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. One of the many controversies surrounding chronic fatigue syndrome (CFS) is the possible impact of the diagnostic label: is it disabling or enabling? In this paper, we discuss the pros and cons of labelling CFS.

Method. A narrative synthesis of the literature.

Results. Diagnosed CFS patients have a worse prognosis than fatigue syndrome patients without such a label. The ways in which CFS patients perceive themselves, label their symptoms and appraise stressors may perpetuate or exacerbate their symptoms, a process that involves psychological, psychosocial and cultural factors. Labels can also lead to conflicts with doctors who fear diagnosis might lead to worse outcomes. However, on the other hand, finding a label that fits one's condition can provide meaning, emotional relief and recognition, whilst the denial of the diagnosis of CFS in those who have already reached their own conclusion can be very counter productive. The act of diagnosis therefore seems to be a trade-off between empowerment, illness validation and group support, contrasted with the risk of diagnosis as self-fulfilling prophecy of non-recovery.

Conclusions. The answer to the question of ‘to label or not to label’ may turn out to depend not on the label, but on what that label implies. It is acceptable and often beneficial to make diagnoses such as CFS, provided that this is the beginning, and not the end, of the therapeutic encounter.

Background. Despite an extensive literature, there have been widely divergent findings regarding the direction of the association between area socio-economic characteristics and area suicide rates, with high-quality studies finding either a direct relation (higher rates of suicide in higher socio-economic areas), an inverse relation (lower rates of suicide in higher socio-economic areas) or no association.

Method. We performed a systematic review of the literature dating from 1897 to 2004 and identified 86 publications with 221 separate analyses that met our inclusion criteria. We examined the percent of direct, inverse and null findings stratified by key study characteristics including size of aggregated area, socio-economic measure used, region of study, control variables and study design.

Results. Analyses at the community level are significantly more likely to demonstrate lower rates of suicide among higher socio-economic areas than studies using larger areas of aggregation. Measures of area poverty and deprivation are most likely to be inversely associated with suicide rates and median income is least likely to be inversely associated with suicide rates. Analyses using measures of unemployment and education and occupation were equally likely to demonstrate inverse associations. Study results did not vary significantly by gender or by study design.

Conclusions. The heterogeneity of associations is mostly accounted for by study design features that have largely been neglected in this literature. Enhanced attention to size of region and measurement strategies provide a clearer picture of how suicide rates vary by region. Resources for suicide prevention should be targeted to high poverty/deprivation and high unemployment areas.

Background. The idea that superior cognitive function acts as a protective factor against dementia and the consequences of head injury is well established. Here we suggest the hypothesis that cognitive reserve is also important in neuropsychiatric disorders including schizophrenia, bipolar disorder and depression.

Method. We review the history of passive and active models of reserve, and apply the concept to neuropsychiatric disorders. Schizophrenia is used as an exemplar because the effects of premorbid IQ and cognitive function in this disorder have been extensively studied.

Results. Cognitive reserve may impact on neuropsychiatric disorders in three ways: by affecting the risk for developing the disorder, in the expression of symptoms within disorders, and in patients' functional outcome. Cognitive failure below a certain threshold may alone, or in combination with common psychiatric symptoms, produce neuropsychiatric syndromes.

Conclusions. Consideration of cognitive reserve may considerably improve our understanding of individual differences in the causes and consequences of neuropsychiatric disorders. For these reasons, the concept of cognitive reserve should be incorporated in future studies of neuropsychiatric disorder. It may be possible to enhance cognitive reserve through pharmacological or non-pharmacological means, such as education, neurocognitive activation or other treatment programmes.

Background. Eye movement desensitization and reprocessing (EMDR) and trauma-focused cognitive-behavioral therapy (CBT) are both widely used in the treatment of post-traumatic stress disorder (PTSD). There has, however, been debate regarding the advantages of one approach over the other. This study sought to determine whether there was any evidence that one treatment was superior to the other.

Method. We performed a systematic review of the literature dating from 1989 to 2005 and identified eight publications describing treatment outcomes of EMDR and CBT in active–active comparisons. Seven of these studies were investigated meta-analytically.

Results. The superiority of one treatment over the other could not be demonstrated. Trauma-focused CBT and EMDR tend to be equally efficacious. Differences between the two forms of treatment are probably not of clinical significance. While the data indicate that moderator variables influence treatment efficacy, we argue that because of the small number of original studies, little benefit is to be gained from a closer examination of these variables. Further research is needed within the framework of randomized controlled trials.

Conclusions. Our results suggest that in the treatment of PTSD, both therapy methods tend to be equally efficacious. We suggest that future research should not restrict its focus to the efficacy, effectiveness and efficiency of these therapy methods but should also attempt to establish which trauma patients are more likely to benefit from one method or the other. What remains unclear is the contribution of the eye movement component in EMDR to treatment outcome.

Background. Deficits in the care of depression lead to poor medication adherence, which increases the risk of an unfavourable outcome for this care. This review evaluates effects on symptoms and medication adherence of case management in primary health care.

Method. A systematic literature search was performed. The quality of the studies was rated according to the Cochrane Effective Practice and Organization of Care Group (EPOC) criteria. To conduct a subgroup analysis interventions were classified as either ‘standard’ or ‘complex’ case management.

Results. Thirteen studies met the inclusion criteria. In a meta-analysis we calculated a standard mean difference/effect size on symptom severity after 6–12 months of −0·40 (95% CI −0·60 to –0·20). Patients in the intervention groups were more likely to achieve remission after 6–12 months [relative risk (RR) 1·39, 95% CI 1·30–1·48]. The relative risk for clinical response was 1·82 (95% CI 1·68–2·05). Patients in intervention groups had better medication adherence than the control group (RR 1·5, 95% CI 1·28–1·86). We found heterogeneous results when assessing effects of different types of intervention.

Conclusions. We conclude that case management improves management of major depression in primary health-care settings.

Background. Behavioural brain reserve is a property of the central nervous system related to sustained and complex mental activity which can lead to differential expression of brain injury. Behavioural brain reserve has been assessed using autobiographical data such as education levels, occupational complexity and mentally stimulating lifestyle pursuits. So far there have been several epidemiological reports but no systematic review to put conflicting results into context. Our aim was to quantitatively review evidence for the effect of brain reserve on incident dementia.

Method. Cohort studies of the effects of education, occupation, premorbid IQ and mental activities on dementia risk were of interest. Abstracts were identified in MEDLINE (1966–September 2004), CURRENT CONTENTS (to September, 2004), PsychINFO (1984–September 2004), Cochrane Library Databases and reference lists from relevant articles. Twenty-two studies met inclusion criteria. Key information was extracted by both reviewers onto a standard template with a high level of agreement. Studies were combined through a quantitative random-effects meta-analysis.

Results. Higher brain reserve was associated with a lowered risk for incident dementia (summary odds ratio, 0·54; 95% confidence interval, 0·49–0·59). This effect was found over a median of 7·1 years follow-up and resulted from integrating data across more than 29000 individuals. Notably, increased complex mental activity in late life was associated with lower dementia rates independent of other predictors; a dose–response relationship was also evident between extent of complex mental activities in late life and dementia risk.

Conclusions. This study demonstrates robust evidence that complex patterns of mental activity in the early, mid- and late-life stages is associated with a significant reduction in dementia incidence. Randomized control trials based on brain-reserve principles are now required.

Background. Demonstrating differences between euthymic bipolar subjects and healthy controls in response to positive (happy) mood induction may help elucidate how mania evolves. This pilot study evaluates the Go task in a reward paradigm as a method for inducing a happy mood state and compares the response of euthymic bipolar subjects and healthy controls.

Method. The Sense of Hyperpositive Self Scale, the Tellegen positive and negative adjectives, the Global-Local task and a visual analogue scale for measuring positive affect were administered to 15 euthymic bipolar subjects and 19 age-and-sex-matched healthy control subjects before and after they had performed the Go task in a reward paradigm.

Results. Significant differences were found between subjects and controls on several measures at each time-point but there were no differences across the groups across time except for the visual analogue scales, where subjects had a more sustained duration in self-reported happiness compared with controls.

Conclusions. This pilot study has shown that a positive affect can be induced in bipolar subjects and controls which can be demonstrated by changes in scores on several tasks. However, only the visual analogue scales showed a significant difference between cases and controls over time. Such tests may prove valuable in furthering understanding about the evolution of manic mood states.

Objective. To examine the relative and combined impact of depressive and chronic physical conditions on functional status and health-care use in the general population.

Method. Canadian, representative, population-based cross-sectional survey (n=130880). Major depressive disorder (MDD) in the past 12 months was assessed by structured interview, and physical disorders, activity reduction, role impairment and work absence by self-report. The relative impact of MDD and six common chronic physical illnesses (asthma, arthritis, back problems, chronic obstructive pulmonary disease, heart disease and diabetes) was estimated using multivariate regression, adjusting for sociodemographic characteristics and overall chronic physical illness burden.

Results. After adjusting for sociodemographic characteristics, alcohol dependence and chronic physical illness burden, the presence of co-morbid MDD was associated with significantly greater (approximately double the) likelihood of health-care utilization and increased functional disability and work absence compared to the presence of a chronic physical illness without co-morbid MDD. This impact of MDD was seen across each of the six chronic physical illnesses examined in this study, with the strongest associations seen for work absence.

Conclusions. These observations confirm prior findings of a strong association at the population level between major depression and health-care use and role impairment among persons with chronic physical disorders. They also point to the significant impact of co-morbid major depression on health-care seeking, disability and work absence in persons with chronic physical illness, underscoring the need for greater efforts to design and test the impact of detection and treatment programs for such individuals.

Background. Traditional instruments that measure self-esteem may not relate directly to the schema construct as outlined in recent cognitive models. The Brief Core Schema Scales (BCSS) aim to provide a theoretically coherent self-report assessment of schemata concerning self and others in psychosis. The scales assess four dimensions of self and other evaluation: negative-self, positive-self, negative-other, positive-other.

Method. We analysed the psychometric properties of the BCSS using a sample of 754 students recruited by email and 252 people with psychosis recruited as part of a trial of cognitive therapy. We report the internal consistency, stability and the factor structure of the scale, and the association of the BCSS with measures of self-esteem and with symptoms of paranoia and grandiosity.

Results. The BCSS have good psychometric properties and have more independence from mood than the Rosenberg Self-Esteem Schedule. People with chronic psychosis reported extreme negative evaluations of both self and others on these scales, but their levels of self-esteem and positive evaluations of self and others were similar to the student sample.

Conclusions. Extreme negative evaluations of self and others appear to be characteristic of the appraisals of people with chronic psychosis, and are associated with symptoms of grandiosity and paranoia in the non-clinical population. The BCSS may provide a more useful measure of schemata about self and others than traditional measures of self-esteem.

Background. A previous companion paper to this report (Valenzuela & Sachdev, Psychological Medicine 2006, 36, 441–454) suggests a link between behavioural brain reserve and incident dementia; however, the issues of covariate control and ascertainment bias were not directly addressed. Our aim was to quantitatively review an independent set of longitudinal studies of cognitive change in order to clarify these factors.

Method. Cohort studies of the effects of education, occupation, and mental activities on cognitive decline were of interest. Abstracts were identified in MEDLINE (1966–September 2004), CURRENT CONTENTS (to September 2004), PsychINFO (1984–September 2004), Cochrane Library Databases and reference lists from relevant articles. Eighteen studies met inclusion criteria. Key information was extracted by both reviewers onto a standard template with a high level of agreement. Cognitive decline studies were integrated using a non-parametric method after converting outcome data onto a common effect size metric.

Results. Higher behavioural brain reserve was related to decreased longitudinal cognitive decline after control for covariates in source studies (ϕ=1·70, p<0·001). This effect was robust to correction for both multiple predictors and multiple outcome measures and was the result of integrating data derived from more than 47000 individuals.

Conclusions. This study affirms that the link between behavioural brain reserve and incident dementia is most likely due to fundamentally different cognitive trajectories rather than confound factors.

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.

Recent pharmaceutical company and regulatory body circulars warning against the use of selective serotonin reuptake inhibitors (SSRIs) in late pregnancy have left clinicians in somewhat of a quandary as to how to manage their more severely depressed patients in pregnancy. Conversely, up to 75% of depressed women ceasing their antidepressants periconceptually will relapse. Studies reporting on adverse neonatal outcomes following exposure to SSRIs in the latter half of pregnancy suggest that the fetus is exposed to significant concentrations of these medications during this time. Adverse neonatal effects affecting the respiratory, gastrointestinal and neurological systems are, however, predominantly mild and self-limiting. One small retrospective case study suggests that SSRI exposure in the latter half of pregnancy may be associated with an increased risk of persistent pulmonary hypertension of the neonate (PPHN), however, the absolute risk of developing PPHN remains very small and these findings will require replication with a prospective study. While the studies to date suggest the need to closely monitor SSRI-exposed neonates in the immediate postnatal period, preferably with a neonatal withdrawal scale and access to neonatology services, there is currently no clear argument for women to be weaned off their SSRI in late pregnancy. The decision to use SSRIs at this time will have to be made on a case-by-case basis in close consultation with the mother and her partner.

Background. To investigate the available data regarding possible associations between phases of the menstrual cycle and suicidal behaviour.

Method. A systematic search of major relevant databases was performed using appropriate search terms.

Results. Forty-four relevant studies were identified in total, 13 pertaining to suicide, two pertaining to both attempted and completed suicide, 23 to suicide attempts, three to suicide attempts in those suffering from the premenstrual syndrome (PMS), three to suicidal ideation and two to repetitive self-harming behaviours. A variety of methodologies were used in these studies and there were notable differences in the conclusions reached. Studies with better methodology suggest that a positive relationship exists between aspects of the menstrual cycle and non-fatal suicidal behaviour. Such behaviour appears to be more common in those phases of the menstrual cycle when oestrogen levels are lowest (the late luteal and follicular phases), and in those suffering from PMS.

Conclusions. There appears to be an association between the menstrual cycle and non-fatal suicidal behaviours. Interaction between oestrogen and the serotonergic system may provide a possible mechanism.

Background. This study examined the persistence of attention deficit hyperactivity disorder (ADHD) into adulthood.

Method. We analyzed data from published follow-up studies of ADHD. To be included in the analysis, these additional studies had to meet the following criteria: the study included a control group and it was clear from the methods if the diagnosis of ADHD included subjects who did not meet full criteria but showed residual and impairing signs of the disorder. We used a meta-analysis regression model to separately assess the syndromatic and symptomatic persistence of ADHD.

Results. When we define only those meeting full criteria for ADHD as having ‘persistent ADHD’, the rate of persistence is low, ~15% at age 25 years. But when we include cases consistent with DSM-IV's definition of ADHD in partial remission, the rate of persistence is much higher, ~65%.

Conclusions. Our results show that estimates of ADHD's persistence rely heavily on how one defines persistence. Yet, regardless of definition, our analyses show that evidence for ADHD lessens with age. More work is needed to determine if this reflects true remission of ADHD symptoms or is due to the developmental insensitivity of diagnostic criteria for the disorder.

Background. Risk-taking behavior is a major cause of morbidity and mortality in adolescence. In the context of decision theory and motivated (goal-directed) behavior, risk-taking reflects a pattern of decision-making that favors the selection of courses of action with uncertain and possibly harmful consequences. We present a triadic, neuroscience systems-based model of adolescent decision-making.

Method. We review the functional role and neurodevelopmental findings of three key structures in the control of motivated behavior, i.e. amygdala, nucleus accumbens, and medial/ventral prefrontal cortex. We adopt a cognitive neuroscience approach to motivated behavior that uses a temporal fragmentation of a generic motivated action. Predictions about the relative contributions of the triadic nodes to the three stages of a motivated action during adolescence are proposed.

Results. The propensity during adolescence for reward/novelty seeking in the face of uncertainty or potential harm might be explained by a strong reward system (nucleus accumbens), a weak harm-avoidant system (amygdala), and/or an inefficient supervisory system (medial/ventral prefrontal cortex). Perturbations in these systems may contribute to the expression of psychopathology, illustrated here with depression and anxiety.

Conclusions. A triadic model, integrated in a temporally organized map of motivated behavior, can provide a helpful framework that suggests specific hypotheses of neural bases of typical and atypical adolescent behavior.

Background. It is our contention that both categorical and dimensional approaches to diagnosis are important for clinical work and research alike, and that each approach has its drawbacks and advantages. As the processes toward developing DSM-V and ICD-11 progress, we suggest that another exclusively categorical revision of psychiatric taxonomies will no longer be sufficient and that adding a dimensional component is a necessary step if these taxonomies are to continue serving the future clinical and research needs of psychiatry as they have so effectively done in the past.

Method. We begin the paper with a review of terminology related to categories and dimensions and briefly review literature on advantages and disadvantages of both approaches.

Results. A review of relevant literature supports both the need for and feasibility of augmenting traditional categorical diagnoses with dimensional information.

Conclusion. We conclude with a proposal for preserving traditional categorical diagnostic definitions, but adding a dimensional component that would be reflective of and directly referable back to the categorical definitions. We also offer a specific proposal for adding a dimensional component to official taxonomies such as the DSM and the ICD in a way that fully preserves the traditional categorical approach.

Background. Several studies have found an association between indicators of fetal growth and/or obstetric complications and schizophrenia but only a few studies have investigated the possible association between these factors and bipolar disorder. Furthermore, the results of these studies have been contradictory. The aim of this study was to investigate whether the risk of bipolar disorder is associated with exposure to indicators of fetal growth.

Method. A national population nested case-control study based on Danish longitudinal register databases was carried out. Conditional logistic regression was used, controlling for potential confounding factors such as parental age at birth, socio-economic indicators and psychiatric history. We identified 196 cases, and each case was time-, age- and sex-matched with 25 normal population-based controls. All cases were between the ages of 12 and 26 years at the time of diagnosis, were born between 1973 and 1983 and were admitted and diagnosed between 1987 and 1999.

Results. During the study period 1973–1983, none of the individual variables available for analyses (birthweight, birth length, gestational age and number of previous pregnancies in the mother) was associated with receiving a diagnosis of bipolar disorder.

Conclusions. None of the indicators of fetal growth under study could be identified as risk factors for bipolar disorder, suggesting that the etiologies of schizophrenia and bipolar disorder, at least in part, are different.

Background and purpose. Depressive symptoms are frequently associated with heart failure (HF), but the brain mechanisms underlying such association are unclear. We hypothesized that the presence of major depressive disorder (MDD) emerging after the onset of HF would be associated with regional cerebral blood flow (rCBF) abnormalities in medial temporal regions previously implicated in primary MDD, namely the hippocampus and parahippocampal gyrus.

Method. Using 99mTc-SPECT, we measured rCBF in 17 elderly MDD-HF patients, 17 non-depressed HF patients, and 18 healthy controls, matched for demographic variables. Group differences were investigated with Statistical Parametric Mapping.

Results. Significant rCBF reductions in MDD-HF patients relative to both non-depressed HF patients and healthy controls were detected in the left anterior parahippocampal gyrus and hippocampus (ANOVA, p=0·008 corrected for multiple comparisons) and the right posterior hippocampus and parahippocampal gyrus (p=0·005 corrected). In the overall HF group, there was a negative correlation between the severity of depressive symptoms and rCBF in the right posterior hippocampal/parahippocampal region (p=0·045 corrected).

Conclusions. These findings are consistent with the notion that the medial temporal region is vulnerable to brain perfusion deficits associated with HF, and provide evidence that such functional deficits may be specifically implicated in the pathophysiology of MDD associated with HF.

Background. Depression is a highly prevalent, often recurring or persistent disorder. The majority of patients are initially seen and treated in primary care. Effective treatments are available, but possibilities for providing adequate follow-up care are often limited in this setting. This study assesses the effectiveness of primary-care-based enhanced treatment modalities on short-term patient outcomes.

Method. In a randomized controlled trial we evaluated a psycho-educational self-management intervention. We included 267 adult patients meeting criteria for a DSM-IV diagnosis of major depressive disorder, assessed by a structured psychiatric interview. Patients were randomly assigned to: the Depression Recurrence Prevention (DRP) program (n=112); a combination of the DRP program with psychiatric consultation (PC+DRP, n=39); a combination with brief cognitive behavior therapy (CBT+DRP, n=44); and care as usual (CAU, n=72). Follow-up assessments were made at 3 months (response 90%) and 6 months (85%).

Results. Patient acceptance of enhanced care was good. The mean duration of the index episode was 11 weeks (S.D.=9·78) and similar in CAU and enhanced care. Recovery rate after 6 months was 67% overall; 17% of all participants remained depressed for the entire 6-month period.

Conclusion. Enhanced care did not result in better short-term outcomes. We found no evidence that the DRP program was more effective than CAU and no indications for added beneficial effects of either the psychiatric evaluation or the CBT treatment to the basic format of the DRP program. Observed depression treatment rates in CAU were high.