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Genomic prediction has the potential to contribute to precision medicine. However, to date, the utility of such predictors is limited due to low accuracy for most traits. Here theory and simulation study are used to demonstrate that widespread pleiotropy among phenotypes can be utilised to improve genomic risk prediction. We show how a genetic predictor can be created as a weighted index that combines published genome-wide association study (GWAS) summary statistics across many different traits. We apply this framework to predict risk of schizophrenia and bipolar disorder in the Psychiatric Genomics consortium data, finding substantial heterogeneity in prediction accuracy increases across cohorts. For six additional phenotypes in the UK Biobank data, we find increases in prediction accuracy ranging from 0.7% for height to 47% for type 2 diabetes, when using a multi-trait predictor that combines published summary statistics from multiple traits, as compared to a predictor based only on one trait., Genetic prediction of complex traits so far has limited accuracy because of insufficient understanding of the genetic risk. Here, Maier et al. develop an improved method for trait prediction that makes use of genetic correlations between traits and apply it to summary statistics of psychiatric diseases.

Christina M van der Feltz-Cornelis,1–3 Jim van Os,4,6 Susanne Knappe,5 Gunter Schumann,6 Eduard Vieta,7 Hans-Ulrich Wittchen,5 Shôn W Lewis,8 Iman Elfeddali,2,9 Kristian Wahlbeck,10,11 Donald Linszen,4 Carla Obradors-Tarragó,12,13 Josep Maria Haro12–141Trimbos Instituut, Utrecht, 2Tilburg University, Tranzo Department, Tilburg, 3GGz Breburg, Tilburg, 4Department of Psychiatry and Psychology, South Limburg Mental Health Research and Teaching Network, Euron, Maastricht University Medical Center, Maastricht, the Netherlands; 5Institute of Clinical Psychology and Psychotherapy and Center for Epidemiology and Longitudinal Studies, Technische Universität Dresden, Dresden, Germany; 6Institute of Psychiatry, King’s College London, London, UK; 7Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain; 8School of Community-Based Medicine, University of Manchester, Manchester, UK; 9Department of Health Promotion/School of Public Health and Primary Care, Maastricht University, Maastricht, the Netherlands; 10The Nordic School of Public Health, Gothenburg, Sweden; 11National Institute for Health and Welfare, Helsinki, Finland; 12Centro de Investigación Biomédica en Red de Salud Mental, Madrid, 13Research and Development Unit, Parc Sanitari Sant Joan de Déu, Fundació Sant Joan de Déu, Sant Boi de Llobregat, 14Universitat de Barcelona, Barcelona, SpainBackground: The size and increasing burden of disease due to mental disorders in Europe poses substantial challenges to its population and to the health policy of the European Union. This warrants a specific research agenda concerning clinical mental health research as one of the cornerstones of sustainable mental health research and health policy in Europe. The aim of this research was to identify the top priorities needed to address the main challenges in clinical research for mental disorders.Methods: The research was conducted as an expert survey and expert panel discussion during a scientific workshop.Results: Eighty-nine experts in clinical research and representing most European countries participated in this survey. Identified top priorities were the need for new intervention studies, understanding the diagnostic and therapeutic implications of mechanisms of disease, and research in the field of somatic-psychiatric comorbidity. The “subjectivity gap” between basic neuroscience research and clinical reality for patients with mental disorders is considered the main challenge in psychiatric research, suggesting that a shift in research paradigms is required.Conclusion: Innovations in clinical mental health research should bridge the gap between mechanisms underlying novel therapeutic interventions and the patient experience of mental disorder and, if present, somatic comorbidity. Clinical mental health research is relatively underfunded and should receive specific attention in Horizon 2020 funding programs.Keywords: clinical research, mental health, randomized clinical trials, Horizon 2020, expert survey, challenge, research agenda, Europe

BackgroundSchizophrenia is associated with lower pre-morbid intelligence (IQ) in addition to (pre-morbid) cognitive decline. Both schizophrenia and IQ are highly heritable traits. Therefore, we hypothesized that genetic variants associated with schizophrenia, including copy number variants (CNVs) and a polygenic schizophrenia (risk) score (PSS), may influence intelligence.MethodIQ was estimated with the Wechsler Adult Intelligence Scale (WAIS). CNVs were determined from single nucleotide polymorphism (SNP) data using the QuantiSNP and PennCNV algorithms. For the PSS, odds ratios for genome-wide SNP data were calculated in a sample collected by the Psychiatric Genome-Wide Association Study (GWAS) Consortium (8690 schizophrenia patients and 11 831 controls). These were used to calculate individual PSSs in our independent sample of 350 schizophrenia patients and 322 healthy controls.ResultsAlthough significantly more genes were disrupted by deletions in schizophrenia patients compared to controls (p = 0.009), there was no effect of CNV measures on IQ. The PSS was associated with disease status (R2 = 0.055, p = 2.1 × 10−7) and with IQ in the entire sample (R2 = 0.018, p = 0.0008) but the effect on IQ disappeared after correction for disease status.ConclusionsOur data suggest that rare and common schizophrenia-associated variants do not explain the variation in IQ in healthy subjects or in schizophrenia patients. Thus, reductions in IQ in schizophrenia patients may be secondary to other processes related to schizophrenia risk.

We examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects. The combined stage 1 and 2 analysis yielded genome-wide significant associations with schizophrenia for seven loci, five of which are new (1p21.3, 2q32.3, 8p23.2, 8q21.3 and 10q24.32-q24.33) and two of which have been previously implicated (6p21.32-p22.1 and 18q21.2). The strongest new finding (P = 1.6 × 10 -11) was with rs1625579 within an intron of a putative primary transcript for MIR137 (microRNA 137), a known regulator of neuronal development. Four other schizophrenia loci achieving genome-wide significance contain predicted targets of MIR137, suggesting MIR137-mediated dysregulation as a previously unknown etiologic mechanism in schizophrenia. In a joint analysis with a bipolar disorder sample (16,374 affected individuals and 14,044 controls), three loci reached genome-wide significance: CACNA1C (rs4765905, P = 7.0 × 10 -9), ANK3 (rs10994359, P = 2.5 × 10 -8) and the ITIH3-ITIH4 region (rs2239547, P = 7.8 × 10 -9). © 2011 Nature America, Inc. All rights reserved.

Objective: The first aim was to determine the cost-effectiveness of CBT to prevent first-episode psychosis in ultra-high risk (UHR). The second aim was to develop an optimized prediction model of a first episode psychosis, as with current UHR criteria only 20 % have a psychotic outcome after 2 years. Methods: 196 help-seeking UHR patients participated in the Dutch EDIE study. All individuals were treated with routine care (RC) for non-psychotic disorders. The experimental group received adjuvant CBT to prevent psychosis. We report intervention, medical, and travel costs; costs arising from productivity losses, treatment response defined as psychosis-free survival and quality-adjusted life years gained. Furthermore, baseline data on symptomatology, and environmental and psychological factors were analyzed with Cox proportional hazard analyses. Results: In the cost-effectiveness analysis, the proportion of averted psychoses was significantly higher in the CBT condition. CBT was less costly than RC by US$ 844 per prevented psychosis. The Cox proportional hazard model included five predictors: observed blunted affect, subjective complaints of impaired motor function, beliefs about social marginalization, decline in social functioning, and distress associated with non-bizarre ideas. The resulting prognostic index stratified the general risk into 3 risk classes with significantly different survival curves. In the highest risk class, transition to psychosis emerged on average ≥ 8 months earlier than in the lowest risk class. Conclusion: Firstly, add-on CBT for individuals at UHR resulted in significant prevention of psychosis, for lower costs compared with RC. Secondly, predicting a first-episode psychosis in UHR seems improved using a five-factor prediction model.

To investigate the predictive value of the Strauss and Carpenter Prognostic Scale (SCPS) for transition to a first psychotic episode in subjects clinically at high risk (CHR) of psychosis. Two hundred and forty-four CHR subjects participating in the European Prediction of Psychosis Study were assessed with the SCPS, an instrument that has been shown to predict outcome in patients with schizophrenia reliably. At 18-month follow-up, 37 participants had made the transition to psychosis. The SCPS total score was predictive of a first psychotic episode (P < 0.0001). SCPS items that remained as independent predictors in the Cox proportional hazard model were as follows: most usual quality of useful work in the past year (P = 0.006), quality of social relations (P = 0.006), presence of thought disorder, delusions or hallucinations in the past year (P = 0.001) and reported severity of subjective distress in past month (P = 0.003). The SCPS could make a valuable contribution to a more accurate prediction of psychosis in CHR subjects as a second-step tool. SCPS items assessing quality of useful work and social relations, positive symptoms and subjective distress have predictive value for transition. Further research should focus on investigating whether targeted early interventions directed at the predictive domains may improve outcomes

Objective: Numerous studies have found a robust association between cannabis use and the onset of psychosis. Nevertheless, the relationship between cannabis use and the onset of early ( or, in retrospect, prodromal) symptoms of psychosis remains unclear. The study focused on investigating the relationship between cannabis use and early and high-risk symptoms in subjects at clinical high risk for psychosis. Method: Prospective multicenter, naturalistic field study with an 18-month follow-up period in 245 help-seeking individuals clinically at high risk. The Composite International Diagnostic Interview was used to assess their cannabis use. Age at onset of high risk or certain early symptoms was assessed retrospectively with the Interview for the Retrospective Assessment of the Onset of Schizophrenia. Results: Younger age at onset of cannabis use or a cannabis use disorder was significantly related to younger age at onset of six symptoms (0.33

Rietdijk J, Klaassen R, Ising H, Dragt S, Nieman DH, van de Kamp J, Cuijpers P, Linszen D, van der Gaag M. Detection of people at risk of developing a first psychosis: comparison of two recruitment strategies. Objective: Better recruitment strategies are needed to improve the identification of people at ultra-high risk of developing psychosis. This study explores the effectiveness of two recruitment strategies: a screening method in a consecutive help-seeking population entering secondary mental health services for non-psychotic problems vs. a population referred to the diagnostic center of an early-psychosis clinic. Method: From February 2008 to February 2010, all general practitioner and self-referrals (aged 1835 years) to the secondary mental healthcare service in The Hague and Zoetermeer were screened with the Prodromal Questionnaire; patients who scored above the cutoff of 18 and had a decline in social functioning were assessed using the Comprehensive Assessment of At-Risk Mental States (CAARMS). All referrals (aged 1435 years) to the diagnostic center in Amsterdam were also assessed with the CAARMS. Results: The screening detected a three-fold higher prevalence of at-risk mental states: these subjects were older and more often female. manova showed significantly higher scores for the screened population on depression, social anxiety, distress with positive symptoms, and a higher rate of transition to psychosis within 12 months. Conclusion: The screening method detects more patients with at-risk mental states than the referral method. The latter method is biased to young male patients in an earlier prodromal stage and a lower transition rate

Objective: The investigation into the course of ultra high risk (UHR) symptomatology of those patients who eventually do not meet the psychosis-threshold criteria within the 3-year timeframe of the study. Method: The course of UHR symptoms, GAF score and employment status was investigated in 57 patients who did not make a transition to psychosis and who were examined within the Dutch Prediction of Psychosis Study in Amsterdam, the Netherlands. Results: At the 3- year follow-up, 75% of the patients who did not make a transition to psychosis had remitted from UHR status. With a Generalized Estimation Equation Model it was shown that this group recovered from positive (F = 52.7, P

BACKGROUND: Gender differences play a role in the origin and course of schizophrenia. It has been hypothesised that the gonadal hormone, oestrogen, may possibly perform a protective function in the development of certain forms of schizophrenia. AIM: To review neurobiological hypotheses concerning the role of oestrogen in the development and course of schizophrenia. METHOD: The relevant literature was consulted with the help of PubMed, textbooks and bibliographic references; the search terms used were 'oestrogen', 'schizophrenia', 'gender', 'epigenetics', 'psychosis', 'women' and 'brain'. There were no restrictions with regards to the time-period. RESULTS: Neuro-imaging, animal experiments and hormone-therapy studies showed several effects of oestrogen in the field of epigenetics, morphology of the brain, interaction with neurotransmitters and neuroprotection. CONCLUSION: Oestrogen is an important link in a complex of factors that clearly play a role in the varying development of schizophrenia in men and women. So far, however, there is insufficient evidence to support the existence of a specific mechanism that would explain why oestrogen may perform a protective function in schizophrenia.

Background. Cannabis use is common in patients with recent-onset schizophrenia and this is associated with poor disease outcome. More insight in the cognitive-motivational processes related to cannabis use in schizophrenia may inform treatment strategies. The present study is the first known to compare implicit and explicit cannabis associations in individuals with and without psychotic disorder. Method. Participants consisted of 70 patients with recent-onset psychotic disorder and 61 healthy controls with various levels of cannabis use. Three Single-Category Implicit Association Tests (SC-IAT) were used to assess 'relaxed', 'active' and 'negative' implicit associations towards cannabis use. Explicit expectancies of cannabis use were assessed with a questionnaire using the same words as the SC-IAT. Results. There were no differences in implicit associations between patients and controls; however, patients scored significantly higher on explicit negative affect expectancies than controls. Both groups demonstrated strong negative implicit associations towards cannabis use. Explicit relaxed expectancies were the strongest predictors of cannabis use and craving. There was a trend for implicit active associations to predict craving. Conclusions. The findings indicate that patients suffering from schizophrenia have associations towards cannabis similar to controls, but they have stronger negative explicit cannabis associations. The strong negative implicit associations towards cannabis could imply that users of cannabis engage in a behaviour they do not implicitly like. Explicit relaxing expectancies of cannabis might be an important mediator in the continuation of cannabis use in patients and controls.

It has been hypothesised that in subjects with 22q11 deletion syndrome (22q11DS) disturbances of the dopamine (DA) system contribute to their increased risk for cognitive deficits and psychiatric problems. However, central DAergic neurotransmission in 22q11DS has not been investigated. We measured striatal D₂ receptor binding potential (D₂R BP(ND)) using (S)-(-)-3-iodo-2-hydroxy-6-methoxy-N-[(1-ethyl-2-pyrrolidinyl)methyl] benzamide-single photon emission computed tomography ([¹²³I]IBZM SPECT) in 12 adults with 22q11DS and 12 matched controls. Correlations between D₂R BP(ND) and plasma prolactin (pPRL) levels were also determined. 22q11DS subjects and controls had similar D₂R BP( ND). There was a positive correlation between D₂R BP( ND) and pPRL values in controls, but no such relation was found in 22q11DS subjects. This study suggests that a 22q11 deletion does not affect striatal DAergic neurotransmission in the living human brain. However, the disturbed relationship between D₂R BP(ND) and pPRL values suggests DAergic dysfunction at a different level. Further studies on DAergic function in extra-striatal brain regions and under challenged conditions are needed

Schizophrenia is a complex disorder, caused by both genetic and environmental factors and their interactions. Research on pathogenesis has traditionally focused on neurotransmitter systems in the brain, particularly those involving dopamine. Schizophrenia has been considered a separate disease for over a century, but in the absence of clear biological markers, diagnosis has historically been based on signs and symptoms. A fundamental message emerging from genome-wide association studies of copy number variations (CNVs) associated with the disease is that its genetic basis does not necessarily conform to classical nosological disease boundaries. Certain CNVs confer not only high relative risk of schizophrenia but also of other psychiatric disorders. The structural variations associated with schizophrenia can involve several genes and the phenotypic syndromes, or the ĝ€ genomic disordersĝ€™, have not yet been characterized. Single nucleotide polymorphism (SNP)-based genome-wide association studies with the potential to implicate individual genes in complex diseases may reveal underlying biological pathways. Here we combined SNP data from several large genome-wide scans and followed up the most significant association signals. We found significant association with several markers spanning the major histocompatibility complex (MHC) region on chromosome 6p21.3-22.1, a marker located upstream of the neurogranin gene (NRGN) on 11q24.2 and a marker in intron four of transcription factor 4 (TCF4) on 18q21.2. Our findings implicating the MHC region are consistent with an immune component to schizophrenia risk, whereas the association with NRGN and TCF4 points to perturbation of pathways involved in brain development, memory and cognition. © 2009 Macmillan Publishers Limited., link_to_OA_fulltext

Deletions within the neurexin 1 gene (NRXN1; 2p16.3) are associated with autism and have also been reported in two families with schizophrenia. We examined NRXN1, and the closely related NRXN2 and NRXN3 genes, for copy number variants (CNVs) in 2977 schizophrenia patients and 33 746 controls from seven European populations (Iceland, Finland, Norway, Germany, The Netherlands, Italy and UK) using microarray data. We found 66 deletions and 5 duplications in NRXN1, including a de novo deletion: 12 deletions and 2 duplications occurred in schizophrenia cases (0.47%) compared to 49 and 3 (0.15%) in controls. There was no common breakpoint and the CNVs varied from 18 to 420 kb. No CNVs were found in NRXN2 or NRXN3. We performed a Cochran-Mantel-Haenszel exact test to estimate association between all CNVs and schizophrenia (P = 0.13; OR = 1.73; 95% CI 0.81-3.50). Because the penetrance of NRXN1 CNVs may vary according to the level of functional impact on the gene, we next restricted the association analysis to CNVs that disrupt exons (0.24% of cases and 0.015% of controls). These were significantly associated with a high odds ratio (P = 0.0027; OR 8.97, 95% CI 1.8-51.9). We conclude that NRXN1 deletions affecting exons confer risk of schizophrenia. © The Author 2008. Published by Oxford University Press. All rights reserved., link_to_OA_fulltext

BACKGROUND: Many studies have reported an interactive vulnerability between adolescence, schizophrenia and drug abuse. aim To discuss neurobiological and psychosocial developmental factors in adolescence and early adulthood which may contribute to this co-occurrence. METHOD: We studied the literature by means of PubMed, manuals and bibliographic references and used the search terms: 'adolescence', 'neurodevelopment', 'psychosis', 'schizophrenia', 'dopamine', 'substance (ab)use'. results Adolescence is a period of psychosocial challenges and changes in the brain which, in the case of predisposed persons, can increase the probability of the onset of both schizophrenia and substance abuse. The loss of exceptionally large numbers of dopaminergic neurons can lead to mesocortical hypofrontality combined with anhedonia and dysphoria, both of which are important risk factors for substance abuse. In turn, mesocortical hypofrontality can contribute to hyperactivity of the mesolimbic system, a condition associated with psychoses. We failed to find any other neurobiological explanations for the simultaneous occurrence of schizophrenia and substance abuse and for the fact that they both begin in adolescence and early adulthood. It should be noted, however, that there is a possible interaction between the gaba-glutamate and the dopaminergic neurotransmission. CONCLUSION: The partly overlapping pathogenesis and the simultaneous occurrence of drug abuse and schizophrenia call for integrated treatment. In treatment involving antipsychotics it is important to prevent the development of dysphoria and anhedonia which can adversely affect the patient's well-being and treatment compliance and even increase drug abuse

BACKGROUND: If schizophrenia and related disorders are diagnosed and treated early, symptoms will be less severe and the prognosis will be more favourable. There is little point in screening for schizophrenia in the general population because the illness has such a low incidence. However, we do need to find out whether it is meaningful to screen genetically impaired individuals (high risk group) and specific groups of psychiatric patients (ultra high risk group). AIM: To survey the research into the (high and ultra high) risk factors for developing a first psychosis and to find out whether it makes good sense to screen certain groups of persons. METHOD: We conducted extensive desk-research and a wide-ranging search of the literature from 1990 to 2004. The key words we used in our search were 'prodrome', 'high risk', 'ultra high risk', in conjunction with 'psychosis' and 'schizophrenia'. RESULTS: In the genetically impaired group risk factors for developing schizophrenia seem to be transient psychiatric problems in childhood, schizotypical traits, anxiety, behavioural problems in adolescence, being brought up in an unstable environment and producing deviant results in neurocognitive tests. Among the patients referred to a psychiatrist it is possible to identify a special group of patients with an ultra high risk of developing a psychosis. Within ayear 40% of patients who had mild or short-term psychotic symptoms or who were genetically impaired adolescents with decreased functioning had developed a psychosis. CONCLUSION: Screening all genetically vulnerable persons in the general population has no consequencesfor treatment. Early diagnosis by psychiatrists is certainly advisable. However, larger groups and longer studies are needed in order to demonstrate conclusively the preventive effect of interventions prior to a first psychosis

BACKGROUND: An important question that arises in policy discussions concerning the use of cannabis is whether the possible harmful effects of cannabis are reversible. AIM: To review studies on residual neuropsychological, structural and functional brain abnormalities that may have resulted from the long-term use of cannabis. METHOD: When we searched Medline (January 1966 - December 2003) and EMBASE (January 1988 - December 2003) using the key words 'cannabis', 'marijuana', 'neuropsychological test', 'cognition', 'CT-scan', 'MRI', 'PET', 'SPECT' and 'brain', we found 29 studies in our area of interest. We selected only those neuropsychological and functional brain imaging studies in which the patients had a controlled abstinence period longer than 98 hours. RESULTS: On the basis of six studies we concluded that there was insufficient evidence to prove conclusively that long-term cannabis use causes or does not cause residual abnormalities. The results of our review were also inconclusive whether cannabis use during adolescence may have a lasting effect on cognitive functioning and brain structure. However, we could not rule out the possibility that (1) certain cognitive and cerebral abnormalities existed in patients before cannabis use began and (2) that patients were suffering from subacute effects of cannabis. CONCLUSION: So far, research into the residual effects of cannabis use has been inadequate. Future studies should concentrate on the effect of cannabis use during early adolescence. More insight should come from longitudinal studies involving neuropsychological measurements and brain imaging before cannabis use begins. The abstinence period should be at least seven weeks

RATIONALE: In vitro data have shown anticholinergic properties of the atypical antipsychotic drug olanzapine. Substantial occupancy of muscarinic receptors may be an explanation for the low incidence of extrapyramidal side effects induced by olanzapine. OBJECTIVES: To obtain an in vivo measurement of muscarinic receptor occupancy by olanzapine compared with risperidone in patients with schizophrenia stabilised on medication. METHODS: Five patients with schizophrenia treated with olanzapine and five patients treated with risperidone were studied. Muscarinic receptor occupancy in the striatum and cortex was studied in vivo with SPECT using [123I]-IDEX as a radioligand. SPECT data were compared with those of six healthy subjects. RESULTS: Patients stabilised on olanzapine showed significantly lower mean (+/-SD) striatal and cortical (1.50+/-0.21 and 1.51+/-0.22, respectively) muscarinic receptor binding ratios of [123I]-IDEX (reflecting higher levels of muscarinic receptor occupancy) than controls (3.91+/-0.61 and 3.65+/-0.70, respectively). Furthermore, [123I]-IDEX binding ratios in patients treated with risperidone were slightly lower than controls, reaching significance only in the striatum (2.99+/-0.27 versus 3.91+/-0.61, for risperidone and controls). CONCLUSIONS: The substantial occupancy of muscarinic receptors in the striatum and cortex by olanzapine may be an explanation for the low incidence and severity of extrapyramidal side effects of this antipsychotic drug. Furthermore, it may also explain the anticholinergic side effects of olanzapine

OBJECTIVES: To elucidate pathophysiologic mechanisms involved in abnormal antisaccade task performance in schizophrenia by investigating a possible relationship among antisaccade task performance, neuropsychological test results, and symptomatology in a group of young patients with recent-onset schizophrenia; to compare the effects of olanzapine and risperidone on antisaccades and reflexive saccades. BACKGROUND: Patients with schizophrenia consistently perform worse than controls on the antisaccade task in which the subject is required to inhibit a reflexive saccade to a suddenly appearing visual target and look in the opposite direction. METHODS: In 37 young (mean age 21 years), medicated patients with recent-onset schizophrenia the authors assessed antisaccades, reflexive saccades, neuropsychological test performance, and symptomatology. A subgroup of 18 patients was treated with olanzapine, and 15 patients were treated with risperidone. Reflexive-saccade and antisaccade task results were compared with those obtained in 13 control subjects. RESULTS: The antisaccade error rate was significantly higher in the patients than in the control subjects. In the patients, poor working memory function was related to increased antisaccade error rate. Severity of disorganization symptoms at intake was related to prolonged mean latency of the correct antisaccades. Patients on risperidone had a prolonged mean latency in the reflexive saccade task compared with patients using olanzapine. CONCLUSIONS: Abnormal antisaccade task performance is already present in early schizophrenia and may reflect working memory dysfunction. In future studies, medication effects should be considered in interpreting eye movement test results of patients with schizophrenia

In the context of a prospective, controlled treatment study, contrasting family interventions with individual treatment, the role of expressed emotion (EE) as a predictor of relapse was examined in patients with recent-onset schizophrenia and related disorders (n = 97). EE was compared with 13 predictor variables. The variables, taken from EE and family intervention studies, related to demography, premorbid functioning, present and past illness history, and comorbid substance abuse. Psychotic relapse was operationalized with a conservatively measured relapse criterion, composed of monthly ratings based on the Brief Psychiatric Rating Scale and on clinical judgment during the 12 months of outpatient treatment. Of the 14 predictor variables entered in stepwise survival analyses, 6 variables had probable predictive power on the conservative relapse criterion. These variables were entered in a Cox regression model. EE turned out to be the major predictor of relapse in the overall sample (hazard ratio [HR] 4.90; confidence interval [CI] 1.05-22.92). This finding remained when only patients with a first psychotic episode (p = 0.02) and patients in the individual treatment condition (p = 0.001) were examined. Cannabis abuse was the major predictor of relapse in patients with high-EE families (HR 4.27; CI 1.12-16.29)

We sought to examine the relation between cannabis abuse and the symptomatic course of recent-onset schizophrenia and related disorders. A prospective cohort study over a year using monthly Brief Psychiatric Rating Scale assessments. Cannabis-abusing patients (n = 24) were compared with nonabusers (n = 69). Eleven patients were mild and 13 were heavy cannabis-abusing patients. Significantly more and earlier psychotic relapses occurred in the cannabis-abusing group (P = .03). This association became stronger when mild and heavy cannabis abuse were distinguished (P = .002). No confounding effect of other variables, eg, other street drugs, was found. In all but one patient, cannabis abuse preceded the onset of the first psychotic symptoms for at least 1 year. Cannabis abuse and particularly heavy abuse can be considered a stressor eliciting relapse in patients with schizophrenia and related disorders and possibly a premorbid precipitant

Sixty-five patients with recent-onset schizophrenia were assessed with two widely used symptom scales, the Brief Psychiatric Rating Scale-Expanded (BPRS-E) and the Psychiatric Assessment Scale (Manchester scale). Principal components analysis of the BPRS-E scores yielded a four-dimensional structure: positive symptoms, negative symptoms, disorganization, and depression. With the Psychiatric Assessment Scale, three dimensions were found: the positive symptoms (delusions, hallucinations) and disorganization (incoherence) appeared in one dimension. A categorical analysis resulted in predominantly positive, negative, and disorganized clusters, but more than half of the sample could not be allocated to any of these groups

The déjà vu experience is a common phenomenon, occurring in pathological as well as nonpathological conditions. It has been defined as any subjectively inappropriate impression of familiarity of a present experience with an undefined past. The authors discuss the epidemiologic data, clinical features, and etiology of the phenomenon of déjà vu. They also review the different hypotheses on the psychopathogenesis of the déjà vu experience and introduce an explanation based on the hologram as a mnestic model

This is the submitted version of a work that was accepted for publication in: The Lancet Psychiatry. A definitive version was subsequently published in The Lancet Psychiatry 2.11 (2015), DOI: 10.1016/S2215-0366(15)00332-6, Mental and brain disorders represent the greatest health burden to Europe—not only for directly affected individuals, but also for their caregivers and the wider society. They incur substantial economic costs through direct (and indirect) health-care and welfare spending, and via productivity losses, all of which substantially affect European development. Funding for research to mitigate these effects lags far behind the cost of mental and brain disorders to society. Here, we describe a comprehensive, coordinated mental health research agenda for Europe and worldwide. This agenda was based on systematic reviews of published work and consensus decision making by multidisciplinary scientific experts and affected stakeholders (more than 1000 in total): individuals with mental health problems and their families, health-care workers, policy makers, and funders. We generated six priorities that will, over the next 5–10 years, help to close the biggest gaps in mental health research in Europe, and in turn overcome the substantial challenges caused by mental disorders, The research leading to these results has received funding from the European Commission’s Seventh Framework Programme (FP7, 2007–13) under grant agreement number 282586, and from the National R&D Internationalisation Programme of the Spanish Ministry of Science and Technology under Reference ACI-PRO-2011- 1080. TW and GT acknowledge financial support from the UK National Institute for Health Research (NIHR) Biomedical Research Centre and Dementia Unit awarded to South London and Maudsley National Health Service (NHS) Foundation Trust in partnership with King’s College London. GT is supported by the NIHR Collaboration for Leadership in Applied Health Research and Care South London at King’s College London Foundation Trust. TW is supported by an NIHR Senior Investigator Award.

Despite the high impact of mental disorders in society, European mental health research is at a critical situation with a relatively low level of funding, and few advances been achieved during the last decade. The development of coordinated research policies and integrated research networks in mental health is lagging behind other disciplines in Europe, resulting in lower degree of cooperation and scientific impact. To reduce more efficiently the burden of mental disorders in Europe, a concerted new research agenda is necessary. The ROAMER (Roadmap for Mental Health Research in Europe) project, funded under the European Commission's Seventh Framework Programme, aims to develop a comprehensive and integrated mental health research agenda within the perspective of the European Union (EU) Horizon 2020 programme, with a translational goal, covering basic, clinical and public health research. ROAMER covers six major domains: infrastructures and capacity building, biomedicine, psychological research and treatments, social and economic issues, public health and well-being. Within each of them, state-of-the-art and strength, weakness and gap analyses were conducted before building consensus on future research priorities. The process is inclusive and participatory, incorporating a wide diversity of European expert researchers as well as the views of service users, carers, professionals and policy and funding institutions.