The potential of first-episode studies in schizophrenia is maximised through systematic epidemiological, clinical and biological comparisons between homogeneous populations of the psychoses.

To conduct prolonged accrual of ‘all’ cases of non-affective and affective psychotic illness on an epidemiologically complete basis.

Within the region covered by Cavan–Monaghan psychiatric service (population 102 810), all putative cases of first-episode psychosis were diagnosed using DSM–IV.

From 1995 to 2000, 69 cases of psychosis were ascertained, the incidence being 2.3-fold lower in females than in males. On resolving the ‘core’ diagnoses of schizophrenia and bipolar disorder, incidence of schizophrenia among women was 7.5-fold lower than among men whereas incidence of bipolar disorder among women was 6.6-fold lower than among men.

This homogeneous population, which eliminates factors associated with urbanicity and minimises confounding factors such as socioeconomic, ethnic and geographical diversity, shows a markedly reduced incidence among females both of schizophrenia and of bipolar disorder.

Childhood hallucinations of voices occur in a variety of contexts and have variable long-term outcomes.

To study the course of experience of voices sequentially over a 3-year period in those with and those without a need for mental health care (patient status).

In a group of 80 children of mean age 12.9 years (s.d.=3.1), of which around 50% were not receiving mental health care, baseline measurement of voice characteristics, voice attributions, psychopathology, stressful life events, coping mechanisms and receipt of professional care were used to predict 3-year course and patient status.

The rate of voice discontinuation over the 3-year period was 60%. Patient status was associated with more perceived influence on behaviour and feelings and more negative affective appraisals in relation to the voices. Predictors of persistence of voices were severity and frequency of the voices, associated anxiety/depression and lack of clear triggers in time and place.

Need for care in the context of experience of voices is associated with appraisal of the voices in terms of intrusiveness and ‘omnipotence’. Persistence of voices is related to voice appraisals, suggesting that experience of voices by children should be the target of specific interventions.

The risk for schizophrenia has been associated with a family history of this and other psychiatric disorders. The relationship between age at first contact and family history of psychiatric illness is not certain.

To estimate the risks for schizophrenia associated with a range of psychiatric diagnoses in family members and to investigate the relationship between these risks and age at first contact for schizophrenia.

A nested case–control study design was employed. Psychiatric admission data and socio-economic data were available for 7704 cases admitted between 1981 and 1998 in Denmark, 192 590 gender- and age-matched controls, and for the parents and siblings of all subjects.

Controlling for socio-economic factors, risk for schizophrenia was associated with a family history of all psychiatric disorders except substance misuse and independently with a family history of suicide. The risk for schizophrenia associated with a family history of psychiatric disorders decreased as age at first contact increased.

Risk for schizophrenia is associated with a range of psychiatric disorders in family members and these risks are not constant across the risk period.

High-risk’ studies of schizophrenia have the potential to clarify the pathogenesis of schizophrenia. Here, results of extreme outcome groups in the Edinburgh High-Risk Study are presented.

To compare groups of good and poor outcome from the Edinburgh High-Risk Study and clarify the nature of the change from the state of vulnerability to that of developing psychosis.

The recruitment procedure is described. Good and poor outcome are defined. These groups are compared in terms of genetic liability and of baseline and change in neuropsychology and neuroanatomy.

Demographic characteristics and genetic liability do not differ between the groups. The good outcome group perform better at baseline in some neuropsychological tests, but there is little neuroanatomical difference. The poor outcome group show consistently impaired memory function and a tendency to reduction in temporal lobe size.

In genetically predisposed subjects, the change from vulnerability to developing psychosis may be marked by a reduced size and impaired function of the temporal lobe.

Predicting transitions to psychosis is difficult. Neuropsychology might facilitate predictions.

To report preliminary data on self-perceived and objectively measurable neurocognition in prodromal patients of the first German early recognition centre.

Subjective neuropsychological disturbances were assessed in 51 patients with potentially prodromal symptoms of schizophrenia. Initial neurocognitive functioning was compared with matched normals and patients with schizophrenia.

Self-perceived deficits mostly concerned perception, cognition and stress reactivity. Five transitions happened during the 15-month follow-up. Recently emerging or intensifying deficits were to some extent predictive of transition. Persons at risk performed worse than controls on objectively measured verbal capacity, attention and memory functions.

Neuropsychological deficits, either self-perceived or objectively measured, characterise persons at risk for schizophrenia and may contribute to predicting transitions.

Many studies have demonstrated early generalised cognitive impairment in schizophrenia.

To examine executive function in first-episode schizophrenia, characterise the nature of the impairment and specify any relationships with symptoms and duration of untreated psychosis (DUP).

Patients (n=136) and normal controls (n=81) were assessed with the Cambridge Automated Neuropsychological Test Battery, National Adult Reading Test IQ, and Scales for the Assessment of Positive and Negative Symptoms.

Memory and executive impairments in patients were independent of IQ level. Spatial working memory was impaired because of inadequate strategy use. On a planning task, patients showed reduced planning times and suboptimal problem-solving. On an attentional set-shifting task, 75% of patients were able to perform an extra-dimensional shift thought to be a core attribute of prefrontal cortex function. Those who failed had significantly longer DUP.

Prefrontal cortex function deteriorates at the onset of psychosis and continues to worsen over time.

The efficacies of second-generation antipsychotic medications in reducing symptoms are reasonably well-documented, but their effects on cognition are less clearly understood.

To undertake an interim analysis of an open label, 2-year study examining the effects of quetiapine on cognition in patients with a first episode of schizophrenia and related disorders.

Cognitive testing was performed before quetiapine was initiated and repeated after 3, 6 and 12 months of treatment. To date, 13 patients have been fully assessed (mean dose 517.9 mg/day; s.d.=225.8).

Statistically significant improvement was noted on measures of attention (Continuous Performance Test; CPT), verbal productivity (Verbal Fluency Test) and executive function (Object Alternation Test) after 6 and 12 months of treatment. For the CPT, improvement was also noted after 3 months of treatment.

During treatment for 1 year with quetiapine, cognitive performance was improved in young patients with psychosis. Continued controlled investigations of the effects of quetiapine on cognition are desirable.

Neurological soft signs (NSS) are minor neurological signs indicating non-specific cerebral dysfunction. Their presence has been documented extensively in schizophrenia but not during the first psychotic episode.

To review studies that have specifically investigated NSS at the time of the first psychotic episode.

A review of studies investigating neurological function in first-episode psychosis, using a clinical examination.

Patients with first-episode psychosis show an excess of NSS, particularly in the areas of motor coordination and sequencing, sensory integration and in developmental reflexes. Furthermore, NSS may be associated with a specific laterality pattern.

More studies on first-onset schizophrenia are needed, evaluating both sensory and motor neurological domains (scoring separately for the two sides of the body), integrating this knowledge with neuroimaging findings and clarifying the role of NSS as markers of cognitive dysfunction.

Structural brain abnormalities are prevalent in patients with schizophrenia and affective disorders.

To study how regional brain volumes and their ratios differ between patients with schizophrenia, psychotic depression, severe non-psychotic depression and healthy controls.

Magnetic resonance imaging scans of the brain on first-episode patients and on healthy controls.

Patients with schizophrenia had a smaller left frontal grey matter volume than the other three groups. Patients with psychotic depression had larger ventricular and posterior sulcal cerebrospinal fluid (CSF) volumes than controls. Patients with depression had larger white matter volumes than the other patients.

Left frontal lobe, especially its grey matter volume, seems to be specifically reduced in first-episode schizophrenia. Enlarged cerebral ventricles and sulcal CSF volumes are prevalent in psychotic depression. Preserved or expanded white matter is typical of non-psychotic depression.

Although brain volume changes are found in schizophrenia, only a limited number of structural magnetic resonance imaging studies have exclusively examined antipsychotic-naïve patients.

To comprehensively investigate multiple brain structures in a single sample of patients who were antipsychotic-naïve.

Twenty antipsychotic-naïve patients with first-episode schizophrenia and 20 healthy comparison subjects were included. Intracranial, total brain, frontal lobe, grey and white matter, cerebellar, hippocampal, parahippocampal, thalamic, caudate nucleus and lateral and third ventricular volumes were measured. Repeated-measures analyses of (co)variance were conducted with intracranial volume as covariate.

Third ventricle volume enlargement was found in patients compared with the healthy subjects. No differences were found in other brain regions.

These findings suggest that some brain abnormalities are present in the early stages of schizophrenia. Moreover, it suggests that brain abnormalities reported in patients with chronic schizophrenia develop in a later stage of the disease and/or are medication induced.

Studies have consistently found that many individuals with first-episode psychosis experience significant delays before receiving treatment. Current research investigating treatment delays has focused on the relationship between demographic factors and duration of untreated psychosis (DUP). However, treatment-seeking behaviours in this group have not been investigated.

To examine psychological processes that influence the decision-making process to contact primary care, in individuals with emerging psychosis.

The influence of coping style, health locus of control and past health help-seeking behaviour on DUP was investigated in clients with a first episode of psychosis. This involved scrutiny of general practitioner (GP) records in an average of 6 years before the first treatment.

Shorter DUP was associated with more frequent GP attendance in the 6 years before the onset of psychosis and lower health threat avoidant coping scores.

Patients with short DUP have a history of higher contact with their GP and, as a group, tend not to avoid health threats. The study underlines the importance of engaging young people and their families with primary care as one of a series of strategies to reduce DUP.

There is interest in the possibility of indicated prevention of psychosis. There is a strong case for using psychological approaches to prevent transition to psychosis in high-risk patients.

To identify individuals at high risk of transition to psychosis, and psychological characteristics relevant to the development of psychosis in this group.

The design of a randomised controlled trial of cognitive therapy for the prevention of psychosis in people at high risk (meeting operational criteria of brief or attenuated psychotic symptoms, or first-degree family history with functional decline) is outlined. The first patients recruited are compared with non-patient samples on cognitive and personality factors; an interim analysis of transition rate is reported.

Cases (n=31) were recruited mainly from primary care. Of the 23 high-risk patients monitored for 6–12 months, 5 (22%) made the transition to psychosis. The high-risk group scored significantly higher than non-patients on measures of schizotypy, metacognitive beliefs and dysfunctional self-schemas (sociotropy).

The findings validate the methods of identifying individuals at high risk of experiencing a psychotic episode. Compared with non-patient controls, the cases showed dysfunctional metacognitive beliefs and self-schemas.

Assessment of neurocognitive dysfunction in schizophrenia is hampered by the multitude of tests used in the literature.

We aimed to identify the main dimensions of an assessment battery for patients with first-episode psychosis and to estimate the relationship between dimension scores and gender, age, education, diagnosis and symptoms.

Eight frequently used neuropsychological tests were used. We tested 219 patients 3 months after start of therapy or at remission, whichever occurred first.

We identified five dimensions: working memory (WM); verbal learning (VL); executive function (EF); impulsivity (Im); and motor speed (MS). Significant findings were that the MS score was higher for men, and the WM and VL scores were correlated with years of education.

Neurocognitive function in first-episode psychosis is described by at least five independent dimensions.

Cognitive–behavioural therapy (CBT) improves persistent psychotic symptoms.

To test the effectiveness of added CBT in accelerating remission from acute psychotic symptoms in early schizophrenia.

A 5-week CBT programme plus routine care was compared with supportive counselling plus routine care and routine care alone in a multi-centre trial randomising 315 people with DSM–IV schizophrenia and related disorders in their first (83%) or second acute admission. Outcome assessments were blinded.

Linear regression over 70 days showed predicted trends towards faster improvement in the CBT group. Uncorrected univariate comparisons showed significant benefits at 4 but not 6 weeks for CBTv. routine care alone on Positive and Negative Syndrome Scale total and positive sub-scale scores and delusion score and benefits v. supportive counselling for auditory hallucinations score.

CBT shows transient advantages over routine care alone or supportive counselling in speeding remission from acute symptoms in early schizophrenia.

Patients with first-episode psychosis comprise a high-risk group in terms of suicide.

To identify predictive factors for suicidal behaviour and to examine the effect of integrated treatment on suicidal behaviour and hopelessness.

A total of 341 patients with a first-episode schizophrenia-spectrum disorder were randomised to integrated treatment or treatment as usual.

During the 1-year follow-up period, 11% attempted suicide. This was associated with female gender, hopelessness, hallucinations and suicide attempt reported at baseline, with the two latter variables being the only significant ones in the final multivariate model. The integrated treatment reduced hopelessness.

Hallucinations and suicide attempt before inclusion in the study were the most significant predictors of suicide attempt in the follow-up period.