The coronavirus disease 2019 (COVID-19) pandemic has been a global challenge. High mortality rates have been reported in some risk groups, including patients with pre-existing mental disorders.

We used electronic health records to retrospectively identify people infected due to COVID-19 (between March 2020 and March 2021) in the three territories of the Basque Country. COVID-19 cases were defined as individuals who had tested positive on a reverse transcription-polymerase chain reaction (PCR) test. Univariate and multivariate logistic regression models and multilevel analyses with generalized estimated equations were used to determine factors associated with COVID-19-related mortality and hospital admission.

The COVID-19 mortality rate was increased for patients with psychotic disorders [odds ratio (OR) adjusted: 1.45, 95% confidence interval (CI) (1.09–1.94), p = 0.0114] and patients with substance abuse [OR adjusted: 1.88, 95% CI (1.13–3.14, p < 0.0152)]. The mortality rate was lower for patients with affective disorders [OR adjusted: 0.80, 95% CI (0.61–0.99), p = 0.0407]. Hospital admission rates due to COVID-19 were higher in psychosis [OR adjusted: 2.90, 95% CI (2.36–3.56), p < 0.0001] and anxiety disorder groups [OR adjusted: 1.54, 95% CI (1.37–1.72), p < 0.0001]. Among admitted patients, COVID-19 mortality rate was decreased for those with affective disorders rate [OR adjusted: 0.72, 95% CI (0.55–0.95), p = 0.0194].

COVID-19-related mortality and hospitalizations rates were higher for patients with a pre-existing psychotic disorder.

Under standard care, psychotic disorders can have limited response to treatments, high rates of chronicity and disability, negative impacts on families, and wider social and economic costs. In an effort to improve early detection and care of individuals developing a psychotic illness, early intervention in psychosis services and early detection services have been set up in various countries since the 1980s. In April 2016, NHS England implemented a new ‘access and waiting times’ standard for early intervention in psychosis to extend the prevention of psychosis across England. Unfortunately, early intervention and early detection services are still not uniformly distributed in the UK, leaving gaps in service provision. The aim of this paper is to provide a business case model that can guide clinicians and services looking to set up or expand early detection services in their area. The paper also focuses on some existing models of care within the Pan-London Network for Psychosis Prevention teams.

The clinical outcomes of individuals at clinical high risk of psychosis (CHR-P) who do not transition to psychosis are heterogeneous and inconsistently reported. We aimed to comprehensively evaluate longitudinally a wide range of outcomes in CHR-P individuals not developing psychosis.

“Preferred Reporting Items for Systematic reviews and Meta-Analyses” and “Meta-analysis Of Observational Studies in Epidemiology”-compliant meta-analysis (PROSPERO: CRD42021229212) searching original CHR-P longitudinal studies in PubMed and Web of Science databases up to 01/11/2021. As primary analysis, we evaluated the following outcomes within CHR-P non-transitioning individuals: (a) change in the severity of attenuated psychotic symptoms (Hedge's g); (b) change in the severity of negative psychotic symptoms (Hedge's g); (c) change in the severity of depressive symptoms (Hedge's g); (d) change in the level of functioning (Hedge's g); (e) frequency of remission (at follow-up). As a secondary analysis, we compared these outcomes in those CHR-P individuals who did not transition vs. those who did transition to psychosis at follow-up. We conducted random-effects model meta-analyses, sensitivity analyses, heterogeneity analyses, meta-regressions and publication bias assessment. The risk of bias was assessed using a modified version of the Newcastle-Ottawa Scale (NOS).

Twenty-eight studies were included (2756 CHR-P individuals, mean age = 20.4, 45.5% females). The mean duration of follow-up of the included studies was of 30.7 months. Primary analysis: attenuated psychotic symptoms [Hedges’ g = 1.410, 95% confidence interval (CI) 1.002–1.818]; negative psychotic symptoms (Hedges’ g = 0.683, 95% CI 0.371–0.995); depressive symptoms (Hedges’ g = 0.844, 95% CI 0.371–1.317); and functioning (Hedges’ g = 0.776, 95% CI 0.463–1.089) improved in CHR-P non-transitioning individuals; 48.7% remitted at follow-up (95% CI 39.3–58.2%). Secondary analysis: attenuated psychotic symptoms (Hedges’ g = 0.706, 95% CI 0.091–1.322) and functioning (Hedges’ g = 0.623, 95% CI 0.375–0.871) improved in CHR-P individuals not-transitioning compared to those transitioning to psychosis, but there were no differences in negative or depressive symptoms or frequency of remission (p > 0.05). Older age was associated with higher improvements of attenuated psychotic symptoms (β = 0.225, p = 0.012); publication years were associated with a higher improvement of functioning (β = −0.124, p = 0.0026); a lower proportion of Brief Limited Intermittent Psychotic Symptoms was associated with higher frequencies of remission (β = −0.054, p = 0.0085). There was no metaregression impact for study continent, the psychometric instrument used, the quality of the study or proportion of females. The NOS scores were 4.4 ± 0.9, ranging from 3 to 6, revealing the moderate quality of the included studies.

Clinical outcomes improve in CHR-P individuals not transitioning to psychosis but only less than half remit over time. Sustained clinical attention should be provided in the longer term to monitor these outcomes.

Accumulating evidence suggests that alterations in inflammatory biomarkers are important in depression. However, previous meta-analyses disagree on these associations, and errors in data extraction may account for these discrepancies.

PubMed/MEDLINE, Embase, PsycINFO, and the Cochrane Library were searched from database inception to 14 January 2020. Meta-analyses of observational studies examining the association between depression and levels of tumor necrosis factor-α (TNF-α), interleukin 1-β (IL-1β), interleukin-6 (IL-6), and C-reactive protein (CRP) were eligible. Errors were classified as follows: incorrect sample sizes, incorrectly used standard deviation, incorrect participant inclusion, calculation error, or analysis with insufficient data. We determined their impact on the results after correction thereof.

Errors were noted in 14 of the 15 meta-analyses included. Across 521 primary studies, 118 (22.6%) showed the following errors: incorrect sample sizes (20 studies, 16.9%), incorrect use of standard deviation (35 studies, 29.7%), incorrect participant inclusion (7 studies, 5.9%), calculation errors (33 studies, 28.0%), and analysis with insufficient data (23 studies, 19.5%). After correcting these errors, 11 (29.7%) out of 37 pooled effect sizes changed by a magnitude of more than 0.1, ranging from 0.11 to 1.15. The updated meta-analyses showed that elevated levels of TNF- α, IL-6, CRP, but not IL-1β, are associated with depression.

These findings show that data extraction errors in meta-analyses can impact findings. Efforts to reduce such errors are important in studies of the association between depression and peripheral inflammatory biomarkers, for which high heterogeneity and conflicting results have been continuously reported.

To determine the proportion of patients in symptomatic remission and recovery following a first-episode of psychosis (FEP).

A multistep literature search using the Web of Science database, Cochrane Central Register of Reviews, Ovid/PsychINFO, and trial registries from database inception to November 5, 2020, was performed. Cohort studies and randomized control trials (RCT) investigating the proportion of remission and recovery following a FEP were included. Two independent researchers searched, following PRISMA and MOOSE guidelines and using a PROSPERO protocol. We performed meta-analyses regarding the proportion of remission/recovery (symptomatic plus functional outcomes). Heterogeneity was measured employing Q statistics and I2 test. To identify potential predictors, meta-regression analyses were conducted, as well as qualitative reporting of studies included in a systematic review. Sensitivity analyses were performed regarding different times of follow-up and type of studies.

One hundred articles (82 cohorts and 18 RCTs) were included in the meta-analysis. The pooled proportion of symptomatic remission was 54% (95%CI [30, 49–58]) over a mean follow-up period of 43.57 months (SD = 51.82) in 76 studies. After excluding RCT from the sample, the proportion of remission remained similar (55%). The pooled proportion of recovery was 32% (95%CI [27–36]) over a mean follow-up period of 71.85 months (SD = 73.54) in 40 studies. After excluding RCT from the sample, the recovery proportion remained the same. No significant effect of any sociodemographic or clinical predictor was found.

Half of the patients are in symptomatic remission around 4 years after the FEP, while about a third show recovery after 5.5 years.

The European impact of the clinical high risk for psychosis (CHR-P) paradigm is constrained by the lack of critical mass (detection) to power prognostic and preventive interventions.

An ITAlian partnership for psychosis prevention (ITAPP) was created across CHR-P centers, which were surveyed to describe: (a) service, catchment area, and outreach; (b) service users; and (c) interventions and outcomes. Descriptive statistics and Kaplan–Meier failure function complemented the analyses.

The ITAPP included five CHR-P clinical academic centers established from 2007 to 2018, serving about 13 million inhabitants, with a recruitment capacity of 277 CHR-P individuals (mean age: 18.7 years, SD: 4.8, range: 12–39 years; 53.1% females; 85.7% meeting attenuated psychotic symptoms; 85.8% without any substance abuse). All centers were multidisciplinary and included adolescents and young adults (transitional) primarily recruited through healthcare services. The comprehensive assessment of at-risk mental state was the most widely used instrument, while the duration of follow-up, type of outreach, and preventive interventions were heterogeneous. Across 205 CHR-P individuals with follow up (663.7 days ± 551.7), the cumulative risk of psychosis increased from 8.7% (95% CI 5.3–14.1) at 1 year to 15.9% (95% CI 10.6–23.3) at 2 years, 21.8% (95% CI 14.9–31.3) at 3 years, 34.8% (95% CI 24.5–47.9) at 4 years, and 51.9% (95% CI 36.3–69.6) at 5 years.

The ITAPP is one of the few CHR-P clinical research partnerships in Europe for fostering detection, prognosis, and preventive care, as well as for translating research innovations into practice.

Individuals at clinical high risk of psychosis (CHR-P) recruited in randomized clinical trials (RCTs) and observational cohorts may display a different enrichment and hence risk of transition to psychosis. No meta-analysis has ever addressed this issue.

“Preferred Reporting Items for Systematic reviews and Meta-Analyses” (PRISMA) and “Meta-analysis Of Observational Studies in Epidemiology” (MOOSE)–compliant meta-analysis. PubMed and Web of Science were searched until November 2020 (PROSPERO:CRD42021229223). We included nonoverlapping longitudinal studies (RCTs-control condition and observational cohorts) reporting the transition to psychosis in CHR-P individuals. The primary effect size measure was the cumulative risk of transition at 0.5, 1, and 2 years follow-up in RCTs compared to observational cohorts. Random effects meta-analyses, heterogeneity assessment, quality assessment, and meta-regressions were conducted.

Ninety-four independent studies (24 RCTs, 70 observational cohorts) and 9,243 individuals (mean age = 20.1 ± 3.0 years; 43.7% females) were included. The meta-analytical risk of transitioning to psychosis from a CHR-P stage was 0.091 (95% confidence intervals [CI] = 0.068–0.121) at 0.5 years, 0.140 (95% CI = 0.101–0.191) at 1 year and 0.165 (95% CI = 0.097–0.267) at 2 years follow-up in RCTs, and 0.081 (95% CI = 0.067–0.099) at 0.5 years, 0.138 (95% CI = 0.114–0.167) at 1 year, and 0.174 (95% CI = 0.156–0.193) at 2 years follow-up in observational cohorts. There were no between-group differences in transition risks (p > 0.05). The proportion of CHR-P individuals with substance use disorders (excluding alcohol and cannabis) was higher in observational cohorts (16.8, 95% CI = 13.3–21.0%) than in RCTs (3.4, 95% CI = 0.8–12.7%; p = 0.018).

There is no meta-analytic evidence supporting sampling biases in RCTs of CHR-P individuals. Further RCTs are needed to detect effective interventions to prevent psychosis in this at-risk group.

Assessment of risks of illnesses has been an important part of medicine for decades. We now have hundreds of ‘risk calculators’ for illnesses, including brain disorders, and these calculators are continually improving as more diverse measures are collected on larger samples.

We first replicated an existing psychosis risk calculator and then used our own sample to develop a similar calculator for use in recruiting ‘psychosis risk’ enriched community samples. We assessed 632 participants age 8–21 (52% female; 48% Black) from a community sample with longitudinal data on neurocognitive, clinical, medical, and environmental variables. We used this information to predict psychosis spectrum (PS) status in the future. We selected variables based on lasso, random forest, and statistical inference relief; and predicted future PS using ridge regression, random forest, and support vector machines.

Cross-validated prediction diagnostics were obtained by building and testing models in randomly selected sub-samples of the data, resulting in a distribution of the diagnostics; we report the mean. The strongest predictors of later PS status were the Children's Global Assessment Scale; delusions of predicting the future or having one's thoughts/actions controlled; and the percent married in one's neighborhood. Random forest followed by ridge regression was most accurate, with a cross-validated area under the curve (AUC) of 0.67. Adjustment of the model including only six variables reached an AUC of 0.70.

Results support the potential application of risk calculators for screening and identification of at-risk community youth in prospective investigations of developmental trajectories of the PS.

Acute and transient psychotic disorders (ATPD) are characterized by an acute onset and a remitting course, and overlap with subgroups of the clinical high-risk state for psychosis. The long-term course and outcomes of ATPD are not completely clear.

Electronic health record-based retrospective cohort study, including all patients who received a first index diagnosis of ATPD (F23, ICD-10) within the South London and Maudsley (SLaM) National Health Service Trust, between 1 st April 2006 and 15th June 2017. The primary outcome was risk of developing persistent psychotic disorders, defined as the development of any ICD-10 diagnoses of non-organic psychotic disorders. Cumulative risk of psychosis onset was estimated through Kaplan-Meier failure functions (non-competing risks) and Greenwood confidence intervals.

A total of 3074 patients receiving a first index diagnosis of ATPD (F23, ICD-10) within SLaM were included. The mean follow-up was 1495 days. After 8-year, 1883 cases (61.26%) retained the index diagnosis of ATPD; the remaining developed psychosis. The cumulative incidence (Kaplan-Meier failure function) of risk of developing any ICD-10 non-organic psychotic disorder was 16.10% at 1-year (95%CI 14.83–17.47%), 28.41% at 2-year (95%CI 26.80–30.09%), 33.96% at 3-year (95% CI 32.25–35.75%), 36.85% at 4-year (95%CI 35.07–38.69%), 40.99% at 5-year (95% CI 39.12–42.92%), 42.58% at 6-year (95%CI 40.67–44.55%), 44.65% at 7-year (95% CI 42.66–46.69%), and 46.25% at 8-year (95% CI 44.17–48.37%). The cumulative risk of schizophrenia-spectrum disorder at 8-year was 36.14% (95% CI 34.09–38.27%).

Individuals with ATPD have a very high risk of developing persistent psychotic disorders and may benefit from early detection and preventive treatments to improve their outcomes.

To investigate clinical outcomes and unmet needs in individuals at Clinical High Risk for Psychosis presenting with Brief and Limited Intermittent Psychotic Symptoms (BLIPS).

Prospective naturalistic long-term (up to 9 years) cohort study in individuals meeting BLIPS criteria at the Outreach And Support In South-London (OASIS) up to April 2016. Baseline sociodemographic and clinical characteristics, specific BLIPS features, preventive treatments received and clinical outcomes (psychotic and non-psychotic) were measured. Analyses included Kaplan Meier survival estimates and Cox regression methods.

One hundred and two BLIPS individuals were followed up to 9 years. Across BLIPS cases, 35% had an abrupt onset; 32% were associated with acute stress, 45% with lifetime trauma and 20% with concurrent illicit substance use. The vast majority (80%) of BLIPS individuals, despite being systematically offered cognitive behavioural therapy for psychosis, did not fully engage with it and did not receive the minimum effective dose. Only 3% of BLIPS individuals received the appropriate dose of cognitive behavioural therapy. At 4-year follow-up, 52% of the BLIPS individuals developed a psychotic disorder, 34% were admitted to hospital and 16% received a compulsory admission. At 3-year follow-up, 52% of them received an antipsychotic treatment; at 4-year follow-up, 26% of them received an antidepressant treatment. The presence of seriously disorganising and dangerous features was a strong poor prognostic factor.

BLIPS individuals display severe clinical outcomes beyond their very high risk of developing psychosis and show poor compliance with preventive cognitive behavioural therapy. BLIPS individuals have severe needs for treatment that are not met by current preventive strategies.

Co-occurrence of common mental disorders (CMD) with psychotic experiences is well-known. There is little research on the public mental health relevance of concurrent psychotic experiences for service use, suicidality, and poor physical health. We aim to: (1) describe the distribution of psychotic experiences co-occurring with a range of non-psychotic psychiatric disorders [CMD, depressive episode, anxiety disorder, probable post-traumatic stress disorder (PTSD), and personality dysfunction], and (2) examine associations of concurrent psychotic experiences with secondary mental healthcare use, psychological treatment use for CMD, lifetime suicide attempts, and poor self-rated health.

We linked a prospective cross-sectional community health survey with a mental healthcare provider database. For each non-psychotic psychiatric disorder, patients with concurrent psychotic experiences were compared to those without psychotic experiences on use of secondary mental healthcare, psychological treatment for CMD, suicide attempt, physical functioning, and a composite multimorbidity score, using logistic regression and Cox regressions.

In all disorders except for anxiety disorder, concurrent psychotic experiences were accompanied by a greater odds of all outcomes (odds ratios) for a unit change in composite multimorbidity score ranged between 2.21 [95% confidence interval (CI) 1.49–3.27] and 3.46 (95% CI 1.52–7.85). Hazard ratios for secondary mental health service use for non-psychotic disorders with concurrent psychotic experiences, ranged from 0.53 (95% CI 0.15–1.86) for anxiety disorders with psychotic experiences to 4.99 (95% CI 1.22–20.44) among those with PTSD with psychotic experiences.

Co-occurring psychotic experiences indicate greater public mental health burden, suggesting psychotic experiences could be a marker for future preventive strategies improving public mental health.

A multitude of risk/protective factors for anxiety and obsessive-compulsive disorders have been proposed. We conducted an umbrella review to summarize the evidence of the associations between risk/protective factors and each of the following disorders: specific phobia, social anxiety disorder, generalized anxiety disorder, panic disorder, and obsessive-compulsive disorder, and to assess the strength of this evidence whilst controlling for several biases.

Publication databases were searched for systematic reviews and meta-analyses examining associations between potential risk/protective factors and each of the disorders investigated. The evidence of the association between each factor and disorder was graded into convincing, highly suggestive, suggestive, weak, or non-significant according to a standardized classification based on: number of cases (>1000), random-effects p-values, 95% prediction intervals, confidence interval of the largest study, heterogeneity between studies, study effects, and excess of significance.

Nineteen systematic reviews and meta-analyses were included, corresponding to 216 individual studies covering 427 potential risk/protective factors. Only one factor association (early physical trauma as a risk factor for social anxiety disorder, OR 2.59, 95% CI 2.17–3.1) met all the criteria for convincing evidence. When excluding the requirement for more than 1000 cases, five factor associations met the other criteria for convincing evidence and 22 met the remaining criteria for highly suggestive evidence.

Although the amount and quality of the evidence for most risk/protective factors for anxiety and obsessive-compulsive disorders is limited, a number of factors significantly increase the risk for these disorders, may have potential prognostic ability and inform prevention.

The predictive accuracy of the Clinical High Risk criteria for Psychosis (CHR-P) regarding the future development of the disorder remains suboptimal. It is therefore necessary to incorporate refined risk estimation tools which can be applied at the individual subject level. The aim of the study was to develop an easy-to use, short refined risk estimation tool to predict the development of psychosis in a new CHR-P cohort recruited in European country with less established early detection services.

A cohort of 105 CHR-P individuals was assessed with the Comprehensive Assessment of At Risk Mental States12/2006, and then followed for a median period of 36 months (25th-75th percentile:10–59 months) for transition to psychosis. A multivariate Cox regression model predicting transition was generated with preselected clinical predictors and was internally validated with 1000 bootstrap resamples.

Speech disorganization and unusual thought content were selected as potential predictors of conversion on the basis of published literature. The prediction model was significant (p < 0.0001) and confirmed that both speech disorganization (HR = 1.69; 95%CI: 1.39–2.05) and unusual thought content (HR = 1.51; 95%CI: 1.27–1.80) were significantly associated with transition. The prognostic accuracy of the model was adequate (Harrell’s c- index = 0.79), even after optimism correction through internal validation procedures (Harrell’s c-index = 0.78).

The clinical prediction model developed, and internally validated, herein to predict transition from a CHR-P to psychosis may be a promising tool for use in clinical settings. It has been incorporated into an online tool available at: https://link.konsta.com.pl/psychosis. Future external replication studies are needed.

Patients with acute and transient psychotic disorders (ATPDs) are by definition remitting, but have a high risk of developing persistent psychoses, resembling a subgroup of individuals at Clinical High Risk for Psychosis (CHR-P). Their pathways to care, treatment offered and long-term clinical outcomes beyond risk to psychosis are unexplored. We conducted an electronic health record-based retrospective cohort study including patients with ATPDs within the SLaM NHS Trust and followed-up to 8 years.

A total of 2561 ATPDs were included in the study. A minority were detected (8%) and treated (18%) by Early Intervention services (EIS) and none by CHR-P services. Patients were offered a clinical follow-up of 350.40 ± 589.90 days. The cumulative incidence of discharges was 40% at 3 months, 60% at 1 year, 69% at 2 years, 77% at 4 years, and 82% at 8 years. Treatment was heterogeneous: the majority of patients received antipsychotics (up to 52%), only a tiny minority psychotherapy (up to 8%).

Over follow-up, 32.88% and 28.54% of ATPDS received at least one mental health hospitalization or one compulsory hospital admission under the Mental Health Act, respectively. The mean number of days spent in psychiatric hospital was 66.39 ± 239.44 days.

The majority of ATPDs are not detected/treated by EIS or CHR-P services, receive heterogeneous treatments and short-term clinical follow-up. ATPDs have a high risk of developing severe clinical outcomes beyond persistent psychotic disorders and unmet clinical needs that are not targeted by current mental health services.

Formal thought disorder is a cardinal feature of psychosis. However, the extent to which formal thought disorder is evident in ultra-high-risk individuals and whether it is linked to the progression to psychosis remains unclear.

Examine the severity of formal thought disorder in ultra-high-risk participants and its association with future psychosis.

The Thought and Language Index (TLI) was used to assess 24 ultra-high-risk participants, 16 people with first-episode psychosis and 13 healthy controls. Ultra-high-risk individuals were followed up for a mean duration of 7 years (s.d.=1.5) to determine the relationship between formal thought disorder at baseline and transition to psychosis.

TLI scores were significantly greater in the ultra-high-risk group compared with the healthy control group (effect size (ES)=1.2), but lower than in people with first-episode psychosis (ES=0.8). Total and negative TLI scores were higher in ultra-high-risk individuals who developed psychosis, but this was not significant. Combining negative TLI scores with attenuated psychotic symptoms and basic symptoms predicted transition to psychosis (P=0.04; ES=1.04).

TLI is beneficial in evaluating formal thought disorder in ultra-high-risk participants, and complements existing instruments for the evaluation of psychopathology in this group.