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.

Psychosis is associated with a reasoning bias, which manifests as a tendency to ‘jump to conclusions’. We examined this bias in people at clinical high-risk for psychosis (CHR) and investigated its relationship with their clinical outcomes.

In total, 303 CHR subjects and 57 healthy controls (HC) were included. Both groups were assessed at baseline, and after 1 and 2 years. A ‘beads’ task was used to assess reasoning bias. Symptoms and level of functioning were assessed using the Comprehensive Assessment of At-Risk Mental States scale (CAARMS) and the Global Assessment of Functioning (GAF), respectively. During follow up, 58 (16.1%) of the CHR group developed psychosis (CHR-T), and 245 did not (CHR-NT). Logistic regressions, multilevel mixed models, and Cox regression were used to analyse the relationship between reasoning bias and transition to psychosis and level of functioning, at each time point.

There was no association between reasoning bias at baseline and the subsequent onset of psychosis. However, when assessed after the transition to psychosis, CHR-T participants showed a greater tendency to jump to conclusions than CHR-NT and HC participants (55, 17, 17%; χ2 = 8.13, p = 0.012). There was a significant association between jumping to conclusions (JTC) at baseline and a reduced level of functioning at 2-year follow-up in the CHR group after adjusting for transition, gender, ethnicity, age, and IQ.

In CHR participants, JTC at baseline was associated with adverse functioning at the follow-up. Interventions designed to improve JTC could be beneficial in the CHR population.

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.

While recent research points to the potential benefits of clinical intervention before the first episode of psychosis, the logistical feasibility of this is unclear.

To assess the feasibility of providing a clinical service for people with prodromal symptoms in an inner city area where engagement with mental health services is generally poor.

Following a period of liaison with local agencies to promote the service, referrals were assessed and managed in a primary care setting. Activity of the service was audited over 30 months.

People with prodromal symptoms were referred by a range of community agencies and seen at their local primary care physician practice. Over 30 months, 180 clients were referred; 58 (32.2%) met criteria for an at risk mental state, most of whom (67.2%) had attenuated psychotic symptoms. Almost 30% were excluded due to current or previous psychotic illness, of which two-thirds were in the first episode of psychosis. The socio-demographic composition of the 'at risk' group reflected that of the local population, with an over-representation of clients from an ethnic minority. Over 90% of suitable clients remained engaged with the service after 1 year.

It is feasible to provide a clinical service for people with prodromal symptoms in a deprived inner city area with a large ethnic minority population.

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.

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.

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.

Previous studies using resting-state functional neuroimaging have revealed alterations in whole-brain images, connectome-wide functional connectivity and graph-based metrics in groups of patients with schizophrenia relative to groups of healthy controls. However, it is unclear which of these measures best captures the neural correlates of this disorder at the level of the individual patient.

Here we investigated the relative diagnostic value of these measures. A total of 295 patients with schizophrenia and 452 healthy controls were investigated using resting-state functional Magnetic Resonance Imaging at five research centres. Connectome-wide functional networks were constructed by thresholding correlation matrices of 90 brain regions, and their topological properties were analyzed using graph theory-based methods. Single-subject classification was performed using three machine learning (ML) approaches associated with varying degrees of complexity and abstraction, namely logistic regression, support vector machine and deep learning technology.

Connectome-wide functional connectivity allowed single-subject classification of patients and controls with higher accuracy (average: 81%) than both whole-brain images (average: 53%) and graph-based metrics (average: 69%). Classification based on connectome-wide functional connectivity was driven by a distributed bilateral network including the thalamus and temporal regions.

These results were replicated across the three employed ML approaches. Connectome-wide functional connectivity permits differentiation of patients with schizophrenia from healthy controls at single-subject level with greater accuracy; this pattern of results is consistent with the ‘dysconnectivity hypothesis’ of schizophrenia, which states that the neural basis of the disorder is best understood in terms of system-level functional connectivity alterations.

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.

Smoking is the largest single contributor to poor physical health and increased mortality in people with serious mental illnesses. The aim of the study was to investigate the utility of electronic cigarettes (e-cigarettes) as a harm reduction intervention in this population.

Fifty tobacco smokers with a psychotic disorder were enrolled onto a 24-week pilot study (ClinicalTrials.gov: NCT02212041) investigating the efficacy of a 6-week free e-cigarette intervention to reduce smoking. Cigarette and e-cigarette use was self-reported at weekly visits, and verified using carbon monoxide tests. Psychopathology, e-cigarette acceptability and adverse effects were assessed using standardised scales.

There was a significant (⩾50%) reduction in cigarettes consumed per day between baseline and week 6 [F(2.596,116.800) = 25.878, p < 0.001], and e-cigarette use was stable during this period [F(2.932,46.504) = 2.023, p = 0.115]. These changes were verified by significant carbon monoxide reductions between these time points [F(3.335,126.633) = 5.063, p = 0.002].

The provision of e-cigarettes is a potentially useful harm reduction intervention in smokers with a psychotic disorder.

The authors have no competing financial interests to declare in relation to the current work. Sarah McAllister was supported by a King's Undergraduate Research Fellowship.

Although psychotic experiences in people without diagnosed mental health problems are associated with mental health service use, few studies have assessed this prospectively or measured service use by real-world clinical data.

To describe and investigate the association between psychotic experiences and later mental health service use, and to assess the role of symptoms of common mental health disorders in this association.

We linked a representative survey of south-east London (SELCoH-1, n=1698) with health records from the local mental healthcare provider. Cox regression estimated the association of PEs with rate of mental health service use.

After adjustments, psychotic experiences were associated with a 1.75-fold increase in the rate of subsequent mental health service use (hazard ratio (HR) 1.75, 95% CI 1.03–2.97) compared with those without PEs. Participants with PEs experienced longer care episodes compared with those without.

Psychotic experiences in the general population are important predictors of public mental health need, aside from their relevance for psychoses. We found psychotic experiences to be associated with later mental health service use, after accounting for sociodemographic confounders and concurrent psychopathology.

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.

There is no consensus as to whether magnetic resonance imaging (MRI) should be used as part of the initial clinical evaluation of patients with first-episode psychosis (FEP).

(a) To assess the logistical feasibility of routine MRI; (b) to define the clinical significance of radiological abnormalities in patients with FEP.

Radiological reports from MRI scans of two FEP samples were reviewed; one comprised 108 patients and 98 healthy controls recruited to a research study and the other comprised 241 patients scanned at initial clinical presentation plus 66 healthy controls.

In the great majority of patients, MRI was logistically feasible. Radiological abnormalities were reported in 6% of the research sample and in 15% of the clinical sample (odds ratio (OR) = 3.1, 95% CI 1.26–7.57, χ2(1) = 6.63, P = 0.01). None of the findings necessitated a change in clinical management.

Rates of neuroradiological abnormalities in FEP are likely to be underestimated in research samples that often exclude patients with organic abnormalities. However, the majority of findings do not require intervention.