The 20-year longitudinal trajectories of social functioning in individuals with psychotic disorders

Objective: Social impairment is a long-recognized core feature of schizophrenia and is common in other psychotic disorders. Still, to date the long-term trajectories of social impairment in psychotic disorders have rarely been studied systematically. Methods: Data came from the Suffolk County Mental Health Project, a 20-year prospective study of first-admission patients with psychotic disorders. A never-psychotic comparison group was also assessed. Latent class growth analysis was applied to longitudinal data on social functioning from 485 respondents with schizophrenia spectrum disorders and psychotic mood disorders, and associations of the empirically derived trajectories with premorbid social adjustment, diagnosis, and 20-year outcomes were examined. Results: Four mostly stable trajectories of preserved (N=82; 59th percentile of comparison group sample distribution), moderately impaired (N=148; 17th percentile), severely impaired (N=181; 3rd percentile), and profoundly impaired (N=74; 1st percentile) functioning best described the 20-year course of social functioning across diagnoses. The outcome in the group with preserved functioning did not differ from that of never-psychotic individuals at 20 years, but the other groups functioned significantly worse. Differences among trajectories were already evident in childhood. The two most impaired trajectories started to diverge in early adolescence. Poorer social functioning trajectories were strongly associated with other real-world outcomes at 20 years. Multiple trajectories were represented within each disorder. However, more participants with schizophrenia spectrum disorders had impaired trajectories, and more with mood disorders had better functioning trajectories. Conclusions: The results highlight substantial variability of social outcomes within diagnoses—albeit overall worse social outcomes in schizophrenia spectrum disorders—and show remarkably stable long-term impairments in social functioning after illness onset across all diagnoses

Declining Clinical Course of Psychotic Disorders Over the Two Decades Following First Hospitalization: Evidence From the Suffolk County Mental Health Project

OBJECTIVE: Kraepelin considered declining course a hallmark of schizophrenia, but others have suggested that outcomes usually stabilize or improve after treatment initiation. The authors investigated this question in an epidemiologically defined cohort with psychotic disorders followed for 20 years after first hospitalization. METHOD: The Suffolk County Mental Health Project recruited first-admission patients with psychosis from all inpatient units of Suffolk County, New York (response rate, 72%). Participants were assessed in person six times over two decades; 373 completed the 20-year follow-up (68% of survivors); 175 had schizophrenia/schizoaffective disorder. Global Assessment of Functioning (GAF), psychotic symptoms, and mood symptoms were rated at each assessment. Month 6, when nearly all participants were discharged from the index hospitalization, was used as a reference. RESULTS: In the schizophrenia group, mean GAF scores declined from 49 at month 6 to 36 at year 20. Negative and positive symptoms also worsened (Cohen's d values, 0.45-0.73). Among participants without schizophrenia, GAF scores were higher initially (a mean of approximately 64) but declined by 9 points over the follow-up period. Worsening began between years 5 and 8. Neither aging nor changes in antipsychotic treatment accounted for the declines. In all disorders, depression improved and manic symptoms remained low across the 20 years. CONCLUSIONS: The authors found substantial symptom burden across disorders that increased with time and ultimately may undo initial treatment gains. Previous studies have suggested that better health care delivery models may preempt this decline. In the United States, these care needs are often not met, and addressing them is an urgent priority

Ethnicity and baseline symptomatology in patients with an At Risk Mental State for psychosis

Ethnicity has been associated with different incidence rates and different symptom profiles in young patients with psychotic-like disorders. No studies so far have examined the effect of ethnicity on symptoms in people with an At Risk Mental State (ARMS). In this cross-sectional study, we analysed the relationship between ethnicity and baseline data on the severity of psychopathology scores in 201 help-seeking patients who met the ARMS criteria and agreed to participate in the Dutch Early Detection and Intervention (EDIE-NL) trial. Eighty-seven of these patients had a non-Dutch ethnicity. We explored the possible mediating role of ethnic identity. Higher rates of negative symptoms, and of anhedonia in particular, were found in the ethnic minority group. This result could be attributed mainly to the Moroccan-Dutch and Turkish-Dutch subgroups, who also presented with more depression symptoms when the groups were examined separately. The ethnic minority group displayed a lower level of ethnic group identity compared to the immigrants of the International Comparative Study of Ethnocultural Youth (ICSEY). Ethnic identity was inversely related to symptoms in the Moroccan-Dutch patient group. The prevalence of more severe negative symptoms and depression symptoms in ethnic minority groups deserves more attention, as the experience of attenuated positive symptoms when accompanied by negative symptoms or distress has proven to be predictive for transition to a first psychotic episod

Prescription of antipsychotic medication to patients at ultra high risk of developing psychosis

Little is known about medication prescription in a naturalistic setting to patients at ultra high risk (UHR) of developing psychosis. Antipsychotic medication prescription to UHR patients is not recommended in clinical practice guidelines based on the current evidence. The aim of this study is to investigate medication prescription to UHR patients in the Netherlands. The frequency of antipsychotic medication prescription to UHR patients (n=72) was compared with the frequency of antipsychotic medication prescription to patients who were diagnosed with a Diagnostic and Statistical Manual of Mental Disorders, fourth edition psychotic disorder at first diagnostic evaluation (n=90). Within the UHR group, frequency of antipsychotic medication prescription at baseline was compared between UHR patients who did make the transition to psychosis (n=18) and UHR patients who did not (n=54). No significant differences were found in antipsychotic medication prescription to UHR patients and to patients who turned out to have a florid psychosis: 51% in the psychotic group and 58% in the UHR group used no medication. Thirty-four percent in the psychotic group and 21% in the UHR group used antipsychotic medication. There was also no difference in medication prescription between UHR patients who did and did not make the transition to psychosis. More research should be aimed at developing and implementing clinical practice guidelines for the treatment of UHR patients

The use of the multivariate Principal Response Curve (PRC) for community analysis: a case study on the effects of carbendazim on enchytraeids in Terrestrial Model Ecosystems (TME).

The effects of the fungicide carbendazim (formulation Derosal®) on enchytraeids were determined in Terrestrial Model Ecosystem (TME) tests. TMEs consisted of intact soil columns (diameter 17.5 cm; length 40 cm) taken from three grassland sites (Amsterdam (The Netherlands), Bangor (Wales, England) and Flörsheim (Germany)) or an arable site (Coimbra (Portugal)). Results for each TME site were evaluated using the multivariate Principal Response Curve (PRC) method. The resulting No-Observable Effect Concentrations (NOECs) for the community were compared with the NOECs generated by univariate statistical methods. Furthermore, the E

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.The European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) Project is funded by grant agreement HEALTH-F2-2010-241909 (Project EU-GEI) from the European Community’s Seventh Framework Programme. The Brazilian study was funded by grant 2012/0417-0 from the São Paulo Research Foundation. Dr Kirkbride is funded by the Wellcome Trust and grant 101272/Z/13/Z from the Royal Society. Ms Jongsma and Dr Jones are funded by the National Institute of Health Research Collaboration of Leadership in Applied Health Research and Care East of England

Lifespan evolution of neurocognitive impairment in schizophrenia - A narrative review

Cognitive impairment is a well-recognized key feature of schizophrenia. Here we review the evidence on (1) the onset and sensitive periods of change in cognitive impairment before and after the first psychotic episode, and (2) heterogeneity in neurocognitive presentations across cognitive domains between and within individuals. Overall, studies suggest that mild cognitive impairment in individuals who develop schizophrenia or related disorders is already present during early childhood. Cross-sectional studies further suggest increasing cognitive impairments from pre- to post-psychosis onset, with the greatest declines between adolescence, the prodrome, and the first psychotic episode and with some variability between domains. Longitudinal studies with more than 10 years of observation time are scarce but support mild cognitive declines after psychosis onset until late adulthood. Whether and how much this cognitive decline exceeds normal aging, proceeds further in older patients, and is specific to certain cognitive domains and subpopulations of patients remains to be investigated. Finally, studies show substantial heterogeneity in cognitive performance in schizophrenia and suggest a variety of impairment profiles. This review highlights a clear need for long-term studies that include a control group and individuals from adolescence to old age to better understand critical windows of cognitive change and its predictors. The available evidence stresses the importance of interventions that aim to counter cognitive decline during the prodromal years, as well as careful assessment of cognition in order to determine who will profit most from which cognitive training

The social cognitive and neural mechanisms that underlie social functioning in individuals with schizophrenia - a review

In many individuals with a diagnosis of schizophrenia social functioning is impaired across the lifespan. Social cognition has emerged as one of the possible factors that may contribute to these challenges. Neuroimaging research can give further insights into the underlying mechanisms of social (cognitive) difficulties. This review summarises the evidence on the associations between social cognition in the domains of theory of mind and emotion perception and processing, and individuals' social functioning and social skills, as well as associated neural mechanisms. Eighteen behavioural studies were conducted since the last major review and meta-analysis in the field (inclusion between 7/2017 and 1/2022). No major review has investigated the link between the neural mechanisms of social cognition and their association with social functioning in schizophrenia. Fourteen relevant studies were included (from 1/2000 to 1/2022). The findings of the behavioural studies showed that associations with social outcomes were slightly stronger for theory of mind than for emotion perception and processing. Moreover, performance in both social cognitive domains was more strongly associated with performance on social skill measures than questionnaire-based assessment of social functioning in the community. Studies on the underlying neural substrate of these associations presented mixed findings. In general, higher activation in various regions of the social brain was associated with better social functioning. The available evidence suggests some shared regions that might underlie the social cognition-social outcome link between different domains. However, due to the heterogeneity in approaches and findings, the current knowledge base will need to be expanded before firm conclusions can be drawn

Pathways from speech illusions to psychotic symptoms in subjects at Ultra-High Risk for psychosis: combining an experimental measure of aberrant experiences with network analysis

Background One of the oldest and most influential theories of psychosis formation states that delusions arise in an attempt to explain unusual experiences, including perceptual aberrations. The White Noise Task by Galdos et al (2011) was developed as an experimental task to assess the tendency to attribute meaning to random perceptual stimuli: speech illusions in white noise. Studies to date have demonstrated that speech illusions as assessed with the White Noise Task are associated with a composite measure of positive symptoms in patients with psychotic disorders (Galdos et al, 2011; Catalan et al, 2014). However, findings in non-clinical samples have been inconsistent: one study found an association with a composite measure of subclinical positive symptoms, including support for a relation with familial psychosis liability (Galdos et al, 2011), whereas other studies did not find any association in non-clinical samples or only partly (Catalan et al, 2014; Rimvall et al, 2016; Pries et al, 2017). The current study aims to further examine whether speech illusions as assessed with the White Noise Task are indicative of psychosis liability and to explore specific symptomatic pathways. Methods We conducted symptom-based network analyses in Ultra-High Risk (UHR) subjects participating in the European network of national networks studying gene-environment interactions in schizophrenia project (EU-GEI, 2014; www.eu-gei.eu). Psychotic symptoms were assessed with the Brief Psychiatric Rating Scale (BPRS). Transition to clinical psychosis was assessed with the Comprehensive Assessment of At Risk Mental State (CAARMS). We used a conservative measure of speech illusions, as described in Catalan et al (2014). Results The current sample consisted of 339 UHR subjects, of which 9.1% (N=31) experienced speech illusions. Preliminary network analyses in cross-sectional baseline data showed potential pathways from speech illusions to delusional ideation, through hallucinatory experiences. We also found evidence of prospective relations between speech illusions at baseline and transition to clinical psychosis. Pathways ran via baseline psychotic symptoms and affective symptoms, as well as a ‘direct’ pathway. Discussion As far as we are aware, this is the first study combining an experimental measure of aberrant experiences with symptom-based network analysis. Although the current reported findings are preliminary and exploratory, they tentatively support a relation between speech illusions as assessed with the White Noise Task and psychosis liability. This relation may be dependent on sample composition, and not generalizable to the general population as a whole. Future studies may benefit from focusing on more detailed trajectories of both susceptibility to speech illusions and course of (sub)clinical psychotic symptom severity in subjects with increased risk for psychosis, with use of more frequent, short assessment periods and inclusion of environmental risk factors for transition to clinical disorder