Cognitive models of psychosis suggest that whether anomalous experiences lead to clinically relevant psychotic symptoms depends on how they are appraised, the context in which they occur and the individual's emotional response

To develop and validate a semi-structured interview (the Appraisals of Anomalous Experiences Interview; AANEX) to assess (a) anomalous experiences and (b) appraisal, contextual and response variables

Following initial piloting, construct validity was tested via cross-sectional comparison of data from clinical and non-clinical samples with anomalous experiences. Interrater reliability was also assessed

Scores from AANEX measuring appraisals, responses and social support differentiated the clinical and nonclinical groups. Interrater reliability was satisfactory for 65 of the 71 items. Six items were subsequently amended

The AANEX is avalid multidimensional instrument that provides a detailed assessment of psychotic-like experiences and subjective variables relevant to the development of a need for clinical care

Depression is a frequent condition in early psychosis. Therefore, early detection instruments should distinguish depression from beginning psychosis

To examine whether basic symptoms, i.e. subtle subjective deficits, differ between participants suffering from a potential prodrome (n = 146), first-episode schizophrenia (n= 153) and non-psychotic depression (n = 115)

Basic symptoms were assessed with the Schizophrenia Proneness Instrument

The prodrome and schizophrenia groups did not differ in level of basic symptoms but both had higher levels than the depression group. DSM – IV depression was frequent in those suffering from a potential prodrome (38%) and first-episode schizophrenia (21%). In both groups, participants with and without depression did not differ in basic symptoms. In multivariate analyses, consideration of current depression generally facilitated correct group classification, except for participants suffering from both a potential prodrome and depression

Cognitive basic symptoms distinguished well between all three groups. However, identification of persons suffering from a potential prodrome might be enhanced by considering current affective status

Cognitive models propose that faulty appraisal of anomalous experiences is critical in developing psychosis, particularly delusions. A data gathering bias may be fundamental to abnormal appraisal

To examine whether there is a data gathering bias in people at high risk of developing psychosis

Individuals with an at-risk mental state (n=35) were compared with a matched group of healthy volunteers (n=23). Participants were tested using a modified version of the ‘beads’ reasoning task with different levels of task difficulty

When task demands were high, the at-risk group made judgements on the basis of less information than the control group (P < 0.05). Within both groups, jumping to conclusions was directly correlated with the severity of abnormal beliefs and intolerance of uncertainty (P<0.05). In the at-risk group it was also associated with impaired working memory (P<0.05), whereas in the control group poor working memory was associated with a more conservative response style (P<0.05)

People with an at-risk mental state display a jumping to conclusions reasoning style, associated with impaired working memory and intolerance of uncertainty. This may underlie a tendency to develop abnormal beliefs and a vulnerability to psychosis

Cognitive disturbances have been demonstrated in individuals with potentially prodromal symptoms in objective–neuropsychological as well as subjective-symptomatic studies. Yet, the relation between subjective and objective deficits and to different prodromal states is unclear

To explore interactions between subjective and objective cognitive measures in different prodromal states

In participants with an early (n=33) or late (n=69) initial prodromal state, cognitive subjective and objective deficits were assessed with the Schizophrenia Proneness Instrument and a comprehensive neuropsychological test battery

Participants with an early initial prodromal state were less impaired than those with a late initial state. Subjective and objective cognitive deficits were unrelated, excepttime-limited neurocognitive speed measures and subjectively reduced stress tolerance, especially in participants with an early initial prodromal state

Subjective and objective cognitive deficits are generally unrelated in the psychosis prodrome and as such they can add complementary information valuable for prediction. However, possible associations between the two levels might be better detectable in the less impaired early initial prodromal state

The origin of cognitive impairments in psychotic disorders is still unclear. Although some deficits are apparent prior to the onset of frank illness, it is unknown if they progress

To investigate whether cognitive function declined over the transition to psychosis in a group of ultra-high risk individuals

Participants consisted of two groups: controls (n = 17) and individuals at ultra-high risk for development of psychosis (n = 16). Seven of the latter group later developed psychosis. Neuropsychological testing was conducted at baseline and again after at least a 12-month interval

Both the Visual Reproduction sub-test of the Wechsler Memory Scale-Revised and Trail-Making Test B showed a decline over the follow-up period that was specific to the group who became psychotic. In addition, both high-risk groups showed a decline in digit span performance. No other task showed significant change over time

These preliminary data suggest that as psychosis develops there may be a specific decline in visual memory and attentional set-shifting, reflecting impairments in efficient organisation of visual stimuli. This may be caused by either the illness itself or treatment with antipsychotic medication

A disorder of self-monitoring may underlie the positive symptoms of psychosis. The cognitive mechanisms associated with these symptoms may also be detectable in individuals at risk of psychosis

To investigate (a) whether patients with psychosis show impaired self-monitoring, (b) to what degree this is associated with positive symptoms, and (c) whether this is associated with liability to psychotic symptoms

The sample included: individuals with a lifetime history of non-affective psychosis (n=37), a genetically defined risk group (n=41), a psychometrically defined risk group (n=40), and control group (n=49). All participants carried out an action-recognition task

Number of action – recognition errors was associated with psychosis risk (OR linear trend over 3 levels: 1.12, 95% CI 1.04–1.20) and differential error rate was associated with the degree of delusional ideation in a dose–response fashion (OR linear trend over 3 levels: 1.13, 95% CI 1.00–1.26)

Alterations in self-monitoring are associated with psychosis with evidence of specificity for delusional ideation. In the risk state, this is expressed more as failure to recognise self-generated actions, whereas in illness failure to recognise alien sources come to the fore

Virtual reality provides a means of studying paranoid thinking in controlled laboratory conditions. However, this method has not been used with a clinical group

To establish the feasibility and safety of using virtual reality methodology in people with an at-risk mental state and to investigate the applicability of a cognitive model of paranoia to this group

Twenty-one participants with an at-risk mental state were assessed before and after entering a virtual reality environment depicting the inside of an underground train

Virtual reality did not raise levels of distress at the time of testing or cause adverse experiences over the subsequent week. Individuals attributed mental states to virtual reality characters including hostile intent. Persecutory ideation in virtual reality was predicted by higher levels of trait paranoia, anxiety, stress, immersion in virtual reality, perseveration and interpersonal sensitivity

Virtual reality is an acceptable experimental technique for use with individuals with at-risk mental states. Paranoia in virtual reality was understandable in terms of the cognitive model of persecutory delusions

Neuroanatomical abnormalities are a well-established feature of schizophrenia. However, the timing of their emergence and the extent to which they are related to vulnerability to the disorder as opposed to psychotic illness itself is unclear

To assess regional grey matter volume in the at-risk individuals who subsequently developed psychosis

Magnetic resonance imaging data from at-risk individuals who developed psychosis (n = 12) within the following 25 months were compared with data from healthy volunteers (n=22) and people with first-episode psychosis (n=25)

Compared with healthy volunteers, individuals who subsequently developed psychosis had smaller grey matter volume in the posterior cingulate gyrus, precuneus, and paracentral lobule bilaterally and in the left superior parietal lobule, and greater grey matter volume in a left parietal/posterior temporal region. Compared with first-episode patients, they had relatively greater grey matter volume in the temporal gyrus bilaterally and smaller grey matter volume in the right lentiform nucleus

Some of the structural brain abnormalities in individuals with an at-risk mental state may be related to an increased vulnerability to psychosis, while others are associated with the development of a psychotic illness

The nosological status of auditory hallucinations in non-clinical samples is unclear

To investigate the functional neural basis of non-clinical hallucinations

After selection from 1206 people, 68 participants of high, medium and low hallucination proneness completed a task designed to elicit verbal hallucinatory phenomena under conditions of stimulus degradation. Eight subjects who reported hearing a voice when none was present repeated the task during functional imaging

During the signal detection task, the high hallucination-prone participants reported a voice to be present when it was not (false alarms) significantly more often than the average or low participants (P<0.03, d.f. =2). On functional magnetic resonance imaging, patterns of activation during these false alarms showed activation in the superior and middle temporal cortex (P<0.001)

Auditory hallucinatory experiences reported in non-clinical samples appear to be mediated by similar patterns of cerebral activation as found during hallucinations in schizophrenia

There have been recent advances in the identification of people at high risk of psychosis and psychological treatments have shown promise for prevention

To compare the longitudinal course of psychotic experiences and emotional dysfunction in high-risk participants receiving cognitive therapy with those receiving treatment as usual

Data from a recent randomised controlled trial of cognitive therapy for people at risk of developing psychosis were utilised to examine three different statistical models that were based on 432 measurements of psychotic experiences and 421 of emotional dysfunction (anxiety–depression) contributed by 57 participants across the 13 measurement occasions (monthly monitoring for a year)

Psychotic experiences and emotional dysfunction were correlated and decreased significantly over the course of the study, with most improvement in the early months. The reduction in positive symptoms, but not emotional dysfunction, was enhanced by allocation to cognitive therapy

Psychotic experiences and emotional dysfunction appear to interact in people at risk of developing psychosis. There appears to be a specific benefit of cognitive therapy

People in a putatively late prodromal state not only have an enhanced risk for psychosis but already suffer from mental and functional disturbances

To evaluate the acute effects of a combined supportive and antipsychotic treatment on prodromal symptoms

Putatively prodromal individuals were randomly assigned to a needs-focused intervention without (n=59) or with amisulpride (n=65). Outcome measures at 12-weeks effects were prodromal symptoms, global functioning and extrapyramidal side-effects

Amisulpride plus the needs-focused intervention produced superior effects on attenuated and full-blown psychotic symptoms, basic, depressive and negative symptoms, and global functioning. Main side-effects were prolactin associated

Coadministration of amisulpride yielded a marked symptomatic benefit. Effects require confirmation by a placebo-controlled study

Research studies for the treatment of the putative prodromal phase of psychotic disorders have begun to appear

To obtain preliminary evidence of the short-term efficacy and safety of aripiprazole treatment in people with the psychosis prodrome

Fifteen participants meeting prodrome criteria (mean age 17.1 years, s.d.=5.5) enrolled in an open-label, single-site trial with fixed-flexible dosing of aripiprazole (5–30 mg/day) for 8 weeks

In the mixed-effects repeated-measures analysis, improvement from baseline on the Scale of Prodromal Symptoms total score was statistically significant by the first week. No participant converted to psychosis and 13 completed treatment. Neuropsychological measures showed no consistent improvement; mean weight gain was 1.2 kg. Akathisia emerged in 8 participants, but the mean Barnes Akathisia Scale score fell to baseline levels by the final visit. Adverse events were otherwise minimal

Aripiprazole shows a promising efficacy and safety profile for the psychosis prodrome. Placebo-controlled studies are indicated

Little is known about the incidence of first-episode psychosis in urban centres of low- or middle-income countries

To estimate the incidence of psychosis in São Paulo, a large metropolis of Brazil

Prospective survey of first-episode psychosis among residents aged 18–64 years resident in a defined area of São Paulo, over a 30-month period (July 2002- December 2004). Assessments were carried out with the SCID–I, and diagnoses given according to DSM – IV criteria. Population at risk was drawn from the 2000 Census data

There were 367 first-episode cases identified (51% women), and almost 40% fulfilled criteria for schizophrenia or schizophreniform disorder. The incidence rate for any psychosis was 15.8/100 000 person-years at risk (95% CI 14.3–17.6). Incidence of non-affective psychoses was higher among younger males

Incidence of psychosis in São Paulo was lower than expected for a large metropolis

Speed of processing is a cognitive process underlying cognitive dysfunction in people with chronic schizophrenia

To investigate the contribution of speed of processing to the cognitive deficits observed in a representative large sample with first-episode schizophrenia

People with a diagnosis of first-episode schizophrenia-spectrum disorders (n=26) and healthy controls (n=28) were compared on several cognitive measures before and after controlling for speed of processing

Before controlling for speed of processing, patients and controls differed significantly on all cognitive measures. All significant differences in cognitive functioning disappeared when the result of the Digital Symbol Substitution Test was included as an additional covariate

Speed of information processing may be considered a core cognitive deficit in schizophrenia and might be mediating a broader diversity of cognitive disturbances

Grey matter and other structural brain abnormalities are consistently reported in first-onset schizophrenia, but less is known about the extent of neuroanatomical changes in first-onset affective psychosis

To determine which brain abnormalities are specific to (a) schizophrenia and (b) affective psychosis

We obtained dual-echo (proton density/T2-weighted) magnetic resonance images and carried out voxel-based analysis on the images of 73 patients with first-episode psychosis (schizophrenia n=44, affective psychosis n=29) and 58 healthy controls

Both patients with schizophrenia and patients with affective psychosis had enlarged lateral and third ventricle volumes. Regional cortical grey matter reductions (including bilateral anterior cingulate gyrus, left insula and left fusiform gyrus) were evident in affective psychosis but not in schizophrenia, although patients with schizophrenia displayed decreased hippocampal grey matter and increased striatal grey matter at a more liberal statistical threshold

Both schizophrenia and affective psychosis are associated with volumetric abnormalities at the onset of frank psychosis, with some of these evident in common brain areas

In low-and middle-income countries people with schizophrenia are reported to experience better outcomes than those in high-income countries

To examine structural brain differences in people with first-episode psychosis and controls in Brazil

Magnetic resonance imaging using voxel-based morphometry was performed on 122 people with first-episode psychosis and 94 controls

There were significant decreases in grey matter in the left superior temporal and inferior prefrontal cortices, insula bilaterally and the right hippocampal region in first-episode psychosis (P<0.05, corrected for multiple comparisons). The subgroup of people with schizophrenia (n=62) exhibited a similar pattern of decrease in grey matter relative to controls

Structural abnormalities reported in psychosis in high-income countries are also present in first-episode psychosis in Brazil