Structural brain abnormalities have been described in individuals with an at-risk mental state for psychosis. However, the neuroanatomical underpinnings of the early and late at-risk mental state relative to clinical outcome remain unclear.

To investigate grey matter volume abnormalities in participants in a putatively early or late at-risk mental state relative to their prospective clinical outcome.

Voxel-based morphometry of magnetic resonance imaging data from 20 people with a putatively early at-risk mental state (ARMS–E group) and 26 people with a late at-risk mental state (ARMS–L group) as well as from 15 participants with at-risk mental states with subsequent disease transition (ARMS–T group) and 18 participants without subsequent disease transition (ARMS–NT group) were compared with 75 healthy volunteers.

Compared with healthy controls, ARMS–L participants had grey matter volume losses in frontotemporolimbic structures. Participants in the ARMS–E group showed bilateral temporolimbic alterations and subtle prefrontal abnormalities. Participants in the ARMS–T group had prefrontal alterations relative to those in the ARMS–NT group and in the healthy controls that overlapped with the findings in the ARMS–L group.

Brain alterations associated with the early at-risk mental state may relate to an elevated susceptibility to psychosis, whereas alterations underlying the late at-risk mental state may indicate a subsequent transition to psychosis.

The Early Detection and Intervention Programme of the German Research Network on Schizophrenia (GRNS) investigates the initial prodromal phase of psychosis in a multidimensional approach. Two intervention strategies are being studied by two large-scale multicentre projects.

To present the concept of the intervention studies, and to provide an interim report of the recruitment procedure.

Comprehensive cognitive-behavioural therapy has been developed for patients in the ‘early initial prodromal state’. For patients in the ‘late initial prodromal state’ the atypical neuroleptic amisulpride is explored. Both interventions are evaluated in randomised controlled trials using clinical management as the control condition.

Between January 2001 and March 2003, 1212 individuals seeking help for mental health problems were screened for putative prodromal symptoms at four university centres. More than 388 individuals fulfilled criteria for both interventions and 188 (48. 5%) gave informed consent to participate in the trials.

The screening procedure appears to be feasible and trial participation seems to be acceptable to a relevant proportion of people at increased risk of developing psychosis.