Several often-cited meta-analyses have reported that the efficacy of antidepressant medications depends on the severity of depression. They found that drug–placebo differences increased as a function of initial severity, which was attributed to decreased responsiveness to placebo among patients with severe depression rather than to increased responsiveness to medication. We retested this using patient-level data and also undertaking a meta-analysis of trial-level data from 34 randomised placebo controlled trials (n = 10 737) from the NEWMEDS registry. Although our trial-level data support prevous findings, patient-level data did not show any significant effect of initial depression severity on drug v. placebo difference.

Schizophrenia is usually classified based on clinical presentation. However, the conventional paranoid–disorganised–residual distinctions have had limited clinical utility. Here we draw on the evidence for differences in pathophysiology underlying treatment response to propose a subclassification based on neurobiology to guide diagnostic testing and treatment.

Thousands of papers have been published on the biological associations with psychosis yet this has had a limited impact on the routine clinical care of people with psychosis. Cognitive dysfunction, genetics and neuroimaging are the research areas likely to integrate into clinical practice in psychosis most rapidly. Clinical and academic collaborations in partnership with patients and carers are necessary to make progress, along with an acceptance that not all new approaches will necessarily prove effective in the longer term. Most discoveries do not just jump from bench to bedside, but require active interactions between scientists and clinicians.

Background. Deficits in a patient's ‘theory of mind’ (TOM) have been proposed to lead to psychosis. However, it remains unclear whether TOM deficits constitute a trait- or a state-related deficit and whether they respond to antipsychotic treatment, and also whether the change in TOM and change in psychosis are associated.

Method. In the cross-sectional component of this study, 71 patients with psychotic disorders were included and TOM ability was measured using a hinting task in which subjects had to infer real intentions behind indirect speech. In the longitudinal study, a different cohort of 17 drug-free patients were included wherein they received antipsychotic treatment for 6 weeks and the effect on psychotic symptoms and TOM was measured every 2 weeks. Associations between TOM and psychopathology were assessed and a mixed effects model was used to investigate the rate of change over time.

Results. Positive and Negative Syndrome Scale (PANSS) total scores were significantly associated with TOM scores. The hinting task was not associated with positive symptoms but was significantly associated with negative and general symptoms. The longitudinal arm of the study showed that both PANSS positive scores and TOM improved after medication was started, particularly during the first 2 weeks of antipsychotic treatment, but these changes were not associated. The TOM response at 2 weeks of antipsychotic treatment reached similar values to those obtained in the cross-sectional sample.

Conclusions. Although TOM and psychotic symptoms are related to each other, antipsychotic treatment impacts each independently, suggesting a dissimilar cognitive or neurobiological substrate for the two.

Background A growing interest in first-episode schizophrenia reflects the belief that this line of investigation will lead to further developments regarding schizophrenia's aetiology, course and outcome.

Method Evidence from more recent clinical trials involving first-episode schizophrenia is integrated with neuroimaging data, specifically positron emission tomography, to provide direction regarding pharmacotherapy.

Results Individuals with a first episode of schizophrenia appear particularly responsive to pharmacotherapy, as well as quite sensitive to side-effects. At the same time, current clinical and receptor-binding data support the efficacy of low-dose neuroleptic treatment.

Conclusions Early and effective treatment of schizophrenia has been associated with better long-term outcome. Low-dose neuroleptic therapy is an effective treatment strategy and the diminished risk of side-effects with this approach may further enhance compliance and outcome.