Charlotte Gayer-Anderson

Life Events and Psychosis: A Review and Meta-analysis

Introduction:Recent models of psychosis implicate stressful events in its etiology. However, while evidence has accumulated for childhood trauma, the role of adult life events has received less attention. Therefore, a review of the existing literature on the relationship between life events and onset of psychotic disorder/experiences is timely. Methods: A search was conducted using PsychInfo, Medline, Embase, and Web of Science to identify studies of life events and the onset of psychosis or psychotic experiences within the general population. Given previous methodological concerns, this review included a novel quality assessment tool and focused on findings from the most robust studies. A meta-analysis was performed on a subgroup of 13 studies. Results: Sixteen studies published between 1968 and 2012 were included. Of these, 14 reported positive associations between exposure to adult life events and subsequent onset of psychotic disorder/experiences. The meta-analysis yielded an overall weighted OR of 3.19 (95% CI 2.15–4.75). However, many studies were limited by small sample sizes and the use of checklist measures of life events, with no consideration of contextual influences on the meaning and interpretation of events. Conclusions: Few studies have assessed the role of adult life events in the onset of psychosis. There was some evidence that reported exposure to adult life events was associated with increased risk of psychotic disorder and subclinical psychotic experiences. However, the methodological quality of the majority of studies was low, which urges caution in interpreting the results and points toward a need for more methodologically robust studies.

Social networks, support and early psychosis: a systematic review

Background. There is strong evidence that those with a long-standing psychotic disorder have fewer social contacts and less social support than comparison groups. There is less research on the extent of social contacts and support prior to or at the onset of psychosis. In the light of recent evidence implicating a range of social experiences and contexts at the onset of psychosis, it is relevant to establish whether social networks and support diminished before or at the time of onset and whether the absence of such supports might contribute to risk, either directly or indirectly. We, therefore, conducted a systematic review of this literature to establish what is currently known about the relationship between social networks, support and early psychosis. Methods. We identified all studies investigating social networks and support in first episode psychosis samples and in general population samples with measures of psychotic experiences or schizotype by conducting systematic searches of electronic databases using pre-defined search terms and criteria. Findings were synthesized using non-quantitative approaches. Results. Thirty-eight papers were identified that met inclusion criteria. There was marked methodological heterogeneity, which limits the capacity to draw direct comparisons. Nonetheless, the existing literature suggests social networks (particularly close friends) and support diminished both among first episode samples and among non-clinical samples reporting psychotic experiences or with schizotype traits, compared with varying comparison groups. These differences may be more marked for men and for those from minority ethnic populations. Conclusions. Tentatively, reduced social networks and support appear to pre-date onset of psychotic disorder. However, the substantial methodological heterogeneity among the existing studies makes comparisons difficult and suggests a need for more robust and comparable studies on networks, support and early psychosis.

A systematic review of the activity of the hypothalamic-pituitary-adrenal axis in first episode psychosis.

Up to now studies on hypothalamic-pituitary-adrenal (HPA) axis activity in psychosis have shown inconsistent findings. These inconsistencies have been often ascribed to confounding effects of long duration of illness and chronic treatment with psychotropic medications of the subjects studied (chronic psychosis). In the last years, several studies have focused on the study of subjects at their first episode of psychosis to overcome these possible confounders. The aim of this paper was to review the literature investigating HPA axis activity in first episode psychosis. Findings from these studies support the presence of HPA axis hyperactivity and a blunted HPA axis response to stress at the onset of psychosis. Possible biological pathways linking these HPA axis abnormalities to the development of psychosis are discussed.

Stress Sensitivity, Aberrant Salience, and Threat Anticipation in Early Psychosis: An Experience Sampling Study

While contemporary models of psychosis have proposed a number of putative psychological mechanisms, how these impact on individuals to increase intensity of psychotic experiences in real life, outside the research laboratory, remains unclear. We aimed to investigate whether elevated stress sensitivity, experiences of aberrant novelty and salience, and enhanced anticipation of threat contribute to the development of psychotic experiences in daily life. We used the experience sampling method (ESM) to assess stress, negative affect, aberrant salience, threat anticipation, and psychotic experiences in 51 individuals with first-episode psychosis (FEP), 46 individuals with an at-risk mental state (ARMS) for psychosis, and 53 controls with no personal or family history of psychosis. Linear mixed models were used to account for the multilevel structure of ESM data. In all 3 groups, elevated stress sensitivity, aberrant salience, and enhanced threat anticipation were associated with an increased intensity of psychotic experiences. However, elevated sensitivity to minor stressful events (χ2 = 6.3, P = 0.044), activities (χ2 = 6.7, P = 0.036), and areas (χ2 = 9.4, P = 0.009) and enhanced threat anticipation (χ2 = 9.3, P = 0.009) were associated with more intense psychotic experiences in FEP individuals than controls. Sensitivity to outsider status (χ2 = 5.7, P = 0.058) and aberrantly salient experiences (χ2 = 12.3, P = 0.002) were more strongly associated with psychotic experiences in ARMS individuals than controls. Our findings suggest that stress sensitivity, aberrant salience, and threat anticipation are important psychological processes in the development of psychotic experiences in daily life in the early stages of the disorder.

Childhood adversities and psychosis: evidence, challenges, implications.

There is a substantial body of research reporting evidence of associations between various forms of childhood adversity and psychosis, across the spectrum from experiences to disorder. This has been extended, more recently, to include studies of cumulative effects, of interactions with other factors, of specific effects, and of putative biological and psychological mechanisms. In this paper we evaluate this research and highlight the remaining methodological issues and gaps that temper, but do not dismiss, conclusions about the causal role of childhood adversity. We also consider the emerging work on cumulative, synergistic, and specific effects and on mechanisms; and discuss the broader implications of this line of research for our understanding of psychosis. We conclude that the current balance of evidence is that childhood adversities – particularly exposure to multiple adversities involving hostility and threat – do, in some people, contribute to the onset of psychotic experiences and psychotic disorders.

Effects of continuation, frequency, and type of cannabis use on relapse in the first 2 years after onset of psychosis: an observational study

BACKGROUND Although cannabis use after a first episode of psychosis has been associated with relapse, little is known about the determinants of this most preventable risk factor for relapse of psychosis. Here we aimed to study whether the effects on outcome vary depending on the type of cannabis consumed and usage pattern. METHODS In this observational study, we prospectively recruited and followed up patients aged 18-65 years who presented with their first episode of psychosis to psychiatric services in south London, London, UK. Relapse of psychosis within 2 years after onset of psychosis was defined as risk of subsequent admission to hospital. We classified patients into different patterns of cannabis use based on continuity of use after onset of psychosis, potency of cannabis consumed, and frequency of use after the onset of their illness. We used multiple regression analyses (logistic or binominal) to compare the different cannabis use groups and propensity score analysis to validate the results. FINDINGS Between April 12, 2002, and July 26, 2013, 256 patients presented with a first episode of psychosis. We did follow-up assessments for these patients until September, 2015. Simple analyses showed that former regular users of cannabis who stopped after the onset of psychosis had the most favourable illness course with regards to relapse. In multiple analysis, continued high-frequency users (ie, daily use in all 24 months) of high-potency (skunk-like) cannabis had the worst outcome, indexed as an increased risk for a subsequent relapse (odds ratio [OR] 3·28; 95% CI 1·22-9·18), more relapses (incidence rate ratio 1·77; 95% CI 0·96-3·25), fewer months until a relapse occurred (b -0·22; 95% CI -0·40 to -0·04), and more intense psychiatric care (OR 3·16; 95% CI 1·26-8·09) after the onset of psychosis. INTERPRETATION Adverse effects associated with continued use of cannabis after the onset of a first episode of psychosis depend on the specific patterns of use. Possible interventions could focus on persuading cannabis-using patients with psychosis to reduce use or shift to less potent forms of cannabis. FUNDING National Institute for Health Research (NIHR).

Treated Incidence of Psychotic Disorders in the Multinational EU-GEI Study

Importance Psychotic disorders contribute significantly to the global disease burden, yet the latest international incidence study of psychotic disorders was conducted in the 1980s. Objectives To estimate the incidence of psychotic disorders using comparable methods across 17 catchment areas in 6 countries and to examine the variance between catchment areas by putative environmental risk factors. Design, Setting, and Participants An international multisite incidence study (the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions) was conducted from May 1, 2010, to April 1, 2015, among 2774 individuals from England (2 catchment areas), France (3 catchment areas), Italy (3 catchment areas), the Netherlands (2 catchment areas), Spain (6 catchment areas), and Brazil (1 catchment area) with a first episode of nonorganic psychotic disorders (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision [ICD-10] codes F20-F33) confirmed by the Operational Criteria Checklist. Denominator populations were estimated using official national statistics. Exposures Age, sex, and racial/ethnic minority status were treated as a priori confounders. Latitude, population density, percentage unemployment, owner-occupied housing, and single-person households were treated as catchment area–level exposures. Main Outcomes and Measures Incidence of nonorganic psychotic disorders (ICD-10 codes F20-F33), nonaffective psychoses (ICD-10 codes F20-F29), and affective psychoses (ICD-10 codes F30-F33) confirmed by the Operational Criteria Checklist. Results A total of 2774 patients (1196 women and 1578 men; median age, 30.5 years [interquartile range, 23.0-41.0 years]) with incident cases of psychotic disorders were identified during 12.9 million person-years at risk (crude incidence, 21.4 per 100 000 person-years; 95% CI, 19.4-23.4 per 100 000 person-years). A total of 2183 patients (78.7%) had nonaffective psychotic disorders. After direct standardization for age, sex, and racial/ethnic minority status, an 8-fold variation was seen in the incidence of all psychotic disorders, from 6.0 (95% CI, 3.5-8.6) per 100 000 person-years in Santiago, Spain, to 46.1 (95% CI, 37.3-55.0) per 100 000 person-years in Paris, France. Rates were elevated in racial/ethnic minority groups (incidence rate ratio, 1.6; 95% CI, 1.5-1.7), were highest for men 18 to 24 years of age, and were lower in catchment areas with more owner-occupied homes (incidence rate ratio, 0.8; 95% CI, 0.7-0.8). Similar patterns were observed for nonaffective psychoses; a lower incidence of affective psychoses was associated with higher area-level unemployment (incidence rate ratio, 0.3; 95% CI, 0.2-0.5). Conclusions and Relevance This study confirmed marked heterogeneity in risk for psychotic disorders by person and place, including higher rates in younger men, racial/ethnic minorities, and areas characterized by a lower percentage of owner-occupied houses.

Psychological processes underlying the association between childhood trauma and psychosis in daily life: an experience sampling study

Background Evidence has accumulated that implicates childhood trauma in the aetiology of psychosis, but our understanding of the putative psychological processes and mechanisms through which childhood trauma impacts on individuals and contributes to the development of psychosis remains limited. We aimed to investigate whether stress sensitivity and threat anticipation underlie the association between childhood abuse and psychosis. Method We used the Experience Sampling Method to measure stress, threat anticipation, negative affect, and psychotic experiences in 50 first-episode psychosis (FEP) patients, 44 At-Risk Mental State (ARMS) participants, and 52 controls. Childhood abuse was assessed using the Childhood Trauma Questionnaire. Results Associations of minor socio-environmental stress in daily life with negative affect and psychotic experiences were modified by sexual abuse and group (all pFWE < 0.05). While there was strong evidence that these associations were greater in FEP exposed to high levels of sexual abuse, and some evidence of greater associations in ARMS exposed to high levels of sexual abuse, controls exposed to high levels of sexual abuse were more resilient and reported less intense negative emotional reactions to socio-environmental stress. A similar pattern was evident for threat anticipation. Conclusions Elevated sensitivity and lack of resilience to socio-environmental stress and enhanced threat anticipation in daily life may be important psychological processes underlying the association between childhood sexual abuse and psychosis.

Modeling the Interplay Between Psychological Processes and Adverse, Stressful Contexts and Experiences in Pathways to Psychosis: An Experience Sampling Study

Several integrated models of psychosis have implicated adverse, stressful contexts and experiences, and affective and cognitive processes in the onset of psychosis. In these models, the effects of stress are posited to contribute to the development of psychotic experiences via pathways through affective disturbance, cognitive biases, and anomalous experiences. However, attempts to systematically test comprehensive models of these pathways remain sparse. Using the Experience Sampling Method in 51 individuals with first-episode psychosis (FEP), 46 individuals with an at-risk mental state (ARMS) for psychosis, and 53 controls, we investigated how stress, enhanced threat anticipation, and experiences of aberrant salience combine to increase the intensity of psychotic experiences. We fitted multilevel moderated mediation models to investigate indirect effects across these groups. We found that the effects of stress on psychotic experiences were mediated via pathways through affective disturbance in all 3 groups. The effect of stress on psychotic experiences was mediated by threat anticipation in FEP individuals and controls but not in ARMS individuals. There was only weak evidence of mediation via aberrant salience. However, aberrant salience retained a substantial direct effect on psychotic experiences, independently of stress, in all 3 groups. Our findings provide novel insights on the role of affective disturbance and threat anticipation in pathways through which stress impacts on the formation of psychotic experiences across different stages of early psychosis in daily life.

The 2nd Schizophrenia International Research Society Conference, 10-14 April 2010, Florence, Italy: summaries of oral sessions.

The 2nd Schizophrenia International Research Society Conference, was held in Florence, Italy, April 10-15, 2010. Student travel awardees served as rapporteurs of each oral session and focused their summaries on the most significant findings that emerged from each session and the discussions that followed. The following report is a composite of these reviews. It is hoped that it will provide an overview for those who were present, but could not participate in all sessions, and those who did not have the opportunity to attend, but who would be interested in an update on current investigations ongoing in the field of schizophrenia research.