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The EUGEI project was supported by the European Community's Seventh Framework Program under grant agreement No. HEALTH-F2-2009-241909 (Project EU-GEI). Dr O'Donovan is supported by MRC programme grant (G08005009) and an MRC Centre grant (MR/L010305/1), Henquet, C., Van Os, J., Pries, L.K., Rauschenberg, C., Delespaul, P., Kenis, G., Luykx, J.J., Lin, B.D., Richards, A.L., Akdede, B., Binbay, T., Altlnyazar, V., Yallnçetin, B., Gümüş-Akay, G., Cihan, B., Soygür, H., Ulaş, H., Cankurtaran, E.S., Kaymak, S.U., Mihaljevic, M.M., Petrovic, S.S., Mirjanic, T., Bernardo, M., Mezquida, G., Amoretti, S., Bobes, J., Saiz, P.A., Garciá-Portilla, M.P., Sanjuan, J., Aguilar, E.J., Santos, J.L., Jiménez-López, E., Arrojo, M., Carracedo, A., López, G., González-Penãs, J., Parellada, M., Maric, N.P., Atbaşoelu, C., Ucok, A., Alptekin, K., Saka, M.C., Arango, C., O'Donovan, M., Rutten, B.P.F., Gülöksüz, S.

Δ(9) -Tetrahydrocannabinol, the main psychoactive component of cannabis, exerts its central effects through activation of the cerebral type 1 cannabinoid (CB1 ) receptor. Pre-clinical studies have provided evidence that chronic cannabis exposure is linked to decreased CB1 receptor expression and this is thought to be a component underlying drug tolerance and dependence. In this study, we make first use of the selective high-affinity positron emission tomography (PET) ligand [(18) F]MK-9470 to obtain in vivo measurements of cerebral CB1 receptor availability in 10 chronic cannabis users (age = 26.0 ± 4.1 years). Each patient underwent [(18) F]MK-9470 PET within the first week following the last cannabis consumption. A population of 10 age-matched healthy subjects (age = 23.0 ± 2.9 years) was used as control group. Parametric modified standardized uptake value images, reflecting CB1 receptor availability, were calculated. Statistical parametric mapping and volume-of-interest (VOI) analyses of CB1 receptor availability were performed. Compared with controls, cannabis users showed a global decrease in CB1 receptor availability (-11.7 percent). VOI-based analysis demonstrated that the CB1 receptor decrease was significant in the temporal lobe (-12.7 percent), anterior (-12.6 percent) and posterior cingulate cortex (-13.5 percent) and nucleus accumbens (-11.2 percent). Voxel-based analysis confirmed this decrease and regional pattern in CB1 receptor availability in cannabis users. These findings revealed that chronic cannabis use may alter specific regional CB1 receptor expression through neuroadaptive changes in CB1 receptor availability, opening the way for the examination of specific CB1 -cannabis addiction interactions which may predict future cannabis-related treatment outcome.

Resumen Los estudios epidemiologicos efectuados en la poblacion general han demostrado sistematicamente que el consumo de Cannabis aumenta de modo dependiente de la dosis el riesgo de desarrollar trastornos psicoticos. Aunque los indicios epidemiologicos entre el consumo de Cannabis y las psicosis han obtenido una atencion considerable, apenas se conoce el mecanismo biologico mediante el que esta droga aumenta el riesgo de psicosis. La investigacion en estudios efectuados en animales sugiere que el delta-9-tetrahidrocanabinol (THC, el componente psicoactivo principal del Cannabis ) aumenta los niveles de dopamina en diversas regiones del cerebro, incluido el nucleo estriado y el area prefrontal. Dado que se ha formulado la hipotesis de que la dopamina representa una via final comun decisiva entre la biologia del cerebro y la experiencia real de psicosis, inicialmente prestar atencion a este neurotransmisor podria ser productivo en el examen de los efectos psicotomimeticos del Cannabis . Por consiguiente, en la presente revision se examinan las pruebas concernientes a las interacciones entre el THC, los endocanabinoides y la dopamina en la region tanto cortical como subcortical implicadas en las psicosis, y se consideran los posibles mecanismos por los que una disregulacion de la dopamina inducida por el consumo de Cannabis podria dar lugar a delirios y alucinaciones. Se concluye que podrian emprenderse productivamente estudios adicionales sobre los mecanismos subyacentes que relacionan el consumo de Cannabis y las psicosis desde una perspectiva de una sensibilizacion progresiva del desarrollo, como consecuencia de interacciones genes-ambiente.

Gene–environment interactions involving the catechol-O-methyltransferase Val158Met polymorphism (COMTVal158Met) have been implicated in the causation of psychosis. Evidence from general population studies suggests that Met/Met subjects are sensitive to stress, a trait associated with psychosis. We hypothesized that the Met allele would moderate the effects of stress on negative affect (NA) in controls, and on NA and psychosis in patients with a psychotic disorder. Thirty-one patients with a psychotic disorder and comorbid cannabis misuse and 25 healthy cannabis users were studied with the experience sampling method (ESM), a structured diary technique assessing current context and emotional and psychotic experiences in daily life. A significant interaction between COMTVal158Met genotype and ESM stress in the model of NA was found for patients (interaction χ2 = 7.4, P = 0.02), but not for controls (interaction χ2 = 3.8, P = 0.15). In the model of ESM psychosis, a significant interaction between COMTVal158Met genotype and ESM stress was also apparent (interaction χ2 = 11.6, P

Cannabis has been known for at least 4,000 years to have profound effects on the mind--effects that have provoked dramatically divergent attitudes towards it. Some societies have regarded cannabis as a sacred boon for mankind that offers respite from the tribulations of everyday life, whereas others have demonized it as inevitably leading to 'reefer madness'. The debate between the protagonists and prohibitionists has recently been re-ignited, but unfortunately this debate continues mainly in ignorance of our new understanding of the effects of cannabis on the brain and of studies that have quantified the extent of the risks of long-term use.

Background Cannabis use is common in patients with bipolar disorder, however little is known about cannabis as a risk factor for mania. In order to investigate the association between exposure to cannabis and subsequent development of manic symptoms whilst controlling for psychotic symptoms, a longitudinal population-based study was carried out. Methods 4815 individuals aged 18 to 64 years were interviewed using the Composite International Diagnostic Interview at baseline, 1 year follow up and 3 year follow up, including assessment of substance use, manic symptoms and psychotic symptoms. Results Use of cannabis at baseline increased the risk for manic symptoms during follow-up (adjusted OR 2.70, 95% CI: 1.54, 4.75), adjusted for age, sex, educational level, ethnicity, single marital status, neuroticism, use of other drugs, use of alcohol, depressive symptoms and manic symptoms at baseline. The association between cannabis use and mania was independent of the prevalence and the incidence of psychotic symptoms. There was no evidence for reverse causality, as manic symptoms at baseline did not predict the onset of cannabis use during follow-up (OR = 0.35, 95% CI: 0.03, 3.49). Limitations As 3 years is a relative short period of follow-up, long-term effects of cannabis use on mania outcomes could not be detected. Conclusion The results suggest that cannabis use may affect population expression of manic symptoms (and subsequent risk to develop bipolar disorder [Regeer, E.J., Krabbendam, L., R, DE Graaf, Ten Have, M., Nolen, W.A., Van Os, J., 2006. A prospective study of the transition rates of subthreshold (hypo)mania and depression in the general population. Psychol Med, 1-9.]). These findings may not be due to the emergence of psychotic symptoms or the effects of self-medication.

Victimisation in childhood may be associated with adult psychosis. The current study examined this association in the crucial developmental period of early adolescence and investigated whether (1) unwanted sexual experiences, and (2) being bullied, were associated with non-clinical delusional ideation and hallucinatory experiences in a general population sample of 14 year olds.Data were derived from standard health screenings of the Youth Health Care Divisions of the Municipal Health Services in Maastricht, the Netherlands. A self-report questionnaire was filled out by a total of 1290 adolescents to assess non-clinical psychotic experiences, as well as experiences of being bullied and sexual trauma.Non-clinical psychotic experiences were strongly and independently associated with both bullying (OR=2.9, 95% CI 1.8-4.8) and sexual trauma (OR=4.8, 95% CI 2.3-10.1).The results suggest that reported associations between childhood victimisation and adult psychosis can be understood in a developmental framework of onset of at-risk mental states in early adolescence. In addition, the data suggest that the traumatic experience of being bullied may also feed the cognitive and biological mechanisms underlying formation of psychotic ideation.

Research on the effect of acute stress and high levels of glucocorticoids on memory has largely focused on memory tasks involving the medial temporal lobe (e.g., declarative memory). Less is known, however, about the effects of stress and glucocorticoids on more strategic memory processes regulated by the prefrontal cortex (e.g., source monitoring). In the current study, the authors investigated whether exposure to acute psychosocial stress would result in altered source monitoring performance relative to the performance of a nonstressed control group. To this end, the authors assigned nonsmoking, healthy, young men to either a stress (n = 22) or a control (n = 18) condition, after which the men were given an internal source monitoring test. Results show that relative to control participants, stressed participants made fewer source monitoring errors. This study suggests that stress may have differential effects on memory, depending on whether the memory test is regulated by the prefrontal cortex or the medial temporal lobe.

Observational studies have suggested that psychometric psychosis liability and a functional polymorphism in the catechol-O-methyltransferase (COMT Val(158)Met) gene moderate the psychosis-inducing effect of cannabis. To replicate and extend this finding, a double-blind, placebo-controlled cross-over design was used in which patients with a psychotic disorder (n=30), relatives of patients with a psychotic disorder (n=12), and healthy controls (n=32) were exposed to Delta-9-tetrahydrocannabinol (Delta-9-THC, the principal component of cannabis) or placebo, followed by cognitive assessment and assessment of current psychotic experiences. Previous expression of psychometric psychosis liability was also assessed. Models of current psychotic experiences and cognition were examined with multilevel random regression analyses to assess (i) main effects of genotype and condition, (ii) interactions between condition and genotype, and (iii) three-way interactions between condition, genotype, and psychometric psychosis liability. Carriers of the Val allele were most sensitive to Delta-9-THC-induced psychotic experiences, but this was conditional on prior evidence of psychometric psychosis liability. Delta-9-THC impacted negatively on cognitive measures. Carriers of the Val allele were also more sensitive to Delta-9-THC-induced memory and attention impairments compared to carriers of the Met allele. Experimental effects of Delta-9-THC on cognition and psychosis are moderated by COMT Val(158)Met genotype, but the effects may in part be conditional on the additional presence of pre-existing psychosis liability. The association between cannabis and psychosis may represent higher order gene-environment and gene-gene interactions.

A rapid and sensitive method for the analysis of delta9-tetrahydrocannabinol (THC) in preserved oral fluid was developed and fully validated. Oral fluid was collected with the Intercept, a Food and Drug Administration (FDA) approved sampling device that is used on a large scale in the U.S. for workplace drug testing. The method comprised a simple liquid-liquid extraction with hexane, followed by liquid chromatography-tandem mass spectrometry (LC-MS-MS) analysis. Chromatographic separation was achieved using a XTerra MS C18 column, eluted isocratically with 1 mM ammonium formate-methanol (10:90, v/v). Selectivity of the method was achieved by a combination of retention time, and two precursor-product ion transitions. The use of the liquid-liquid extraction was demonstrated to be highly effective and led to significant decreases in the interferences present in the matrix. Validation of the method was performed using both 100 and 500 MicroL of oral fluid. The method was linear over the range investigated (0.5-100 ng/mL and 0. 1-10 ng/mL when 100 and 500 microL, respectively, of oral fluid were used) with an excellent intra-assay and inter-assay precision (relative standard deviations, RSD

To explore the idea that deficits in source monitoring may underlie positive symptoms of schizophrenia, the current study compared schizophrenic patients' performance (n=15) on an internal source-monitoring task with that of normal controls (n=15). On the basis of a source-monitoring task in which participants had to recall whether they had verbalized answers or merely thought about these answers, overall source monitoring performance, discrimination index, and response bias were calculated. In addition, participants completed cognitive tests and symptomatology questionnaires. Relative to controls, patients had significantly more difficulties with monitoring their own actions and showed a tendency towards misclassifying imagined thoughts as verbalized thoughts. Source-monitoring performance was related to selective attention, but not to other cognitive domains. No relationship was found between source-monitoring and symptomatology. Failures in internal source monitoring are a prominent feature of schizophrenia, and our results suggest that they form a more enduring characteristic of this disorder than has previously been assumed.

Enkele weken na zijn 38ste verjaardag krijgt meneer Dirksen last van neerslachtigheid. Hij klaagt over slaapproblemen, eet veel minder dan normaal en heeft geen interesse meer in zijn grote hobby, het bespelen van de trombone. Eigenlijk ziet meneer Dirksen het leven niet meer zo zitten. Hij komt via de huisarts bij een psychiater terecht. Op basis van dsm-iv-criteria stelt deze een depressie vast. Omdat meneer Dirksen ook over zijn geheugen klaagt, verwijst de psychiater hem naar een klinisch psycholoog met het verzoek om eventuele cognitieve functiestoornissen te objectiveren. Met behulp van een aantal neuropsychologische instrumenten concludeert deze dat er sprake is van stoornissen in het leren en herinneren van verbale informatie, alsmede van een verminderde planning en organisatie van gedrag. Meneer Dirksen krijgt fluoxetine voorgeschreven en wordt na enige maanden wederom naar de klinisch psycholoog verwezen om het effect van de medicatie op zijn cognitief functioneren na te gaan. De psycholoog maakt tijdens dit herhalingsonderzoek van dezelfde instrumenten gebruik als de vorige keer en constateert dat meneer Dirksens prestaties vergeleken met het eerste onderzoek sterk zijn verbeterd. Vooral het geheugen en de planning en organisatie van gedrag zijn vooruitgegaan. Zijn deze verbeterde prestaties echter zonder problemen aan het effect van de therapie toe te schrijven?

BackgroundThe psychometric properties of an online test are not necessarily identical to its paper and pencil original. The aim of this study is to test whether the factor structure of the Community Assessment of Psychic Experiences (CAPE) is measurement invariant with respect to online vs. paper and pencil assessment.MethodThe factor structure of CAPE items assessed by paper and pencil (N = 796) was compared with the factor structure of CAPE items assessed by the Internet (N = 21,590) using formal tests for Measurement Invariance (MI). The effect size was calculated by estimating the Signed Item Difference in the Sample (SIDS) index and the Signed Test Difference in the Sample (STDS) for a hypothetical subject who scores 2 standard deviations above average on the latent dimensions.ResultsThe more restricted Metric Invariance model showed a significantly worse fit compared to the less restricted Configural Invariance model (χ(2)(23) = 152.75, pConclusionsOur findings did not support measurement invariance with respect to assessment method. Because of the small effect sizes, the measurement differences between the online assessed CAPE and its paper and pencil original can be neglected without major consequences for research purposes. However, a person with a high vulnerability for psychotic symptoms would score 4.80 points lower on the total scale if the CAPE is assessed online compared to paper and pencil assessment. Therefore, for clinical purposes, one should be cautious with online assessment of the CAPE.

Δ(9) -Tetrahydrocannabinol, the main psychoactive component of cannabis, exerts its central effects through activation of the cerebral type 1 cannabinoid (CB1 ) receptor. Pre-clinical studies have provided evidence that chronic cannabis exposure is linked to decreased CB1 receptor expression and this is thought to be a component underlying drug tolerance and dependence. In this study, we make first use of the selective high-affinity positron emission tomography (PET) ligand [(18) F]MK-9470 to obtain in vivo measurements of cerebral CB1 receptor availability in 10 chronic cannabis users (age = 26.0 ± 4.1 years). Each patient underwent [(18) F]MK-9470 PET within the first week following the last cannabis consumption. A population of 10 age-matched healthy subjects (age = 23.0 ± 2.9 years) was used as control group. Parametric modified standardized uptake value images, reflecting CB1 receptor availability, were calculated. Statistical parametric mapping and volume-of-interest (VOI) analyses of CB1 receptor availability were performed. Compared with controls, cannabis users showed a global decrease in CB1 receptor availability (-11.7 percent). VOI-based analysis demonstrated that the CB1 receptor decrease was significant in the temporal lobe (-12.7 percent), anterior (-12.6 percent) and posterior cingulate cortex (-13.5 percent) and nucleus accumbens (-11.2 percent). Voxel-based analysis confirmed this decrease and regional pattern in CB1 receptor availability in cannabis users. These findings revealed that chronic cannabis use may alter specific regional CB1 receptor expression through neuroadaptive changes in CB1 receptor availability, opening the way for the examination of specific CB1 -cannabis addiction interactions which may predict future cannabis-related treatment outcome.

Background.The potential inclusion of cognitive assessments in the DSM-V and large time-consuming assessments drive a need for short tests of cognitive impairments. We examined the reliability and validity of a brief, 15-minute, version of the Wechsler Adult Intelligence Scale-III (WAIS-III).Methods.The sample consisted of patients diagnosed with schizophrenia (n=75), their siblings without schizophrenia (n=74) and unrelated healthy controls (n=84). A short WAIS-III consists of the Digit Symbol Coding subtest, and every second (or third) item of Block Design, Information, and Arithmetic. Psychometric analyses were implemented using item-response theory (IRT) to determine the best minimal item short version, while maintaining the sensitivity and reliability of the IQ score.Results.The proposed 15-minute WAIS-III gave reliable estimates of the Full Scale IQ (FSIQ) in all three groups in the sample. The 15-minute (select-item) version yielded an overall R of.95 (R-2=.92) and IRT yielded an R of .96 (R-2=.92). All four subtests performed well in differentiating patients, relatives, and healthy controls. Multivariate analysis showed a significant difference in FSIQ-estimate between patients, relatives, and healthy controls, F(2, 202) = 19.00, p

This chapter explores the policy implications of the evidence on cannabis and psychosis for mental health services, health education about the risks of cannabis use, and public policy toward recreational cannabis use. It is useful to compare the strength of the evidence on cannabis and psychosis with that of observational evidence on relationships between adverse health effects and other types of drug use. These comparisons facilitate more consistent, even-handed appraisals of the comparative strengths and weakness of evidence on the adverse effects of different drugs. Providing credible advice to young people on the mental health risks of cannabis use is complicated by the polarized views on the health risks of cannabis expressed in the larger cannabis policy debate. It seems likely that governments in most developed countries will continue to prohibit cannabis use by adults, regardless of whether they do so by imposing criminal or civil penalties for use.

Objective To determine whether use of cannabis in adolescence increases the risk for psychotic outcomes by affecting the incidence and persistence of subclinical expression of psychosis in the general population (that is, expression of psychosis below the level required for a clinical diagnosis). Design Analysis of data from a prospective population based cohort study in Germany (early developmental stages of psychopathology study). Setting Population based cohort study in Germany. Participants 1923 individuals from the general population, aged 14-24 at baseline. Main outcome measure Incidence and persistence of subthreshold psychotic symptoms after use of cannabis in adolescence. Cannabis use and psychotic symptoms were assessed at three time points (baseline, T2 (3.5 years), T3 (8.4 years)) over a 10 year follow-up period with the Munich version of the composite international diagnostic interview (M-CIDI). Results In individuals who had no reported lifetime psychotic symptoms and no reported lifetime cannabis use at baseline, incident cannabis use over the period from baseline to T2 increased the risk of later incident psychotic symptoms over the period from T2 to T3 (adjusted odds ratio 1.9, 95% confidence interval 1.1 to 3.1; P=0.021). Furthermore, continued use of cannabis increased the risk of persistent psychotic symptoms over the period from T2 to T3 (2.2, 1.2 to 4.2; P=0.016). The incidence rate of psychotic symptoms over the period from baseline to T2 was 31% (152) in exposed individuals versus 20% (284) in non-exposed individuals; over the period from T2 to T3 these rates were 14% (108) and 8% (49), respectively. Conclusion Cannabis use is a risk factor for the development of incident psychotic symptoms. Continued cannabis use might increase the risk for psychotic disorder by impacting on the persistence of symptoms.

BackgroundLittle is known about the experiential dynamics of the interaction between cannabis and vulnerability to psychosis.AimsTo examine the effects of cannabis on psychotic symptoms and mood in patients with psychosis and healthy controls.MethodPatients with a psychotic disorder (η = 42) and healthy controls (η = 38) were followed in their daily lives using a structured time-sampling technique.ResultsDaily life cannabis use predicted subsequent increases in positive affect and in patients, but not in controls, decreases in negative affect. In patients, but not in controls, cannabis use predicted increased levels of hallucinatory experiences. Mood-enhancing properties of cannabis were acute, whereas psychosis-inducing effects were sub-acute. There was no direct evidence for self-medication effects in daily life.ConclusionsPatients with psychosis are more sensitive to both the psychosis-inducing and mood-enhancing effects of cannabis. The temporal dissociation between acute rewarding effects and sub-acute toxic influences may be instrumental in explaining the vicious circle of deleterious use in these patients.

Cannabis use is considered a contributory cause of schizophrenia and psychotic illness. However, only a small proportion of cannabis users develop psychosis. This can partly be explained by the amount and duration of the consumption of cannabis and by its strength but also by the age at which individuals are first exposed to cannabis. Genetic factors, in particular, are likely to play a role in the short- and the long-term effects cannabis may have on psychosis outcome. This review will therefore consider the interplay between genes and exposure to cannabis in the development of psychotic symptoms and schizophrenia. Studies using genetic, epidemiological, experimental, and observational techniques will be discussed to investigate gene-environment correlation gene-environment interaction, and higher order interactions within the cannabis-psychosis association. Evidence suggests that mechanisms of gene-environment interaction are likely to underlie the association between cannabis and psychosis. In this respect, multiple variations within multiple genes--rather than single genetic polymorphisms--together with other environmental factors (eg, stress) may interact with cannabis to increase the risk of psychosis. Further research on these higher order interactions is needed to better understand the biological pathway by which cannabis use, in some individuals, may cause psychosis in the short- and long term.

BackgroundExposure to stressful life events increases the risk of developing a psychotic disorder. Moreover, increased reactivity to stress seems to represent part of the vulnerability for psychosis. This study aimed to investigate whether a functional polymorphism in the catechol-O-methyltransferase (COMT Val158Met) gene moderates the psychosis-inducing effects of stress.MethodA semi-experimental stress exposure paradigm was used in a sample of 306 genotyped young men (aged 19–24 years), in whom measures of psychotic symptoms were obtained at recruitment in the Greek army (exposed condition) and again after 18 months of military training (unexposed condition).ResultsStress exposure at army induction was associated with an increased level of psychotic symptoms. In addition, carriers of the COMT Val158Met Val allele were more susceptible to the effect of stress on the psychosis outcome than those with the Met/Met genotype (test for interaction: χ2=5·02, df=1, p=0·025).ConclusionThe COMT Val158Met genotype may moderate the effect of stress on psychotic symptoms.

Background. Research suggests that low-grade psychotic experiences in the general population are a common but transitory developmental phenomenon. Using two independent general population samples, the hypothesis was examined that common, non-clinical developmental expression of psychosis may become abnormally persistent when synergistically combined with developmental exposures that may impact on behavioural and neurotransmitter sensitization such as cannabis, trauma and urbanicity. Method. The amount of synergism was estimated from the additive statistical interaction between baseline cannabis use, childhood trauma and urbanicity on the one hand, and baseline psychotic experiences on the other, in predicting 3-year follow-up psychotic experiences, using data from two large. longitudinal, random population samples from the Netherlands [The Netherlands Mental Health Survey and Incidence Study (NEMESIS)] and Germany [The Early Developmental Stages of Psychopathology (EDSP) study]. Results. The 3-year persistence rates of psychotic experiences were low at 26% in NEMESIS and 31% in EDSP. However, persistence rates were progressively higher with greater baseline number of environmental exposures in predicting follow-up psychotic experiences (chi(2)=6.9, df=1, p=0009 in NEMESIS and chi(2)=4.2, df=1, p=0.04 in EDSP). Between 21% and 83% (NEMESIS) and 29% and 51% (EDSP) of the subjects exposed to both environmental exposures and psychotic experiences at baseline had persistence of psychotic experiences at follow-up because of the synergistic action of the two factors. Conclusion. The findings suggest that environmental risks for psychosis act additively, and that the level of environmental risk combines synergistically with non-clinical developmental expression of psychosis to cause abnormal persistence and, eventually, need for care.

Contains fulltext : 48314.pdf (Publisher’s version ) (Open Access) OBJECTIVE: To investigate the relation between cannabis use and psychotic symptoms in individuals with above average predisposition for psychosis who first used cannabis during adolescence. DESIGN: Analysis of prospective data from a population based sample. Assessment of substance use, predisposition for psychosis, and psychotic symptoms was based on standardised personal interviews at baseline and at follow up four years later. PARTICIPANTS: 2437 young people (aged 14 to 24 years) with and without predisposition for psychosis. MAIN OUTCOME MEASURE: Psychotic symptoms at follow up as a function of cannabis use and predisposition for psychosis at baseline. RESULTS: After adjustment for age, sex, socioeconomic status, urbanicity, childhood trauma, predisposition for psychosis at baseline, and use of other drugs, tobacco, and alcohol, cannabis use at baseline increased the cumulative incidence of psychotic symptoms at follow up four years later (adjusted odds ratio 1.67, 95% confidence interval 1.13 to 2.46). The effect of cannabis use was much stronger in those with any predisposition for psychosis at baseline (23.8% adjusted difference in risk, 95% confidence interval 7.9 to 39.7, P = 0.003) than in those without (5.6%, 0.4 to 10.8, P = 0.033). The risk difference in the "predisposition" group was significantly greater than the risk difference in the "no predisposition" group (test for interaction 18.2%, 1.6 to 34.8, P = 0.032). There was a dose-response relation with increasing frequency of cannabis use. Predisposition for psychosis at baseline did not significantly predict cannabis use four years later (adjusted odds ratio 1.42, 95% confidence interval 0.88 to 2.31). CONCLUSION: Cannabis use moderately increases the risk of psychotic symptoms in young people but has a much stronger effect in those with evidence of predisposition for psychosis.

OBJECTIVE: The hygiene hypothesis suggests that the protective 'siblings effect' against atopic diseases such as atopic dermatitis, allergic asthma and hay fever is a result of recurrent infections during early childhood. A recent study and review have indicated that this protective effect may already arise in utero. Lower n-3 essential fatty acid (EFA) status is associated with increased parity, and EFA status has also been related to atopy. The present study confirms the negative association between parity and neonatal immunoglobulin E (IgE) levels and further unravel the role of perinatal EFA status. METHODOLOGY: In a prospective cohort study in 184 atopic mothers and their neonates, we simultaneously measured serum total IgE and EFA levels in plasma phospholipids, both in the mother at 34-36 weeks of gestation and in the neonate at the age of 1 week. Linear regression analysis was used to estimate the effect of parity on maternal and neonatal IgE and EFA status, and the independent effects of parity and EFA status on IgE, controlling for confounding factors such as maternal age and birth season. RESULTS: Parity was associated with lower neonatal IgE level (P < 0.01), as well as with lower docosahexanoic acid (DHA, 22:6n-3) status of the mother (P = 0.01) but not of the neonate (P > 0.69). In the multivariate analysis, higher parity, higher maternal IgE, lower maternal age and birth in the first 3 months of the year were independently associated with neonatal IgE level. No association was detected between maternal or neonatal EFA status and neonatal IgE. CONCLUSIONS: As neonatal total serum IgE is predictive of later atopy, our results support the hypothesis that the sibling effect in atopy is already being programmed in utero. Our data also confirm earlier findings that DHA status is lower in multiparous women, but this did not confound the relation between parity and neonatal IgE.

The Behavioural Assessment of the Dysexecutive Syndrome (BADS) is a relatively new test battery designed to measure disorders of executive functions. We studied the temporal stability of the BADS in a sample of 22 adult psychiatric patients. All patients were administered the BADS twice with an interval of 3 weeks. Test-retest correlations for the BADS tests ranged from .22 to .85. On the repeat administration, patients obtained higher scores on one test as well as on the total BADS. Our results suggest that the BADS should not be administered on two occasions a few weeks apart.

SummaryA recent study by Morgan and colleagues found that cannabidiol attenuates the acute cognitive effects of delta-9-tetrahydrocannabinol (THC). This is of interest as THC has been associated with the detrimental effects of cannabis on mental health in at-risk users, and the potency of cannabis is increasing across Europe.