend for hanging did not reach statistical significance. Although the number of post-discharge suicides fell, the risk of post-discharge suicide (using admissions as a denominator) may have increased by as much as 10% during the study period.

Conclusion. The rate of suicide among psychiatric in-patients appears to have fallen. The fall may reflect falling general population rates, changes in in-patient case mix, service improvements, or a transfer of risk to the post-discharge period. Services need to be aware of the importance of providing high quality aftercare following discharge from hospital.