Youth adversity and trajectories of depression/anxiety symptoms in adolescence in the context of intersectionality in the United Kingdom.

BACKGROUND: Youth adversity is associated with persistence of depression and anxiety symptoms. This association may be greater for disadvantaged societal groups (such as females) compared with advantaged groups (e.g. males). Given that persistent symptoms are observed across a range of disadvantaged, minoritized, and neurodivergent groups (e.g. low compared with high socio-economic status [SES]), the intersection of individual characteristics may be an important moderator of inequality. METHODS: Data from HeadStart Cornwall (N = 4441) was used to assess the effect of youth adversity on combined symptoms of depression and anxiety (Strengths and Difficulties Questionnaire emotional problems subscale) measured at three time-points in 11-14-year-olds. Latent trajectories and regressions were estimated for eight intersectionality profiles (based on gender, SES, and hyperactivity/inattention), and moderating effects of the individual characteristics and their intersections were estimated. RESULTS: Youth adversity was associated with higher average depression/anxiety symptoms at baseline (11-12-years) across all intersectionality profiles. The magnitude of effects differed across profiles, with suggestive evidence for a moderating effect of youth adversity on change over time in depression/anxiety symptoms attributable to the intersection between (i) gender and SES; and (ii) gender, SES, and hyperactivity/inattention. CONCLUSIONS: The detrimental effects of youth adversity pervade across intersectionality profiles. The extent to which these effects are moderated by intersectionality is discussed in terms of operational factors. The current results provide a platform for further research, which is needed to determine the importance of intersectionality as a moderator of youth adversity on the development of depression and anxiety symptoms in adolescence.

The temporal association between social isolation, distress, and psychotic experiences in individuals at clinical high-risk for psychosis.

BACKGROUND: Psychotic experiences (PEs) and social isolation (SI) seem related during early stages of psychosis, but the temporal dynamics between the two are not clear. Literature so far suggests a self-perpetuating cycle wherein momentary increases in PEs lead to social withdrawal, which, subsequently, triggers PEs at a next point in time, especially when SI is associated with increased distress. The current study investigated the daily-life temporal associations between SI and PEs, as well as the role of SI-related and general affective distress in individuals at clinical high risk (CHR) for psychosis. METHODS: We used experience sampling methodology in a sample of 137 CHR participants. We analyzed the association between SI, PEs, and distress using time-lagged linear mixed-effects models. RESULTS: SI did not predict next-moment fluctuations in PEs, or vice versa. Furthermore, although SI-related distress was not predictive of subsequent PEs, general affective distress during SI was a robust predictor of next-moment PEs. CONCLUSIONS: Our results suggest that SI and PEs are not directly related on a moment-to-moment level, but a negative emotional state when alone does contribute to the risk of PEs. These findings highlight the role of affective wellbeing during early-stage psychosis development.

Variation of subclinical psychosis across 16 sites in Europe and Brazil: findings from the multi-national EU-GEI study.

BACKGROUND: Incidence of first-episode psychosis (FEP) varies substantially across geographic regions. Phenotypes of subclinical psychosis (SP), such as psychotic-like experiences (PLEs) and schizotypy, present several similarities with psychosis. We aimed to examine whether SP measures varied across different sites and whether this variation was comparable with FEP incidence within the same areas. We further examined contribution of environmental and genetic factors to SP. METHODS: We used data from 1497 controls recruited in 16 different sites across 6 countries. Factor scores for several psychopathological dimensions of schizotypy and PLEs were obtained using multidimensional item response theory models. Variation of these scores was assessed using multi-level regression analysis to estimate individual and between-sites variance adjusting for age, sex, education, migrant, employment and relational status, childhood adversity, and cannabis use. In the final model we added local FEP incidence as a second-level variable. Association with genetic liability was examined separately. RESULTS: Schizotypy showed a large between-sites variation with up to 15% of variance attributable to site-level characteristics. Adding local FEP incidence to the model considerably reduced the between-sites unexplained schizotypy variance. PLEs did not show as much variation. Overall, SP was associated with younger age, migrant, unmarried, unemployed and less educated individuals, cannabis use, and childhood adversity. Both phenotypes were associated with genetic liability to schizophrenia. CONCLUSIONS: Schizotypy showed substantial between-sites variation, being more represented in areas where FEP incidence is higher. This supports the hypothesis that shared contextual factors shape the between-sites variation of psychosis across the spectrum.

Exploring the mediation of DNA methylation across the epigenome between childhood adversity and First Episode of Psychosis-findings from the EU-GEI study.

ABTRACT: Studies conducted in psychotic disorders have shown that DNA-methylation (DNAm) is sensitive to the impact of Childhood Adversity (CA). However, whether it mediates the association between CA and psychosis is yet to be explored. Epigenome wide association studies (EWAS) using the Illumina Infinium-Methylation EPIC array in peripheral blood tissue from 366 First-episode of psychosis and 517 healthy controls was performed. Adversity scores were created for abuse, neglect and composite adversity with the Childhood Trauma Questionnaire (CTQ). Regressions examining (I) CTQ scores with psychosis; (II) with DNAm EWAS level and (III) between DNAm and caseness, adjusted for a variety of confounders were conducted. Divide-Aggregate Composite-null Test for the composite null-hypothesis of no mediation effect was conducted. Enrichment analyses were conducted with missMethyl package and the KEGG database. Our results show that CA was associated with psychosis (Composite: OR = 1.68; p = <0.001; abuse: OR = 2.16; p < 0.001; neglect: OR = 2.27; p = <0.001). None of the CpG sites significantly mediated the adversity-psychosis association after Bonferroni correction (p < 8.1 × 10-8). However, 28, 34 and 29 differentially methylated probes associated with 21, 27, 20 genes passed a less stringent discovery threshold (p < 5 × 10-5) for composite, abuse and neglect respectively, with a lack of overlap between abuse and neglect. These included genes previously associated to psychosis in EWAS studies, such as PANK1, SPEG TBKBP1, TSNARE1 or H2R. Downstream gene ontology analyses did not reveal any biological pathways that survived false discovery rate correction. Although at a non-significant level, DNAm changes in genes previously associated with schizophrenia in EWAS studies may mediate the CA-psychosis association. These results and associated involved processes such as mitochondrial or histaminergic disfunction, immunity or neural signalling requires replication in well powered samples. The lack of overlap between mediating genes associated with abuse and neglect suggests differential biological trajectories linking CA subtypes and psychosis.

Sociodemographic and clinical predictors of delay to and length of stay with early intervention for psychosis service: findings from the CRIS-FEP study.

PURPOSE: We investigated the influence of sociodemographic and clinical characteristics on delay to early intervention service (EIS) and the length of stay (LOS) with EIS. METHODS: We used incidence data linked to the Clinical Record Interactive Search-First Episode Psychosis (CRIS-FEP) study. We followed the patients from May 2010 to March 2016. We performed multivariable Cox regression to estimate hazard ratios of delay to EIS. Negative binomial regression was used to determine LOS with EIS by sociodemographic and clinical characteristics, controlling for confounders. RESULTS: 343 patients were eligible for an EIS, 34.1% of whom did not receive the service. Overall, the median delay to EIS was 120 days (IQR; 15-1668); and the median LOS was 130.5 days (IQR 0-663). We found that women (adj.HR 0.58; 95%C I 0.42-0.78), living alone (adj.HR: 0.63; 95% CI 0.43-0.92) and ethnicity ('Other': adj.HR 0.47; 95% CI 0.23-0.98) were associated with prolonged delay to EIS. However, family involvement in help-seeking for psychosis (adj.HR 1.37; 95% CI 1.01-1.85) was strongly associated with a shorter delay to EIS. Patients who have used mental health services previously also experienced long delays to EIS. CONCLUSIONS: Our analyses highlight the link between sociodemographic status, help-seeking behaviours, and delay to EIS. Our findings also show the vulnerability faced by those with a previous mental health problem who later develop psychosis in receiving specialist treatment for psychosis. Initiatives that ameliorate indicators of social disadvantage are urgently needed to reduce health inequalities and improve clinical outcomes.

Understanding social and clinical associations with unemployment for people with schizophrenia and bipolar disorders: large-scale health records study.

PURPOSE: People with severe mental illness (SMI) experience high levels of unemployment. We aimed to better understand the associations between clinical, social, and demographic inequality indicators and unemployment. METHODS: Data were extracted from de-identified health records of people with SMI in contact with secondary mental health services in south London, UK. A Natural Language Processing text-mining application was applied to extract information on unemployment in the health records. Multivariable logistic regression was used to assess associations with unemployment, in people with SMI. RESULTS: Records from 19,768 service users were used for analysis, 84.9% (n = 16,778) had experienced unemployment. In fully adjusted models, Black Caribbean and Black African service users were more likely to experience unemployment compared with White British service users (Black Caribbean: aOR 1.62, 95% CI 1.45-1.80; Black African: 1.32, 1.15-1.51). Although men were more likely to have experienced unemployment relative to women in unadjusted models (OR 1.36, 95% CI 1.26-1.47), differences were no longer apparent in the fully adjusted models (aOR 1.05, 95% CI 0.97-1.15). The presence of a non-affective (compared to affective) diagnosis (1.24, 1.13-1.35), comorbid substance use (2.02, 1.76-2.33), previous inpatient admissions (4.18, 3.71-4.70), longer inpatient stays (78 + days: 7.78, 6.34-9.54), and compulsory admissions (3.45, 3.04-3.92) were associated with unemployment, in fully adjusted models. CONCLUSION: People with SMI experience high levels of unemployment, and we found that unemployment was associated with several clinical and social factors. Interventions to address low employment may need to also address these broader inequalities.

Immersive virtual reality as a novel approach to investigate the association between adverse events and adolescent paranoid ideation.

PURPOSE: Paranoid ideation is common among adolescents, yet little is known about the precursors. Using a novel immersive virtual reality (VR) paradigm, we tested whether experiences of bullying, and other interpersonal/threatening events, are associated with paranoid ideation to a greater degree than other types of (i) non-interpersonal events or (ii) adverse childhood experiences. METHODS: Self-reported exposure to adverse life events and bullying was collected on 481 adolescents, aged 11-15. We used mixed effects (multilevel) linear regression to estimate the magnitude of associations between risk factors and paranoid ideation, assessed by means of adolescents' reactions to ambiguously behaving avatars in a VR school canteen, adjusting for putative confounders (gender, year group, ethnicity, free school meal status, place of birth, family mental health problems). RESULTS: Lifetime exposure to interpersonal/threatening events, but not non-interpersonal events or adverse circumstances, was associated with higher levels of state paranoid ideation, with further evidence that the effect was cumulative (1 type: ϐadj 0.07, 95% CI -0.01-0.14; 2 types: ϐadj 0.14, 95% CI 0.05-0.24; 3 + types: ϐadj 0.24, 95% CI 0.12-0.36). More tentatively, for girls, but not boys, recent bullying was associated with heightened paranoid ideation with effect estimates ranging from ϐadj 0.06 (95% CI -0.02-0.15) for physical bullying to ϐadj 0.21 (95% CI 0.10-0.32) for cyber bullying. CONCLUSIONS: Our data suggest a degree of specificity for adversities involving interpersonal threat or hostility, i.e. those that involve unwanted interference and/or attempted control of an individual's personal boundaries being associated with heightened levels of state paranoid ideation among adolescents.

A cross-sectional investigation into the role of intersectionality as a moderator of the relation between youth adversity and adolescent depression/anxiety symptoms in the community.

BACKGROUND: Adolescents exposed to adversity show higher levels of depression and anxiety, with the strongest links seen in socially/societally disadvantaged individuals (e.g., females, low socioeconomic status [SES]), as well as neurodivergent individuals. The intersection of these characteristics may be important for the differential distribution of adversity and mental health problems, though limited findings pertain to the extent to which intersectional effects moderate this association. METHODS: Combined depression/anxiety symptoms were measured using the emotional problems subscale of the Strengths and Difficulties Questionnaire in 13-14-year-olds in Cornwall, United Kingdom in 2017-2019. In a cross-sectional design (N = 11,707), multiple group structural equation modeling was used to estimate the effects of youth adversity on depression/anxiety symptoms across eight intersectionality profiles (based on gender [female/male], SES [lower/higher], and traits of hyperactivity/inattention [high/low]). Moderation effects of these characteristics and their intersections were estimated. RESULTS: Youth adversity was associated with higher levels of depression/anxiety (compared to an absence of youth adversity), across intersectional profiles. This effect was moderated by gender (stronger in males; ß = 0.22 [0.11, 0.36]), and SES (stronger in higher SES; ß = 0.26 [0.14,0.40]); with indications of moderation attributable to the intersection between gender and hyperactivity/inattention (ß = 0.21 [-0.02,0.44]). CONCLUSIONS: Youth adversity is associated with heightened depression/anxiety across intersectional profiles in 13-14-year-olds. The stronger effects observed for males, and for higher SES, may be interpreted in terms of structural privilege. Preliminary findings suggest that vulnerability and resilience to the effects of youth adversity may partially depend on specific intersectional effects. Importantly, the current results invite further investigation in this emerging line of inquiry.

Long-term psychological distress trajectories and the COVID-19 pandemic in three British birth cohorts: A multi-cohort study.

BACKGROUND: Growing evidence suggests that population mental health outcomes have worsened since the pandemic started. The extent that these changes have altered common age-related trends in psychological distress, where distress typically rises until midlife and then falls after midlife in both sexes, is unknown. We aimed to analyse whether long-term pre-pandemic psychological distress trajectories were disrupted during the pandemic, and whether these changes have been different across cohorts and by sex. METHODS AND FINDINGS: We used data from three nationally representative birth cohorts comprising all people born in Great Britain in a single week of 1946 (National Survey of Health and Development, NSHD), 1958 (National Child Development Study, NCDS), or 1970 (British Cohort Study, BCS70). The follow-up data used spanned 39 years in NSHD (1982 to 2021), 40 years in NCDS (1981 to 2001), and 25 years in BCS70 (1996 to 2021). We used psychological distress factor scores, as measured by validated self-reported questionnaires (NSHD: Present State Examination, Psychiatric Symptoms Frequency, and 28- and 12-item versions of General Health Questionnaire; NCDS and BCS70: Malaise Inventory; all: 2-item versions of Generalized Anxiety Disorder scale and Patient Health Questionnaire). We used a multilevel growth curve modelling approach to model the trajectories of distress across cohorts and sexes and obtained estimates of the differences between the distress levels observed during the pandemic and those observed at the most recent pre-pandemic assessment and at the peak in the cohort-specific pre-pandemic distress trajectory, located at midlife. We further analysed whether pre-existing cohort and sex inequalities had changed with the pandemic onset using a difference-in-differences (DiD) approach. The analytic sample included 16,389 participants. By September/October 2020, distress levels had reached or exceeded the levels of the peak in the pre-pandemic life-course trajectories, with larger increases in younger cohorts (standardised mean differences [SMD] and 95% confidence intervals of SMDNSHD,pre-peak = -0.02 [-0.07, 0.04], SMDNCDS,pre-peak = 0.05 [0.02, 0.07], and SMDBCS70,pre-peak = 0.09 [0.07, 0.12] for the 1946, 1958, and 1970 birth cohorts, respectively). Increases in distress were larger among women than men, widening pre-existing sex inequalities (DiD and 95% confidence intervals of DiDNSHD,sex,pre-peak = 0.17 [0.06, 0.28], DiDNCDS,sex,pre-peak = 0.11 [0.07, 0.16], and DiDBCS70,sex,pre-peak = 0.11 [0.05, 0.16] when comparing sex inequalities in the pre-pandemic peak in midlife to those observed by September/October 2020). As expected in cohort designs, our study suffered from high proportions of attrition with respect to the original samples. Although we used non-response weights to restore sample representativeness to the target populations (those born in the United Kingdom in 1946, 1958, and 1970, alive and residing in the UK), results may not be generalisable to other sections within the UK population (e.g., migrants and ethnic minority groups) and countries different than the UK. CONCLUSIONS: Pre-existing long-term psychological distress trajectories of adults born between 1946 and 1970 were disrupted during the COVID-19 pandemic, particularly among women, who reached the highest levels ever recorded in up to 40 years of follow-up data. This may impact future trends of morbidity, disability, and mortality due to common mental health problems.

Generational, sex, and socioeconomic inequalities in mental and social wellbeing during the COVID-19 pandemic: prospective longitudinal observational study of five UK cohorts.

BACKGROUND: Research suggests that there have been inequalities in the impact of the coronavirus disease 2019 (COVID-19) pandemic and related non-pharmaceutical interventions on population mental health. We explored generational, sex, and socioeconomic inequalities during the first year of the pandemic using nationally representative cohorts from the UK. METHODS: We analysed data from 26772 participants from five longitudinal cohorts representing generations born between 1946 and 2000, collected in May 2020, September-October 2020, and February-March 2021 across all five cohorts. We used a multilevel growth curve modelling approach to investigate generational, sex, and socioeconomic differences in levels of anxiety and depressive symptomatology, loneliness, and life satisfaction (LS) over time. RESULTS: Younger generations had worse levels of mental and social wellbeing throughout the first year of the pandemic. Whereas these generational inequalities narrowed between the first and last observation periods for LS [-0.33 (95% CI -0.51 to -0.15)], they became larger for anxiety [0.22 (0.10, 0.33)]. Generational inequalities in depression and loneliness did not change between the first and last observation periods, but initial depression levels of the youngest cohort were worse than expected if the generational inequalities had not accelerated. Women and those experiencing financial difficulties had worse initial mental and social wellbeing levels than men and those financially living comfortably, respectively, and these gaps did not substantially differ between the first and last observation periods. CONCLUSIONS: By March 2021, mental and social wellbeing inequalities persisted in the UK adult population. Pre-existing generational inequalities may have been exacerbated with the pandemic onset. Policies aimed at protecting vulnerable groups are needed.