Structural brain abnormalities linked to an “early” at-risk mental state may dictate an elevated susceptibility to psychosis, while those seen during a “late” state may indicate a subsequent transition to psychosis, suggest study results.

Previous studies have indicated that brain alterations exist 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,” say Eva Meisenzahl (Ludwig “Maximilians University, Munich, Germany) and co-authors.

To investigate, the researchers compared voxel-based morphometry (VBM) of magnetic resonance imaging (MRI) data from 20 individuals with putatively early at-risk mental state (ARMS “E group) and 26 individuals with a late at-risk mental state (ARMS “L group).

Mesenzahl and team then compared 15 at-risk mental state individuals with subsequent transition to psychosis (ARMS “T group) with 18 participants without disease transition (ARMS “NT group). All individuals were compared with 75 healthy volunteers.

ARMS “L individuals showed a greater extent and magnitude of brain abnormalities compared with ARMS “E individuals, with extended volume losses spanning the prefrontal and orbitofrontal cortices and involving parts of the anterior cingulated cortex, insula, and medial and lateral temporal brain regions.

Structural abnormalities in the ARMS “E group did not involve the pre- or orbitofrontal areas, but were restricted to the temporolimbic structures.

Furthermore, gray matter volume abnormalities increased as symptoms progressed towards a diagnosis of psychosis.

The authors note that it was not possible to ascertain whether the differences between the groups are a result of a longitudinal course of brain changes leading to psychosis, or whether they represent two risk levels for psychosis with distinct neuroanatomical underpinnings.

The study also showed that prefrontal structural alterations in ARMS “T participants were seen on average 6 months prior to disease transition, and overlapped with abnormalities of the ARMS “L sample.

Further analysis showed that ARMS “T participants had more pronounced prefrontal gray matter volume reductions compared with those in the ARMS “L group. Individuals in the ARMS “NT group also showed gray matter volume reductions similar to those seen in the ARMS “T group.

“Based on [previous] results and our own findings, we may cautiously interpret prefrontal brain alterations pre-dating psychosis as a marker of clinical outcome and not only as a marker of liability to attenuated or transient psychotic symptoms,” write the authors in the British Journal of Psychiatry.

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a part of Springer Science+Business Media. © Current Medicine Group Ltd; 2009

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