Risk Factor For Psychosis Research Articles

Associations between acute and chronic lifetime stressors and psychosis-risk symptoms in individuals with 22q11.2 copy number variants

The 22q11.2 deletion (22q11Del) is among the strongest known genetic risk factors for psychosis. Stress, a known risk factor for psychosis in the general population, has seldom been studied in 22q11Del. We investigated how lifetime stressors related to symptomatic outcomes in patients with 22q11Del. We also explored this association in individuals with 22q11.2 duplications (22q11Dup), which may be potentially protective against psychosis. One hundred individuals (46 with 22q11Del, 30 with 22q11Dup, and 24 healthy controls; Mage = 17.30 years±10.15) were included. Logistic models were used to examine cross-sectional associations between lifetime acute and chronic stressors (severity and count) and the presence (score ⩾3) of positive, negative, and general symptoms, assessed via the Structured Interview for Psychosis-risk Syndromes (SIPS). The 22q11Dup group reported the greatest number and severity of acute lifetime stressors, but did not differ from 22q11Del in chronic stressor count or severity. Lifetime chronic and acute stressors were uniquely associated with positive symptoms in 22q11Del (chronic count: odds ratio [OR] = 2.35, p = 0.02; chronic severity: OR = 1.88, p = 0.03; acute count: OR = 1.78, p = 0.03), but not with negative or general symptoms (ps > 0.05). Findings suggest that stress may play a role in psychotic symptoms in 22q1Del, while the 22q11Dup CNV appears protective against psychotic symptoms despite higher rates of stressors. Interventions that mitigate effects of stressors in 22qDel may reduce the odds of psychosis in this group. Prospective longitudinal research is needed to replicate these findings.

Association between visual impairment and psychosis: A longitudinal study and nested case-control study of adults.

Theories propose that visual impairment might increase the risk of psychosis, and vice versa. We aimed to investigate the relationship between visual impairment and psychosis in the UK Biobank cohort. In a nested case control study of ~116,000 adults, we tested whether a Schizophrenia Spectrum Disorder (SSD) diagnosis as exposure was associated with visual impairment. We also tested longitudinally whether poorer visual acuity, and thinner retinal structures on Optical Coherence Tomography (OCT) scans in 2009 were associated with psychotic experiences in 2016. We adjusted for age, sex, depression and anxiety symptoms; and socioeconomic variables and vascular risk factors where appropriate. We compared complete case with multiple imputation models, designed to reduce bias potentially introduced by missing data. People with visual impairment had greater odds of SSD than controls in multiply imputed data (Adjusted Odds Ratio [AOR] 1.42, 95% Confidence Interval [CI] 1.05-1.93, p=0.021). We also found evidence that poorer visual acuity was associated with psychotic experiences during follow-up (AOR per 0.1 point worse visual acuity score 1.06, 95% CI 1.01-1.11, p=0.020; and 1.04, 95% CI 1.00-1.08, p=0.037 in right and left eye respectively). In complete case data (15% of this cohort) we found no clear association, although confidence intervals included the multiple imputation effect estimates. OCT measures were not associated with psychotic experiences. Our findings highlight the importance of eye care for people with psychotic illnesses. We could not conclude whether visual impairment is a likely causal risk factor for psychosis.

Associations of neurodevelopmental risk factors with psychosis proneness: Findings from a non-clinical sample of young adults

Psychotic disorders often develop as the continuum of subclinical symptoms that include hallucination-like and delusion-like experiences, and are commonly referred to as psychotic-like experiences (PLEs). To date, a number of neurodevelopmental risk factors of psychosis have been detected, yet their mutual interplay remains unknown. Therefore, we aimed to investigate the additive association of childhood trauma history, reading disabilities and symptoms of attention-deficit/hyperactivity disorder (ADHD) with psychosis proneness. A total of 3000 young adults (58.3% females, aged 18–35 years) with a negative history of psychiatric treatment were recruited to the cross-sectional study through computer-assisted web interview. Self-reports were administered to measure childhood trauma history, ADHD symptoms and reading disabilities. Linear regression analyses revealed significant main associations of childhood trauma history and reading disabilities with higher levels of PLEs. There were no significant main associations of ADHD with the level of PLEs. However, the associations of all possible interactions between neurodevelopmental risk factors with the level of PLEs were significant. Our findings suggest that childhood trauma history and reading disabilities may additively increase a risk of psychosis. The present findings bring new implications for early intervention strategies in psychosis and posit the rationale of recording the accumulation of neurodevelopmental vulnerabilities in clinical practice.

Cyst of Septum Pellucidum in mental disorders: Schizophrenia and Mental Retardation: Two case reports

IntroductionA septum pellucidum cyst is defined as a fluid collection between the lateral ventricles whose walls have a lateral curvature and are separated by 10 mm or more . Most of these cysts are benign and their clinical significance should be considered as a neurodevelopmental anomaly that may contribute to neuropsychiatric abnormalities . It is often of incidental finding, of little clinical significance. However, an association between this developmental anomaly and a mental disorder, such as schizophrenia and/or intellectual disability, has been reportedObjectivesThe objective of this study is to discuss the relationship between the septum pellucidum cyst and mental disorders, especially schizophrenia and intellectual disability.MethodsWe report in this study two clinical cases, diagnosed with schizophrenia comorbid with intellectual disability and in whom brain imaging has objectified a cyst of the septum pellucidumResultsmultiple cases reports of patients with Schizophrenia and/or mental retardation revealed, on brain imaging, significant abnormalities in midline brain regions such as Septum Pellucidum. It is suggested that CSP, particularly if large, should be considered a developmental anomaly that may contribute to neuropsychiatric abnormalities.ConclusionsWhether the CSP may serve as a risk factor for psychosis or is only a reflection of neuroanatomical changes in individuals with chronic psychotic disorders remains ambiguous. More studies and case reports will be needed to establish the veritable association of CSP and neuropsychiatric disorders in the future, and perhaps to acknowledge the CSP as an early marker and predictor of psychosis.Disclosure of InterestNone Declared

Increased affective reactivity to daily social stressors is associated with more severe psychotic symptoms in youths with 22q11.2 deletion syndrome.

Increased reactivity to minor stressors is considered a risk factor for psychosis, especially in vulnerable individuals. In the present study, we investigated affective and psychotic stress reactivity as well as its link with psychotic symptoms and psychopathology in youths with 22q11.2 deletion syndrome (22q11DS), a neurogenetic condition associated with a high risk for psychosis. A 6-day ecological momentary assessment protocol was used to assess perceived daily-life stress as well as affective and psychotic reactivity to stress in participants with 22q11DS (n = 38, age = 18.4) and healthy controls (HC; n = 53, age = 19.1). Psychotic symptoms, general psychopathology, and coping strategies were also assessed through clinical interviews and questionnaires. Participants with 22q11DS reported higher levels of perceived social stress (b = 0.21, p = 0.036) but lower levels of activity-related stress (b = -0.31, p = 0.003) in their daily lives compared to HC. The groups did not differ in affective or psychotic reactivity to stress, but individuals with 22q11DS who reported increased affective reactivity to social stressors showed more severe positive psychotic symptoms (rs = 0.505, p = 0.008). Finally, avoidance coping strategies moderated the association between stress and negative affects. Our results suggest an increased vulnerability for daily social stress in youths with 22q11DS, and link elevated social stress reactivity to heightened psychotic symptom severity. Given the high risk for psychosis in 22q11DS, interventions should focus on reducing social stress and developing adaptive coping strategies.

Risk of violent behaviour in young people at clinical high risk for psychosis from the North American Prodrome Longitudinal Studies consortium.

Although violent behaviour has been studied in schizophrenia, violence risk has received little attention in individuals at clinical high risk for psychosis (CHR). This manuscript aims to report and discuss the overall results of the Structured Assessment for Violence Risk in Youth (SAVRY) from the NAPLS-3 project to explore the risk of violence in CHR youth and to determine the relationship between SAVRY violence risk scores, psychosis risk symptoms, and global functioning. We hypothesized that CHR young people are at higher risk of violence as compared to healthy comparison participants due to a similarity between risk factors for psychosis and risk factors for violence, and that this risk is associated with greater severity of symptoms, poor functioning, and risk for conversion to psychosis. Participants from the North American Prodrome Longitudinal Study consortium phase 3 (NAPLS-3) included 684 CHR and 96 HC. Assessments included the Structural Assessment of Violence Risk in Youth (SAVRY), clinical and functional measures. The majority of participants across groups were deemed to be at low risk for violence. There were significantly more CHR participants (29.8%) who had moderate or high scores on the SAVRY Summary Risk Rating compared to HC participants (3.1%). Low versus moderate-high SAVRY scores were associated with better social (p < .005) and role (p < .002) functioning and fewer positive (p < .002), negative (p < .002), disorganized (p < .01) and general symptoms (p < .002). CHR participants with higher SAVRY scores were more likely to be diagnosed with borderline personality disorder, ADHD and substance misuse. Among CHR, overall violence risk was not associated with conversion to psychosis. However, those who converted to psychosis scored lower on the protective factors index, primarily driven by less prosocial involvement and fewer resilient personality traits. This is the first study to assess violence risk in CHR adolescents. Violence risk factors overlap with risk factors for psychosis in general, perhaps accounting for the association. These findings have implications for intervention efforts to reduce violence risk and bolster resiliency in CHR youth.

History of trauma is a critical treatment target for individuals at clinical high-risk for psychosis.

People meeting criteria for a clinical high-risk (CHR) for psychosis syndrome frequently represent a heterogeneous, help-seeking, and dynamic population. Among the numerous symptoms and risk factors for psychosis, exposure to trauma stands out as both highly prevalent and poorly understood. Indeed, while up to 80% of individuals meeting criteria for a CHR syndrome report trauma histories, there is currently limited research dedicated to this specific area. This is particularly problematic as trauma is tied to risk for conversion, leads to a range of clinical issues, and contributes to disability and poor quality of life. Fortunately, recent research in the general population has led to a significant evolution in the way trauma is assessed and understood, and further, some studies have indicated that targeted trauma interventions in formal psychotic disorders are highly effective. However, direct adoption is challenging as the CHR syndrome holds a number of unique concerns (e.g., clinical heterogeneity, developmental trauma), and characteristically, involves a developing pediatric or young adult population that also comes with specific considerations (e.g., living with caregivers, transitionary period in roles). In this "perspective" we frame the issues around understanding trauma in CHR individuals, discuss viable treatments and unique considerations, and provide suggestions for future steps in developing and incorporating trauma-focused interventions in this population.

Association between Symptom Dimensions and Psychosis Risk Factors with Functioning in First Episode Psychosis: A Six Months Prospective Study.

This study aims to assess the associations of the severity of different symptom dimensions and psychosis risk factors with the overall functioning levels in first-episode psychosis (FEP) patients over a 6-month follow-up period. Psychosis symptom dimensions (positive, negative, depression, mania, attention and other cognitive), sociodemographic characteristics and environmental risk factors (alcohol-substance use, childhood traumas, current stressful life events) were prospectively assessed in 32 patients who were hospitalized for FEP during the six-month follow-up period. The associations of these variables with the longitudinal Global Assessment of Functioning (GAF) scores of these patients were analyzed using linear regression or repeated measures ANOVA. The severity of positive, negative, depression and mania dimensions reduced (p<0.001) during the follow-up period, while no significant change was found in Stroop interference effect scores (F=0.4, p=0.53). FEP patients with substance or alcohol use had significantly worse functioning during the follow-up period (F=11.2, p=0.001; F=5.3, p=0.02, respectively), and those patients' functioning improved significantly less (F=10.0, p=0.002; F=4.3; p=0.04, respectively). Stroop test performance detected at the first month of the follow-up period significantly predicted the final general functioning scores of the follow-up [Stroop test word reading time (sec): B=-0.58 (-1.13-0.03); color telling speed (sec): B=-0.35 (-0.59-0.1); interference effect: B=-0.28 (-0.57-0.01)]. The stable course and prognostic value of attention and other types of cognitive functioning in FEP patients is remarkable. Interventions for alcohol-substance use in FEP patients should be a part of routine practice.

Influence of glutathione-related genetic variants on the oxidative stress profile of Mexican patients with psychotic disorders.

The clinical trajectories of patients with psychotic disorders have divergent outcomes, which may result in part from glutathione (GSH)-related high-risk genotypes. We aimed to determine pharmacokinetics of clozapine, GSH levels, GSH peroxidase (GPx) activity, gene variants involved in the synthesis and metabolism of GSH, and their association with psychotic disorders in Mexican patients on clozapine monotherapy and controls. The sample included 75 patients with psychotic disorders on clozapine therapy and 40 paired healthy controls. Plasma clozapine/N-desmethylclozapine, GSH concentrations, and GPx activity were determined, along with genotyping of GCLC and GSTP1 variants and copy number variations of GSTP1, GSTT1, and GSTM1. Clinical, molecular and biochemical data were analyzed with a logistic regression model. GSH levels were significantly reduced and, conversely, GPx activity was higher in PD patients compared to controls. GCLC_GAG-7/9 genotype (OR=4.3, CI95=1.40-14.31, p=0.019) and hetero-/homozygous genotypes of GCLC_rs761142 (OR=6.09, CI95=1.93-22.59, p=0.003) were found as risk factors for psychosis. The genetic variants were not related to clozapine/N-desmethylclozapine levels or to metabolic ratio. GCLC variants were associated with the oxidative stress profile of PD patients raising opportunities for intervention to improve their antioxidant defenses. Further studies with larger samples should explore this proposal.

Investigating Specific Associations Between Childhood Victimization Profiles and Positive Psychosis Symptoms: The Mediating Roles of Anxiety, Depression, and Schema.

Childhood trauma is a risk factor for psychosis. It is proposed this is due to traumatic events giving rise to psychological mechanisms that are implicated in the development and maintenance of symptoms. Investigation of the psychological mechanisms accounting for relationships between trauma and psychosis will be assisted by focusing on specific trauma profiles, hallucination modalities, and delusion subtypes. In 171 adults with schizophrenia-spectrum diagnoses and high-conviction delusions, associations between childhood trauma classes, and hallucination and delusion factors, were tested using structural equation models (SEMs). Anxiety, depression, and negative schema were examined as potential mediators of trauma class-psychosis symptom factor links. Significant associations were found between the emotional abuse/neglect and poly-victimization classes with persecutory delusions and delusions of influence, that were all mediated through anxiety (β = 1.24-0.23, P = < .05). There was an association between the physical abuse class and grandiose/religious delusions that was not explained by the mediators (β = 1.86, P = < .05). Trauma class was not significantly associated with any hallucination modality (β = 0.004-1.46, P = > .05). In a sample of people with strongly held delusions, this study demonstrates that childhood victimization is associated with delusions of influence and grandiose beliefs, as well as with persecutory delusions in psychosis. Consistent with previous findings, the potent, mediating role of anxiety supports affective pathway theories and the utility of targeting threat-related processes when treating trauma effects in psychosis.

Phenotypic divergence in sleep and circadian cycles linked by affective state and environmental risk related to psychosis.

Environmental cues influence circadian rhythm timing and neurochemicals involved in the regulation of affective behavior. How this interplay makes them a probable nonspecific risk factor for psychosis is unclear. We aimed to identify the relationship between environmental risk for psychosis and circadian timing phenotypes sampled from the general population. Using an online survey, we devised a cumulative risk exposure score for each of the 1898 survey respondents based on 23 empirically verified transdiagnostic risks for psychosis, three dimensions of affect severity, psychotic-like experiences, and help-seeking behavior. Quantitative phenotyping of sleep and circadian rhythms was undertaken using at-home polysomnography, melatonin and cortisol profiles, and 3-week rest-activity behavior in individuals with a high-risk exposure load (top 15% of survey respondents, n = 22) and low-risk exposure load (bottom 15% of respondents, n = 22). Psychiatric symptoms were present in 100% of the high-load participants and 14% of the low-load participants. Compared to those with a low-load, high-load participants showed a later melatonin phase which was reflected by a greater degree of dispersion in circadian timing. Phase relationships between later circadian melatonin phase and later actigraphic sleep onsets were maintained and these were strongly correlated with self-reported sleep mid-points. No differences were identified from polysomnography during sleep between groups. Distinguishing circadian timing from other sleep phenotypes will allow adaptation for dosage of time-directed intervention, useful in stabilizing circadian timekeeping physiology and potentially reducing the multisystemic disruption in mental health disorders.

Effect of stressful life events on subclinical psychotic symptoms in first-degree relatives and healthy controls

Exposure to Stressful Life Events (SLEs) has been linked to psychosis. However, the combined effect of SLEs and familial risk on subclinical psychotic symptoms over time remains unknown. The objective of the present study was to investigate the effect of SLEs on the level of subclinical psychotic symptoms in individuals with and without familial vulnerability for psychosis. Data were collected from siblings of individuals diagnosed with psychotic disorder and healthy controls at baseline (N = 293) and three years later at follow-up (N = 928). We assessed self-reported and observer-rated subclinical positive, negative, and depressive psychotic symptoms. Participants reported the number of SLEs in the preceding 6 months. A multilevel multivariate regression analysis revealed a positive association between the retrospectively assessed number of SLEs and symptom levels, regardless of vulnerability status (p < .001 for all outcomes). The prospective analysis demonstrated that exposure to SLEs at baseline predicted higher levels of subclinical psychotic symptoms at follow-up. However, after controlling for the level of symptoms at baseline, these associations were no longer significant. Again, the vulnerability status did not modify these results. Nevertheless, siblings in our sample were approximating the end of the critical period for the development of psychotic disorder (mean age at baseline M = 29 and follow-up M = 34). The findings partly support the vulnerability-stress model of psychosis, yet do not confirm the role of familial risk in this association. SLEs may represent a risk factor for psychosis at a population level, thus supporting the continuity of the psychosis spectrum in terms of associated risk factors.

Migrant status, clinical symptoms and functional outcome in youth at clinical high risk for psychosis: findings from the NAPLS-3 study.

Migrant status is a known risk factor for psychosis, but the underlying causes of this vulnerability are poorly understood. Recently, studies have begun to explore whether migrant status predicts transition to psychosis in individuals at clinical high risk (CHR) for psychosis. Results, however, have been inconclusive. The present study assessed the impact of migrant status on clinical symptoms and functional outcome in individuals at CHR for psychosis who took part in the NAPLS-3 study. Participants' migrant status was classified as native-born, first-generation, or second-generation migrant. Clinical symptoms were assessed using the Structured Interview for Psychosis-Risk Syndromes (SIPS); functional outcome was measured using the Global Functioning Scales:Social and Role (GF:S; GF:R). Assessments were conducted at baseline, 12-months, 18-months, and 24-months follow-up. Generalized linear mixed models for repeated measures were used to examine changes over time and differences between groups. The overall sample included 710 individuals at CHR for psychosis (54.2% males; Age: M = 18.19; SD = 4.04). A mixed model analysis was conducted, and no significant differences between groups in symptoms or functioning were observed at any time point. Over time, significant improvement in symptoms and functioning was observed within each group. Transition rates did not differ across groups. We discuss potential factors that might explain the lack of group differences. Overall, migrants are a heterogeneous population. Discerning the impact of migration from that of neighborhood ethnic density, social disadvantage or socio-economic status of different ethnic groups could help better understand vulnerability and resilience to psychosis.

Cumulative Environmental Risk in Early Life: Associations With Schizotypy in Childhood.

Psychotic disorders are associated with a growing number of recognized environmental exposures. Cumulative exposure to multiple environmental risk factors in childhood may contribute to the development of different patterns of schizotypy evident in early life. Hypotheses were that distinct profiles of schizotypy would have differential associations with a cumulative score of environmental risk factors. We prospectively examined the relationship between 19 environmental exposures (which had demonstrated replicated associations with psychosis) measured from the prenatal period through to age 11 years, and 3 profiles of schizotypy in children (mean age = 11.9 years, n = 20 599) that have been established in population data from the New South Wales-Child Development Study. Multinomial logistic regression was used to examine associations between membership in each of 3 schizotypy profiles (true schizotypy, introverted schizotypy, and affective schizotypy) and exposure to a range of 19 environmental risk factors for psychosis (both individually and summed as a cumulative environmental risk score [ERS]), relative to children showing no risk. Almost all environmental factors were associated with at least 1 schizotypy profile. The cumulative ERS was most strongly associated with the true schizotypy profile (OR = 1.61, 95% CI = 1.52-1.70), followed by the affective (OR = 1.33, 95% CI = 1.28-1.38), and introverted (OR = 1.32, 95% CI = 1.28-1.37) schizotypy profiles. Consistent with the cumulative risk hypothesis, results indicate that an increased number of risk exposures is associated with an increased likelihood of membership in the 3 schizotypy profiles identified in middle childhood, relative to children with no schizotypy profile.

Genetic and Geographical Associations With Six Dimensions of Psychotic Experiences in Adolesence.

Large-scale epidemiological and genetic research have shown that psychotic experiences in the community are risk factors for adverse physical and psychiatric outcomes. We investigated the associations of six types of specific psychotic experiences and negative symptoms assessed in mid-adolescence with well-established environmental and genetic risk factors for psychosis. Fourteen polygenic risk scores (PRS) and nine geographical environmental variables from 3590 participants of the Twins Early Development Study (mean age 16) were associated with paranoia, hallucinations, cognitive disorganization, grandiosity, anhedonia, and negative symptoms scales. The predictors were modeled using LASSO regularization separately (Genetic and Environmental models) and jointly (GE model). In joint GE models, we found significant genetic associations of negative symptoms with educational attainment PRS (β = -.07; 95% CI = -0.12 to -0.04); cognitive disorganization with neuroticism PRS (β = .05; 95% CI = 0.03-0.08); paranoia with MDD (β = .07; 95% CI = 0.04-0.1), BMI (β = .05; 95% CI = 0.02-0.08), and neuroticism PRS (β = .05; 95% CI = 0.02-0.08). From the environmental measures only family SES (β = -.07, 95% CI = -0.10 to -0.03) and regional education levels (β = -.06; 95% CI = -0.09 to -0.02) were associated with negative symptoms. Our findings advance understanding of how genetic propensity for psychiatric, cognitive, and anthropometric traits, as well as environmental factors, together play a role in creating vulnerability for specific psychotic experiences and negative symptoms in mid-adolescence.

Potential for prediction of psychosis and bipolar disorder in Child and Adolescent Mental Health Services: a longitudinal register study of all people born in Finland in 1987.

Current strategies to predict psychosis identify only a small proportion of individuals at risk. Additional strategies are needed to increase capacity forpre-diction and prevention of serious mental illness, ideally during childhood and adolescence. One possible approach would be to investigate systems in which psychosis risk factors are concentrated during childhood. One notable such system is represented by Child and Adolescent Mental Health Services (CAMHS). Although psychotic disorders are uncommon in CAMHS, many risk factors for psychosis are highly prevalent in young people who enter this system. We hypothesized, therefore, that youth attending CAMHS would be a high-risk group for psychosis if followed into adulthood and, furthermore, that CAMHS systems would capture a substantial proportion of future psychosis cases. We constructed a total population cohort study of all Finns born in 1987 (N=55,875), linking together extensive register data on health care contacts from birth through age 28years. We identified all individuals diagnosed with a psychotic or bipolar disorder by age 28 (N=1,785). The risk of psychosis/bipolar disorder by age 28years was 1.8% for individuals who had not attended CAMHS during childhood or adolescence, whereas it was 12.8% for those with a history of any outpatient CAMHS contact (odds ratio, OR=7.9, 95% CI: 7.2-8.7). Furthermore, the risk of psychosis/bipolar disorder by age 28years was 2.3% for individuals without a history of inpatient CAMHS admission, whereas it was 24.0% for those with a history of inpatient CAMHS admission (OR=13.3, 95% CI: 11.9-14.9), and 36.5% for those with a history of inpatient CAMHS admission in adolescence (age 13-17years) (OR=24.2, 95% CI: 21.2-27.6). Individuals who attended CAMHS but received no mental disorder diagnosis had an equally high risk of subsequently developing a psychosis/bipolar disorder as individuals who did receive a diagnosis (OR=0.9, 99.5% CI: 0.7-1.1). Compared to other CAMHS attendees, individuals who developed psychosis or bipolar disorder were more likely to have had an initial CAMHS diagnosis of depressive or other mood disorder (OR=2.3, 99.5% CI: 1.6-3.0) and disruptive behaviour disorder (OR=1.7, 99.5% CI: 1.2-2.5). Of all psychosis/bipolar diagnoses by age 28years, 50.2% occurred in individuals who had, at some point in childhood or adolescence, attended CAMHS, indicating that CAMHS represent not only a high-risk but also a high-capacity system for prediction of psychosis/bipolar disorder. These findings suggest an enormous, untapped potential for large-scale psychosis/bipolar disorder prediction and prevention research within existing specialist CAMHS.

Childhood maltreatment mediates the effect of the genetic background on psychosis risk in young adults

Childhood maltreatment (CM) and genetic vulnerability are both risk factors for psychosis, but the relations between them are not fully understood. Guided by the recent identification of genetic risk to CM, this study investigates the hypothesis that genetic risk to schizophrenia also increases the risk of CM and thus impacts psychosis risk. The relationship between schizophrenia polygenetic risk, CM, and psychotic-like experiences (PLE) was investigated in participants from the Utrecht Cannabis Cohort (N = 1262) and replicated in the independent IMAGEN cohort (N = 1740). Schizophrenia polygenic risk score (SZ-PRS) were calculated from the most recent GWAS. The relationship between CM, PRS, and PLE was first investigated using multivariate linear regression. Next, mediation of CM in the pathway linking SZ-PRS and PLE was examined by structural equation modeling, while adjusting for a set of potential mediators including cannabis use, smoking, and neuroticism. In agreement with previous studies, PLE were strongly associated with SZ-PRS (B = 0.190, p = 0.009) and CM (B = 0.575, p < 0.001). Novel was that CM was also significantly associated with SZ-PRS (B = 0.171, p = 0.001), and substantially mediated the effects of SZ-PRS on PLE (proportion mediated = 29.9%, p = 0.001). In the replication cohort, the analyses yielded similar results, confirming equally strong mediation by CM (proportion mediated = 34.7%, p = 0.009). Our results suggest that CM acts as a mediator in the causal pathway linking SZ-PRS and psychosis risk. These findings open new perspectives on the relations between genetic and environmental risks and warrant further studies into potential interventions to reduce psychosis risk in vulnerable people.

Risk factors of psychosis in immigrant population: case report and literature review

IntroductionThere is now compelling evidence that migrant groups in several countries have an elevated risk of developing psychotic disorders.ObjectivesTo identify risk factors for psychosis in immigrant population.Methodscase report and Computerised literature search of MEDLINE and PUBMED and PsycINFO databases was performed using the keywords: immigration, psychosis, schizophrenia.Results Mrs AM is 22 years old, Ivorian, without any personal or family psychiatric history, married and mother of an 11 months old baby. Because of the poor socio-economic conditions, she immigrated illegally to tunisia 3 months ago, accompanied by her husband, leaving her child in her native country. since then, she has been working in cleaning jobs with very low salaries and several conflicts in the workplace, which pushed AMto leave the job. One month before her admission, according to her husband, she became isolated, distrustful, she often watches herself in the mirror, refuses to take a shower, with some bizarre behaviors and persecutory words, then she became aggressive with her husband andneighbors, hence her admission.The interview revealed a dissociative and delusional syndrome, vague and poorly systematized, with hallucinatory and intuitive mechanisms. In view of the subsequent evolution, the diagnosis of schizophrenia was retained. After stabilization under antipsychotic drugs, the patient asked to be repatriated to join her child.Conclusions The evidence is still thin, and there is a clear need for further research to replicate and extend findings linking specific aspects of the social environment and risk of psychosis in migrant groups.DisclosureNo significant relationships.

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.

Sociodemographic characteristics of immigrants hospitalized for first episode of psychosis

Introduction European researchers have observed that psychosis is 3 times more frequent in immigrants than in native-born subjects.Objectivesour study aims to determine the sociodemographic characteristics of immigrants hospitalized for first episode of psychosis (FEP)Methodsit’s is a descriptive retrospective study. 21 files were recruited from the psychiatry department archive. Only files of immigrant patients hospitalized, during the period between 2016 to 2021, for FEP and with neither personal nor family medical history of psychosis were included in our study.Results A total number of 11 patients was included in our study. The analyse of sociodemographic characteristics revealed that; 62.5% of patients were female. The average age was 31 years. About half of them were dark skinned (particularly African), 25% were divorced, and 75% having university level. The majority of cases, have had a clandestine access to Tunisia, and were either unemployed or doing cleaning tasks with a low economic level and frequent conflicts in their workplaces. The average period between entering Tunisia and the onset of symptoms was 11.375 months.ConclusionsA comparative study on a larger sample would be beneficial in order to determine the risk factors for psychosis in immigrants and, consequently, leads to effective preventive measures.DisclosureNo significant relationships.