Dissociation of fractional anisotropy and resting-state functional connectivity alterations in antipsychotic-naive first-episode schizophrenia

Altered resting-state functional connectivity (rsFC) has been demonstrated between multiple brain regions in schizophrenia. However, whether these alterations are related to fractional anisotropy (FA) alterations in pathways that connect regions with altered rsFC remains unknown. In this study, diffusion tensor imaging and resting-state functional magnetic resonance imaging were performed with 181 antipsychotic-naïve first-episode schizophrenia patients and 173 matched healthy controls. FA was measured using tensor-guided tractography in identifiable pathways between selected pairs of brain regions with altered rsFC as determined by prior meta-analysis. Compared with controls, patients showed significantly decreased FA between right caudate nucleus and right pallidum, right caudate nucleus and right putamen, and right hippocampus and right thalamus. Decreased rsFC was observed between right pallidum and right thalamus, and right insula and right superior temporal gyrus. No significant correlation was observed between FA and rsFC. FA between right caudate nucleus and right putamen was inversely correlated with negative symptoms while rsFC between right pallidum and right thalamus was inversely correlated with positive symptoms. The lack of robust correlations between FA and rsFC and no overlap of these abnormalities indicate that regional rsFC alterations in the early course of schizophrenia are not primarily associated with FA alterations. The observation that positive and negative symptoms are related to different functional and structural disturbances is consistent with this dissociation, and with prior work suggests that different pathophysiological mechanism may underlie positive and negative symptoms in the early course of schizophrenia.