Search

Background and Hypothesis Recent findings suggest the incidence of first-episode psychotic disorders (FEP) varies according to setting-level deprivation and cannabis use, but these factors have not been investigated together. We hypothesized deprivation would be more strongly associated with variation in FEP incidence than the prevalence of daily or high-potency cannabis use between settings. Study Design We used incidence data in people aged 18–64 years from 14 settings of the EU-GEI study. We estimated the prevalence of daily and high-potency cannabis use in controls as a proxy for usage in the population at-risk; multiple imputations by chained equations and poststratification weighting handled missing data and control representativeness, respectively. We modeled FEP incidence in random intercepts negative binomial regression models to investigate associations with the prevalence of cannabis use in controls, unemployment, and owner-occupancy in each setting, controlling for population density, age, sex, and migrant/ethnic group. Study Results Lower owner-occupancy was independently associated with increased FEP (adjusted incidence rate ratio [aIRR]: 0.76, 95% CI: 0.61–0.95) and non-affective psychosis incidence (aIRR: 0.68, 95% CI: 0.55–0.83), after multivariable adjustment. Prevalence of daily cannabis use in controls was associated with the incidence of affective psychoses (aIRR: 1.53, 95% CI: 1.02–2.31). We found no association between FEP incidence and unemployment or high-potency cannabis use prevalence. Sensitivity analyses supported these findings. Conclusions Lower setting-level owner-occupancy and increased prevalence of daily cannabis use in controls independently contributed to setting-level variance in the incidence of different psychotic disorders. Public health interventions that reduce exposure to these harmful environmental factors could lower the population-level burden of psychotic disorders. [ABSTRACT FROM AUTHOR]

Psychosis risk prediction is one of the leading challenges in psychiatry. Previous investigations have suggested that plasma proteomic data may be useful in accurately predicting transition to psychosis in individuals at clinical high risk (CHR). We hypothesized that an a priori-specified proteomic prediction model would have strong predictive accuracy for psychosis risk and aimed to replicate longitudinal associations between plasma proteins and transition to psychosis. This study used plasma samples from participants in 3 CHR cohorts: the North American Prodrome Longitudinal Studies 2 and 3, and the NEURAPRO randomized control trial (total n  = 754). Plasma proteomic data were quantified using mass spectrometry. The primary outcome was transition to psychosis over the study follow-up period. Logistic regression models were internally validated, and optimism-corrected performance metrics derived with a bootstrap procedure. In the overall sample of CHR participants (age: 18.5, SD : 3.9; 51.9% male), 20.4% (n  = 154) developed psychosis within 4.4 years. The a priori-specified model showed poor risk-prediction accuracy for the development of psychosis (C -statistic: 0.51 [95% CI: 0.50, 0.59], calibration slope: 0.45). At a group level, Complement C8B, C4B, C5, and leucine-rich α-2 glycoprotein 1 (LRG1) were associated with transition to psychosis but did not surpass correction for multiple comparisons. This study did not confirm the findings from a previous proteomic prediction model of transition from CHR to psychosis. Certain complement proteins may be weakly associated with transition at a group level. Previous findings, derived from small samples, should be interpreted with caution. [ABSTRACT FROM AUTHOR]

Background Social cognitive impairment is a recognized feature of psychotic disorders. However, potential age-related differences in social cognitive impairment have rarely been studied. Study Design Data came from 905 individuals with a psychotic disorder, 966 unaffected siblings, and 544 never-psychotic controls aged 18–55 who participated in the Genetic Risk and Outcome of Psychosis (GROUP) study. Multilevel linear models were fitted to study group main effects and the interaction between group and age on emotion perception and processing (EPP; degraded facial affect recognition) and theory of mind (ToM; hinting task) performance. Age-related differences in the association between socio-demographic and clinical factors, and EPP and ToM were also explored. Study Results Across groups, EPP performance was associated with age (β = −0.02, z = −7.60, 95% CI: −0.02, −0.01, P <.001), with older participants performing worse than younger ones. A significant group-by-age interaction on ToM (X 2(2) = 13.15, P =.001) indicated that older patients performed better than younger ones, while no age-related difference in performance was apparent among siblings and controls. In patients, the association between negative symptoms and ToM was stronger for younger than older patients (z = 2.16, P =.03). Conclusions The findings point to different age-related performance patterns on tests of 2 key social cognitive domains. ToM performance was better in older individuals, although this effect was only observed for patients. EPP was less accurate in older compared with younger individuals. These findings have implications with respect to when social cognitive training should be offered to patients. [ABSTRACT FROM AUTHOR]

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

Background and hypothesis Around 20% of people at clinical high risk (CHR) for psychosis later develop a psychotic disorder, but it is difficult to predict who this will be. We assessed the incidence of hearing speech (termed speech illusions [SIs]) in noise in CHR participants and examined whether this was associated with adverse clinical outcomes. Study design At baseline, 344 CHR participants and 67 healthy controls were presented with a computerized white noise task and asked whether they heard speech, and whether speech was neutral, affective, or whether they were uncertain about its valence. After 2 years, we assessed whether participants transitioned to psychosis, or remitted from the CHR state, and their functioning. Study results CHR participants had a lower sensitivity to the task. Logistic regression revealed that a bias towards hearing targets in stimuli was associated with remission status (OR = 0.21, P = 042). Conversely, hearing SIs with uncertain valence at baseline was associated with reduced likelihood of remission (OR = 7.72. P =.007). When we assessed only participants who did not take antipsychotic medication at baseline, the association between hearing SIs with uncertain valence at baseline and remission likelihood remained (OR = 7.61, P =.043) and this variable was additionally associated with a greater likelihood of transition to psychosis (OR = 5.34, P =.029). Conclusions In CHR individuals, a tendency to hear speech in noise, and uncertainty about the affective valence of this speech, is associated with adverse outcomes. This task could be used in a battery of cognitive markers to stratify CHR participants according to subsequent outcomes. [ABSTRACT FROM AUTHOR]

Background and hypothesis Although maintenance treatment with antipsychotics protects against psychotic relapse, high doses may hamper recovery. Therefore, dose reduction or discontinuation may be considered in patients with chronic schizophrenia. Here, we identified risk factors for psychotic relapse when doses are reduced. Study Design We systematically searched MEDLINE, EMBASE, and PsycINFO from January 1950 through January 2021 and reviewed randomized controlled trials (RCTs) that reported relapse rates after antipsychotic dose reduction or discontinuation in patients with chronic schizophrenia. We calculated relative risks (RRs) with 95% confidence intervals (CIs) per person-year and sought to identify potential risk factors for relapse. The study is registered with PROSPERO (CRD42017058296). Study Results Forty-seven RCTs (54 patient cohorts, 1746 person-years) were included. The RR for psychotic relapse with dose reduction/discontinuation versus maintenance treatment was 2.3 per person-year (95% CI: 1.9 to 2.8). The RR was higher with antipsychotic discontinuation, dose reduction to less than 3–5 mg haloperidol equivalent (HE), or relatively rapid dose reduction (<10 weeks). The RR was lower with long-acting injectable agents versus oral antipsychotic dose reduction. Other factors that increased the risk of psychotic relapse were younger age and short follow-up time. Conclusions Clinicians should take several risk factors for psychotic relapse into account when considering dose reduction in patients with chronic schizophrenia. Studies of a relatively fast reduction in antipsychotic dose support a minimum dose of 3–5 mg HE. However, if the dose is tapered more gradually, relapses related to medication withdrawal might be avoided, possibly enabling lower-end doses to be achieved. [ABSTRACT FROM AUTHOR]

Cluster studies identified a subgroup of patients with psychosis whose premorbid adjustment deteriorates before the onset, which may reflect variation in genetic influence. However, other studies reported a complex relationship between distinctive patterns of cannabis use and cognitive and premorbid impairment that is worthy of consideration. We examined whether: (1) premorbid social functioning (PSF) and premorbid academic functioning (PAF) in childhood and adolescence and current intellectual quotient (IQ) define different clusters in 802 first-episode of psychosis (FEP) patients; resulting clusters vary in (2) polygenic risk scores (PRSs) for schizophrenia (SCZ_PRS), bipolar disorder (BD_PRS), major depression (MD_PRS), and IQ (IQ_PRS), and (3) patterns of cannabis use, compared to 1,263 population-based controls. Four transdiagnostic clusters emerged (BIC = 2268.5): (1) high-cognitive-functioning (n  = 205), with the highest IQ (Mean = 106.1, 95% CI: 104.3, 107.9) and PAF, but low PSF. (2) Low-cognitive-functioning (n  = 223), with the lowest IQ (Mean = 73.9, 95% CI: 72.2, 75.7) and PAF, but normal PSF. (3) Intermediate (n  = 224) (Mean_IQ = 80.8, 95% CI: 79.1, 82.5) with low-improving PAF and PSF. 4) Deteriorating (n  = 150) (Mean_IQ = 80.6, 95% CI: 78.5, 82.7), with normal-deteriorating PAF and PSF. The PRSs explained 7.9% of between-group membership. FEP had higher SCZ_PRS than controls [ F (4,1319) = 20.4, P  < .001]. Among the clusters, the deteriorating group had lower SCZ_PRS and was likelier to have used high-potency cannabis daily. Patients with FEP clustered according to their premorbid and cognitive abilities. Pronounced premorbid deterioration was not typical of most FEP, including those more strongly predisposed to schizophrenia, but appeared in a cluster with a history of high-potency cannabis use. [ABSTRACT FROM AUTHOR]

Background and Hypothesis It is argued that availability of diagnostic models will facilitate a more rapid identification of individuals who are at a higher risk of first episode psychosis (FEP). Therefore, we developed, evaluated, and validated a diagnostic risk estimation model to classify individual with FEP and controls across six countries. Study Design We used data from a large multi-center study encompassing 2627 phenotypically well-defined participants (aged 18–64 years) recruited from six countries spanning 17 research sites, as part of the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions study. To build the diagnostic model and identify which of important factors for estimating an individual risk of FEP, we applied a binary logistic model with regularization by the least absolute shrinkage and selection operator. The model was validated employing the internal-external cross-validation approach. The model performance was assessed with the area under the receiver operating characteristic curve (AUROC), calibration, sensitivity, and specificity. Study Results Having included preselected 22 predictor variables, the model was able to discriminate adults with FEP and controls with high accuracy across all six countries (rangesAUROC = 0.84–0.86). Specificity (range = 73.9–78.0%) and sensitivity (range = 75.6–79.3%) were equally good, cumulatively indicating an excellent model accuracy; though, calibration slope for the diagnostic model showed a presence of some overfitting when applied specifically to participants from France, the UK, and The Netherlands. Conclusions The new FEP model achieved a good discrimination and good calibration across six countries with different ethnic contributions supporting its robustness and good generalizability. [ABSTRACT FROM AUTHOR]

Background and Hypothesis Facial Emotion Recognition is a key domain of social cognition associated with psychotic disorders as a candidate intermediate phenotype. In this study, we set out to investigate global and specific facial emotion recognition deficits in first-episode psychosis, and whether polygenic liability to psychotic disorders is associated with facial emotion recognition. Study Design 828 First Episode Psychosis (FEP) patients and 1308 population-based controls completed assessments of the Degraded Facial Affect Recognition Task (DFAR) and a subsample of 524 FEP and 899 controls provided blood or saliva samples from which we extracted DNA, performed genotyping and computed polygenic risk scores for schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MD). Study Results A worse ability to globally recognize facial emotion expressions was found in patients compared with controls [ B = −1.5 (0.6), 95% CI −2.7 to −0.3], with evidence for stronger effects on negative emotions (fear [ B = −3.3 (1.1), 95% CI −5.3 to −1.2] and anger [ B = −2.3 (1.1), 95% CI −4.6 to −0.1]) than on happiness [ B = 0.3 (0.7), 95% CI −1 to 1.7]. Pooling all participants, and controlling for confounds including case/control status, facial anger recognition was associated significantly with Schizophrenia Polygenic Risk Score (SZ PRS) [ B = −3.5 (1.7), 95% CI −6.9 to −0.2]. Conclusions Psychosis is associated with impaired recognition of fear and anger, and higher SZ PRS is associated with worse facial anger recognition. Our findings provide evidence that facial emotion recognition of anger might play a role as an intermediate phenotype for psychosis. [ABSTRACT FROM AUTHOR]

Objective: People at ultra-high risk (UHR) for psychosis have a high prevalence of tobacco smoking, and rates are even higher among the subgroup that later develop a psychotic disorder. However, the longitudinal relationship between the course of tobacco smoking and clinical outcomes in UHR subjects is unknown. Methods: We investigated associations between tobacco smoking and clinical outcomes in a prospective study of UHR individuals (n = 324). Latent class mixed model analyses were used to identify trajectories of smoking severity. Mixed effects models were applied to investigate associations between smoking trajectory class and the course of attenuated psychotic symptoms (APS) and affective symptoms, as assessed using the CAARMS. Results: We identified four different classes of smoking trajectory: (i) Persistently High (n = 110), (ii) Decreasing (n = 29), (iii) Persistently Low (n = 165) and (iv) Increasing (n = 20). At two-year follow-up, there had been a greater increase in APS in the Persistently High class than for both the Persistently Low (ES = 9.77, SE = 4.87, p = 0.046) and Decreasing (ES = 18.18, SE = 7.61, p = 0.018) classes. There were no differences between smoking classes in the incidence of psychosis. There was a greater reduction in the severity of emotional disturbance and general symptoms in the Decreasing class than in the High (ES = -10.40, SE = 3.41, p = 0.003; ES = -22.36, SE = 10.07, p = 0.027), Increasing (ES = -11.35, SE = 4.55, p = 0.014; ES = -25.58, SE = 13.17, p = 0.050) and Low (ES = -11.38, SE = 3.29, p = 0.001; ES = -27.55, SE = 9.78, p = 0.005) classes, respectively. Conclusions: These findings suggests that in UHR subjects persistent tobacco smoking is associated with an unfavorable course of psychotic symptoms, whereas decrease in the number of cigarettes smoked is associated with improvement in affective symptoms. Future research into smoking cessation interventions in the early stages of psychoses is required to shine light on the potential of modifying smoking behavior and its relation to clinical outcomes. [ABSTRACT FROM AUTHOR]

Psychotic and autistic symptoms are related to social functioning in individuals with psychotic disorders (PD). The present study used a network approach to (1) evaluate the interactions between autistic symptoms, psychotic symptoms, and social functioning, and (2) investigate whether relations are similar in individuals with and without PD. We estimated an undirected network model in a sample of 504 PD, 572 familial risk for psychosis (FR), and 337 typical comparisons (TC), with a mean age of 34.9 years. Symptoms were assessed with the Autism Spectrum Quotient (AQ; 5 nodes) and the Community Assessment of Psychic Experiences (CAPE; 9 nodes). Social functioning was measured with the Social Functioning Scale (SFS; 7 nodes). We identified statistically significant differences between the FR and PD samples in global strength (P <.001) and network structure (P <.001). Our results show autistic symptoms (social interaction nodes) are negatively and more closely related to social functioning (withdrawal, interpersonal behavior) than psychotic symptoms. More and stronger connections between nodes were observed for the PD network than for FR and TC networks, while the latter 2 were similar in density (P =.11) and network structure (P =.19). The most central items in strength for PD were bizarre experiences , social skills , and paranoia. In conclusion, specific autistic symptoms are negatively associated with social functioning across the psychosis spectrum, but in the PD network symptoms may reinforce each other more easily. These findings emphasize the need for increased clinical awareness of comorbid autistic symptoms in psychotic individuals. [ABSTRACT FROM AUTHOR]

Objective To examine the association between baseline alterations in grey matter volume (GMV) and clinical and functional outcomes in people at clinical high risk (CHR) for psychosis. Methods 265 CHR individuals and 92 healthy controls were recruited as part of a prospective multi-center study. After a baseline assessment using magnetic resonance imaging (MRI), participants were followed for at least two years to determine clinical and functional outcomes, including transition to psychosis (according to the Comprehensive Assessment of an At Risk Mental State, CAARMS), level of functioning (according to the Global Assessment of Functioning), and symptomatic remission (according to the CAARMS). GMV was measured in selected cortical and subcortical regions of interest (ROI) based on previous studies (ie orbitofrontal gyrus, cingulate gyrus, gyrus rectus, inferior temporal gyrus, parahippocampal gyrus, striatum, and hippocampus). Using voxel-based morphometry, we analysed the relationship between GMV and clinical and functional outcomes. Results Within the CHR sample, a poor functional outcome (GAF < 65) was associated with relatively lower GMV in the right striatum at baseline (P <.047 after Family Wise Error correction). There were no significant associations between baseline GMV and either subsequent remission or transition to psychosis. Conclusions In CHR individuals, lower striatal GMV was associated with a poor level of overall functioning at follow-up. This finding was not related to effects of antipsychotic or antidepressant medication. The failure to replicate previous associations between GMV and later psychosis onset, despite studying a relatively large sample, is consistent with the findings of recent large-scale multi-center studies. [ABSTRACT FROM AUTHOR]

Understanding longitudinal cognitive performance in individuals at ultra-high risk for psychosis (UHR) is important for informing theoretical models and treatment. A vital step in this endeavor is to determine whether there are UHR subgroups that have similar patterns of cognitive change over time. The aims were to: i) identify latent class trajectories of cognitive performance over 12-months in UHR individuals, ii) identify baseline demographic and clinical predictors of the resulting classes, and iii) determine whether trajectory classes were associated with transition to psychosis or functional outcomes. Cognition was assessed using the Brief Assessment of Cognition in Schizophrenia (BACS) at baseline, 6- and 12-months (N = 288). Using Growth Mixture Modeling, a single unimpaired improving trajectory class was observed for motor function, speed of processing, verbal fluency, and BACS composite. A two-class solution was observed for executive function and working memory, showing one unimpaired and a second impaired class. A three-class solution was found for verbal learning and memory: unimpaired, mildly impaired, and initially extremely impaired, but improved ("caught up") to the level of the mildly impaired. IQ, omega-3 index, and premorbid adjustment were associated with class membership, whereas clinical variables (symptoms, substance use), including transition to psychosis, were not. Working memory and verbal learning and memory trajectory class membership was associated with functioning outcomes. These findings suggest there is no short-term progressive cognitive decline in help-seeking UHR individuals, including those who transition to psychosis. Screening of cognitive performance may be useful for identifying UHR individuals who may benefit from targeted cognitive interventions. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

In the last 2 decades, several neuroimaging studies investigated brain abnormalities associated with the early stages of psychosis in the hope that these could aid the prediction of onset and clinical outcome. Despite advancements in the field, neuroimaging has yet to deliver. This is in part explained by the use of univariate analytical techniques, small samples and lack of statistical power, lack of external validation of potential biomarkers, and lack of integration of nonimaging measures (eg, genetic, clinical, cognitive data). PSYSCAN is an international, longitudinal, multicenter study on the early stages of psychosis which uses machine learning techniques to analyze imaging, clinical, cognitive, and biological data with the aim of facilitating the prediction of psychosis onset and outcome. In this article, we provide an overview of the PSYSCAN protocol and we discuss benefits and methodological challenges of large multicenter studies that employ neuroimaging measures. [ABSTRACT FROM AUTHOR]

Deficits in motivational behavior and psychotic symptoms often observed in schizophrenia (SZ) may be driven by dysfunctional reward processing (RP). RP can be divided in two different stages; reward anticipation and reward consumption. Aberrant processing during reward anticipation seems to be related to SZ. Studies in patients with SZ have found less activation in the ventral striatum (VS) during anticipation of reward, but these findings do not provide information on effect of the genetic load on reward processing. Therefore, this study investigated RP in healthy first-degree relatives of SZ patients. The sample consisted of 94 healthy siblings of SZ patients and 57 healthy controls. Participants completed a classic RP task, the Monetary Incentive Delay task, during functional magnetic resonance imaging (fMRI). As expected, there were no behavioral differences between groups. In contrast to our expectations, we found no differences in any of the anticipatory reward related brain areas (region of interest analyses). Whole-brain analyses did reveal group differences during both reward anticipation and reward consumption; during reward anticipation siblings showed less deactivation in the insula, posterior cingulate cortex (PCC) and medial frontal gyrus (MFG) than controls. During reward consumption siblings showed less deactivation in the PCC and the right MFG compared to controls and activation in contrast to deactivation in controls in the precuneus and the left MFG. Exclusively in siblings, MFG activity correlated positively with subclinical negative symptoms. These regions are typically associated with the default mode network (DMN), which normally shows decreases in activation during task-related cognitive processes. Thus, in contrast to prior literature in patients with SZ, the results do not point to altered brain activity in classical RP brain areas, such as the VS. However, the weaker deactivation found outside the reward-related network in siblings could indicate reduced task-related suppression (i.e. hyperactivation) of the DMN. The presence of DMN hyperactivation during reward anticipation and reward consumption might indicate that siblings of patients with SZ have a higher baseline level of DMN activation and possible abnormal network functioning. [ABSTRACT FROM AUTHOR]

Background Negative symptoms largely account for poor outcome in psychotic disorders but remain difficult to treat. A cognitive– behavioral approach to these symptoms showed promise in chronic schizophrenia patients. We explored whether a combination of group and individual treatment focused on social activation (CBTsa) could benefit patients recently diagnosed with a psychotic disorder. Methods A single-blind randomized controlled trial enrolled 99 participants recently diagnosed with schizophrenia or a related disorder that received treatment as usual (TAU; n 50), or TAU plus CBTsa (n 49). Negative symptoms (Brief Negative Symptom Scale) and social withdrawal (Positive and Negative Syndrome Scale) were primary outcomes. Secondary outcome measures included dysfunctional beliefs (Dysfunctional Attitudes Scale-Defeatist Performance Attitude), stigma (ISMIS), and symptom severity and functioning as measured with the Global Assessment of Functioning (GAF). Outcomes were compared directly posttreatment and at follow-up (6 months posttreatment). Results Intention-to-treat analyses showed significant improvement in GAF symptoms (p.02, d 0.36) and a decrease in negative symptoms on trend level (p.08, d 0.29) in CBTsa compared to TAU at posttreatment. These group differences were no longer apparent at 6 months follow-up. Social withdrawal and negative symptoms improved over time in both conditions. Conclusions The current trial showed small positive effects on symptom severity posttreatment but did not demonstrate maintenance of longer-term effects in favor of the CBTsa group. Findings suggest that the treatment duration may have been too short to change dysfunctional beliefs, a potentially important maintaining factor of negative symptom severity. Longer intervention periods in later, more stable stages of the illness when intensive standard treatment has tapered off may yield more beneficial effects. [ABSTRACT FROM AUTHOR]

Background Individuals at clinical high risk (CHR) for psychosis have approximately a 25% chance of transitioning to psychosis in the first 2 years after first presentation to clinical services. A key aim in this field is to determine the risk of conversion for an individual meeting the criteria for CHR based on clinical, demographic and neuropsychological measures. An individualized risk calculator incorporating 8 risk factors based on these measures has recently been developed by the researchers from the North American Prodrome Longitudinal Study (NAPLS-2) and tested in their dataset of CHR participants. Methods We examined the risk factors from the NAPLS risk calculator in the EU-GEI (EU funded gene environment interaction) high risk study. The EU-GEI high risk study is a longitudinal multi-centre study including 9 sites in Europe, 1 site in Australia and 1 site in Brazil. At baseline, the study included 345 CHR individuals of which 65 later developed psychosis. The NAPLS risk calculator includes 8 risk factors and for each risk factor we attempted to harmonise the EU-GEI measures to the corresponding NAPLS measure. We used multivariate cox regression to determine the standardised hazard ratio for transition to psychosis for the 8 risk factors. To compare each of the NAPLS and EU-GEI hazard ratios we used a meta-analytical framework to calculate a combined hazard ratio and to examine heterogeneity between the effect sizes. Results In terms of the 8 risk factors, only the CAARMS unusual thought + non-bizarre ideas (corresponding to NAPLS SIPS P1+P2) was significantly associated with transition to psychosis, standardised hazard ratio = 1.51 (95%CI 1.01–2.23), p=0.046. Hazard ratios for the remaining risk factors varied from 0.73 to 1.41. The meta-analysis combining EU-GEI and NAPLS data did not indicate heterogeneity for any of the 8 measures, suggesting no systematic differences in the risk factors between the two studies. Discussion The test of the NAPLS risk factors in the independent EU-GEI high risk sample showed support for unusual thought content and non-bizarre ideas being predictive of later transition to psychosis. We were not able to replicate decline in functioning and lower scores in verbal learning memory as predictive of transition to psychosis as seen in the NAPLS study. However, our meta-analytical comparison showed no systematic differences in the hazard ratios for all 8 risk factors between both studies suggesting broad comparability between the samples. [ABSTRACT FROM AUTHOR]

Background Autism traits are present at elevated rates in individuals with psychotic disorders (PD). However, prevalence varies across clinical samples and it is unclear whether individuals with a genetic risk for psychosis (GR) also report more symptoms. Furthermore, it is unknown to what extent comorbid autism symptoms may have an impact on social functioning in psychotic disorders. Methods A large sample of 504 individuals with a PD, 572 individuals with GR (siblings) and 337 typical comparison (TC) individuals was recruited. Autism traits were assessed with the Autism Spectrum Quotient (AQ) and social functioning was measured with the Social Functioning Scale. Results The proportion of AQ scores >32 (indicative of autism diagnosis) was 6.6% for PD, 1.1% for GR and 1.2% for TC. For AQ scores >26 (indicative of high autism traits) respective percentages were: 21.4%, 2.8% and 2.4%. Mean group differences for autism traits (PD > GR > TC) and social functioning (PD < GR < TC) were all significant, albeit with small effect sizes for GR vs TC. Within the PD and GR group, autistic traits showed a negative impact on overall social functioning above and beyond the effect of positive psychotic symptoms. Discussion At least 1 in 5 individuals with a psychotic disorder is characterized by elevated levels of autism traits. In addition, levels of social functioning are negatively affected by autisms traits in individuals with (a genetic predisposition to) psychotic disorders. These findings warrant specific clinical guidelines for psychotic patients who present themselves with autistic comorbidity. [ABSTRACT FROM AUTHOR]

Background The concept of a psychosis continuum implies that the same symptoms seen in patients with psychotic disorders can be measured in a healthy population. The assumption is that experiencing symptoms of psychosis such as delusions and hallucinations is not inevitably associated with the presence of the disorder. Surveys of unselected general population samples have consistently shown that a large number of individuals report experiences that strongly resemble the symptoms seen in psychotic patients. Only a fraction of these individuals met criteria for a clinical disorder such as schizophrenia. Alterations in the metabolic system in antipsychotic-naïve first-episode schizophrenia have been described, posing the question whether these metabolic markers are altered in persons with subclinical psychotic experiences as well. Methods We used cross-sectional data of 1890 participants of a prospective population-based cohort study, 'the Rotterdam Study (ERGO)'. The ages ranged from 45 to 54 years and the participants filled in a self-report questionnaire, 'The Community Assessment of Psychic Experience'. To assess subclinical psychotic symptoms, the frequency and distress ratings of the positive symptom dimension from this questionnaire were used. These items were offset against metabolic measured parameters. The metabolic parameters used were body-mass index (BMI; body weight in kg/m2), fasting glucose levels, low-density lipoproteins (LDL), high-density lipoproteins (HDL), triglycerides and cholesterol. Linear regression analyses were used with adjustment for age, gender, ethnicity, education level, employment status and marital status. The influences of psychopharmacology use, anxiety disorder, depressive symptoms and use of lipid reducing agents on the subclinical psychotic symptoms were analysed in sensitivity analyses. Results We observed a strong positive association between BMI and the frequency of subpsychotic symptoms, and also with the perceived distress of these subpsychotic symptoms. In participants with a BMI ≥ 30 we observed an even stronger association with the frequency score and distress rating of subpsychotic symptoms. In a restricted sample to non-lipid reducing agent users only, we observed that LDL is negatively associated with the frequency of subpsychotic symptoms and perceived distress of these subpsychotic symptoms. For HDL, we observed a negative association with only the frequency of subpsychotic symptoms. The other metabolic markers, total cholesterol, triglycerides and fasting glucose, did not show any significant associations with subpsychotic symptoms. The use of psychopharmaceuticals, the presence of an anxiety disorder or experiencing depressive symptoms did not alter our results. Discussion In this study of a large community sample we found that increased BMI and metabolic dysfunctions are associated with subclinical psychotic experiences. Our findings add to the evidence that psychotic phenomena are related to alterations in the metabolism and obesity even without antipsychotic medication use. Noticeably, this association seems also to hold for subclinical psychotic phenomena, present in the normal population. [ABSTRACT FROM AUTHOR]

• Sleep satisfaction was associated with severity of negative symptoms on (sub)clinical level. • Sleep onset insomnia was associated with negative symptoms in patients. • Early morning insomnia was associated with negative symptoms in siblings. • Hypersomnia was associated with negative symptoms in patients and siblings. • Several associations were mediated by depressive symptoms. Sleep disturbances in patients with psychotic disorders are common and associated with poor clinical outcomes, but research on negative symptoms is limited. This study aimed to examine the association between subjective sleep disturbances and negative symptoms in 525 patients with non-affective psychotic disorders, 569 unaffected siblings and 265 healthy controls (HC) from the Genetic Risk and Outcome of Psychosis (GROUP) study. Several aspects of subjective sleep disturbances were assessed: sleep satisfaction, sleep onset insomnia, midnocturnal insomnia, early morning insomnia, and hypersomnia. Regression analyses revealed significant negative associations between sleep satisfaction and negative symptoms in all three groups. In addition, significant associations with sleep onset insomnia and hypersomnia were found in patients and with early morning insomnia and hypersomnia in siblings. Exploratory mediation analyses showed that depressive symptoms partly mediated all associations on the subclinical level in siblings and healthy controls, whereas only the association with sleep onset insomnia was mediated in patients. The results of this study implicate specific sleep disturbances and depressive symptoms as potential targets in prevention or intervention strategies focussed on negative symptoms in individuals suffering from, or at risk of non-affective psychotic disorders. [ABSTRACT FROM AUTHOR]

Background: Patients are often treated with high doses or combinations of antipsychotics. High doses are associated with more severe side effects and reduction of motivation and drive, which may hamper recovery. Nevertheless, dose-reduction (DR) or discontinuation of antipsychotic medication in chronic patients, carries the risk of psychotic relapse. In order to identify risk factors of psychotic relapse after DR or discontinuation, we performed a meta-analysis, aimed (i) to determine the rate of relapse after DR or discontinuation in patients with chronic schizophrenia, and (ii) to assess risk factors for psychotic relapse. Methods: We searched PubMed, EMBASE and PsycINFO for studies on dose-reduction of antipsychotics from January 1950 through June 2019. We extracted data and calculated event rates (ER=relapse rate) per person-years including 95% confidence intervals (95%CI). The following data were extracted: (1) patient characteristics (age, percentage of male subjects, setting, duration of illness), (2) dose-reduction/discontinuation characteristics (start-dose before dose-reduction, end-dose after dose-reduction, dose-reduction in milligrams, dose-reduction as percentage of start-dose, time period of dose-reduction), (3) follow-up characteristics (time after dose-reduction), and (4) study characteristics (blinding, year of publication and relapse definition). To account for sample variation we pooled the results following the Dersimonian and Laird random effects method (CMA; Borenstein et al 2009). Between-study heterogeneity was assessed with Cochran’s I2-statistic. We examined the risk of bias in the included studies based on five aspects that could affect the association between exposure and outcome from the Newcastle-Ottawa scale (NOS). Results: 46 unique cohorts, presenting 1677 patients in which doses were reduced/discontinued were included in meta-analysis. Most included patients were man at middle age, and with a mean duration of illness of 15 years. There was a considerable risk of bias in studies (48% of studies with NOS≤3). We found an overall event rate (ER) per person-years on psychotic relapse of 0.55 (CI95% 0.46–0.65; p<0.0001; I2 =79). We present various variables that influence event rates. Highest rates were found for inpatients with a short duration of illness. Most robust event rates for psychotic relapse were seen for discontinuing antipsychotics, and if not discontinuing, dose-reduction till under 5mg haloperidol equivalents daily (HE). Abrupt reduction yielded higher rates than gradual reduction. During short follow-up time more relapses occurred than in studies with long follow-up time. Older studies and studies in which relapse was defined as a clinical decision (without applying a psychometric scale) also yielded high event rates, explained by the fact that older studies mostly reduced antipsychotics abruptly till zero or at least doses under 5mgHE, while more recent studies did not, and used rating scales for relapse. Discussion: In patients with chronic schizophrenia discontinuing, and to a lesser extent DR till end-dose <5mgHE, patients who reduce doses abrupt, inpatients, and patients with a short duration of illness carry highest relapse risk. Most relapses occur during the first half year after DR. [ABSTRACT FROM AUTHOR]