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Various psychological and biological pathways have been proposed as mediators between childhood adversity (CA) and psychosis. A systematic review of the evidence in this domain is needed. Our aim is to systematically review the evidence on psychological and biological mediators between CA and psychosis across the psychosis spectrum. This review followed PRISMA guidelines. Articles published between 1979 and July 2019 were identified through a literature search in OVID (PsychINFO, Medline and Embase) and Cochrane Libraries. The evidence by each analysis and each study is presented by group of mediator categories found. The percentage of total effect mediated was calculated. Forty-eight studies were included, 21 in clinical samples and 27 in the general population (GP) with a total of 82 352 subjects from GP and 3189 from clinical studies. The quality of studies was judged as ‘fair’. Our results showed (i) solid evidence of mediation between CA and psychosis by negative cognitive schemas about the self, the world and others (NS); by dissociation and other post-traumatic stress disorder symptoms; and through an affective pathway in GP but not in subjects with disorder; (iii) lack of studies exploring biological mediators. We found evidence suggesting that various overlapping and not competing pathways involving post-traumatic and mood symptoms, as well as negative cognitions contribute partially to the link between CA and psychosis. Experiences of CA, along with relevant mediators should be routinely assessed in patients with psychosis. Evidence testing efficacy of interventions targeting such mediators through cognitive behavioural approaches and/or pharmacological means is needed in future.
The association between childhood adversity (CA) and psychosis has been extensively investigated in recent years. An increasing body of research has also focused on the mediating or moderating role of biological and psychological mechanisms, as well as other risk factors that might account for the link between CA and psychosis. We conducted a systematic search of the PsychINFO, Embase, Ovid, and Web of Science databases for original articles investigating the role of genetic vulnerabilities, environmental factors, psychological and psychopathological mechanisms in the association between CA and psychosis up to August 2019. We included studies with individuals at different stages of the psychosis continuum, from subclinical psychotic experiences to diagnosed disorders. From the 28 944 records identified, a total of 121 studies were included in this review. Only 26% of the studies identified met the criteria for methodological robustness. Overall, the current evidence suggests that CA may be associated with psychosis largely independently of genetic vulnerabilities. More consistent and robust evidence supports interaction between early and recent adversities, as well as the mediating role of attachment and mood symptoms, which is suggestive of an affective pathway between CA and psychosis across the continuum from subclinical experiences to diagnosable disorder. This review highlighted numerous methodological issues with the existing literature, including selection bias, heterogeneity of measurement instruments utilised, and lack of control for potential confounders. Future research should address these limitations to more accurately estimate mediation and moderation effects on the CA-psychosis association to inform the development of preventive interventions.
It remains poorly understood how negative symptoms are experienced in the daily lives of individuals in the early stages of psychosis. We aimed to investigate whether altered affective experience, anhedonia, social anhedonia, and asociality were more pronounced in individuals with an at-risk mental state for psychosis (ARMS) and individuals with first-episode psychosis (FEP) than in controls.
We used the experience sampling methodology (ESM) to assess negative symptoms, as they occurred in the daily life of 51 individuals with FEP and 46 ARMS, compared with 53 controls.
Multilevel linear regression analyses showed no overall evidence for a blunting of affective experience. There was some evidence for anhedonia in FEP but not in ARMS, as shown by a smaller increase of positive affect (BΔat−risk v. FEP = 0.08, p = 0.006) as the pleasantness of activities increased. Against our expectations, no evidence was found for greater social anhedonia in any group. FEP were more often alone (57%) than ARMS (38%) and controls (35%) but appraisals of the social situation did not point to asociality.
Overall, altered affective experience, anhedonia, social anhedonia and asociality seem to play less of a role in the daily life of individuals in the early stages of psychosis than previously assumed. With the experience of affect and pleasure in daily life being largely intact, changing social situations and appraisals thereof should be further investigated to prevent development or deterioration of negative symptoms.
First episode psychosis (FEP) patients who use cannabis experience more frequent psychotic and euphoric intoxication experiences compared to controls. It is not clear whether this is consequent to patients being more vulnerable to the effects of cannabis use or to their heavier pattern of use. We aimed to determine whether extent of use predicted psychotic-like and euphoric intoxication experiences in patients and controls and whether this differs between groups.
We analysed data on patients who had ever used cannabis (n = 655) and controls who had ever used cannabis (n = 654) across 15 sites from six countries in the EU-GEI study (2010–2015). We used multiple regression to model predictors of cannabis-induced experiences and to determine if there was an interaction between caseness and extent of use.
Caseness, frequency of cannabis use and money spent on cannabis predicted psychotic-like and euphoric experiences (p ⩽ 0.001). For psychotic-like experiences (PEs) there was a significant interaction for caseness × frequency of use (p < 0.001) and caseness × money spent on cannabis (p = 0.001) such that FEP patients had increased experiences at increased levels of use compared to controls. There was no significant interaction for euphoric experiences (p > 0.5).
FEP patients are particularly sensitive to increased psychotic-like, but not euphoric experiences, at higher levels of cannabis use compared to controls. This suggests a specific psychotomimetic response in FEP patients related to heavy cannabis use. Clinicians should enquire regarding cannabis related PEs and advise that lower levels of cannabis use are associated with less frequent PEs.
The ‘jumping to conclusions’ (JTC) bias is associated with both psychosis and general cognition but their relationship is unclear. In this study, we set out to clarify the relationship between the JTC bias, IQ, psychosis and polygenic liability to schizophrenia and IQ.
A total of 817 first episode psychosis patients and 1294 population-based controls completed assessments of general intelligence (IQ), and JTC, and provided blood or saliva samples from which we extracted DNA and computed polygenic risk scores for IQ and schizophrenia.
The estimated proportion of the total effect of case/control differences on JTC mediated by IQ was 79%. Schizophrenia polygenic risk score was non-significantly associated with a higher number of beads drawn (B = 0.47, 95% CI −0.21 to 1.16, p = 0.17); whereas IQ PRS (B = 0.51, 95% CI 0.25–0.76, p < 0.001) significantly predicted the number of beads drawn, and was thus associated with reduced JTC bias. The JTC was more strongly associated with the higher level of psychotic-like experiences (PLEs) in controls, including after controlling for IQ (B = −1.7, 95% CI −2.8 to −0.5, p = 0.006), but did not relate to delusions in patients.
Our findings suggest that the JTC reasoning bias in psychosis might not be a specific cognitive deficit but rather a manifestation or consequence, of general cognitive impairment. Whereas, in the general population, the JTC bias is related to PLEs, independent of IQ. The work has the potential to inform interventions targeting cognitive biases in early psychosis.
Increasing evidence suggests psychosis may be more meaningfully viewed in dimensional terms rather than as discrete categorical states and that specific symptom clusters may be identified. If so, particular risk factors and premorbid factors may predict these symptom clusters.
(i) To explore, using principal component analysis, whether specific factors for psychotic symptoms can be isolated. (ii) To establish the predictors of the different symptom factors using multiple regression techniques.
One hundred and eighty-nine inpatients with psychotic illness were recruited and information on family history, premorbid factors and current symptoms obtained from them and their mothers.
Seven distinct symptom components were identified. Regression analysis failed to identify any developmental predictors of depression or mania. Delusions/hallucinations were predicted by a family history of schizophrenia and by poor school functioning in spite of normal premorbid IQ (F = 6.5; P < 0.001); negative symptoms by early onset of illness, developmental delay and a family history of psychosis (F = 4.1; P = 0.04). Interestingly disorganisation was predicted by the combination of family history of bipolar disorder and low premorbid IQ (F = 4.9; P = 0.003), and paranoia by obstetric complications (OCs) and poor school functioning (F = 4.2; P = 0.01).
Delusions and hallucinations, negative symptoms and paranoia all appeared to have a developmental origin though they were associated with different childhood problems. On the other hand, neither mania nor depression was associated with childhood dysfunction. Our most striking finding was that disorganisation appeared to arise when a familial predisposition to mania was compounded by low premorbid IQ.
To test the hypothesis that recent onset psychotic patients who use cannabis will have psychotic symptoms that are more severe and more persistent than those who do not use cannabis.
Subjects and methods
We carried out a 4-year follow-up study of a cohort of 119 patients with recent onset of psychosis. The patients were divided into four groups according to duration of cannabis use, taking index admission and follow-up as reference points.
Those subjects who persisted in the use of cannabis had more positive (but not negative) symptoms and a more continuous illness at follow-up.
The main limitations of the study were: the relatively small sample size, and that the excess of male subjects and the presence of cannabis induced psychosis could have a confusing impact on the interpretation of the results.
It is possible that psychotic patients who use cannabis are at a greater risk of a more continuous illness with more positive symptoms than those who do not.
While it is known that patients with schizophrenia recognize facial emotions, specifically negative emotions, less accurately, little is known about how they misattribute these emotions to other emotions and whether such misattribution biases are associated with symptoms, course of the disorder, or certain cognitive functions.
Outpatients with schizophrenia or schizoaffective disorder (n = 73) and healthy controls (n = 30) performed a computerised Facial Emotion Attribution Test and Wisconsin Card Sorting Test (WCST). Patients were also rated on the Positive and Negative Syndrome Scale (PANSS).
Patients were poor at recognizing fearful and angry emotions and attributed fear to angry and angry to neutral expressions. Fear-as-anger misattributions were predicted independently by a longer duration of illness and WCST perseverative errors.
The findings show a bias towards misattributing fearful and angry facial emotions. The propensity for fear-as-anger misattribution biases increases as the length of time that the disorder is experienced increases and a more rigid style of information processing is used. This, at least in part, may be perpetuated by subtle fearfulness expressed by others while interacting with people with schizophrenia.
Daily use of high-potency cannabis has been reported to carry a high risk for developing a psychotic disorder. However, the evidence is mixed on whether any pattern of cannabis use is associated with a particular symptomatology in first-episode psychosis (FEP) patients.
We analysed data from 901 FEP patients and 1235 controls recruited across six countries, as part of the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study. We used item response modelling to estimate two bifactor models, which included general and specific dimensions of psychotic symptoms in patients and psychotic experiences in controls. The associations between these dimensions and cannabis use were evaluated using linear mixed-effects models analyses.
In patients, there was a linear relationship between the positive symptom dimension and the extent of lifetime exposure to cannabis, with daily users of high-potency cannabis having the highest score (B = 0.35; 95% CI 0.14–0.56). Moreover, negative symptoms were more common among patients who never used cannabis compared with those with any pattern of use (B = −0.22; 95% CI −0.37 to −0.07). In controls, psychotic experiences were associated with current use of cannabis but not with the extent of lifetime use. Neither patients nor controls presented differences in depressive dimension related to cannabis use.
Our findings provide the first large-scale evidence that FEP patients with a history of daily use of high-potency cannabis present with more positive and less negative symptoms, compared with those who never used cannabis or used low-potency types.
Ethnic minority groups in Western countries face an increased risk of psychotic disorders. Causes of this long-standing public health inequality remain poorly understood. We investigated whether social disadvantage, linguistic distance and discrimination contributed to these patterns.
We used case–control data from the EUropean network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI) study, carried out in 16 centres in six countries. We recruited 1130 cases and 1497 population-based controls. Our main outcome measure was first-episode ICD-10 psychotic disorder (F20–F33), and exposures were ethnicity (white majority, black, mixed, Asian, North-African, white minority and other), generational status, social disadvantage, linguistic distance and discrimination. Age, sex, paternal age, cannabis use, childhood trauma and parental history of psychosis were included as a priori confounders. Exposures and confounders were added sequentially to multivariable logistic models, following multiple imputation for missing data.
Participants from any ethnic minority background had crude excess odds of psychosis [odds ratio (OR) 2.03, 95% confidence interval (CI) 1.69–2.43], which remained after adjustment for confounders (OR 1.61, 95% CI 1.31–1.98). This was progressively attenuated following further adjustment for social disadvantage (OR 1.52, 95% CI 1.22–1.89) and linguistic distance (OR 1.22, 95% CI 0.95–1.57), a pattern mirrored in several specific ethnic groups. Linguistic distance and social disadvantage had stronger effects for first- and later-generation groups, respectively.
Social disadvantage and linguistic distance, two potential markers of sociocultural exclusion, were associated with increased odds of psychotic disorder, and adjusting for these led to equivocal risk between several ethnic minority groups and the white majority.
Neuroanatomical abnormalities in first-episode psychosis (FEP) tend to be subtle and widespread. The vast majority of previous studies have used small samples, and therefore may have been underpowered. In addition, most studies have examined participants at a single research site, and therefore the results may be specific to the local sample investigated. Consequently, the findings reported in the existing literature are highly heterogeneous. This study aimed to overcome these issues by testing for neuroanatomical abnormalities in individuals with FEP that are expressed consistently across several independent samples.
Structural Magnetic Resonance Imaging data were acquired from a total of 572 FEP and 502 age and gender comparable healthy controls at five sites. Voxel-based morphometry was used to investigate differences in grey matter volume (GMV) between the two groups. Statistical inferences were made at p < 0.05 after family-wise error correction for multiple comparisons.
FEP showed a widespread pattern of decreased GMV in fronto-temporal, insular and occipital regions bilaterally; these decreases were not dependent on anti-psychotic medication. The region with the most pronounced decrease – gyrus rectus – was negatively correlated with the severity of positive and negative symptoms.
This study identified a consistent pattern of fronto-temporal, insular and occipital abnormalities in five independent FEP samples; furthermore, the extent of these alterations is dependent on the severity of symptoms and duration of illness. This provides evidence for reliable neuroanatomical alternations in FEP, expressed above and beyond site-related differences in anti-psychotic medication, scanning parameters and recruitment criteria.
A higher incidence of psychotic disorders has been consistently reported among black and other minority ethnic groups, particularly in northern Europe. It is unclear whether these rates have changed over time.
We identified all individuals with a first episode psychosis who presented to adult mental health services between 1 May 2010 and 30 April 2012 and who were resident in London boroughs of Lambeth and Southwark. We estimated age-and-gender standardised incidence rates overall and by ethnic group, then compared our findings to those reported in the Aetiology and Ethnicity of Schizophrenia and Other Psychoses (ÆSOP) study that we carried out in the same catchment area around 10 years earlier.
From 9109 clinical records we identified 558 patients with first episode psychosis. Compared with ÆSOP, the overall incidence rates of psychotic disorder in southeast London have increased from 49.4 (95% confidence interval (CI) 43.6–55.3) to 63.1 (95% CI 57.3–69.0) per 100 000 person-years at risk. However, the overall incidence rate ratios (IRR) were reduced in some ethnic groups: for example, IRR (95% CI) for the black Caribbean group reduced from 6.7 (5.4–8.3) to 2.8 (2.1–3.6) and the ‘mixed’ group from 2.7 (1.8–4.2) to 1.4 (0.9–2.1). In the black African group, there was a negligible difference from 4.1 (3.2–5.3) to 3.5 (2.8–4.5).
We found that incidence rates of psychosis have increased over time, and the IRR varied by the ethnic group. Future studies are needed to investigate more changes over time and determinants of change.
Positive symptoms are a useful predictor of aggression in schizophrenia. Although a similar pattern of abnormal brain structures related to both positive symptoms and aggression has been reported, this observation has not yet been confirmed in a single sample.
To study the association between positive symptoms and aggression in schizophrenia on a neurobiological level, a prospective meta-analytic approach was employed to analyze harmonized structural neuroimaging data from 10 research centers worldwide. We analyzed brain MRI scans from 902 individuals with a primary diagnosis of schizophrenia and 952 healthy controls.
The result identified a widespread cortical thickness reduction in schizophrenia compared to their controls. Two separate meta-regression analyses revealed that a common pattern of reduced cortical gray matter thickness within the left lateral temporal lobe and right midcingulate cortex was significantly associated with both positive symptoms and aggression.
These findings suggested that positive symptoms such as formal thought disorder and auditory misperception, combined with cognitive impairments reflecting difficulties in deploying an adaptive control toward perceived threats, could escalate the likelihood of aggression in schizophrenia.
Risk prediction algorithms have long been used in health research and practice (e.g. prediction of cardiovascular disease and diabetes). However, similar tools have not been developed for mental health. For example, for psychotic disorders, attempts to sum environmental risk are rare, unsystematic and dictated by available data. In light of this, we sought to develop a valid, easy to use measure of the aggregate environmental risk score (ERS) for psychotic disorders.
We reviewed the literature to identify well-replicated and validated environmental risk factors for psychosis that combine a significant effect and large-enough prevalence. Pooled estimates of relative risks were taken from the largest available meta-analyses. We devised a method of scoring the level of exposure to each risk factor to estimate ERS. Relative risks were rounded as, due to the heterogeneity of the original studies, risk effects are imprecisely measured.
Six risk factors (ethnic minority status, urbanicity, high paternal age, obstetric complications, cannabis use and childhood adversity) were used to generate the ERS. A distribution for different levels of risk based on simulated data showed that most of the population would be at low/moderate risk with a small minority at increased environmental risk for psychosis.
This is the first systematic approach to develop an aggregate measure of environmental risk for psychoses in asymptomatic individuals. This can be used as a continuous measure of liability to disease; mostly relevant to areas where the original studies took place. Its predictive ability will improve with the collection of additional, population-specific data.
The first episode of psychosis is a critical period in the emergence of cardiometabolic risk.
We set out to explore the influence of individual and lifestyle factors on cardiometabolic outcomes in early psychosis.
This was a prospective cohort study of 293 UK adults presenting with first-episode psychosis investigating the influence of sociodemographics, lifestyle (physical activity, sedentary behaviour, nutrition, smoking, alcohol, substance use) and medication on cardiometabolic outcomes over the following 12 months.
Rates of obesity and glucose dysregulation rose from 17.8% and 12%, respectively, at baseline to 23.7% and 23.7% at 1 year. Little change was seen over time in the 76.8% tobacco smoking rate or the quarter who were sedentary for over 10 h daily. We found no association between lifestyle at baseline or type of antipsychotic medication prescribed with either baseline or 1-year cardiometabolic outcomes. Median haemoglobin A1c (HbA1c) rose by 3.3 mmol/mol in participants from Black and minority ethnic (BME) groups, with little change observed in their White counterparts. At 12 months, one-third of those with BME heritage exceeded the threshold for prediabetes (HbA1c >39 mmol/mol).
Unhealthy lifestyle choices are prevalent in early psychosis and cardiometabolic risk worsens over the next year, creating an important window for prevention. We found no evidence, however, that preventative strategies should be preferentially directed based on lifestyle habits. Further work is needed to determine whether clinical strategies should allow for differential patterns of emergence of cardiometabolic risk in people of different ethnicities.
To determine the baseline individual characteristics that predicted symptom recovery and functional recovery at 10-years following the first episode of psychosis.
AESOP-10 is a 10-year follow up of an epidemiological, naturalistic population-based cohort of individuals recruited at the time of their first episode of psychosis in two areas in the UK (South East London and Nottingham). Detailed information on demographic, clinical, and social factors was examined to identify which factors predicted symptom and functional remission and recovery over 10-year follow-up. The study included 557 individuals with a first episode psychosis. The main study outcomes were symptom recovery and functional recovery at 10-year follow-up.
At 10 years, 46.2% (n = 140 of 303) of patients achieved symptom recovery and 40.9% (n = 117) achieved functional recovery. The strongest predictor of symptom recovery at 10 years was symptom remission at 12 weeks (adj OR 4.47; CI 2.60–7.67); followed by a diagnosis of depression with psychotic symptoms (adj OR 2.68; CI 1.02–7.05). Symptom remission at 12 weeks was also a strong predictor of functional recovery at 10 years (adj OR 2.75; CI 1.23–6.11), together with being from Nottingham study centre (adj OR 3.23; CI 1.25–8.30) and having a diagnosis of mania (adj OR 8.17; CI 1.61–41.42).
Symptom remission at 12 weeks is an important predictor of both symptom and functional recovery at 10 years, with implications for illness management. The concepts of clinical and functional recovery overlap but should be considered separately.
Reducing hospitalisation and length of stay (LOS) in hospital following first episode psychosis (FEP) is important, yet reliable measures of these outcomes and their moderators are lacking. We conducted a systematic review and meta-analysis to investigate the proportion of FEP cases who were hospitalised after their first contact with services and the LOS in a hospital during follow-up.
Studies were identified from a systematic search across major electronic databases from inception to October 2017. Random effects meta-analyses and meta-regression analyses were conducted.
81 longitudinal studies encompassing data for 23 280 FEP patients with an average follow-up length of 7 years were included. 55% (95% CI 50.3–60.5%) of FEP cases were hospitalised at least once during follow-up with the pooled average LOS of 116.7 days (95% CI 95.1–138.3). Older age of illness onset and being in a stable relationship were associated with a lower proportion of people who were hospitalised. While the proportion of hospitalised patients has not decreased over time, LOS has, with the sharpest reduction in the latest time period. The proportion of patients hospitalised during follow-up was highest in Australia and New Zealand (78.4%) compared to Europe (58.1%) and North America (48.0%); and lowest in Asia (32.5%). Black ethnicity and longer duration of untreated psychosis were associated with longer LOS; while less severe psychotic symptoms at baseline were associated with shorter LOS.
One in two FEP cases required hospitalisation at least once during a 7-year follow-up with an average length of hospitalisation of 4 months during this period. LOS has declined over time, particularly in those countries in which it was previously longest.