White matter alterations evident before psychosis development

Results from a UK study show that white matter (WM) integrity is reduced in patients at ultra-high risk (UHR) for psychosis, although to a lesser extent than in first-episode psychosis (FEP) patients.

The team also found that UHR patients who go on to develop full-blown psychosis have greater WM deficits than those who do not.

The findings, published in Schizophrenia Bulletin, suggest that "the onset of schizophrenia may be associated with a progressive reduction in the integrity of the frontal WM," say Francesco Carletti (King's College London) and team.

The researchers studied 32 individuals at UHR for psychosis, 15 patients with FEP, and 32 mentally healthy individuals (controls).

All of the participants were assessed for WM integrity using magnetic resonance imaging. Patients in the UHR group were also scanned 28 months later and differences between those who did (n=8) and did not (n=24) develop schizophrenia during the interval were analyzed.

At baseline, the team found significant differences among the groups in fractional anisotropy values (FA) in two brain clusters. The first cluster comprised the splenium and body of the corpus callosum, the left inferior and superior longitudinal fasciculus (SLF), and the left inferior frontooccipital fasciculus. The second cluster included the right external capsule, the retrolenticular part of the right internal capsule, and the right posterior corona radiata.

In both clusters, FA values were lowest in the FEP group, highest in controls, and intermediate in the UHR group.

The three groups also showed significant differences in radial diffusivity across widespread brain regions, with diffusivity being greatest in the FEP group, lowest in controls, and intermediate in the UHR group.

Among the UHR patients, those who subsequently developed schizophrenia showed a progressive reduction in FA values in the left frontal region, whereas no such progressive reductions were observed in those who did not develop schizophrenia.

Carletti et al conclude: "These data suggest that the UHR state is associated with reduced WM integrity in similar areas to those affected in first-episode psychosis, but to a lesser degree.

"Furthermore, we have provided the first evidence that the onset of psychosis in UHR subjects may be associated with a longitudinal progression of abnormalities in the left frontal WM."

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