Since the neurotoxicity hypothesis was launched in 1991, it has generated a great deal of interest and given rise to several studies investigating the validity of the hypothesis that being psychotic has a toxic effect on the brain. The toxicity argument is used to justify early treatment. This review attempts to assess the studies that have addressed the question: Does an active psychosis, indexed by the duration of untreated psychosis (DUP), cause neurobiological pathology?

The validity of the hypothesis has been studied primarily by correlation analyses that assess whether there are significant correlations between DUP and changes in neurocognitive functioning or brain structure. In this review, relevant reports were identified by a literature survey.

Of the 35 studies (33 papers) evaluated, six neurocognitive studies supported the hypothesis and 16 did not. Eight morphology studies supported the hypothesis and five did not. In general, the studies that did not support the neurotoxicity hypothesis were larger in size and had more adequate designs (longitudinal) than those that supported the hypothesis.

Overall, there is limited empirical evidence for the neurotoxicity hypothesis in the studies reviewed. However, it is possible that there is a threshold value for a toxic effect of psychosis, rather than a linear relationship between DUP and a neurotoxic effect, and that several of the studies evaluated did not have a long enough DUP to detect a toxic effect of active psychosis.

During the last decades we have seen a new focus on early treatment of psychosis. Several reviews have shown that duration of untreated psychosis (DUP) is correlated to better outcome. However, it is still unknown whether early treatment will lead to a better long-term outcome. This study reports the effects of reducing DUP on 5-year course and outcome.

During 1997–2000 a total of 281 consecutive patients aged >17 years with first episode non-affective psychosis were recruited, of which 192 participated in the 5-year follow-up. A comprehensive early detection (ED) programme with public information campaigns and low-threshold psychosis detection teams was established in one healthcare area (ED-area), but not in a comparable area (no-ED area). Both areas ran equivalent treatment programmes during the first 2 years and need-adapted treatment thereafter.

At the start of treatment, ED-patients had shorter DUP and less symptoms than no-ED-patients. There were no significant differences in treatment (psychotherapy and medication) for the 5 years. Mixed-effects modelling showed better scores for the ED group on the Positive and Negative Syndrome Scale negative, depressive and cognitive factors and for global assessment of functioning for social functioning at 5-year follow-up. The ED group also had more contacts with friends. Regression analysis did not find that these differences could be explained by confounders.

Early treatment had positive effects on clinical and functional status at 5-year follow-up in first episode psychosis.

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.