Few studies have evaluated the development in the use of antipsychotic medication and psychotic symptoms in patients with first-episode psychosis on a long-term basis. Our objective was to investigate how psychotic symptoms and the use of antipsychotic medication changed over a 10-year period in a cohort of patients with first-episode psychosis.

The study is a longitudinal prospective cohort study over 10 years with follow-ups at years 1, 2, 5 and 10. A total of 496 patients with first-episode psychosis were included in a multi-centre study initiated between 1998 and 2000 in Copenhagen and Aarhus, Denmark.

At all follow-ups, a large proportion (20–30%) of patients had remission of psychotic symptoms without use of antipsychotic medication at the time of the follow-up. Patients who were in this group at the 5-year follow-up had an 87% [95% confidence interval (CI) 77–96%] chance of being in the same group at the 10-year follow-up. This stability was also the case for patients who had psychotic symptoms and were treated with antipsychotic medication at year 5, where there was a 67% (95% CI 56–78%) probability of being in this group at the consecutive follow-up.

A large group of patients with psychotic illness were in remission without the use of antipsychotic medication, peaking at year 10. Overall there was a large degree of stability in disease courses over the 10-year period. These results suggest that the long-term outcome of psychotic illness is heterogeneous and further investigation on a more individualized approach to long-term treatment is needed.

The boundaries of psychotic illness and the extent to which operational diagnostic categories are distinct in the long term remain poorly understood. Clarification of these issues requires prospective evaluation of diagnostic trajectory, interplay and convergence/divergence across psychotic illness, without a priori diagnostic or other restrictions.

The Cavan-Monaghan First Episode Psychosis Study (CAMFEPS), conducted using methods to attain the closest approximation to epidemiological completeness, incepts all 12 DSM-IV psychotic diagnoses. In this study we applied methodologies to achieve diagnostic reassessments on follow-up, at a mean of 6.4 years after first presentation, for 196 (97%) of the first 202 cases, with quantification of prospective and retrospective consistency.

Over 6 years, the 12 initial psychotic diagnoses were characterized by numerous transitions but only limited convergence towards a smaller number of more stable diagnostic nodes. In particular, for initial brief psychotic disorder (BrP), in 85% of cases this was the harbinger of long-term evolution to serious psychotic illness of diagnostic diversity; for initial major depressive disorder with psychotic features (MDDP), in 18% of cases this was associated with mortality of diverse causality; and for initial psychotic disorder not otherwise specified (PNOS), 31% of cases continued to defy DSM-IV criteria.

CAMFEPS methodology revealed, on an individual case basis, a diversity of stabilities in, and transitions between, all 12 DSM-IV psychotic diagnoses over 6 years; thus, psychotic illness showed longitudinal disrespect to current nosology and may be better accommodated by a dimensional model. In particular, a first episode of BrP or MDDP may benefit from more vigorous, sustained interventions.

Psychotic illness is strongly associated with the maternal uniparental disomy (mUPD) genetic subtype of Prader–Willi syndrome (PWS), but not the deletion subtype (delPWS). This study investigates the clinical features of psychiatric illness associated with PWS. We consider possible genetic and other mechanisms that may be responsible for the development of psychotic illness, predominantly in those with mUPD.

The study sample comprised 119 individuals with genetically confirmed PWS, of whom 46 had a history of psychiatric illness. A detailed clinical and family psychiatric history was obtained from these 46 using the PAS-ADD, OPCRIT, Family History and Life Events Questionnaires.

Individuals with mUPD had a higher rate of psychiatric illness than those with delPWS (22/34 v. 24/85, p<0.001). The profile of psychiatric illness in both genetic subtypes resembled an atypical affective disorder with or without psychotic symptoms. Those with delPWS were more likely to have developed a non-psychotic depressive illness (p=0.005) and those with mUPD a bipolar disorder with psychotic symptoms (p=0.00005). Individuals with delPWS and psychotic illness had an increased family history of affective disorder. This was confined exclusively to their mothers.

Psychiatric illness in PWS is predominately affective with atypical features. The prevalence and possibly the severity of illness are greater in those with mUPD. We present a ‘two-hit’ hypothesis, involving imprinted genes on chromosome 15, for the development of affective psychosis in people with PWS, regardless of genetic subtype.