Investigation of brain white matter and social cognition in schizophrenia and schizotypal personality disorder using neurite orientation dispersion and density imaging

Schizotypal personality disorder (SPD) is biologically and phenotypically similar to schizophrenia, but without frank psychosis and a general pattern of attenuated brain abnormalities. No studies have investigated the brain white matter in schizophrenia and SPD using neurite orientation dispersion density imaging (NODDI) to distinguish between intracellular vs. extracellular alterations to elucidate neurobiological mechanisms of resilience in the schizophrenia spectrum. In this study we used diffusion tensor imaging and NODDI to investigate putative white matter abnormalities common to schizophrenia (n = 42) and SPD (n = 31) compared to healthy controls (n = 40) and their relationship to social cognition. Individuals with schizophrenia had lower fractional anisotropy (FA) within the inferior fronto-occipital fasciculus and splenium of the corpus callosum compared to healthy controls. The SPD group had FA in these same regions that was intermediate to and significantly different from both groups. Group differences in FA could be attributed specifically to alterations in extracellular fiber coherence in contrast to intracellular neurite density. Lower FA was associated with worse ability to infer sarcasm both in the SPD and schizophrenia groups. These findings implicate attenuated (sparing of) putative white matter abnormalities in SPD in the same brain regions as schizophrenia and comparable structure-function relations in these patient groups. The finding that group differences in FA were driven by alterations in the orientational coherence of neurites suggests that it could serve as an intermediate phenotype in future diffusion imaging studies in the schizophrenia spectrum.