Association of trauma, post-traumatic stress disorder and non-affective psychosis across the life course: a nationwide prospective cohort study.

BACKGROUND: We aimed to examine the temporal relationships between traumatic events (TE), post-traumatic stress disorder (PTSD) and non-affective psychotic disorders (NAPD). METHODS: A prospective cohort study of 1 965 214 individuals born in Sweden between 1971 and 1990 examining the independent effects of interpersonal and non-interpersonal TE on incidence of PTSD and NAPD using data from linked register data (Psychiatry-Sweden). Mediation analyses tested the hypothesis that PTSD lies on a causal pathway between interpersonal trauma and NAPD. RESULTS: Increasing doses of interpersonal and non-interpersonal TE were independently associated with increased risk of NAPD [linear-trend incidence rate ratios (IRR)adjusted = 2.17 [95% confidence interval (CI) 2.02-2.33] and IRRadjusted = 1.27 (95% CI 1.23-1.31), respectively]. These attenuated to a relatively small degree in 5-year time-lagged models. A similar pattern of results was observed for PTSD [linear-trend IRRadjusted = 3.43 (95% CI 3.21-3.66) and IRRadjusted = 1.45 (95% CI 1.39-1.50)]. PTSD was associated with increased risk of NAPD [IRRadjusted = 8.06 (95% CI 7.23-8.99)], which was substantially attenuated in 5-year time-lagged analyses [IRRadjusted = 4.62 (95% CI 3.65-5.87)]. There was little evidence that PTSD diagnosis mediated the relationship between interpersonal TE and NAPD [IRRadjusted = 0.92 (percentile CI 0.80-1.07)]. CONCLUSION: Despite the limitations to causal inference inherent in observational designs, the large effect-sizes observed between trauma, PTSD and NAPD in this study, consistent across sensitivity analyses, suggest that trauma may be a component cause of psychotic disorders. However, PTSD diagnosis might not be a good proxy for the likely complex psychological mechanisms mediating this association.

Associations between plasma inflammatory markers and psychotic disorder, depressive disorder and generalised anxiety disorder in early adulthood: A nested case-control study.

BACKGROUND: Low-grade inflammation may occur in association with several mental disorders of early adulthood, though associations with markers of chronic inflammation such as soluble urokinase plasminogen activator receptor (suPAR) are less well-established. We aimed to examine associations between acute and chronic inflammatory markers and mental disorders, as well as psychiatric co-morbidity, in young adults aged 24 years in the Avon Longitudinal Study of Parents and Children. METHODS: Included were 781 participants (of 4019 who attended at age 24 years) who completed psychiatric assessments and provided plasma samples. Of these, 377 met criteria for psychotic disorder, depressive disorder or generalised anxiety disorder and 404 did not. Plasma concentrations of IFN-γ, IL-6, IL-8, IL-10, TNF-α, CRP, sVCAM1, sICAM1, suPAR and alpha-2-macroglobulin were measured using immunoassays. Logistic regression compared standardised inflammatory marker levels in cases and controls. Negative binomial regression evaluated associations between inflammatory markers and co-morbidity (number of mental disorders). Models were adjusted for sex, body mass index, cigarette smoking, cannabis use and employment status, then additionally for childhood trauma. RESULTS: For psychotic disorder, there was evidence for associations with IL-6 (odds ratio[OR] 1.68, 95 %CI 1.20-2.34) and suPAR (OR 1.74, 95 %CI 1.17-2.58). There was weaker evidence for an association between suPAR and depressive disorder (OR 1.31, 95 %CI 1.05-1.62). There was little evidence for associations between inflammatory markers and generalised anxiety disorder. There was weak evidence for an association between suPAR and co-morbidity (ß 0.10, 95 %CI 0.01-0.19). There was little evidence for additional confounding by childhood trauma. CONCLUSIONS: There was evidence that 24-year-olds with psychotic disorder had raised plasma IL-6 and suPAR concentrations compared to controls. These findings have implications regarding the role of inflammation in mental disorders in early adulthood.

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

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.

Longitudinal population subgroups of CRP and risk of depression in the ALSPAC birth cohort.

BACKGROUND: Meta-analyses confirm increased circulating C-reactive protein (CRP) levels in depression. Longitudinal studies have linked one-off measurements of CRP at baseline with increased risk of developing depressive symptoms subsequently at follow-up, but studies with repeat CRP measures from the same individuals are scarce. METHODS: We have examined whether longitudinal patterns of inflammation, based on three CRP measurements from childhood to early-adulthood, are associated with the risk of depression in early-adulthood in the Avon Longitudinal Study of Parents and Children, a prospective birth cohort. RESULTS: Using Gaussian mixture modelling of available CRP data from age 9, 15 and 18 years, we identified four population clusters/sub-groups reflecting different longitudinal patterns of CRP: persistently low (N=463, 29.5%); persistently high (N=371, 24%); decreasing (N=360, 23%); increasing (N=367, 23.5%). The increasing group showed a steep increase in CRP levels between adolescence and early-adulthood. Participants in this group had a higher risk of moderate/severe depression at age 18 years, compared with those with persistently low CRP; adjusted odds ratio (OR)=3.78 (95% Confidence Interval (CI), 1.46-9.81; p=0.006). The odds of moderate/severe depression were also increased for the persistently high CRP group, but this was not statistically significant; OR=2.54 (95% CI, 0.90-7.16). LIMITATIONS: Repeat CRP measures were available for a subset, who may not be representative of all cohort participants. CONCLUSIONS: The results suggest that an increasing pattern of inflammation from adolescence to early-adulthood is associated with risk of depression in early-adulthood.

Longitudinal association between inflammatory markers and specific symptoms of depression in a prospective birth cohort.

BACKGROUND: Low-grade inflammation is associated with depression, but studies of specific symptoms are relatively scarce. Association between inflammatory markers and specific symptoms may provide insights into potential mechanism of inflammation-related depression. Using longitudinal data, we have tested whether childhood serum interleukin 6 (IL-6) and C-reactive protein (CRP) levels are associated with specific depressive symptoms in early adulthood. METHODS: In the ALSPAC birth cohort, serum IL-6 and CRP levels were assessed at age 9 years and 19 depressive symptoms were assessed at age 18 years. We used modified Poisson generalised linear regression with robust error variance to estimate the risk ratio (RR) and 95% confidence interval (95% CI) for each depressive symptom. In addition, we used confirmatory factor analysis to create two continuous latent variables representing somatic/neurovegetative and psychological dimension scores. Structural equation modelling was used to test the associations between IL-6 and these dimension scores. RESULTS: Based on data from 2731 participants, IL-6 was associated with diurnal mood variation, concentration difficulties, fatigue and sleep disturbances. The adjusted RRs for these symptoms at age 18 years for participants in top, compared with bottom, third of IL-6 at age 9 years were 1.75 (95% CI, 1.13-2.69) for diurnal mood variation, 1.50 (95% CI, 1.11-2.02) for concentration difficulties, 1.31 (95% CI, 1.12-1.54) for fatigue, and 1.24 (95% CI, 1.01-1.52) for sleep disturbances. At dimension level, IL-6 was associated with both somatic/neurovegetative (ß = 0.059, SE = 0.024, P = 0.013) and psychological (ß = 0.056, SE = 0.023, P = 0.016) scores. CONCLUSIONS: Inflammation is associated with specific symptoms of depression. Associations with so-called somatic/neurovegetative symptoms of depression such as fatigue, sleep disturbances and diurnal mood variation indicate that these symptoms could be useful treatment targets and markers of treatment response in clinical trials of anti-inflammatory treatment for depression.

Undetected post-traumatic stress disorder in secondary-care mental health services: systematic review.

BACKGROUND: Comorbid post-traumatic stress disorder (PTSD) is associated with poorer outcomes of other disorders, but is treatable. Aims To estimate the frequency of clinically undetected PTSD in secondary care. METHOD: A systematic review of studies that screened for PTSD and reported on PTSD documentation in clinical records. Frequency of undetected PTSD was estimated, and reasons for heterogeneity explored. RESULTS: The median proportion of participants with undetected PTSD (29 studies) was 28.6% (interquartile range 18.2-38.6%). There was substantial heterogeneity, with studies conducted in the USA and those with the highest proportions of in-patients and patients with psychotic disorder reporting higher frequencies of undetected PTSD. CONCLUSIONS: Undetected PTSD is common in secondary care, even if the true value is at the lower limit of the estimates reported here. Trials examining the impact of routine screening for PTSD are required to determine whether such programmes should be standard procedure for all mental health services. Declaration of interest None.

Trauma exposure and undetected posttraumatic stress disorder among adults with a mental disorder.

BACKGROUND: Trauma exposure and posttraumatic stress disorder (PTSD) are common among individuals with a mental disorder, but symptoms often go undetected and untreated. METHODS: The aim of this study was to determine the prevalence of PTSD among a large sample of adults with psychiatric diagnoses and to establish factors associated with symptoms going undetected. Participants were 1,946 adults recruited by the National Centre for Mental Health. Structured interviews and validated self-report questionnaires were used to ascertain clinical and demographic information for analysis. RESULTS: The prevalence of participants screening positive for PTSD that had not been detected by clinical services was 13.9% [12.4-15.5%, 95% confidence interval]). Factors associated with undetected PTSD were female gender, younger age of first contact with psychiatric services, and lower household income. Especially, poor rates of detection were observed after traumatic events, such as child abuse and sexual assault. CONCLUSIONS: Our findings demonstrate the need for routine assessment of trauma histories and symptoms of PTSD among individuals with anymental disorder.

Association of copy number variation across the genome with neuropsychiatric traits in the general population.

Copy number variants (CNVs) are associated with psychiatric conditions in clinical populations. The relationship between rare CNV burden and neuropsychiatric traits in young, general populations is underexplored. A total of 6,807 children from the Avon Longitudinal Study of Parents and Children (ALSPAC) were studied. CNVs were inferred from single nucleotide polymorphism-array data using PennCNV. After excluding children with known candidate CNVs for schizophrenia (SCZ), rare (<1%) CNV burden (total number of genes affected by CNVs, total length of CNVs, and largest CNV carried) was analyzed in relation to: psychotic experiences (PEs) and anxiety/depression in adolescence; autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD), ASD and ADHD traits, and cognitive measures during childhood. Outcomes were also assessed in relation to known SCZ CNVs. The number of genes affected by rare CNVs was associated with a continuous measure of ASD: the standardized mean difference [SMD] per gene affected was increased by 0.018 [95%CI 0.011,0.025], p = 3e-07 for duplications and by 0.021 [95%CI 0.010, 0.032], p = 1e-04 for deletions. In line with our published results on educational attainment in ALSPAC, intelligence quotient (IQ) was associated with CNV burden: the SMD per gene affected was -0.017 [95%CI -0.025, -0.008] p = 1e-04 for duplications and -0.023 [95%CI -0.037, -0.009], p = .002 for deletions. Associations were also observed for measures of coherence, attention, memory, and social cognition. SCZ-associated deletions were associated with IQ (SMD: -0.617 [95%CI -0.936, -0.298], p = 2e-04), but not with PEs or other traits. We found that rare CNV burden and known SCZ candidate CNVs are associated with neuropsychiatric phenotypes in a nonclinically ascertained sample of young people.

The longitudinal association between external locus of control, social cognition and adolescent psychopathology.

PURPOSE: To investigate the longitudinal associations between social cognitive ability an external locus of control (externality) and adolescent psychopathology. METHODS: 7058 participants from a prospective population-based cohort provided data on externality, social communication, and emotion perception between 7 and 16 years and psychotic experiences and depressive symptoms at 12 and 18 years. Bivariate probit modelling was used to investigate associations between these risk factors and psychopathological outcomes. RESULTS: Externality was associated with psychopathology at 12 (psychotic experiences OR 1.23 95% CI 1.14, 1.33; depression OR 1.12 95% CI 1.02, 1.22) and 18 years (psychotic experiences OR 1.38 95% CI 1.23, 1.55; depression OR 1.40 95% CI 1.28, 1.52). Poor social communication was associated with depression at both ages (12 years OR 1.22 95% CI 1.11, 1.34; 18 years OR 1.21 95% CI 1.10, 1.33) and marginally associated with psychotic experiences. There was marginal evidence of a larger association between externality and psychotic experiences at 12 years (p = 0.06) and between social communication and depression at 12 years (p = 0.03). CONCLUSIONS: Externality was more strongly associated with psychotic experiences. At 18 years change in externality, between 8 and 16 years were associated with a larger increase in the risk of depression. Poor social communication was more strongly associated with depression.

The longitudinal association between psychotic experiences, depression and suicidal behaviour in a population sample of adolescents.

PURPOSE: Whilst psychotic experiences are associated with suicidal behaviour in a number of studies the value of psychotic experiences for the prediction of suicidal behaviour and the role of depressive symptoms in this relationship is not clear. We examined the association between psychotic experiences and subsequent suicidal behaviour and examine the role of depressive symptoms in this relationship. METHODS: Psychotic experiences and depressive symptoms at age 12 and 16 years, and suicidal behaviour at age 16 years were assessed in participants (prospective analysis n = 3171; cross-sectional analysis n = 3952) from a population-based cohort. RESULTS: Psychotic experiences (OR 1.75 95 % CI 1.20, 2.54) and depression (OR 3.97 95 % CI 2.56, 6.15) at 12 years were independently associated with suicidal behaviour at 16 years after adjustment for confounding. There was no evidence that the relationship between psychotic experiences and suicidal behaviour was stronger in participants who were also depressive. A ROC analysis showed that adding information on psychotic experiences to measures of depressive symptoms had hardly any effect on improving prediction of suicidal behaviour (AUC increased from 0.64 to 0.65). Whereas adding a measure of depressive symptoms to the measure of psychotic experiences improved prediction substantially (AUC 0.56-0.65). CONCLUSIONS: Psychotic experiences and depression are independently associated with suicidal behaviour although the association with depression is substantially stronger. Psychotic experiences alone are not a strong predictor of later suicidal behaviour and add little to predicting the risk of suicidal behaviour over and above the information provided by depressive symptoms.

Longitudinal Trajectories of Plasma Polyunsaturated Fatty Acids and Associations With Psychosis Spectrum Outcomes in Early Adulthood.

BACKGROUND: Evidence supports associations between polyunsaturated fatty acids such as docosahexaenoic acid (DHA) and psychosis. However, polyunsaturated fatty acid trajectories in the general population have not been characterized, and associations with psychosis spectrum outcomes in early adulthood are unknown. METHODS: Plasma omega-6 to omega-3 ratio and DHA (expressed as percentage of total fatty acids) were measured by nuclear magnetic spectroscopy at 7, 15, 17, and 24 years of age in participants of ALSPAC (Avon Longitudinal Study of Parents and Children). Curvilinear growth mixture modeling evaluated body mass index-adjusted trajectories of both measures. Outcomes were assessed at 24 years. Psychotic experiences (PEs), at-risk mental state status, psychotic disorder, and number of PEs were assessed using the Psychosis-Like Symptoms interview (n = 3635; 2247 [61.8%] female). Negative symptoms score was measured using the Community Assessment of Psychic Experiences (n = 3484; 2161 [62.0%] female). Associations were adjusted for sex, ethnicity, parental social class, and cumulative smoking and alcohol use. RESULTS: Relative to stable average, the persistently high omega-6 to omega-3 ratio trajectory was associated with increased odds of PEs and psychotic disorder, but attenuated on adjustment for covariates (PEs adjusted odds ratio [aOR] = 1.63, 95% CI = 0.92-2.89; psychotic disorder aOR = 1.69, 95% CI = 0.71-4.07). This was also the case for persistently low DHA (PEs aOR = 1.42, 95% CI = 0.84-2.37; psychotic disorder aOR = 1.14, 95% CI = 0.49-2.67). Following adjustment, persistently high omega-6 to omega-3 ratio was associated with increased number of PEs (ß = 0.41, 95% CI = 0.05-0.78) and negative symptoms score (ß = 0.43, 95% CI = 0.14-0.72), as was persistently low DHA (number of PEs ß = 0.45, 95% CI = 0.14-0.76; negative symptoms ß = 0.35, 95% CI = 0.12-0.58). CONCLUSIONS: Optimization of polyunsaturated fatty acid status during development warrants further investigation in relation to psychotic symptoms in early adulthood.

Eye-movement desensitisation and reprocessing therapy (EMDR) to prevent transition to psychosis in people with an at-risk mental state (ARMS): mixed method feasibility study.

BACKGROUND: Trauma plays an important role in the development of psychosis, but no studies have investigated whether a trauma-focused therapy could prevent psychosis. AIMS: This study aimed to establish whether it would be feasible to conduct a multicentre randomised controlled trial (RCT) to prevent psychosis in people with an at-risk mental state (ARMS), using eye-movement desensitisation and reprocessing therapy (EMDR). METHOD: This started as a mixed-method randomised study comparing EMDR to treatment as usual but, as a result of low participant recruitment, was changed to a single-arm feasibility study. The proposed primary outcome for an RCT was transition to psychosis at 12-month follow-up. Data on secondary outcomes were also collected. Qualitative interviews were conducted with patients and therapists. RESULTS: Fourteen participants were recruited from the Early Intervention teams. Most people who expressed an interest in taking part attended an assessment to determine eligibility. All those eligible consented to take part. A total of 64% (7 of 11) of participants who were offered EMDR were followed up at 12 months. Of the 11 participants offered EMDR, one (11%, 95% CI: 0.2%, 48%) transitioned to psychosis. Nine patients and three therapists were interviewed. Participants who completed therapy (n = 4; mean 10.5 sessions) found EMDR helpful, but those who discontinued (n = 6; mean 5.2 sessions) said it had not benefitted them overall. Therapists said EMDR could be effective, although not for all patients. CONCLUSIONS: Future studies recruiting people with an ARMS to an RCT may need to extend recruitment beyond Early Intervention teams. Although some individuals found EMDR helpful, reasons for discontinuing need to be addressed in future studies.

The identification and management of people with an at-risk mental state (ARMS) for psychosis in primary and secondary care services: A qualitative interview study.

AIMS: Early intervention in people with an at-risk mental state (ARMS) for psychosis can prevent the onset of psychosis. Clinical guidelines recommend that ARMS are referred to triage services, and then to Early Intervention (EI) teams in secondary care for assessment and treatment. However, little is known about how ARMS patients are identified and managed in UK primary and secondary care. This study explored patients' and clinicians' views of ARMS patients' care pathways. METHODS: Eleven patients, 20 GPs, 11 clinicians from the triaging Primary Care Liaison Services (PCLS) and 10 EI clinicians were interviewed. Data were analysed thematically. RESULTS: Most patients said their symptoms started in adolescence with depression and anxiety. Before being referred to EI teams, most patients were referred by their GP to well-being services for talking therapies, which they had not found helpful. Some GPs said secondary care's high acceptance thresholds and scarce treatment availability made them reluctant to refer to EI teams. Triage in PCLS was influenced by patients' risk of self-harm, and formulation of psychotic symptoms; only those without clear evidence of other pathology and not at high risk of self-harm were referred to EI teams, the others being referred to Recovery/Crisis services. Although patients referred to EI teams were offered an assessment, only some EI teams were commissioned to treat ARMS. CONCLUSIONS: Individuals meeting ARMS criteria might not receive early intervention due to high treatment thresholds and limited treatment availability in secondary care, suggesting clinical guidelines are not being met for this patient group.

Provision of online eye movement and desensitisation therapy (EMDR) for people with post-traumatic stress disorder (PTSD): a multi-method service evaluation.

Background: The evidence for the effectiveness of online EMDR for PTSD is scarce.Objective: This service evaluation aimed to assess how online EMDR compared to in-person EMDR, in terms of its potential effectiveness and acceptability to therapists and patients.Method: The evaluation was carried out in the Cardiff and Vale University Health Board Traumatic Stress Service. We compared the outcome of therapy (PTSD scores at end of treatment), number of sessions, drop-out rate, and adverse events using linear/logistic regression in those receiving online EMDR over a 12-month period with those who had received in-person therapy in the year previous to that. Interviews with therapists and clients who had provided or undertaken online EMDR explored their views and experiences of treatment. Interviews were analysed thematically.Results: 33 people received in-person EMDR (15.3 sessions, SD = 1.4), and 45 received online EMDR (12.4 sessions, SD = 0.9). 24 individuals completed therapy in-person, and 32 online. There was no evidence of a difference in therapy completion, drop-out rates or adverse events between the two delivery modes. There was weak evidence that those who completed EMDR online and had available data (N = 29), had slightly lower PTSD scores at the end of therapy compared to those who received in-person EMDR (N = 24) (17.1 (SD = 3.2) versus 24.5 (SD = 3.0), mean difference = 7.8, 95% CI -0.3, 15.9, p = .06). However, groups were not randomised and only those who completed treatment were analysed, so estimates may be biased. 11 patients and five therapists were interviewed. Overall, both therapists and clients viewed online EMDR as safe and effective. Benefits mentioned by clients included feeling more in control and not having to travel. Clients' concerns related to lack of privacy and 'transition time/space' between therapy and their daily lives.Conclusion: Results suggest that online EMDR is an acceptable, safe and effective alternative to in-person EMDR for PTSD in this service.

This service evaluation assessed how online Eye Movement Desensitisation and Reprocessing (EMDR) compared to in-person EMDR in people with PTSD.Individuals receiving online EMDR had lower PTSD scores at the end of therapy, but the evidence for this was weak and as this was not a randomised trial we do not know whether this was due to the mode of therapy or other characteristics of clients receiving online therapy.Clients and therapists generally viewed online EMDR as being safe and effective, and supported the availability of online EMDR for PTSD.

Examining the Relationship Between Trauma, Post-Traumatic Stress Disorder and Psychosis in Patients in a UK Secondary Care Service.

Objective: Traumatic experiences and post-traumatic stress disorder (PTSD) are common in schizophrenia. However, few studies screening for PTSD have established the temporality of PTSD-related traumatic events to psychosis onset. Furthermore, it is unclear how many patients attribute a trauma-based contribution to their psychosis or would find trauma-focused therapy acceptable. We examine the prevalence and timing of trauma in psychosis, as well as patient views on the relationship between their trauma experiences and mental health difficulties, and on receiving trauma-focused therapy. Methods: Sixty-eight patients with an at-risk mental state (ARMS) or psychotic disorder in a UK secondary-care setting completed self-report measures of trauma and PTSD, and undertook research interviews. Proportions and odds ratios were derived with 95% confidence intervals. Results: We recruited 68 participants (estimated response rate 62%; psychotic disorder n = 61, ARMS n = 7). Sixty three (95%) reported traumatic events and 32 (47%) reported childhood abuse. Twenty-six individuals (38%) met criteria for PTSD, though for >95% this was not recorded in their notes, and 25 (37%) had sub-threshold PTSD. For 69% of participants, their worst trauma occurred before the onset of their psychosis symptoms. Most (65%) believed their psychosis symptoms were related to past traumas and 82% of these were interested in receiving trauma-focused therapy. Conclusions: PTSD is common in and often pre-dates onset of psychosis. Most patients believe their symptoms and traumas are related and would be interested in trauma-focused therapy if available. Studies evaluating the effectiveness of trauma-focused therapies for those with or at high-risk of psychosis are required.

Polygenic risk of Social-isolation and its influence on social behavior, psychosis, depression and autism spectrum disorder.

Social-isolation has been linked to a range of psychiatric issues, but the behavioral component that drives it is not well understood. Here, a GWAS is carried out to identify genetic variants which contribute to Social-isolation behaviors in up to 449,609 participants from the UK Biobank. 17 loci were identified at genome-wide significance, contributing to a 4% SNP heritability estimate. Using the Social-isolation GWAS, polygenic risk scores (PRS) were derived in ALSPAC, an independent, developmental cohort, and used to test for association with friendship quality. At age 18, friendship scores were associated with the Social-isolation PRS, demonstrating that the genetic factors are able to predict related social traits. LD score regression using the GWAS demonstrated genetic correlation with autism spectrum disorder, schizophrenia, and major depressive disorder. However, no evidence of causality was found using a conservative Mendelian randomization approach other than that of autism spectrum disorder on Social-isolation. Our results show that Social-isolation has a small heritable component which may drive those behaviors which is associated genetically with other social traits such as friendship satisfaction as well as psychiatric disorders.

Adverse childhood experiences and adolescent cannabis use trajectories: findings from a longitudinal UK birth cohort.

BACKGROUND: Adverse childhood experiences (ACEs) are classically defined as physical abuse, sexual abuse, emotional abuse, emotional neglect, bullying, parental substance use or abuse, violence between parents, parental mental health problems or suicide, parental separation, or a parent convicted of criminal offence. Exposure to ACEs can be associated with cannabis use, but no comparisons across all adversities have been made while also considering timing and frequency of cannabis use. We aimed to explore the association between ACEs and cannabis use timing and frequency in adolescence, considering the cumulative number of ACEs and individual ACEs. METHODS: We used data from the Avon Longitudinal Study of Parents and Children, a longitudinal UK birth cohort study. Longitudinal latent classes of cannabis use frequency were derived from self-reported data at multiple timepoints in participants aged 13-24 years. ACEs between ages 0 years and 12 years were derived from prospective and retrospective reports at multiple timepoints by parents and the participant. Multinomial regression was used to analyse the effect of both cumulative exposure to all ACEs and the ten individual ACEs on cannabis use outcomes. FINDINGS: 5212 participants (3132 [60·0%] were female and 2080 [40·0%] were male; 5044 [96·0%] were White and 168 [4·0%] were Black, Asian, or minority ethnic) were included in this study. After adjustment for polygenic risk and environmental risk factors, participants who had 4 or more ACEs at age 0-12 years were at increased risk of early persisting regular cannabis use (relative risk ratio [RRR] 3·15 [95% CI 1·81-5·50]), later onset regular use (1·99 [1·14-3·74]), and early persisting occasional use (2·55 [1·74-3·73]) compared with low or no cannabis use. After adjustment, early persisting regular use was associated with parental substance use or abuse (RRR 3·90 [95% CI 2·10-7·24]), parental mental health problems (2·02 [1·26-3·24]), physical abuse (2·27 [1·31-3·98]), emotional abuse (2·44 [1·49-3·99]), and parental separation (1·88 [1·08-3·27]) compared with low or no cannabis use. INTERPRETATION: Risks for problematic adolescent cannabis use are highest for individuals reporting 4 or more ACEs, and were particularly raised for those with parental substance use or abuse. Public health measures to address ACEs might reduce adolescent cannabis use. FUNDING: The Wellcome Trust, UK Medical Research Council, Alcohol Research UK.

Trauma-specific mindfulness-based cognitive therapy for women with post-traumatic stress disorder and a history of domestic abuse: intervention refinement and a randomised feasibility trial (coMforT study).

BACKGROUND: Women who have experienced domestic violence and abuse (DVA) are at increased risk of developing post-traumatic stress disorder (PTSD) and complex PTSD (CPTSD). In 2014-2015, we developed a prototype trauma-specific mindfulness-based cognitive therapy curriculum (TS-MBCT) for the treatment of PTSD in a DVA population. This study aimed to refine the prototype TS-MBCT and evaluate the feasibility of conducting a randomised controlled trial (RCT) testing its effectiveness and cost-effectiveness. METHODS: Intervention refinement phase was informed by evidence synthesis from a literature review, qualitative interviews with professionals and DVA survivors, and a consensus exercise with experts in trauma and mindfulness. We tested the refined TS-MBCT intervention in an individually randomised parallel group feasibility trial with pre-specified progression criteria, a traffic light system, and embedded process and health economics evaluations. RESULTS: The TS-MBCT intervention consisted of eight group sessions and home practice. We screened 109 women in a DVA agency and recruited 20 (15 TS-MBCT, 5 self-referral to National Health Service (NHS) psychological treatment), with 80% follow-up at 6 months. Our TS-MBCT intervention had 73% uptake, 100% retention, and high acceptability. Participants suggested recruitment via multiple agencies, and additional safety measures. Randomisation into the NHS control arm did not work due to long waiting lists and previous negative experiences. Three self-administered PTSD/CPTSD questionnaires produced differing outcomes thus a clinician administered measure might work better. We met six out of nine feasibility progression criteria at green and three at amber targets demonstrating that it is possible to conduct a full-size RCT of the TS-MBCT intervention after making minor amendments to recruitment and randomisation procedures, the control intervention, primary outcomes measures, and intervention content. At 6 months, none of the PTSD/CPTSD outcomes ruled out a clinically important difference between trial arms indicating that it is reasonable to proceed to a full-size RCT to estimate these outcomes with greater precision. CONCLUSIONS: A future RCT of the coMforT TS-MBCT intervention should have an internal pilot, recruit from multiple DVA agencies, NHS and non-NHS settings, have an active control psychological treatment, use robust randomisation and safety procedures, and clinician-administered measures for PTSD/CPTSD. TRIAL REGISTRATION: ISRCTN64458065 11/01/2019.

Childhood Trauma As a Mediator of the Association Between Autistic Traits and Psychotic Experiences: Evidence From the Avon Longitudinal Study of Parents and Children Cohort.

BACKGROUND: Little is known on whether associations between childhood autistic traits and psychotic experiences persist into adulthood and whether genetic confounding and childhood trauma influence them. Here we investigate the associations between childhood autistic traits and psychotic experiences until young adulthood and assess the influence of schizophrenia polygenic risk and childhood traumatic experiences, using the Avon Longitudinal Study of Parents and Children (ALSPAC) population-based birth cohort. STUDY DESIGN: We used a measure of broad autistic traits (autism factor mean score), and four dichotomised measures of autistic traits capturing social communication difficulties (age 7), repetitive behaviours (age 5), sociability (age 3), and pragmatic language (age 9). Psychotic experiences were assessed at ages 18 and 24 using the semi-structured Psychosis-Like Symptoms interview (PLIKSi). Traumatic experiences between ages 5 and 11 were assessed with questionnaires and interviews administered to children and parents at multiple ages. STUDY RESULTS: Broad autistic traits, as well as social communication difficulties, were associated with psychotic experiences that were distressing and/or frequent until age 24 (autism factor mean score, n = 3707: OR 1.19, 95%CI 1.01-1.39; social communication difficulties, n = 3384: OR 1.54, 95%CI 0.97-2.45). Childhood trauma mediated a substantial proportion of the identified associations (~28% and 36% respectively, maximum n = 3577). Schizophrenia polygenic risk did not appear to confound the associations. Multiple imputation analyses (maximum n = 13 105) yielded comparable results. CONCLUSIONS: Childhood trauma may be an important, potentially modifiable pathway between autistic features and later onset of psychotic psychopathology.

Prevalence and correlates of self-stigma in Post-Traumatic Stress Disorder (PTSD).

Background: Self-stigma refers to the internalisation of negative societal views and stereotypes. Self-stigma has been well-characterised in the context of mental disorders such as schizophrenia but has received little attention in relation to post-traumatic stress disorder (PTSD). Objective: This work aimed to determine the prevalence of self-stigma in a sample of adults with PTSD and to establish factors associated with the internalisation of stigma in this population. Method: Participants were 194 adults (mean age 46.07 (SD = 12.39); 64.4% female; 96.6% white Caucasian; residing in the UK), who self-reported a diagnosis of PTSD and currently screened positive for the disorder according to the PTSD Checklist for DSM-5 (PCL-5). Structured interviews and validated self-report questionnaires were used to ascertain clinical and sociodemographic information for analysis. Results: The prevalence of self-stigma measured by the Internalized Stigma of Mental Illness Scale (ISMIS) was 41.2% (95% CI 34.24-48.22). There was no evidence of an association between self-stigma and gender (ß = -2.975 (95% CI -7.046-1.097) p = .151), age (ß = 0.007 (95% CI -0.152-0.165) p = .953), sexual trauma (ß = 0.904 (95% CI -3.668-5.476) p = .697), military trauma (ß = -0.571 (95% CI -4.027-7.287) p = .571). Self-stigma was associated with lower income and higher levels of anxiety (ß = 5.722 (95% CI 2.922-8.522) p = <.001), depression (ß = 6.937 (95% CI 4.287-9.588) p = <.000), and traumatic stress symptoms (ß = 3.880 (95% CI 1.401-6.359) p = .002). Conclusions: The results indicate that self-stigma may be a significant issue among people with a diagnosis of PTSD. Further work is needed to understand the long-term impact and to develop interventions to address the internalisation of stigma in this population. HIGHLIGHTS: The prevalence of self-stigma among a sample of participants with PTSD was 41.2%.There was no evidence of an association between self-stigma and gender, age or sexual / military trauma.Self-stigma was associated with lower income and higher levels of anxiety, depression, and traumatic stress symptoms.

Antecedentes: El autoestigma se refiere a la internalización de opiniones y estereotipos sociales negativos. El autoestigma ha sido bien caracterizado en los contextos de trastornos mentales como la esquizofrenia, pero ha recibido poca atención en relación al trastorno de estrés postraumático (TEPT).Objetivo: Este trabajo tuvo como objetivo determinar la prevalencia del autoestigma en una muestra de adultos con TEPT y establecer los factores asociados con la internalización del estigma en esta población.Método: Los participantes fueron 194 adultos (edad media 46,09 (DE = 12.39); 64.4% mujeres; 96.6% caucásicos blancos; que residían en el Reino Unido), quienes autoinformaron un diagnóstico de TEPT y que actualmente dieron positivo para el trastorno de acuerdo a la Lista de chequeo de TEPT para el DSM-5 (PCL-5). Se usaron entrevistas estructuradas y cuestionarios de auto-reporte validados para determinar la información clínica y sociodemográfica para el análisis.Resultados: La prevalencia del autoestigma medido por la Escala de Estigma Internalizado de Enfermedad Mental (ISMIS por sus siglas en inglés) fue de 41,2% (95% IC 34.24­48.22). No hubo evidencia de asociación entre estigma y género (ß = −2.975 (95% IC −7.046­1.097) p = .151), edad (ß = 0.007 (95% IC −0.152­0.165) p = .953), trauma sexual (ß = 0.904 (95% IC −3.668­5.476) p = .697), trauma militar (ß = −0.571 (95% IC −4.027­7.287) p = .571). El autoestigma se asoció con menores ingresos y mayores niveles de ansiedad (ß = 5.722 (95% IC 2.922­8.522), p = <.001), depresión (ß = 6.937 (95% IC 4.287­9.588) p = <.000) y síntomas de estrés traumático (ß = 3.880 (95% IC 1.401­6.359) p = .002).Conclusiones: Los resultados indican que el autoestigma puede ser un problema importante entre las personas con un diagnóstico de TEPT. Se necesita más trabajo para comprender el impacto a largo plazo y desarrollar intervenciones que se dirijan a la internalización del estigma en esta población.