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Purpose: Higher rates of non-affective psychotic disorders (NAPD) in minority groups have been reported in many countries. However, few studies have explored how rates differ between refugees and other minority groups and none with an international comparative angle. A comparative perspective makes it possible to relate group differences to aspects national context that underpin the social determinants of disease. Methods: We compared the incidence of treated NAPD among youth born in or who immigrated to Denmark/Sweden before turning 18. Youth aged 18–35 during 2006–2018 were included (NDenmark/NSweden = 1,606,423/2,614,721) and were followed until first NAPD treatment (cases [Denmark/Sweden] = 12,193/9,641), 36th birthday, emigration or death. Incidence rates (IR) and ratios (IRR) comparing refugees, non-refugee migrants, descendants of non-refugee migrants and majority youth were obtained through Poisson regression on data aggregated by country, sex and age, contrasted by sex and country. Complementary analyses on individual-level data adjusting for further socio-demographic factors were conducted in each country separately. Results: Incidence rates were higher in all groups compared with the majority group (IRRrange = 1.4–2.9, 95% CI[min, max] = 1.2–3.1). Relative differences between the three minority groups were smaller (IRRrange = 0.7–1.0, 95% CI[min, max] = 0.5–1.2). Although incidence rates were higher in Denmark than Sweden, relative group differences were similar. Conclusion: Exposures shared between young refugees and other minority groups growing up in Denmark and Sweden may be especially important for their excess risk of NAPD. Further studies should investigate the mechanisms behind the elevated rates in minority groups with special paid attention to factors such as discrimination, social exclusion and acculturation stress. [ABSTRACT FROM AUTHOR]

Background Unemployment and work disability are common among individuals with non-affective psychotic disorders (NAPDs) but it is unknown whether rates differ among migrants and native-born individuals. The present study aimed to compare the risk of these outcomes during the first 5 years of illness in non-refugee migrants, refugees and native-born individuals with NAPDs in Sweden and Denmark—two countries with different immigration policies and models of early psychosis care. Methods Using national registers, we identified all individuals aged 18–35 years in Sweden and Denmark who received an incident NAPD diagnosis between 2006 and 2013 (N  = 6750 and 8320, respectively). Cohorts were followed for 5 years to determine the days of unemployment and sickness absence (analyzed using zero-inflated negative binomial models) and the time to receipt of disability pension (analyzed using complementary log-log models). Results Relative to their native-born peers, refugees and non-refugee migrants in Sweden and non-refugee migrants in Denmark were significantly less likely to have zero unemployment days (OR range: 0.54–0.72) and all migrant groups experienced more unemployment days (IRR range: 1.26–1.37). Results were largely unchanged after adjustment for sociodemographic and clinical factors. In the adjusted model, both Swedish migrant groups and refugees in Denmark were more likely to experience zero sickness absence days than native-born individuals (OR range: 1.48–1.56). Only refugees in Denmark were at greater risk of disability pension. Conclusions Non-refugee migrants and refugees with NAPDs in both Sweden and Denmark are particularly vulnerable to experiencing unemployment. Targeted interventions may help to reduce these disparities and promote long-term work ability among migrant groups. [ABSTRACT FROM AUTHOR]

Background: The clinical high-risk for psychosis (CHR-P) paradigm was introduced to detect individuals at risk of developing psychosis and to establish preventive strategies. While current prediction of outcomes in the CHR-P state is based mostly on the clinical assessment of presenting features, several emerging biomarkers have been investigated in an attempt to stratify CHR-P individuals according to their individual trajectories and refine the diagnostic process. However, heterogeneity across subgroups is a key challenge that has limited the impact of the CHR-P prediction strategies, as the clinical validity of the current research is limited by a lack of external validation across sites and modalities. Despite these challenges, electroencephalography (EEG) biomarkers have been studied in this field and evidence suggests that EEG used in combination with clinical assessments may be a key measure for improving diagnostic and prognostic accuracy in the CHR-P state. The PSYSCAN EEG study is an international, multi-site, multimodal longitudinal project that aims to advance knowledge in this field. Methods: Participants at 6 international sites take part in an EEG protocol including EEG recording, cognitive and clinical assessments. CHR-P participants will be followed up after 2 years and subcategorised depending on their illness progression regarding transition to psychosis. Differences will be sought between CHR-P individuals and healthy controls and between CHR-P individuals who transition and those who do not transition to psychosis using data driven computational analyses. Discussion: This protocol addresses the challenges faced by previous studies of this kind to enable valid identification of predictive EEG biomarkers which will be combined with other biomarkers across sites to develop a prognostic tool in CHR-P. The PSYSCAN EEG study aims to pave the way for incorporating EEG biomarkers in the assessment of CHR-P individuals, to refine the diagnostic process and help to stratify CHR-P subjects according to risk of transition. This may improve our understanding of the CHR-P state and therefore aid the development of more personalized treatment strategies. [ABSTRACT FROM AUTHOR]

This document is an editorial published in the journal Frontiers in Psychiatry. It discusses the role of hormones in psychosis disorders and presents recent research on the topic. The editorial highlights the influence of endocrine disorders and altered hormone levels on the risk, clinical course, and prognosis of psychotic illnesses. The research studies included in the editorial explore the relationships between thyroid function, structural and functional mechanisms, neuropeptides, psychosocial stress, and perinatal hormonal changes in relation to psychosis. The editorial emphasizes the need for further investigation into the role of hormones in psychosis and the potential for hormonal markers to serve as biomarkers for severe mental illness. [Extracted from the article]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

Aims: Around 15% of patients at clinical high risk for psychosis (CHR‐P) experience symptomatic remission and functional recovery at follow‐up, yet the definition of a good outcome (GO) in this population requires further development. Outcomes are typically designed and rated by clinicians rather than patients, to measure adverse as opposed to GOs. Here we investigate how CHR‐P subjects define a GO, with the aim of developing a checklist that could be used to measure GO in this clinical group. Methods: A set of GO‐focused questions were designed in collaboration with a service‐user. CHR‐P patients (n = 48) were asked to rate the importance of items that could indicate short‐term (1 year) and long‐term (5 years) GO. These items were then ranked using the relative importance index (RII). Results: Patients rated improvement in subjective wellbeing (RII = 0.829) and non‐specific presenting symptoms (RII = 0.817) amongst the factors most important for indicating GO in the short‐term, and improved resilience (RII = 0.879) and negative symptoms (RII = 0.858) as key items for indicating long‐term GO. Patients regarded building resilience (RII = 0.842) and having support from mental health services (RII = 0.833) as being protective for their mental health. These measures were included in a preliminary 12‐item GO checklist (GO‐12) for assessing GO in CHR‐P subjects. Conclusions: Patient‐defined measures of GO included items that are not incorporated into conventional measures of outcomes in CHR‐P subjects, such as subjective wellbeing and resilience. Integrating patient‐defined metrics of GO may improve the assessment of outcomes in the CHR‐P population. [ABSTRACT FROM AUTHOR]

Relapse rates among individuals with psychotic disorders are high. In addition to the financial burden placed on clinical services, relapse is associated with worse long-term prognosis and poorer quality of life. Robust evidence indicates that stressful life events commonly precede the onset of the first psychotic episode; however, the extent to which they are associated with relapse remains unclear. The aim of this systematic review is to summarize available research investigating the association between recent stressful life events and psychotic relapse or relapse of bipolar disorder if the diagnosis included psychotic symptoms. PsycINFO, Medline and EMBASE were searched for cross-sectional, retrospective and prospective studies published between 01/01/1970 and 08/01/2020 that investigated the association between adult stressful life events and relapse of psychosis. Study quality was assessed using the Effective Public Health Practice Project guidelines. Twenty-three studies met eligibility criteria (prospective studies: 14; retrospective studies: 6; cross-sectional: 3) providing data on 2046 participants in total (sample size range: 14–240 participants). Relapse was defined as a return of psychotic symptoms (n = 20), a return of symptoms requiring hospitalization (n = 2) and a return of symptoms or hospitalization (n = 1). Adult stressful life events were defined as life events occurring after the onset of psychosis. Stressful life events included but were not limited to adult trauma, bereavement, financial problems and conflict. Eighteen studies found a significant positive association between adult stressful life events and psychotic relapse and five studies found a non-significant association. We conclude that adult stressful life events, occurring after psychosis onset, appear to be associated with psychotic relapse. [ABSTRACT FROM AUTHOR]

Background: Individuals with established psychosis and those at high-risk for the disorder have been found to show abnormalities within the hypothalamic-pituitary-adrenal (HPA) axis, including elevations in basal and diurnal cortisol, but a blunted cortisol awakening response. However, the extent to which these features are associated with psychosocial stressors encountered in the natural environment (which are known to be more commonly experienced by these groups, and more distressing) is currently unclear. We therefore conducted a systematic review and meta-analysis to investigate the concordance between naturally-occurring psychosocial stressors and cortisol levels in these populations. Methods: PubMed, PsycINFO, and EMBASE were searched up to November 2019 to identify studies examining the concordance between psychosocial stressors and cortisol in healthy controls and individuals on the psychosis spectrum (patients with established psychosis and/or high-risk individuals). An overall meta-analysis (including data for all stressor-cortisol pairings) was performed to determine the degree of concordance irrespective of group status, with meta-regression employed to test whether the degree of concordance differed in established psychosis and high-risk groups compared to controls. Planned stratified analyses were then performed to examine group differences (where established psychosis and high-risk groups were combined) within individual stressor-cortisol pairings. Results: Eighteen studies (16 datasets) were eligible for inclusion. The overall model, comprising 134 effect sizes, showed that stressors and cortisol measures were only weakly correlated [ r= 0.05 (95% CI: -0.00 to 0.10), p =0.059] and that neither established psychosis status (r= 0.01, p =0.838) nor high-risk status (r= 0.02, p =0.477) had a significant effect of the strength of correlation. In stratified analyses, significant differences between healthy controls and psychosis spectrum groups were observed for only one of the six stressor-cortisol pairings examined, where life event exposure and diurnal cortisol were positively correlated in controls [ r= 0.25 (95% CI: 0.01 to 0.46)], but negatively correlated in the psychosis spectrum group [ r= -0.28 (95% CI: -0.49 to -0.04)]. Conclusions: Overall, we observed poor concordance between naturally-occurring psychosocial stressors and cortisol irrespective of stressor type, cortisol measure, or group status. We consider a range of methodological factors that may have obscured the ability to detect "true" associations and provide recommendations for future studies in this field. [ABSTRACT FROM AUTHOR]

Psychotic disorders can be exacerbated by the hormonal changes associated with childbirth, but the extent to which exacerbations occur with the menstrual cycle is unclear. We addressed this issue by conducting a systematic review. Embase, Medline, and PsychINFO databases were searched for studies that measured exacerbations of psychotic disorders in relation to the menstrual cycle. We extracted exacerbation measure, definition of menstrual cycle phase, and measurement of menstrual cycle phase. Standard incidence ratios were calculated for the perimenstrual phase based on the observed admissions during this phase divided by the expected number of admissions if the menstrual cycle had no effect. Random effects models were used to examine pooled rates of psychiatric admission in the perimenstrual phase. Nineteen studies, comprising 1193 participants were eligible for inclusion. Eleven studies examined psychiatric admission rates, 5 examined symptoms scores, 2 examined self-reported exacerbation, and 1 examined both admission rates and symptom scores. A random effects model demonstrated the rate of admissions during the perimenstrual phase was 1.48 times higher than expected (95% CI: 1.31–1.67), with no significant heterogeneity detected. Four of six symptom score studies reported perimenstrual worsening, but lack of consistency in timepoints precluded meta-analysis. Two studies examining self-reported menstrual exacerbations reported prevalences ranging from 20% to 32.4%. Psychiatric admission rates are significantly higher than expected during the perimenstrual phase. There is some evidence that a worsening of psychotic symptoms also occurs during this phase, but further research with more precise measurement of the menstrual cycle and symptomatology is required. [ABSTRACT FROM AUTHOR]

Abstract Background A relationship between non-neurological autoimmune (NNAI) disorders and psychosis has been widely reported but not yet subjected to meta-analysis. We conducted the first meta-analysis examining the association between NNAI disorders and psychosis and investigated the effect of 1) temporality (as determined by study design), 2) psychiatric diagnosis, and 3) specific autoimmune disorders. Methods Major databases were searched for articles published until April 2018; 31 studies, comprising data for >25 million individuals, were eligible. Using random-effects models, we examined the overall association between all NNAI disorders and psychosis; rheumatoid arthritis was examined separately given the well-established negative association with psychosis. Stratified analyses investigated the effect of temporality, psychiatric diagnosis, and specific NNAI disorders. Results We observed a positive overall association between NNAI disorders and psychosis (odds ratio [OR] = 1.26; 95% confidence interval [CI], 1.12–1.41) that was consistent across study designs and psychiatric diagnoses; however, considerable heterogeneity was detected (I 2 = 88.08). Patterns varied across individual NNAI disorders; associations were positive for pernicious anemia (OR = 1.91; 95% CI, 1.29–2.84), pemphigoid (OR = 1.90; 95% CI, 1.62–2.24), psoriasis (OR = 1.70; 95% CI, 1.51–1.91), celiac disease (OR = 1.53; 95% CI, 1.12–2.10), and Graves' disease (OR = 1.33; 95% CI, 1.03–1.72) and negative for ankylosing spondylitis (OR = 0.72; 95% CI, 0.54–0.98) and rheumatoid arthritis (OR = 0.65; 95% CI, 0.50–0.84). Conclusions While we observed a positive overall association between NNAI disorders and psychosis, this was not consistent across all NNAI disorders. Specific factors, including distinct inflammatory pathways, genetic influences, autoantibodies targeting brain proteins, and exposure to corticosteroid treatment, may therefore underlie this association. [ABSTRACT FROM AUTHOR]

Summary: Abnormal hypothalamic-pituitary-adrenal (HPA) axis function, as indexed by elevated diurnal cortisol levels and/or a blunted cortisol awakening response (CAR), has been observed among patients with first episode psychosis and associated with neurocognitive deficits in this population. However, the extent to which these features precede illness onset is unclear. The current study aimed to determine whether children who are at putatively elevated risk for psychosis because they present multiple antecedents of schizophrenia (ASz), and high-risk children with a family history of illness (FHx), are characterized by abnormal cortisol levels when compared with their typically developing (TD) peers. A further aim was to investigate the extent to which cortisol levels are associated with psychosocial stress and neurocognitive function. Thirty-three ASz children, 22 FHx children, and 40 TD children were identified at age 9–12 years using a novel community-based screening procedure or as relatives of individuals with schizophrenia. All participants were antipsychotic-naive and not currently seeking treatment for their symptoms. At age 11–14 years, participants provided salivary cortisol samples and completed psychosocial stress measures and tests of memory and executive function. Results indicated that FHx children, but not ASz children, were characterized by a blunted CAR relative to their TD peers (effect size=−0.73, p =0.01) that was not explained by psychosocial stress exposure or by distress relating to these experiences. Neither FHx nor ASz children were characterized by elevated diurnal cortisol. Among both FHx and ASz children, more pronounced HPA axis function abnormalities (i.e., higher diurnal cortisol levels and greater blunting of the CAR) were associated with poorer performance on tests of verbal memory and executive function. These findings support the notion that at least some HPA axis abnormalities described in psychosis precede illness onset, rather than being a subsequent epiphenomenon. We speculate that the blunted CAR may constitute an early (potentially genetically mediated) marker of psychosis vulnerability, whilst elevated diurnal cortisol levels may emerge only proximally to disease onset. [ABSTRACT FROM AUTHOR]

Abstract: Background: Persisting psychotic-like experiences (PLEs) are associated with an increased risk of internalising symptoms in adolescence. Whether this association holds similarly for externalising symptoms, and from mid-childhood, is unclear. This prospective study investigated the extent to which PLE persistence was associated with internalising and externalising psychopathology in a community sample of children aged 9–11years at study commencement. Methods: 8099 children (mean age 10.4years) completed questionnaires assessing PLEs, externalising and internalising symptoms. A subsample of 547 children completed reassessment, on average, two years later. Results: Two-thirds (66%) of children reported PLEs at baseline. Approximately two years later, PLEs persisted in 39% of those children. After adjustment for previous psychopathology and other potential confounds, children with persisting PLEs were at higher risk for internalising (odds ratio [OR]=1.94; 95% confidence interval [CI] 1.13–3.34) and externalising (OR=1.97; 95% CI 1.19–3.26) psychopathology than children whose PLEs remitted; and, than children who never presented PLEs. Conclusions: Persistent PLEs from mid-childhood are associated with later internalising and externalising psychopathology in the general population, whereas transitory PLEs may be part of a spectrum of normative childhood development. Interventions that target persistent PLEs may contribute to a reduction in common childhood psychopathology. [Copyright &y& Elsevier]

Studies evaluating the implementation of cognitive skills programs with mentally disordered offenders (MDOs) have reported high dropout rates, but little is known about the factors associated with treatment noncompletion. The authors analyzed data from the first randomized controlled trial of the Reasoning and Rehabilitation (R&R) program with MDOs to determine predictors of treatment dropout. Patients with psychotic disorders were recruited from medium-secure hospitals in the United Kingdom. Fifty percent of the 44 participants allocated to receive R&R prematurely terminated treatment. Program dropout was significantly predicted by scores on the Clinical and Risk Management scales of the Historical, Clinical, Risk Management—20, Factor 2 scores of the Psychopathy Checklist—Screening Version, antisocial personality disorder (ASPD), psychopathy, and recent violence. Psychopathy, ASPD, and recent violence emerged as the strongest predictors of dropout in multivariate analyses. Strategies to improve treatment retention should be targeted at MDOs who display high levels of impulsivity, poor behavioral controls, and antisocial or psychopathic traits. [ABSTRACT FROM AUTHOR]

• CHR youth showed greater psychosocial stressor exposure and distress than controls. • Only CHR youth who later developed psychosis had higher basal cortisol at baseline. • Pooled stressor-cortisol concordance values were highest in CHR converters. • The degree of concordance distinguished CHR converters from CHR non-converters. • Concordance in controls was intermediate to CHR converters and non-converters. Whilst elevations in basal cortisol levels have been reported among individuals at-risk for psychosis, the extent to which this represents hyperresponsivity of the hypothalamic-pituitary-adrenal (HPA) axis to psychosocial stressors encountered in the natural environment is currently unclear. We aimed to examine stressor-cortisol concordance among youth at clinical high-risk (CHR) for psychosis in the North American Prodrome Longitudinal Study 2 (NAPLS 2) and the relationship with clinical outcome. At baseline, CHR (N = 457) and healthy (N = 205) individuals provided salivary cortisol samples and completed daily stressor, life event, and childhood trauma measures. CHR youth were categorised as remitted, symptomatic, progression of positive symptoms, or psychosis conversion at the two-year follow-up. Within-group regression models tested associations between psychosocial stressors and cortisol; standardised beta coefficients (Stβ) were subsequently derived to enable within-group pooling of effect sizes across stressor types. After adjustment for potential confounders, all CHR subgroups reported greater exposure to life events and daily stressors, and more distress in relation to these events, relative to controls. All CHR groups were also more likely to experience childhood trauma; only CHR converters, however, were characterised by elevated basal cortisol. Daily stressor distress was significantly associated with cortisol in controls (β = 0.60, 95% CI: 0.12–1.08) and CHR youth who converted to psychosis (β = 0.91, 95% CI: 0.05–1.78). In controls only, life event exposure was associated with cortisol (β = 0.45, 95% CI: 0.08–0.83). When pooled across stressors, stressor-cortisol concordance was substantially higher among CHR converters (Stβ = 0.26, 95% CI: 0.07 to 0.44) relative to CHR progressed (Stβ = 0.02, 95% CI: -0.11 to 0.15), symptomatic (Stβ = 0.01, 95% CI: -0.11 to 0.12), and remitted groups (Stβ = 0.00, 95% CI: -0.13 to 0.13); however, unexpectedly, healthy controls showed intermediate levels of concordance (Stβ = 0.15, 95% CI: 0.05 to 0.26). In conclusion, whilst all CHR subgroups showed increased psychosocial stress exposure and distress relative to controls, only those who later converted to psychosis were characterised by significantly elevated basal cortisol levels. Moreover, only CHR converters showed a higher magnitude of stressor-cortisol concordance compared to controls, although confidence intervals overlapped considerably between these two groups. These findings do not support the notion that all individuals at CHR for psychosis show HPA hyperresponsiveness to psychosocial stressors. Instead, CHR individuals vary in their response to stressor exposure/distress, perhaps driven by genetic or other vulnerability factors. [ABSTRACT FROM AUTHOR]

Robust epidemiological evidence of risk and protective factors for psychosis is essential to inform preventive interventions. Previous evidence syntheses have classified these risk and protective factors according to their strength of association with psychosis. In this critical review we appraise the distinct and overlapping mechanisms of 25 key environmental risk factors for psychosis, and link these to mechanistic pathways that may contribute to neurochemical alterations hypothesised to underlie psychotic symptoms. We then discuss the implications of our findings for future research, specifically considering interactions between factors, exploring universal and subgroup-specific factors, improving understanding of temporality and risk dynamics, standardising operationalisation and measurement of risk and protective factors, and developing preventive interventions targeting risk and protective factors. • Many risk factors for psychosis have shared causal mechanisms. • Many factors are associated with psychosocial stress. • Other risk factors may more directly impact core neurobiological mechanisms. • Combined measurement of these factors may improve prevention efforts. • More research is needed to understand the complexities of risk/protective factors. [ABSTRACT FROM AUTHOR]

Background: Pituitary volume (PV) abnormalities, representing one of several markers of hypothalamic-pituitary-adrenal (HPA) axis dysregulation, have been observed in psychosis, with variable patterns across illness stages. Typically, enlargements characterise first-episode patients, with reductions observed in those with chronic illness relative to healthy controls. Findings in high-risk populations have been inconsistent, highlighting the need for an updated review of the evidence.Methods: We searched PubMed, PsycINFO, and EMBASE for studies examining PV in high-risk [clinical high-risk (CHR), family history of psychosis (FHx), schizotypal personality disorder (SPD), and psychotic-experiences (PEs)] and healthy individuals. Random effects models were used to examine group differences in PV (Hedges g) with stratified analyses and meta-regression employed to investigate the effect of high-risk category, transition status, age, sex, and antipsychotic medication.Results: Ten studies, yielding 11 effect sizes, were eligible for inclusion. Overall, high-risk individuals had significantly larger PV relative to healthy controls (g = 0.16 [95% CI: 0.01 to 0.32] p = 0.04), despite showing a reduction in whole brain volume (g = -0.17, [95% CI. -0.30 to -0.03] p = 0.020). Individual sub-group analyses for CHR and FHx groups showed no significant differences relative to controls; however, larger PV increases characterised those who later transitioned to psychosis (g = 0.55, [95% CI. 0.06 to 1.04] p = 0.028). Larger effect sizes were positively associated with the proportion of high-risk individuals receiving antipsychotic medication.Conclusions: PV enlargements characterise high-risk individuals and are more pronounced among those who later develop psychosis. We provide recommendations for future studies. [ABSTRACT FROM AUTHOR]