Increased Risk Of Psychosis Research Articles

Age-at-migration, ethnicity and psychosis risk: Findings from the EU-GEI case-control study

Several studies have highlighted increased psychosis risk in migrant and minority ethnic populations. Migration before age 18 appears to increase risk, but further evidence is required. We investigated this issue in a European case-control study. We hypothesized that migration during two key socio-developmental periods, childhood and adolescence, would be most strongly associated with increased odds of psychosis, and that this would be more pronounced for racialised minorities. We used data from five countries in the EUropean network of national schizophrenia networks studying Gene-Environment Interactions [EU-GEI] study. We examined the association between migration in infancy (0–4 years), childhood (5–10 years), adolescence (11–17 years) or adulthood (18+ years) and first episode psychotic disorder. We fitted unadjusted and adjusted logistic regression models to estimate odds ratios [OR] and 95% confidence intervals [95%CI] for associations between age-at-migration and psychosis. In stratified models, we also examined whether these associations varied by ethnicity. The sample consisted of 937 cases and 1,195 controls. Migration at all ages, including infancy (OR: 2.03, 95%CI: 1.01–4.10), childhood (OR: 2.07, 95%CI: 1.04–4.14), adolescence (OR: 3.26, 95%CI: 1.89–5.63) and adulthood (OR: 1.71, 95%CI: 1.21–2.41), was associated with increased odds of psychosis compared with the white majority non-migrant group, after adjustment for all confounders except ethnoracial identity. After additional adjustment for ethnoracial identity, only migration during adolescence remained associated with psychosis (OR 1.94, 95%CI: 1.11–3.36). In stratified analyses, migration during adolescence was associated with increased odds of psychosis in Black (OR: 6.52, 95%CI: 3.00–14.20) and North African (OR: 16.43, 95%CI: 1.88–143.51) groups.Migration during adolescence increased psychosis risk, particularly in racially minoritised young people. This suggests that development of interventions for minoritised young migrants that alleviate stressors associated with migration and acculturation are warranted.

Altered neurobehavioral reward response predicts psychotic-like experiences in youth exposed to cannabis prenatally.

Rates of prenatal cannabis exposure (PCE) are rising with increasingly permissive legislation regarding cannabis use, which may be a risk factor for psychosis. Disrupted reward-related neural circuitry may underlie this relationship. To elucidate neural mechanisms involved in the association between PCE and youth-onset psychotic-like experiences by probing correlates of reward anticipation, a neurobehavioral marker of endocannabinoid-mediated dopaminergic function. This longitudinal, prospective study analyzed task-related functional neuroimaging data from baseline (n=11,368), 2-year follow-up (n=7,928), and 4-year follow-up (n=2,982) of the ongoing Adolescent Brain and Cognitive Development (ABCD) Study, which recruited children aged 9 to 10 years old at baseline from 22 sites across the United States. PCE (n=652 exposed youth) is longitudinally associated with psychotic-like experiences. Blunted neural response to reward anticipation is associated with psychotic-like experiences, with stronger effects observed in PCE youth (all |β| > 0.5; false discovery rate [FDR]-corrected P < .05). This hypoactivation at baseline predicts psychosis symptomatology in middle adolescence (4-year follow-up visit; β=-.004; FDR-corrected P < .05). Dampened behavioral reward sensitivity is associated with psychotic-like experiences across baseline, 2-year follow-up visit, and 4-year follow-up visit (|β| = .21; FDR-corrected P < .001). Psychotic-like experiences are positively associated with trait-level measures of reward motivation and impulsivity, with stronger effects for PCE youth (all |β| > 0.1; all FDR-corrected P < .05). Blunted activation in reward-related brain regions may serve as a biomarker for disrupted reward processing and increased psychosis risk during development. PCE may affect childhood behaviors and traits related to altered reward sensitivity.

The contribution of cannabis use to the increased psychosis risk among minority ethnic groups in Europe.

We examined whether cannabis use contributes to the increased risk of psychotic disorder for non-western minorities in Europe. We used data from the EU-GEI study (collected at sites in Spain, Italy, France, the United Kingdom, and the Netherlands) on 825 first-episode patients and 1026 controls. We estimated the odds ratio (OR) of psychotic disorder for several groups of migrants compared with the local reference population, without and with adjustment for measures of cannabis use. The OR of psychotic disorder for non-western minorities, adjusted for age, sex, and recruitment area, was 1.80 (95% CI 1.39-2.33). Further adjustment of this OR for frequency of cannabis use had a minimal effect: OR = 1.81 (95% CI 1.38-2.37). The same applied to adjustment for frequency of use of high-potency cannabis. Likewise, adjustments of ORs for most sub-groups of non-western countries had a minimal effect. There were two exceptions. For the Black Caribbean group in London, after adjustment for frequency of use of high-potency cannabis the OR decreased from 2.45 (95% CI 1.25-4.79) to 1.61 (95% CI 0.74-3.51). Similarly, the OR for Surinamese and Dutch Antillean individuals in Amsterdam decreased after adjustment for daily use: from 2.57 (95% CI 1.07-6.15) to 1.67 (95% CI 0.62-4.53). The contribution of cannabis use to the excess risk of psychotic disorder for non-western minorities was small. However, some evidence of an effect was found for people of Black Caribbean heritage in London and for those of Surinamese and Dutch Antillean heritage in Amsterdam.

Reduced amplitude and slowed latency of the acoustic startle response in adolescents and adults with 22q11.2 deletion syndrome

Background22q11.2 deletion syndrome (22q11DS) is one of the most robust genetic predictors of psychosis and other psychiatric illnesses. In this study, we examined 22q11DS subjects' acoustic startle responses (ASRs), which putatively index psychosis risk. Latency of the ASR is a presumptive marker of neural processing speed and is prolonged (slower) in schizophrenia. ASR measures correlate with increased psychosis risk, depend on glutamate and dopamine receptor signaling, and could serve as translational biomarkers in interventions for groups at high psychosis risk. MethodsStartle magnitude, latency, and prepulse inhibition were assessed with a standard acoustic startle paradigm in 31 individuals with 22q11.2DS and 32 healthy comparison (HC) subjects. Surface electrodes placed on participants' orbicularis oculi recorded the electromyographic signal in ASR eyeblinks. Individuals without measurable startle blinks in the initial habituation block were classified as non-startlers. ResultsAcross the startle session, the ASR magnitude was significantly lower in 22q11DS subjects than HCs because a significantly higher proportion of 22q11DS subjects were non-startlers. Latency of the ASR to pulse-alone stimuli was significantly slower in 22q11DS than HC subjects. Due to the overall lower 22q11DS startle response frequency and magnitudes prepulse inhibition could not be analyzed. ConclusionsReduced magnitude and slow latency of 22q11DS subjects' responses suggest reduced central nervous system and neuronal responsiveness. These findings are consistent with significant cognitive impairments observed in 22q11DS subjects. Further research is needed to untangle the connections among basic neurotransmission dysfunction, psychophysiological responsiveness, and cognitive impairment.

Life narratives of individuals with psychosis in ethnic minority and migrant communities in Canada and the Netherlands

AbstractBackground Increased psychosis risk has long been reported for some migrant and ethnic minority populations, a finding has been replicated in different parts of the world, with risk seeming to persist for further generations. Several explanations such as genetic liability or selective migration, higher cannabis-use or higher exposure to neurodevelopmental risk factors were considered unlikely explanations. Rather, exposure to adversity experiences found to be a determinant of psychotic disorders, such as parental separation, social and economic disadvantage, discrimination, social exclusion and marginalization. Additionally, migrants often live in cities, where high population density, low social cohesion and social fragmentation and deprivation, combined with lack of green space and urban stress increase the psychosis risk. Although previous research work has emphasized the quantitative exploration of social-environmental determinants of psychosis, qualitative studies allow for the generation of innovative, rich and nuanced understandings about a given phenomenon, being an ideal approach in face of complex social dynamics and contexts. Concretely, the associations are established, however, the underlying mechanisms and experiences remain largely unknown. This study aims to address several research gaps identified in research on the issues of psychosis, socio-environmental determinants of mental health, migration and ethnicity, and inequalities by exploring the life narratives and experiences of service-users with first psychosis with distinct ethnic, racial and migrant backgrounds.Methods Participants aged between 18 and 35 years old, who have been diagnosed with a first psychosis are recruited in Montreal, Canada, and in the Netherlands. The aim is to recruit at least 20-25 individuals from each site, but recruitment is still ongoing. Qualitative interviews of about an hour are being held, and transcripts will be analyzed with Nvivo, software for qualitative data. Categories and clusters will be formed from the narratives, resulting in common themes that are important to the patients, in their understanding of the development of their psychosis, and the help they have received.ResultsPreliminary data show that the patients have predominantly African or (Eastern)European background, moved around a lot, and experiences inequities. Help and care were not always available for them, not always beneficial. Participants experiences a lot of isolation and deplacement, together with socio-economic disadvantages. Common themes as to by which mechanisms these aspects play a role will further be explored.DiscussionThese findings will be discussed in light of the quantitative data already existing. Implications for prevention and interventions will be discussed.Disclosure of InterestNone Declared

Disparities in Psychosis Risk Symptoms for New Zealand Māori May Be Explained by Systemic Stressors and Inappropriate Conceptualization of Culturally Normative Experiences.

Māori, the indigenous peoples of New Zealand, experience increased rates of psychotic disorders and first-episode psychosis. However, it is unclear whether they also present with increased psychosis risk symptoms, such as subclinical psychotic-like experiences (PLEs). Measurement of risk symptoms is key for early intervention. Further, it is unclear if systemic factors such as the increased rates of social adversity and discrimination or cultural biases contribute to this disparity in psychosis rates. This study surveyed 466 18- to 30-year olds in New Zealand, and compared Māori to non-Māori participant responses on the Prodromal Questionnaire Brief, alongside the history of childhood trauma, discrimination, and financial adversity. Māori reported a higher number of PLEs compared to non-Māori-however, this was not associated with increased distress related to these experiences. The increased number of psychosis-like experiences reported by Māori was likely explained by systemic factors such as childhood trauma, discrimination, and financial stress. Māori were more likely to report that the PLEs were positive. Measurement of psychosis risk for Māori is nuanced, and increased scores on these tools may reflect pathologizing potentially normative experiences for Māori, such as spiritual encounters or discrimination, alongside the impact of increased rates of systemic discrimination, trauma, and financial stress.

Racism and the Social Defeat Hypothesis of Psychosis

IntroductionThe social defeat hypothesis of psychosis posits that an outsider status or subordinate position is a common denominator of several psychosis risk factors, leads to elevated striatal dopamine function and thereby to an increased risk for the disorder. The purpose of this paper is to examine whether this hypothesis offers a good explanation for the increased psychosis risk for migrants from developing countries. Method: Review of literature. Results: The outsider status and subordinate position of many migrants from developing countries in Europe, and of Africans in particular, is evident. It is also clear that racism contributes to this situation. An interpretation of racism as psychotogenic is supported by findings of increased risks for other discriminated groups, such as homosexuals, individuals with a low IQ or a hearing impairment. The single study that examined dopamine function in migrants reported indeed elevated stress-induced dopamine release and dopamine synthesis capacity (Egerton et al., 2017). Recently, we examined the time course of the RR of treatment for psychosis for all migrants to the Netherlands (Termorshuizen &amp; Selten, submitted). Contrary to our expectations, the RR for migrants from sub-Saharan Africa was already increased in the year of arrival (RR=2.5; 2.0-3.1), particularly for those aged 10-20 years (RR=6.1; 2.9-12.6). Conclusion: The social defeat hypothesis accords well with a psychotogenic effect of racism, but replications of the dopamine study are needed. The finding of an increased risk for Africans in the year of arrival suggests that racism is not the single cause of their increased risk.DisclosureNo significant relationships.

Childhood Trauma May Increase Risk of Psychosis and Mood Disorder in Genetically High-risk Children and Adolescents by Enhancing the Accumulation of Risk Indicators.

Genetically high-risk children carry indicators of brain dysfunctions that adult patients with schizophrenia or bipolar disorder display. The accumulation of risk indicators would have a higher predictive value of a later transition to psychosis or mood disorder than each individual risk indicator. Since more than 50% of adult patients report having been exposed to childhood trauma, we investigated whether exposure to trauma during childhood was associated with the early accumulation of risk indicators in youths at genetic risk. We first inspected the characteristics of childhood trauma in 200 young offspring (51% male) born to a parent affected by DSM-IV schizophrenia, bipolar disorder, or major depressive disorder. A subsample of 109 offspring (51% male) had measurements on four risk indicators: cognitive impairments, psychotic-like experiences, nonpsychotic nonmood childhood DSM diagnoses, poor global functioning. Trauma was assessed from direct interviews and reviews of lifetime medical and school records of offspring. Trauma was present in 86 of the 200 offspring (43%). The relative risk of accumulating risk indicators in offspring exposed to trauma was 3.33 (95% CI 1.50, 7.36), but more pronounced in males (RR = 4.64, 95% CI 1.71, 12.6) than females (RR = 2.01, 95% CI 0.54, 7.58). Childhood trauma would be related to the accumulation of developmental precursors of major psychiatric disorders and more so in young boys at high genetic risk. Our findings may provide leads for interventions targeting the early mechanisms underlying the established relation between childhood trauma and adult psychiatric disorders.

Methamphetamine use and psychotic symptoms: findings from a New Zealand longitudinal birth cohort.

This study examined the association between methamphetamine use and psychotic symptoms in a New Zealand general population birth cohort (n = 1265 at birth). At age 18, 21, 25, 30, and 35, participants reported on their methamphetamine use and psychotic symptoms in the period since the previous interview. Generalized estimating equations modelled the association between methamphetamine use and psychotic symptoms (percentage reporting any symptom, and number of symptoms per participant). Confounding factors included childhood individual characteristics, family socioeconomic circumstances and family functioning. Long term effects of methamphetamine use on psychotic symptoms were assessed by comparing the incidence of psychotic symptoms at age 30-35 for those with and without a history of methamphetamine use prior to age 30. After adjusting for confounding factors and time-varying covariate factors including concurrent cannabis use, methamphetamine use was associated with a modest increase in psychosis risk over five waves of data (adjusted odds ratio (OR) 1.33, 95% confidence interval (CI) 1.03-1.72 for the percentage measure; and IRR 1.24, 95% CI 1.02-1.50 for the symptom count measure). The increased risk of psychotic symptoms was concentrated among participants who had used at least weekly at any point (adjusted OR 2.85, 95% CI 1.21-6.69). Use of methamphetamine less than weekly was not associated with increased psychosis risk. We found no evidence for a persistent vulnerability to psychosis in the absence of continuing methamphetamine use. Methamphetamine use is associated with increased risk of psychotic symptoms in the general population. Increased risk is chiefly confined to people who ever used regularly (at least weekly), and recently.

M136. PSYCHOSIS POLYRISK SCORE (PPS): IMPROVING DETECTION OF INDIVIDUALS AT-RISK AND PREDICTION OF CLINICAL OUTCOMES

BackgroundPrimary prevention in Clinical High Risk for psychosis (CHR-P) can ameliorate the course of psychotic disorders. Further advancements of knowledge have been slowed by the standstill of the field, which is mostly attributed to its epidemiological weakness. This underlies the limited identification power for at-risk individuals and the relatively modest ability of CHR-P interviews to rule-in a state of risk for psychosis. One potential avenue for improving identification of individuals at risk for psychosis is a Psychosis Polyrisk Score (PPS) integrating genetic and non-genetic risk and protective factors for psychosis. The PPS hinges on recent findings that risk enrichment in CHR-P samples is accounted for by the accumulation of non-genetic factors e.g. parental and sociodemographic risk factors, perinatal risk factors, later risk factors, and antecedents.MethodsA prototype of the PPS has been developed encompassing 26 non-genetic risk and protective factors, utilising Relative Risks (RR) from an umbrella review of risk and protective factors for psychosis onset in the general population. This was combined with prevalence data to ensure positive scores indicated increased psychosis risk and negative scores indicated decreased psychosis risk. To pilot this, patients referred for a CHR-P assessment (n=15) and healthy controls (n=66) were recruited and assessed with the PPS. Additionally, to investigate the range and distribution of these scores in the general population, 10,000,000 permutations were run utilising prevalence data to produce a simulated dataset.ResultsIn the simulated general population data, scores ranged from -15 (least risk, equivalent RR = 0.03) to 39.5 (highest risk, RR = 8912.51). 50% of individuals had an RR < 1 (PPS < 0), 26.7% of individuals had an RR > 3 (PPS > 5), and 2.7% RR > 30 (PPS > 15). Patients referred for a CHR-P assessment had higher PPS scores (median=9, IQR=12.75) than healthy controls (median=-1.75, IQR=8.875). PPS scores in the simulated general population dataset (median=0, IQR=9.5) were similarly lower than patients.DiscussionThe PPS has potential for improving identification of individuals at risk for psychosis. Its distribution in a simulated general population is reflective of expected psychosis risk, with the vast majority of people not being at-risk and very few being at high risk. In addition to supplementing current assessments for CHR-P, this could be implemented at an earlier stage to stratify individuals based on psychosis risk and inform prognoses and clinical decision-making. This promise warrants further research to ascertain its prognostic accuracy and optimal thresholds for clinical intervention.

Examining associations between two different jumping to conclusions scores with positive schizotypy and recent distress

ABSTRACTIntroduction: Jumping to conclusions is associated with delusions. It is unclear whether positive schizotypy, which refers to delusion-like and hallucination-like symptoms, is associated with jumping to conclusions. Relatedly, the relative validity of two jumping to conclusions scores, extreme responding and draws to decision, is unclear, particularly whether extreme responding (responding after one or two draws) reflects the same bias as decreased draws to decision on non-extreme responding trials.Methods: Extreme positive schizotypy individuals with increased psychosis risk (n = 69) and controls (n = 95) completed the Probabilistic Reasoning Task and reported on recent distress, which was previously associated with jumping to conclusions. We calculated extreme responding, draws to decision (number of draws), and draws to decision/non-extreme responding (number of draws on trials with three or more draws).Results: Positive schizotypy was associated with extreme responding, but not draws to decision/non-extreme responding. Furthermore, draws to decision and draws to decision/non-extreme responding were associated with recent distress, whereas extreme responding was not.Conclusion: Positive schizotypy was specifically associated with extreme responding and not draws to decision/non-extreme responding, which suggests that the nature of extreme responding and of draws to decision might be different. This could have relevance for assessing and treating jumping to conclusions.

Assessment and treatment of individuals at high risk for psychosis

SUMMARYEarly detection and specialised early intervention for people at high risk for psychotic disorders have received growing attention in the past few decades, with the aim of delaying or preventing the outbreak of explicit psychotic symptoms and improving functional outcomes. This article summarises criteria for a diagnosis of high psychosis risk, the implications for such a diagnosis and recommendations for treatment.LEARNING OBJECTIVESAfter reading this article you will be able to: •recognise signs and symptoms indicating increased psychosis risk•understand uses and limitations of screening for high psychosis risk, and interpretation of results•recognise evidence-based treatment options for patients at clinical high risk for psychosis.DECLARATION OF INTERESTC.A. has received non-financial support from Sunovion and Lundbeck in the past 36 months.

Family networks during migration and risk of non-affective psychosis: A population-based cohort study

ObjectiveThe determinants of increased psychosis risk among immigrants remain unclear. Given ethnic density may be protective, we investigated whether the presence of immediate family, or “family networks”, at time of immigration was associated with risk of non-affective psychosis. MethodsWe followed a cohort of migrants (n = 838,717) to Sweden, born 1968–1997, from their 14th birthday, or earliest immigration thereafter, until diagnosis of non-affective psychosis (ICD-9/ICD-10), emigration, death, or 2011. Using record linkage, we measured family network as the presence of adult first-degree relatives immigrating with the cohort participant or already residing in Sweden. We used Cox proportional hazards regression to examine whether risk varied between those migrating with family, migrating to join family, or migrating alone. ResultsMigrating with immediate family was associated with increased psychosis risk amongst males compared to males who did not migrate with family (adjusted Hazard Ratio [aHR]: 1.16, 95% CI: 1.00–1.34). Migrating with family did not increase risk among females (aHR: 0.91, 95% CI: 0.78–1.07); similar observations were observed for males who immigrated to join family (aHR: 1.35, 95% CI: 1.21–1.51). In contrast, females who migrated alone were at increased risk compared to females who did not migrate alone (aHR: 1.31, 95% CI: 1.11–1.54). ConclusionFamily networks at the time of immigration were associated with differential patterns of non-affective psychotic disorders for males and females. These results suggest sex-specific differences in the perceived role of family networks during the migration process.

Financial difficulties and psychosis risk in British undergraduate students: a longitudinal analysis

PurposeThe purpose of this paper is to examine whether financial variables impact psychosis risk over time in students.Design/methodology/approachIn total, 408 first-year British undergraduate students completed measures assessing psychosis risk and finances at three time points.FindingsGreater financial difficulties increased psychosis risk cross sectionally both in terms of symptoms and distress. Other financial variables such as student loan amount were not significant. In longitudinal analysis financial difficulties increase psychotic symptoms and distress over time, but there was no impact of psychotic symptoms on later financial difficulties.Research limitations/implicationsThe study used a relatively small and heavily female sample. Future research is needed to confirm the findings.Practical implicationsWhilst amount of debt does not appear to impact psychotic symptoms in students, greater financial difficulties appear to increase the risk of psychosis over time. Professionals working with students should be aware of this potential link.Originality/valueThis is the first time a longitudinal study has examined the effect of finances on psychosis symptoms.

Smokin‘ hot: adolescent smoking and the risk of psychosis

Daily smoking has been associated with a greater risk of psychosis. However, we are still lacking studies to adjust for baseline psychotic experiences and other substance use. We examined associations between daily smoking and psychosis risk in a 15-year follow-up while accounting for these covariates in a prospective sample (N = 6081) from the Northern Finland Birth Cohort 1986. Self-report questionnaires on psychotic experiences (PROD-screen), tobacco smoking and other substance use were completed when the cohort members were 15-16 years old. Tobacco smoking was categorized into three groups (non-smokers, 1-9 cigarettes and ≥10 cigarettes/day). Psychosis diagnoses were obtained from national registers until the age of 30 years. Subjects in heaviest smoking category were at increased risk of subsequent psychosis (unadjusted HR = 3.15; 95% CI 1.94-5.13). When adjusted for baseline psychotic experiences the association persisted (HR = 2.87; 1.76-4.68) and remained significant even after adjustments for multiple known risk factors such as cannabis use, frequent alcohol use, other illicit substance use, parental substance abuse, and psychosis. Furthermore, number of smoked cigarettes increased psychosis risk in a dose-response manner (adjusted OR = 1.05; 1.01-1.08). Heavy tobacco smoking in adolescence was associated with a greater risk for psychosis even after adjustment for confounders.

Amygdala reactivity in ethnic minorities and its relationship to the social environment: an fMRI study.

Ethnic minority individuals have an increased risk of developing a psychotic disorder, particularly if they live in areas of ethnic segregation, or low own group ethnic density. The neurobiological mechanisms underlying this ethnic minority associated risk are unknown. We used functional MRI to investigate neural responses to faces of different ethnicity, in individuals of black ethnicity, and a control group of white British ethnicity individuals. In total 20 individuals of black ethnicity, and 22 individuals of white British ethnicity underwent a 3T MRI scan while viewing faces of black and white ethnicity. Own group ethnic density was calculated from the 2011 census. Neighbourhood segregation was quantified using the Index of Dissimilarity method. At the within-group level, both groups showed greater right amygdala activation to outgroup faces. Between groups, the black ethnicity group showed greater right amygdala activation to white faces, compared to the white ethnicity group. Within the black ethnicity group, individuals living in areas of lower own group ethnic density showed greater right amygdala reactivity to white faces (r = -0.61, p = 0.01). This is the first time an increased amygdala response to white faces has been demonstrated in individuals of black ethnicity. In the black ethnicity group, correlations were observed between amygdala response and neighbourhood variables associated with increased psychosis risk. These results may have relevance for our understanding of the increased rates of paranoia and psychotic disorders in ethnic minority individuals.

Inadequate Weight Gain During Pregnancy May Increase Risk of Psychosis in Offspring

Inadequate Weight Gain During Pregnancy May Increase Risk of Psychosis in Offspring

M60. Examining the Role of Cultural Distance and Psychosocial Disempowerment in Higher Rates of Psychotic Disorders in Ethnic Minority Groups: A Multi-National Case-Control Study

Background: Ethnic minorities have an increased risk of developing psychotic disorders, but the causes remain largely unknown. Theories such as social defeat have been suggested as possible explanatory frameworks, but empirical evidence is lacking. Here, we investigated whether psychosocial disempowerment (a perceived lack of control over one’s life), and cultural distance from the majority ethnic group accounted for the excess psychosis risk in ethnic minority groups. Methods: We used case-control data from the EU-GEI study, a 16-centre case-control study in 6 countries (England, France, the Netherlands, Italy, Spain and Brazil). Within defined epidemiological catchment areas, incidence cases with an OPCRIT-confirmed first episode of ICD-10 psychotic disorder (F10-33) were invited to participate. Population-based controls were sampled via primary care. We created a binary measure of psychosocial disempowerment, using a self-perceived discrimination questionnaire, where participants were asked if they had ever felt unfairly treated in 12 situations. We approximated cultural distance using the linguistic distance of a participant’s primary language from the majority language in each setting, informed by linguistic decision trees. Age and sex were included as confounders. Following multiple imputation to account for missing data we used logistic regression to investigate whether our exposures explained any increased psychosis risk in ethnic minority groups. Results: We recruited 1168 cases and 1498 controls, who were representative of the population at-risk. Ethnic minority status was associated with increased odds of psychotic disorder after controlling for age and sex (OR: 1.66; 95% CI: 1.59–1.73). Inclusion of psychosocial disempowerment and cultural distance in the model did not attenuate risk in ethnic minority groups (OR: 1.63; 95% CI: 1.54–1.72), despite greater exposure to psychosocial disempowerment (OR: 1.54; 95% CI: 1.47–1.62) and cultural distance (OR: 3.99; 95% CI: 3.83–4.17). Both psychosocial disempowerment (OR: 1.16; 95% CI: 1.13–1.19) and cultural distance (OR: 1.17; 95% CI: 1.14–1.22) independently predicted psychosis risk, after control for age, sex and minority status. Conclusion: Ethnic minorities had a higher risk of developing a psychotic disorder. Psychosocial disempowerment and cultural distance did not explain this risk, but had independent additional effects which appeared to follow dose-response relationships. These preliminary analyses suggest the social environment of ethnic minorities might be a significant predictor of psychosis risk, independent of ethnic minority status.

Ethnicity, the amygdala, and the social environment: a neuroimaging study

BackgroundEthnic minorities have greatly increased rates of schizophrenia. The risk is most pronounced when individuals are living in areas with few people of the same ethnicity as them. Amygdala hyperactivity has been linked to paranoid symptoms in psychosis, and increased levels of paranoia have been observed in ethnic minority individuals. White individuals show an increased amygdala response when viewing black faces; however, whether a similar effect is seen in black individuals is not clear. Methods20 individuals of white British ethnicity, and 20 of black ethnicity underwent a 3T MRI scan while viewing faces of black and white ethnicity. Participants were aged 18–45 years, with no history of mental illness. Population density, indices of multiple deprivation, and percentage own-group ethnic density were obtained from the 2011 census. Neighbourhood segregation was quantified with the Index of Dissimilarity method. Ethics approval was granted by the West London National Research Ethics Service Committee. FindingsAt the within-group level, both groups individually showed greater right amygdala activation to the out-group faces (white ethnicity t=2·08, p=0·02; black ethnicity t=2·38, p=0·015). Between groups, the black ethnicity group showed a greater increase in right amygdala activation for the white faces compared with baseline than did the white ethnicity group (t=1·84, p=0·038). Within the black ethnicity group, amygdala reactivity to white faces showed significant correlations with measures of neighbourhood population density (r=0·61, p=0·01), segregation (r=0·71, p=0·003), deprivation (r=0·67, p=0·04), and own-group ethnic density (r=–0·51, p=0·04). InterpretationWe have shown for the first time, to our knowledge, increased amygdala response to white faces in individuals of black ethnicity. Significant correlations were observed between amygdala response and neighbourhood variables associated with increased psychosis risk. This finding has relevance for our understanding of the increased rates of paranoia and psychotic disorders in ethnic minority individuals. Further research in patient populations will help clarify aetiological relevance. FundingNational Institute for Health Research, Medical Research Council, Wellcome Trust.

PHARMACOLOGY OF CANNABINOIDS

The discovery of cannabinoid receptors and endocannabinoid system has led to the potential therapeutic use of cannabis derivatives. Cannabinoids acting through the CB1 receptors modulate the release of other neurotransmitters in central nervous system, whereas the activation of peripheral CB2 receptors results in decreased inflammatory response and increased apoptosis of some tumor cells populations. The cannabinoids have been authorized for chemotherapy-induced nausea and vomiting; stimulation of appetite; to alleviate neuropathic pain and spasticity in multiple sclerosis, and to reduce pain in cancer patients. Efficacy in other diseases and clinical conditions should be proven in ongoing or future clinical trials. Isolation and identification of different cannabinoids from cannabis and synthesis of novel, more selective, derivatives widens their therapeutic potential. However, there are numerous adverse effects reported, especially when cannabinoids formulations with unknown quantitative and qualitative composition are used. Addiction, tolerance, withdrawal symptoms, increased risk of acute myocardial re-infarction, and increased risk of psychosis or worsening of psychosis are the most common adverse effects of cannabinoids. Acute adverse effects e. g. severe central nervous system depression, are more pronounced in children than in adults. Potential cannabinoid medicines should be subject to the same regulations as other potential drugs. Safety and efficacy of any potential drug candidate, regardless whether it is plant-derived or synthesized, should be proven in non-clinical studies and clinical trials, as well as the marketing authorization must be issued by the appropriate drug authority. Patients deserve a quality manufactured product, which always contains the specified amount of "Remedium cardinale."