There is increasing acceptance of migration as a risk factor for schizophrenia and related disorders; however, the magnitude of the risk among second-generation immigrants (SGIs) remains unclear. Generational differences in the incidence of psychotic disorders among migrants might improve our understanding of the relationship between migration, ethnicity and psychotic disorders. This meta-analysis aimed at determining the risk of psychotic disorders among SGIs in comparison with non-migrants and first-generation immigrants (FGIs).

Medline, EMBASE and PsycINFO databases were searched systematically for population-based studies on migration and psychotic disorders published between 1977 and 2008. We also contacted experts, tracked citations and screened bibliographies. All potential publications were screened by two independent reviewers in a threefold process. Studies were included in the meta-analysis if they reported incidence data, differentiated FGIs from SGIs and provided age-adjusted data. Data extraction and quality assessment were conducted for each study.

Twenty-one studies met all inclusion criteria. A meta-analysis of 61 effect sizes for FGIs and 28 for SGIs yielded mean-weighted incidence rate ratios (IRRs) of 2.3 [95% confidence interval (CI) 2.0–2.7] for FGIs and 2.1 (95% CI 1.8–2.5) for SGIs. There was no significant risk difference between generations, but there were significant differences according to ethno-racial status and host country.

The increased risk of schizophrenia and related disorders among immigrants clearly persists into the second generation, suggesting that post-migration factors play a more important role than pre-migration factors or migration per se. The observed variability suggests that the risk is mediated by the social context.

Experimental studies have indicated that social contact, even when it is neutral, triggers paranoid thinking in people who score high on clinical or subclinical paranoia. We investigated whether contextual variables are predictive of momentary increases in the intensity of paranoid thinking in a sample of participants ranging across a psychometric paranoia continuum.

The sample (n=154) consisted of 30 currently paranoid patients, 34 currently non-paranoid patients, 15 remitted psychotic patients, 38 high-schizotypy participants, and 37 control subjects. Based on their total score on Fenigstein's Paranoia Scale (PS), three groups with different degrees of paranoia were defined. The Experience Sampling Method (ESM), a structured diary technique, was used to assess momentary social context, perceived social threat and paranoia in daily life.

There were differences in the effect of social company on momentary levels of paranoia and perceived social threat across the range of trait paranoia. The low and medium paranoia groups reported higher levels of perceived social threat when they were with less-familiar compared to familiar individuals. The medium paranoia group reported more paranoia in less-familiar company. The high paranoia group reported no difference in the perception of social threat or momentary paranoia between familiar and unfamiliar contacts.

Paranoid thinking is context dependent in individuals with medium or at-risk levels of trait paranoia. Perceived social threat seems to be context dependent in the low paranoia group. However, at high levels of trait paranoia, momentary paranoia and momentary perceived social threat become autonomous and independent of social reality.

Paranoia is an unregarded but pervasive attribute of human populations. In this study we carried out the most comprehensive investigation so far of the demographic, economic, social and clinical correlates of self-reported paranoia in the general population.

Data weighted to be nationally representative were analysed from the Adult Psychiatric Morbidity Survey in England (APMS 2007; n=7281).

The prevalence of paranoid thinking in the previous year ranged from 18.6% reporting that people were against them, to 1.8% reporting potential plots to cause them serious harm. At all levels, paranoia was associated with youth, lower intellectual functioning, being single, poverty, poor physical health, poor social functioning, less perceived social support, stress at work, less social cohesion, less calmness, less happiness, suicidal ideation, a great range of other psychiatric symptoms (including anxiety, worry, phobias, post-traumatic stress and insomnia), cannabis use, problem drinking and increased use of treatment and services.

Overall, the results indicate that paranoia has the widest of implications for health, emotional well-being, social functioning and social inclusion. Some of these concomitants may contribute to the emergence of paranoid thinking, while others may result from it.

Deficits in face emotion recognition (FER) in schizophrenia are well documented, and have been proposed as a potential intermediate phenotype for schizophrenia liability. However, research on the relationship between psychosis vulnerability and FER has mixed findings and methodological limitations. Moreover, no study has yet characterized the relationship between FER ability and level of psychosis-proneness. If FER ability varies continuously with psychosis-proneness, this suggests a relationship between FER and polygenic risk factors.

We tested two large internet samples to see whether psychometric psychosis-proneness, as measured by the Schizotypal Personality Questionnaire-Brief (SPQ-B), is related to differences in face emotion identification and discrimination or other face processing abilities.

Experiment 1 (n=2332) showed that psychosis-proneness predicts face emotion identification ability but not face gender identification ability. Experiment 2 (n=1514) demonstrated that psychosis-proneness also predicts performance on face emotion but not face identity discrimination. The tasks in Experiment 2 used identical stimuli and task parameters, differing only in emotion/identity judgment. Notably, the relationships demonstrated in Experiments 1 and 2 persisted even when individuals with the highest psychosis-proneness levels (the putative high-risk group) were excluded from analysis.

Our data suggest that FER ability is related to individual differences in psychosis-like characteristics in the normal population, and that these differences cannot be accounted for by differences in face processing and/or visual perception. Our results suggest that FER may provide a useful candidate intermediate phenotype.

Early Intervention in Psychosis Services (EIS) for young people in England experiencing first-episode psychosis (FEP) were commissioned in 2002, based on an expected incidence of 15 cases per 100 000 person-years, as reported by schizophrenia epidemiology in highly urban settings. Unconfirmed reports from EIS thereafter have suggested higher than anticipated rates. The aim of this study was to compare the observed with the expected incidence and delineate the clinical epidemiology of FEP using epidemiologically complete data from the CAMEO EIS, over a 6-year period in Cambridgeshire, for a mixed rural–urban population.

A population-based study of FEP (ICD-10, F10–39) in people aged 17–35 years referred between 2002 and 2007; the denominator was estimated from mid-year census statistics. Sociodemographic variation was explored by Poisson regression. Crude and directly standardized rates (for age, sex and ethnicity) were compared with pre-EIS rates from two major epidemiological FEP studies conducted in urban English settings.

A total of 285 cases met FEP diagnoses in CAMEO, yielding a crude incidence of 50 per 100 000 person-years [95% confidence interval (CI) 44.5–56.2]. Age- and sex-adjusted rates were raised for people from black ethnic groups compared with the white British [incidence rate ratio (IRR) 2.1, 95% CI 1.1–3.8]. Rates in our EIS were comparable with pre-EIS rates observed in more urban areas after age, sex and ethnicity standardization.

Our findings suggest that the incidence observed in EIS is far higher than originally anticipated and is comparable to rates observed in more urban settings prior to the advent of EIS. Sociodemographic variation due to ethnicity and other factors extend beyond urban populations. Our results have implications for psychosis aetiology and service planning.

Patients with schizophrenia (SZ) characteristically exhibit supranormal levels of cortical activity to self-induced sensory stimuli, ostensibly because of abnormalities in the neural signals (corollary discharges, CDs) normatively involved in suppressing the sensory consequences of self-generated actions. The nature of these abnormalities is unknown. This study investigated whether SZ patients experience CDs that are abnormally delayed in their arrival at the sensory cortex.

Twenty-one patients with SZ and 25 matched control participants underwent electroencephalography (EEG). Participants' level of cortical suppression was calculated as the amplitude of the N1 component evoked by a button press-elicited auditory stimulus, subtracted from the N1 amplitude evoked by the same stimulus presented passively. In the three experimental conditions, the auditory stimulus was delivered 0, 50 or 100 ms subsequent to the button-press. Fifteen SZ patients and 17 healthy controls (HCs) also underwent diffusion tensor imaging (DTI), and the fractional anisotropy (FA) of participants' arcuate fasciculus was used to predict their level of cortical suppression in the three conditions.

While the SZ patients exhibited subnormal N1 suppression to undelayed, self-generated auditory stimuli, these deficits were eliminated by imposing a 50-ms, but not a 100-ms, delay between the button-press and the evoked stimulus. Furthermore, the extent to which the 50-ms delay normalized a patient's level of N1 suppression was linearly related to the FA of their arcuate fasciculus.

These data suggest that SZ patients experience temporally delayed CDs to self-generated auditory stimuli, putatively because of structural damage to the white-matter (WM) fasciculus connecting the sites of discharge initiation and destination.

Although cognitive deficits in bipolar disorder have been associated with diminished functional outcome, this relationship has been studied primarily through cross-sectional designs, and has not been studied in patients early in the course of illness. The purpose of this study was to evaluate the impact of cognitive functioning on longitudinal 6-month functional and clinical outcome in recently diagnosed clinically stable patients with bipolar disorder.

A total of 53 recently diagnosed patients with DSM-IV bipolar disorder type I were assessed within 3 months of their first manic episode using a neuropsychological battery measuring verbal/pre-morbid intellectual functioning, learning/memory, spatial/non-verbal reasoning, attention/processing speed and executive function. Functional outcome was assessed at baseline and 6 months using the Multidimensional Scale of Independent Functioning (MSIF) and DSM-IV Global Assessment of Functioning Scale (GAF). Clinical outcome was assessed with symptom ratings and by monitoring onset of new mood episodes.

Memory, particularly verbal learning/memory, was robustly associated with 6-month functional outcome on the MSIF, even after partialling out the influence of mood symptoms and substance abuse co-morbidity. Depression ratings at 6 months, but not cognitive variables, were associated with 6-month GAF scores. Cognitive functioning was not associated with 6-month clinical outcome.

Memory was associated with 6-month longitudinal functional but not clinical outcome in recently diagnosed patients with bipolar disorder. These data further support the distinction between clinical and functional outcome, and emphasize the need for identification of, and development of treatments for, cognitive impairments early in the course of bipolar disorder.

The pretreatment neuropsychological profile of drug-resistant patients with major depressive disorder (MDD) referred for electroconvulsive therapy (ECT) may differ from that of their drug-respondent MDD counterparts. Such differences could help in identifying distinct MDD subtypes, thus offering insights into the neuropathology underlying differential treatment responses.

Depressed patients with ECT referral (ECTs), depressed patients with no ECT referral (NECTs) and non-psychiatric Controls (matched groups, n=15) were assessed with memory and executive function tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB).

ECTs scored significantly lower than NECTs in the Mini-Mental State Examination (MMSE; p=0.01). NECTs performed worse than Controls in the Paired Associates Learning (PAL) task (p<0.03; Control/NECT p<0.01) and the Spatial Recognition Memory (SRM) task (p<0.05; Controls/NECTs p<0.05); ECTs performed between Controls and NECTs, not differing from either. In the Intra/Extradimensional (IED) set-shifting task, ECTs performed worse that Controls and NECTS (IED: p<0.01; Controls/ECTs p<0.01), particularly in the shift phases, which suggests reduced attentional flexibility. In Stockings of Cambridge (SOC), ECTs abandoned the test early more often than Controls and NECTs (H=11, p<0.01) but ECTs who completed SOC performed comparably to the other two groups.

A double dissociation emerged from the comparison of cognitive profiles of ECT and NECT patients. ECTs showed executive deficits, particularly in attentional flexibility, but mild deficits in tests of visuospatial memory. NECTs presented the opposite pattern. This suggests predominantly frontostriatal involvement in ECT versus temporal involvement in NECT depressives.

Recent work suggests that epigenetic differences may be associated with psychiatric disorders. Here we investigate, in a community-based sample, whether methylation profiles distinguish between individuals with and without lifetime depression. We also investigate the physiologic consequences that may be associated with these profiles.

Using whole blood-derived genomic DNA from a subset of participants in the Detroit Neighborhood Health Study (DNHS), we applied methylation microarrays to assess genome-wide methylation profiles for over 14 000 genes in 33 persons who reported a lifetime history of depression and 67 non-depressed adults. Bioinformatic functional analyses were performed on the genes uniquely methylated and unmethylated in each group, and inflammatory biomarkers [interleukin (IL)-6 and C-reactive protein (CRP)] were measured to investigate the possible functional significance of the methylation profiles observed.

Uniquely unmethylated gene sets distinguished between those with versus without lifetime depression. In particular, some processes (e.g. brain development, tryptophan metabolism) showed patterns suggestive of increased methylation among individuals with depression whereas others (e.g. lipoprotein) showed patterns suggestive of decreased methylation among individuals with depression. IL-6 and CRP levels were elevated among those with lifetime depression and, among those with depression only, IL-6 methylation showed an inverse correlation with circulating IL-6 and CRP.

Genome-wide methylation profiles distinguish individuals with versus without lifetime depression in a community-based setting, and show coordinated signals with pathophysiological mechanisms previously implicated in the etiology of this disorder. Examining epigenetic mechanisms in concert with other dynamic markers of physiologic functioning should improve our understanding of the neurobiology of depression.

Generalized anxiety disorder (GAD) is under-researched despite its high prevalence and large impact on the healthcare system. There is a paucity of functional magnetic resonance imaging (fMRI) studies that explore the neural correlates of emotional processing in GAD. The present study investigated the blood oxygen level dependent (BOLD) response to processing positive and negative facial emotions in patients with GAD.

A total of 15 female GAD patients and 16 female controls undertook an implicit face emotion task during fMRI scanning. They also performed a face emotion recognition task outside the scanner.

The only behavioural difference observed in GAD patients was less accurate detection of sad facial expressions compared with control participants. However, GAD patients showed an attenuated BOLD signal in the prefrontal cortex to fearful, sad, angry and happy facial expressions and an attenuated signal in the anterior cingulate cortex to happy and fearful facial expressions. No differences were found in amygdala response.

In contrast with previous research, this study found BOLD signal attenuation in the ventrolateral and medial prefrontal cortex and the anterior cingulate cortex during face emotion processing, consistent with a hypothesis of hypo-responsivity to external emotional stimuli in GAD. These decreases were in areas that have been implicated in emotion and cognition and may reflect an altered balance between internally and externally directed attentional processes.

This study prospectively examined the natural clinical course of six anxiety disorders over 7 years of follow-up in individuals with personality disorders (PDs) and/or major depressive disorder. Rates of remission, relapse, new episode onset and chronicity of anxiety disorders were examined for specific associations with PDs.

Participants were 499 patients with anxiety disorders in the Collaborative Longitudinal Personality Disorders Study, who were assessed with structured interviews for psychiatric disorders at yearly intervals throughout 7 years of follow-up. These data were used to determine probabilities of changes in disorder status for social phobia (SP), generalized anxiety disorder (GAD), obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), panic disorder and panic disorder with agoraphobia.

Estimated remission rates for anxiety disorders in this study group ranged from 73% to 94%. For those patients who remitted from an anxiety disorder, relapse rates ranged from 34% to 67%. Rates for new episode onsets of anxiety disorders ranged from 3% to 17%. Specific PDs demonstrated associations with remission, relapse, new episode onsets and chronicity of anxiety disorders. Associations were identified between schizotypal PD with course of SP, PTSD and GAD; avoidant PD with course of SP and OCD; obsessive-compulsive PD with course of GAD, OCD, and agoraphobia; and borderline PD with course of OCD, GAD and panic with agoraphobia.

Findings suggest that specific PD diagnoses have negative prognostic significance for the course of anxiety disorders underscoring the importance of assessing and considering PD diagnoses in patients with anxiety disorders.

Certain aspects of sleep co-occur with externalizing behaviours in youth, yet little is known about these associations in adults. The present study: (1) examines the associations between diurnal preference (morningness versus eveningness), sleep quality and externalizing behaviours; (2) explores the extent to which genetic and environmental influences are shared between or are unique to these phenotypes; (3) examines the extent to which genetic and environmental influences account for these associations.

Questionnaires assessing diurnal preference, sleep quality and externalizing behaviours were completed by 1556 young adult twins and siblings.

A preference for eveningness and poor sleep quality were associated with greater externalizing symptoms [r=0.28 (95% CI 0.23–0.33) and 0.34 (95% CI 0.28–0.39), respectively]. A total of 18% of the genetic influences on externalizing behaviours were shared with diurnal preference and sleep quality and an additional 14% were shared with sleep quality alone. Non-shared environmental influences common to the phenotypes were small (2%). The association between diurnal preference and externalizing behaviours was mostly explained by genetic influences [additive genetic influence (A)=80% (95% CI 0.56–1.01)], as was the association between sleep quality and externalizing behaviours [A=81% (95% CI 0.62–0.99)]. Non-shared environmental (E) influences accounted for the remaining variance for both associations [E=20% (95% CI −0.01 to 0.44) and 19% (95% CI 0.01–0.38), respectively].

A preference for eveningness and poor sleep quality are moderately associated with externalizing behaviours in young adults. There is a moderate amount of shared genetic influences between the phenotypes and genetic influences account for a large proportion of the association between sleep and externalizing behaviours. Further research could focus on identifying specific genetic polymorphisms common to both sleep and externalizing behaviours.

Borderline personality disorder (BPD) shows high levels of co-morbidity with an array of psychiatric disorders. The meaning and causes of this co-morbidity are not fully understood. Our objective was to investigate and clarify the complex co-morbidity of BPD by integrating it into the structure of common mental disorders.

We conducted exploratory and confirmatory factor analyses on diagnostic interview data from a representative US population-based sample of 34 653 civilian, non-institutionalized individuals aged ⩾18 years. We modeled the structure of lifetime DSM-IV diagnoses of BPD and antisocial personality disorder (ASPD), major depressive disorder, dysthymic disorder, panic disorder with agoraphobia, social phobia, specific phobia, generalized anxiety disorder, post-traumatic stress disorder, alcohol dependence, nicotine dependence, marijuana dependence, and any other drug dependence.

In both women and men, the internalizing–externalizing structure of common mental disorders captured the co-morbidity among all disorders including BPD. Although BPD was unidimensional in terms of its symptoms, BPD as a disorder showed associations with both the distress subfactor of the internalizing dimension and the externalizing dimension.

The complex patterns of co-morbidity observed with BPD represent connections to other disorders at the level of latent internalizing and externalizing dimensions. BPD is meaningfully connected with liabilities shared with common mental disorders, and these liability dimensions provide a beneficial focus for understanding the co-morbidity, etiology and treatment of BPD.

Monoamine oxidase A (MAOA) is an important enzyme that metabolizes monoamines such as serotonin, norepinephrine and dopamine in the brain. In prefrontal cortex, low MAOA binding is associated with aggression and high binding is associated with major depressive disorder (MDD) and also risk for recurrence of depressive episodes. In rodent models, low MAOA levels are associated with increased aggression and fear conditioning, and decreased social and exploratory investigative behaviors. Our objective was to measure MAOA binding in prefrontal cortex and concurrently evaluate a broad range of validated personality traits. We hypothesized that prefrontal MAOA binding would correlate negatively with angry-hostility, a trait related to aggression/anger, and positively with traits intuitively related to adaptive investigative behavior.

Participants were aged 19–49 years, healthy and non-smoking. MAOA binding was measured with [11C]harmine positron emission tomography (PET) in prefrontal brain regions and personality traits were measured with the NEO Personality Inventory Revised (NEO PI-R).

Prefrontal MAOA binding correlated negatively with angry-hostility (r=−0.515, p=0.001) and positively with deliberation (r=0.514, p=0.001). In a two-factor regression model, these facets explained 38% of variance in prefrontal MAOA binding. A similar relationship was found in prefrontal cortex subregions.

We propose a new continuum describing the relationship between personality and MAOA: deliberate/thoughtful contrasting aggressive/impulsive. Additionally, the association between high MAOA binding and greater deliberation may explain why some people have moderately high levels of MAOA, although very high levels occur during MDD. In health, higher MAOA binding is associated with an adaptive personality facet.

Few data exist examining the longer-term outcome of bulimia nervosa (BN) following treatment with cognitive behavioral therapy (CBT) and exposure with response prevention (ERP).

One hundred and thirty-five women with purging BN received eight sessions of individual CBT and were then randomly assigned to either relaxation training (RELAX) or one of two ERP treatments, pre-binge (B-ERP) or pre-purge cues (P-ERP). Participants were assessed yearly following treatment and follow-up data were recorded.

Eighty-one per cent of the total sample attended long-term follow-up. At 5 years, abstinence rates from binging were significantly higher for the two exposure treatments (43% and 54%) than for relaxation (27%), with no difference between the two forms of exposure. Over 5 years, the frequency of purging was lower for the exposure treatments than for relaxation training. Rates of recovery varied according to definition of recovery. Recovery continued to increase to 5 years. At 5 years, 83% no longer met DSM-III-R criteria for BN, 65% received no eating disorder diagnosis, but only 36% had been abstinent from bulimic behaviors for the past year.

This study provides possible evidence of a conditioned inoculation from exposure treatment compared with relaxation training in long-term abstinence from binge eating at 5 years, and the frequency of purging over 5 years, but not for other features of BN. Differences among the groups were not found prior to 5 years. CBT is effective for BN, yet a substantial group remains unwell in the long term. Definition of recovery impacts markedly on recovery rates.

Among adolescents and young adults with DSM-IV alcohol use disorders (AUDs), there are inter-individual differences in the speed of transition from initial alcohol use (AU) to AUD. AUDs are highly co-morbid with other mental disorders. The factors associated with rapid transition from first AU to AUD remain unknown and the role of mental disorders in rapid transitions is unclear. Given this background we examined (1) whether prior anxiety, mood, externalizing and non-alcohol substance use disorders are related to the risk and speed of transition from first AU to DSM-IV alcohol abuse (AA) and alcohol dependence (AD) and (2) whether early age of onset of prior mental disorders (PMDs) is a promoter of rapid transition.

A total of 3021 community subjects (97.7% lifetime AU) aged 14–24 years at baseline were followed up prospectively for up to 10 years. AU and mental disorders were assessed with the DSM-IV/M-CIDI.

Among subjects with lifetime AU, several PMDs, such as specific phobia, bipolar disorder and nicotine dependence, were associated with an increased risk of AUD independent of externalizing disorders. Associations of PMDs with the speed of transition to AUDs were mostly weak and inconsistent. Only social phobia and externalizing disorders were associated with faster transitions to AD even after adjustment for other PMDs. Earlier age of onset of PMD was not associated with rapid transition.

Mental disorders are associated with the risk of AUD. With the possible exception of social phobia and externalizing disorders, they do not promote rapid transition, even if they occur particularly early. Future research needs to identify factors relevant to rapid transition to AUD.

Early diagnosis of dementia requires knowledge about associated predictors. The aim of this study was to determine the impact of mild cognitive impairment (MCI) and impairment in instrumental activities of daily living (IADL) on the time to an incident dementia diagnosis.

Data were derived from the Leipzig Longitudinal Study of the Aged (LEILA75+), a population-based study of individuals aged ⩾75 years. Kaplan-Meier survival analysis was used to determine time to incident dementia. Cox proportional hazards models were applied to determine the impact of MCI and IADL impairment on the time to incident dementia.

In total, 180 (22.0%) of 819 initially dementia-free subjects developed dementia by the end of the study. Mean time to incident dementia was 6.7 years [95% confidence interval (CI) 6.5–6.9]. MCI combined with IADL impairment was associated with a higher conversion rate to dementia, a shorter time to clinically manifest diagnosis and a lower chance of reversibility to cognitive normal. The highest risk for a shorter time to incident dementia was found for amnestic MCI combined with IADL impairment. The mean time to incident dementia was 3.7 years (95% CI 2.9–4.4) and thus half as long as in subjects without MCI and IADL impairment.

Subjects with MCI and IADL impairment constitute a high-risk population for future dementia. The consideration of both – MCI and IADL impairment – might help to improve the prediction of dementia.

The cognitive behavioural model of chronic fatigue syndrome (CFS) suggests that the illness is caused through reciprocal interactions between physiology, cognition, emotion and behaviour. The purpose of this study was to investigate whether the psychological factors operationalized in this model could predict the onset of CFS following an acute episode of infectious mononucleosis commonly known as glandular fever (GF).

A total of 246 patients with GF were recruited into this prospective cohort study. Standardized self-report measures of perceived stress, perfectionism, somatization, mood, illness beliefs and behaviour were completed at the time of their acute illness. Follow-up questionnaires determined the incidence of new-onset chronic fatigue (CF) at 3 months and CFS at 6 months post-infection.

Of the participants, 9.4% met the criteria for CF at 3 months and 7.8% met the criteria for CFS at 6 months. Logistic regression revealed that factors proposed to predispose people to CFS including anxiety, depression, somatization and perfectionism were associated with new-onset CFS. Negative illness beliefs including perceiving GF to be a serious, distressing condition, that will last a long time and is uncontrollable, and responding to symptoms in an all-or-nothing behavioural pattern were also significant predictors. All-or-nothing behaviour was the most significant predictor of CFS at 6 months. Perceived stress and consistently limiting activity at the time of GF were not significantly associated with CFS.

The findings from this study provide support for the cognitive behavioural model and a good basis for developing prevention and early intervention strategies for CFS.