Reduced fractional anisotropy of corpus callosum in first-contact, antipsychotic drug-naive patients with schizophrenia.

Background: Corpus callosum is the most important commissure of the brain and therefore represents a first-choice candidate to challenge hypotheses of disrupted inter-hemispheric connectivity and white matter pathology in patients with schizophrenia. Recent studies on diffusion tensor imaging (DTI) of corpus callosum yielded promising but equivocal evidence of reduced fractional anisotropy (FA) in schizophrenia patients who were, for the most part, chronic cases on medication for a lengthy period of time. To exclude potentially confounding effects of the course of the disorder and its treatment, we compared callosal FA of first-contact, antipsychotic drug-naive schizophrenia patients (n=21) and healthy controls (n=21).

Methods: Splenium and genu FA were obtained by two independent observers utilizing large, rectangular, tractography-guided regions of interest outlined on directional color-coded maps. Inter-observer agreement on FA was evaluated by means of the Bland and Altman and the Passing and Bablok procedures together with an estimate of the intra-class correlation coefficient.

Results: Strong inter-observer agreement of FA values emerged from each of the three statistical approaches utilized. ANCOVA showed a significant effect on FA for the interaction between patient-control membership and callosal region (F=5.354; p=0.026); post hoc multiple comparisons demonstrated that, when compared to the controls, the patients had lower mean FA values (p=0.005) in the splenium but not in the genu and that this difference tended to be more evident in males (p=0.090).

Conclusions: Lowered mean FA values in the splenium of first-contact, antipsychotic drug-naive patients with respect to healthy controls strongly support the hypothesis that processes operant at least since the earliest phases of the disorder and independent from exposition to antipsychotic drugs contribute to reduced anisotropy in schizophrenia.