Research on the long-term course of major depressive disorder (MDD) is hindered by the absence of established course criteria and by idiosyncratic definitions of chronicity. The aims of this study were to derive an empirical index of MDD course, to examine its predictive validity, and to identify the adulthood outcomes associated with a chronic course.

Indicators for a MDD course factor were rationally selected and subjected to principal components (PCA) and confirmatory factor analyses (CFA) among 426 subjects with a lifetime history of MDD by age 30. Scores on the index prior to age 19 were examined as predictors of course from age 19 to 30. Associations between the index and outcomes of interest at age 30 were examined.

Three indicators loaded highly on a chronic course index and displayed adequate internal consistency: early onset age, number of episodes, and duration of ill time. Predictive validity of the index was supported. A more chronic course was associated with greater symptom severity, greater likelihood of treatment utilization, and greater psychosocial impairment in multiple domains. Treatment utilization interacted with chronicity to predict relatively few outcomes and did not reduce the negative impact of a chronic course.

The course of MDD through early adulthood is best represented by a composite of early onset age, number of episodes, and duration of ill time. A chronic course through early adulthood is associated with numerous indicators of psychosocial impairment. Mental health treatment utilization in a naturalistic setting does not appear to reduce the negative impact of chronic MDD.

Little is known about the magnitude of improvement associated with psychotherapy control conditions for adult anxiety disorders. This information is important for the design of psychosocial treatment efficacy studies.

We performed a computerized search of treatment outcome studies of anxiety disorders conducted between the first available year and 1 March 2007. In addition, we examined the reference lists from identified articles and asked international experts to identify eligible studies. We included studies that randomly assigned adult patients suffering from anxiety disorders to either cognitive–behavioral treatment or psychotherapy control condition. For each study, the two authors independently selected psychometrically sound measures of anxiety disorder severity. In addition, we collected data on attrition and treatment response.

Of the 1165 studies that were initially identified, 19 studies (454 patients) met inclusion criteria and were included in the analyses. The random effects analysis yielded a pre- to post-treatment Hedges' g effect size of 0.45 (95% confidence interval 0.35–0.46, z=8.50, p<0.001). The mean weighted response and attrition rates were 25.0% and 14.2%, respectively. There was no evidence for publication bias, nor was there a significant relationship between the effect size and diagnostic group, study year or number of treatment sessions.

Psychotherapy control conditions are associated with significant improvements when administered to adults suffering from anxiety disorders. In addition, they are associated with a relatively low attrition rate. These findings can inform the design of future psychotherapy outcome studies.

Non-clinical psychosis-like symptoms (PLIKS) occur in about 15% of the population. It is not clear whether adverse events during early development alter the risk of developing PLIKS. We aimed to examine whether maternal infection, diabetes or pre-eclampsia during pregnancy, gestational age, perinatal cardiopulmonary resuscitation or 5-min Apgar score were associated with development of psychotic symptoms during early adolescence.

A longitudinal study of 6356 12-year-old adolescents who completed a semi-structured interview for psychotic symptoms in the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort. Prenatal and perinatal data were obtained from obstetric records and maternal questionnaires completed during pregnancy.

The presence of definite psychotic symptoms was associated with maternal infection during pregnancy [adjusted odds ratio (OR) 1.44, 95% confidence interval (CI) 1.11–1.86, p=0.006], maternal diabetes (adjusted OR 3.43, 95% CI 1.14–10.36, p=0.029), need for resuscitation (adjusted OR 1.50, 95% CI 0.97–2.31, p=0.065) and 5-min Apgar score (adjusted OR per unit decrease 1.30, 95% CI 1.12–1.50, p<0.001). None of these associations were mediated by childhood IQ score. Most associations persisted, but were less strong, when including suspected symptoms as part of the outcome. There was no association between PLIKS and gestational age or pre-eclampsia.

Adverse events during early development may lead to an increased risk of developing PLIKS. Although the status of PLIKS in relation to clinical disorders such as schizophrenia is not clear, the similarity between these results and findings reported for schizophrenia indicates that future studies of PLIKS may help us to understand how psychotic experiences and clinical disorders develop throughout the life-course.

Verbal memory is frequently and severely affected in schizophrenia and has been implicated as a mediator of poor clinical outcome. Whereas encoding deficits are well demonstrated, it is unclear whether retention is impaired. This distinction is important because accelerated forgetting implies impaired consolidation attributable to medial temporal lobe (MTL) dysfunction whereas impaired encoding and retrieval implicates involvement of prefrontal cortex.

We assessed a group of healthy volunteers (n=97) and pre-morbid IQ- and sex-matched first-episode psychosis patients (n=97), the majority of whom developed schizophrenia. We compared performance of verbal learning and recall with measures of visuospatial working memory, planning and attentional set-shifting, and also current IQ.

All measures of performance, including verbal memory retention, a memory savings score that accounted for learning impairments, were significantly impaired in the schizophrenia group. The difference between groups for delayed recall remained even after the influence of learning and recall was accounted for. Factor analyses showed that, in patients, all variables except verbal memory retention loaded on a single factor, whereas in controls verbal memory and fronto-executive measures were separable.

The results suggest that IQ, executive function and verbal learning deficits in schizophrenia may reflect a common abnormality of information processing in prefrontal cortex rather than specific impairments in different cognitive domains. Verbal memory retention impairments, however, may have a different aetiology.

Cognitive performance is often impaired in depression, and these impairments can persist even after remission from psychopathological symptoms. However, it is still unclear whether cognitive dysfunction is associated with psychopathological symptoms or represents a genuine disorder. This study examined cognitive performance in acute depression, after remission, and 6 months after remission in order to determine the nature and specificity of cognitive dysfunction as well as its relevance for the further course of depression.

Assessments of cognitive function and psychopathology were carried out on admission and prior to discharge in 53 in-patients with unipolar depression. Twenty patients were retested 6 months after discharge. To correct for practice effects, 13 healthy subjects were included and assessed twice with the same cognitive tests.

In acute depression, we found impairments of information processing/attention, memory, and executive functions. Cognitive impairments remained in a high proportion of patients, even after remission of psychopathological symptoms. After correcting for practice effects, a significant improvement was observed only for some tests of executive functioning. Severity of depression was only weakly correlated with one single cognitive measure, indicating that psychopathological and neuropsychological symptoms are dissociable. Furthermore, we found no evidence for specific cognitive dysfunction.

Our results support the hypothesis that cognitive impairments in depression are neither selective nor specific; they have trait-like features and are, therefore, not merely an epiphenomenon of depression. Whether or not cognitive dysfunction is a prognostic marker for the course of depression remains still an open issue.

Stalking is often viewed as a precursor to violence, but determining which stalkers might attack is a difficult task. This study overcomes shortfalls in previous investigations by adopting a pseudo-prospective design and examining potential risk factors for different types of stalker.

Demographic, behavioural and diagnostic information was collected from stalkers referred to a community forensic mental health service (n=211). Potential risk factors for stalking violence were identified using odds ratios and χ2 tests, and entered into logistic regression models. Model utility was assessed using receiver operating characteristic curves.

Amongst Rejected ex-intimate stalkers, violence was best predicted by previous violence, making threats and being employed (area under the curve=0.75), while for stalkers with other motives and relationships to the victim, being aged less than 30 years, substance use at the time of stalking and prior violence best predicted stalking violence (area under the curve=0.80).

Stalkers at increased risk of violence can be accurately identified by examining motivational and relationship type in conjunction with specific relevant risk factors. Previous violence is a particularly important risk factor, as are threats amongst ex-intimate stalkers. Approach behaviours and psychosis were shown to be less useful in predicting violence.

This study reports on a preliminary evaluation of a cognitive behavioural intervention to improve social recovery among young people in the early stages of psychosis showing persistent signs of poor social functioning and unemployment. The study was a single-blind randomized controlled trial (RCT) with two arms, 35 participants receiving cognitive behaviour therapy (CBT) plus treatment as usual (TAU), and 42 participants receiving TAU alone. Participants were assessed at baseline and post-treatment.

Seventy-seven participants were recruited from secondary mental health teams after presenting with a history of unemployment and poor social outcome. The cognitive behavioural intervention was delivered over a 9-month period with a mean of 12 sessions. The primary outcomes were weekly hours spent in constructive economic and structured activity. A range of secondary and tertiary outcomes were also assessed.

Intention-to-treat analysis on the combined affective and non-affective psychosis sample showed no significant impact of treatment on primary or secondary outcomes. However, analysis of interactions by diagnostic subgroup was significant for secondary symptomatic outcomes on the Positive and Negative Syndrome Scale (PANSS) [F(1, 69)=3.99, p=0.05]. Subsequent exploratory analyses within diagnostic subgroups revealed clinically important and significant improvements in weekly hours in constructive and structured activity and PANSS scores among people with non-affective psychosis.

The primary study comparison provided no clear evidence for the benefit of CBT in a combined sample of patients. However, planned analyses with diagnostic subgroups showed important benefits for CBT among people with non-affective psychosis who have social recovery problems. These promising results need to be independently replicated in a larger, multi-centre RCT.

There is increasing evidence that the frequently reported working memory impairments in schizophrenia might be partly due to an alteration in the functional connectivity between task-relevant areas. However, little is known about the functional connectivity patterns in schizophrenia patients during learning processes. In a previous study, Koch et al. [Neuroscience (2007) 146, 1474–1483] have demonstrated stronger exponential activation decreases in schizophrenia patients during overlearning of short-term memory material. The question arises whether these differential temporal patterns of activation in schizophrenia patients and controls are going along with changes in task-related functional connectivity.

Therefore, in the current study, 13 patients with schizophrenia and 13 controls were studied while performing a short-term memory task associated with increasing overlearning of verbal stimulus material. Functional connectivity was investigated by analyses of psychophysiological interactions (PPI).

Results revealed significant task-related modulation of functional connectivity between the left dorsolateral prefrontal cortex (DLPFC) and a network including the right DLPFC, left ventrolateral prefrontal cortex, premotor cortex, right inferior parietal cortex, left and right cerebellum as well as the left occipital lobe in patients during the course of overlearning and practice. No significant PPI results were detectable in controls.

Activation changes with practice were associated with high functional connectivity between task-relevant areas in schizophrenia patients. This could be interpreted as a compensatory resource allocation and network integration in the context of cortical inefficiency and may be a specific neurophysiological signature underlying the pathophysiology of schizophrenia.

Epidemiological evidence suggests a link between cannabis use and psychosis. A variety of factors have been proposed to mediate an individual's vulnerability to the harmful effects of the drug, one of which is their psychosis proneness. We hypothesized that highly psychosis-prone individuals would report more marked psychotic experiences under the acute influence of cannabis.

A group of cannabis users (n=140) completed the Psychotomimetic States Inventory (PSI) once while acutely intoxicated and again when free of cannabis. A control group (n=144) completed the PSI on two parallel test days. All participants also completed a drug history and the Schizotypal Personality Questionnaire (SPQ). Highly psychosis-prone individuals from both groups were then compared with individuals scoring low on psychosis proneness by taking those in each group scoring above and below the upper and lower quartiles using norms for the SPQ.

Smoking cannabis in a naturalistic setting reliably induced marked increases in psychotomimetic symptoms. Consistent with predictions, highly psychosis-prone individuals experienced enhanced psychotomimetic states following acute cannabis use.

These findings suggest that an individual's response to acute cannabis and their psychosis-proneness scores are related and both may be markers of vulnerability to the harmful effects of this drug.

Risk for mood and anxiety disorders associated with US-nativity may vary across immigrant groups.

Using data from the National Epidemiological Study of Alcohol and Related Conditions (NESARC), we examined the association of lifetime risk for mood and anxiety disorders with US-nativity and age at immigration across seven subgroups of the US population defined by country or region of ancestral origin: Mexico, Puerto-Rico, Cuba, Central and South America, Western Europe, Eastern Europe, and Africa and the Caribbean. Discrete time survival models were used to compare lifetime risk between the US-born, immigrants who arrived in the USA prior to the age of 13 years and immigrants who arrived in the USA at the age of 13 years or older.

The association of risk for mood and anxiety disorders with US-nativity varies significantly across ancestral origin groups (p<0.001). Among people from Mexico, Eastern Europe, and Africa or the Caribbean, risk for disorders is lower relative to the US-born among immigrants who arrived at the age of 13 years or higher (odds ratios in the range 0.34–0.49) but not among immigrants who arrived prior to the age of 13 years. There is no association between US-nativity and risk for disorder among people from Western Europe and Puerto Rico.

Low risk among immigrants relative to the US-born is limited to groups among whom risk for mood and anxiety disorder is low in immigrants who spent their pre-adolescent years outside of the USA.

For more than a decade high-frequency repetitive transcranial magnetic stimulation (rTMS) has been applied to the left dorsolateral prefrontal cortex (DLPFC) in search of an alternative treatment for depression. The aim of this study was to provide an update on its clinical efficacy by performing a meta-analysis involving double-blind sham-controlled studies.

A literature search was conducted in the databases PubMed and Web of Science in the period between January 1980 and November 2007 with the search terms ‘depression’ and ‘transcranial magnetic stimulation’. Thirty double-blind sham-controlled parallel studies with 1164 patients comparing the percentage change in depression scores from baseline to endpoint of active versus sham treatment were included. A random effects meta-analysis was performed to investigate the clinical efficacy of fast-frequency rTMS over the left DLPFC in depression.

The test for heterogeneity was not significant (QT=30.46, p=0.39). A significant overall weighted mean effect size, d=0.39 [95% confidence interval (CI) 0.25–0.54], for active treatment was observed (z=6.52, p<0.0001). Medication resistance and intensity of rTMS did not play a role in the effect size.

These findings show that high-frequency rTMS over the left DLPFC is superior to sham in the treatment of depression. The effect size is robust and comparable to at least a subset of commercially available antidepressant drug agents. Current limitations and future prospects are discussed.

Suicide is a leading cause of death and has been strongly associated with affective disorders. The influence of affective disorder polarity on subsequent suicide attempts or completions and any differential effect of suicide risk factors by polarity were assessed in a prospective cohort.

Participants with major affective disorders in the National Institute of Mental Health (NIMH) Collaborative Depression Study (CDS) were followed prospectively for up to 25 years. A total of 909 participants meeting prospective diagnostic criteria for major depressive and bipolar disorders were followed through 4204 mood cycles. Suicidal behavior was defined as suicide attempts or completions. Mixed-effects, grouped-time survival analysis assessed risk of suicidal behavior and differential effects of risk factors for suicidal behavior by polarity. In addition to polarity, the main effects of age, gender, hopelessness, married status, prior suicide attempts and active substance abuse were modeled, with mood cycle as the unit of analysis.

After controlling for age of onset, there were no differences in prior suicide attempts by polarity although bipolar participants had more prior severe attempts. During follow-up, 40 cycles ended in suicide and 384 cycles contained at least one suicide attempt. Age, hopelessness and active substance abuse but not polarity predicted suicidal behavior. The effects of risk factors did not differ by polarity.

Bipolarity does not independently influence risk of suicidal behavior or alter the influence of well-established suicide risk factors within affective disorders. Suicide risk assessment strategies may continue to appraise these common risk factors without regard to mood polarity.

The organization of mental disorders into 16 DSM-IV and 10 ICD-10 chapters is complex and based on clinical presentation. We explored the feasibility of a more parsimonious meta-structure based on both risk factors and clinical factors.

Most DSM-IV disorders were allocated to one of five clusters as a starting premise. Teams of experts then reviewed the literature to determine within-cluster similarities on 11 predetermined validating criteria. Disorders were included and excluded as determined by the available data. These data are intended to inform the grouping of disorders in the DSM-V and ICD-11 processes.

The final clusters were neurocognitive (identified principally by neural substrate abnormalities), neurodevelopmental (identified principally by early and continuing cognitive deficits), psychosis (identified principally by clinical features and biomarkers for information processing deficits), emotional (identified principally by the temperamental antecedent of negative emotionality), and externalizing (identified principally by the temperamental antecedent of disinhibition).

Large groups of disorders were found to share risk factors and also clinical picture. There could be advantages for clinical practice, public administration and research from the adoption of such an organizing principle.

Older meta-analyses of the effects of psychological treatments of social anxiety disorder have found that these treatments have moderate to large effects. However, these earlier meta-analyses also included non-randomized studies, and there are many featured studies in this area which were published after the recent meta-analysis.

We conducted a systematic literature search and identified 29 randomized studies examining the effects of psychological treatments, with a total of 1628 subjects. The quality of studies varied. For the analyses, we used the computer program comprehensive meta-analysis (version 2.2.021; Biostat, Englewood, NJ, USA).

The mean effect size on social anxiety measures (47 contrast groups) was 0.70, 0.80 on cognitive measures (26 contrast groups) and 0.70 both on depression (19 contrast groups) and general anxiety measures (16 contrast groups). We found some heterogeneity, so we conducted a series of subgroup analyses for different variables of the studies. Studies with waiting-list control groups had significantly larger effect sizes than studies with placebo and treatment-as-usual control groups. Studies aimed at subjects who met Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria for social anxiety disorder had smaller effect sizes than studies in which other inclusion criteria were used.

This study once more makes it clear that psychological treatments of social anxiety disorder are effective in adults, but that they may be less effective in more severe disorders and in studies in which care-as-usual and placebo control groups are used.

Bipolar disorder and schizophrenia have both been associated with deficits in extra-dimensional set shifting (EDS). Deficits in reversal learning (RL) have also been shown in schizophrenia but not in bipolar disorder. This study sought to assess the specificity of these findings in a direct comparison of clinically stable patients with each disorder.

The intra-dimensional/extra-dimensional (IDED) set-shifting task, part of the Cambridge Neuropsychological Test Automated Battery (CANTAB), was administered to 30 patients with schizophrenia, 47 with bipolar disorder and a group of 44 unaffected controls. EDS and RL errors were compared between the groups and related to measures of current and past psychiatric symptoms and medication.

Both groups of patients with schizophrenia or bipolar disorder made more EDS and RL errors than controls. Neither measure separated the two disorders, even when the analysis was restricted to euthymic patients. No relationship was found with prescribed medication.

Patients with bipolar disorder or schizophrenia show common deficits in EDS and RL. These deficits do not seem to be attributable to current symptoms and are consistent with disrupted networks involving the ventral prefrontal cortex.

A lack of longitudinal studies has made it difficult to establish the direction of associations between circulating concentrations of low-grade chronic inflammatory markers, such as C-reactive protein and interleukin-6, and cognitive symptoms of depression. The present study sought to assess whether C-reactive protein and interleukin-6 predict cognitive symptoms of depression or whether these symptoms predict inflammatory markers.

In a prospective occupational cohort study of British white-collar civil servants (the Whitehall II study), serum C-reactive protein, interleukin-6 and cognitive symptoms of depression were measured at baseline in 1991–1993 and at follow-up in 2002–2004, an average follow-up of 11.8 years. Symptoms of depression were measured with four items describing cognitive symptoms of depression from the General Health Questionnaire. The number of participants varied between 3339 and 3070 (mean age 50 years, 30% women) depending on the analysis.

Baseline C-reactive protein (β=0.046, p=0.004) and interleukin-6 (β=0.046, p=0.005) predicted cognitive symptoms of depression at follow-up, while baseline symptoms of depression did not predict inflammatory markers at follow-up. After full adjustment for sociodemographic, behavioural and biological risk factors, health conditions, medication use and baseline cognitive systems of depression, baseline C-reactive protein (β=0.038, p=0.036) and interleukin-6 (β=0.041, p=0.018) remained predictive of cognitive symptoms of depression at follow-up.

These findings suggest that inflammation precedes depression at least with regard to the cognitive symptoms of depression.

There are few theoretical proposals that attempt to account for the variation in affective processing across different affective states of bipolar disorder (BD). The Interacting Cognitive Subsystems (ICS) framework has been recently extended to account for manic states. Within the framework, positive mood state is hypothesized to tap into an implicational level of processing, which is proposed to be more extreme in states of mania.

Thirty individuals with BD and 30 individuals with no history of affective disorder were tested in euthymic mood state and then in induced positive mood state using the Question–Answer task to examine the mode of processing of schemas. The task was designed to test whether individuals would detect discrepancies within the prevailing schemas of the sentences.

Although the present study did not support the hypothesis that the groups differ in their ability to detect discrepancies within schemas, we did find that the BD group was significantly more likely than the control group to answer questions that were consistent with the prevailing schemas, both before and after mood induction.

These results may reflect a general cognitive bias, that individuals with BD have a tendency to operate at a more abstract level of representation. This may leave an individual prone to affective disturbance, although further research is required to replicate this finding.

This study examined the magnitude of neurocognitive change during 1 year of community-based psychosocial intervention, whether neurocognitive change and functional change were linked, and how neurocognitive change combined with service intensity to facilitate functional change.

A total of 130 individuals diagnosed with schizophrenia were recruited upon admission to four community-based psychosocial rehabilitation programs. Subjects were assessed at baseline, 6 and 12 months on role functioning and symptom measures. Neurocognition was measured at baseline and 12 months. Service intensity was the number of days of treatment attendance during the study period. Latent mean difference tests and Latent Growth Curve Models (LCGMs) were used to examine the study hypotheses.

There was statistically and clinically significant functional improvement over 12 months. Neurocognition improved significantly over time. Seventy-six (58%) of the sample showed neurocognitive improvement and 54 (42%) did not. There was a significant rate of functional enhancement in the neurocognitive improver group. There was a non-significant rate of functional change in the neurocognitive non-improver group. Neurocognitive improvers showed functional improvement that was 350% greater than neurocognitive non-improvers. Service intensity did not vary between neurocognitive improvers and non-improvers but there was a strong interaction between neurocognitive improvement, service intensity and rate of functional improvement such that service intensity was strongly related to functional improvement for neurocognitive improvers but not for neurocognitive non-improvers. Medication usage and symptomatology did not confound these findings.

These findings suggest that neurocognitive improvement may be a foundation for functional change and treatment responsiveness during community-based psychosocial rehabilitation for individuals with schizophrenia.

Public figures are at increased risk of attracting unwanted attention in the form of intrusions, stalking and, occasionally, attack. Whereas the potential threat to the British Royal Family from terrorists and organized groups is clearly defined, there is a dearth of knowledge about that from individual harassers and stalkers. This paper reports findings from the first systematic study of this group.

A retrospective study was conducted of a randomly selected stratified sample (n=275) of 8001 files compiled by the Metropolitan Police Service's Royalty Protection Unit over 15 years on inappropriate communications or approaches to members of the British Royal Family. Cases were split into behavioural types. Evidence of major mental illness was recorded from the files. Cases were classified according to a motivational typology. An analysis was undertaken of associations between motivation, type of behaviour and mental illness.

Of the study sample, 83.6% were suffering from serious mental illness. Different forms of behaviour were associated with different patterns of symptomatology. Cases could be separated into eight motivational groups, which also showed significant differences in mental state. Marked differences in the intrusiveness of behaviour were found between motivational groups.

The high prevalence of mental illness indicates the relevance of psychiatric intervention. This would serve the health interests of psychotic individuals and alleviate protection concerns without the necessity of attempting large numbers of individual risk predictions. The finding that some motivations are more likely to drive intrusive behaviours than others may help focus both health and protection interventions.

Suicide tends to concentrate in disadvantaged neighborhoods, and neighborhood disadvantage is associated with many important risk factors for youth suicide. However, no study has directly investigated the link between neighborhood poverty and youth suicidal behaviors, while controlling for pre-existing vulnerabilities. The objective of this study was to determine whether living in a poor neighborhood is associated with suicidal thoughts and attempts in late adolescence over and above background vulnerabilities, and whether this association can be explained by late-adolescence psychosocial risks: depression, social support, negative life events (NLEs), delinquent activities, substance abuse and exposure to suicide. The potential moderating role of neighborhood poverty was also examined.

A subset of 2776 participants was selected from the Canadian National Longitudinal Survey of Children and Youth (NLSCY). Late-adolescence suicidal behaviors and risk factors were self-reported. The 2001 Canadian Census was used to characterize neighborhoods during early and middle adolescence. Late-childhood family and individual controls were assessed through parent-report.

At the bivariate level, the odds of reporting suicidal thoughts were about twice as high in poor than non-poor neighborhoods, and the odds of attempting suicide were about four times higher. After controlling for background vulnerabilities, neighborhood poverty remained significantly associated with both suicidal thoughts and attempts. However, these associations were not explained by late-adolescence psychosocial risks. Rather, youth living in poor neighborhoods may be at greater risk through the amplification of other risk factors in disadvantaged neighborhoods.

Potential explanations for the increased vulnerability of youth living in poor neighborhoods are discussed.