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Background: During the last decades, an abundance of studies has investigated childhood adversity in relation to psychosis. This systematic review critically examines the methodologies employed to investigate childhood adversity in psychosis over the past decade, including operational definitions, measurement tools and characteristics, and psychometric properties of instruments used in these studies., Study Design: This systematic review followed the PRISMA guidelines (registration number CRD42022307096), and the search used the following electronic databases: PsychINFO, SCOPUS, Web of Science, African Index Medicus (AIM), LILACS, CINAHL, EMBASE, and MEDLINE. The search included variations and combinations of the terms targeting childhood adversity and psychosis., Study Results: Out of 585 identified studies published between 2010 and 2023, 341 employed a validated instrument to investigate childhood adversity. Our findings show "childhood trauma" being the most frequently examined construct, followed by "child maltreatment" or "child abuse." The short version of the Childhood Trauma Questionnaire was the dominant instrument. Physical abuse, emotional abuse, and sexual abuse were most frequently investigated, and indeed the field appears generally to focus on child abuse and neglect over other adversities. Significant psychometric heterogeneity was observed in the selection and summarization of instrument items, with only 59% of studies documenting original psychometric validation and 22% reporting reliability in their datasets., Conclusion: This review highlights substantial methodological heterogeneity in the field, pointing out biases in the research on childhood adversity and psychosis. These findings underline the need for standardized definitions and high-quality measurement tools to enhance the validity of future research in this area., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)

This study investigated if the association between childhood maltreatment and cognition among psychosis patients and community controls was partially accounted for by genetic liability for psychosis. Patients with first-episode psychosis (N = 755) and unaffected controls (N = 1219) from the EU-GEI study were assessed for childhood maltreatment, intelligence quotient (IQ), family history of psychosis (FH), and polygenic risk score for schizophrenia (SZ-PRS). Controlling for FH and SZ-PRS did not attenuate the association between childhood maltreatment and IQ in cases or controls. Findings suggest that these expressions of genetic liability cannot account for the lower levels of cognition found among adults maltreated in childhood., (© 2023. The Author(s).)

A parenting style with high amounts of control combined with low caring or nurturing behaviour has been reported in association with mental disorders including schizophrenia. However, the association of parenting style with illness severity in individuals with schizophrenia has never been evaluated retrospectively or over a longitudinal time course. In a subset (n = 84) of the participants included in the AESOP (Aetiology and Ethnicity in Schizophrenia and Other Psychoses)-10 study, we evaluated participants' perceptions of their own parents' bonding style at the time of their first episode of psychosis using the parental bonding instrument (PBI). We then examined the association between different bonding styles, illness course and severity, and global functioning over a 10-year follow-up. Participants who perceived that their fathers had a more caring and less controlling parenting style showed better functioning at follow-up. However, in contrast to previous research, participants who reported having been subject to uncaring and controlling parenting styles were not found to have a notably worse course of illness or symptom severity over the follow-up period. These results indicate that more optimal parental bonding styles may be associated with better overall functioning in individuals with psychosis but not with other measures of illness outcome., (© 2023. The Author(s).)

Background and Hypothesis: Children exposed to socioenvironmental adversities (eg, urbanicity, pollution, neighborhood deprivation, crime, and family disadvantage) are more likely to subsequently develop subclinical psychotic experiences during adolescence (eg, hearing voices, paranoia). However, the pathways through which this occurs have not been previously investigated. We hypothesized that cognitive ability and inflammation would partly explain this association., Study Design: Data were utilized from the Environmental-Risk Longitudinal Twin Study, a cohort of 2232 children born in 1994-1995 in England and Wales and followed to age 18. Socioenvironmental adversities were measured from birth to age 10 and classified into physical risk (defined by high urbanicity and air pollution) and socioeconomic risk (defined by high neighborhood deprivation, neighborhood disorder, and family disadvantage). Cognitive abilities (overall, crystallized, fluid, and working memory) were assessed at age 12; and inflammatory markers (C-reactive protein, interleukin-6, soluble urokinase plasminogen activator receptor) were measured at age 18 from blood samples. Participants were interviewed at age 18 regarding psychotic experiences., Study Results: Higher physical risk and socioeconomic risk were associated with increased odds of psychotic experiences in adolescence. The largest mediation pathways were from socioeconomic risk via overall cognitive ability and crystallized ability, which accounted for ~11% and ~19% of the association with psychotic experiences, respectively. No statistically significant pathways were found via inflammatory markers in exploratory (partially cross-sectional) analyses., Conclusions: Cognitive ability, especially crystallized ability, may partly explain the association between childhood socioenvironmental adversity and adolescent psychotic experiences. Interventions to support cognitive development among children living in disadvantaged settings could buffer them against developing subclinical psychotic phenomena., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)

A recent suicidal drive hypothesis posits that psychotic experiences (PEs) may serve to externalize internally generated and self-directed threat (i.e., self-injurious/suicidal behavior [SIB]) in order to optimize survival; however, it must first be demonstrated that such internal threat can both precede and inform PEs. The current study conducted the first known bidirectional analysis of SIB and PEs to test whether SIB could be considered as a plausible antecedent for PEs. Prospective data were utilized from the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally representative birth cohort of 2232 twins, that captured SIB (any self-harm or suicidal attempt) and PEs at ages 12 and 18 years. Cross-lagged panel models demonstrated that the association between SIB at age 12 and PEs at age 18 was as strong as the association between PEs at age 12 and SIB at age 18. Indeed, the best representation of the data was a model where these paths were constrained to be equal ( OR = 2.48, 95% CI = 1.63-3.79). Clinical interview case notes for those who reported both SIB and PEs at age 18, revealed that PEs were explicitly characterized by SIB/threat/death-related content for 39% of cases. These findings justify further investigation of the suicidal drive hypothesis.

Background and Hypothesis: Evidence suggests that childhood maltreatment (ie, childhood abuse and childhood neglect) affects educational attainment and cognition. However, the association between childhood maltreatment and Intelligence Quotient (IQ) seems stronger among controls compared to people with psychosis. We hypothesised that: the association between childhood maltreatment and poor cognition would be stronger among community controls than among people with first-episode of psychosis (FEP); compared to abuse, neglect would show stronger associations with educational attainment and cognition; the association between childhood maltreatment and IQ would be partially accounted for by other risk factors; and the association between childhood maltreatment, educational attainment, and IQ would be stronger among patients with affective psychoses compared to those with nonaffective psychoses., Study Design: 829 patients with FEP and 1283 community controls from 16 EU-GEI sites were assessed for child maltreatment, education attainment, and IQ., Study Results: In both the FEP and control group, childhood maltreatment was associated with lower educational attainment. The association between childhood maltreatment and lower IQ was robust to adjustment for confounders only among controls. Whereas childhood neglect was consistently associated with lower attainment and IQ in both groups, childhood abuse was associated with IQ only in controls. Among both patients with affective and nonaffective psychoses, negative associations between childhood maltreatment and educational attainment were observed, but the crude association with IQ was only evident in affective psychoses., Conclusions: Our findings underscore the role of childhood maltreatment in shaping academic outcomes and cognition of people with FEP as well as controls., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: In individuals at clinical high-risk for psychosis, elevated cortisol levels predict subsequent onset of psychotic disorder. However, it is unclear whether cortisol alterations are evident at an earlier clinical stage and promote progression of psychosis expression. This study aimed to address this issue by investigating whether cortisol levels in childhood were associated with the emergence of attenuated psychotic symptoms in early adulthood. In exploratory analyses, we examined whether cortisol and psychosocial stress measures interacted in predicting attenuated psychotic symptoms., Methods: A sample of children (N = 109) enriched for psychosis risk factors were recruited at age 9-12 years and assessed at age 11-14 years (T1) and 17-21 years (T2). Measures of psychopathology, psychosocial stressors, and salivary cortisol were obtained at T1. Attenuated psychotic symptoms were assessed at T2 using the Prodromal Questionnaire., Results: Diurnal cortisol (β = 0.915, 95% CI: 0.062-1.769) and daily stressors (β = 0.379, 95% CI: 0.034-0.723) at T1 were independently associated with total Prodromal Questionnaire scores at T2 after accounting for demographic factors and T1 psychopathology. Exploratory analyses indicated a significant interaction between T1 diurnal cortisol and daily stressors (β = 0.743, 95% CI: 0.081-1.405), with the highest predicted T2 total Prodromal Questionnaire scores occurring when both diurnal cortisol and daily stressors were increased., Conclusions: Our findings suggest that daily stressors and elevations in diurnal cortisol in late childhood/early adolescence increases risk for developing attenuated psychotic symptoms. These findings emphasize the importance of assessing environmental and biological risk factors for psychosis during neurodevelopmentally vulnerable time periods., (Copyright © 2021 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Exposure to victimization in childhood has been linked to the development of psychosis. However, little is known about how childhood victimization is translated into biological risk for psychosis. One possibility is via increased inflammation. This study aimed to investigate the association between childhood victimization, psychotic experiences (PEs) in adolescence and inflammatory markers using data from a general population cohort. Participants were 1,419 British-born children followed from birth to age 18 years as part of the Environmental Risk Longitudinal Twin Study. Childhood victimization was measured prospectively using multiple sources from birth to age 12 years. PEs were assessed during private interviews with participants at age 18 years for the period since age 12. Plasma C-reactive protein (CRP), interleukin-6 (IL-6), and soluble urokinase plasminogen activator receptor (suPAR) levels were measured from plasma samples collected from participants at 18 years. Young people with both PEs and childhood victimization were more likely to belong to a group with elevated suPAR, CRP and IL-6 levels at 18 years of age (OR = 3.34, 95% CI 1.69-6.59, p = 0.001) than those with no childhood victimization and without PEs. However, this association was attenuated when adjusted for other risk factors for elevated inflammation at age 18 (OR = 1.94, 95% CI 0.94-4.04, p = 0.075). In contrast, presence of PEs without childhood victimization was not significantly associated with age-18 inflammatory markers and neither was childhood victimization without PEs (all p's greater than 0.05). The current study highlights that inflammatory dysregulation is mostly present in adolescents reporting PEs who also experienced childhood victimization, though this seemed to be largely due to concurrent inflammation-related risk factors., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: A growing body of research suggests that childhood adversities are associated with later psychosis, broadly defined. However, there remain several gaps and unanswered questions. Most studies are of low-level psychotic experiences and findings cannot necessarily be extrapolated to psychotic disorders. Further, few studies have examined the effects of more fine-grained dimensions of adversity such as type, timing and severity., Aims: Using detailed data from the Childhood Adversity and Psychosis (CAPsy) study, we sought to address these gaps and examine in detail associations between a range of childhood adversities and psychotic disorder., Method: CAPsy is population-based first-episode psychosis case-control study in the UK. In a sample of 374 cases and 301 controls, we collected extensive data on childhood adversities, in particular household discord, various forms of abuse and bullying, and putative confounders, including family history of psychotic disorder, using validated, semi-structured instruments., Results: We found strong evidence that all forms of childhood adversity were associated with around a two- to fourfold increased odds of psychotic disorder and that exposure to multiple adversities was associated with a linear increase in odds. We further found that severe forms of adversity, i.e. involving threat, hostility and violence, were most strongly associated with increased odds of disorder. More tentatively, we found that some adversities (e.g. bullying, sexual abuse) were more strongly associated with psychotic disorder if first occurrence was in adolescence., Conclusions: Our findings extend previous research on childhood adversity and suggest a degree of specificity for severe adversities involving threat, hostility and violence.

Background: Social support has been shown to be associated with a reduced likelihood of developing psychotic experiences in the general population and even amongst those at high risk due to exposure to multiple forms of victimisation (poly-victimised). However, it is unclear whether this association is merely due to the confounding effects of shared environmental and genetic influences, or reverse causality. Therefore, we investigated whether social support has a unique environmentally mediated effect on adolescent psychotic experiences after accounting for familial factors, including genetic factors, and also prior psychopathology., Methods: Participants were from the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally-representative cohort of 2232 UK-born twins. Adolescents were interviewed at age 18 about psychotic experiences and victimisation exposure since age 12, and their perceptions of social support. Prior childhood mental health problems and psychotic symptoms were assessed at age 12. The discordant twin method was used to disentangle the relative family-wide and unique-environmental effects of social support on psychotic experiences in the general population and among poly-victimised adolescents., Results: Perceived social support, particularly from friends, was found to have a unique environmentally mediated buffering effect on adolescent psychotic experiences in the whole sample and in the high-risk poly-victimised group., Conclusions: The protective effects of social support on adolescent psychotic experiences cannot be accounted for by shared environmental or genetic factors, nor by earlier psychopathology. Our findings suggest that early intervention programmes focused on increasing perceptions of social support have the potential to prevent the emergence of psychotic experiences amongst adolescents.

The association between childhood adversity (CA) and psychosis has been extensively investigated in recent years. An increasing body of research has also focused on the mediating or moderating role of biological and psychological mechanisms, as well as other risk factors that might account for the link between CA and psychosis. We conducted a systematic search of the PsychINFO, Embase, Ovid, and Web of Science databases for original articles investigating the role of genetic vulnerabilities, environmental factors, psychological and psychopathological mechanisms in the association between CA and psychosis up to August 2019. We included studies with individuals at different stages of the psychosis continuum, from subclinical psychotic experiences to diagnosed disorders. From the 28 944 records identified, a total of 121 studies were included in this review. Only 26% of the studies identified met the criteria for methodological robustness. Overall, the current evidence suggests that CA may be associated with psychosis largely independently of genetic vulnerabilities. More consistent and robust evidence supports interaction between early and recent adversities, as well as the mediating role of attachment and mood symptoms, which is suggestive of an affective pathway between CA and psychosis across the continuum from subclinical experiences to diagnosable disorder. This review highlighted numerous methodological issues with the existing literature, including selection bias, heterogeneity of measurement instruments utilised, and lack of control for potential confounders. Future research should address these limitations to more accurately estimate mediation and moderation effects on the CA-psychosis association to inform the development of preventive interventions.

Objective: Stressful life events have been implicated in the onset of psychotic disorders, but there are few robust studies. We sought to examine the nature and magnitude of associations between adult life events and difficulties and first-episode psychoses, particularly focusing on contextual characteristics, including threat, intrusiveness, and independence., Method: This study forms part of the Childhood Adversity and Psychosis Study (CAPsy), an epidemiological case-control study in London, United Kingdom. Data on life events and difficulties (problems lasting 4 wk or more) during 1 year prior to onset (cases) or interview (controls) were assessed using the semi-structured Life Events and Difficulties Schedule (LEDS). Data were available on 253 individuals with a first episode of psychosis and 301 population-based controls., Results: We found strong evidence that odds of exposure to threatening and intrusive events in the 1 year prior to onset were substantially higher among cases compared with controls, independent of age, gender, ethnicity, and social class (ORs > 3). This was consistent across diagnostic categories. We found further evidence that the effect of threatening events and difficulties was cumulative (1 event odds ratio [OR] 2.69 [95% confidence interval (CI) 1.51-4.79]; 2 events OR 4.87 [95% CI 2.34-10.16]; ≥3 events OR 5.27 [95% CI 1.83-15.19]; 1 difficulty OR 3.02 [95% CI 1.79-5.09]; 2 difficulties OR 9.71 [95% CI 4.20-22.40]; ≥3 difficulties OR 12.84 [95% CI 3.18-51.85])., Conclusions: Threatening and intrusive life events and difficulties are common in the year pre-onset among individuals with a first episode of psychosis. Such experiences may contribute to the development of psychotic disorders., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)

Background: Psychotic symptoms are common during childhood and adolescence and may indicate transdiagnostic risk of future psychiatric disorders. Lower visual memory ability has been suggested as a potential indicator of future risk of mental illness. The relationship between visual memory and clinician-confirmed definite psychotic symptoms in youth has not yet been explored., Methods: We examined visual memory and psychotic symptoms among 205 participants aged 7-27 years in a cohort enriched for parental mood and psychotic disorders. We assessed visual memory using the Rey Complex Figure Test (RCFT) and psychotic symptoms using validated semi-structured interview measures. We tested the relationship between visual memory and psychotic symptoms using mixed-effects logistic regression., Results: After accounting for age, sex, and family clustering, we found that psychotic symptoms were significantly associated with lower visual memory (OR = 1.80, 95% CI 1.06-3.06, p  = 0.030). This result was unchanged after accounting for general cognitive ability., Conclusion: Lower visual memory performance is associated with psychotic symptoms among youth, regardless of general cognitive ability. This finding may inform future targeted early interventions.

The typical reliance on self-report questionnaires in retrospective case-control studies of childhood abuse and psychotic disorders has been criticised, due to the potential for recall bias associated with, amongst other factors, cognitive impairments and detachment from reality, among individuals with psychosis. One way to establish if any substantial bias may exist is to examine whether the concordance of reports of childhood abuse established from retrospective self-report methods versus more comprehensive interviewer-rated assessments differ between individuals with psychosis and controls. Data from the Childhood Adversity and Psychosis (CAPsy) study were used to examine the accuracy, strength of agreement, and convergent validity of two distinct retrospective measures of childhood abuse: a self-report questionnaire (the Childhood Trauma Questionnaire; CTQ) and a comprehensive interview (the Childhood Experiences of Care and Abuse schedule; CECA). In a sample of 234 cases with first-episode psychosis and 293 controls, we found no strong evidence that the validity of the two measures differed between cases and controls. For reports of sexual and emotional abuse, we found fair levels of agreement between CECA and CTQ ratings in both groups (kappa coefficients 0.43-0.53), moderate to high sensitivity and specificity, and reasonably high convergent validity (tetrachoric correlations of 0.78-0.80). For physical abuse, convergent validity was slightly lower in cases compared with controls. Both measures can be used in future studies to retrospectively assess associations between childhood abuse and psychotic phenomena, but time-permitting, the CECA is preferable as it provides additional important contextual details of abuse exposure., Competing Interests: Declarations of competing interest None., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Childhood psychotic symptoms have been associated with various psychiatric disorders in adulthood but their role as early markers of poor outcomes during the crucial transition to adulthood is largely unknown. Therefore, we investigated associations between age-12 psychotic symptoms and a range of mental health problems and functional outcomes at age 18., Methods: Data were used from the Environmental Risk Longitudinal Twin Study, a nationally representative birth cohort of 2232 twins born in 1994-1995 in England and Wales, followed to age 18 with 93% retention. Childhood psychotic symptoms were assessed in structured interviews at age 12. At age 18, study members' mental health problems, functional outcomes, risky behaviors, and offending were measured using self-reports and official records., Results: Children with psychotic symptoms (N = 125, 5.9%) were more likely to experience a range of mental health problems in young adulthood than children without such symptoms. They were also more likely to be obese, smoke cigarettes, be lonely, be parents, and report a lower quality of life, but not more likely to commit crimes. Childhood psychotic symptoms predicted these poor outcomes over and above other emotional and behavioral problems during childhood. Nevertheless, twin analyses indicated that these associations were largely accounted for by shared family factors., Conclusions: Psychotic symptoms in childhood signal risk for pervasive mental health and functional difficulties in young adulthood and thus may provide a useful screen for an array of later problems. However, early psychotic symptoms and poor outcomes may be manifestations of shared environmental and genetic risks., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)

Aim: Duration of untreated psychosis (DUP) is considered as a key prognostic variable in psychosis. Yet, it is unclear whether a longer DUP causes worse outcomes or whether reported associations have alternative explanations., Methods: Data from 2 cohorts of patients with first episode psychosis were used (n = 2134). Measures of DUP were assessed at baseline and outcomes at 12 months. Regression models were used to investigate the associations between DUP and outcomes. We also investigated whether any associations were replicated using instrumental variables (IV) analysis to reduce the effect of residual confounding and measurement bias., Results: There were associations between DUP per 1-year increase and positive psychotic symptoms (7.0% in symptom score increase 95% confidence interval (CI) 4.0%, 10.0%, P < .001), worse recovery (risk difference [RD] 0.78, 95%, CI 0.68, 0.83, P < .001) and worse global functioning (0.62 decrease in functioning score 95% CI -1.19, -0.04, P = .035). There was no evidence of an association with negative psychotic symptoms (1.0%, 95%, CI -2.0%, 5.0%, P = .455). The IV analysis showed weaker evidence of associations in the same direction between DUP per 1-year increase and positive psychotic symptoms, recovery and global functioning. However, there was evidence of an inverse association with negative psychotic symptoms (decrease of 15.0% in symptom score 95% CI -26.0%, -3.0%, P = .016)., Conclusions: We have confirmed previous findings of a positive association between positive psychotic symptoms, global functioning and recovery and DUP using regression analysis. IV analysis shows some support for these findings. Future investigation using IV analysis should be repeated in large data sets., (© 2018 John Wiley & Sons Australia, Ltd.)

Aim: Negative symptoms (NS) have been associated with poor outcome and remain difficult to treat in patients with psychosis. This study examined the association of NS with clinical features at first presentation to mental health services for psychosis and with outcomes at 1-year follow-up., Methods: Clinical data were utilized from five London Early Intervention Services (EIS) included in the MiData audit database. The sample comprised 484 first-episode psychosis patients with complete Positive and Negative Syndrome Scale data at baseline and 1-year follow-up. Multiple imputation (N = 50) was conducted to account for missing follow-up data., Results: Baseline NS were associated with male gender (B = -1.63, P < .05), younger age at onset (B = -.15, P <. 05), a higher level of impairment on the Global Assessment of Functioning (disability) Scale at baseline (B = -.19, P <. 010), an absence of reported substance misuse prior to baseline assessment (B = -3.05, P <. 001) and unemployment at baseline (B = -.93, P <. 01). At 1-year follow-up, NS at presentation were associated with worse Global Assessment of Functioning Scale for symptom (B = -.28, P < .01) and disability (B = -.27, P <. 05) and with hospital admission (OR = 1.06, P < .01)., Conclusions: Negative symptoms at presentation to EIS were associated with worse functioning at entry and poorer outcomes 1 year later. Future research is required to better understand the aetiology and trajectories of NS in early psychosis and propose novel targeted interventions., (© 2017 John Wiley & Sons Australia, Ltd.)

Importance: Urbanicity is a well-established risk factor for clinical (eg, schizophrenia) and subclinical (eg, hearing voices and paranoia) expressions of psychosis. To our knowledge, no studies have examined the association of air pollution with adolescent psychotic experiences, despite air pollution being a major environmental problem in cities., Objectives: To examine the association between exposure to air pollution and adolescent psychotic experiences and test whether exposure mediates the association between urban residency and adolescent psychotic experiences., Design, Setting, and Participants: The Environmental-Risk Longitudinal Twin Study is a population-based cohort study of 2232 children born during the period from January 1, 1994, through December 4, 1995, in England and Wales and followed up from birth through 18 years of age. The cohort represents the geographic and socioeconomic composition of UK households. Of the original cohort, 2066 (92.6%) participated in assessments at 18 years of age, of whom 2063 (99.9%) provided data on psychotic experiences. Generation of the pollution data was completed on October 4, 2017, and data were analyzed from May 4 to November 21, 2018., Exposures: High-resolution annualized estimates of exposure to 4 air pollutants-nitrogen dioxide (NO2), nitrogen oxides (NOx), and particulate matter with aerodynamic diameters of less than 2.5 (PM2.5) and less than 10 μm (PM10)-were modeled for 2012 and linked to the home addresses of the sample plus 2 commonly visited locations when the participants were 18 years old., Main Outcomes and Measures: At 18 years of age, participants were privately interviewed regarding adolescent psychotic experiences. Urbanicity was estimated using 2011 census data., Results: Among the 2063 participants who provided data on psychotic experiences, sex was evenly distributed (52.5% female). Six hundred twenty-three participants (30.2%) had at least 1 psychotic experience from 12 to 18 years of age. Psychotic experiences were significantly more common among adolescents with the highest (top quartile) level of annual exposure to NO2 (odds ratio [OR], 1.71; 95% CI, 1.28-2.28), NOx (OR, 1.72; 95% CI, 1.30-2.29), and PM2.5 (OR, 1.45; 95% CI, 1.11-1.90). Together NO2 and NOx statistically explained 60% of the association between urbanicity and adolescent psychotic experiences. No evidence of confounding by family socioeconomic status, family psychiatric history, maternal psychosis, childhood psychotic symptoms, adolescent smoking and substance dependence, or neighborhood socioeconomic status, crime, and social conditions occurred., Conclusions and Relevance: In this study, air pollution exposure-particularly NO2 and NOx-was associated with increased odds of adolescent psychotic experiences, which partly explained the association between urban residency and adolescent psychotic experiences. Biological (eg, neuroinflammation) and psychosocial (eg, stress) mechanisms are plausible.

Aim: To investigate the relationship between the presenting clinical and demographic characteristics in first-episode psychosis (FEP) patients with their clinical diagnostic grouping 1 year later., Methods: Data from 1014 first-presentation psychosis patients from seven London-based Early Intervention Services were extracted from the MiData audit database. Associations between clinical and demographic measures at presentation and clinical diagnosis made at 1 year were assessed with analysis of variance (ANOVA) and Chi-square tests., Results: The sample comprised 76% of patients with schizophrenia-spectrum diagnoses, 9% with manic psychoses (MP) and 6% with depressive psychoses. Compared to the other 2 groups, patients who were diagnosed as having MP were younger, with higher education and shorter duration of untreated psychosis, and had higher Young Mania Rating Scale scores at presentation and lower Positive and Negative Syndrome Scale (PANSS) negative scores. Patients diagnosed at 1 year as having depressive psychosis were older and more likely to be white, with the lowest PANSS positive scores at baseline. Patients diagnosed at 1 year as having schizophrenia spectrum diagnoses were more likely to be males. Patients in the 3 diagnostic subgroups of psychosis differed on both clinical and demographic characteristics at presentation., Conclusions: There were significant clinical and demographic differences at presentation between FEP patients who received different clinical diagnoses at 1 year. Future work should determine the extent to which these differences can be used to guide clinical care., (© 2017 John Wiley & Sons Australia, Ltd.)

Background: There is consistent evidence of a cumulative relationship between childhood adversity and psychosis, with number of adversities experienced increasing the probability of psychosis onset. It is possible that genetic factors moderate the association between childhood adversity and psychosis, potentially by influencing how an individual reacts biologically and/or psychologically following exposure to adversity, in such a way as to set them off on the path to psychosis. However, identifying the specific genetic variants involved and how they interact with childhood adversity remains challenging. We examined whether the association between cumulative exposure to childhood adversity and development of psychotic disorder was moderated by the COMT Val 158 Met, AKT1 rs2494732 or DRD2 rs1076560 polymorphisms, known to affect dopamine levels., Methods: Participants were 285 first-presentation psychosis cases and 256 geographically-matched controls drawn from the Genetics and Psychosis (GAP) study. Childhood adversity was assessed using the Childhood Experience of Care and Abuse Questionnaire (CECA.Q) and blood- and cheek-derived genotype data were collected., Results: Our findings revealed no main effect of COMT Val 158 Met, AKT1 rs2494732 and DRD2 rs1076560 polymorphisms on psychosis case status or reports of childhood adversity. Individuals reporting a history of multiple adversities were more likely to be psychosis patients than controls, regardless of their genetic risk. There was no evidence of candidate genotype by childhood adversity interactions in relation to psychosis onset., Conclusion: These findings did not provide evidence of a possible role of COMT Val 158 Met, AKT1 rs2494732 or DRD2 rs1076560 genotypes in modifying the association between childhood adversity and onset of psychosis., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Childhood abuse is highly prevalent in psychosis patients, but whether/how it affects hypothalamic-pituitary-adrenal (HPA) axis at the onset of psychosis remains unclear. We aimed to investigate the effects of severity of childhood abuse on HPA axis activity, in first-episode psychosis (FEP) and healthy controls., Methods: We recruited 169 FEP patients and 133 controls with different degrees of childhood physical and sexual abuse (i.e. no abuse exposure, non-severe abuse exposure, and severe abuse exposure). Saliva samples were collected to measure cortisol awakening response with respect to ground (CARg), increase (CARi) and diurnal (CDD) cortisol levels. Two-way ANOVA analyses were conducted to test the relationships between severity of childhood abuse and psychosis on cortisol levels in individuals with psychosis and healthy controls with and without childhood abuse history., Results: A statistically significant interaction between childhood abuse and psychosis on CARg was found (F (2,262)  = 4.60, p = 0.011, ω 2  = 0.42). Overall, controls showed a U-shaped relationship between abuse exposure and CARg, while patients showed an inverted U-shaped relationship. CARg values were markedly different between patients and controls with either no abuse history or exposure to severe childhood abuse. No significant differences were found when looking at CARi and CDD., Conclusions: Our results show a divergent effect of severe childhood abuse on HPA axis activity in patients with first-episode psychosis and in controls. In the presence of exposure to severe childhood abuse, a blunted CARg and a less reactive HPA axis may represent one of the biological mechanisms involved in the development of psychosis., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Childhood psychotic experiences (PEs), such as seeing or hearing things that others do not, or extreme paranoia, are relatively common with around 1 in 20 children reporting them at age 12. Childhood PEs are often distressing and can be predictive of schizophrenia, other psychiatric disorders, and suicide attempts in adulthood, particularly if they persist during adolescence. Previous research has demonstrated that methylomic signatures in blood could be potential biomarkers of psychotic phenomena. This study explores the association between DNA methylation (DNAm) and the emergence, persistence, and remission of PEs in childhood and adolescence. DNAm profiles were obtained from the ALSPAC cohort at birth, age 7, and age 15/17 (n = 901). PEs were assessed through interviews with participants at ages 12 and 18. We identified PE-associated probes (p < 5 × 10 -5 ) and regions (corrected p < 0.05) at ages 12 and 18. Several of the differentially methylated probes were also associated with the continuity of PEs across adolescence. One probe (cg16459265), detected consistently at multiple timepoints in the study sample, was replicated in an independent sample of twins (n = 1658). Six regions, including those spanning the HLA-DBP2 and GDF7 genes, were consistently differentially methylated at ages 7 and 15-17. Findings from this large, population-based study suggest that DNAm at multiple stages of development may be associated with PEs in late childhood and adolescence, though further replication is required. Research uncovering biomarkers associated with pre-clinical PEs is important as it has the potential to facilitate early identification of individuals at increased risk who could benefit from preventive interventions.

Purpose: To investigate whether social support is protective for psychotic experiences similarly among poly-victimised adolescent girls and boys., Methods: We utilised data from the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally-representative sample of 2232 UK-born twins. Participants were privately interviewed at age 18 about victimisation, psychotic experiences, and social support during adolescence., Results: Perceived social support (overall and from friends) was found to be protective against psychotic experiences amongst poly-victimised adolescent girls, but not boys. Though boys were similarly protected by family support., Conclusions: Social support-focused interventions targeting psychotic phenomena amongst poly-victimised adolescents may be more effective for girls.

Little is known about the impact of different forms of childhood adversity on outcomes in first-episode psychosis (FEP) patients beyond the first year of treatment. We investigated associations between different types of childhood adversity and outcomes of FEP patients over the 5 years following their first contact with mental health services for psychosis. 237 FEP cases aged 18-65 years were followed on average for 5 years after first presentation to psychiatric services in South London, UK. Childhood adversity prior to 17 years of age was assessed at baseline using the Childhood Experience of Care and Abuse Questionnaire (CECA.Q). The results showed that exposure to at least one type of childhood adversity was significantly associated with a lower likelihood of achieving symptomatic remission, longer inpatient stays, and compulsory admission over the 5-year follow-up. There was no evidence though of a dose-response effect. Some specificity was evident. Childhood parental separation was associated with significantly greater likelihood of non-compliance with antipsychotic medications, compulsory admission, and substance dependence. Institutional care was significantly associated with longer total length of inpatient stays; and parental death was significantly associated with compulsory admissions. Clinicians should screen FEP patients for childhood adversity and tailor interventions accordingly to improve outcomes., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Experiencing multiple types of victimization (poly-victimization) during adolescence is associated with the onset of psychotic experiences (such as hearing voices, having visions, or being extremely paranoid). However, many poly-victimized adolescents will not develop such subclinical phenomena and the factors that protect them are unknown. This study investigated whether individual, family, or community-level characteristics were associated with an absence of psychotic experiences amongst poly-victimized adolescents. Participants were from the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally-representative cohort of 2232 UK-born twins. Exposure to seven different types of victimization between ages 12-18 was ascertained using a modified version of the Juvenile Victimization Questionnaire at age 18. Adolescents were also interviewed about psychotic experiences at age 18. Protective factors were measured at ages 12 and 18. We found that exposure to poly-victimization during adolescence was associated with age-18 psychotic experiences (OR = 4.62, 95% CI 3.59-5.94, P < 0.001), but more than a third of the poly-victimized adolescents reported having no psychotic experiences (40.1%). Greater social support was found to be protective against adolescent psychotic experiences even amongst those exposed to poly-victimization. Engaging in physical activity and greater neighborhood social cohesion were also associated with a reduced likelihood of age-18 psychotic experiences in the whole sample, with non-significant trends in the poly-victimized group. Increasing social support and promoting physical activity appear to be important areas for future research into the development of preventive interventions targeting adolescent psychotic experiences. This adds further weight to calls to increase the promotion of these factors on a public health scale., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aim: The early intervention (EI) model appears to improve outcomes of psychosis for younger people, and there is now interest in implementing it in older groups. In the UK, the National Institute of Clinical Excellence advised that EI should be accessible to all individuals with first episode psychosis (FEP). We aimed to explore the likely impact on EI workloads and clinical populations of extending age range., Methods: Data were collected on all patients aged 36-65 years who were referred to an inner London EI service from 2011-2014 using the MiData 2 tool at entry and at 1-year follow up., Results: People aged between 36 and 65 represented 30% of all referrals to the service. There were high levels of recorded past trauma in the sample (62.5%), half had dependent children (58.3%) and just under half physical comorbidity (48.6%). Duration of untreated psychosis was less than a year for the majority. At 1-year follow up, inpatient admission rates were lower than in previously studied younger EI populations, but only 15% experienced a single episode with full remission., Conclusions: These findings indicate that admitting over 35-year-olds to EI results in a substantial increase in workload. A large proportion had become unwell relatively recently, indicating that the concept of EI may not be redundant in this age range. Evidence is needed on EI effectiveness in this group., (© 2016 The Authors Early Intervention in Psychiatry Published by John Wiley & Sons Australia, Ltd.)

Background: Experiencing victimization in early life has been repeatedly shown to be associated with the emergence of psychotic symptoms in childhood. However, most victimized children do not develop psychotic symptoms and why this occurs is not fully understood. This study investigated which individual, family-level, and wider community characteristics were associated with an absence of psychotic symptoms among children at risk for psychosis by virtue of their exposure to multiple victimization experiences (poly-victimization)., Methods: Participants were from the Environmental Risk Longitudinal Twin Study, a nationally representative cohort of 2232 UK-born twins. Exposure to maltreatment, bullying and domestic violence prior to age 12 was determined from interviews with mothers, children, and observations by research workers at ages 5, 7, 10, and 12. Children were interviewed about psychotic symptoms at age 12. Protective factors were measured at ages 5, 7, 10, and 12., Results: Childhood poly-victimization was associated with age-12 psychotic symptoms (OR = 4.61, 95% CI 2.82-7.52), but the majority of poly-victimized children did not report symptoms (80.7%). Having a relatively high IQ, more positive atmosphere at home, and higher levels of neighborhood social cohesion were found to be protective against childhood psychotic symptoms among poly-victimized children and also in the whole sample. However, "protected" poly-victimized children displayed elevated levels of other mental health problems compared to nonvictimized children., Conclusions: Children's characteristics, family context, and the wider community were all found to protect children from developing early psychotic symptoms, even when they were victimized multiple times. These findings indicate targets for multilevel preventive interventions.

Aim: Several studies have suggested that lifetime cannabis consumption and childhood abuse synergistically contribute to the risk for psychotic disorders. This study aimed to extend existing findings regarding an additive interaction between childhood abuse and lifetime cannabis use by investigating the moderating role of type and frequency of cannabis use., Methods: Up to 231 individuals presenting for the first time to mental health services with psychotic disorders and 214 unaffected population controls from South London, United Kingdom, were recruited as part of the Genetics and Psychosis study. Information about history of cannabis use was collected using the Cannabis Experiences Questionnaire. Childhood physical and sexual abuse was assessed using the Childhood Experience of Care and Abuse Questionnaire., Results: Neither lifetime cannabis use nor reported exposure to childhood abuse was associated with psychotic disorder when the other environmental variable was taken into account. Although the combination of the two risk factors raised the odds for psychosis by nearly three times (adjusted OR = 2.94, 95% CI: 1.44-6.02, P = 0.003), no evidence of interaction was found (adjusted OR = 1.46, 95% CI: -0.54 to 3.46, P = 0.152). Furthermore, the association of high-potency cannabis and daily consumption with psychosis was at least partially independent of the effect of childhood abuse., Conclusions: The heavy use of high-potency cannabis increases the risk of psychosis but, in addition, smoking of traditional resin (hash) and less than daily cannabis use may increase the risk for psychosis when combined with exposure to severe childhood abuse., (© 2015 Wiley Publishing Asia Pty Ltd.)

There has been much recent debate concerning the relative clinical utility of symptom dimensions versus conventional diagnostic categories in patients with psychosis. We investigated whether symptom dimensions rated at presentation for first-episode psychosis (FEP) better predicted time to first remission than categorical diagnosis over a four-year follow-up. The sample comprised 193 FEP patients aged 18-65years who presented to psychiatric services in South London, UK, between 2006 and 2010. Psychopathology was assessed at baseline with the Positive and Negative Syndrome Scale and five symptom dimensions were derived using Wallwork/Fortgang's model; baseline diagnoses were grouped using DSM-IV codes. Time to start of first remission was ascertained from clinical records. The Bayesian Information Criterion (BIC) was used to find the best fitting accelerated failure time model of dimensions, diagnoses and time to first remission. Sixty percent of patients remitted over the four years following first presentation to psychiatric services, and the average time to start of first remission was 18.3weeks (SD=26.0, median=8). The positive (BIC=166.26), excited (BIC=167.30) and disorganised/concrete (BIC=168.77) symptom dimensions, and a diagnosis of schizophrenia (BIC=166.91) predicted time to first remission. However, a combination of the DSM-IV diagnosis of schizophrenia with all five symptom dimensions led to the best fitting model (BIC=164.35). Combining categorical diagnosis with symptom dimension scores in FEP patients improved the accuracy of predicting time to first remission. Thus our data suggest that the decision to consign symptom dimensions to an annexe in DSM-5 should be reconsidered at the earliest opportunity., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Little is known about the impact of urbanicity, adverse neighborhood conditions and violent crime victimization on the emergence of adolescent psychotic experiences., Methods: Participants were from the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally-representative cohort of 2232 British twins who were interviewed about adolescent psychotic experiences at age 18. Urbanicity, neighborhood characteristics, and personal victimization by violent crime were measured during childhood and adolescence via geocoded census data, surveys of over 5000 immediate neighbors of the E-Risk participants, and interviews with participants themselves., Results: Adolescents raised in urban vs rural neighborhoods were significantly more likely to have psychotic experiences (OR = 1.67, 95% CI = 1.21-2.30, P = .002). This association remained significant after considering potential confounders including family socioeconomic status, family psychiatric history, and adolescent substance problems (OR = 1.43, 95% CI = 1.01-2.03, P = .042), but became nonsignificant after considering adverse social conditions in urban neighborhoods such as low social cohesion and high neighborhood disorder (OR = 1.35, 95% CI = 0.94-1.92, P = .102). The combined association of adverse neighborhood social conditions and personal crime victimization with adolescent psychotic experiences (adjusted OR = 4.86, 95% CI = 3.28-7.20, P < .001) was substantially greater than for either exposure alone, highlighting a potential interaction between neighborhood conditions and crime victimization (interaction contrast ratio = 1.81, 95% CI = -0.03 to 3.65) that was significant at the P = .054 level., Conclusions: Cumulative effects of adverse neighborhood social conditions and personal victimization by violent crime during upbringing partly explain why adolescents in urban settings are more likely to report psychotic experiences. Early intervention efforts for psychosis could be targeted towards victimized youth living in urban and socially adverse neighborhoods.

Adolescent psychotic experiences increase risk for schizophrenia and other severe psychopathology in adulthood. Converging evidence implicates urban and adverse neighborhood conditions in the etiology of adolescent psychotic experiences, but the role of young people's personal perceptions of disorder (i.e., physical and social signs of threat) in their neighborhood is unknown. This was examined using data from the Environmental Risk Longitudinal Twin Study, a nationally representative birth cohort of 2,232 British twins. Participants were interviewed at age 18 about psychotic phenomena and perceptions of disorder in the neighborhood. Multilevel, longitudinal, and genetically sensitive analyses investigated the association between perceptions of neighborhood disorder and adolescent psychotic experiences. Adolescents who perceived higher levels of neighborhood disorder were significantly more likely to have psychotic experiences, even after accounting for objectively/independently measured levels of crime and disorder, neighborhood- and family-level socioeconomic status, family psychiatric history, adolescent substance and mood problems, and childhood psychotic symptoms: odds ratio = 1.62, 95% confidence interval [1.27, 2.05], p < .001. The phenotypic overlap between adolescent psychotic experiences and perceptions of neighborhood disorder was explained by overlapping common environmental influences, rC = .88, 95% confidence interval [0.26, 1.00]. Findings suggest that early psychological interventions to prevent adolescent psychotic experiences should explore the role of young people's (potentially modifiable) perceptions of threatening neighborhood conditions.

Aim: Men and women have historically been shown to differ in their presentation and outcome of psychotic disorders and thus are likely to have different treatment needs. It is unclear whether Early Intervention Services (EIS) are able to provide equitable care for both men and women presenting for the first time with psychosis. The main aim of this study was to explore gender differences for first-presentation psychosis patients at the time of their referral to inner-city EIS and their outcomes 1 year later., Methods: Audit data were utilized from 1098 first-presentation psychosis patients from seven EIS across London, UK, collected via the computerized MiData package. Binary logistic regression was employed to detect potential associations between gender and (i) initial clinical presentation (including duration of untreated psychosis, pathways to care, risk behaviours); and (ii) 1-year clinical and functional outcomes., Results: At entry to EIS, male patients presented with more violent behaviour whereas female patients had more suicide attempts. Following 1 year of EIS care, men still presented as more violent towards others whereas women were more likely to have been admitted to a psychiatric ward., Conclusion: Gender differences in clinical outcome, service use and risk behaviours were apparent within the first year of specialist psychosis care. This may be partly due to the different pathways to care taken by men and women and differences in clinical presentation. Greater focus on the specific needs of each gender by EIS in detection and intervention is required to improve equality of outcome., (© 2015 Wiley Publishing Asia Pty Ltd.)

Aim: To investigate the clinical and social correlates of a lifetime history of crime victimization among first-episode psychosis patients at entry to an Early Intervention Service and following 18 months of specialist care., Methods: Face-to-face interviews were conducted with 149 individuals who presented to an Early Intervention Service for the first time with psychosis in the London borough of Lambeth, UK. A range of demographic and clinical measures were completed including self-reported history of victimization along with the type of crime and its subjective effect on the patient. Clinical and functional outcomes at 18-month follow up were ascertained from clinical case notes by a psychiatrist., Results: A large proportion of patients (n = 64, 43%) reported a history of crime victimization. This was associated with significantly higher levels of depression and substance misuse at initial presentation. Being a victim of a crime was not significantly associated with poorer clinical or functional outcomes after 18 months of specialist care. However, non-significant differences were found for those who reported crime victimization in terms of their increased use of illegal substances or having assaulted someone else during the follow-up period., Conclusion: Past experience of being a victim of crime appears to be common in patients presenting for the first time with psychosis and is associated with increased likelihood of comorbidity. Thus, Early Intervention Services should consider screening for past victimization and be prepared to deal with comorbid problems. The impact of crime victimization on clinical and functional outcomes requires investigation over a longer period of time., (© 2015 Wiley Publishing Asia Pty Ltd.)

Background: Urban upbringing is associated with a 2-fold adulthood psychosis risk, and this association replicates for childhood psychotic symptoms. No study has investigated whether specific features of urban neighborhoods increase children's risk for psychotic symptoms, despite these early psychotic phenomena elevating risk for schizophrenia and other psychiatric disorders in adulthood., Methods: Analyses were conducted on over 2000 children from the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally-representative cohort of UK-born twins. Neighborhood-level characteristics were assessed for each family via: a geodemographic discriminator indexing neighborhood-level deprivation, postal surveys of over 5000 residents living alongside the children, and in-home interviews with the children's mothers. Children were interviewed about psychotic symptoms at age 12. Analyses were adjusted for important family-level confounders including socioeconomic status (SES), psychiatric history, and maternal psychosis., Results: Urban residency at age-5 (OR = 1.80, 95% CI = 1.16-2.77) and age-12 (OR = 1.76, 95% CI = 1.15-2.69) were both significantly associated with childhood psychotic symptoms, but not with age-12 anxiety, depression, or antisocial behavior. The association was not attributable to family SES, family psychiatric history, or maternal psychosis, each implicated in childhood mental health. Low social cohesion, together with crime victimization in the neighborhood explained nearly a quarter of the association between urbanicity and childhood psychotic symptoms after considering family-level confounders., Conclusions: Low social cohesion and crime victimization in the neighborhood partly explain why children in cities have an elevated risk of developing psychotic symptoms. Greater understanding of the mechanisms leading from neighborhood-level exposures to psychotic symptoms could help target interventions for emerging childhood psychotic symptoms., (© The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)

A history of childhood adversity is associated with psychotic disorder, with an increase in risk according to number or severity of exposures. However, it is not known why only some exposed individuals go on to develop psychosis. One possibility is pre-existing genetic vulnerability. Research on gene-environment interaction in psychosis has primarily focused on candidate genes, although the genetic effects are now known to be polygenic. This pilot study investigated whether the effect of childhood adversity on psychosis is moderated by the polygenic risk score for schizophrenia (PRS). Data were utilised from the Genes and Psychosis (GAP) study set in South London, UK. The GAP sample comprises 285 first-presentation psychosis cases and 256 unaffected controls with information on childhood adversity. We studied only white subjects (80 cases and 110 controls) with PRS data, as the PRS has limited predictive ability in patients of African ancestry. The occurrence of childhood adversity was assessed with the Childhood Experience of Care and Abuse Questionnaire (CECA.Q) and the PRS was based on genome-wide meta-analysis results for schizophrenia from the Psychiatric Genomics Consortium. Higher schizophrenia PRS and childhood adversities each predicted psychosis status. Nevertheless, no evidence was found for interaction as departure from additivity, indicating that the effect of polygenic risk scores on psychosis was not increased in the presence of a history of childhood adversity. These findings are compatible with a multifactorial threshold model in which both genetic liability and exposure to environmental risk contribute independently to the etiology of psychosis., Competing Interests: RMM reports honoraria from Otsuka, Lundbeck, and Janssen, which he received for lecturing on the report of the Schizophrenia Commission. All other authors declare no competing interests. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

While contemporary models of psychosis have proposed a number of putative psychological mechanisms, how these impact on individuals to increase intensity of psychotic experiences in real life, outside the research laboratory, remains unclear. We aimed to investigate whether elevated stress sensitivity, experiences of aberrant novelty and salience, and enhanced anticipation of threat contribute to the development of psychotic experiences in daily life. We used the experience sampling method (ESM) to assess stress, negative affect, aberrant salience, threat anticipation, and psychotic experiences in 51 individuals with first-episode psychosis (FEP), 46 individuals with an at-risk mental state (ARMS) for psychosis, and 53 controls with no personal or family history of psychosis. Linear mixed models were used to account for the multilevel structure of ESM data. In all 3 groups, elevated stress sensitivity, aberrant salience, and enhanced threat anticipation were associated with an increased intensity of psychotic experiences. However, elevated sensitivity to minor stressful events (χ(2)= 6.3,P= 0.044), activities (χ(2)= 6.7,P= 0.036), and areas (χ(2)= 9.4,P= 0.009) and enhanced threat anticipation (χ(2)= 9.3,P= 0.009) were associated with more intense psychotic experiences in FEP individuals than controls. Sensitivity to outsider status (χ(2)= 5.7,P= 0.058) and aberrantly salient experiences (χ(2)= 12.3,P= 0.002) were more strongly associated with psychotic experiences in ARMS individuals than controls. Our findings suggest that stress sensitivity, aberrant salience, and threat anticipation are important psychological processes in the development of psychotic experiences in daily life in the early stages of the disorder., (© The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)

While the role of childhood adversity in increasing the risk of psychosis has been extensively investigated, it is not clear what the impact of early adverse experiences is on the outcomes of psychotic disorders. Therefore, we investigated associations between childhood adversity and 1-year outcomes in 285 first-presentation psychosis patients. Exposure to childhood adversity prior to 17 years of age was assessed using the Childhood Experience of Care and Abuse Questionnaire. Data on illness course, symptom remission, length of psychiatric hospitalization, compliance with medication, employment, and relationship status were extracted from clinical records for the year following first contact with mental health services for psychosis. Seventy-one percent of patients reported exposure to at least 1 type of childhood adversity (physical abuse, sexual abuse, parental separation, parental death, disrupted family arrangements, or being taken into care). No robust associations were found between childhood adversity and illness course or remission. However, childhood physical abuse was associated with almost 3-fold increased odds of not being in a relationship at 1-year follow-up compared to patients who did not report such adverse experiences. There was also evidence of a significant association between parental separation in childhood and longer admissions to psychiatric wards during 1-year follow-up and 2-fold increased odds of noncompliance with medication compared to those not separated from their parents. Therefore, our findings suggest that there may be some specificity in the impact of childhood adversity on service use and social functioning among psychosis patients over the first year following presentation to mental health services., (© The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)

Background: Stimulants, such as methylphenidate, are among the most commonly used medications in children and adolescents. Psychotic symptoms have been reported as rare adverse reactions to stimulants but have not been systematically inquired about in most previous studies. Family history of mental illness may increase the vulnerability to drug-induced psychotic symptoms. We examined the association between stimulant use and psychotic symptoms in sons and daughters of parents with major mood and psychotic disorders., Methods: We assessed psychotic symptoms, psychotic-like experiences, and basic symptoms in 141 children and youth (mean ± SD age: 11.8 ± 4.0 years; range: 6-21 years), who had 1 or both parents with major depressive disorder, bipolar disorder, or schizophrenia, and of whom 24 (17.0%) had taken stimulant medication., Results: Psychotic symptoms were present in 62.5% of youth who had taken stimulants compared with 27.4% of participants who had never taken stimulants. The association between stimulant use and psychotic experiences remained significant after adjustment for potential confounders (odds ratio: 4.41; 95% confidence interval: 1.82-10.69; P = .001) and was driven by hallucinations occurring during the use of stimulant medication. A temporal relationship between use of stimulants and psychotic symptoms was supported by an association between current stimulant use and current psychotic symptoms and co-occurrence in cases that were assessed on and off stimulants., Conclusions: Psychotic symptoms should be monitored during the use of stimulants in children and adolescents. Family history of mood and psychotic disorders may need to be taken into account when considering the prescription of stimulants., (Copyright © 2016 by the American Academy of Pediatrics.)

Aim: Work and educational activities are an important part of recovery for young people with psychosis, and improving vocational outcomes is a key target for early intervention services (EIS). This study evaluated predictors of vocational activity for first-episode psychosis (FEP) patients during the first year of EIS care. It was hypothesized that longer duration of untreated psychosis (DUP) and minority ethnic status would predict poorer vocational outcomes, whereas a history of good vocational functioning would predict better vocational functioning during follow up., Methods: FEP patients aged 14-35 years, who presented to seven EIS in London, UK, between 2003 and 2010, were followed for 1 year. Sociodemographic, clinical and vocational information (qualifications obtained and paid employment) were collected using the MiData audit tool at entry to EIS and 1 year later., Results: Approximately one-third of patients (n = 345/1013) were studying or employed at some point during the first year of EIS care. Baseline vocational activity was the strongest predictor of vocational functioning during 1 year of follow up. Moreover, employment prior to entry into EIS strongly predicted change in vocational activity during 1 year of follow up. Individuals with DUP <6 months or of Asian or black African origin were more likely to be studying than their white British counterparts., Conclusion: This study confirms that a significant proportion of FEP patients are able to engage in meaningful vocational activities even within the first year of EIS care. However, services need to focus more resources on getting patients with poor educational or employment histories into training programmes to improve their vocational outcomes., (© 2014 Wiley Publishing Asia Pty Ltd.)

Purpose: Childhood adversity (variously defined) is a robust risk factor for psychosis, yet the mitigating effects of social support in adulthood have not yet been explored. This study aimed to investigate the relationships between childhood sexual and physical abuse and adult psychosis, and gender differences in levels of perceived social support., Methods: A sample of 202 individuals presenting for the first time to mental health services with psychosis and 266 population-based controls from south-east London and Nottingham, UK, was utilised. The Childhood Experience of Care and Abuse Questionnaire was used to elicit retrospective reports of exposure to childhood adversity, and the Significant Others Questionnaire was completed to collect information on the current size of social networks and perceptions of emotional and practical support., Results: There was evidence of an interaction between severe physical abuse and levels of support (namely, number of significant others; likelihood ratio test χ(2) = 3.90, p = 0.048). When stratified by gender, there were no clear associations between childhood physical or sexual abuse, current social support and odds of psychosis in men. In contrast, for women, the highest odds of psychosis were generally found in those who reported severe abuse and low levels of social support in adulthood. However, tests for interaction by gender did not reach conventional levels of statistical significance., Conclusions: These findings highlight the importance of investigating the potential benefits of social support as a buffer against the development of adult psychosis amongst those, particularly women, with a history of early life stress.

Childhood psychotic symptoms are associated with increased rates of schizophrenia, other psychiatric disorders, and suicide attempts in adulthood; thus, elucidating early risk indicators is crucial to target prevention efforts. There is considerable discordance for psychotic symptoms between monozygotic twins, indicating that child-specific non-genetic factors must be involved. Epigenetic processes may constitute one of these factors and have not yet been investigated in relation to childhood psychotic symptoms. Therefore, this study explored whether differences in DNA methylation at age 10 were associated with monozygotic twin discordance for psychotic symptoms at age 12. The Environmental Risk (E-Risk) Longitudinal Twin Study cohort of 2,232 children (1,116 twin pairs) was assessed for age-12 psychotic symptoms and 24 monozygotic twin pairs discordant for symptoms were identified for methylomic comparison. Children provided buccal samples at ages 5 and 10. DNA was bisulfite modified and DNA methylation was quantified using the Infinium HumanMethylation450 array. Differentially methylated positions (DMPs) associated with psychotic symptoms were subsequently tested in post-mortem prefrontal cortex tissue from adult schizophrenia patients and age-matched controls. Site-specific DNA methylation differences were observed at age 10 between monozygotic twins discordant for age-12 psychotic symptoms. Similar DMPs were not found at age 5. The top-ranked psychosis-associated DMP (cg23933044), located in the promoter of the C5ORF42 gene, was also hypomethylated in post-mortem prefrontal cortex brain tissue from schizophrenia patients compared to unaffected controls. These data tentatively suggest that epigenetic variation in peripheral tissue is associated with childhood psychotic symptoms and may indicate susceptibility to schizophrenia and other mental health problems.

Background: Childhood abuse is considered one of the main environmental risk factors for the development of psychotic symptoms and disorders. However, this association could be due to genetic factors influencing exposure to such risky environments or increasing sensitivity to the detrimental impact of abuse. Therefore, using a large epidemiological case-control sample, we explored the interplay between a specific form of childhood abuse and family psychiatric history (a proxy for genetic risk) in the onset of psychosis., Methods: Data were available on 172 first presentation psychosis cases and 246 geographically matched controls from the Aetiology and Ethnicity of Schizophrenia and Other Psychoses study. Information on childhood abuse was obtained retrospectively using the Childhood Experience of Care and Abuse Questionnaire and occurrence of psychotic and affective disorders in first degree relatives with the Family Interview for Genetic Studies., Results: Parental psychosis was more common among psychosis cases than unaffected controls (adjusted OR = 5.96, 95% CI: 2.09-17.01, P = .001). Parental psychosis was also associated with physical abuse from mothers in both cases (OR = 3.64, 95% CI: 1.06-12.51, P = .040) and controls (OR = 10.93, 95% CI: 1.03-115.90, P = .047), indicative of a gene-environment correlation. Nevertheless, adjusting for parental psychosis did not measurably impact on the abuse-psychosis association (adjusted OR = 3.31, 95% CI: 1.22-8.95, P = .018). No interactions were found between familial liability and maternal physical abuse in determining psychosis caseness., Conclusions: This study found no evidence that familial risk accounts for associations between childhood physical abuse and psychotic disorder nor that it substantially increases the odds of psychosis among individuals reporting abuse., (© The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)

Recent models of psychosis have implicated specific psychological processes in the aetiology of this disorder, and these factors may form a route to later symptoms-either directly or via a mediating pathway after exposure to adversity. Researchers are beginning to bring together findings that look into specific pathways between early experiences of adversity and different symptoms of psychosis, including thought disorder, hallucinations and persecutory delusions. The adversity-specific pathways include parental communication deviance, source monitoring biases, and insecure attachment. Researchers have also begun to utilise specific psychological factors as targets for treatment, and these include a focus on a worrying thinking style, negative beliefs about the self, interpersonal sensitivity, sleep disturbance, anomalous internal experience, and reasoning biases. Research on the impact of psychological processes is beginning to mount and is likely to improve our understanding of aetiology and lead to significant advances in the treatment of psychotic symptoms and disorders.

Background: The Brain-derived Neurotrophic Factor (BDNF) modulates cognitive processes and is associated with increased risk of schizophrenia. Childhood trauma (CT) is frequent in patients with psychosis and severely affects course and outcome., Aims: We investigated the hypothesis that BDNF is associated with both CT and cognitive deficits in a sample of first-episode psychosis (FEP) cases and unaffected controls., Method: Participants with FEP and healthy controls were recruited between August 2008 and July 2011 from South London, UK. Childhood traumatic events were detected using the Childhood Experience of Care and Abuse Questionnaire (CECA-Q). Neuropsychological data were also collected. BDNF plasma levels were measured from fasting blood samples., Results: Data were available on 87 FEP patients and 152 controls. Our results showed a significant effect of separation (F=5.5; df=1,115; p=.02), physical (F=4.7; df=1, 118; p=.03) and sexual abuse (F=5.4; df=1,117; p=.02) on BDNF levels with lower levels among those who experienced the traumatic event compared to those who did not. Physical abuse predicted lower plasma levels of BDNF (β=-.30; p=.03) whereas sexual and/or physical abuse showed a trend (β=-.26; p=.06) in FEP patients but not in unaffected controls. No association between BDNF plasma levels and cognitive functions was found among patients with FEP and controls., Conclusion: Our findings suggest the possible involvement of BDNF in the onset of first-episode psychosis in individuals exposed to early trauma and propose BDNF as a potential clinical biomarker to detect the detrimental effects of CT on human brain plasticity., (Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.)

Background: Marked ethnic variations in incidence, pathways to care and outcomes have been demonstrated in psychosis. Less research has focused specifically on first-episode psychosis (FEP), particularly adverse contacts such as compulsory detention and hospitalization. This is despite international initiatives to promote equity of care and active early intervention., Aim: Systematically review current evidence for ethnic variations in rates of compulsory admission and hospitalization in FEP., Methods: Relevant articles published before December 2012 were identified from PubMed, PSYCInfo, and CINAHL together with manual searching of reference lists. Studies providing quantitative data on compulsory detention rates and/or hospitalization, comparing ethnic groups in FEP, were included and quality rated by independent raters., Results: All included studies (n = 7) provided data on compulsory detention while fewer (n = 3) focused on admission rates. Three studies reported increased detention in Black and minority ethnic groups, while one reported more hospitalization in White patients. Only two studies covered early intervention services (EIS)., Conclusions: There is a paucity of high quality, well powered studies addressing this important issue, especially in EIS settings. In order to best inform and evaluate fast-developing services, it will be essential to combine large methodologically robust studies with qualitative analysis of patient, carer, and staff experiences.

Study Objectives: To examine associations between specific parasomnias and psychotic experiences in childhood., Design: Birth cohort study. Information on the presence of frequent nightmares in children was obtained prospectively from mothers during multiple assessments conducted when children were aged between 2.5 and 9 y. Children were interviewed at age 12 y about nightmares, night terrors, sleepwalking, and psychotic experiences (delusions, hallucinations, and thought interference) occurring in the previous 6 mo., Setting: Assessments were completed in participants' homes or a University clinic within the UK., Patients or Participants: There were 6,796 children (3,462 girls, 50.9%) who completed the psychotic experiences interview., Measurements and Results: Children who were reported by their mothers as experiencing frequent nightmares between 2.5 and 9 y of age were more likely to report psychotic experiences at age 12 y, regardless of sex, family adversity, emotional or behavioral problems, IQ and potential neurological problems (odds ratio (OR) = 1.16, [95% confidence intervals (CI) = 1.00, 1.35], P = 0.049). Children reporting any of the parasomnias at age 12 y also had higher rates of concurrent psychotic experiences than those without such sleeping problems, when adjusting for all confounders (OR = 3.62 [95% CI = 2.57, 5.11], P < 0.001). Difficulty getting to sleep and night waking were not found to be associated with psychotic experiences at age 12 y when controlling for confounders., Conclusion: Nightmares and night terrors, but not other sleeping problems, in childhood were associated with psychotic experiences at age 12 years. These findings tentatively suggest that arousal and rapid eye movement forms of sleep disorder might be early indicators of susceptibility to psychotic experiences.

Background: Duration of Untreated Psychosis (DUP) is an important measure associated with outcome of psychosis. This first study in the UK compared DUP between adolescent and adult-onset individuals and explored whether the adolescent-onset group showed variations in DUP that could be accounted for by sociodemographic and selected risk factors., Methods: This naturalistic cohort study included 940 new first-episode psychosis cases aged 14-35years (136 adolescent-onset versus 804 adult-onset psychotic individuals) referred to nine Early Intervention Services for Psychosis in London (2003-2009). Sociodemographic characteristics, age of onset, family history of mental illness, duration of untreated psychosis, suicidality and substance use information were collected at entry to the services., Results: Adolescents presented with significantly greater median DUP (179days) than adults (81days, p=0.005). Large differences in DUP were found amongst adolescent ethnic groups (median DUP: White: 454days; Black: 103days; Asian and mixed: 28.5days). In addition, younger age of onset and higher lifetime cannabis use were associated with longer treatment delay amongst adolescents., Conclusions: This study of DUP in adolescent-onset psychosis found it to be approximately twice the length of DUP amongst adults. For the adolescent White sub-group, DUP was far greater than the UK Department of Health target (<3months). Both the high rates of lifetime cannabis use and the lower age of onset might explain the long DUP in this ethnic group. Physicians need to be particularly vigilant about identifying and managing early psychosis in adolescents., (© 2013.)

Background: Despite increasing evidence suggesting that childhood maltreatment is significantly associated with psychosis, the specific role of bullying in the onset of psychotic disorders is still unclear. This study aimed to examine whether bullying was more prevalent amongst individuals presenting to services for the first time with a psychotic disorder than in unaffected community controls., Methods: Data on exposure to bullying, psychotic symptoms, cannabis use and history of conduct disorder were collected cross-sectionally from 222 first-presentation psychosis cases and 215 geographically-matched controls. Bullying victimisation was assessed retrospectively as part of the Brief Life Events schedule. Logistic regression was used to examine associations between exposure to bullying and case-control status, while controlling for potential confounders., Results: Psychosis cases were approximately twice as likely to report bullying victimisation when compared to controls. No significant interactions between bullying and either gender or cannabis use were found. Controls reporting being a victim of bullying were approximately twice as likely to also report at least one psychosis-like symptom., Conclusions: Our results extend previous research by suggesting that bullying victimisation may contribute to vulnerability to develop a psychotic disorder in some individuals., (© 2013 Elsevier B.V. All rights reserved.)

Background: Several large population-based studies have demonstrated associations between adverse childhood experiences and later development of psychotic symptoms. However, little attention has been paid to the mechanisms involved in this pathway and the few existing studies have relied on cross-sectional assessments., Methods: Prospective data on 6692 children from the UK Avon Longitudinal Study of Parents and Children (ALSPAC) were used to address this issue. Mothers reported on children's exposure to harsh parenting and domestic violence in early childhood, and children self-reported on bullying victimization prior to 8.5 years. Presence of children's anxiety at 10 years and their depressive symptoms at 9 and 11 years were ascertained from mothers, and children completed assessments of self-esteem and locus of control at 8.5 years. Children were interviewed regarding psychotic symptoms at a mean age of 12.9 years. Multiple mediation analysis was performed to examine direct and indirect effects of each childhood adversity on psychotic symptoms., Results: The association between harsh parenting and psychotic symptoms was fully mediated by anxiety, depressive symptoms, external locus of control, and low self-esteem. Bullying victimization and exposure to domestic violence had their associations with psychotic symptoms partially mediated by anxiety, depression, locus of control, and self-esteem. Similar results were obtained following adjustment for a range of confounders and when analyses were conducted for boys and girls separately., Conclusions: These findings tentatively suggest that specific cognitive and affective difficulties in childhood could be targeted to minimize the likelihood of adolescents exposed to early trauma from developing psychotic symptoms.