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24-06-2013 | Mental health | Article

White matter changes a family affair in schizophrenia


Free abstract

medwireNews: Similar but attenuated loss of white matter integrity to that found in patients with schizophrenia can also be observed in their first-degree relatives, researchers report.

"This suggests that genetic risk factors present in the relatives differ from those in the probands, perhaps indicating that protective genetic variants are exerting effects visible at a DTI [diffusion tensor imaging] level," say lead researcher Pawel Skudlarski (Yale School of Medicine, New Haven, Connecticut, USA) and co-workers.

Their study included 125 patients with schizophrenia and 82 with psychotic bipolar disorder. Both groups of patients had significant fractional anisotropy changes relative to 104 mentally healthy controls, indicating loss of white matter integrity, both at the whole-brain level and in 29 of 76 regions analyzed. But there were no significant differences between the schizophrenia and bipolar disorder patients.

However, fractional anisotropy changes did correlate with changes on the Schizo-Bipolar Scale, report the researchers in the American Journal of Psychiatry. They suggest that "scores on the Schizo-Bipolar Scale may capture subtle differences between those diseases better than clinical diagnosis."

The whole-brain changes seen in the patients were also present in 119 first-degree relatives of the schizophrenia patients. Of the 29 regions that differed in schizophrenia patients, their relatives differed significantly from controls in two.

Furthermore, there was a significant clinical regression effect for most of the 29 regions, such that fractional anisotropy values decreased from healthy controls, to mentally healthy relatives, to relatives with subthreshold psychotic or affective traits, to schizophrenia patients.

On the other hand, 83 relatives of the bipolar disorder patients had significantly lower fractional anisotropy values than controls in just one region (superior aspect of the left posterior corona radiate) and had significantly higher values than bipolar disorder patients in just five areas. A clinical regression effect was found for just one region.

The strongest confounding factor was age, report Skudlarski et al. White matter integrity declined with age, and this effect was exaggerated in patients with schizophrenia, but not those with bipolar disorder, "suggesting more pronounced progressive white matter abnormalities in schizophrenia."

They say: "In psychotic bipolar disorder, fractional anisotropy decreases may occur early and not progress thereafter."

The team suggests: "Perhaps the younger relatives of the bipolar probands included subjects who will later develop clinical symptoms, or perhaps endophenotypic white matter features in relatives of individuals with psychotic bipolar disorder manifest early and do not progress with age."

medwireNews ( is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2013

By Eleanor McDermid, Senior medwireNews Reporter