Publications by authors named "Peter B Jones"

397 Publications

Risk and protective factors for mental disorders beyond genetics: an evidence-based atlas.

World Psychiatry 2021 Oct;20(3):417-436

Early Psychosis: Interventions and Clinical-detection (EPIC) Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.

Decades of research have revealed numerous risk factors for mental disorders beyond genetics, but their consistency and magnitude remain uncer-tain. We conducted a "meta-umbrella" systematic synthesis of umbrella reviews, which are systematic reviews of meta-analyses of individual studies, by searching international databases from inception to January 1, 2021. We included umbrella reviews on non-purely genetic risk or protective factors for any ICD/DSM mental disorders, applying an established classification of the credibility of the evidence: class I (convincing), class II (highly suggestive), class III (suggestive), class IV (weak). Sensitivity analyses were conducted on prospective studies to test for temporality (reverse causation), TRANSD criteria were applied to test transdiagnosticity of factors, and A Measurement Tool to Assess Systematic Reviews (AMSTAR) was employed to address the quality of meta-analyses. Fourteen eligible umbrella reviews were retrieved, summarizing 390 meta-analyses and 1,180 associations between putative risk or protective factors and mental disorders. We included 176 class I to III evidence associations, relating to 142 risk/protective factors. The most robust risk factors (class I or II, from prospective designs) were 21. For dementia, they included type 2 diabetes mellitus (risk ratio, RR from 1.54 to 2.28), depression (RR from 1.65 to 1.99) and low frequency of social contacts (RR=1.57). For opioid use disorders, the most robust risk factor was tobacco smoking (odds ratio, OR=3.07). For non-organic psychotic disorders, the most robust risk factors were clinical high risk state for psychosis (OR=9.32), cannabis use (OR=3.90), and childhood adversities (OR=2.80). For depressive disorders, they were widowhood (RR=5.59), sexual dysfunction (OR=2.71), three (OR=1.99) or four-five (OR=2.06) metabolic factors, childhood physical (OR=1.98) and sexual (OR=2.42) abuse, job strain (OR=1.77), obesity (OR=1.35), and sleep disturbances (RR=1.92). For autism spectrum disorder, the most robust risk factor was maternal overweight pre/during pregnancy (RR=1.28). For attention-deficit/hyperactivity disorder (ADHD), they were maternal pre-pregnancy obesity (OR=1.63), maternal smoking during pregnancy (OR=1.60), and maternal overweight pre/during pregnancy (OR=1.28). Only one robust protective factor was detected: high physical activity (hazard ratio, HR=0.62) for Alzheimer's disease. In all, 32.9% of the associations were of high quality, 48.9% of medium quality, and 18.2% of low quality. Transdiagnostic class I-III risk/protective factors were mostly involved in the early neurodevelopmental period. The evidence-based atlas of key risk and protective factors identified in this study represents a benchmark for advancing clinical characterization and research, and for expanding early intervention and preventive strategies for mental disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/wps.20894DOI Listing
October 2021

Role of inflammation in depression and anxiety: Tests for disorder specificity, linearity and potential causality of association in the UK Biobank.

EClinicalMedicine 2021 Aug 26;38:100992. Epub 2021 Jun 26.

Department of Psychiatry, University of Cambridge, Cambridge, UK.

Background: Concentrations of C-reactive protein (CRP), interleukin 6 (IL-6) and other inflammatory markers are elevated in people with depression and anxiety compared to controls, but evidence for disorder-specificity, linearity and potential causality is sparse.

Methods: Using population-based data from up to 144,890 UK Biobank cohort participants, we tested associations of circulating CRP concentrations with depression and anxiety symptom scores and probable diagnosis, including tests for linearity, disorder-specificity and sex difference. We examined potential causality using 1-sample and 2-sample Mendelian randomisation (MR) analyses testing associations of genetically-predicted CRP concentration and IL-6 activity with depression and anxiety. The study was conducted from June 2019 to February 2021.

Findings: CRP concentration was associated with depressive and anxiety symptom scores and with probable diagnoses of depression and generalised anxiety disorder (GAD) in a dose-response fashion. These associations were stronger for depression than for anxiety, and for women than for men although less consistently. MR analyses provided consistent results suggesting that genetically predicted higher IL-6 activity was associated with increased risk for depressive symptoms, while genetically-predicted higher CRP concentration was associated with decreased risks of depressive and anxiety symptoms.

Interpretation: Altered activity of the IL-6/IL-6R pathway could be a risk factor for depression. The field now requires experimental studies of IL-6 modulation in humans and animal models to further examine causality, mechanisms and treatment potential. Such studies are also needed to elucidate mechanisms for divergent associations of genetically-predicted higher IL-6 activity (risk increasing) and higher CRP concentrations (protective) with depression/anxiety.

Funding: This research was funded in whole, or in part, by the Wellcome Trust (grant code: 201486/Z/16/Z). For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. This work was supported by a Data Science Award from the MQ: Transforming Mental Health (grant code: MQDS17/40) to GMK and PBJ, which also supported ZY. GMK also acknowledges funding support from the Wellcome Trust (grant code: 201486/Z/16/Z), the Medical Research Council UK (grant code: MC_PC_17213 and MR/S037675/1), and the BMA Foundation (J Moulton grant 2019). NK and SM are supported by the International Max Planck Research School of Translational Psychiatry (IMPRS-TP). GDS works in the Medical Research Council Integrative Epidemiology Unit at the University of Bristol, which is supported by the Medical Research Council (MC_UU_00011/1).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.eclinm.2021.100992DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8413248PMC
August 2021

Using epidemiological evidence to forecast population need for early treatment programmes in mental health: a generalisable Bayesian prediction methodology applied to and validated for first-episode psychosis in England.

Br J Psychiatry Suppl 2021 Jul 8;219(1):383-391. Epub 2021 Mar 8.

Division of Psychiatry, University College London, UK.

Background: Mental health policy makers require evidence-based information to optimise effective care provision based on local need, but tools are unavailable.

Aims: To develop and validate a population-level prediction model for need for early intervention in psychosis (EIP) care for first-episode psychosis (FEP) in England up to 2025, based on epidemiological evidence and demographic projections.

Method: We used Bayesian Poisson regression to model small-area-level variation in FEP incidence for people aged 16-64 years. We compared six candidate models, validated against observed National Health Service FEP data in 2017. Our best-fitting model predicted annual incidence case-loads for EIP services in England up to 2025, for probable FEP, treatment in EIP services, initial assessment by EIP services and referral to EIP services for 'suspected psychosis'. Forecasts were stratified by gender, age and ethnicity, at national and Clinical Commissioning Group levels.

Results: A model with age, gender, ethnicity, small-area-level deprivation, social fragmentation and regional cannabis use provided best fit to observed new FEP cases at national and Clinical Commissioning Group levels in 2017 (predicted 8112, 95% CI 7623-8597; observed 8038, difference of 74 [0.92%]). By 2025, the model forecasted 11 067 new treated cases per annum (95% CI 10383-11740). For every 10 new treated cases, 21 and 23 people would be assessed by and referred to EIP services for suspected psychosis, respectively.

Conclusions: Our evidence-based methodology provides an accurate, validated tool to inform clinical provision of EIP services about future population need for care, based on local variation of major social determinants of psychosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1192/bjp.2021.18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611597PMC
July 2021

Understanding the excess psychosis risk in ethnic minorities: the impact of structure and identity.

Soc Psychiatry Psychiatr Epidemiol 2021 Aug 24. Epub 2021 Aug 24.

Department of Psychiatry, University of Cambridge, Herchel Smith Building, Forvie Site, Robinson Way, Cambridge, CB2 0SZ, UK.

Purpose: Psychotic disorders, which are associated with substantially increased morbidity and mortality, are up to five times more common in some ethnic minority groups compared with the white majority in Western countries. This long-standing and well-replicated public mental health disparity has hitherto largely eluded adequate explanation. We argue that this might have arisen in part due to the lack of attention given to theoretical work characterising the complex and multidimensional social nature of ethnicity by those epidemiological investigations that have dominated the literature.

Methods: To bridge this gap, we draw on theoretical and empirical literature from across the social sciences considering the ontological significance of ethnicity (as biology, migration, racialised structures and identity) and its relationships with psychotic disorders to illuminate probable drivers of excess psychosis risk.

Results: The largest gains in our theoretical understanding of excess psychosis risk among ethnic minority groups are to be made by considering ethnicity in relation to disempowerment resulting from structural and identity-based exclusion. The former is readily studied through the social gradient in health: socioeconomic disadvantage clusters in some ethnic minorities and increases the risk of poor health outcomes, including psychosis. Furthermore, limitations on identity acquisition and expression imposed by the ethnic majority can further contribute to alienate ethnic minorities and increase psychosocial disempowerment (a lack of control over one's life).

Conclusion: We theorise that structural and identity-based exclusion act as the primary drivers shaping variation in rates of psychotic disorder by ethnic minority status.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00127-021-02042-8DOI Listing
August 2021

The relationship of symptom dimensions with premorbid adjustment and cognitive characteristics at first episode psychosis: Findings from the EU-GEI study.

Schizophr Res 2021 Aug 14;236:69-79. Epub 2021 Aug 14.

Department of Psychiatry, Early Psychosis Section, Amsterdam UMC, University of Amsterdam, Meibergdreef 5, 1105 AZ Amsterdam, the Netherlands; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, USA.

Premorbid functioning and cognitive measures may reflect gradients of developmental impairment across diagnostic categories in psychosis. In this study, we sought to examine the associations of current cognition and premorbid adjustment with symptom dimensions in a large first episode psychosis (FEP) sample. We used data from the international EU-GEI study. Bifactor modelling of the Operational Criteria in Studies of Psychotic Illness (OPCRIT) ratings provided general and specific symptom dimension scores. Premorbid Adjustment Scale estimated premorbid social (PSF) and academic adjustment (PAF), and WAIS-brief version measured IQ. A MANCOVA model examined the relationship between symptom dimensions and PSF, PAF, and IQ, having age, sex, country, self-ascribed ethnicity and frequency of cannabis use as confounders. In 785 patients, better PSF was associated with fewer negative (B = -0.12, 95% C.I. -0.18, -0.06, p < 0.001) and depressive (B = -0.09, 95% C.I. -0.15, -0.03, p = 0.032), and more manic (B = 0.07, 95% C.I. 0.01, 0.14, p = 0.023) symptoms. Patients with a lower IQ presented with slightly more negative and positive, and fewer manic, symptoms. Secondary analysis on IQ subdomains revealed associations between better perceptual reasoning and fewer negative (B = -0.09, 95% C.I. -0.17, -0.01, p = 0.023) and more manic (B = 0.10, 95% C.I. 0.02, 0.18, p = 0.014) symptoms. Fewer positive symptoms were associated with better processing speed (B = -0.12, 95% C.I. -0.02, -0.004, p = 0.003) and working memory (B = -0.10, 95% C.I. -0.18, -0.01, p = 0.024). These findings suggest that the negative and manic symptom dimensions may serve as clinical proxies of different neurodevelopmental predisposition in psychosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.schres.2021.08.008DOI Listing
August 2021

Risk factors for excess deaths during lockdown among older users of secondary care mental health services without confirmed COVID-19: A retrospective cohort study.

Int J Geriatr Psychiatry 2021 Aug 11. Epub 2021 Aug 11.

Department of Psychiatry, University of Cambridge, Cambridge, UK.

Objective: To investigate factors contributing to excess deaths of older patients during the initial 2020 lockdown beyond those attributable to confirmed COVID-19.

Methods: Retrospective cohort study comparing patients treated between 23 March 2020 and 14 June 2020, deemed exposed to the pandemic/lockdown, to patients treated between 18 December 2019 and 10 March 2020, deemed to be unexposed. Data came from electronic clinical records from secondary care mental health services in Cambridgeshire and Peterborough NHS Foundation Trust (CPFT), UK (catchment area population ∼0.86 million). Eligible patients were aged 65 years or over at baseline with at least 14 days' follow-up, excluding patients diagnosed with confirmed or suspected SARS-CoV-2 infection. The primary outcome was all-cause mortality.

Findings: In the two cohorts, 3,073 subjects were exposed to lockdown and 4,372 subjects were unexposed; the cohorts were followed up for an average of 74 and 78 days, respectively. After controlling for confounding by sociodemographic factors, smoking status, mental comorbidities, and physical comorbidities, patients with dementia suffered an additional 53% risk of death (HR = 1.53, 95% CI = 1.02-2.31), and patients with severe mental illness suffered an additional 123% risk of death (HR = 2.23, 95% CI = 1.42-3.49). No significant additional mortality risks were identified from physical comorbidities, potentially due to low statistical power in that respect.

Conclusion: During lockdown people with dementia or severe mental illness had a higher risk of death without confirmed COVID-19. These data could inform future health service responses and policymaking to help prevent avoidable excess death during future outbreaks of this or a similar infectious disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/gps.5610DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8420159PMC
August 2021

The continuity of effect of schizophrenia polygenic risk score and patterns of cannabis use on transdiagnostic symptom dimensions at first-episode psychosis: findings from the EU-GEI study.

Transl Psychiatry 2021 Aug 10;11(1):423. Epub 2021 Aug 10.

Department of Psychiatry, Early Psychosis Section, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands.

Diagnostic categories do not completely reflect the heterogeneous expression of psychosis. Using data from the EU-GEI study, we evaluated the impact of schizophrenia polygenic risk score (SZ-PRS) and patterns of cannabis use on the transdiagnostic expression of psychosis. We analysed first-episode psychosis patients (FEP) and controls, generating transdiagnostic dimensions of psychotic symptoms and experiences using item response bi-factor modelling. Linear regression was used to test the associations between these dimensions and SZ-PRS, as well as the combined effect of SZ-PRS and cannabis use on the dimensions of positive psychotic symptoms and experiences. We found associations between SZ-PRS and (1) both negative (B = 0.18; 95%CI 0.03-0.33) and positive (B = 0.19; 95%CI 0.03-0.35) symptom dimensions in 617 FEP patients, regardless of their categorical diagnosis; and (2) all the psychotic experience dimensions in 979 controls. We did not observe associations between SZ-PRS and the general and affective dimensions in FEP. Daily and current cannabis use were associated with the positive dimensions in FEP (B = 0.31; 95%CI 0.11-0.52) and in controls (B = 0.26; 95%CI 0.06-0.46), over and above SZ-PRS. We provide evidence that genetic liability to schizophrenia and cannabis use map onto transdiagnostic symptom dimensions, supporting the validity and utility of the dimensional representation of psychosis. In our sample, genetic liability to schizophrenia correlated with more severe psychosis presentation, and cannabis use conferred risk to positive symptomatology beyond the genetic risk. Our findings support the hypothesis that psychotic experiences in the general population have similar genetic substrates as clinical disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41398-021-01526-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8355107PMC
August 2021

Associations of immunological proteins/traits with schizophrenia, major depression and bipolar disorder: A bi-directional two-sample mendelian randomization study.

Brain Behav Immun 2021 10 16;97:176-185. Epub 2021 Jul 16.

Department of Psychiatry, University of Cambridge School of Clinical Medicine, Cambridge, England; Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, England; MRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, England; Centre for Academic Mental Health, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, England; Avon and Wiltshire Mental Health Partnership NHS Trust, Bristol England.

Background: Schizophrenia, bipolar disorder and depression are associated with inflammation. However, it is unclear whether associations of immunological proteins/traits with these disorders are likely to be causal, or could be explained by reverse causality/residual confounding.

Methods: We used bi-directional two-sample Mendelian randomization (MR) and multi-variable MR (MVMR) analysis to examine evidence of causality, specificity and direction of association of 20 immunological proteins/traits (pro-inflammatory cytokines: interleukin (IL)-6, tumour necrosis factor (TNF)-α, IL-12, IL-16, IL-17, IL-18; anti-inflammatory cytokines: IL-1 receptor antagonist (RA), IL-10, IL-13; chemokines: IL-8, monocyte chemo-attractant protein-1 (MCP-1); lymphoid growth-factors: soluble (s) IL-2Rα, IL-4, IL-7, IL-9; myeloid growth-factor: IL-5; acute phase protein: C-Reactive Protein (CRP); immune cells: neutrophils, lymphocytes; neurotrophic factor: brain derived neurotrophic factor (BDNF)) with schizophrenia, major depression and bipolar disorder.

Results: Genetically-predicted IL-6 was associated with increased risk of schizophrenia in univariable MR (OR = 1.24; 95% C.I., 1.05-1.47) and with major depression in MVMR (OR = 1.08; 95% C.I., 1.03-1.12). These results survived Bonferroni-correction. Genetically-predicted sIL-2Rα (OR = 1.07; 95% C.I., 1.01-1.12) and IL-9 (OR = 1.06; 95% C.I., 1.01-1.11) were associated with increased schizophrenia risk. Genetically-predicted BDNF (OR = 0.97; 95% C.I., 0.94-1.00) and MCP-1 (OR = 0.96; 95% C.I., 0.91-0.99) were associated with reduced schizophrenia risk. However, these findings did not survive correction for multiple testing. The CRP-schizophrenia association attenuated completely after taking into account IL-6 and sIL-2Rα in MVMR (OR = 1.02; 95% C.I., 0.81-1.28). No significant associations were observed for bipolar disorder. Evidence from bidirectional MR did not support reverse causality.

Conclusions: We report evidence in support of potential causal associations of several immunological proteins/traits with schizophrenia, and of IL-6 with depression. Some of the findings did not survive correction for multiple testing and so replication in larger samples is required. Experimental studies are also required to further examine causality, mechanisms, and treatment potential for these immunological proteins/pathways for schizophrenia and depression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbi.2021.07.009DOI Listing
October 2021

Longitudinal association between cardiovascular risk factors and depression in young people: a systematic review and meta-analysis of cohort studies.

Psychol Med 2021 Jun 25:1-11. Epub 2021 Jun 25.

Department of Psychiatry, University of Cambridge, Cambridge, UK.

Background: Depression is a common and serious mental illness that begins early in life. An association between cardiovascular disease (CVD) and subsequent depression is clear in adults. We examined associations between individual CVD risk factors and depression in young people.

Methods: We searched MEDLINE, EMBASE, and PsycINFO databases from inception to 1 January 2020. We extracted data from cohort studies assessing the longitudinal association between CVD risk factors [body mass index (BMI), smoking, systolic blood pressure (SBP), total cholesterol, high-density lipoprotein] and depression, measured using a validated tool in individuals with mean age of 24 years or younger. Random effect meta-analysis was used to combine effect estimates from individual studies, including odds ratio (OR) for depression and standardised mean difference for depressive symptoms.

Results: Based on meta-analysis of seven studies, comprising 15 753 participants, high BMI was associated with subsequent depression [pooled OR 1.61; 95% confidence interval (CI) 1.21-2.14; I2 = 31%]. Based on meta-analysis of eight studies, comprising 30 539 participants, smoking was associated with subsequent depression (pooled OR 1.73; 95% CI 1.36-2.20; I2 = 74%). Low, but not high, SBP was associated with an increased risk of depression (pooled OR 3.32; 95% CI 1.68-6.55; I2 = 0%), although this was based on a small pooled high-risk sample of 893 participants. Generalisability may be limited as most studies were based in North America or Europe.

Conclusions: Targeting childhood/adolescent smoking and obesity may be important for the prevention of both CVD and depression across the lifespan. Further research on other CVD risk factors including blood pressure and cholesterol in young people is required.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/S0033291721002488DOI Listing
June 2021

Preference uncertainty accounts for developmental effects on susceptibility to peer influence in adolescence.

Nat Commun 2021 06 22;12(1):3823. Epub 2021 Jun 22.

Max Planck UCL Centre for Computational Psychiatry and Ageing Research, University College London, London, UK.

Adolescents are prone to social influence from peers, with implications for development, both adaptive and maladaptive. Here, using a computer-based paradigm, we replicate a cross-sectional effect of more susceptibility to peer influence in a large dataset of adolescents 14 to 24 years old. Crucially, we extend this finding by adopting a longitudinal perspective, showing that a within-person susceptibility to social influence decreases over a 1.5 year follow-up time period. Exploiting this longitudinal design, we show that susceptibility to social influences at baseline predicts an improvement in peer relations over the follow-up period. Using a Bayesian computational model, we demonstrate that in younger adolescents a greater tendency to adopt others' preferences arises out of a higher uncertainty about their own preferences in the paradigmatic case of delay discounting (a phenomenon called 'preference uncertainty'). This preference uncertainty decreases over time and, in turn, leads to a reduced susceptibility of one's own behaviour to an influence from others. Neuro-developmentally, we show that a measure of myelination within medial prefrontal cortex, estimated at baseline, predicts a developmental decrease in preference uncertainty at follow-up. Thus, using computational and neural evidence, we reveal adaptive mechanisms underpinning susceptibility to social influence during adolescence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-021-23671-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8219700PMC
June 2021

Direction of association between Cardiovascular risk and depressive symptoms during the first 18 years of life: A prospective birth cohort study.

J Affect Disord 2021 09 9;292:508-516. Epub 2021 Jun 9.

Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom; Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, United Kingdom; MRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom; Centre for Academic Mental Health, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom; Avon and Wiltshire Mental Health Partnership NHS Trust, Bristol, United Kingdom.

Background: Cardiovascular disease (CVD) and depression are bidirectionally associated in adults. However, the direction of association between CVD risk and depressive symptoms in young people and potential mechanisms are poorly understood.

Methods: Using longitudinal birth cohort data, we created a CVD risk score age at 15 using age, ethnicity, physical activity, maternal social status, maternal smoking, own smoking, BMI, systolic blood pressure, LDL, HDL and triglycerides. We used regression analysis to test: (1) association between CVD risk score at age 15 and depressive symptoms at ages 12 and 18; (2) association of IL-6 and CRP at age 9 with depressive symptoms at age 12 and CVD risk score at age 15; and (3) mediating effects of CVD risk score on associations of IL-6/CRP at age 9 with depressive symptoms at age 18.

Results: The risk set comprised 5007 participants. CVD risk score in mid-adolescence was associated with depressive symptoms in early-adulthood (adjusted beta=0.06; standard error (SE)=0.02; p<0.001). Depressive symptoms in childhood were not associated with CVD risk score in mid-adolescence (adjusted beta=0.03; SE=0.02; p=0.11). Childhood inflammatory markers were associated with CVD risk score in mid-adolescence. Adolescent CVD risk score mediated the associations between childhood inflammatory markers and depressive symptoms in early-adulthood.

Limitations: The cohort primarily comprises White individuals, limiting generalisability. Sample attrition required imputation for missing data.

Conclusions: Association between CVD risk and depression in childhood/adolescence is unidirectional, with higher CVD risk increasing the risk of depressive symptoms. Childhood inflammation may increase risk of depression by influencing adolescent CVD risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jad.2021.05.094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8324768PMC
September 2021

Association of inflammation with depression and anxiety: evidence for symptom-specificity and potential causality from UK Biobank and NESDA cohorts.

Mol Psychiatry 2021 Jun 16. Epub 2021 Jun 16.

Department of Psychiatry, University of Cambridge, Cambridge, England.

We examined whether inflammation is uniformly associated with all depressive and anxiety symptoms, and whether these associations are potentially causal. Data was from 147,478 individuals from the UK Biobank (UKB) and 2,905 from the Netherlands Study of Depression and Anxiety (NESDA). Circulating C-reactive protein (CRP) was measured in both cohorts and interleukin-6 (IL-6) in NESDA. Genetic instruments for these proteins were obtained from published GWAS and UKB. Depressive and anxiety symptoms were assessed with self-report questionnaires. In NESDA, neurovegetative (appetite, sleep, psychomotor) symptoms were disaggregated as increased vs. decreased. In joint analyses, higher CRP was associated with depressive symptoms of depressed mood (OR = 1.06, 95% CI = 1.05-1.08), altered appetite (OR = 1.25, 95%CI = 1.23-1.28), sleep problems (OR = 1.05, 95%CI = 1.04-1.06), and fatigue (OR = 1.12, 95% CI = 1.11-1.14), and with anxiety symptoms of irritability (OR = 1.06, 95% CI = 1.05-1.08) and worrying control (OR = 1.03, 95% CI = 1.02-1.04). In NESDA, higher IL-6 was additionally associated with anhedonia (OR = 1.30, 95% CI = 1.12-1.52). Higher levels of both CRP (OR = 1.27, 95% CI = 1.13-1.43) and IL-6 (OR = 1.26, 95% CI = 1.07-1.49) were associated with increased sleep. Higher CRP was associated with increased appetite (OR = 1.21, 95% CI = 1.08-1.35) while higher IL-6 with decreased appetite (OR = 1.45, 95% CI = 1.18-1.79). In Mendelian Randomisation analyses, genetically predicted higher IL-6 activity was associated with increased risk of fatigue (estimate = 0.25, SE = 0.08) and sleep problems (estimate = 0.19, SE = 0.07). Inflammation was associated with core depressive symptoms of low mood and anhedonia and somatic/neurovegetative symptoms of fatigue, altered sleep and appetite changes. Less consistent associations were found for anxiety. The IL-6/IL-6R pathway could be causally linked to depression. Experimental studies are required to further evaluate causality, mechanisms, and usefulness of immunotherapies for depressive symptoms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41380-021-01188-wDOI Listing
June 2021

The progression of disorder-specific brain pattern expression in schizophrenia over 9 years.

NPJ Schizophr 2021 Jun 14;7(1):32. Epub 2021 Jun 14.

Department of Psychiatry and Psychotherapy, Ludwig-Maximilian-University, Munich, Germany.

Age plays a crucial role in the performance of schizophrenia vs. controls (SZ-HC) neuroimaging-based machine learning (ML) models as the accuracy of identifying first-episode psychosis from controls is poor compared to chronic patients. Resolving whether this finding reflects longitudinal progression in a disorder-specific brain pattern or a systematic but non-disorder-specific deviation from a normal brain aging (BA) trajectory in schizophrenia would help the clinical translation of diagnostic ML models. We trained two ML models on structural MRI data: an SZ-HC model based on 70 schizophrenia patients and 74 controls and a BA model (based on 561 healthy individuals, age range = 66 years). We then investigated the two models' predictions in the naturalistic longitudinal Northern Finland Birth Cohort 1966 (NFBC1966) following 29 schizophrenia and 61 controls for nine years. The SZ-HC model's schizophrenia-specificity was further assessed by utilizing independent validation (62 schizophrenia, 95 controls) and depression samples (203 depression, 203 controls). We found better performance at the NFBC1966 follow-up (sensitivity = 75.9%, specificity = 83.6%) compared to the baseline (sensitivity = 58.6%, specificity = 86.9%). This finding resulted from progression in disorder-specific pattern expression in schizophrenia and was not explained by concomitant acceleration of brain aging. The disorder-specific pattern's progression reflected longitudinal changes in cognition, outcomes, and local brain changes, while BA captured treatment-related and global brain alterations. The SZ-HC model was also generalizable to independent schizophrenia validation samples but classified depression as control subjects. Our research underlines the importance of taking account of longitudinal progression in a disorder-specific pattern in schizophrenia when developing ML classifiers for different age groups.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41537-021-00157-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203625PMC
June 2021

Development and external validation of the Psychosis Metabolic Risk Calculator (PsyMetRiC): a cardiometabolic risk prediction algorithm for young people with psychosis.

Lancet Psychiatry 2021 07 1;8(7):589-598. Epub 2021 Jun 1.

Department of Psychiatry, University of Cambridge, Cambridge, UK; Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, UK; Centre for Academic Mental Health, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK; MRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.

Background: Young people with psychosis are at high risk of developing cardiometabolic disorders; however, there is no suitable cardiometabolic risk prediction algorithm for this group. We aimed to develop and externally validate a cardiometabolic risk prediction algorithm for young people with psychosis.

Methods: We developed the Psychosis Metabolic Risk Calculator (PsyMetRiC) to predict up to 6-year risk of incident metabolic syndrome in young people (aged 16-35 years) with psychosis from commonly recorded information at baseline. We developed two PsyMetRiC versions using the forced entry method: a full model (including age, sex, ethnicity, body-mass index, smoking status, prescription of a metabolically active antipsychotic medication, HDL concentration, and triglyceride concentration) and a partial model excluding biochemical results. PsyMetRiC was developed using data from two UK psychosis early intervention services (Jan 1, 2013, to Nov 4, 2020) and externally validated in another UK early intervention service (Jan 1, 2012, to June 3, 2020). A sensitivity analysis was done in UK birth cohort participants (aged 18 years) who were at risk of developing psychosis. Algorithm performance was assessed primarily via discrimination (C statistic) and calibration (calibration plots). We did a decision curve analysis and produced an online data-visualisation app.

Findings: 651 patients were included in the development samples, 510 in the validation sample, and 505 in the sensitivity analysis sample. PsyMetRiC performed well at internal (full model: C 0·80, 95% CI 0·74-0·86; partial model: 0·79, 0·73-0·84) and external validation (full model: 0·75, 0·69-0·80; and partial model: 0·74, 0·67-0·79). Calibration of the full model was good, but there was evidence of slight miscalibration of the partial model. At a cutoff score of 0·18, in the full model PsyMetRiC improved net benefit by 7·95% (sensitivity 75%, 95% CI 66-82; specificity 74%, 71-78), equivalent to detecting an additional 47% of metabolic syndrome cases.

Interpretation: We have developed an age-appropriate algorithm to predict the risk of incident metabolic syndrome, a precursor of cardiometabolic morbidity and mortality, in young people with psychosis. PsyMetRiC has the potential to become a valuable resource for early intervention service clinicians and could enable personalised, informed health-care decisions regarding choice of antipsychotic medication and lifestyle interventions.

Funding: National Institute for Health Research and Wellcome Trust.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S2215-0366(21)00114-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211566PMC
July 2021

Longitudinal association between CRP levels and risk of psychosis: a meta-analysis of population-based cohort studies.

NPJ Schizophr 2021 May 28;7(1):31. Epub 2021 May 28.

Department of Psychiatry, University of Cambridge, Cambridge, UK.

Meta-analyses of cross-sectional studies suggest that patients with psychosis have higher circulating levels of C-reactive protein (CRP) compared with healthy controls; however, cause and effect is unclear. We examined the prospective association between CRP levels and subsequent risk of developing a psychotic disorder by conducting a systematic review and meta-analysis of population-based cohort studies. Databases were searched for prospective studies of CRP and psychosis. We obtained unpublished results, including adjustment for age, sex, body mass index, smoking, alcohol use, and socioeconomic status and suspected infection (CRP > 10 mg/L). Based on random effect meta-analysis of 89,792 participants (494 incident cases of psychosis at follow-up), the pooled odds ratio (OR) for psychosis for participants with high (>3 mg/L), as compared to low (≤3 mg/L) CRP levels at baseline was 1.50 (95% confidence interval [CI], 1.09-2.07). Evidence for this association remained after adjusting for potential confounders (adjusted OR [aOR] = 1.31; 95% CI, 1.03-1.66). After excluding participants with suspected infection, the OR for psychosis was 1.36 (95% CI, 1.06-1.74), but the association attenuated after controlling for confounders (aOR = 1.23; 95% CI, 0.95-1.60). Using CRP as a continuous variable, the pooled OR for psychosis per standard deviation increase in log(CRP) was 1.11 (95% CI, 0.93-1.34), and this association further attenuated after controlling for confounders (aOR = 1.07; 95% CI, 0.90-1.27) and excluding participants with suspected infection (aOR = 1.07; 95% CI, 0.92-1.24). There was no association using CRP as a categorical variable (low, medium or high). While we provide some evidence of a longitudinal association between high CRP (>3 mg/L) and psychosis, larger studies are required to enable definitive conclusions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41537-021-00161-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163886PMC
May 2021

The Independent Effects of Psychosocial Stressors on Subclinical Psychosis: Findings From the Multinational EU-GEI Study.

Schizophr Bull 2021 May 19. Epub 2021 May 19.

Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University Medical Centre, Maastricht, The Netherlands.

The influence of psychosocial stressors on psychosis risk has usually been studied in isolation and after the onset of the disorder, potentially ignoring important confounding relationships or the fact that some stressors that may be the consequence of the disorder rather than preexisting. The study of subclinical psychosis could help to address some of these issues. In this study, we investigated whether there was (i) an association between dimensions of subclinical psychosis and several psychosocial stressors including: childhood trauma, self-reported discrimination experiences, low social capital, and stressful life experiences, and (ii) any evidence of environment-environment (ExE) interactions between these factors. Data were drawn from the EUGEI study, in which healthy controls (N = 1497) and siblings of subjects with a psychotic disorder (N = 265) were included in six countries. The association between psychosocial stressors and subclinical psychosis dimensions (positive, negative and depressive dimension as measured by the Community Assessment of Psychic Experiences (CAPE) scale) and possible ExE interactions were assessed using linear regression models. After adjusting for sex, age, ethnicity, country, and control/sibling status, childhood trauma (β for positive dimension: 0.13, negative: 0.49, depressive: 0.26) and stressful life events (positive: 0.08, negative: 0.16, depressive: 0.17) were associated with the three dimensions. Lower social capital was associated with the negative and depression dimensions (negative: 0.26, depressive: 0.13), and self-reported discrimination experiences with the positive dimension (0.06). Our findings are in favor of independent, cumulative and non-specific influences of social adversities in subclinical psychosis in non-clinical populations, without arguments for E × E interactions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/schbul/sbab060DOI Listing
May 2021

Sexual and physical abuse and depressive symptoms in the UK Biobank.

BMC Psychiatry 2021 05 11;21(1):248. Epub 2021 May 11.

Department of Psychiatry, University of Cambridge, Cambridge, UK.

Background: The association between sexual and physical abuse and subsequent depression is well-established, but the associations with specific depressive symptoms and sex differences remain relatively understudied. We investigated the associations of sexual and physical abuse with depressive symptoms in men and women in a large population cohort.

Methods: Observational study based on 151,396 UK Biobank participants. Exposures included self-reported experiences of childhood physical abuse and sexual abuse. Mid-life outcomes included current depressive symptoms score, individual depressive symptoms, and lifetime depression. We used logistic regression to test associations of childhood sexual/physical abuse with depressive outcomes.

Results: Recalled childhood sexual and physical abuse were both associated with current depressive symptoms score in adults. Results for individual symptoms-based analyses suggest that sexual and physical abuse are associated with all depressive symptoms, particularly suicidal behaviours. The associations between lifetime depression and sexual/physical abuse were not fully explained by current depressive symptoms score, indicating that these findings may not be fully attributable to recall bias. There was no indication of differential risk for specific depressive symptoms among men and women.

Conclusions: Sexual and physical abuse are robust risk factors for depression/depressive symptoms regardless of sex. Higher risk of suicidal behaviours associated with childhood sexual/physical abuse are of particular concern. Longitudinal research into sex-specific associations for individual depressive symptoms is required.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12888-021-03207-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127207PMC
May 2021

A qualitative study of experiences of NHS mental healthcare workers during the Covid-19 pandemic.

BMC Psychiatry 2021 05 12;21(1):250. Epub 2021 May 12.

Department of Psychiatry, Cambridgeshire & Peterborough NHS Foundation Trust, University of Cambridge, Cambridge, CB2 0SZ, UK.

Background: The Covid-19 pandemic has imposed extraordinary strains on healthcare workers. But, in contrast with acute settings, relatively little attention has been given to those who work in mental health settings. We aimed to characterise the experiences of those working in English NHS secondary mental health services during the first wave of the pandemic.

Methods: The design was a qualitative interview-based study. We conducted semi-structured, remote (telephone or online) interviews with 35 members of staff from NHS secondary (inpatient and community) mental health services in England. Analysis was based on the constant comparative method.

Results: Participants reported wide-ranging changes in the organisation of secondary mental health care and the nature of work in response to the pandemic, including pausing of all services deemed to be "non-essential", deployment of staff across services to new and unfamiliar roles, and moves to remote working. The quality of participants' working life was impaired by increasing levels of daily challenge associated with trying to provide care in trying and constrained circumstances, the problems of forging new ways of working remotely, and constraints on ability to access informal support. Participants were confronted with difficult dilemmas relating to clinical decision-making, prioritisation of care, and compromises in ability to perform the therapeutic function of their roles. Other dilemmas centred on trying to balance the risks of controlling infection with the need for human contact. Many reported features of moral injury linked to their perceived failures in providing the quality or level of care that they felt service users needed. They sometimes sought to compensate for deficits in care through increased advocacy, taking on additional tasks, or making exceptions, but this led to further personal strain. Many experienced feelings of grief, helplessness, isolation, distress, and burnout. These problems were compounded by sometimes poor communication about service changes and by staff feeling that they could not take time off because of the potential impact on others. Some reported feeling poorly supported by organisations.

Conclusions: Mental health workers faced multiple adversities during the pandemic that were highly consequential for their wellbeing. These findings can help in identifying targets for support.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12888-021-03261-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113793PMC
May 2021

Shared goals for mental health research: what, why and when for the 2020s.

J Ment Health 2021 May 9:1-9. Epub 2021 May 9.

Department of Experimental Psychology and Psychiatry, University of Oxford, Oxford, UK.

Mental health problems bring substantial individual, community and societal costs and the need for innovation to promote good mental health and to prevent and treat mental health problems has never been greater. However, we know that research findings can take up to 20 years to implement. One way to push the pace is to focus researchers and funders on shared, specific goals and targets. We describe a consultation process organised by the Department of Health and Social Care and convened by the Chief Medical Officer to consider high level goals for future research efforts and to begin to identify UK-specific targets to measure research impact. The process took account of new scientific methods and evidence, the UK context with a universal health care system (the NHS) and the embedded research support from the National Institute for Health Research Clinical Research Network, as well as the views of individual service users and service user organisations. The result of the consultation is a set of four overarching goals with the potential to be measured at intervals of three, five or ten years.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/09638237.2021.1898552DOI Listing
May 2021

Duration of Untreated Psychosis in First-Episode Psychosis is not Associated With Common Genetic Variants for Major Psychiatric Conditions: Results From the Multi-Center EU-GEI Study.

Schizophr Bull 2021 May 8. Epub 2021 May 8.

Department of Experimental Biomedicine and Clinical Neuroscience, University of Palermo, Palermo, Italy.

Duration of untreated psychosis (DUP) is associated with clinical outcomes in people with a diagnosis of first-episode psychosis (FEP), but factors associated with length of DUP are still poorly understood. Aiming to obtain insights into the possible biological impact on DUP, we report genetic analyses of a large multi-center phenotypically well-defined sample encompassing individuals with a diagnosis of FEP recruited from 6 countries spanning 17 research sites, as part of the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study. Genetic propensity was measured using polygenic scores for schizophrenia (SZ-PGS), bipolar disorder (BD-PGS), major depressive disorder (MDD-PGS), and intelligence (IQ-PGS), which were calculated based on the results from the most recent genome-wide association meta-analyses. Following imputation for missing data and log transformation of DUP to handle skewedness, the association between DUP and polygenic scores (PGS), adjusting for important confounders, was investigated with multivariable linear regression models. The sample comprised 619 individuals with a diagnosis of FEP disorders with a median age at first contact of 29.0 years (interquartile range [IQR] = 22.0-38.0). The median length of DUP in the sample was 10.1 weeks (IQR = 3.8-30.8). One SD increases in SZ-PGS, BD-PGS, MDD-PGS or IQ-PGS were not significantly associated with the length of DUP. Our results suggest that genetic variation does not contribute to the DUP in patients with a diagnosis of FEP disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/schbul/sbab055DOI Listing
May 2021

Duration of Untreated Psychosis in First-Episode Psychosis is not Associated With Common Genetic Variants for Major Psychiatric Conditions: Results From the Multi-Center EU-GEI Study.

Schizophr Bull 2021 May 8. Epub 2021 May 8.

Department of Experimental Biomedicine and Clinical Neuroscience, University of Palermo, Palermo, Italy.

Duration of untreated psychosis (DUP) is associated with clinical outcomes in people with a diagnosis of first-episode psychosis (FEP), but factors associated with length of DUP are still poorly understood. Aiming to obtain insights into the possible biological impact on DUP, we report genetic analyses of a large multi-center phenotypically well-defined sample encompassing individuals with a diagnosis of FEP recruited from 6 countries spanning 17 research sites, as part of the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study. Genetic propensity was measured using polygenic scores for schizophrenia (SZ-PGS), bipolar disorder (BD-PGS), major depressive disorder (MDD-PGS), and intelligence (IQ-PGS), which were calculated based on the results from the most recent genome-wide association meta-analyses. Following imputation for missing data and log transformation of DUP to handle skewedness, the association between DUP and polygenic scores (PGS), adjusting for important confounders, was investigated with multivariable linear regression models. The sample comprised 619 individuals with a diagnosis of FEP disorders with a median age at first contact of 29.0 years (interquartile range [IQR] = 22.0-38.0). The median length of DUP in the sample was 10.1 weeks (IQR = 3.8-30.8). One SD increases in SZ-PGS, BD-PGS, MDD-PGS or IQ-PGS were not significantly associated with the length of DUP. Our results suggest that genetic variation does not contribute to the DUP in patients with a diagnosis of FEP disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/schbul/sbab055DOI Listing
May 2021

Inflammation and Depression: A Public Health Perspective.

Brain Behav Immun 2021 07 18;95:1-3. Epub 2021 Apr 18.

Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK; MRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK; Department of Psychiatry, University of Cambridge, Herchel Smith Building, Robinson Way, Cambridge, UK; Cambridgeshire and Peterborough NHS Foundation Trust, Elizabeth House, Fulbourn Hospital, Cambridge, UK; Centre for Academic Mental Health, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.

The multifaceted role of low-grade systemic inflammation in depression and physical illnesses like cardiovascular disease highlights complex interactions between the body, brain and mind. While current research on inflammation and depression has largely focused on exploring possible disease mechanisms and therapeutic potential, we seek to broaden the current discussion by introducing a public health perspective. In this Viewpoint, we propose that inflammation and its contributing sources could represent important targets for public health strategies aimed at improving both mental and physical health. We discuss potential universal, selective and indicated primary prevention strategies for inflammation-related depression. We consider potential approaches to secondary prevention, including scope for anti-inflammatory treatment and CRP testing for guiding treatment allocation and prognosis. Preventive strategies discussed here could also be relevant for other inflammation-mediated mental health conditions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbi.2021.04.015DOI Listing
July 2021

The potential shared role of inflammation in insulin resistance and schizophrenia: A bidirectional two-sample mendelian randomization study.

PLoS Med 2021 03 12;18(3):e1003455. Epub 2021 Mar 12.

Department of Psychiatry, University of Cambridge School of Clinical Medicine, Cambridge, England.

Background: Insulin resistance predisposes to cardiometabolic disorders, which are commonly comorbid with schizophrenia and are key contributors to the significant excess mortality in schizophrenia. Mechanisms for the comorbidity remain unclear, but observational studies have implicated inflammation in both schizophrenia and cardiometabolic disorders separately. We aimed to examine whether there is genetic evidence that insulin resistance and 7 related cardiometabolic traits may be causally associated with schizophrenia, and whether evidence supports inflammation as a common mechanism for cardiometabolic disorders and schizophrenia.

Methods And Findings: We used summary data from genome-wide association studies of mostly European adults from large consortia (Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) featuring up to 108,557 participants; Diabetes Genetics Replication And Meta-analysis (DIAGRAM) featuring up to 435,387 participants; Global Lipids Genetics Consortium (GLGC) featuring up to 173,082 participants; Genetic Investigation of Anthropometric Traits (GIANT) featuring up to 339,224 participants; Psychiatric Genomics Consortium (PGC) featuring up to 105,318 participants; and Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium featuring up to 204,402 participants). We conducted two-sample uni- and multivariable mendelian randomization (MR) analysis to test whether (i) 10 cardiometabolic traits (fasting insulin, high-density lipoprotein and triglycerides representing an insulin resistance phenotype, and 7 related cardiometabolic traits: low-density lipoprotein, fasting plasma glucose, glycated haemoglobin, leptin, body mass index, glucose tolerance, and type 2 diabetes) could be causally associated with schizophrenia; and (ii) inflammation could be a shared mechanism for these phenotypes. We conducted a detailed set of sensitivity analyses to test the assumptions for a valid MR analysis. We did not find statistically significant evidence in support of a causal relationship between cardiometabolic traits and schizophrenia, or vice versa. However, we report that a genetically predicted inflammation-related insulin resistance phenotype (raised fasting insulin (raised fasting insulin (Wald ratio OR = 2.95, 95% C.I, 1.38-6.34, Holm-Bonferroni corrected p-value (p) = 0.035) and lower high-density lipoprotein (Wald ratio OR = 0.55, 95% C.I., 0.36-0.84; p = 0.035)) was associated with schizophrenia. Evidence for these associations attenuated to the null in multivariable MR analyses after adjusting for C-reactive protein, an archetypal inflammatory marker: (fasting insulin Wald ratio OR = 1.02, 95% C.I, 0.37-2.78, p = 0.975), high-density lipoprotein (Wald ratio OR = 1.00, 95% C.I., 0.85-1.16; p = 0.849), suggesting that the associations could be fully explained by inflammation. One potential limitation of the study is that the full range of gene products from the genetic variants we used as proxies for the exposures is unknown, and so we are unable to comment on potential biological mechanisms of association other than inflammation, which may also be relevant.

Conclusions: Our findings support a role for inflammation as a common cause for insulin resistance and schizophrenia, which may at least partly explain why the traits commonly co-occur in clinical practice. Inflammation and immune pathways may represent novel therapeutic targets for the prevention or treatment of schizophrenia and comorbid insulin resistance. Future work is needed to understand how inflammation may contribute to the risk of schizophrenia and insulin resistance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pmed.1003455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954314PMC
March 2021

Childhood inflammatory markers and risks for psychosis and depression at age 24: Examination of temporality and specificity of association in a population-based prospective birth cohort.

Schizophr Res 2021 04 5;230:69-76. Epub 2021 Mar 5.

Department of Psychiatry, University of Cambridge School of Clinical Medicine, Cambridge, UK; Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, UK; Centre for Academic Mental Health, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK; MRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK; Avon and Wiltshire Mental Health Partnership NHS Trust, UK.

Background: Cross-sectional studies have reported elevated concentrations of inflammatory markers in psychosis and depression. However, questions regarding temporality and specificity of association, crucial for understanding the potential role of inflammation, remain.

Methods: Based on 2224 ALSPAC birth cohort participants, we used regression analyses to test associations of interleukin-6 (IL-6) and C-reactive protein (CRP) levels at age 9 with risks for psychosis (psychotic experiences; negative symptoms; psychotic disorder), and depression (depressive episode; symptom score) at age 24. Regression models were adjusted for sex, ethnicity, social class and body mass index. We tested for linearity (using quadratic terms) and specificity (using bi-variate probit regression) of association, and used multiple imputation to explore the impact of missing data.

Results: After adjustments, higher IL-6 levels at age 9 were associated with increased risk of psychotic disorder (OR = 1.56; 95% C.I., 1.09-2.21 per SD increase in IL-6; OR=2.60; 95% C.I., 1.04-6.53 for the top compared with bottom third of IL-6) and depressive episode (OR = 1.14; 95% C.I., 0.99-1.32 per SD increase in IL-6; OR = 1.49; 95% C.I., 1.02-2.18 for the top compared with bottom third of IL-6). IL-6 was associated with negative symptoms after adjusting for depression (β = 0.09; 95% C.I., 0.01-0.22). There was no evidence for outcome-specific associations of IL-6. Childhood CRP was not associated with adult psychosis or depression.

Conclusions: Evidence for similar, longitudinal, dose-response associations suggest that elevated childhood IL-6 could be a shared risk factor for adult psychosis and depression. The IL-6 pathway may represent a novel target for treatment and prevention of these disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.schres.2021.02.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224182PMC
April 2021

Determinants of patient-reported outcome trajectories and symptomatic recovery in Improving Access to Psychological Therapies (IAPT) services.

Psychol Med 2021 Mar 8:1-10. Epub 2021 Mar 8.

Department of Psychiatry, University of Cambridge, Cambridge, UK.

Background: Despite evidence for the general effectiveness of psychological therapies, there exists substantial heterogeneity in patient outcomes. We aimed to identify factors associated with baseline severity of depression and anxiety symptoms, rate of symptomatic change over the course of therapy, and symptomatic recovery in a primary mental health care setting.

Methods: Using data from a service evaluation involving 35 527 patients in England's psychological and wellbeing [Improving Access to Psychological Therapies (IAPT)] services, we applied latent growth models to explore which routinely-collected sociodemographic, clinical, and therapeutic variables were associated with baseline symptom severity and rate of symptomatic change. We used a multilevel logit model to determine variables associated with symptomatic recovery.

Results: Being female, younger, more functionally impaired, and more socioeconomically disadvantaged was associated with higher baseline severity of both depression and anxiety symptoms. Being older, less functionally impaired, and having more severe baseline symptomatology was associated with more rapid improvement of both depression and anxiety symptoms (male gender and greater socioeconomic disadvantage were further associated with rate of change for depression only). Therapy intensity and appointment frequency seemed to have no correlation with rate of symptomatic improvement. Patients with lower baseline symptom severity, less functional impairment, and older age had a greater likelihood of achieving symptomatic recovery (as defined by IAPT criteria).

Conclusions: We must continue to investigate how best to tailor psychotherapeutic interventions to fit patients' needs. Patients who begin therapy with more severe depression and/or anxiety symptoms and poorer functioning merit special attention, as these characteristics may negatively impact recovery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/S0033291720005395DOI Listing
March 2021

Perceived major experiences of discrimination, ethnic group, and risk of psychosis in a six-country case-control study.

Psychol Med 2021 Mar 2:1-9. Epub 2021 Mar 2.

Department of Psychiatry, University of Cambridge, CambridgeCB2 0SZ, UK.

Background: Perceived discrimination is associated with worse mental health. Few studies have assessed whether perceived discrimination (i) is associated with the risk of psychotic disorders and (ii) contributes to an increased risk among minority ethnic groups relative to the ethnic majority.

Methods: We used data from the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions Work Package 2, a population-based case-control study of incident psychotic disorders in 17 catchment sites across six countries. We calculated odds ratios (OR) and 95% confidence intervals (95% CI) for the associations between perceived discrimination and psychosis using mixed-effects logistic regression models. We used stratified and mediation analyses to explore differences for minority ethnic groups.

Results: Reporting any perceived experience of major discrimination (e.g. unfair treatment by police, not getting hired) was higher in cases than controls (41.8% v. 34.2%). Pervasive experiences of discrimination (≥3 types) were also higher in cases than controls (11.3% v. 5.5%). In fully adjusted models, the odds of psychosis were 1.20 (95% CI 0.91-1.59) for any discrimination and 1.79 (95% CI 1.19-1.59) for pervasive discrimination compared with no discrimination. In stratified analyses, the magnitude of association for pervasive experiences of discrimination appeared stronger for minority ethnic groups (OR = 1.73, 95% CI 1.12-2.68) than the ethnic majority (OR = 1.42, 95% CI 0.65-3.10). In exploratory mediation analysis, pervasive discrimination minimally explained excess risk among minority ethnic groups (5.1%).

Conclusions: Pervasive experiences of discrimination are associated with slightly increased odds of psychotic disorders and may minimally help explain excess risk for minority ethnic groups.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/S0033291721000453DOI Listing
March 2021

Modernising measurement in psychiatry: item banks and computerised adaptive testing.

Lancet Psychiatry 2021 05 17;8(5):354-356. Epub 2021 Feb 17.

Department of Psychiatry, Cambridge Biomedical Campus, Herschel Smith Building for Brain & Mind Sciences, University of Cambridge, Cambridge CB2 0SZ, UK; Applied Research Collaboration East of England, National Institute for Health Research, Cambridge, UK; Cambridgeshire & Peterborough NHS Foundation Trust, Cambridge, UK.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S2215-0366(21)00041-9DOI Listing
May 2021
-->