A clinical tool to estimate the risk of treatment-resistant schizophrenia (TRS) in people with first-episode psychosis (FEP) would inform early detection of TRS and overcome the delay of up to 5 years in starting TRS medication.

To develop and evaluate a model that could predict the risk of TRS in routine clinical practice.

We used data from two UK-based FEP cohorts (GAP and AESOP-10) to develop and internally validate a prognostic model that supports identification of patients at high-risk of TRS soon after FEP diagnosis. Using sociodemographic and clinical predictors, a model for predicting risk of TRS was developed based on penalised logistic regression, with missing data handled using multiple imputation. Internal validation was undertaken via bootstrapping, obtaining optimism-adjusted estimates of the model's performance. Interviews and focus groups with clinicians were conducted to establish clinically relevant risk thresholds and understand the acceptability and perceived utility of the model.

We included seven factors in the prediction model that are predominantly assessed in clinical practice in patients with FEP. The model predicted treatment resistance among the 1081 patients with reasonable accuracy; the model's C-statistic was 0.727 (95% CI 0.723–0.732) prior to shrinkage and 0.687 after adjustment for optimism. Calibration was good (expected/observed ratio: 0.999; calibration-in-the-large: 0.000584) after adjustment for optimism.

We developed and internally validated a prediction model with reasonably good predictive metrics. Clinicians, patients and carers were involved in the development process. External validation of the tool is needed followed by co-design methodology to support implementation in early intervention services.

We examined longitudinally the course and predictors of treatment resistance in a large cohort of first-episode psychosis (FEP) patients from initiation of antipsychotic treatment. We hypothesized that antipsychotic treatment resistance is: (a) present at illness onset; and (b) differentially associated with clinical and demographic factors.

The study sample comprised 323 FEP patients who were studied at first contact and at 10-year follow-up. We collated clinical information on severity of symptoms, antipsychotic medication and treatment adherence during the follow-up period to determine the presence, course and predictors of treatment resistance.

From the 23% of the patients, who were treatment resistant, 84% were treatment resistant from illness onset. Multivariable regression analysis revealed that diagnosis of schizophrenia, negative symptoms, younger age at onset, and longer duration of untreated psychosis predicted treatment resistance from illness onset.

The striking majority of treatment-resistant patients do not respond to first-line antipsychotic treatment even at time of FEP. Clinicians must be alert to this subgroup of patients and consider clozapine treatment as early as possible during the first presentation of psychosis.

Dextromethorphan (DM)/quinidine (Q) is an approved treatment for pseudobulbar affect (PBA) based on trials in amyotrophic lateral sclerosis or multiple sclerosis. PRISM II evaluated DM/Q effectiveness and tolerability for PBA secondary to dementia, stroke, or traumatic brain injury; dementia cohort results are reported.

This was an open-label, multicenter, 90 day trial; patients received DM/Q 20/10 mg twice daily. Primary outcome was change in Center for Neurologic Study–Lability Scale (CNS-LS) score. Secondary outcomes included PBA episode count and Clinical and Patient/Caregiver Global Impression of Change scores with respect to PBA (CGI-C/PGI-C).

134 patients were treated. CNS-LS improved by a mean (SD) of 7.2 (6.0) points at Day 90/Endpoint (P<.001) vs. baseline. PBA episodes were reduced 67.7% (P<.001) vs. baseline; global measures showed 77.5% CGI-C and 76.5% PGI-C “much”/”very much” improved. Adverse events included headache (7.5%), urinary tract infection (4.5%), and diarrhea (3.7%); few patients dropped out for adverse events (10.4%).

DM/Q significantly reduced PBA symptoms in patients with dementia; reported adverse events were consistent with the known safety profile of DM/Q.

clinicaltrials.gov identifier: NCT01799941.

A lack of an aetiologically based nosology classification has contributed to instability in psychiatric diagnoses over time. This study aimed to examine the diagnostic stability of psychosis diagnoses using data from an incidence sample of psychosis cases, followed up after 10 years and to examine those baseline variables which were associated with diagnostic change.

Data were examined from the ÆSOP and ÆSOP-10 studies, an incidence and follow-up study, respectively, of a population-based cohort of first-episode psychosis cases from two sites. Diagnosis was assigned using ICD-10 and DSM-IV-TR. Diagnostic change was examined using prospective and retrospective consistency. Baseline variables associated with change were examined using logistic regression and likelihood ratio tests.

Slightly more (59.6%) cases had the same baseline and lifetime ICD-10 diagnosis compared with DSM-IV-TR (55.3%), but prospective and retrospective consistency was similar. Schizophrenia, psychotic bipolar disorder and drug-induced psychosis were more prospectively consistent than other diagnoses. A substantial number of cases with other diagnoses at baseline (ICD-10, n = 61; DSM-IV-TR, n = 76) were classified as having schizophrenia at 10 years. Many variables were associated with change to schizophrenia but few with overall change in diagnosis.

Diagnoses other than schizophrenia should to be regarded as potentially provisional.

Studies of the long-term course and outcome of psychoses tend to focus on cohorts of prevalent cases. Such studies bias samples towards those with poor outcomes, which may distort our understanding of prognosis. Long-term follow-up studies of epidemiologically robust first-episode samples are rare.

AESOP-10 is a 10-year follow-up study of 557 individuals with a first episode of psychosis initially identified in two areas in the UK (South East London and Nottingham). Detailed information was collated on course and outcome in three domains (clinical, social and service use) from case records, informants and follow-up interviews.

At follow-up, of 532 incident cases identified, at baseline 37 (7%) had died, 29 (6%) had emigrated and eight (2%) were excluded. Of the remaining 458, 412 (90%) were traced and some information on follow-up was collated for 387 (85%). Most cases (265, 77%) experienced at least one period of sustained remission; at follow-up, 141 (46%) had been symptom free for at least 2 years. A majority (208, 72%) of cases had been employed for less than 25% of the follow-up period. The median number of hospital admissions, including at first presentation, was 2 [interquartile range (IQR) 1–4]; a majority (299, 88%) were admitted a least once and a minority (21, 6%) had 10 or more admissions. Overall, outcomes were worse for those with a non-affective diagnosis, for men and for those from South East London.

Sustained periods of symptom remission are usual following first presentation to mental health services for psychosis, including for those with a non-affective disorder; almost half recover.

The extent to which different symptom dimensions vary according to epidemiological factors associated with categorical definitions of first-episode psychosis (FEP) is unknown. We hypothesized that positive psychotic symptoms, including paranoid delusions and depressive symptoms, would be more prominent in more urban environments.

We collected clinical and epidemiological data on 469 people with FEP (ICD-10 F10–F33) in two centres of the Aetiology and Ethnicity in Schizophrenia and Other Psychoses (AESOP) study: Southeast London and Nottinghamshire. We used multilevel regression models to examine neighbourhood-level and between-centre differences in five symptom dimensions (reality distortion, negative symptoms, manic symptoms, depressive symptoms and disorganization) underpinning Schedules for Clinical Assessment in Neuropsychiatry (SCAN) Item Group Checklist (IGC) symptoms. Delusions of persecution and reference, along with other individual IGC symptoms, were inspected for area-level variation.

Reality distortion [estimated effect size (EES) 0.15, 95% confidence interval (CI) 0.06–0.24] and depressive symptoms (EES 0.21, 95% CI 0.07–0.34) were elevated in people with FEP living in more urban Southeast London but disorganized symptomatology was lower (EES –0.06, 95% CI –0.10 to –0.02), after controlling for confounders. Delusions of persecution were not associated with increased neighbourhood population density [adjusted odds ratio (aOR) 1.01, 95% CI 0.83–1.23], although an effect was observed for delusions of reference (aOR 1.41, 95% CI 1.12–1.77). Hallucinatory symptoms showed consistent elevation in more densely populated neighbourhoods (aOR 1.32, 95% CI 1.09–1.61).

In people experiencing FEP, elevated levels of reality distortion and depressive symptoms were observed in more urban, densely populated neighbourhoods. No clear association was observed for paranoid delusions; hallucinations were consistently associated with increased population density. These results suggest that urban environments may affect the syndromal presentation of psychotic disorders.

There is evidence that a range of socio-environmental exposures is associated with an increased risk of psychosis. However, despite the fact that such factors probably combine in complex ways to increase risk, the majority of studies have tended to consider each exposure separately. In light of this, we sought to extend previous analyses of data from the AESOP (Aetiology and Ethnicity in Schizophrenia and Other Psychoses) study on childhood and adult markers of disadvantage to examine how they combine to increase risk of psychosis, testing both mediation (path) models and synergistic effects.

All patients with a first episode of psychosis who made contact with psychiatric services in defined catchment areas in London and Nottingham, UK (n = 390) and a series of community controls (n = 391) were included in the AESOP study. Data relating to clinical and social variables, including parental separation and loss, education and adult disadvantage, were collected from cases and controls.

There was evidence that the effect of separation from, but not death of, a parent in childhood on risk of psychosis was partially mediated through subsequent poor educational attainment (no qualifications), adult social disadvantage and, to a lesser degree, low self-esteem. In addition, there was strong evidence that separation from, but not death of, a parent combined synergistically with subsequent disadvantage to increase risk. These effects held for all ethnic groups in the sample.

Exposure to childhood and adult disadvantage may combine in complex ways to push some individuals along a predominantly sociodevelopmental pathway to psychosis.

To date, magnetic resonance imaging (MRI) has made little impact on the diagnosis and monitoring of psychoses in individual patients. In this study, we used a support vector machine (SVM) whole-brain classification approach to predict future illness course at the individual level from MRI data obtained at the first psychotic episode.

One hundred patients at their first psychotic episode and 91 healthy controls had an MRI scan. Patients were re-evaluated 6.2 years (s.d.=2.3) later, and were classified as having a continuous, episodic or intermediate illness course. Twenty-eight subjects with a continuous course were compared with 28 patients with an episodic course and with 28 healthy controls. We trained each SVM classifier independently for the following contrasts: continuous versus episodic, continuous versus healthy controls, and episodic versus healthy controls.

At baseline, patients with a continuous course were already distinguishable, with significance above chance level, from both patients with an episodic course (p=0.004, sensitivity=71, specificity=68) and healthy individuals (p=0.01, sensitivity=71, specificity=61). Patients with an episodic course could not be distinguished from healthy individuals. When patients with an intermediate outcome were classified according to the discriminating pattern episodic versus continuous, 74% of those who did not develop other episodes were classified as episodic, and 65% of those who did develop further episodes were classified as continuous (p=0.035).

We provide preliminary evidence of MRI application in the individualized prediction of future illness course, using a simple and automated SVM pipeline. When replicated and validated in larger groups, this could enable targeted clinical decisions based on imaging data.

To assess the extent to which psychiatric history, with specific regard to compulsory psychiatric admission, is questioned in visa, insurance and permit applications. Application forms for the top UK destinations for immigration, work and travel visas, six types of insurance, and driving, sporting and vocational permits were analysed.

Psychiatric history is questioned in some applications across all visa types. Hospital admission, but not compulsory psychiatric admission, is questioned in some immigration visas. Psychiatric history is not questioned in mortgage protection, car or pet insurance but it is questioned in some travel, life and health insurance applications, as is hospital admission. The majority of permit applications questioned psychiatric history and one vocational permit considered compulsory psychiatric admission.

The majority of visa, insurance and permit application forms enquire about past medical and psychiatric history. Information concerning detention under the Mental Health Act is very rarely questioned, indicating that a direct link between detention and access restriction is not evident.

Childhood adversity has been associated with onset of psychosis in adulthood but these studies have used only general definitions of this environmental risk indicator. Therefore, we sought to explore the prevalence of more specific adverse childhood experiences amongst those with and without psychotic disorders using detailed assessments in a large epidemiological case-control sample (AESOP).

Data were collected on 182 first-presentation psychosis cases and 246 geographically matched controls in two UK centres. Information relating to the timing and frequency of exposure to different types of childhood adversity (neglect, antipathy, physical and sexual abuse, local authority care, disrupted living arrangements and lack of supportive figure) was obtained using the Childhood Experience of Care and Abuse Questionnaire.

Psychosis cases were three times more likely to report severe physical abuse from the mother that commenced prior to 12 years of age, even after adjustment for other significant forms of adversity and demographic confounders. A non-significant trend was also evident for greater prevalence of reported severe maternal antipathy amongst those with psychosis. Associations with maternal neglect and childhood sexual abuse disappeared after adjusting for maternal physical abuse and antipathy. Paternal maltreatment and other forms of adversity were not associated with psychosis nor was there evidence of a dose–response effect.

These findings suggest that only specific adverse childhood experiences are associated with psychotic disorders and only in a minority of cases. If replicated, this greater precision will ensure that research into the mechanisms underlying the pathway from childhood adversity to psychosis is more fruitful.

To evaluate the introduction of service user-led teaching on experiences of psychiatric services and interview style into the educational programme of trainee psychiatrists. A ten-session programme was devised and delivered in conjunction with a local service user organisation. Twelve trainees underwent the training programme. Evaluation was undertaken through analysis of the feedback forms completed by the trainees.

No significant difference was found between service user-led and psychiatrist-led sessions in content, relevance or presentation.

The study demonstrated that service user-led teaching can be integrated into a trainee's education programme without reducing the perceived quality or relevance of their education.

Numerous studies have reported high rates of psychosis in the Black Caribbean population in the UK. Recent speculation about the reasons for these high rates has focused on social factors. However, there have been few empirical studies. We sought to compare the prevalence of specific indicators of social disadvantage and isolation, and variations by ethnicity, in subjects with a first episode of psychosis and a series of healthy controls.

All cases with a first episode of psychosis who made contact with psychiatric services in defined catchment areas in London and Nottingham, UK and a series of community controls were recruited over a 3-year period. Data relating to clinical and social variables were collected from cases and controls.

On all indicators, cases were more socially disadvantaged and isolated than controls, after controlling for potential confounders. These associations held when the sample was restricted to those with an affective diagnosis and to those with a short prodrome and short duration of untreated psychosis. There was a clear linear relationship between concentrated disadvantage and odds of psychosis. Similar patterns were evident in the two main ethnic groups, White British and Black Caribbean. However, indicators of social disadvantage and isolation were more common in Black Caribbean subjects than White British subjects.

We found strong associations between indicators of disadvantage and psychosis. If these variables index exposure to factors that increase risk of psychosis, their greater prevalence in the Black Caribbean population may contribute to the reported high rates of psychosis in this population.

An increased prevalence of minor physical anomalies (MPAs) has been extensively documented in schizophrenia but their specificity for the disorder remains unclear. We investigated the prevalence and the predictive power of MPAs in a large sample of first-episode psychotic patients across a range of diagnoses.

MPAs were examined in 242 subjects with first-episode psychosis (50% schizophrenia, 45% affective psychosis and 5% substance-induced psychosis) and 158 healthy controls. Categorical principal components analysis and analysis of variance were undertaken, and individual items with the highest loading were tested using the χ2 test.

Overall facial asymmetry, assymetry of the orbital landmarks, and frankfurt horizontal significantly differentiated patients with schizophrenia and affective psychosis from controls, as did a ‘V-shaped’ palate, reduced palatal ridges, abnormality of the left ear surface and the shape of the left and right ears. Patients with affective psychosis had significantly lowered eye fissures compared with control subjects.

MPAs are not specific to schizophrenia, suggesting a common developmental pathway for non-affective and affective psychoses. The topographical distribution of MPAs in this study is suggestive of an insult occurring during organogenesis in the first trimester of pregnancy.

Large substernal goitres present a challenge to the otolaryngologist due to their size and location. Predicting which patients will require sternotomy can enable planning of surgery in a specialist centre, with the assistance of a thoracic surgeon. Our aim for this study was to establish clinical and radiological predictors which would aid the otolaryngologist in the pre-operative planning of such cases.

A retrospective medical record review was conducted for all patients undergoing thyroidectomy for substernal goitre who required sternotomy in our institution over a 10-year period.

During the study period, 140 patients with substernal goitres underwent thyroidectomy. Three patients (2 per cent) required sternotomy. These cases are described.

Radiological evidence of extension of a substernal goitre to the aortic knuckle, or loss of tissue planes on computed tomography, should raise suspicion that the patient may require sternotomy for safe delivery of the gland. The otolaryngologist should plan surgery for these patients in a specialist centre, with the help of a thoracic surgeon.

It is reported that people with mild learning disability have a higher point prevalence of schizophrenia than the normal population, the reasons for which are unclear.

Thirty-nine subjects with mild learning disability and schizophrenia, 34 control subjects with schizophrenia and 28 control subjects with mild learning disability were seen. Interviews with relatives and carers were also conducted. Assessments were made of clinical variables, psychopathology, neurological ‘soft'signs, IQ, memory and family history. Blood was taken for karyotypic analysis from comorbid subjects.

The comorbid group had more negative symptoms, episodic memory deficits, soft neurological signs, epilepsy and receive more community supports than control subjects with schizophrenia. Comorbid subjects had a tendency to belong to multiply affected families and show high rates of chromosomal variants on routine karyotypic testing.

Future work on the generality of schizophrenia should include people with premorbid learning disability, as a discrete subtype from whom valuable genetic aetiological clues may be obtained.