Association of early-life exposure to air and noise pollution with youth mental health: findings from the ALSPAC cohort.

BACKGROUND: Increasing evidence suggests that air pollution exposure contributes to the development of mental health problems, including psychosis and depression. However, little is known about the importance of early-life exposure, nor the potential role of noise pollution, a correlate of air pollution. We examined the association of exposure to air and noise pollution from pregnancy to age 12 years with three mental health problems assessed at ages 12, 18, and 24 years. METHODS: Data were from the Avon Longitudinal Study of Parents and Children (ALSPAC), which tracks the development of about 14 000 babies who had expected delivery dates between April 1, 1991, and Dec 31, 1992, in Avon, UK. This was linked with novel data on nitrogen dioxide, PM2·5, and noise pollution in pregnancy, childhood (ages 1-9 years), and adolescence (ages 10-12 years). Psychotic experiences, depression, and anxiety were measured at ages 12, 18, and 24 years. Logistic regression models were controlled for individual-level, family-level, and area-level confounders, and e-values were calculated to estimate residual confounding. FINDINGS: Participants exposed to higher PM2.5, particularly during pregnancy, had greater odds for psychotic experiences (adjusted odds ratio 1·17 [95% CI 1·05-1·30]) and depression (1·11 [1·01-1·22]). There was little evidence associating nitrogen dioxide or noise pollution with psychotic experiences or depression. Conversely, higher nitrogen dioxide (but not PM2·5) exposure in pregnancy (1·16 [1·01-1·33]), and higher noise pollution in childhood (1·20 [1·06-1·37]) and adolescence (1·17 [1·02-1·35]), were associated with greater odds for anxiety. INTERPRETATION: Our study builds on evidence linking air pollution to psychosis and depression and provides rare longitudinal evidence linking noise pollution to anxiety. Our findings indicate that air pollution exposure earlier in development (eg, during pregnancy) might be particularly important, and suggest a degree of specificity in terms of pollutant-outcome associations. If causal, our findings suggest that interventions to reduce air pollution would improve global mental health. FUNDING: Wellcome Trust, UK Medical Research Council-Wellcome, and University of Bristol.

Implementing and Evaluating a National Integrated Digital Registry and Clinical Decision Support System in Early Intervention in Psychosis Services (Early Psychosis Informatics Into Care): Co-Designed Protocol.

BACKGROUND: Early intervention in psychosis (EIP) services are nationally mandated in England to provide multidisciplinary care to people experiencing first-episode psychosis, which disproportionately affects deprived and ethnic minority youth. Quality of service provision varies by region, and people from historically underserved populations have unequal access. In other disease areas, including stroke and dementia, national digital registries coupled with clinical decision support systems (CDSSs) have revolutionized the delivery of equitable, evidence-based interventions to transform patient outcomes and reduce population-level disparities in care. Given psychosis is ranked the third most burdensome mental health condition by the World Health Organization, it is essential that we achieve the same parity of health improvements. OBJECTIVE: This paper reports the protocol for the program development phase of this study, in which we aimed to co-design and produce an evidence-based, stakeholder-informed framework for the building, implementation, piloting, and evaluation of a national integrated digital registry and CDSS for psychosis, known as EPICare (Early Psychosis Informatics into Care). METHODS: We conducted 3 concurrent work packages, with reciprocal knowledge exchange between each. In work package 1, using a participatory co-design framework, key stakeholders (clinicians, academics, policy makers, and patient and public contributors) engaged in 4 workshops to review, refine, and identify a core set of essential and desirable measures and features of the EPICare registry and CDSS. Using a modified Delphi approach, we then developed a consensus of data priorities. In work package 2, we collaborated with National Health Service (NHS) informatics teams to identify relevant data currently captured in electronic health records, understand data retrieval methods, and design the software architecture and data model to inform future implementation. In work package 3, observations of stakeholder workshops and individual interviews with representative stakeholders (n=10) were subject to interpretative qualitative analysis, guided by normalization process theory, to identify factors likely to influence the adoption and implementation of EPICare into routine practice. RESULTS: Stage 1 of the EPICare study took place between December 2021 and September 2022. The next steps include stage 2 building, piloting, implementation, and evaluation of EPICare in 5 demonstrator NHS Trusts serving underserved and diverse populations with substantial need for EIP care in England. If successful, this will be followed by stage 3, in which we will seek NHS adoption of EPICare for rollout to all EIP services in England. CONCLUSIONS: By establishing a multistakeholder network and engaging them in an iterative co-design process, we have identified essential and desirable elements of the EPICare registry and CDSS; proactively identified and minimized potential challenges and barriers to uptake and implementation; and addressed key questions related to informatics architecture, infrastructure, governance, and integration in diverse NHS Trusts, enabling us to proceed with the building, piloting, implementation, and evaluation of EPICare. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/50177.

Refugee status and the incidence of affective psychotic disorders and non-psychotic bipolar disorder: A register-based cohort study of 1.3m people in Sweden.

BACKGROUND: Refugees are at increased risk of non-affective psychotic disorders, but it is unclear whether this extends to affective psychotic disorders [APD] or non-psychotic bipolar disorder [NPB]. METHODS: We conducted a nationwide cohort study in Sweden of all refugees, non-refugee migrants and the Swedish-born population, born 1 Jan 1984-31 Dec 2016. We followed participants from age 14 years until first ICD-10 diagnosis of APD or NPB. We fitted Cox proportional hazards models to estimate hazard ratios [HR] and 95 % confidence intervals [95%CI], adjusted for age, sex and family income. Models were additionally stratified by region-of-origin. RESULTS: We followed 1.3 million people for 15.1 million person-years, including 2428 new APD cases (rate: 16.0 per 100,000 person-years; 95%CI: 15.4-16.7) and 9425 NPB cases (rate: 63.8; 95%CI: 62.6-65.1). Rates of APD were higher in refugee (HRadjusted: 2.07; 95%CI: 1.55-2.78) and non-refugee migrants (HRadjusted: 1.40; 95%CI: 1.16-1.68), but lower for NPBs for refugee (HRadjusted: 0.24; 95%CI: 0.16-0.38) and non-refugee migrants (HRadjusted: 0.34; 95%CI: 0.28-0.41), compared with the Swedish-born. APD rates were elevated for both migrant groups from Asia and sub-Saharan Africa, but not other regions. Migrant groups from all regions-of-origin experienced lower rates of NPB. LIMITATIONS: Income may have been on the causal pathway making adjustment inappropriate. CONCLUSIONS: Refugees experience elevated rates of APD compared with Swedish-born and non-refugee migrants, but lower rates of NPB. This specificity of excess risk warrants clinical and public health investment in appropriate psychosis care for these vulnerable populations.

The effect of immigration policy reform on mental health in people from minoritised ethnic groups in England: an interrupted time series analysis of longitudinal data from the UK Household Longitudinal Study cohort.

BACKGROUND: In 2012, the UK Government announced a series of immigration policy reforms known as the hostile environment policy, culminating in the Windrush scandal. We aimed to investigate the effect of the hostile environment policy on mental health for people from minoritised ethnic backgrounds. We hypothesised that people from Black Caribbean backgrounds would have worse mental health relative to people from White ethnic backgrounds after the Immigration Act 2014 and the Windrush scandal media coverage in 2017, since they were particularly targeted. METHODS: Using data from the UK Household Longitudinal Study, we performed a Bayesian interrupted time series analysis, accounting for fixed effects of confounders (sex, age, urbanicity, relationship status, number of children, education, physical or mental health impairment, housing, deprivation, employment, place of birth, income, and time), and random effects for residual temporal and spatial variation. We measured mental ill health using a widely used, self-administered questionnaire on psychological distress, the 12-item General Health Questionnaire (GHQ-12). We compared mean differences (MDs) and 95% credible intervals (CrIs) in mental ill health among people from minoritised ethnic groups (Black Caribbean, Black African, Indian, Bangladeshi, and Pakistani) relative to people of White ethnicity during three time periods: before the Immigration Act 2014, after the Immigration Act 2014, and after the start of the Windrush scandal media coverage in 2017. FINDINGS: We included 58 087 participants with a mean age of 45·0 years (SD 34·6; range 16-106), including 31 168 (53·6%) female and 26 919 (46·3%) male participants. The cohort consisted of individuals from the following ethnic backgrounds: 2519 (4·3%) Black African, 2197 (3·8%) Black Caribbean, 3153 (5·4%) Indian, 1584 (2·7%) Bangladeshi, 2801 (4·8%) Pakistani, and 45 833 (78·9%) White. People from Black Caribbean backgrounds had worse mental health than people of White ethnicity after the Immigration Act 2014 (MD in GHQ-12 score 0·67 [95% CrI 0·06-1·28]) and after the 2017 media coverage (1·28 [0·34-2·21]). For Black Caribbean participants born outside of the UK, mental health worsened after the Immigration Act 2014 (1·25 [0·11-2·38]), and for those born in the UK, mental health worsened after the 2017 media coverage (2·00 [0·84-3·15]). We did not observe effects in other minoritised ethnic groups. INTERPRETATION: Our finding that the hostile environment policy worsened the mental health of people from Black Caribbean backgrounds in the UK suggests that sufficient, appropriate mental health and social welfare support should be provided to those affected. Impact assessments of new policies on minority mental health should be embedded in all policy making. FUNDING: Wellcome Trust.

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.

The social determinants of mental health and disorder: evidence, prevention and recommendations.

People exposed to more unfavourable social circumstances are more vulnerable to poor mental health over their life course, in ways that are often determined by structural factors which generate and perpetuate intergenerational cycles of disadvantage and poor health. Addressing these challenges is an imperative matter of social justice. In this paper we provide a roadmap to address the social determinants that cause mental ill health. Relying as far as possible on high-quality evidence, we first map out the literature that supports a causal link between social determinants and later mental health outcomes. Given the breadth of this topic, we focus on the most pervasive social determinants across the life course, and those that are common across major mental disorders. We draw primarily on the available evidence from the Global North, acknowledging that other global contexts will face both similar and unique sets of social determinants that will require equitable attention. Much of our evidence focuses on mental health in groups who are marginalized, and thus often exposed to a multitude of intersecting social risk factors. These groups include refugees, asylum seekers and displaced persons, as well as ethnoracial minoritized groups; lesbian, gay, bisexual, transgender and queer (LGBTQ+) groups; and those living in poverty. We then introduce a preventive framework for conceptualizing the link between social determinants and mental health and disorder, which can guide much needed primary prevention strategies capable of reducing inequalities and improving population mental health. Following this, we provide a review of the evidence concerning candidate preventive strategies to intervene on social determinants of mental health. These interventions fall broadly within the scope of universal, selected and indicated primary prevention strategies, but we also briefly review important secondary and tertiary strategies to promote recovery in those with existing mental disorders. Finally, we provide seven key recommendations, framed around social justice, which constitute a roadmap for action in research, policy and public health. Adoption of these recommendations would provide an opportunity to advance efforts to intervene on modifiable social determinants that affect population mental health.

Measuring social exclusion and its distribution in England.

BACKGROUND: Social exclusion is a multidimensional concept referring processes which restrict the ability of individuals or groups to participate fully in society. While social exclusion has been used to explore patterns of disadvantage, it has been difficult to measure. Thus, we aimed to use population-based data to measure social exclusion and its constituent domains and to describe its distribution in England. METHODS: We used data from Understanding Society in 2009/2010 develop a multidimensional measurement approach, replicated in 2018/2019. We defined five domains of social exclusion from the literature and expert consultation: material, relational, political, digital, and structural. In both waves, we identified measures for each domain, then conducted principal component analysis to identify the components. We generated domain scores and an overall social exclusion score. We described the distribution of social exclusion and its domains by sex, region, age, and ethnicity. RESULTS: We found the level of social exclusion was higher in the youngest age group and decreased by age. We found elevated levels of overall social exclusion for ethnic minoritised groups including African, Arab, and Caribbean groups compared to White British groups. We found distinct patterns within each domain. DISCUSSION: We developed an overall measure of social exclusion with five domains, and finding distinct patterns of social exclusion by age, ethnicity, and region which varied across domain. These findings suggest that attention should be paid to the separate domains due to different population distributions. This measurement approach moves beyond conceptual discussions of social exclusion and demonstrates the utility of a quantitative measure of social exclusion for use in health and social research.

Immune-neuroendocrine patterning and response to stress. A latent profile analysis in the English longitudinal study of ageing.

Psychosocial stress exposure can disturb communication signals between the immune, nervous, and endocrine systems that are intended to maintain homeostasis. This dysregulation can provoke a negative feedback loop between each system that has high pathological risk. Here, we explore patterns of immune-neuroendocrine activity and the role of stress. Using data from the English Longitudinal Study of Ageing (ELSA), we first identified the latent structure of immune-neuroendocrine activity (indexed by high sensitivity C-reactive protein [CRP], fibrinogen [Fb], hair cortisol [cortisol], and insulin growth-factor-1 [IGF-1]), within a population-based cohort using latent profile analysis (LPA). Then, we determined whether life stress was associated with membership of different immune-neuroendocrine profiles. We followed 4,934 male and female participants, with a median age of 65 years, over a four-year period (2008-2012). A three-class LPA solution offered the most parsimonious fit to the underlying immune-neuroendocrine structure in the data, with 36 %, 40 %, and 24 % of the population belonging to profiles 1 (low-risk), 2 (moderate-risk), and 3 (high-risk), respectively. After adjustment for genetic predisposition, sociodemographics, lifestyle, and health, higher exposure to stress was associated with a 61 % greater risk of belonging to the high-risk profile (RRR: 1.61; 95 %CI = 1.23-2.12, p = 0.001), but not the moderate-risk profile (RRR = 1.10, 95 %CI = 0.89-1.35, p = 0.401), as compared with the low-risk profile four years later. Our findings extend existing knowledge on psychoneuroimmunological processes, by revealing how inflammation and neuroendocrine activity cluster in a representative sample of older adults, and how stress exposure was associated with immune-neuroendocrine responses over time.

Cannabis use as a potential mediator between childhood adversity and first-episode psychosis: results from the EU-GEI case-control study.

BACKGROUND: Childhood adversity and cannabis use are considered independent risk factors for psychosis, but whether different patterns of cannabis use may be acting as mediator between adversity and psychotic disorders has not yet been explored. The aim of this study is to examine whether cannabis use mediates the relationship between childhood adversity and psychosis. METHODS: Data were utilised on 881 first-episode psychosis patients and 1231 controls from the European network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI) study. Detailed history of cannabis use was collected with the Cannabis Experience Questionnaire. The Childhood Experience of Care and Abuse Questionnaire was used to assess exposure to household discord, sexual, physical or emotional abuse and bullying in two periods: early (0-11 years), and late (12-17 years). A path decomposition method was used to analyse whether the association between childhood adversity and psychosis was mediated by (1) lifetime cannabis use, (2) cannabis potency and (3) frequency of use. RESULTS: The association between household discord and psychosis was partially mediated by lifetime use of cannabis (indirect effect coef. 0.078, s.e. 0.022, 17%), its potency (indirect effect coef. 0.059, s.e. 0.018, 14%) and by frequency (indirect effect coef. 0.117, s.e. 0.038, 29%). Similar findings were obtained when analyses were restricted to early exposure to household discord. CONCLUSIONS: Harmful patterns of cannabis use mediated the association between specific childhood adversities, like household discord, with later psychosis. Children exposed to particularly challenging environments in their household could benefit from psychosocial interventions aimed at preventing cannabis misuse.

Ethnic differences in receipt of psychological interventions in Early Intervention in Psychosis services in England - a cross-sectional study.

There is some evidence of differences in psychosis care provision by ethnicity. We investigated variations in the receipt of Cognitive Behavioural Therapy for psychosis (CBTp) and family intervention across ethnic groups in Early Intervention in Psychosis (EIP) teams throughout England, where national policy mandates offering these interventions to all. We included data on 29,610 service users from the National Clinical Audit of Psychosis (NCAP), collected between 2018 and 2021. We conducted mixed effects logistic regression analyses to examine odds ratios of receiving an intervention (CBTp, family intervention, either intervention) across 17 ethnic groups while accounting for the effect of years and variance between teams and adjusting for individual- (age, gender, occupational status) and team-level covariates (care-coordinator caseload, inequalities strategies). Compared with White British people, every minoritized ethnic group, except those of mixed Asian-White and mixed Black African-White ethnicities, had significantly lower adjusted odds of receiving CBTp. People of Black African, Black Caribbean, non-African/Caribbean Black, non-British/Irish White, and of "any other" ethnicity also experienced significantly lower adjusted odds of receiving family intervention. Pervasive inequalities in receiving CBTp for first episode psychosis exist for almost all minoritized ethnic groups, and family intervention for many groups. Investigating how these inequalities arise should be a research priority.

Investigating social deprivation and comorbid mental health diagnosis as predictors of treatment access among patients with an opioid use disorder using substance use services: a prospective cohort study.

BACKGROUND: Opioid use is a major public health concern across the globe. Opioid use and subsequent access to care is often shaped by co-occurring issues faced by people using opioids, such as deprivation, mental ill-health, and other forms of substance use. We investigated the role of social deprivation and comorbid mental health diagnoses in predicting re-engagement with substance use services or contact with crisis and inpatient services for individuals with opioid use disorder in secondary mental health care in inner-city London. METHODS: We conducted a prospective cohort study which followed individuals diagnosed with a first episode of opioid use disorder who accessed substance use services between September 2015 and May 2020 for up to 12 months, using anonymised electronic health records. We employed negative binominal regression and Cox proportional survival analyses to assess associations between exposures and outcomes. RESULTS: Comorbid mental health diagnoses were associated with higher contact rates with crisis/inpatient services among people with opioid use disorder: incidence rate ratios (IRR) and 95% confidence intervals (CI) were 3.91 (1.74-9.14) for non-opioid substance use comorbidity, 8.92 (1.81-64.4) for a single comorbid mental health diagnosis, and 15.9 (5.89-47.5) for multiple comorbid mental health diagnoses. Social deprivation was not associated with contact rates with crisis/inpatient services within this sample. Similar patterns were found with time to first crisis/inpatient contact. Social deprivation and comorbid mental health diagnoses were not associated with re-engagement with substance use services. CONCLUSION: Comorbid substance and mental health difficulties amongst people with an opioid use disorder led to earlier and more frequent contact with crisis/inpatient mental health services during the first 12 months of follow up. Given the common co-occurrence of mental health and substance use disorders among those who use opioids, a better understanding of their wider needs (such as social, financial and other non-medical concerns) will ensure they are supported in their treatment journeys.

Social Deprivation and Population Density Trajectories Before and After Psychotic Disorder Diagnosis.

Importance: People with psychosis are more likely to be born and live in densely populated and socioeconomically deprived environments, but it is unclear whether these associations are a cause or consequence of disorder. Objective: To investigate whether trajectories of exposure to deprivation and population density before and after diagnosis are associated with psychotic disorders or nonpsychotic bipolar disorder. Design, Setting, and Participants: This nested case-control study included all individuals born in Sweden between January 1, 1982, and December 31, 2001, diagnosed for the first time with an International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) psychotic disorder or nonpsychotic bipolar disorder between their 15th birthday and cohort exit (December 31, 2016). One sex- and birth year-matched control participant per case was selected. Data analysis was performed from July 2021 to June 2023. Exposures: The main exposures were quintiles of neighborhood-level deprivation and population density each year from birth to age 14 years and from first diagnosis until cohort exit. Main Outcomes and Measures: The main outcomes were the odds of a serious mental illness outcome associated with trajectories of deprivation and population density, before and after diagnosis in cases. Group-based trajectory modeling was used to derive trajectories of each exposure in each period. Logistic regression was used to examine associations with outcomes. Results: A total of 53 458 individuals (median [IQR] age at diagnosis in case patients, 23.2 [15.0-34.8] years; 30 746 [57.5%] female), including 26 729 case patients and 26 729 control participants, were studied. From birth to early adolescence, gradients were observed in exposure to deprivation and population density trajectories during upbringing and psychotic disorder, with those in the most vs least deprived (adjusted odds ratio [AOR], 1.17; 95% CI, 1.08-1.28) and most vs least densely populated (AOR, 1.49; 95% CI, 1.34-1.66) trajectories at greatest risk. A strong upward mobility trajectory to less deprived neighborhoods was associated with similar risk to living in the least deprived trajectory (AOR, 1.01; 95% CI, 0.91-1.12). Only 543 case patients (2.0%) drifted into more deprived areas after diagnosis; people with psychotic disorder were more likely to belong to this trajectory (AOR, 1.38; 95% CI, 1.16-1.65) or remain in the most deprived trajectory (AOR, 1.36; 95% CI, 1.24-1.48) relative to controls. Patterns were similar for nonpsychotic bipolar disorder and deprivation but weaker for population density. Conclusions and Relevance: In this case-control study, greater exposure to deprivation during upbringing was associated with increased risk of serious mental illness, but upward mobility mitigated this association. People with serious mental illness disproportionately remained living in more deprived areas after diagnosis, highlighting issues of social immobility. Prevention and treatment should be proportionately located in deprived areas according to need.

Associations between constructs related to social relationships and mental health conditions and symptoms: an umbrella review.

BACKGROUND: Loneliness and social isolation are increasingly recognised as prevalent among people with mental health problems, and as potential targets for interventions to improve quality of life and outcomes, as well as for preventive strategies. Understanding the relationship between quality and quantity of social relationships and a range of mental health conditions is a helpful step towards development of such interventions. PURPOSE: Our aim was to give an overview of associations between constructs related to social relationships (including loneliness and social isolation) and diagnosed mental conditions and mental health symptoms, as reported in systematic reviews of observational studies. METHODS: For this umbrella review (systematic review of systematic reviews) we searched five databases (PsycINFO, MEDLINE, EMBASE, CINAHL, Web of Science) and relevant online resources (PROSPERO, Campbell Collaboration, Joanna Briggs Institute Evidence Synthesis Journal). We included systematic reviews of studies of associations between constructs related to social relationships and mental health diagnoses or psychiatric symptom severity, in clinical or general population samples. We also included reviews of general population studies investigating the relationship between loneliness and risk of onset of mental health problems. RESULTS: We identified 53 relevant systematic reviews, including them in a narrative synthesis. We found evidence regarding associations between (i) loneliness, social isolation, social support, social network size and composition, and individual-level social capital and (ii) diagnoses of mental health conditions and severity of various mental health symptoms. Depression (including post-natal) and psychosis were most often reported on, with few systematic reviews on eating disorders or post-traumatic stress disorder (PTSD), and only four related to anxiety. Social support was the most commonly included social construct. Our findings were limited by low quality of reviews and their inclusion of mainly cross-sectional evidence. CONCLUSION: Good quality evidence is needed on a wider range of social constructs, on conditions other than depression, and on longitudinal relationships between social constructs and mental health symptoms and conditions.

Immune-Neuroendocrine Patterning and Response to Stress. A latent profile analysis in the English Longitudinal Study of Ageing.

Psychosocial stress exposure can disturb communication signals between the immune, nervous, and endocrine systems that are intended to maintain homeostasis. This dysregulation can provoke a negative feedback loop between each system that has high pathological risk. Here, we explore patterns of immune-neuroendocrine activity and the role of stress. Using data from the English Longitudinal Study of Ageing (ELSA), we first identified the latent structure of immune-neuroendocrine activity (indexed by high sensitivity C-reactive protein [CRP], fibrinogen [Fb], hair cortisol [cortisol], and insulin growth-factor-1 [IGF-1]), within a population-based cohort using latent profile analysis (LPA). Then, we determined whether life stress was associated with membership of different immune-neuroendocrine profiles. We followed 4,934 male and female participants with a median age of 65 years over a four-year period (2008-2012). A three-class LPA solution offered the most parsimonious fit to the underlying immune-neuroendocrine structure in the data, with 36%, 40%, and 24% of the population belonging to profiles 1 (low-risk), 2 (moderate-risk), and 3 (high-risk), respectively. After adjustment for genetic predisposition, sociodemographics, lifestyle, and health, higher exposure to stress was associated with a 61% greater risk of belonging to the high-risk profile (RRR: 1.61; 95%CI=1.23-2.12, p=0.001), but not the moderate-risk profile (RRR=1.10, 95%CI=0.89-1.35, p=0.401), as compared with the low-risk profile four years later. Our findings extend existing knowledge on psychoneuroimmunological processes, by revealing how inflammation and neuroendocrine activity cluster in a representative sample of older adults, and how stress exposure was associated with immune-neuroendocrine responses over time.

Differences in Patterns of Stimulant Use and Their Impact on First-Episode Psychosis Incidence: An Analysis of the EUGEI Study.

BACKGROUND: Use of illegal stimulants is associated with an increased risk of psychotic disorder. However, the impact of stimulant use on odds of first-episode psychosis (FEP) remains unclear. Here, we aimed to describe the patterns of stimulant use and examine their impact on odds of FEP. METHODS: We included patients with FEP aged 18-64 years who attended psychiatric services at 17 sites across 5 European countries and Brazil, and recruited controls representative of each local population (FEP = 1130; controls = 1497). Patterns of stimulant use were described. We computed fully adjusted logistic regression models (controlling for age, sex, ethnicity, cannabis use, and education level) to estimate their association with odds of FEP. Assuming causality, we calculated the population-attributable fractions for stimulant use associated with the odds for FEP. FINDINGS: Prevalence of lifetime and recent stimulant use in the FEP sample were 14.50% and 7.88% and in controls 10.80% and 3.8%, respectively. Recent and lifetime stimulant use was associated with increased odds of FEP compared with abstainers [fully adjusted odds ratio 1.74,95% confidence interval (CI) 1.20-2.54, P = .004 and 1.62, 95% CI 1.25-2.09, P < .001, respectively]. According to PAFs, a substantial number of FEP cases (3.35% [95% CI 1.31-4.78] for recent use and 7.61% [95% CI 3.68-10.54] for lifetime use) could have been prevented if stimulants were no longer available and the odds of FEP and PAFs for lifetime and recent stimulant use varied across countries. INTERPRETATION: Illegal stimulant use has a significant and clinically relevant influence on FEP incidence, with varying impacts across countries.

Mental health in Europe during the COVID-19 pandemic: a systematic review.

The COVID-19 pandemic caused immediate and far-reaching disruption to society, the economy, and health-care services. We synthesised evidence on the effect of the pandemic on mental health and mental health care in high-income European countries. We included 177 longitudinal and repeated cross-sectional studies comparing prevalence or incidence of mental health problems, mental health symptom severity in people with pre-existing mental health conditions, or mental health service use before versus during the pandemic, or between different timepoints of the pandemic. We found that epidemiological studies reported higher prevalence of some mental health problems during the pandemic compared with before it, but that in most cases this increase reduced over time. Conversely, studies of health records showed reduced incidence of new diagnoses at the start of the pandemic, which further declined during 2020. Mental health service use also declined at the onset of the pandemic but increased later in 2020 and through 2021, although rates of use did not return to pre-pandemic levels for some services. We found mixed patterns of effects of the pandemic on mental health and social outcome for adults already living with mental health conditions.

The relationship between genetic liability, childhood maltreatment, and IQ: findings from the EU-GEI multicentric case-control study.

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.

Synergistic effects of childhood adversity and polygenic risk in first-episode psychosis: the EU-GEI study.

BACKGROUND: A history of childhood adversity is associated with psychotic disorder, with an increase in risk according to the number of exposures. However, it is not known why only some exposed individuals go on to develop psychosis. One possibility is pre-existing polygenic vulnerability. Here, we investigated, in the largest sample of first-episode psychosis (FEP) cases to date, whether childhood adversity and high polygenic risk scores for schizophrenia (SZ-PRS) combine synergistically to increase the risk of psychosis, over and above the effect of each alone. METHODS: We assigned a schizophrenia-polygenic risk score (SZ-PRS), calculated from the Psychiatric Genomics Consortium (PGC2), to all participants in a sample of 384 FEP patients and 690 controls from the case-control component of the EU-GEI study. Only participants of European ancestry were included in the study. A history of childhood adversity was collected using the Childhood Trauma Questionnaire (CTQ). Synergistic effects were estimated using the interaction contrast ratio (ICR) [odds ratio (OR)exposure and PRS - ORexposure - ORPRS + 1] with adjustment for potential confounders. RESULTS: There was some evidence that the combined effect of childhood adversities and polygenic risk was greater than the sum of each alone, as indicated by an ICR greater than zero [i.e. ICR 1.28, 95% confidence interval (CI) -1.29 to 3.85]. Examining subtypes of childhood adversities, the strongest synergetic effect was observed for physical abuse (ICR 6.25, 95% CI -6.25 to 20.88). CONCLUSIONS: Our findings suggest possible synergistic effects of genetic liability and childhood adversity experiences in the onset of FEP, but larger samples are needed to increase precision of estimates.

The association between reasons for first using cannabis, later pattern of use, and risk of first-episode psychosis: the EU-GEI case-control study.

BACKGROUND: While cannabis use is a well-established risk factor for psychosis, little is known about any association between reasons for first using cannabis (RFUC) and later patterns of use and risk of psychosis. METHODS: We used data from 11 sites of the multicentre European Gene-Environment Interaction (EU-GEI) case-control study. 558 first-episode psychosis patients (FEPp) and 567 population controls who had used cannabis and reported their RFUC.We ran logistic regressions to examine whether RFUC were associated with first-episode psychosis (FEP) case-control status. Path analysis then examined the relationship between RFUC, subsequent patterns of cannabis use, and case-control status. RESULTS: Controls (86.1%) and FEPp (75.63%) were most likely to report 'because of friends' as their most common RFUC. However, 20.1% of FEPp compared to 5.8% of controls reported: 'to feel better' as their RFUC (χ2 = 50.97; p < 0.001). RFUC 'to feel better' was associated with being a FEPp (OR 1.74; 95% CI 1.03-2.95) while RFUC 'with friends' was associated with being a control (OR 0.56; 95% CI 0.37-0.83). The path model indicated an association between RFUC 'to feel better' with heavy cannabis use and with FEPp-control status. CONCLUSIONS: Both FEPp and controls usually started using cannabis with their friends, but more patients than controls had begun to use 'to feel better'. People who reported their reason for first using cannabis to 'feel better' were more likely to progress to heavy use and develop a psychotic disorder than those reporting 'because of friends'.